Sample records for beta stability progress

  1. Progress on plutonium stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Hurt, D. [Defense Nuclear Facilities Safety Board, Washington, DC (United States)


    The Defense Nuclear Facilities Safety Board has safety oversight responsibility for most of the facilities where unstable forms of plutonium are being processed and packaged for interim storage. The Board has issued recommendations on plutonium stabilization and has has a considerable influence on DOE`s stabilization schedules and priorities. The Board has not made any recommendations on long-term plutonium disposition, although it may get more involved in the future if DOE develops plans to use defense nuclear facilities for disposition activities.

  2. Simulated progress in double-beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Miley, H.S. (Pacific Northwest Laboratory, Battelle Blvd., Richland, WA 99352 (United States)); Arthur, R.J. (Pacific Northwest Laboratory, Battelle Blvd., Richland, WA 99352 (United States)); Avignone, F.T. (University of South Carolina, Columbia, SC 29208 (United States)); Barabash, A.S. (Institute for Theoretical and Experimental Physics, 117 259 Moscow (Russian Federation)); Brodzinski, R.L. (Pacific Northwest Laboratory, Battelle Blvd., Richland, WA 99352 (United States)); Collar, J.I. (University of South Carolina, Columbia, SC 29208 (United States)); Courant, H. (University of Minnesota, Minneapolis, MN 55455 (United States)); Garcia, E. (University of Zaragoza, Zaragoza (Spain)); Guerard, C.K. (University of South Carolina, Columbia, SC 29208 (United States)); Hensley, W.K. (Pacific Northwest Laboratory, Battelle Blvd., Richland, WA 99352 (United States)); Kirpichnikov, I.V. (Institute for Theoretical and Experimental Physics, 117 259 Moscow (Russian Federation)); Kl


    A Monte Carlo code has been developed to accurately simulate double-beta decay measurements. Coincident gamma rays, beta spectra, and angular correlations have been added to adequately simulate a complete [sup 100]Mo nuclear decay and provide corrections to experimentally determined detector efficiencies. This code has been used to strip certain low-background spectra obtained in the Homestake gold mine in Lead, SD, for the purpose of extremely sensitive materials assay for the construction of new, large, enriched germanium detectors. Assays as low as 9[mu]Bq/g of [sup 210]Pb in lead shielding were obtained. ((orig.))

  3. Simulated progress in double-beta decay (United States)

    Miley, H. S.; Arthur, R. J.; Avignone, F. T.; Barabash, A. S.; Brodzinski, R. L.; Collar, J. J.; Courant, H.; Garcia, E.; Guerard, C. K.; Hensley, W. K.; Kirpichnikov, I. V.; Klimenko, A. A.; Morales, A.; Morales, J.; Nunez-Lagos, R.; Osetrov, S. B.; Pogosov, V. S.; Puimedon, J.; Reeves, J. H.; Ruddick, K.; Saenz, C.; Salinas, A.; Sarsa, M. L.; Smolnikov, A. A.; Starostin, A. S.; Tamanyan, A. G.; Umatov, V. I.; Vasiliev, S. I.; Villar, J. A.


    A Monte Carlo code has been developed to accurately simulate double-beta decay measurements. Coincident gamma rays, beta spectra, and angular correlations have been added to adequately simulate a complete 100Mo nuclear decay and provide corrections to experimentally determined detector efficiencies. This code has been used to strip certain low-background spectra obtained in the Homestake gold mine in Lead, SD, for the purpose of extremely sensitive materials assay for the construction of new, large, enriched germanium detectors. Assays as low as 9 μBq/g of 210Pb in lead shielding were obtained.

  4. Ideal MHD stability of very high beta tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Chance, M.S.; Jardin, S.C.; Kessel, C.; Manickam, J.; Monticello, D. (Princeton Univ., NJ (USA). Plasma Physics Lab.); Peng, Y.K.M.; Holmes, J.A.; Strickler, D.J.; Whitson, J.C. (Oak Ridge National Lab., TN (USA)); Glasser, A.H. (Los Alamos National Lab., NM (USA)); Sykes, A. (UKAEA Culham Lab., Abingdon (UK)); Ramos, J.J. (Massachusetts Inst. of Tech., Cambridge, MA (USA). Plasma Fusion Center)


    Achieving very high {beta} and high {beta}{sub p} simultaneously in tokamaks generally implies that the second stability region against ballooning modes must be accessed. We describe several approaches for doing this, which are characterized by the choice of constraints imposed on the equilibrium profiles and the cross-sectional shape of the plasma. The combination of high toroidal beta, restricting the current density to vanish at the edge of the plasma and maintaining a monotonic q profile, proves to be the most stringent. Consideration of equilibria with high {epsilon}{beta}{sub p} but low {beta} facilitates accessibility with peaked pressure profiles and high values of q{sub 0}. Allowing the pressure gradient and, hence, the current density to be finite at the plasma edge allows all surfaces to lie within the second stability regime. For free boundary plasmas with divertors, the divertor stabilized edge region remains in the first stability regime while the plasma core reaches into the second regime. Careful tailoring of the profiles must be used to traverse the unstable barrier commonly seen near the edge of these plasmas. The CAMINO code allows us to compute s-{alpha} curves for general tokamak geometry. These diagrams enable us to construct equilibria whose profiles are only constrained, at worst, to be marginally stable everywhere, but do not necessarily satisfy the constraints on the current or {beta}. There are theoretical indications that under certain conditions the external kinks possess a second region of stability at high q{sub 0} that is analogous to that of the ballooning modes. It is found that extremely accurate numerical means must be developed and applied to confidently establish the validity of these results. 14 refs., 5 figs., 1 tab.

  5. Biocompatibility of beta-stabilizing elements of titanium alloys. (United States)

    Eisenbarth, E; Velten, D; Müller, M; Thull, R; Breme, J


    In comparison to the presently used alpha + beta titanium alloys for biomedical applications, beta-titanium alloys have many advantageous mechanical properties, such as an improved wear resistance, a high elasticity and an excellent cold and hot formability. This will promote their future increased application as materials for orthopaedic joint replacements. Not all elements with beta-stabilizing properties in titanium alloys are suitable for biomaterial applications-corrosion and wear processes cause a release of these alloying elements to the surrounding tissue. In this investigation, the biocompability of alloying elements for beta- and near beta-titanium alloys was tested in order to estimate their suitability for biomaterial components. Titanium (grade 2) and the implant steel X2CrNiMo18153 (AISI 316 L) were tested as reference materials. The investigation included the corrosion properties of the elements, proliferation, mitochondrial activity, cell morphology and the size of MC3T3-E1 cells and GM7373 cells after 7 days incubation in direct contact with polished slices of the metals. The statistical significance was considered by Weir-test and Lord-test (alpha = 0.05). The biocompatibility range of the investigated metals is (decreasing biocompatibility): niobium-tantalum, titanium, zirconium-aluminium-316 L-molybdenum.

  6. Progress with large N{sub f} {beta}-functions

    Energy Technology Data Exchange (ETDEWEB)

    Gracey, J.A. [Liverpool Univ. (United Kingdom). Dept. of Math. Sci.


    We report on the progress in the computation of the {beta}-functions of {phi}{sup 4} theory and QCD in the large N expansion. For the former we give an analytic formula for the critical exponent which encodes higher order coefficients in the series beyond those currently known in the MS scheme at O(1/N{sup 2}) in a large N expansion. This allows us to deduce new coefficients in the field anomalous dimension which relate to Kreimer`s knot theory of the divergences of a quantum field theory. A similar exponent is computed for the {beta}-function of QCD at O(1/N{sub f}). (orig.).

  7. Gyrokinetic studies of the effect of beta on drift-wave stability in NCSX

    CERN Document Server

    Baumgaertel, J A; Mikkelsen, D R; Nunami, M; Xanthopoulos, P


    The gyrokinetic turbulence code GS2 was used to investigate the effects of plasma beta on linear, collisionless ion temperature gradient (ITG) modes and trapped electron modes (TEM) in National Compact Stellarator Experiment (NCSX) geometry. Plasma beta affects stability in two ways: through the equilibrium and through magnetic fluctuations. The first was studied here by comparing ITG and TEM stability in two NCSX equilibria of differing beta values, revealing that the high beta equilibrium was marginally more stable than the low beta equilibrium in the adiabatic-electron ITG mode case. However, the high beta case had a lower kinetic-electron ITG mode critical gradient. Electrostatic and electromagnetic ITG and TEM mode growth rate dependencies on temperature gradient and density gradient were qualitatively similar. The second beta effect is demonstrated via electromagnetic ITG growth rates' dependency on GS2's beta input parameter. A linear benchmark with gyrokinetic codes GENE and GKV-X is also presented.

  8. Progress Toward the Analysis of the Kinetic Stabilizer Concept

    Energy Technology Data Exchange (ETDEWEB)

    Post, R F; Byers, J A; Cohen, R H; Fowler, T K; Ryutov, D D; Tung, L S


    The Kinetic Stabilizer (K-S) concept [1] represents a means for stabilizing axisymmetric mirror and tandem-mirror (T-M) magnetic fusion systems against MHD interchange instability modes. Magnetic fusion research has given us examples of axisymmetric mirror confinement devices in which radial transport rates approach the classical ''Spitzer'' level, i.e. situations in which turbulence if present at all, is at too low a level to adversely affect the radial transport [2,3,4]. If such a low-turbulence condition could be achieved in a T-M system it could lead to a fusion power system that would be simpler, smaller, and easier to develop than one based on closed-field confinement, e.g., the tokamak, where the transport is known to be dominated by turbulence. However, since conventional axisymmetric mirror systems suffer from the MHD interchange instability, the key to exploiting this new opportunity is to find a practical way to stabilize this mode. The K-S represents one avenue to achieving this goal. The starting point for the K-S concept is a theoretical analysis by Ryutov [5]. He showed that a MHD-unstable plasma contained in an axisymmetric mirror cell can be MHD-stabilized by the presence of a low-density plasma on the expanding field lines outside the mirrors. If this plasma communicates well electrically with the plasma in the then this exterior plasma can stabilize the interior, confined, plasma. This stabilization technique was conclusively demonstrated in the Gas Dynamic Trap (GDT) experiment [6] at Novosibirsk, Russia, at mirror-cell plasma beta values of 40 percent. The GDT operates in a high collisionality regime. Thus the effluent plasma leaking through the mirrors, though much lower in density than that of the confined plasma, is still high enough to satisfy the stabilization criterion. This would not, however, be the case in a fusion T-M with axisymmetric plug and central cell fields. In such a case the effluent plasma would be far

  9. Sustained Rotational Stabilization of DIII-D Plasmas Above the No-Wall Beta Limit (United States)

    Garofalo, A. M.


    Sustained stabilization of the n=1 kink mode by plasma rotation at beta approaching twice the stability limit calculated without a wall has been achieved in DIII-D by a combination of error field reduction and sufficient rotation drive. Previous experiments have transiently exceeded the no-wall beta limit, but demonstration of sustained rotational stabilization has remained elusive. Recent theory(A. Boozer, Phys. Rev. Lett. 86), 5059 (2001). predicts a resonant response to error fields in a plasma approaching marginal stability to a low-n kink mode. Enhancement of magnetic non-axisymmetry in the plasma leads to strong damping of the toroidal rotation, precisely in the high-beta regime where it is needed for stabilization. This ``error field amplification," EFA, is demonstrated in DIII-D experiments: applied n=1 error fields cause enhanced plasma response and strong rotation damping at beta above the no-wall limit, but have little effect at lower beta. The discovery of EFA has led to sustained operation above the no-wall limit through improved error field correction using an external coil set. The required correction is determined both by optimizing the external currents with respect to the plasma rotation, and by use of feedback to detect and minimize the plasma response to error fields as beta increases. Stability analysis and rotation braking experiments at different beta values show that beta is maintained 50% higher than the no-wall stability limit for duration greater than 1 second, and approaches beta twice the no-wall limit in several cases, with steady-state rotation levels. The results suggest that improved error field correction could allow plasmas to be maintained well above no-wall beta limit for as long as sufficient torque is provided.

  10. Progress toward the genetic treatment of the beta-thalassemias. (United States)

    Sadelain, Michel; Lisowski, Leszek; Samakoglu, Selda; Rivella, Stefano; May, Chad; Riviere, Isabelle


    The beta-thalassemias are congenital anemias that are caused by mutations that reduce or abolish expression of the beta-globin gene. They can be cured by allogeneic hematopoietic stem cell (HSC) transplantation, but this therapeutic option is not available to most patients. The transfer of a regulated beta-globin gene in autologous HSCs is a highly attractive alternative treatment. This strategy, which is simple in principle, raises major challenges in terms of controlling expression of the globin transgene, which ideally should be erythroid specific, differentiation- and stage-restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, May et al. demonstrated in 2000 that an optimized combination of proximal and distal transcriptional control elements permits lineage-specific and elevated beta-globin expression, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Several groups have by now replicated and extended these findings to various mouse models of severe hemoglobinopathies, thus fueling enthusiasm for a potential treatment of beta-thalassemia based on globin gene transfer. Current investigation focuses on safety issues and the need for improved vector production methodologies. The safe implementation of stem cell-based gene therapy requires the prevention of the formation of replication-competent viral genomes and minimization of the risk of insertional oncogenesis. Importantly, globin vectors, in which transcriptional activity is highly restricted, have a lesser risk of activating oncogenes in hematopoietic progenitors than non-tissue-specific vectors, by virtue of their late-stage erythroid specificity. As such, they provide a general paradigm for improving vector safety in stem cell-based gene therapy.

  11. AU-rich elements and alternative splicing in the beta-catenin 3'UTR can influence the human beta-catenin mRNA stability.

    NARCIS (Netherlands)

    Thiele, A.; Nagamine, Y.; Hauschildt, S.; Clevers, J.C.


    Beta-catenin, the central player of the Wnt signaling cascade, is a well-known oncogene. The regulation of beta-catenin protein stability has been studied extensively while other mechanisms that control cellular levels of beta-catenin have hardly been addressed. In this study, we show that there are

  12. Electromagnetic stabilization of tokamak microturbulence in a high-$\\beta$ regime

    CERN Document Server

    Citrin, J; Goerler, T; Jenko, F; Mantica, P; Told, D; Bourdelle, C; Hatch, D R; Hogeweij, G M D; Johnson, T; Pueschel, M J; Schneider, M


    The impact of electromagnetic stabilization and flow shear stabilization on ITG turbulence is investigated. Analysis of a low-$\\beta$ JET L-mode discharge illustrates the relation between ITG stabilization, and proximity to the electromagnetic instability threshold. This threshold is reduced by suprathermal pressure gradients, highlighting the effectiveness of fast ions in ITG stabilization. Extensive linear and nonlinear gyrokinetic simulations are then carried out for the high-$\\beta$ JET hybrid discharge 75225, at two separate locations at inner and outer radii. It is found that at the inner radius, nonlinear electromagnetic stabilization is dominant, and is critical for achieving simulated heat fluxes in agreement with the experiment. The enhancement of this effect by suprathermal pressure also remains significant. It is also found that flow shear stabilization is not effective at the inner radii. However, at outer radii the situation is reversed. Electromagnetic stabilization is negligible while the flow...

  13. Stabilization of TRAIL, an all-{beta}-sheet multimeric protein, using computational redesign

    NARCIS (Netherlands)

    van der Sloot, Almer Martinus; Mullally, Margaret; Fernandez-Ballester, G.; Serrano, L.; Quax, Wim


    Protein thermal stability is important for therapeutic proteins, both influencing the pharmacokinetic and pharmacodynamic properties and for stability during production and shelf-life of the final product. In this paper we show the redesign of a therapeutically interesting trimeric all-beta-sheet pr

  14. Stabilization of TRAIL, an all-beta-sheet multimeric protein, using computational redesign

    NARCIS (Netherlands)

    van der Sloot, AM; Mullally, MM; Fernandez-Ballester, G; Serrano, L; Quax, WJ


    Protein thermal stability is important for therapeutic proteins, both influencing the pharmacokinetic and pharmacodynamic properties and for stability during production and shelf-life of the final product. In this paper we show the redesign of a therapeutically interesting trimeric all-beta-sheet pr

  15. Enhanced thermal stability of lysosomal beta-D-galactosidase in parenchymal cells of tumour bearing mice.



    The thermal stability of the enzyme beta-D-galactosidase varies among different organs in normal C57Bl/6 mice, and increases in the same organs in mice with Lewis Lung carcinoma. Thermal stability of this enzyme is also increased by treatment of the mice with cell-free extracts of tumour cells or with inflammatory compounds such as carrageenan or orosomucoid. After desialylation, orosomucoid more effectively increases the heat stability of the enzyme. By contrast talc, which has no galactosyl...

  16. Finite and Infinite Arithmetic Progressions Related to Beta-Expansion

    Directory of Open Access Journals (Sweden)

    Bing Li


    Full Text Available Let 1<β<2 and ε(x,β be the β-expansion of x∈[0,1. Denote by Aβ(x the set of positions where the digit 1 appears in ε(x,β. We consider the sets of points x such that Aβ(x contains arbitrarily long arithmetic progressions and includes infinite arithmetic progressions, respectively. Their sizes are investigated from the topological, metric, and dimensional viewpoints.

  17. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

    DEFF Research Database (Denmark)

    Yde, C W; Olsen, B B; Meek, D


    Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC...... interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found...... regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.Oncogene advance online publication, 12 May 2008; doi:10.1038/onc.2008.146....

  18. The Influence of Maltodextrin on the Physicochemical Properties and Stabilization of Beta-carotene Emulsions. (United States)

    Zhang, Jianpan; Zhang, Xiaoxu; Wang, Xinyi; Huang, Ying; Yang, Beibei; Pan, Xin; Wu, Chuanbin


    Beta-carotene is important for fortification of nutritional products while its application is limited by instability. The influence of maltodextrin (MDX) on physicochemical properties and stability of beta-carotene emulsions stabilized by sodium caseinate (SC) was investigated. The emulsions were characterized by dynamic light scattering (DLS), laser diffraction (LD), transmission electron microscopy (TEM), rheometer, and turbiscan lab expert. The effects of pH, ionic strength, and freeze-thaw on stability of emulsions were observed. The emulsions could tolerate up to 2 mol/L NaCl or 10 mmol/L CaCl2 and showed Newtonian behavior. The droplet diameter, polydispersity index, and zeta-potential did not change obviously after 3 months storage at 4°C in dark conditions. The emulsions with MDX showed excellent freeze-thaw stability and gave favorite protection for beta-carotene. The retention ratio of beta-carotene in the emulsions with MDX was above 92.1% after 3 months storage while that in the one without MDX was only 62.7%. The study may provide a promising strategy to improve stability of sensitive nutraceuticals without adding synthetic antioxidants. The findings obtained could provide fundamental basis for rational design of emulsion delivery systems when freeze-thawing is required during manufacturing process or storage period.

  19. Effects of modified {beta}-cyclodextrin on thermal stability and conformation of lysozyme

    Energy Technology Data Exchange (ETDEWEB)

    Kamiyama, Tadashi, E-mail: [Department of Chemistry, School of Science and Engineering, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502 (Japan); Satoh, Megumi; Tateishi, Takahiro; Nojiri, Tomoaki; Takeuchi, Daisuke; Kimura, Takayoshi [Department of Chemistry, School of Science and Engineering, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502 (Japan)


    Highlights: Black-Right-Pointing-Pointer Effects of cyclodextrin on stability and conformation of lysozyme were clarified. Black-Right-Pointing-Pointer The CD influences the hydrophobic interaction of lysozyme by the inclusion. Black-Right-Pointing-Pointer The CD relatively destabilized the folded state by stabilizing the unfolded state. Black-Right-Pointing-Pointer The destabilization depends on the concentration and the substituent of CD. Black-Right-Pointing-Pointer The conformation of lysozyme was more spread at unfolded state by inclusion of CD. - Abstract: Effects of cyclic oligosaccharide cyclodextrin (CD) on stability and conformation of lysozyme were clarified thermodynamically and rheologically by DSC, viscosity, and circular dichroism measurements. The modified {beta}-CD relatively destabilized the folded state of lysozyme by stabilizing the unfolded state due to inclusion of hydrophobic part into the hydrophobic interior of CD. The order of higher destabilization effect was acetyl-{beta}-CD > methyl-{beta}-CD > hydroxypropyl-{beta}-CD. Apparent number of bound CD to unfolded state for methyl-, hydroxypropyl-, and acetyl-{beta}-CD is 6.7 {+-} 0.7, 4.2 {+-} 1.1, and 18.6 {+-} 4.3 and the binding constant is 5.5 {+-} 0.8, 6.7 {+-} 2.4, and 4.4 {+-} 1.2 L mol{sup -1}, respectively. The viscosity for unfolded state was increased with an increase in the each modified {beta}-CD concentration, suggesting that the inclusion of CD on a part of hydrophobic core at unfolded state leads to break the hydrophobic core, then lysozyme would be more spread structure. The substituent of CD can accelerate instability by directly breaking hydrogen bond and/or can restrain instability by increase in hydrophobic interaction. The fact that the each modified CDs has different destabilization effect shows a possibility to control the stability of protein by the substitution of CD.

  20. Plasma S100 beta and NSE levels and progression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Mostert, Jop; Heersema, Dorothea; Teelken, Albert; De Keyser, Jacques


    Plasma levels of the glial cell marker S100 beta and the neuronal marker neuron-specific enolase (NSE) are elevated in various conditions of central nervous system damage. In this study we investigated whether plasma levels of S 1000 and NSE are related to disease progression in multiple sclerosis (

  1. Microstructure and corrosion behavior of binary titanium alloys with beta-stabilizing elements. (United States)

    Takada, Y; Nakajima, H; Okuno, O; Okabe, T


    Binary titanium alloys with the beta-stabilizing elements of Co, Cr, Cu, Fe, Mn and Pd (up to 30%) and Ag (up to 45%) were examined through metallographic observation and X-ray diffractometry to determine whether beta phases that are advantageous for dental use could be retained. Corrosion behavior was also investigated electrochemically and discussed thermodynamically. Some cast alloys with Co, Cr, Fe, Mn, and Pd retained the beta phase, whereas those with Ag and Cu had no beta phase. In some alloys, an intermetallic compound formed, based on information from the phase diagram. The corrosion resistance deteriorated in the TiAg alloys because Ti2Ag and/or TiAg intermetallic compounds preferentially dissolved in 0.9% NaCl solution. On the other hand, the remaining titanium alloys became easily passive and revealed good corrosion resistance similar to pure titanium since their matrices seemed to thermodynamically form titanium oxides as did pure titanium.

  2. Structure and stability of short beta-peptide nanotubes: a non-natural representative of collagen? (United States)

    Czajlik, András; Beke, Tamás; Bottoni, Andrea; Perczel, András


    Since secondary structure elements are known to play a key role in stabilizing the 3D-fold of proteins for the design of non-natural proteins composed of beta-amino acid residues, the construction of suitable secondary structural elements is mandatory. Folding analogues of alpha-helices and beta-strands of beta-polypeptides were already described (Chem. Biodiversity 2004, 1, 1111 (1)). Here, we present several collagen-like folds composed exclusively of beta-Ala(s). Unlike their natural counterpart, these tubular nanostructures can be composed of more than three polypeptide chains aligned parallel and/or antiparallel. By using ab initio and DFT calculations we have optimized a large number of versatile collagen-like antiparallel nanostructures. In these tubular systems, oligopeptide strands are interconnected by i --> (i) type H-bonds, except for the "closing" set. This latter is called "the H-bond zipper" and is either (i) --> i, ( i + 1) --> i, or ( i + 2) --> i type. Antiparallel, tubular foldamers composed of l number of strands, each of k number of beta-amino acid residues (e.g., apbeta-T(l) i+l ) k , ap(beta-T(l) i+1 ) k , or ap(beta-T(l) i+2 ) k ), are unexpectedly stable supramolecular complexes. Independent of k and l, the local backbone fold of the amino acid residues is usually spiral, abbreviated as "S(P)" or "S*(P)". Nevertheless, in contrast to parallel, in antiparallel nanotubes the backbone fold can occasionally twist out from S(P) or S*(P) type into an alternative local structure. However, the more the local geometry of the strands resembles to S(P) or S*(P), the higher the stability is. Besides the backbone twisting, the overall stability is determined by the type and the geometrical properties of the constituent H-bonds. Interestingly, higher number of total H-bonds can provide a lower overall stability, when H-bond parameters are inferior. In general, the increase of both the number of strands and their length stabilize the supramolecular

  3. Finite beta and compressibility effects on stability of resistive modes in toroidal geometry

    Energy Technology Data Exchange (ETDEWEB)

    Leboeuf, J.-N.G. [Oak Ridge National Lab., TN (United States); Kurita, Gen-ichi


    Linear resistive stability results obtained from the toroidal magnetohydrodynamic codes FAR developed at the Oak Ridge National Laboratory in United States of America and AEOLUS developed at the Japan Atomic Energy Research Institute are compared for carefully constructed benchmark profiles and parameters. These are unstable to a tearing mode with toroidal mode number n=1. The eigenvalues and eigenfunctions calculated with both codes are in close agreement and show that the effect of compressibility is weak for these modes. The effect of finite plasma beta is considered, and the eigenvalues calculated by the FAR and AEOLUS codes also show good agreement. It is shown that the finite beta has a stabilizing effect on the toroidal tearing mode, but that the compressibility also has little effect on finite beta tearing modes. (author)

  4. Enhanced thermal stability of lysosomal beta-D-galactosidase in parenchymal cells of tumour bearing mice. (United States)

    Lenti, L; Lipari, M; Lombardi, D; Zicari, A; Dotta, A; Pontieri, G M


    The thermal stability of the enzyme beta-D-galactosidase varies among different organs in normal C57Bl/6 mice, and increases in the same organs in mice with Lewis Lung carcinoma. Thermal stability of this enzyme is also increased by treatment of the mice with cell-free extracts of tumour cells or with inflammatory compounds such as carrageenan or orosomucoid. After desialylation, orosomucoid more effectively increases the heat stability of the enzyme. By contrast talc, which has no galactosyl groups, is without effect on the stability of the enzyme in vivo. Macrophages of tumour bearing mice release into the culture medium a more heat resistant enzyme than macrophages from control mice. In both cases the heat resistance of the secreted enzyme is higher when fetal calf serum is present in the culture medium. Bovine serum does not modify the thermal stability of beta-D-galactosidase in this system. Incubation of lysosomal fractions of various organs with the synthetic beta-D-galactosidase substrate, p-nitrophenyl-galactopyranoside, also strongly increases the heat resistance of the enzyme. The results suggest that one factor influencing the heat resistance of this enzyme may be complex formation between the enzyme and its substrates, an example of substrate protection of the enzyme. This may not be the only factor involved in enzyme stabilization in vivo.

  5. The Effect of Plasma Beta on High-n Ballooning Stability at Low Magnetic Shear

    CERN Document Server

    Connor, J W; Hastie, R J


    An explanation of the observed improvement in H-mode pedestal characteristics with increasing core plasma pressure or poloidal beta, as observed in MAST and JET, is sought in terms of the impact of the Shafranov shift, d', on ideal ballooning MHD stability.

  6. Estrogen Receptor beta 2 Induces Hypoxia Signature of Gene Expression by Stabilizing HIF-1 alpha in Prostate Cancer


    Prasenjit Dey; Velazquez-Villegas, Laura A.; Michelle Faria; Anthony Turner; Philp Jonsson; Paul Webb; Cecilia Williams; Jan-Åke Gustafsson; Ström, Anders M.


    The estrogen receptor (ER) beta variant ER beta 2 is expressed in aggressive castration-resistant prostate cancer and has been shown to correlate with decreased overall survival. Genome-wide expression analysis after ER beta 2 expression in prostate cancer cells revealed that hypoxia was an overrepresented theme. Here we show that ER beta 2 interacts with and stabilizes HIF-1 alpha protein in normoxia, thereby inducing a hypoxic gene expression signature. HIF-1 alpha is known to stimulate met...

  7. Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

    Directory of Open Access Journals (Sweden)

    Sjoerd M. Bruijn


    Full Text Available Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG during stabilized and normal walking.Subjects walked on a treadmill in two conditions, each lasting 10 minutes; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e. lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability.

  8. Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia. (United States)

    Weiss, Mitchell J; Zhou, Suiping; Feng, Liang; Gell, David A; Mackay, Joel P; Shi, Yigong; Gow, Andrew J


    Hemoglobin (Hb) synthesis is coordinated by homeostatic mechanisms to limit the accumulation of free alpha or beta subunits, which are cytotoxic. Alpha hemoglobin-stabilizing protein (AHSP) is an abundant erythroid protein that specifically binds free alphaHb, stabilizes its structure, and limits its ability to participate in chemical reactions that generate reactive oxygen species. Gene ablation studies in mice demonstrate that AHSP is required for normal erythropoiesis. AHSP-null erythrocytes are short-lived, contain Hb precipitates, and exhibit signs of oxidative damage. Loss of AHSP exacerbates beta-thalassemia in mice, indicating that altered AHSP expression or function could modify thalassemia phenotypes in humans, a topic that is beginning to be explored in clinical studies. We used biochemical, spectroscopic, and crystallographic methods to examine how AHSP stabilizes alphaHb. AHSP binds the G and H helices of alphaHb on a surface that largely overlaps with the alpha1-beta1 interface of HbA. This result explains previous findings that betaHb can competitively displace AHSP from alphaHb to form HbA tetramer. Remarkably, binding of AHSP to oxygenated alphaHb induces dramatic conformational changes and converts the heme-bound iron to an oxidized hemichrome state in which all six coordinate positions are occupied. This structure limits the reactivity of heme iron, providing a mechanism by which AHSP stabilizes alphaHb. These findings suggest a biochemical pathway through which AHSP might participate in normal Hb synthesis and modulate the severity of thalassemias. Moreover, understanding how AHSP stabilizes alphaHb provides a theoretical basis for new strategies to inhibit the damaging effects of free alphaHb that accumulates in beta-thalassemia.

  9. Acquired TGF beta 1 sensitivity and TGF beta 1 expression in cell lines established from a single small cell lung cancer patient during clinical progression

    DEFF Research Database (Denmark)

    Nørgaard, P; Damstrup, L; Rygaard, K;


    was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously administrated TGF beta 1. TGF beta 1 mRNA and protein in its latent form was only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was paralleled...... by a gain in sensitivity to the growth inhibition by TGF beta 1 due to type II TGF beta receptor, and a gain of latent TGF beta 1 protein. Lack of type II receptor expression in GLC 14, which was also resistant to growth inhibition by exogenous TGF beta 1, was not due to gross structural changes in the type...

  10. Fluorescence properties and conformational stability of the beta-hemocyanin of Helix pomatia. (United States)

    Idakieva, Krassimira; Siddiqui, Nurul I; Parvanova, Katja; Nikolov, Peter; Gielens, Constant


    The beta-hemocyanin (beta-HpH) is one of the three dioxygen-binding proteins found freely dissolved in the hemolymph of the gastropodan mollusc Helix pomatia. The didecameric molecule (molecular mass 9 MDa) is built up of only one type of subunits. The fluorescence properties of the oxygenated and apo-form (copper-deprived) of the didecamer and its subunits were characterized. Upon excitation of the hemocyanins at 295 or 280 nm, tryptophyl residues buried in the hydrophobic interior of the protein determine the fluorescence emission. This is confirmed by quenching experiments with acrylamide, cesium chloride and potassium iodide. The copper-dioxygen system at the binuclear active site quenches the tryptophan emission of the oxy-beta-HpH. The removal of this system increases the fluorescence quantum yield and causes structural rearrangement of the microenvironment of the emitting tryptophyl residues in the apo-form. Time-resolved fluorescence measurements show that the oxygenated and copper-deprived forms of the beta-HpH and its subunits exist in different conformations. The thermal stability of the oxy- and apo-beta-HpH is characterized by a transition temperature (Tm) of 84 degrees C and 63 degrees C, respectively, obtained by differential scanning calorimetry. Increase of the temperature influences the active site at lower temperatures than the environments of tryptophans and tyrosines causing a loss of oxygen bound to the copper atoms. This process is, at least partially, reversible as after cooling of the protein samples, around 60% reinstatement of the copper-peroxide band has been observed. The results confirm the role of the copper-dioxygen complex for the stabilization of the hemocyanin structure in solution. The other important stabilizing factor is oligomerization of the hemocyanin molecule.

  11. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. (United States)

    Tseng, Ruo-Chia; Lee, Shih-Hua; Hsu, Han-Shui; Chen, Ben-Han; Tsai, Wan-Ching; Tzao, Ching; Wang, Yi-Ching


    Chromosome 4p15.3 is frequently deleted in late-stage lung cancer. We investigated the significance of the SLIT2 gene located in this region to lung cancer progression. SLIT2 encodes an extracellular glycoprotein that can suppress breast cancer by regulating beta-catenin. In this study, we examined alterations in the structure or expression of SLIT2, its receptor ROBO1, and beta-catenin, along with the AKT/glycogen synthase kinase 3beta (GSK3beta)/beta-transducin repeat-containing protein (betaTrCP) pathway in lung cancer cell lines and patients. Low SLIT2 expression correlated with an upward trend of pathological stage and poorer survival in lung cancer patients. Importantly, SLIT2, betaTrCP, and beta-catenin expression levels predicted postoperative recurrence of lung cancer in patients. Stimulating SLIT2 expression by various methods increased the level of E-cadherin caused by attenuation of its transcriptional repressor SNAI1. Conversely, knocking down SLIT2 expression increased cell migration and reduced cell adhesion through coordinated deregulation of beta-catenin and E-cadherin/SNAI1 in the AKT/GSK3beta/betaTrCP pathway. Our findings indicate that SLIT2 suppresses lung cancer progression, defining it as a novel "theranostic" factor with potential as a therapeutic target and prognostic predictor in lung cancer. Cancer Res; 70(2); 543-51.

  12. Factors contributing to decreased protein stability when aspartic acid residues are in {beta}-sheet regions.

    Energy Technology Data Exchange (ETDEWEB)

    Pokkuluri, P. R.; Cai, X.; Raffen, R.; Gu, M.; Stevens, F. J.; Schiffer, M.


    Asp residues are significantly under represented in {beta}-sheet regions of proteins, especially in the middle of {beta}-strands, as found by a number of studies using statistical, modeling, or experimental methods. To further understand the reasons for this under representation of Asp, we prepared and analyzed mutants of a {beta}-domain. Two Gln residues of the immunoglobulin light-chain variable domain (V{sub L}) of protein Len were replaced with Asp, and then the effects of these changes on protein stability and protein structure were studied. The replacement of Q38D, located at the end of a {beta}-strand, and that of Q89D, located in the middle of a {beta}-strand, reduced the stability of the parent immunoglobulin VL domain by 2.0 kcal/mol and 5.3 kcal/mol, respectively. Because the Q89D mutant of the wild-type V{sub L}-Len domain was too unstable to be expressed as a soluble protein, we prepared the Q89D mutant in a triple mutant background, V{sub L}-Len M4L/Y27dD/T94H, which was 4.2 kcal/mol more stable than the wild-type V{sub L}-Len domain. The structures of mutants V{sub L}-Len Q38D and V{sub L}-Len Q89D/M4L/Y27dD/T94H were determined by X-ray diffraction at 1.6 A resolution. We found no major perturbances in the structures of these QD mutant proteins relative to structures of the parent proteins. The observed stability changes have to be accounted for by cumulative effects of the following several factors: (1) by changes in main-chain dihedral angles and in side-chain rotomers, (2) by close contacts between some atoms, and, most significantly, (3) by the unfavorable electrostatic interactions between the Asp side chain and the carbonyls of the main chain. We show that the Asn side chain, which is of similar size but neutral, is less destabilizing. The detrimental effect of Asp within a {beta}-sheet of an immunoglobulin-type domain can have very serious consequences. A somatic mutation of a {beta}-strand residue to Asp could prevent the expression of the

  13. Physical stability of a microcrystalline beta-sitosterol suspension in oil

    DEFF Research Database (Denmark)

    von Bonsdorff-Nikander, Anna; Karjalainen, Milja; Rantanen, Jukka


    in the particle size. A previous work described how to produce a microcrystalline beta-sitosterol suspension. The present study deals with the stability of that suspension. Recrystallisation was carried out by two different methods; one based on rapid the other based on slow cooling, whereby six different......-ray diffraction. Suspensions can, in most cases, be stored for 16 weeks without any changes to the size and habit. The only evidence of crystal growth came from a suspension with a low sterol concentration at a temperature of +4 degrees C. This is due to the dissolution-diffusion process which is affected...... by temperature and viscosity. Suspensions containing higher amounts of sterol remained stable, if stored at +4 or -19 degrees C, for 16 weeks. The suspensions included both hemihydrous and monohydrous beta-sitosterol crystals. Suspensions containing less sterol showed greater amounts of monohydrated crystals...

  14. Luminosity control and beam orbit stability with beta star leveling at LHC and HL-LHC

    CERN Document Server

    Gorzawski, Arkadiusz Andrzej; Wenninger, Jorg

    This thesis describes the wide subject of the luminosity leveling and its requirements for the LHC and the HL-LHC. We discuss the advantages and disadvantages of different leveling methods focusing the thesis on the beta star leveling technique. We review the beams offset build--up due to the environmental (i.e. natural ground motion) and mechanical (i.e. moving quadrupole) sources. We quantify the instrumentation requirements for the reliable and reproducible operation with small offsets at the interaction points. Last but not least, we propose a novel method for the beam offset stabilization at the collision point based on the feedback from the luminosity.

  15. Disability Progression After Switching from Natalizumab to Fingolimod or Interferon Beta/Glatiramer Acetate Therapies (United States)

    Fox, Robert J.; Tyry, Tuula; Salter, Amber R.; Campagnolo, Denise


    Background: Physicians must weigh the benefits against the risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab, especially beyond 2 years. However, disability progression associated with switching therapies versus continuing natalizumab therapy after 2 years has not been fully evaluated. Methods: In this retrospective analysis using the NARCOMS Registry, disability progression (Patient-Determined Disease Steps [PDDS] scale) and physical health-related quality of life (HRQOL) worsening (12-item Short Form Health Status Survey Physical Component Score [SF-12 PCS]) were compared between participants switching to fingolimod (n = 50) or interferon beta (IFNβ)/glatiramer acetate (GA) (n = 71) therapy and those continuing natalizumab (n = 406) after 2 years or more of treatment (median follow-up: natalizumab, 4 years; fingolimod, 4.5 years; IFNβ/GA, 5 years). Results: Participants continuing to take natalizumab had less disability progression (mean PDDS change: natalizumab, 0.3; fingolimod, 0.6; IFNβ/GA, 0.7; P = .0036), were less likely to report disability progression (proportion with PDDS increase: natalizumab, 31%; fingolimod, 46%; IFNβ/GA, 42%; P = .0296), and had less worsening in physical HRQOL (mean SF-12 PCS change: natalizumab, −1.4; fingolimod, −2.8; IFNβ/GA, −4.6; P = .0476) than those switching treatment. Conclusions: Although all medication groups exhibited some level of worsening, switching from natalizumab treatment after 2 years was associated with increased disability progression and worsening physical HRQOL. The risk of disability progression from disease activity and the risk of PML should be considered when making natalizumab treatment decisions. PMID:27803638

  16. Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Petra Steinacker

    Full Text Available BACKGROUND: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß correlated with clinical subtypes of ALS and were of prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study including patients with ALS (N = 68 with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20, and age-matched controls (N = 40, cerebrospinal fluid (CSF levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35 were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02 and with longer disease duration (p = 0.01 and p = 0.01, respectively. CSF NfH(SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01. High CSF NfH(SMI3 was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively. The ratios CSF NfH(SMI35/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each. CSF Progranulin decreased with ongoing disease (p = 0.04. CONCLUSIONS: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP is linked to progressive neuro-axonal damage (increase of NfH(SMI35 and to progression of disease.

  17. Glucose Driven Changes in Beta Cell Identity Are Important for Function and Possibly Autoimmune Vulnerability during the Progression of Type 1 Diabetes (United States)

    Weir, Gordon C.; Bonner-Weir, Susan


    This commentary explores the hypothesis that when autoimmunity leads to a fall of beta cell mass during the progression of type 1 diabetes (T1D), rising glucose levels cause major changes in beta cell identity. This then leads to profound changes in secretory function and less well-understood changes in beta cell susceptibility to autoimmune destruction, which may influence of rate of progression of beta cell killing. PMID:28174593

  18. Progress on the Implementation of a Neutral Beam for the Lithium Tokamak eXperiment-Beta (United States)

    Merino, Enrique; Kozub, Thomas; Boyle, Dennis; Majeski, Richard; Kaita, Robert; Smirnov, Artem; Catalano, Ryan


    In the Lithium Tokamak eXperiment (LTX), good performance discharges have been achieved with reduced-recycling lithium walls. Two hydrogen neutral beams (NB) have been loaned to the LTX project by Tri-Alpha Energy, Inc. To further improve plasma parameters, one of these neutral beams is being installed as part of an upgrade to LTX (LTX-Beta). Current ohmic input power in LTX is less than 100 kW. The NB will provide core plasma fueling with up to 700 kW of injected power. Requirements for accommodating the NB include the addition of injection and beam-dump ports on the vessel, and their designs have been finalized. Progress has also been made on the NB power supplies, including the preparation of a new room to accommodate them. A description of these activities and the status of other improvements to LTX for LTX-Beta will be presented. Work supported by US DOE contracts DE-AC02- 09CH11466 and DE-AC05- 00OR22725.

  19. Physical metallurgy and magnetic behavior of Cd stabilized bcc (beta)Gd alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jinke, Tang.


    As a continuation of the research on bcc Gd-Mg alloy system by Herchenroeder and Gschneidner, the metastable bcc Gd-Cd alloys were studied with the emphasis on their metallurgical and magnetic properties. An essentially single phase alloy could be retained for Cd concentrations from 15 at. % Cd to 19 at. % Cd, which is in the vicinity of the eutectoid composition of {beta}Gd in the Gd-Cd system. The lattice constants obtained for these alloys were used to determine the lattice constant of pure bcc Gd by extrapolation to 0 at. % Cd. Good agreement between this extrapolated value and that obtained from Gd-Mg alloys by using the same method suggested the validity of such extrapolation method. Thermal stability of these metastable bcc Gd-Cd alloys was examined by using differential thermal analysis (DTA).

  20. Stabilized beta-catenin in thymic epithelial cells blocks thymus development and function. (United States)

    Zuklys, Saulius; Gill, Jason; Keller, Marcel P; Hauri-Hohl, Mathias; Zhanybekova, Saule; Balciunaite, Gina; Na, Kyung-Jae; Jeker, Lukas T; Hafen, Katrin; Tsukamoto, Noriyuki; Amagai, Takashi; Taketo, Makoto M; Krenger, Werner; Holländer, Georg A


    Thymic T cell development is dependent on a specialized epithelial microenvironment mainly composed of cortical and medullary thymic epithelial cells (TECs). The molecular programs governing the differentiation and maintenance of TECs remain largely unknown. Wnt signaling is central to the development and maintenance of several organ systems but a specific role of this pathway for thymus organogenesis has not yet been ascertained. In this report, we demonstrate that activation of the canonical Wnt signaling pathway by a stabilizing mutation of beta-catenin targeted exclusively to TECs changes the initial commitment of endodermal epithelia to a thymic cell fate. Consequently, the formation of a correctly composed and organized thymic microenvironment is prevented, thymic immigration of hematopoietic precursors is restricted, and intrathymic T cell differentiation is arrested at a very early developmental stage causing severe immunodeficiency. These results suggest that a precise regulation of canonical Wnt signaling in thymic epithelia is essential for normal thymus development and function.

  1. Cellular uptake of beta-carotene from protein stabilized solid lipid nano-particles prepared by homogenization-evaporation method (United States)

    Using a homogenization-evaporation method, beta-carotene (BC) loaded nano-particles were prepared with different ratios of food-grade sodium caseinate (SC), whey protein isolate (WPI), or soy protein isolate (SPI) to BC and evaluated for their physiochemical stability, in vitro cytotoxicity, and cel...

  2. Progress Report: Oxidation Stability Studies of Deuterated Esters. (United States)


    esterification goes to completion and hydrolysis does not occur. *i (ii) In the presence of a catalyst (p-toluene sulphonic -" acid ), a fairly low...compounds with the antioxidant. The enhancement in oxidation stability attributable to deuteration (97%) of the acid moiety of the ester appears to be these requirements. These esters exhibit very good thermal and oxidative stability at high temperatures (>2000C), excellent viscosity

  3. Locus stabilization with parallel rectilinear dot-progressions. (United States)

    Holden, E A; Chmiko, M A


    Illusory displacement measures ("straight" or "crooked") were compared for single vs parallel rectilinear light progressions in 24 educable mental retardates and 24 normals of equal MA. For both groups, frequency of perceived "straight" responses was greater for the parallel- than for the single-line progressions. It was concluded that concurrent stimulation by two proximate visual stimuli rather than the presence of supplementary interstimulus mediatory referents is sufficient to facilitate veridical perception of successive light positions. Comparable performance by the normals and retardates substantiates previous findings.

  4. Fatigue crack growth behaviors of a new burn-resistant highly-stabilized beta titanium alloy

    Institute of Scientific and Technical Information of China (English)

    WU Huan; ZHAO Yongqing; ZENG Weidong; QIAN Li


    This article presents the fatigue crack growth (FCG) behaviors of a new burn-resistant highly-stabilized beta Ti40 alloy. The FCG rotes were analyzed. The fracture surfaces and the side surfaces of the test samples were explored. The results show that frequency affects the cracking behaviors of Ti40 alloy. Temperature also plays an important role in Ti40 alloy cracking. At room temperature (25℃), when the frequency increases, the cracking rate changes a little in the range of low stress intensity factor (ΔK), while it changes significantly when ΔK is high. At 500℃, the cracking rate of Ti40 alloy changes significantly during all the course of clacking. The frequency also affects the microstructure patterns of Ti40 alloy. A number of secondary cracks appear in the area more than 200 μm from the main crack at a high ΔK when the fre-quency is 1 Hz, but only a few secondary cracks exist when the frequency is 10 Hz. Facet image is the main image of the fracture surfaces when the frequency is 1 Hz. While, ductile striation occupies most of the area of fracture surfaces when the frequency is 10 Hz.

  5. Recent progress in stability of perovskite solar cells (United States)

    Qin, Xiaojun; Zhao, Zhiguo; Wang, Yidan; Wu, Junbo; Jiang, Qi; You, Jingbi


    Perovskite solar cells have attracted significant attention in just the past few years in solar cell research fields, where the power conversion efficiency was beyond 22.1%. Now, the most important challenge for perovskite solar cells in practical applications is the stability issue. In this mini-review, we will summarize the degradation mechanism of perovskite solar cells, including the perovskite material itself and also the interfaces. While we also provide our opinion on improving the stability of perovskite solar cells. Project supported by China Huaneng Group Project High Performance Perovskite Solar Cells (No. TW-15-HJK01), the National Key Research and Development Program of China (No. 2016YFB0700700), the National 1000 Young Talent Awards, and the National Natural Science Foundation of China (No. 61574133).

  6. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.;


    sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...... for the development of therapeutic approaches to block the stromal desmoplastic reaction that likely plays an important role in the progression of multiple types of human tumors...

  7. Stabilization of Bilateral Progressive Rheumatoid Corneal Melt with Infliximab

    Directory of Open Access Journals (Sweden)

    Sheelah F. Antao


    Results. A patient with rheumatoid arthritis presented with bilateral PUK following a 2-month history of ocular discomfort and redness. His systemic prednisolone (PDN and methotrexate (MTX were increased and, despite an initial favorable response, bilateral recurrent corneal perforations ensued. Both eyes underwent cyanoacrylate glue repair, amniotic membrane transplantation (AMT, and penetrating keratoplasty (PKP. Recurrence of the disease and bilateral perforations of the second PKP in both eyes prompted administration of intravenous infliximab immediately after the fourth PKP. The disease activity rapidly settled in both eyes, and at eighteen-month followup, after 12 infliximab infusions, the PUK remains quiescent with no further graft thinning or perforation. Conclusion. Infliximab can be used to arrest the progression of severe bilateral rheumatoid PUK in cases that are refractory to conventional treatment.

  8. Stability of beta MnOOH and manganese oxide deposition from springwater. (United States)

    Hem, J.D.; Roberson, C.E.; Fournier, R.B.


    beta MnOOH is precipitated preferentially (with respect to Mn3O4) at T near 0oC when Mn2+ is oxidized in aerated aqueous solutions. Upon aging in solutions open to the atmosphere, a slurry of beta MnOOH tends to disproportionate to form MnO2 and Mn2+. In such aged solutions, Mn2+ and H+ activities can be constant, and both the oxidation reaction Mn2+ + 1/4O2(aq) + 3/2H2O rt arrow beta MnOOH(c) + 2H+ and the disproportionation reaction 2beta MnOOH(c) + 2H+ rt arrow MnO2(c) + Mn2+ + 2H2O can have positive reaction affinities. It is not possible for both reactions to be in thermodynamic equilibrium in the same system unless oxygen is almost completely absent. A value for 028DELTA Gof of -129.8 + or - 0.6 kcal/mol was obtained for beta MnOOH from experimental data by assuming that the reaction affinity for the oxidation reaction is equal to that for the disproportionation, and a value of -129.8 + or - 0.5 kcal/mol was determined by measuring the redox potentials for the postulated half-reaction MnO2(c) + H+ + e- rt arrow beta MnOOH(c) at 0o, 5o, and 15oC and extrapolating to 25oC. Both these values are consistent with laboratory observations that beta MnOOH is less stable than gamma MnOOH or Mn3O4 at 25oC. Analytical data for Mn-depositing springwater samples are consistent with a non-equilibrium model involving disproportionation of either beta MnOOH or Mn3O4. (Authors' abstract)-T.R.


    Directory of Open Access Journals (Sweden)

    Min-Yu Chang


    Inadequate calories intake will induce excessive protein catabolism, which can cause accumulation of uremic toxins and acceleration of renal failure. Increasing fats intake is an easy way to achieve adequate calories acquirement and may stabilize the progression of CKD especially in low-fat intake patients.

  10. Are angiotensin converting enzyme inhibitors superior to beta blockers in retarding progressive renal function decline?

    NARCIS (Netherlands)

    vanEssen, GG; Apperloo, AJ; Rensma, PL; Stegeman, CA; Sluiter, WJ; deZeeuw, D; deJong, PE


    We questioned the superiority of angiotensin converting enzyme (ACE) inhibitors to beta blocking drugs with regard to renal function outcome in patients with mild to moderate renal insufficiency and normal to moderately elevated blood pressure (BP). We therefore studied 89 patients in a prospective

  11. Considerations of beta and electron transport in internal dose calculations. Final progress report, 1994--1998

    Energy Technology Data Exchange (ETDEWEB)

    Bolch, W.E. [Univ. of Florida, Gainesville, FL (United States). Dept. of Nuclear and Radiological Engineering


    This research focused on the following major tasks: improved dosimetric models of the head and brain; development of improved skeletal dosimetry models; development of dosimetric techniques for nonuniform activity distributions; pediatric dosimetry phantoms and radionuclide S values; microdosimetry of beta emitters in radioimmunotherapy; and mechanisms of molecular radiation damage.

  12. Progress on Determining the alpha-beta Phase Boundary of Elemental Boron (United States)

    Ogitsu, Tadashi; Schwegler, Eric


    Recently, it was reported that the phase boundary between alpha-boron and beta-boron has been directly determined using high-pressure and temperature experiments down to P˜4GPa and T˜1400K [Scientific Reports 1, 96 (2011)]. Based on linear extrapolation of their results to lower pressure and temperature, these authors proposed that at P=0GPa alpha-boron is the stable form below about T˜933(20)K, in conflict with the recent theoretical works based on DFT total energy calculations [JACS 129, 2458 (2007); PRB 77, 064113 (2008); JACS 131, 1903 (2009) ], where it was concluded that beta-boron is the most stable at all temperature below melting temperature and down to zero Kelvin. At the talk, we show that the theoretical alpha-beta boundary obtained with a few approximations agrees well with the aforementioned experimental results within the error bars except for the lowest P, T point, and in this case, the ground state is still beta-boron [submitted]. We will also discuss on the recent experimental efforts in measuring the specific heat of boron allotropes that lead to a tentative conclusion supporting the aforementioned DFT results.

  13. K-isomers in Hf nuclei at and beyond the neutron-rich edge of {beta}-stability.

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, P.; Alarcao, R. D.; Seabury, E. H.; Walker, P. M.; Wheldon, C.; Ahmad. I.; Carpenter, M. P.; Hackman, G.; Janssens, R. V. F.; Khoo, T. L.; Nisius, D.; Reiter, P.


    New high-K isomers are populated in {sup 180,181,182}Hf nuclei via inelastic excitation and transfer reactions, using pulsed {sup 238}U beams on Hf targets. The new data explore K-hindrances for different multipolarities and the role of residual spin-spin interactions for multi-quasiparticle (qp) configurations at the neutron-rich edge of the {beta}-stability line. The mapping of 4-qp K-isomers in the A {approx} 180 region is extended into neutron-rich territory.

  14. Solid state synthesis and thermal stability of HAP and HAP - beta-TCP composite ceramic powders. (United States)

    Rao, R R; Roopa, H N; Kannan, T S


    Powders of pure beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HAP) and a biphasic composite mixture of HAP+beta-TCP were prepared by solid state reaction between two commercially available calcium-based precursors namely, tricalcium phosphate (TCP) and calcium hydroxide (Ca(OH)2). These reactants mixed in the molar ratios ranging from 3 : 0 to 3 : 4 (designated T0 to T4) in deionized water, milled and slip-cast into discs were heat treated in the temperature range of 600 degrees C to 1250 degrees C. The products formed were characterized by X-ray diffraction (XRD) and i.r. spectroscopic techniques for identification of phases formed and functional groups present in them. While tricalcium phosphate and calcium hydroxide taken in the molar ratio of 3 : 2 and 3 : 3 resulted in pure HAP when heat treated at 1000 degrees C for 8 h, the 3 : 1 and 3 : 1.5 molar ratio compositions resulted in a biphasic mixture of HAP+beta-TCP for similar heat treatments. Heat treatment of 3 : 4 molar ratio composition of tricalcium phosphate and calcium hydroxide at 1000 degrees C yielded HAP with free CaO as the secondary phase. Products of heat treatment at higher temperatures (1150 and 1250 degrees C) for even shorter duration (2 h) while not differing from the products obtained from T0 and T2 cases at 1000 degrees C (pure beta-TCP and pure HAP), change in the case of T1, T1.5, T3 and T4 to products with lesser percentages of HAP containing beta-TCP (in the case of T1 and T1.5) or CaO (in the case of T3 and T4) as the secondary phase.

  15. Comparative studies on the chemical and enzymatic stability of alpa-and beta-arbutin (United States)

    Alpha and beta arbutin are glycoside derivatives used as skin whitening agents. Both compounds interfere with tyrosinases activity in a fashion similar to their aglycone hydroquinone. Hydroquinone has been associated with ochronosis and possible carcinogenic effect. Due to their structural similarit...

  16. Long-Term Stability of Underground Operated CZT Detectors Based on the Analysis of Intrinsic $^{113}$Cd \\beta$^{-}$-Decay

    CERN Document Server

    Ebert, J; Gehre, D; Hagner, C; Heidrich, N; Klingenberg, R; Kroeninger, K; Nitsch, C; Oldorf, C; Quante, T; Rajek, S; Rebber, H; Rohatsch, K; Tebruegge, J; Temminghoff, R; Theinert, R; Timm, J; Wonsak, B; Zatschler, S; Zuber, K


    The COBRA collaboration operates a demonstrator setup at the underground facility LNGS (Laboratori Nazionali del Gran Sasso, located in Italy) to prove the technological capabilities of this concept for the search for neutrinoless double beta-decay. The setup consists of 64 $(1\\times\\!1\\times\\!1)$ cm$^{3}$ CZT detectors in CPG configuration. One purpose of this demonstrator is to test if reliable long-term operation of CZT-CPG detectors in such a setup is possible. The demonstrator has been operated under ultra low-background conditions since more than three years and collected data corresponding to an exposure of 218 kg$\\cdot$days. The presented study focuses on the long-term stability of CZT detectors by analyzing the intrinsic, fourfold forbidden non-unique $^{113}$Cd single beta-decay. It can be shown that CZT detectors can be operated stably for long periods of time and that the $^{113}$Cd single beta-decay can be used as an internal monitor of the detector performance during the runtime of the experimen...

  17. Leu85 in the beta1-beta2 linker of ASIC1 slows activation and decreases the apparent proton affinity by stabilizing a closed conformation. (United States)

    Li, Tianbo; Yang, Youshan; Canessa, Cecilia M


    Acid-sensing ion channels (ASICs) are proton-activated channels expressed in neurons of the central and peripheral nervous systems where they modulate neuronal activity in response to external increases in proton concentration. The size of ASIC1 currents evoked by a given local acidification is determined by the number of channels in the plasma membrane and by the apparent proton affinities for activation and steady-state desensitization of the channel. Thus, the magnitude of the pH drop and the value of the baseline pH both are functionally important. Recent characterization of ASIC1s from an increasing number of species has made evident that proton affinities of these channels vary across vertebrates. We found that in species with high baseline plasma pH, e.g. frog, shark, and fish, ASIC1 has high proton affinity compared with the mammalian channel. The beta1-beta2 linker in the extracellular domain, specifically by the substitution M85L, determines the interspecies differences in proton affinities and also the time course of ASIC1 macroscopic currents. The mechanism underlying these observations is a delay in channel opening after application of protons, most likely by stabilizing a closed conformation that decreases the apparent affinity to protons and also slows the rise and decay phases of the current. Together, the results suggest evolutionary adaptation of ASIC1 to match the value of the species-specific plasma pH. At the molecular level, adaptation is achieved by substitutions of nonionizable residues rather than by modification of the channel proton sensor.

  18. Association thermodynamics and conformational stability of beta-sheet amyloid beta(17-42) oligomers: effects of E22Q (Dutch) mutation and charge neutralization. (United States)

    Blinov, Nikolay; Dorosh, Lyudmyla; Wishart, David; Kovalenko, Andriy


    Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type Abeta(17-42) oligomers with different protonation states of Glu(22), as well the E22Q (Dutch) mutants. The association free energy of small beta-sheet oligomers shows near-linear trend with the dimers being thermodynamically more stable relative to the larger constructs. The linear (within statistical uncertainty) dependence of the association free energy on complex size is a consequence of the unilateral stacking of monomers in the beta-sheet oligomers. The charge reduction of the wild-type Abeta(17-42) oligomers upon protonation of the solvent-exposed Glu(22) at acidic conditions results in lowering the association free energy compared to the wild-type oligomers at neutral pH and the E22Q mutants. The neutralization of the peptides because of the E22Q mutation only marginally affects the association free energy, with the reduction of the direct electrostatic interactions mostly compensated by the unfavorable electrostatic solvation effects. For the wild-type oligomers at acidic conditions such compensation is not complete, and the electrostatic interactions, along with the gas-phase nonpolar energetic and the overall entropic effects, contribute to the lowering of the association free energy. The differences in the association thermodynamics between the wild-type Abeta(17-42) oligomers at neutral pH and the Dutch mutants, on the one hand, and the Abeta(17

  19. Versatile synthesis of PHMB-stabilized silver nanoparticles and their significant stimulating effect on fodder beet (Beta vulgaris L.). (United States)

    Gusev, Alexander А; Kudrinsky, Alexey A; Zakharova, Olga V; Klimov, Alexey I; Zherebin, Pavel M; Lisichkin, George V; Vasyukova, Inna A; Denisov, Albert N; Krutyakov, Yurii A


    Silver nanoparticles (AgNPs) are well-known bactericidal agents. However, information about the influence of AgNPs on the morphometric parameters and biochemical status of most important agricultural crops is limited. The present study reports the influence of AgNPs stabilized with cationic polymer polyhexamethylene biguanide hydrochloride (PHMB) on growth, development, and biochemical status of fodder beet Beta vulgaris L. under laboratory and greenhouse conditions. PHMB-stabilized AgNPs were obtained via sodium borohydride reduction of silver nitrate in an aqueous solution. The average diameter of thus prepared AgNPs was 10 nm. It appears that the results of experiments with laboratory-grown beets in the nanosilver-containing medium, where germination of seeds and growth of roots were suppressed, do not correlate with the results of greenhouse experiments. The observed growth-stimulating action of PHMB-stabilized AgNPs can be explained by the change of activity of oxidases and, consequently, by the change of auxins amount in plant tissues. In beets grown in the presence of PHMB-stabilized AgNPs no negative deviations of biological parameters from normal values were registered. Furthermore, the SEM/EDS examination revealed no presence of silver in the tissues of the studied plants.

  20. The Raven's progressive matrices: change and stability over culture and time. (United States)

    Raven, J


    Data relating to the stability and variation in the norms for the Raven's Progressive Matrices Test (a well-validated measure of basic cognitive functioning) for different cultural, ethnic, and socioeconomic groups on a worldwide and within-country basis are first summarized. Subsequent sections deal with variation over time. A possible explanation for the variation in norms over time and between ethnic groups within countries is offered.

  1. Progress towards precision measurements of beta-decay correlation parameters using atom and ion traps

    CERN Document Server

    Melconian, D; Fenker, B; Mehlman, M; Shidling, P D; Anholm, M; Ashery, D; Behr, J A; Gorelov, A; Gwinner, G; Olchankski, K; Smale, S


    The correlations of the decay products following the beta decay of nuclei have a long history of providing a low-energy probe of the fundamental symmetries of our universe. Over half a century ago, the correlation of the electrons following the decay of polarized 60Co demonstrated that parity is not conserved in weak interactions. Today, the same basic idea continues to be applied to search for physics beyond the standard model: make precision measurements of correlation parameters and look for deviations compared to their standard model predictions. Efforts to measure these parameters to the 0.1% level utilizing atom and ion trapping techniques are described.

  2. Altered Fibroblast Growth Factor Receptor 4 Stability Promotes Prostate Cancer Progression

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    Jianghua Wang


    Full Text Available Fibroblast growth factor receptor 4 (FGFR-4 is expressed at significant levels in almost all human prostate cancers, and expression of its ligands is ubiquitous. A common polymorphism of FGFR-4 in which arginine (Arg388 replaces glycine (Gly388 at amino acid 388 is associated with progression in human prostate cancer. We show that the FGFR-4 Arg388 polymorphism, which is present in most prostate cancer patients, results in increased receptor stability and sustained receptor activation. In patients bearing the FGFR-4 Gly388 variant, expression of Huntingtin-interacting protein 1 (HIP1, which occurs in more than half of human prostate cancers, also results in FGFR-4 stabilization. This is associated with enhanced proliferation and anchorage-independent growth in vitro. Our findings indicate that increased receptor stability and sustained FGFR-4 signaling occur in most human prostate cancers due to either the presence of a common genetic polymorphism or the expression of a protein that stabilizes FGFR-4. Both of these alterations are associated with clinical progression in patients with prostate cancer. Thus, FGFR-4 signaling and receptor turnover are important potential therapeutic targets in prostate cancer.

  3. Simultaneous stimulation of GABA and beta adrenergic receptors stabilizes isotypes of activated adenylyl cyclase heterocomplex

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    Robichon Alain


    Full Text Available Abstract Background We investigated how the synthesis of cAMP, stimulated by isoproterenol acting through β-adrenoreceptors and Gs, is strongly amplified by simultaneous incubation with baclofen. Baclofen is an agonist of δ-aminobutyric acid type B receptors [GABAB], known to inhibit adenylyl cyclase via Gi. Because these agents have opposite effects on cAMP levels, the unexpected increase in cAMP synthesis when they are applied simultaneously has been intensively investigated. From previous reports, it appears that cyclase type II contributes most significantly to this phenomenon. Results We found that simultaneous application of isoproterenol and baclofen specifically influences the association/dissociation of molecules involved in the induction and termination of cyclase activity. Beta/gamma from [GABA]B receptor-coupled Gi has a higher affinity for adenylyl cyclase isoform(s when these isoforms are co-associated with Gs. Our data also suggest that, when beta/gamma and Gαs are associated with adenylyl cyclase isoform(s, beta/gamma from [GABA]B receptor-coupled Gi retards the GTPase activity of Gαs from adrenergic receptor. These reciprocal regulations of subunits of the adenylyl cyclase complex might be responsible for the drastic increase of cAMP synthesis in response to the simultaneous signals. Conclusions Simultaneous signals arriving at a particular synapse converge on molecular detectors of coincidence and trigger specific biochemical events. We hypothesize that this phenomenon comes from the complex molecular architectures involved, including scaffolding proteins that make reciprocal interactions between associated molecules possible. The biochemistry of simultaneous signaling is addressed as a key to synaptic function.

  4. Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

    Directory of Open Access Journals (Sweden)

    Jennifer E Bruin

    Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.

  5. [Recent progress on galacto-oligosaccharides synthesis by microbial beta-galactosidase--a review]. (United States)

    Lu, Lili; Li, Zhengyi; Xiao, Min


    Galacto-oligosaccharides are among the most promising non-digestible oligosaccharides that are recognized as prebiotics. Commercial GOS are synthesized from lactose using the transglycosylation activity of beta-galactosidase from microorganisms. The structure of GOS varies with different enzyme source. The oligosaccharide yields of GOS produced by natural enzymes are generally 20%-45% and they could be improved by artificial enzyme. Reaction conditions also have effect on the oligosaccharide yield. Using enzymes in water-hydrophobic solvent mixtures or reverse micelles may improve the yield to some extent. GOS can be large-scale synthesized by packed bed reactor, plugflow reactor or membrane reactor. The glucose and lactose in the GOS products can be removed by using chromatography, enzyme oxidation, nanofiltration membrane or microbial fermentation.

  6. Cystathionine beta-synthase (CBS contributes to advanced ovarian cancer progression and drug resistance.

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    Sanjib Bhattacharyya

    Full Text Available BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA, in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

  7. Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats. (United States)

    Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi


    The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules.

  8. Insight into the stability of cross-beta amyloid fibril from molecular dynamics simulation. (United States)

    Chen, Yue; He, Yong-Jie; Wu, Maoying; Yan, Guanwen; Li, Yixue; Zhang, Jian; Chen, Hai-Feng


    Amyloid fibrils are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases such as Alzheimer's disease, type II diabetes mellitus, the transmissible spongiform encephalopathies, and prion disease. The mechanism of fibril formation is still hotly debated and remains an important open question. In this study, we utilized molecular dynamics (MD) simulation to analyze the stability of hexamer for eight class peptides. The MD results suggest that VEALYL and MVGGVV-1 are the most stable ones, then SNQNNY, followed by LYQLEN, MVGGVV-2, VQIVYK, SSTSAA, and GGVVIA. The statistics result indicates that hydrophobic residues play a key role in stabilizing the zipper interface. Single point and two linkage mutants of MVGGVV-1 confirmed that both Met1 and Val2 are key hydrophobic residues. This is consistent with the statistics analysis. The stability results of oligomer for MVGGVV-1 suggest that the intermediate state should be trimer (3-0) and tetramer (2-2). These methods can be used in stabilization study of other amyloid fibril.

  9. Improving the phase stability and oxidation resistance of beta-nickel aluminum (United States)

    Brammer, Travis Michael

    This thesis is written in an alternate format. The thesis is composed of a general introduction, four original manuscripts, and a general conclusion. References cited within each chapter are located immediately after that section. In addition, figures and tables are numbered independently within each chapter. The general introduction focuses on the driving force behind this research, and gives an overview of previous work done on nickel-based superalloys. Chapter 2 describes the preliminary experiments and how those experiments guided the rest of the thesis work. Chapter 3 deals specifically with the oxidation performance of platinum group metal (PGM) and hafnium modifications to beta-NiAl intermetallic. Chapter 4 investigates the role of grain size on the oxidation resistance of NiAl based alloys. Chapter 5 focuses on the role of melting temperature on the oxidation resistance of NiAl based alloys. Chapter 6 summarizes the important results of this study.

  10. NO-sensitive guanylyl cyclase beta1 subunit is peripherally associated to chromosomes during mitosis. Novel role in chromatin condensation and cell cycle progression. (United States)

    Pifarré, Paula; Baltrons, María Antonia; Földi, Istvan; García, Agustina


    NO-sensitive guanylyl cyclase (GC(NO)), the major NO target, is involved in important regulatory functions in the cardiovascular, gastrointestinal and central nervous systems. GC(NO) exists as heterodimers of alpha(1/2) and beta1 subunits. Deletion of the obligate beta1 dimerizing partner abrogates NO/cGMP signaling and shortens the life span of KO mice. Localization studies in the CNS have shown that beta1 is more widespread than alpha subunits and in some areas is the only GC(NO) subunit expressed, suggesting that beta1 may have GC(NO)-independent functions. GC(NO) is predominantly cytosolic, but association to membranes and other intracellular structures has been described. Here, we show localization of beta1 in cytoplasm and nucleus of cells expressing alpha subunits and GC(NO) activity (astrocytes, C6 cells), as well as in cells devoid of alpha subunits and GC(NO) activity (microglia). In both cell types beta1 associates peripherally to chromosomes in all phases of mitosis. Immunodepletion of beta1 in C6 cells enhances chromatin condensation in an in vitro assay. Moreover, silencing beta1 by siRNA induces cell cycle re-entry as determined by flow cytometry, and increases proliferation rate in a MTT-assay, whereas infection with beta1-containing adenovirus has the opposite effect. These actions are independent of cGMP formation. We postulate that beta1 is a multifunctional protein that regulates chromatin condensation and cell cycle progression, in addition to being an obligate monomer in functional GC(NO) heterodimers.

  11. Positive association between--1021TT genotype of dopamine beta hydroxylase gene and progressive behavior of injection heroin users. (United States)

    Xie, Xiaohu; Xu, Limin; Liu, Huifen; Chen, Weisheng; Zhuang, Dingding; Zhang, Jianbing; Duan, Shiwei; Zhou, Wenhua


    By balancing the ratios of dopamine and norepinephrine, dopamine beta hydroxylase (DBH) plays an important role in brain reward circuit that is involved with behavioral effects of heroin addiction. DBH -1021C/T (rs1611115) is a functional variant with strong correlation with plasma DBH activity and several nerval and psychic disorders. In the present study, we have collected 333 male cases with heroin addiction and 200 male healthy controls to explore the role of -1021C/T in heroin addiction. There is no evidence of association between -1021C/T and heroin addiction on both genotype and allele levels (P>0.05). In the injection subgroup of cases, -1021TT carriers have longer heroin addiction time (P<0.001) and higher dosage of self-administered heroin (P=0.045) than carriers with -1021CC or -1021CT, suggesting that patients with TT genotype are likely to have more progressive style of heroin users with injection route. In conclusion, our results support -1021TT genotype may be implicated with a more progressive nature of heroin addiction, although DBH -1021C/T is unlikely to be involved in the risk of heroin addiction.

  12. Phase Stability and Stress-Induced Transformations in Beta Titanium Alloys (United States)

    Kolli, R. Prakash; Joost, William J.; Ankem, Sreeramamurthy


    In this article, we provide a brief review of the recent developments related to the relationship between phase stability and stress-induced transformations in metastable body-centered-cubic β-phase titanium alloys. Stress-induced transformations occur during tensile, compressive, and creep loading and influence the mechanical response. These transformations are not fully understood and increased understanding of these mechanisms will permit future development of improved alloys for aerospace, biomedical, and energy applications. In the first part of this article, we review phase stability and discuss a few recent developments. In the second section, we discuss the current status of understanding stress-induced transformations and several areas that require further study. We also provide our perspective on the direction of future research efforts. Additionally, we address the occurrence of the hcp ω-phase and the orthorhombic α″-martensite phase stress-induced transformations.

  13. Disease stabilization of progressive olfactory neuroblastoma (esthesioneuroblastoma) under treatment with sunitinib mesylate. (United States)

    Preusser, M; Hutterer, M; Sohm, M; Koperek, O; Elandt, K; Dieckmann, K; Prayer, D; Marosi, C


    Olfactory neuroblastoma (esthesioneuroblastoma) is a rare neoplasm of the olfactory epithelium in the upper nasal cavity. Here, we report the case of a 69-year-old man who presented with massive progression of a metastatic esthesioneuroblastoma after endonasal resection, functional neck dissection, and radiotherapy of local and distant tumor relapses. After exhaustion of all conventional therapeutic options, we initiated treatment with the oral multityrosinekinase inhibitor sunitinib mesylate. Using this drug, significant improvement of clinical symptoms, disease stabilization, and recovery from Karnofsky index of 40% to 70% could be achieved in the absence of significant adverse drug effects. The patient died 15 months after initiation of sunitinib therapy due to complications of a traumatic femoral neck fracture without evidence of tumor progression. Immunohistochemical analysis of tumor tissue specimens obtained at initial surgery revealed ample expression of platelet-derived growth factor receptor (PDGFR)-b on stromal and endothelial cells. Sunitinib should be considered for palliative therapy of advanced esthesioneuroblastoma.


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    Full Text Available Low back pain (LBP is the commonest pain among individuals affecting more than half of the population. Segmental stabilization exercises gaining popularity among many treatment choices available to the therapist. Transverses abdominis (TA and Multifidi (MF are the two core muscles that were affected by LBP. This descriptive partial review study examines how various exercises recruits TA and MF? Then how do one to prognoses them progressively over short period of time? And what is the dose, volume needed? This review put an attempt to solve the above questions based on recent evidence based practice. Finally we have given exercise schedule for physiotherapists to follow.

  15. Stabilized Conversion Efficiency and Dye-Sensitized Solar Cells from Beta vulgaris Pigment

    Directory of Open Access Journals (Sweden)

    Susana Vargas


    Full Text Available Dye-Sensitized Solar Cells (DSSCs, based on TiO2 and assembled using a dye from Beta vulgaris extract (BVE with Tetraethylorthosilicate (TEOS, are reported. The dye BVE/TEOS increased its UV resistance, rendering an increase in the cell lifetime; the performance of these solar cells was compared to those prepared with BVE without TEOS. The efficiency η for the solar energy conversion was, for BVE and BVE/TEOS, of 0.89% ± 0.006% and 0.68% ± 0.006% with a current density Jsc of 2.71 ± 0.003 mA/cm2 and 2.08 ± 0.003 mA/cm2, respectively, using in both cases an irradiation of 100 mW/cm2 at 25 °C. The efficiency of the BVE solar cell dropped from 0.9 ± 0.006 to 0.85 ± 0.006 after 72 h of operation, whereas for the BVE/TEOS, the efficiency remained practically constant in the same period of time.

  16. Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium. (United States)

    Nociari, Marcelo M; Lehmann, Guillermo L; Perez Bay, Andres E; Radu, Roxana A; Jiang, Zhichun; Goicochea, Shelby; Schreiner, Ryan; Warren, J David; Shan, Jufang; Adam de Beaumais, Ségolène; Ménand, Mickaël; Sollogoub, Matthieu; Maxfield, Frederick R; Rodriguez-Boulan, Enrique


    Accumulation of lipofuscin bisretinoids (LBs) in the retinal pigment epithelium (RPE) is the alleged cause of retinal degeneration in genetic blinding diseases (e.g., Stargardt) and a possible etiological agent for age-related macular degeneration. Currently, there are no approved treatments for these diseases; hence, agents that efficiently remove LBs from RPE would be valuable therapeutic candidates. Here, we show that beta cyclodextrins (β-CDs) bind LBs and protect them against oxidation. Computer modeling and biochemical data are consistent with the encapsulation of the retinoid arms of LBs within the hydrophobic cavity of β-CD. Importantly, β-CD treatment reduced by 73% and 48% the LB content of RPE cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively. Furthermore, intravitreal administration of β-CDs reduced significantly the content of bisretinoids in the RPE of DKO animals. Thus, our results demonstrate the effectiveness of β-CDs to complex and remove LB deposits from RPE cells and provide crucial data to develop novel prophylactic approaches for retinal disorders elicited by LBs.

  17. Stability and design criteria studies for compressed air energy storage reservoirs. Progress report, FY 1977.

    Energy Technology Data Exchange (ETDEWEB)

    Smith, G.C.; Stottlemyre, J.A.; Wiles, L.E.; Loscutoff, W.V.; Pincus, H.J.


    Progress made during FY-1977 in establishing design criteria to ensure the successful operation and long-term stability of Compressed Air Energy Storage (CAES) reservoirs in underground porous media, such as aquifers is summarized. The formulation of pertinent criteria is important since the long-term stability of air storage reservoirs is probably the item of greatest risk to the successful demonstration and commercialization of the CAES concept. The study has been divided into four phases: (1) state-of-the-art survey, (2) analytical modeling studies, (3) laboratory studies, and (4) field testing. The first of these phases, the state-of-the-art survey for air storage in porous reservoirs, has been completed on schedule and is reported in Section 2. Sections 3 and 4 are progress reports on Phases 2 and 3. No work has been done on Phase 4. It is planned that the field testing phase of this study will be carried out in conjunction with the Department of Energy/Electric Power Research Institute (DOE/EPRI) CAES Demonstration Program. This phase is not scheduled to begin until FY-1979.

  18. The astrophysical r-process and its dependence on properties of nuclei far from stability beta strength functions and neutron capture rates

    CERN Document Server

    Klapdor-Kleingrothaus, H V; Metzinger, J; Oda, T; Thielemann, F K


    It is shown that the astrophysical r-process and the question of its site are very sensitive to 'standard' nuclear physics parameters like the beta decay properties and neutron capture rates. Since for these quantities in almost all r-process calculations up to now, and also in all estimates of the production rates of chronometric pairs, only very rough assumptions have been made, it is attempted to present procedures which put the calculation of these quantities for nuclei far from stability on a reliable physical basis. This is done by a microscopic description of the beta strength function and by using a statistical model based on a 'next to first principles' optical potential including effects of deformation for the neutron capture rates. The beta -decay rates for approximately 6000 nuclei between the beta -stability line and the neutron drip line are calculated. The heavy element synthesis by explosive He burning then is calculated using these beta -rates and using realistic star models treating the supe...

  19. G beta gamma signaling reduces intracellular cAMP to promote meiotic progression in mouse oocytes. (United States)

    Gill, Arvind; Hammes, Stephen R


    In nearly every vertebrate species, elevated intracellular cAMP maintains oocytes in prophase I of meiosis. Prior to ovulation, gonadotropins trigger various intra-ovarian processes, including the breakdown of gap junctions, the activation of EGF receptors, and the secretion of steroids. These events in turn decrease intracellular cAMP levels in select oocytes to allow meiotic progression, or maturation, to resume. Studies suggest that cAMP levels are kept elevated in resting oocytes by constitutive G protein signaling, and that the drop in intracellular cAMP that accompanies maturation may be due in part to attenuation of this inhibitory G protein-mediated signaling. Interestingly, one of these G protein regulators of meiotic arrest is the Galpha(s) protein, which stimulates adenylyl cyclase to raise intracellular cAMP in two important animal models of oocyte development: Xenopus leavis frogs and mice. In addition to G(alpha)(s), constitutive Gbetagamma activity similarly stimulates adenylyl cyclase to raise cAMP and prevent maturation in Xenopus oocytes; however, the role of Gbetagamma in regulating meiosis in mouse oocytes has not been examined. Here we show that Gbetagamma does not contribute to the maintenance of murine oocyte meiotic arrest. In fact, contrary to observations in frog oocytes, Gbetagamma signaling in mouse oocytes reduces cAMP and promotes oocyte maturation, suggesting that Gbetagamma might in fact play a positive role in promoting oocyte maturation. These observations emphasize that, while many general concepts and components of meiotic regulation are conserved from frogs to mice, specific differences exist that may lead to important insights regarding ovarian development in vertebrates.

  20. Pazopanib treatment slows progression and stabilizes disease in patients with taxane-resistant cutaneous angiosarcoma. (United States)

    Ogata, Dai; Yanagisawa, Hiroto; Suzuki, Kenji; Oashi, Kohei; Yamazaki, Naoya; Tsuchida, Tetsuya


    Although cutaneous angiosarcoma (cAS) has one of the worst prognoses among malignant skin tumors, few effective drug options for secondary treatment have been discovered to date because of the limited number of cases. Therefore, this study was aimed at determining pazopanib's potential as a new cAS treatment option. We retrospectively evaluated five patients with taxane-resistant unresectable cAS treated with pazopanib at a university hospital. Their characteristics and treatment outcomes were retrieved from their records. Progression-free survival (PFS), overall survival (OS), disease progression, and toxicity were evaluated; furthermore, the response to pazopanib was assessed in relation to the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). The median PFS from the time of pazopanib initiation was 94 days. Two patients showed partial response, two showed stable disease, and one had progressive disease in the case of the best overall response. VEGFR-2 expression was positive in all cases, and patients with high expression had improved median OS compared to that in those with low expression. VEGFR-2 expression was correlated with a longer OS. The most common toxicities were hypertension and anorexia followed by myelosuppression. This is the largest case series reported wherein pazopanib was used for taxane-resistant cAS. Although the cytoreductive effect and survival benefits were not significant in this small sample, we consider pazopanib a valid treatment option for preserving patients' quality of life. Our results suggest pazopanib treatment slows the progression of disease and stabilizes it in patients with taxane-resistant cAS.

  1. Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation - a systematic computational study.

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    Anna Kahler

    Full Text Available Amyloid-[Formula: see text] (A[Formula: see text] oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: see text] oligomerization can lead to protofilaments and protofilament pairs via oligomer elongation and oligomer association, respectively. Small fibrillar oligomers adopt the protofilament topology, whereas fibrils contain at least protofilament pairs. To date, the underlying growth mechanism from oligomers to the mature fibril still remains to be elucidated. Here, we performed all-atom molecular dynamics simulations in explicit solvent on single layer-like protofilaments and fibril-like protofilament pairs of different size ranging from the tetramer to the 48-mer. We found that the initial U-shaped topology per monomer is maintained over time in all oligomers. The observed deviations of protofilaments from the starting structure increase significantly with size due to the twisting of the in-register parallel [Formula: see text]-sheets. This twist causes long protofilaments to be unstable and leads to a breakage. Protofilament pairs, which are stabilized by a hydrophobic interface, exhibit more fibril-like properties such as the overall structure and the twist angle. Thus, they can act as stable conformational templates for further fibril growth. Key properties like the twist angle, shape complementarity, and energetics show a size-dependent behavior so that small oligomers favor the protofilament topology, whereas large oligomers favor the protofilament pair topology. The region for this conformational transition is at the size of approximately twelve A[Formula: see text] monomers. From that, we propose the following growth mechanism from A[Formula: see text] oligomers to fibrils: (1 elongation of short protofilaments; (2 breakage of large protofilaments; (3 formation of short protofilament pairs; and (4 elongation of protofilament pairs.

  2. Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation - a systematic computational study. (United States)

    Kahler, Anna; Sticht, Heinrich; Horn, Anselm H C


    Amyloid-[Formula: see text] (A[Formula: see text]) oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: see text] oligomerization can lead to protofilaments and protofilament pairs via oligomer elongation and oligomer association, respectively. Small fibrillar oligomers adopt the protofilament topology, whereas fibrils contain at least protofilament pairs. To date, the underlying growth mechanism from oligomers to the mature fibril still remains to be elucidated. Here, we performed all-atom molecular dynamics simulations in explicit solvent on single layer-like protofilaments and fibril-like protofilament pairs of different size ranging from the tetramer to the 48-mer. We found that the initial U-shaped topology per monomer is maintained over time in all oligomers. The observed deviations of protofilaments from the starting structure increase significantly with size due to the twisting of the in-register parallel [Formula: see text]-sheets. This twist causes long protofilaments to be unstable and leads to a breakage. Protofilament pairs, which are stabilized by a hydrophobic interface, exhibit more fibril-like properties such as the overall structure and the twist angle. Thus, they can act as stable conformational templates for further fibril growth. Key properties like the twist angle, shape complementarity, and energetics show a size-dependent behavior so that small oligomers favor the protofilament topology, whereas large oligomers favor the protofilament pair topology. The region for this conformational transition is at the size of approximately twelve A[Formula: see text] monomers. From that, we propose the following growth mechanism from A[Formula: see text] oligomers to fibrils: (1) elongation of short protofilaments; (2) breakage of large protofilaments; (3) formation of short protofilament pairs; and (4) elongation of protofilament pairs.

  3. A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells (United States)


    308. 3. Gussow D, Rein R, Ginjaar I, et al. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J...microglobulin. Biochemistry 1973;12:4811–22. 3. Gussow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, et al. The human beta 2...Beta(2)-microglobulin and bone cell metabo- lism. Nephrol Dial Transplant 2001;16:1108–11. 34. Mundy GR. Metastasis to bone: causes, consequences

  4. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression

    Institute of Scientific and Technical Information of China (English)

    Wan Junhu; Chin Y Eugene; Zhang Hongquan; Zhan Jun; Li Shuai; Ma Ji; Xu Weizhi; Liu Chang; Xue Xiaowei; Xie Yuping; Fang Weigang


    Enhancer of zeste homolog 2 ( EZH2 ) is a key epigenetic regulator that catalyzes the trimethyla-tion of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associat-ed factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 ( PRC2 ) . Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients pre-dicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acety-lation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.

  5. Progressive taxation as a tool for providing the budget system stability

    Directory of Open Access Journals (Sweden)

    Margarita A. Vakhtina


    Full Text Available Objective to consider the alternative additional sources of income of the state budget in the framework of the action plan of the Russian government to provide socioeconomic stability of the country in 2016. Methods comparative and dynamic analysis classification and typology description and measurements including using the tools of institutional Economics the data were interpreted using tables. Results it is shown that due to the lack of financial resources the government has to make unpopular decisions that reduce the level of social support of the population for the near future. The adopted laws stipulating the principles of address character and needs when providing regional measures of social support increase the risks of poverty and inequality. The analysis has been made of the ranking position of Russia and member countries of the Organization for Economic Cooperation and Development in terms of GDP per capita human development index and quality of life index. The article grounds the need for institutional change to facilitate transition to progressive taxation and redistribution of the tax burden from the poor and middle classes to the super rich. The flat personal income tax rate has not led to the desired results of growing tax revenues in the budget. Russia is still among the top ten states with the largest tax evasion losses. The weak redistributive mechanisms including a flat scale of personal income tax regressive social security contributions and low property taxes lead to stagnation inequality underfunding of education and health. Scientific novelty the article proves the conclusion about need of institutional transformations associated with changing the current tax policy priorities. The transition to a progressive scale of income and wealth taxation promotes the transfer of tax burden from the middle and poor to the rich. These measures can provide a double economic effect. On the one hand the principle of effective taxation

  6. Role of the beta subunit of casein kinase-2 on the stability and specificity of the recombinant reconstituted holoenzyme

    DEFF Research Database (Denmark)

    Meggio, F; Boldyreff, B; Marin, O;


    Recombinant human alpha subunit from casein kinase-2 (CK-2) was subjected, either alone or in combination with recombinant human beta subunit, to high temperature, tryptic digestion and urea treatment. In all three cases, it was shown that the presence of the beta subunit could drastically reduce...

  7. Cross-strand coupling of a beta-hairpin peptide stabilized with an Aib-Gly turn studied using isotope-edited IR spectroscopy. (United States)

    Huang, Rong; Setnicka, Vladimir; Etienne, Marcus A; Kim, Joohyun; Kubelka, Jan; Hammer, Robert P; Keiderling, Timothy A


    Isotope-edited IR spectroscopy was used to study a series of singly and doubly 13C=O-labeled beta-hairpin peptides stabilized by an Aib-Gly turn sequence. The double-labeled peptides have amide I' IR spectra that show different degrees of vibrational coupling between the 13C-labeled amides due to variations in the local geometry of the peptide structure. The single-labeled peptides provide controls to determine frequencies characteristic of the diagonal force field (FF) contributions at each position for the uncoupled 13C=O modes. Separation of diagonal FF and coupling effects on the spectra are used to explain the cross-strand labeled spectral patterns. DFT calculations based on an idealized model beta-hairpin peptide correctly predict the vibrational coupling patterns. Extending these model results by consideration of frayed ends and the hairpin conformational flexibility yields an alternate interpretation of details of the spectra. Temperature-dependent isotopically labeled IR spectra reveal differences in the thermal stabilities of the individual isotopically labeled sites. This is the first example of using an IR-based isotopic labeling technique to differentiate structural transitions at specific sites along the peptide backbone in model beta-hairpin peptides.

  8. Analysis of beta-catenin, Ki-ras, and microsatellite stability in azoxymethane-induced colon tumors of BDIX/Orl Ico rats

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Kobaek-Larsen, Morten; Bonne, Anita


    The aim of the study reported here was to investigate whether the azoxymethane (AOM)-induced colon cancer rat model mimics the human situation with regard to microsatellite stability, changes in expression of beta-catenin, and/or changes in the sequence of the proto-oncogene Ki-ras. Colon cancer...... was undertaken. The animals were euthanized 28 to 29 weeks after the first AOM injection, and tumor specimens were taken for histologic and DNA analyses. Since microsatellite variation was found in only a few (... is in accordance with those of similar studies in other rat models and with most human colorectal cancers. Immunohistochemical analyses of beta-catenin did not reveal loss of gene activity, nor did the sequencing of Ki-ras reveal mutations. These results are in contrast to most findings in comparable rat studies...

  9. Effect of hydroxypropyl-beta-cyclodextrin on the solubility, stability and in-vitro release of ciprofloxacin for ocular drug delivery. (United States)

    Bozkir, Asuman; Denli, Zeynep Fusun; Basaran, Berrin


    Eye drops in the form of an aqueous solution with a lower viscosity are preferred for local administrations in ophthalmology. In ophthalmic formulations, cyclodextrins (CDs) are frequently used in recent years in order to increase water solubility, stability and bioavailability of an active substance and decrease an irritation to the eye. The scope of the present study was to investigate the influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the solubility, stability and in vitro release of ciprofloxacin (CIP). According to the phase solubility studies, A(L) type solubility curve was obtained. HPCD improved the solubility of CIP 3 times at pH 5.5 and 2 times at pH 7.4. The two month stability studies indicated that CIP was more stable at pH 5.5 than at pH 7.4 and the stability of CIP was significantly increased by HPCD. The stability constant of the HPCD:CIP complex was increased further by a-ddition of 0.1% (w/v) polymer (HPMC and PVP) to the aqueous medium including HPCD. Stability constant of solutions prepared in an ultrasonic water bath was higher than solutions prepared by heating in an autoclave. The results indicated that the CIP:HPCD complex increased in vitro release of CIP and the addition of polymer promoted this increase even more.

  10. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.;


    mediate some of the transforming effects that result from cyclin D1 overexpression in human breast cancers. MMTV-DIK2 cancer cells express the hepatocyte growth factor (HGF) receptor, c-Met. MMTV-D1K2 cancer cells also secrete transforming growth factor beta (TGF beta), but are relatively resistant to TGF......Cyclin D1/cyclin-dependent kinase 2 (Cdk2) complexes are present at high frequency in human breast cancer cell lines, but the significance of this observation is unknown. This report shows that expression of a cyclin D1-Cdk2 fusion protein under the control of the mouse mammary tumor virus (MMITV...... beta antiproliferative effects. Fibroblasts derived from MMTV-DIK2 tumors secrete factors that stimulate the proliferation of MMTV-D1K2 cancer cells, stimulate c-Met tyrosine phosphorylation, and stimulate the phosphorylation of the downstream signaling intermediates p70(s6k) and Akt on activating...

  11. Differential distribution of striatal [{sup 123}I]{beta}-CIT in Parkinson`s disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Messa, C.; Volonte, M.A.; Fazio, F.; Zito, F.; Carpinelli, A.; D`Amico, A.; Rizzo, G.; Moresco, R.M.; Paulesu, E.; Franceschi, M.; Lucignani, G. [INB-CNR, University of Milan, H San Raffaele Institute of Milan (Italy)


    Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-{beta}-carboxymethoxy-3-{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT) is important for the assessment of disease severity and progression in patients with Parkinson`s disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [{sup 123}I]{beta}-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24{+-}2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3``). ANOVA revealed a global reduction of V3`` in all ROIs of PD and PSP patients compared with normal controls (P<0.0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3`` caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [{sup 123}I]{beta}-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with

  12. beta-Arrestin 1 and 2 stabilize the angiotensin II type I receptor in distinct high-affinity conformations

    DEFF Research Database (Denmark)

    Sanni, S J; Hansen, J T; Bonde, M M;


    The angiotensin II type 1 (AT(1)) receptor belongs to family A of 7 transmembrane (7TM) receptors. The receptor has important roles in the cardiovascular system and is commonly used as a drug target in cardiovascular diseases. Interaction of 7TM receptors with G proteins or beta-arrestins often...

  13. Relative stability of major types of beta-turns as a function of amino acid composition: a study based on Ab initio energetic and natural abundance data. (United States)

    Perczel, András; Jákli, Imre; McAllister, Michael A; Csizmadia, Imre G


    Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly.

  14. Simulation of infrared spectra for beta-hairpin peptides stabilized by an Aib-Gly turn sequence: correlation between conformational fluctuation and vibrational coupling. (United States)

    Kim, Joohyun; Huang, Rong; Kubelka, Jan; Bou Rcaron, Petr; Keiderling, Timothy A


    Vibrational spectra of a 12-residue beta-hairpin peptide, RYVEVBGKKILQ (HBG), stabilized by an Aib-Gly turn sequence (B = Aib) were investigated theoretically using a combination of molecular dynamics (MD) and density functional theory (DFT) calculations. Selected conformations of HBG were extracted from a classical MD trajectory and used for spectral simulations. DFT calculations, based on the Cartesian coordinate spectral property transfer protocol, were carried out for peptide structures in which all residues are replaced with Ala, except for the Aib and Gly residues, but the backbone (phi, psi, omega) structure of the original configuration is retained. The simulations provide a basis for interpretation of the HBG amide I infrared spectra in terms of structural variables such as detailed secondary structure and thermal conformational fluctuation as well as vibrational coupling as indicated by spectra of 13C isotope-labeled variants. The characteristic amide I band shape of such small beta-hairpin peptides appears to arise from the structure of the short antiparallel beta-sheet strands. The role of structural parameter fluctuation in vibrational coupling is evaluated by comparison of DFT-derived amide coupling constants for selected configurations and from transition dipole coupling calculations of coupling parameters between (13)C isotopically labeled residues for a MD-derived ensemble of configurations. Calculated results were compared with the experimentally obtained spectra for several (13)C isotope-labeled peptides of this sequence.

  15. Research Progress on Stabilizers Nanosuspensions%纳米混悬剂中稳定剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄平; 毛坤军; 王雪婷; 黄道明; 叶颖俊


    As a new preparation technique, nanosuspensions play an important role on improving the dissolution and bioavailability of poorly soluble drug. The research progress on physical stability of nanosuspensions, the types of stabilizers and the mechanism of action were discussed, which could provide reference value for selecting the appropriate stabilizers to prepare nanosuspensions with good stability and high bioavailability. The physical stability of nanosuspensions is a complex and difficult process, but in the near future, with the deepening of the particle stability theory research and the establishment of the stabilizer high-throughput screening method, the physical stability of nanosuspensions will be solved.%纳米混悬剂作为一种新的制剂技术,在提高难溶性药物的溶出度和生物利用度等方面发挥了重要作用。本文对纳米混悬剂的物理稳定性问题、稳定剂的种类、作用机理等方面进行了综述,这为选择合适的稳定剂,制备稳定性好、生物利用度高的纳米混悬剂提供了参考价值。纳米混悬剂的物理稳定性研究是一个复杂且艰辛的过程,相信在不久的将来,随着微粒稳定理论研究的深入和稳定剂高通量筛选方法的建立,纳米混悬剂的物理稳定性的难题一定能够迎刃而解。

  16. Stabilization of the cyclin-dependent kinase 5 activator, p35, by paclitaxel decreases beta-amyloid toxicity in cortical neurons. (United States)

    Li, Guibin; Faibushevich, Alexander; Turunen, Brandon J; Yoon, Sung Ok; Georg, Gunda; Michaelis, Mary L; Dobrowsky, Rick T


    One hallmark of Alzheimer's disease (AD) is the formation of neurofibrillary tangles, aggregated paired helical filaments composed of hyperphosphorylated tau. Amyloid-beta (Abeta) induces tau hyperphosphorylation, decreases microtubule (MT) stability and induces neuronal death. MT stabilizing agents have been proposed as potential therapeutics that may minimize Abeta toxicity and here we report that paclitaxel (taxol) prevents cell death induced by Abeta peptides, inhibits Abeta-induced activation of cyclin-dependent kinase 5 (cdk5) and decreases tau hyperphosphorylation. Taxol did not inhibit cdk5 directly but significantly blocked Abeta-induced calpain activation and decreased formation of the cdk5 activator, p25, from p35. Taxol specifically inhibited the Abeta-induced activation of the cytosolic cdk5-p25 complex, but not the membrane-associated cdk5-p35 complex. MT-stabilization was necessary for neuroprotection and inhibition of cdk5 but was not sufficient to prevent cell death induced by overexpression of p25. As taxol is not permeable to the blood-brain barrier, we assessed the potential of taxanes to attenuate Abeta toxicity in adult animals using a succinylated taxol analog (TX67) permeable to the blood-brain barrier. TX67, but not taxol, attenuated the magnitude of both basal and Abeta-induced cdk5 activation in acutely dissociated cortical cultures prepared from drug treated adult mice. These results suggest that MT-stabilizing agents may provide a therapeutic approach to decrease Abeta toxicity and neurofibrillary pathology in AD and other tauopathies.

  17. Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a

    Directory of Open Access Journals (Sweden)

    Miller David H


    Full Text Available Abstract S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS is based on data obtained from a randomized, controlled trial of Interferon β-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon β-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon β-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

  18. The Majorana Demonstrator: Progress towards showing the feasibility of a 76Ge neutrinoless double-beta decay experiment

    Energy Technology Data Exchange (ETDEWEB)

    Finnerty, P.; Aguayo, Estanislao; Amman, M.; Avignone, Frank T.; Barabash, Alexander S.; Barton, P. J.; Beene, Jim; Bertrand, F.; Boswell, M.; Brudanin, V.; Busch, Matthew; Chan, Yuen-Dat; Christofferson, Cabot-Ann; Collar, J. I.; Combs, Dustin C.; Cooper, R. J.; Detwiler, Jason A.; Doe, P. J.; Efremenko, Yuri; Egorov, Viatcheslav; Ejiri, H.; Elliott, S. R.; Esterline, James H.; Fast, James E.; Fields, N.; Fraenkle, Florian; Galindo-Uribarri, A.; Gehman, Victor M.; Giovanetti, G. K.; Green, M.; Guiseppe, Vincente; Gusey, K.; Hallin, A. L.; Hazama, R.; Henning, Reyco; Hoppe, Eric W.; Horton, Mark; Howard, Stanley; Howe, M. A.; Johnson, R. A.; Keeter, K.; Kidd, M. F.; Knecht, A.; Kochetov, Oleg; Konovalov, S.; Kouzes, Richard T.; LaFerriere, Brian D.; Leon, Jonathan D.; Leviner, L.; Loach, J. C.; Looker, Q.; Luke, P.; MacMullin, S.; Marino, Michael G.; Martin, R. D.; Merriman, Jason H.; Miller, M. L.; Mizouni, Leila; Nomachi, Masaharu; Orrell, John L.; Overman, Nicole R.; Perumpilly, Gopakumar; Phillips, David; Poon, Alan; Radford, D. C.; Rielage, Keith; Robertson, R. G. H.; Ronquest, M. C.; Schubert, Alexis G.; Shima, T.; Shirchenko, M.; Snavely, Kyle J.; Steele, David; Strain, J.; Timkin, V.; Tornow, Werner; Varner, R. L.; Vetter, Kai; Vorren, Kris R.; Wilkerson, J. F.; Yakushev, E.; Yaver, Harold; Young, A.; Yu, Chang-Hong; Yumatov, Vladimir


    The Majorana Demonstrator will search for the neutrinoless double-beta decay (0*) of the 76Ge isotope with a mixed array of enriched and natural germanium detectors. The observation of this rare decay would indicate the neutrino is its own anti-particle, demonstrate that lepton number is not conserved, and provide information on the absolute mass-scale of the neutrino. The Demonstrator is being assembled at the 4850 foot level of the Sanford Underground Research Facility in Lead, South Dakota. The array will be contained in a lowbackground environment and surrounded by passive and active shielding. The goals for the Demonstrator are: demonstrating a background rate less than 3 counts tonne -1 year-1 in the 4 keV region of interest (ROI) surrounding the 2039 keV 76Ge endpoint energy; establishing the technology required to build a tonne-scale germanium based double-beta decay experiment; testing the recent claim of observation of 0; and performing a direct search for lightWIMPs (3-10 GeV/c2).

  19. Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Alexander W Lange

    Full Text Available The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth factor-beta (TGF-beta-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-beta1-mediated transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.

  20. Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats


    Niu Wen; Zhao Peng-Tao; Dong Ming-Qing; Dong Hai-Ying; Wang Yan-Xia; Xu Min; Zhang Bo; Wang Jing; Liu Yi; Luo Ying; Xu Dun-Quan; Liu Man-Ling; Gao Yu-Qi; Li Zhi-Chao


    Abstract Background Pulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27kip1, one of critical cyclin-dependent kinase inhibitors, has been shown to mediate anti-proliferation effects on various vascular cells. Beta-estradiol (β-E2) has numerous biological protective effects including attenuation of hypoxic pulmonary hypertension (HPH). In the present study, we employed β-E2 to investigate the roles of p27kip1 and its closely-related kinase (Skp-2) in the...

  1. [small beta]-Turn mimetic-based stabilizers of protein-protein interactions for the study of the non-canonical roles of leucyl-tRNA synthetase

    DEFF Research Database (Denmark)

    Kim, Chanwoo; Jung, Jinjoo; Thanh Tung, Truong;


    in the nutrient-dependent mTORC1 signalling pathway. Western blot analysis of phosphorylated S6K1 as well as FRET-based imaging confirmed that 5c3,9 stabilizes the direct interaction between LRS and RagD and activates mTORC1 in live cells under leucine-deprived conditions. Thus, 5c3,9 can be used as a new......For the systematic perturbation of protein-protein interactions, we designed and synthesized tetra-substituted hexahydro-4H-pyrazino[2,1-c][1,2,4]triazine-4,7(6H)-diones as [small beta]-turn mimetics. We then devised a new synthetic route to obtain [small beta]-turn mimetic scaffolds via tandem N......-acyliminium cyclization and constructed a 162-member library of tetra-substituted pyrazinotriazinediones with an average purity of 90% using a solid-phase parallel synthesis platform. Each library member was subjected to ELISA-based modulator screening for the LRS-RagD interaction, which plays a pivotal role...

  2. Processed beetroot (Beta vulgaris L. as a natural antioxidant in mayonnaise: Effects on physical stability, texture and sensory attributes

    Directory of Open Access Journals (Sweden)

    Vassilios Raikos


    Full Text Available The oxidative and physical stability of the reformulated mayonnaise with processed beetroot was investigated and compared with a control (mayonnaise without beetroot and a commercially available product. Processing of beetroot had an impact on the structural integrity of the antioxidants present. Microwaving (960 W for 7 min was advantageous for preserving the betalain and polyphenol content of beetroot compared to roasting (180 °C for 90 min and boiling (100 °C for 30 min. The oxidative stability of mayonnaise samples was determined by Rancimat and the thiobarbituric (TBA assay. The addition of microwaved beetroot significantly enhanced the oxidative stability of mayonnaise at the end of a storage period of 4 weeks (4 °C. Although no significant differences (P > 0.05 were detected between the mayonnaise samples containing beetroot and the commercial control, the latter was less susceptible to oxidation during storage. The turbiscan stability index (TSI revealed that the commercial mayonnaise was less prone to destabilization phenomena. All the textural parameters increased with the incorporation of beetroot. The sensory evaluation revealed that, with the exception of graininess and uniformity, most of the sensory attributes are preserved if not improved with the addition of beetroot.

  3. Detoxification of the estertin stabilizer bis-([beta]-carbobutoxyethyl)tin dichloride in rats by hydrolysis of the ester bond

    NARCIS (Netherlands)

    Penninks, A. H.; Seinen, W.


    In a previous comparative toxicity study with alkyltin and estertin stabilizers, it was recognized that estertim compounds displayed in vitro lymphocytotoxic effects comparable to the dialkyltin compounds, but did not induce lymphoid atrophy when administered in vivo to rats as was found for the dia

  4. Progress Toward a Stabilization and Preconditioning Protocol for Polycrystalline Thin-Film Photovoltaic Modules

    Energy Technology Data Exchange (ETDEWEB)

    del Cueto, J. A.; Deline, C. A.; Rummel, S. R.; Anderberg, A.


    Cadmium telluride (CdTe) and copper indium gallium diselenide (CIGS) thin-film photovoltaic (PV) modules can exhibit substantial variation in measured performance depending on prior exposure history. This study examines the metastable performance changes in these PV modules with the goal of establishing standard preconditioning or stabilization exposure procedures to mitigate measured variations prior to current-voltage (IV) measurements.

  5. A longitudinal investigation into the progression of dynamic postural stability performance in adolescents. (United States)

    Holden, Sinéad; Boreham, Colin; Doherty, Cailbhe; Wang, Dana; Delahunt, Eamonn


    Adolescent female athletes have a higher incidence of certain non-contact lower limb injuries compared to their male counterparts. Decreased postural stability is an established risk factor for lower limb injuries; however developmental-related sex differences in postural stability during adolescence have not been investigated. The objectives of this study were to longitudinally examine changes over time, and potential sex differences in dynamic postural stability performance in adolescents. One hundred and eighty four adolescent athletes participated (mean age=13±0.34 years). Participants were assessed, using the Star Excursion Balance Test (SEBT) at baseline (T1) and at 6 (T2), 12 (T3), 18 (T4) and 24 (T5) months. At each time-point, participants performed 3 trials of the anterior, posterior-medial and posterior-lateral directions of the SEBT on each limb. Reach distance for each direction was averaged across the 3 trials normalised to leg length. General linear mixed model analyses were carried out on each of the dependant variables (reach directions) with sex and time as the categorical independent variables. There was a significant sex×time interaction for the posterior-lateral reach distance scores. There were no significant sex×time interactions for any of the other reach directions. Males increased performance on the posterior-lateral reach direction from T1 to T5, while females only increased performance until T3. Young males and females demonstrate diverging postural stability profiles during adolescence.

  6. Once-weekly 22microg subcutaneous IFN-beta-1a in secondary progressive MS: a 3-year follow-up study on brain MRI measurements and serum MMP-9 levels

    DEFF Research Database (Denmark)

    Wu, X; Kuusisto, H; Dastidar, P;


    OBJECTIVE: To study the effect of weekly injected subcutaneous interferon (IFN)-beta-1a 22 microg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS). SUBJECTS...

  7. Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [{sup 123}I]{beta}-CIT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nocker, Michael; Seppi, Klaus; Wenning, Gregor K.; Poewe, Werner; Scherfler, Christoph [Innsbruck Medical University, Department of Neurology, Innsbruck (Austria); Donnemiller, Eveline; Virgolini, Irene [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria)


    We characterized the progression of dopamine transporter (DAT) decline in the striatum and extrastriatal regions including the midbrain and pons of patients with the Parkinson variant of multiple system atrophy (MSA-P) and compared longitudinally collected SPECT results with those in a cohort of patients with Parkinson's disease (PD). Eight patients with MSA-P (age 60.4 {+-} 7.7 years, disease duration 2.4 {+-} 1 years, UPDRS-III motor score 39.7 {+-} 4.7), and 11 patients with PD (age 61.2 {+-} 6.4 years, disease duration 2.4 {+-} 1.1 years, UPDRS-III motor score 18.9 {+-} 7.6) underwent a baseline and follow-up [{sup 123}I]{beta}-CIT SPECT investigation within a time period of 1.3 years. Statistical parametric mapping (SPM) and a repetitive ANOVA design were used to objectively localize the decline in DAT availability without having to make an a priori hypothesis as to its location. SPM localized significant reductions in [{sup 123}I]{beta}-CIT uptake in the dorsal brainstem of MSA-P patients compared to PD patients (p < 0.001) at baseline. Additional reductions in the DAT signal were localized in the caudate and anterior putamen of patients with MSA-P patients compared to PD patients at the follow-up examination (p < 0.001). Relative decline in tracer binding was evident in the caudate and anterior putamen of MSA-P patients compared to PD patients in the longitudinal analysis (p < 0.05), whereas no significant relative signal alteration was observed in the brainstem. In contrast to PD, the relatively higher rate of signal reduction in the caudate and anterior putamen is consistent with the faster disease progression reported in MSA-P. At baseline, the tracer uptake in the brainstem was already at very low levels in the MSA-P patients compared to that in healthy control subjects and did not progress any further, suggesting that the degeneration of monoaminergic neurons is almost complete early in the disease course. (orig.)

  8. Progress in growth of large {beta}-BaB{sub 2}O{sub 4} single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Perlov, D.; Livneh, S.; Czechowicz, P.; Goldgirsh, A.; Loiacono, D. [Advanced Crystal Group, Coherent Inc., 31 Farinella Drive, East Hanover, NJ 07936 (United States)


    Growth of large {beta}-barium borate (BBO) crystals of high optical quality has been challenging, even 25 years past its discovery. The best results in terms of size and quality have been demonstrated by means of TSSG (Top Seeded Solution Growth). Nevertheless, the maximum available size of nonlinear optical elements lags behind laser industry requirements. Due to increased size and availability, BBO finally started attracting attention for its favorable Q-switch properties. Yet, two or sometimes three crystals aligned together are still necessary to achieve the lengths often required for these applications. Material quality, in terms of optical perfection and optical absorption, is still questionable in many instances. Limited boule size still dictates relatively high material cost as well. Thorough analysis of the growth behavior of BBO helped us to develop production processes for large boules utilizing TSSG with pulling. High quality nonlinear optical crystal devices and Q-switches up to 40 mm in the z-direction have been enabled. We believe that the above size and quality are currently industry leading. (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  9. Progress in the Design of the Stabilized Liner Compressor for MTF/MIF Plasma Target Development (United States)

    Frese, Sherry; Frese, Michael; Turchi, Peter; Gale, Don


    The Stabilized Liner Compressor (SLC) seeks to extend concepts for repetitive, rotationally stabilized, liquid-metal liners driven by free-pistons to much higher drive pressures (25 vs 5 kpsi) and faster implosion speeds (2000 vs 100 m/s) than previously demonstrated. Such extension is needed to enable experiments with magnetized-plasma targets presently offering sizes and lifetimes of 10's cm diam and 10's microsec. SLC represents the confluence of several difficult technologies, including pulsed high pressures, high-speed rotating machinery and alkali-metal (Na, NaK) handling. Solution of the two-dimensional, unsteady, compressible flow of a rotating liquid-metal liner requires advanced numerical techniques. We report the use of the 2-1/2 dimensional MHD code MACH2 to explore flow options, including magnetic flux compression, and to provide pulsed pressure distributions for mechanical design. Supported by ARPA-E ALPHA Program.

  10. Tumour necrosis factor-α inhibition can stabilize disease in progressive vitiligo. (United States)

    Webb, K C; Tung, R; Winterfield, L S; Gottlieb, A B; Eby, J M; Henning, S W; Le Poole, I C


    Tumour necrosis factor (TNF)-α, a proinflammatory cytokine central to many autoimmune diseases, has been implicated in the depigmentation process in vitiligo. We review its role in vitiligo by exploring its pro- and anti-inflammatory properties and examine the effects of blocking its actions with TNF-α antagonist therapeutics in reports available in the literature. We found that TNF-α inhibition halts disease progression in patients with progressive vitiligo but that, paradoxically, treatment can be associated with de novo vitiligo development in some patients when used for other autoimmune conditions, particularly when using adalimumab and infliximab. These studies reinforce the importance of stating appropriate outcomes measures, as most pilot trials propose to measure repigmentation, whereas halting depigmentation is commonly overlooked as a measure of success. We conclude that TNF-α inhibition has proven useful for patients with progressive vitiligo, where TNF-α inhibition is able to quash cytotoxic T-cell-mediated melanocyte destruction. However, a lingering concern for initiating de novo disease will likely prevent more widespread application of TNF inhibitors to treat vitiligo.

  11. Tritiation of protein hormones. Progress report. [Stability of tritium-labelled protein hormones

    Energy Technology Data Exchange (ETDEWEB)


    A non-catalytic tritium exchange system using a microwave discharge technique was bult and calibrated in order to optomize the labelling of small organic molecules such as benzoic acid. Analytical and preparative chromatographic procedures, including ion exchange and molecular sieve chromatography and polyacrylamide gel electrophoresis, were standardized for use in the publication of tritium and labelled bovine ACTH. Results are reported from extensive studies of the control of chemical and biologic stability of labelled and unlabelled ACTH were carried out.

  12. Effects of Tetraethyl Orthosilicate (TEOS on the Light and Temperature Stability of a Pigment from Beta vulgaris and Its Potential Food Industry Applications

    Directory of Open Access Journals (Sweden)

    Gustavo A. Molina


    Full Text Available A novel, simple and inexpensive modification method using TEOS to increase the UV light, pH and temperature stability of a red-beet-pigment extracted from Beta vulgaris has been proposed. The effects on the molecular structure of betalains were studied by FTIR spectroscopy. The presence of betacyanin was verified by UV-Vis spectroscopy and its degradation in modified red-beet-pigment was evaluated and compared to the unmodified red-beet-pigment; performance improvements of 88.33%, 16.84% and 20.90% for UV light, pH and temperature stability were obtained, respectively,. Measurements of reducing sugars, phenol, and antioxidant contents were performed on unmodified and modified red-beet-pigment and losses of close to 21%, 54% and 36%, respectively, were found to be caused by the addition of TEOS. Polar diagrams of color by unmodified and modified red-beet-pigment in models of a beverage and of a yogurt were obtained and the color is preserved, although here is a small loss in the chromaticity parameter of the modified red-beet-pigment.

  13. Beta-endorphin neuron regulates stress response and innate immunity to prevent breast cancer growth and progression. (United States)

    Sarkar, Dipak K; Zhang, Changqing


    Body and mind interact extensively with each other to control health. Emerging evidence suggests that chronic neurobehavioral stress can promote various tumor growth and progression. The biological reaction to stress involves a chemical cascade initiated within the central nervous system and extends to the periphery, encompassing the immune, endocrine, and autonomic systems. Activation of sympathetic nervous system, such as what happens in the "fight or flight" response, downregulates tumor-suppressive genes, inhibits immune function, and promotes tumor growth. On the other hand, an optimistic attitude or psychological intervention helps cancer patients to survive longer via increase in β-endorphin neuronal suppression of stress hormone levels and sympathetic outflows and activation of parasympathetic control of tumor suppressor gene and innate immune cells to destroy and clear tumor cells.

  14. Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments

    Directory of Open Access Journals (Sweden)

    Viviana eCulmone


    Full Text Available Several independent studies show that accumulation of β-amyloid (Aβ peptides , one of the characteristic hallmark of Alzheimer’s Disease (AD, can affect normal neuronal activity in different ways. However, in spite of intense experimental work to explain the possible underlying mechanisms of action, a comprehensive and congruent understanding is still lacking. Part of the problem might be the opposite ways in which Aβ have been experimentally found to affect the normal activity of a neuron; for example, making a neuron more excitable (by reducing the A- or DR-type K+ currents or less excitable (by reducing synaptic transmission and Na+ current. The overall picture is therefore confusing, since the interplay of many mechanisms makes it difficult to link individual experimental findings with the more general problem of understanding the progression of the disease. This is an important issue, especially for the development of new drugs trying to ameliorate the effects of the disease. We addressed these paradoxes through computational models. We first modeled the different stages of AD by progressively modifying the intrinsic membrane and synaptic properties of a realistic model neuron, while accounting for multiple and different experimental findings and by evaluating the contribution of each mechanism to the overall modulation of the cell’s excitability. We then tested a number of manipulations of channel and synaptic activation properties that could compensate for the effects of Aβ. The model predicts possible therapeutic treatments in terms of pharmacological manipulations of channels’ kinetic and activation properties. The results also suggest how and which mechanisms can be targeted by a drug to restore the original firing conditions.

  15. Stabilization

    Directory of Open Access Journals (Sweden)

    Muhammad H. Al-Malack


    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  16. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics. (United States)

    Mateker, William R; McGehee, Michael D


    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect.

  17. Common drugs for stabilization of renal function in the progression of diabetic nephropathy and their relations with hypertension therapy. (United States)

    Wang, Yuxuan; Wang, Chengcheng; Zhang, Xiuli; Gu, Harvest F; Wu, Liang


    Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy. In this review, we first discuss the relationships between diabetic nephropathy and hypertension particularly in the renin-angiotensin-aldosterone system. We then summarize chemical structures, pharmacological characteristics and clinical studies of the common drugs used for treatment of diabetic nephropathy, while these drugs have effects against hypertension. This review may provide the constructive information for further drug development in diabetic nephropathy.

  18. Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway

    Directory of Open Access Journals (Sweden)

    Du Jin-Xing


    Full Text Available Abstract Background Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078, and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1 plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL. However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD. Methods A liver fibrosis model was induced by ligation of the common bile duct (BDL in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFβ1 signaling pathway was evaluated by western blotting and laser confocal microscopy. Results Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFβ1, and activated TGFβ1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFβ1, TGFβ1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression. Conclusion IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFβ1-Smad3 and TGFβ1-ERK1/2 signaling pathways.

  19. Beta Thalassemia (United States)

    Beta thalassemia is found in people of Mediterranean, Middle Eastern, African, South Asian (Indian, Pakistani, etc.), Southeast Asian and Chinese descent. 1 Beta Thalassemia ßß Normal beta globin genes found on chromosomes ...

  20. Subbarrier heavy ion fusion enhanced by nucleon transfer and subbarrier fusion of nuclei far from the line of {beta}-stability

    Energy Technology Data Exchange (ETDEWEB)

    Denisov, V.Yu. [Institute for Nuclear Research, Kiev (Ukraine)]|[Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany)


    We discuss a model for the description of subbarrier fusion of heavy ions which takes into account the coupling to the low-energy surface vibrational states and to the few-nucleon transfer with arbitrary reaction Q-value. The fusion reactions {sup 28,30}Si+{sup 58,62,64}Ni, {sup 40}Ca+{sup 90,96}Zr, {sup 28}S+{sup 94,100}Mo, {sup 16,18,20,22,24}O+{sup 58}Ni and {sup 28}Si+{sup 124,126,128,130,132}Sn are analyzed in detail. The model describes rather well the experimental fusion cross section and mean angular momentum for reactions between nuclei near the {beta}-stability line. It is shown that these quantities are significantly enhanced by few-nucleon transfer with large positive Q-value. A shape independent parameterization of the heavy ion potential at distances smaller then the touching point is proposed. (orig.)

  1. Increased Stability and DNA Site Discrimination of Single Chain Variants of the Dimeric beta-Barrel DNA Binding Domain of the Human Papillomavirus E2 Transcriptional Regulator

    Energy Technology Data Exchange (ETDEWEB)

    Dellarole,M.; Sanchez, I.; Freire, E.; de Prat-Gay, G.


    Human papillomavirus infects millions of people worldwide and is a causal agent of cervical cancer in women. The HPV E2 protein controls the expression of all viral genes through binding of its dimeric C-terminal domain (E2C) to its target DNA site. We engineered monomeric versions of the HPV16 E2C, in order to probe the link of the dimeric {beta}-barrel fold to stability, dimerization, and DNA binding. Two single-chain variants, with 6 and 12 residue linkers (scE2C-6 and scE2C-12), were purified and characterized. Spectroscopy and crystallography show that the native structure is unperturbed in scE2C-12. The single chain variants are stabilized with respect to E2C, with effective concentrations of 0.6 to 6 mM. The early folding events of the E2C dimer and scE2C-12 are very similar and include formation of a compact species in the submillisecond time scale and a non-native monomeric intermediate with a half-life of 25 ms. However, monomerization changes the unfolding mechanism of the linked species from two-state to three-state, with a high-energy intermediate. Binding to the specific target site is up to 5-fold tighter in the single chain variants. Nonspecific DNA binding is up to 7-fold weaker in the single chain variants, leading to an overall 10-fold increased site discrimination capacity, the largest described so far for linked DNA binding domains. Titration calorimetric binding analysis, however, shows almost identical behavior for dimer and single-chain species, suggesting very subtle changes behind the increased specificity. Global analysis of the mechanisms probed suggests that the dynamics of the E2C domain, rather than the structure, are responsible for the differential properties. Thus, the plastic and dimeric nature of the domain did not evolve for a maximum affinity, specificity, and stability of the quaternary structure, likely because of regulatory reasons and for roles other than DNA binding played by partly folded dimeric or monomeric conformers.

  2. Proceedings of the US-Japan workshop and the satellite meeting of ITC-9 on physics of high beta plasma confinement in innovative fusion system

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Seiichi; Yoshimura, Satoru [eds.


    The US-Japan Workshop on Physics of High Beta Plasma Confinement in Innovative Fusion System was held jointly with the Satellite Meeting of ITC-9 at National Institute for Fusion Science (NIFS), Toki-city during December 14-15, 1998. This proceedings book includes the papers of the talks given at the workshop. These include: Theoretical analysis on the stability of field reversed configuration (FRC) plasmas; Theory and Modeling of high {beta} plasmas; Recent progressive experiments in high {beta} systems; Formation of high {beta} plasmas using merging phenomenon; Theory and Modeling of a FRC Fusion Reactor. The 15 papers are indexed individually. (J.P.N.)

  3. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis


    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  4. Long-term progression and therapeutic response of visceral metastatic disease non-invasively monitored in mouse urine using beta-human choriogonadotropin secreting tumor cell lines. (United States)

    Francia, Giulio; Emmenegger, Urban; Lee, Christina R; Shaked, Yuval; Folkins, Christopher; Mossoba, Miriam; Medin, Jeffrey A; Man, Shan; Zhu, Zhenping; Witte, Larry; Kerbel, Robert S


    Historically, the use of mouse models of metastatic disease to evaluate anticancer therapies has been hampered because of difficulties in detection and quantification of such lesions without sacrificing the mice, which in turn may also be dictated by institutional or ethical guidelines. Advancements in imaging technologies have begun to change this situation. A new method to non-invasively measure tumor burden, as yet untested to monitor spontaneous metastases, is the use of transplanted tumors expressing secretable human beta-chorionic gonadotropin (beta-hCG) that can be measured in urine. We describe examples of beta-hCG-transfected tumor cell lines for evaluating the effect of different therapies on metastatic disease, which in some cases involved monitoring tumor growth for >100 days. We used beta-hCG-tagged mouse B16 melanoma and erbB-2/Her-2-expressing human breast cancer MDA-MB-231 models, and drug treatments included metronomic low-dose cyclophosphamide chemotherapy with or without a vascular endothelial growth factor receptor 2-targeting antibody (DC101) or trastuzumab, the erbB-2/Her-2-targeting antibody. Both experimental and spontaneous metastasis models were studied; in the latter case, an increase in urine beta-hCG always foreshadowed the development of lung, liver, brain, and kidney metastases. Metastatic disease was unresponsive to DC101 or trastuzumab monotherapy treatment, as assessed by beta-hCG levels. Our results also suggest that beta-hCG levels may be set as an end point for metastasis studies, circumventing guidelines, which have often hampered the use of advanced disease models. Collectively, our data indicates that beta-hCG is an effective noninvasive preclinical marker for the long term monitoring of untreated or treated metastatic disease.

  5. Applied Beta Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Rich, B.L.


    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  6. Drosophila insulin and target of rapamycin (TOR pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo

    Directory of Open Access Journals (Sweden)

    Parisi Federica


    Full Text Available Abstract Background Genetic studies in Drosophila melanogaster reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways. Results Our biochemical studies show that insulin induces Myc protein accumulation in Drosophila S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3β a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3β activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia. Conclusions Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in Drosophila. At

  7. PVC用水滑石类热稳定剂的研究开发进展%Research Progress of PVC Hydrotalcites Layered Compounds Heat Stabilizer

    Institute of Scientific and Technical Information of China (English)



    The production methods, reaction mechanism and application progress of PVC hydrotalcites layered compounds (LDHs) heat stabilizer are introduced . The development direction of hydrotalcites layered compounds are pointed out.%介绍了PVC用水滑石类化合物(LDHs)热稳定剂的制备方法、作用机理以及应用进展,指出了其今后的发展方向.

  8. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation (United States)

    The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

  9. Research Progress on Oxidative Stress of Islet Beta Cells in Type 2 Diabetes Mellitus%2型糖尿病胰岛β细胞氧化应激的研究进展

    Institute of Scientific and Technical Information of China (English)

    裴晓艳; 张晓梅


    Objective:To investigate the research advancement on oxidative stress of islet beta cells in type 2 diabetes Mellitus (T2 DM).Methods:To explore the research progress on oxidative stress of islet beta cells in T2 DM from the concept of oxidative stress, the oxidative stress factors of islet beta cells and the mechanism of oxidative stress damage in islet beta cells.Results: Because of lower level of antioxidant system in beta cells of islet in T2 DM, oxidative stress will easily occur during metabolic process of hyperglycaemia and hyperlipemia.Oxidative stress impairs β - cell function through many approaches, decreases insulin synthesis and secretion, aggravates T2 DM.Conclusions: Oxidative stress will easily occur in beta cells and it is a complex progress as a result of many factors and pathways.Antioxidant application can protect β - cell function, prevent and treat the incidence and growth of T2 DM.%目的:探讨2型糖尿病(T2DM)胰岛β细胞氧化应激的研究进展.方法:从氧化应激的概念、胰岛β细胞发生氧化应激的因素、氧化应激损伤胰岛β细胞的机制三方面来探讨T2DM胰岛β细胞氧化应激的研究进展.结果:T2DM胰岛β细胞内含有较低水平的抗氧化系统, 在高糖、高脂等作用下,容易发生氧化应激反应, 氧化应激通过多种途径损伤胰岛β细胞, 使胰岛素合成分泌减少,加重T2DM.结论:T2DM胰岛β细胞容易发生氧化应激是多因素多途径共同作用的复杂过程,积极应用抗氧化剂治疗,能保护胰岛β细胞功能,预防和治疗T2DM的发生与发展.

  10. CIP2A modulates cell-cycle progression in human cancer cells by regulating the stability and activity of Plk1. (United States)

    Kim, Jae-Sung; Kim, Eun Ju; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu


    Abnormal cell-cycle control can lead to aberrant cell proliferation and cancer. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is an inhibitor of protein phosphatase 2A (PP2A) that stabilizes c-Myc. However, the precise role of CIP2A in cell division is not understood. Herein, we show that CIP2A is required for mitotic progression by regulating the polo-like kinase (Plk1). With mitotic entry, CIP2A translocated from the cytoplasm to the nucleus, where it was enriched at spindle poles. CIP2A depletion delayed mitotic progression, resulting in mitotic abnormalities independent of PP2A activity. Unexpectedly, CIP2A interacted directly with the polo-box domain of Plk1 during mitosis. This interaction was required to maintain Plk1 stability by blocking APC/C-Cdh1-dependent proteolysis, thereby enhancing the kinase activity of Plk1 during mitosis. We observed strong correlation and in vivo interactions between these two proteins in multiple human cancer specimens. Overall, our results established a novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development.

  11. Responsiveness of the double limb lowering test and lower abdominal muscle progression to core stabilization exercise programs in healthy adults: a pilot study. (United States)

    Haladay, Douglas E; Miller, Sayers J; Challis, John H; Denegar, Craig R


    Low back pain (LBP) is one of the most prevalent and expensive health care problems in the United States. Studies suggest that stabilization exercise may be effective in the management of people with LBP. To accurately assess the effect of stabilization programs on muscle performance, clinicians need an objective measure that is both valid and reliable. The purpose of this study was to determine whether the double limb lowering test (DLLT) and lower abdominal muscle progression (LAMP) can detect a change in abdominal muscle performance after stabilization exercises. Eleven healthy participants (4 men and 7 women) were randomly assigned to either a specific stabilization exercise (SSE) or general stabilization exercise (GSE) group and were evaluated by the DLLT and LAMP before, during, and at the end of 8 weeks of training. Subjects attended exercise sessions twice per week over 8 weeks. No significant difference in pretest performance existed between the 2 groups. No significant difference was detected with the DLLT for either the SSE or GSE over time or when groups were combined. The LAMP detected a significant difference for the combined groups and GSE but not SSE over time. These data indicate that the LAMP is sensitive to change after a spinal stabilization program, whereas the DLLT does not detect a change after these programs. Furthermore, the GSE was more effective in producing these changes. Additional testing of these assessments is necessary to further validate these tests and to identify specific populations for which these tests may be most appropriate.

  12. Reseaech progress on the application of beta blockers in cancer%β受体阻滞剂在癌症中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    房晶雪; 程刚


    Beta blockers were the first-line drugs for the treatment of hypertension. In recent years,studies had shown that beta blockers was benefit for the survival of cancer patients,but there is a controversial. This article reviewed the uses of beta blockers in cancer in preclinical studies and clinical researches over the last three years, in order to study the role of beta blockers in cancer.%β受体阻滞剂是治疗高血压的一线药物. 近年研究表明,β受体阻滞剂的使用对癌症患者的生存有益,但存在一定的争议性. 本文回顾了近3年来β受体阻滞剂在癌症中应用的临床前研究和临床研究进展,为更好地研究β受体阻滞剂在癌症中的作用提供帮助.

  13. TiO/sub 2/ and CdS colloids stabilized by. beta. -cyclodextrins: tailored semiconductor-receptor systems as a means to control interfacial electron-transfer processes

    Energy Technology Data Exchange (ETDEWEB)

    Willner, I.; Eichen, Y.


    The photocatalytic activity of semiconductor particles is of substantial interest in synthesis as well as a means of solar energy conversion and storage. Electron-transfer reactions such as charge ejection or charge injection at semiconductor - solution interfaces are important factors that control the photocatalytic activity of the semiconductors. Electrostatic attraction of solute to the semiconductor surface has improved charge ejection from the excited semiconductor to solute relays. Adsorption of dyes to the semiconductor surface, i.e., by hydrophobic interactions, resulted in effective charge injection to the semiconductor and consequently the photocatalytic activity of semiconductors operative in the UV region could be shifted to the visible absorption spectrum. Substantial efforts have also been directed in recent years toward the preparation of semiconductor particles in colloidal forms to improve their light harvesting and interfacial electron-transfer properties. Stabilization of semiconductor colloids by polymers, microemulsions, and vesicle encapsulation has been reported. Here they report on a novel method for stabilizing semiconductor colloids by ..beta..-cyclodextrin (..beta..-CD).

  14. The MAJORANA DEMONSTRATOR: Progress towards showing the feasibility of a tonne-scale 76Ge neutrinoless double-beta decay experiment

    CERN Document Server

    Finnerty, P; Amman, M; Avignone., F T; Barabash, A S; Barton, P J; Beene, J R; Bertrand, F E; Boswell, M; Brudanin, V; Busch, M; Chan, Y -D; Christofferson, C D; Collar, J I; Combs, D C; Cooper, R J; Detwiler, J A; Doe, P J; Efremenko, Yu; Egorov, V; Ejiri, H; Elliott, S R; Esterline, J; Fast, J E; Fields, N; Fraenkle, F M; Galindo-Uribarri, A; Gehman, V M; Giovanetti, G K; Green, M P; Guiseppe, V E; Gusey, K; Hallin, A L; Hazama, R; Henning, R; Hoppe, E W; Horton, M; Howard, S; Howe, M A; Johnson, R A; Keeter, K J; Kidd, M F; Knecht, A; Kochetov, O; Konovalov, S I; Kouzes, R T; LaFerriere, B D; Leon, J; Leviner, L E; Loach, J C; Luke, P N; MacMullin, S; Marino, M G; Martin, R D; Merriman, J H; Miller, M L; Mizouni, L; Nomachi, M; Orrell, J L; Overman, N R; Perumpilly, G; Phillips., D G; Poon, A W P; Radford, D C; Rielage, K; Robertson, R G H; Ronquest, M C; Schubert, A G; Shima, T; Shirchenko, M; Snavely, K J; Steele, D; Strain, J; Timkin, V; Tornow, W; Varner, R L; Vetter, K; Vorren, K; Wilkerson, J F; Yakushev, E; Yaver, H; Young, A R; Yumatov., C-H Yu and V


    The MAJORANA DEMONSTRATOR will search for the neutrinoless double-beta decay of the 76Ge isotope with a mixed array of enriched and natural germanium detectors. The observation of this rare decay would indicate the neutrino is its own anti-particle, demonstrate that lepton number is not conserved, and provide information on the absolute mass-scale of the neutrino. The DEMONSTRATOR is being assembled at the 4850 foot level of the Sanford Underground Research Facility in Lead, South Dakota. The array will be contained in a low-background environment and surrounded by passive and active shielding. The goals for the DEMONSTRATOR are: demonstrating a background rate less than 3 t$^{-1}$ y$^{-1}$ in the 4 keV region of interest (ROI) surrounding the 2039 keV 76Ge endpoint energy; establishing the technology required to build a tonne-scale germanium based double-beta decay experiment; testing the recent claim of observation of neutrinoless double-beta decay [H. V. Klapdor-Kleingrothaus and I. V. Krivosheina, Mod. Ph...

  15. Evaluation of the geologic relations and seismotectonic stability of the Yucca Mountain area Nevada Nuclear Waste site investigation (NNWSI). Progress report, October 1, 1992--September 30, 1993

    Energy Technology Data Exchange (ETDEWEB)



    This report provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).{close_quotes} A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing Tasks. This report summarizes the geologic and seismotectonic studies conducted at Yucca Mountain during the contract period including Quaternary tectonics, an evaluation of mineral resource potential of the area, caldera geology, and volcano-tectonic activity at and near the site. A report of basinal studies conducted during the contract period is also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  16. Stability criteria for T-S fuzzy systems with interval time-varying delays and nonlinear perturbations based on geometric progression delay partitioning method. (United States)

    Chen, Hao; Zhong, Shouming; Li, Min; Liu, Xingwen; Adu-Gyamfi, Fehrs


    In this paper, a novel delay partitioning method is proposed by introducing the theory of geometric progression for the stability analysis of T-S fuzzy systems with interval time-varying delays and nonlinear perturbations. Based on the common ratio α, the delay interval is unequally separated into multiple subintervals. A newly modified Lyapunov-Krasovskii functional (LKF) is established which includes triple-integral terms and augmented factors with respect to the length of every related proportional subintervals. In addition, a recently developed free-matrix-based integral inequality is employed to avoid the overabundance of the enlargement when dealing with the derivative of the LKF. This innovative development can dramatically enhance the efficiency of obtaining the maximum upper bound of the time delay. Finally, much less conservative stability criteria are presented. Numerical examples are conducted to demonstrate the significant improvements of this proposed approach.

  17. The Progress of Polyurethane Foam Stabilizers and Suggestion%聚氨酯泡沫稳定剂发展现状及建议

    Institute of Scientific and Technical Information of China (English)



    The history of the polyurethane foam stabilizers was summarized, and the technical progress, the market and development trend were analyzed. The future research projects of stabilizers and the problem need to be solved were put forward.%概述了聚氨酯泡沫稳定剂的发展历程,重点分析了中国聚氨酯泡沫稳定剂的现状及发展趋势,提出了中国聚氨酯泡沫稳定剂的未来发展和技术攻关方向,并提出了行业需要解决的课题。

  18. {beta}-decay studies at the N=28 shell closure: indications for a weakening of the spin-orbit force far from stability?

    Energy Technology Data Exchange (ETDEWEB)

    Grevy, S. [Laboratoire de Physique Corpusculaire de Caen, IN2P3-CNRS, ENSICAEN et Universite de Caen, F-14050 Caen Cedex (France)]. E-mail:; Angelique, J.C.; Baumann, P.; Borcea, C.; Buta, A.; Canchel, G.; Catford, W.N.; Courtin, S.; Daugas, J.M.; Oliveira, F. de; Dessagne, P.; Dlouhy, Z.; Knipper, A.; Kratz, K.L.; Lecolley, F.R.; Lecouey, J.L.; Lehrsenneau, G.; Lewitowicz, M.; Lienard, E.; Lukyanov, S.; Marechal, F.; Miehe, C.; Mrazek, J.; Negoita, F.; Orr, N.A.; Pantelica, D.; Penionzhkevich, Y.; Peter, J.; Pfeiffer, B.; Pietri, S.; Poirier, E.; Sorlin, O.; Stanoiu, M.; Stefan, I.; Stodel, C.; Timis, C


    A {beta}-decay experiment on nuclei in the region of N=28 has been performed at the GANIL facility. New measured half-lives for the Si isotopes from N=25 to N=28 are reported and discussed in the light of the deformation occurring in this region. Comparison with QRPA calculations suggests that a weakening of the spin-orbit force occurs for the very neutron-rich Si isotopes.

  19. High-resolution positron Q-value measurements and nuclear-structure studies far from the stability line. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Avignone, F.T. III.


    Extensive data analysis and theoretical analysis has been done to complete the extensive decay scheme investigation of /sup 206/ /sup 208/Fr and the level structures of /sup 206/ /sup 208/Rn. A final version of a journal article is presented in preprint form. Extensive Monte Carlo calculations have been made to correct the end point energies of positron spectra taken with intrinsic Ge detectors for annihilation radiation interferences. These calculations were tested using the decay of /sup 82/Sr which has previously measured positron branches. This technique was applied to the positron spectra collected at the on-line UNISOR isotope separator. The reactions used were /sup 60/Ni(/sup 20/Ne;p2n)/sup 77/Rb and /sup 60/Ni(/sup 20/Ne;pn)/sup 78/Rb. Values for 5, ..gamma..-..beta../sup +/ coincidence positron end point energies are given for the decay of /sup 77/Rb. The implied Q-value is 5.075 +- 0.010 MeV. A complete paper on the calculated corrections is presented. A flow chart of a more complete program which accounts for positrons scattering out of the detector and for bremsstralung radiation is also presented. End-point energies of four ..beta../sup +/ branches in /sup 77/Rb are given as well as a proposed energy level scheme of /sup 75/Kr based on ..gamma..-..gamma.. coincidence data taken at UNISOR.

  20. A reaction–diffusion mechanism influences cell lineage progression as a basis for formation, regeneration, and stability of intestinal crypts

    Directory of Open Access Journals (Sweden)

    Zhang Lei


    Full Text Available Abstract Background Colon crypts, a single sheet of epithelia cells, consist of a periodic pattern of stem cells, transit-amplifying cells, and terminally differentiated cells that constantly renew and turnover. Experimental evidence suggests that Wnt signaling promotes and regulates stem cell division, differentiation, and possible cell migrations while intestinal BMP signaling inhibits stem cell self-renewal and repression in crypt formation. As more molecular details on Wnt and BMP in crypts are being discovered, little is still known about how complex interactions among Wnt, BMP, and different types of cells, and surrounding environments may lead to de novo formation of multiple crypts or how such interactions affect regeneration and stability of crypts. Results We present a mathematical model that contains Wnt and BMP, a cell lineage, and their feedback regulations to study formation, regeneration, and stability of multiple crypts. The computational explorations and linear stability analysis of the model suggest a reaction–diffusion mechanism, which exhibits a short-range activation of Wnt plus a long-range inhibition with modulation of BMP signals in a growing tissue of cell lineage, can account for spontaneous formation of multiple crypts with the spatial and temporal pattern observed in experiments. Through this mechanism, the model can recapitulate some distinctive and important experimental findings such as crypt regeneration and crypt multiplication. BMP is important in maintaining stability of crypts and loss of BMP usually leads to crypt multiplication with a fingering pattern. Conclusions The study provides a mechanism for de novo formation of multiple intestinal crypts and demonstrates a synergetic role of Wnt and BMP in regeneration and stability of intestinal crypts. The proposed model presents a robust framework for studying spatial and temporal dynamics of cell lineages in growing tissues driven by multiple signaling

  1. Recent progress report on DNA B-Z transition modulated by rare earth-amino acid complex and Alzheimer's disease amyloid beta

    Institute of Scientific and Technical Information of China (English)



    Rare earth dements have unique physical, magnetic, luminescent and catalytic properties. They have been successfully used as medicine and probes in luminescent resonance energy transfer (LRET) for bioassays, as well as reagents for diagnosis in magnetic resonance imaging (MRI). In this progress report, we will focus on recent progress on how rare earth amino complexes bind to DNA and change DNA structure, especially on DNA B-Z transition induced by rare earth amino acid complex and its potential impact on Alzheimer's disease (AD).

  2. Research Progress on Thermal Stability of Nanocrystalline Cellulose%纳米微晶纤维素热稳定性的研究进展

    Institute of Scientific and Technical Information of China (English)

    王钱钱; 朱倩倩; 孙建中; 许家兴


    纳米微晶纤维素来自天然高分子聚合物,具有成本低、强度高、轻便等特点,并可循环利用或者生物降解。纳米微晶纤维素研究倍受关注,但纳米微晶纤维素存在一些实用方面的困难。制备过程复杂、热稳定性差等是限制纳米微晶纤维素大规模商业化应用的主要的因素。本文综述了纳米微晶纤维素的热降解机理及其热稳定性影响因素,探讨了提高其热稳定性的途径。%Nanocrystalline cellulose( NCC)isolated from biomass has attracted great attention as a novel nanostructure material due to its low cost,excellent mechanical properties,biodegradability and renewability. However,there are still many challenges that need to be overcome in the application of nanocrystalline cellulose,including large-scale production of nanocrystalline cellulose and improvement of its thermal stability. This paper reviewed the mechanism of nanocrystalline cellulose thermal degradation and summarized the factors which affected its thermal stability. The progress of the methods in improving thermal stability was discussed.

  3. Role of LncRNA-activated by transforming growth factor beta in the progression of hepatitis C virus-related liver fibrosis. (United States)

    Fu, Na; Niu, Xuemin; Wang, Yang; Du, Huijuan; Wang, Baoyu; Du, Jinghua; Li, Ya; Wang, Rongqi; Zhang, Yuguo; Zhao, Suxian; Sun, Dianxing; Qiao, Liang; Nan, Yuemin


    Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-β) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages. Furthermore, increased expression level of LncRNA-ATB was also present in activated hepatic stellate cells (HSCs), and knockdown of LncRNA-ATB inhibited the expression of alpha-smooth muscle actin (α-SMA) and alpha-1 type I collagen (Col1A1). LncRNA-ATB was found to share the common miRNA responsive element of miR-425-5p with TGF-β type II receptor (TGF-βRII) and SMAD2. Ectopic expression of LncRNA-ATB in HSCs could upregulate the protein expression of TGF-βRII and SMAD2 by inhibiting the endogenous miR-425-5p. Moreover, overexpression of miR-425-5p could partly abrogate the expression of TGF-βRII and SMAD2 induced by LncRNA-ATB. Hence, we conclude that LncRNA-ATB promotes HCV-induced liver fibrogenesis by activating HSCs and increasing collagen I production through competitively binding to miR-425-5p. LncRNA-ATB may be a novel diagnostic biomarker and a potential therapeutic target for HCV-related hepatic fibrosis.

  4. Preparation and characterization for mineral elements and total dietary fiber and testing for stability of {beta}-carotene of an ARC/CL carrot powder multipurpose candidate reference material

    Energy Technology Data Exchange (ETDEWEB)

    Kumpulainen, J.T. [Agricultural Research Centre of Finland (Finland). Lab. of Food Chemistry; Hyvaerinen, H. [Agricultural Research Centre of Finland (Finland). Lab. of Food Chemistry; Haegg, M. [Agricultural Research Centre of Finland (Finland). Lab. of Food Chemistry; Plaami, S. [Agricultural Research Centre of Finland (Finland). Lab. of Food Chemistry; Tahvonen, R. [Agricultural Research Centre of Finland (Finland). Lab. of Food Chemistry


    As part of the analytical assurance system of the FAO European Cooperative Research Network on Trace Elements programme an ARC/CL-coded carrot flakes powder (CFP) candidate reference material (RM) has been prepared from a lot of commercial carrot flakes. The candidate RM has been homogenized using a Robot Coupe blender fitted with titanium blades, carefully homogenized in large teflon/polypropylene containers, bottled in 1000 numbered polyethylene containers (20 g samples) and tested for homogeneity. Interlaboratory comparison studies for 9 essential elements, cadmium and total dietary fiber (TDF) based on the AOAC-method resulted in the characterization of the contents of those compounds in the above material. After exclusion of outliers, mean values from at least nine different laboratories based altogether on three independent analytical principles have been used to calculate the recommended concentration ranges for mineral elements. Testing of homogeneity and stability for {beta}-carotene over a period of one year has been additionally carried out. The mean water content in the material amounted to 4.97% and remained stable over a one-year period. Homogeneity of the RM was within 3.0% for almost all included mineral elements as tested for a sample size of 0.5 g. The 95% confidence limits for the mean values of the established recommended concentrations of mineral elements in the present ARC/CL Carrot Powder candidate RM fell within 5% for all the other elements and TDF except for Fe (6.3%) and B (5.7%). The stability of {beta}-carotene in the present candidate RM stored in darkness over a one-year period at room temperature was within 6.3%. (orig.)

  5. Fermi surface-Brillouin-zone-induced pseudogap in {gamma}-Mg{sub 17}Al{sub 12} and a possible stabilization mechanism of {beta}-Al{sub 3}Mg{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, U [Nagoya Industrial Science Research Institute, JST Plaza-Tokai, Ahara-cho, Minami-ku, Nagoya 457-0063 (Japan); Kondo, Y; Nishino, Y [Department of Frontier Materials, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Inukai, M [Japan Synchrotron Radiation Research Institute (JASRI), SPring-8, Kouto, Sayo, Hyogo 679-5198 (Japan); Feuerbacher, M [Institut fuer Mikrostrukturforschung, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany); Sato, H, E-mail: [Department of Physics, Aichi University of Education, Kariya-shi, Aichi 448-8542 (Japan)


    The electronic structure of {gamma} phase in the system Mg{sub 17}Al{sub 12} containing 58 atoms per unit cell with space group I 4-bar 3m has been calculated by using the WIEN2k-FLAPW program package. A pseudogap is found across the Fermi level. The FLAPW-Fourier spectra at the symmetry points N and {Gamma} of the bcc Brillouin zone revealed that electronic states across the Fermi level at these symmetry points are dominated by |G|{sup 2} = 26 and 24 states corresponding to centers of {l_brace}510{r_brace} + {l_brace}431{r_brace} and {l_brace}422{r_brace} zone planes, respectively. The 1253-wave nearly-free-electron (NFE) band calculations identified that a combination of the two Fermi surface-Brillouin-zone (FsBz) interactions associated with |G|{sup 2} = 26 and 24 account well for the observed DOS pseudogap in {gamma}-Mg{sub 17}Al{sub 12}, most likely leading to the stabilization of this complex metallic compound. The {beta}-Al{sub 3}Mg{sub 2} containing 1178 atoms per cubic unit cell is suggested to be stabilized by satisfying the Hume-Rothery matching condition expressed in terms of e/uc, the number of electrons per unit cell, versus critical |G|{sup 2}. A critical |G|{sup 2} is predicted to be 200 in {beta}-Al{sub 3}Mg{sub 2}, which results in 84 Brillouin zone planes interacting almost simultaneously with a more or less spherical Fermi surface.

  6. Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease. (United States)

    Jack, Clifford R; Wiste, Heather J; Vemuri, Prashanthi; Weigand, Stephen D; Senjem, Matthew L; Zeng, Guang; Bernstein, Matt A; Gunter, Jeffrey L; Pankratz, Vernon S; Aisen, Paul S; Weiner, Michael W; Petersen, Ronald C; Shaw, Leslie M; Trojanowski, John Q; Knopman, David S


    Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer's dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer's Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer's dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were 'amyloid positive' (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were 'amyloid negative' (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan-Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter

  7. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression (United States)

    Wang, Jinliang; Liu, Shengqiang


    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  8. [Serum beta 2 microglobulin (beta 2M) following renal transplantation]. (United States)

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B


    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN.

  9. Localization of thymosin beta-4 in tumors

    DEFF Research Database (Denmark)

    Larsson, L. -I.; Holck, Susanne


    Overexpression of thymosin beta-4 has been linked to malignant progression but the localization of this polypeptide within tumors is incompletely known. We therefore examined breast cancers for thymosin beta-4 using immunofluorescence. Reactive cells were identified with monoclonal cell marker...... in the tumor microenvironment may modulate tumor behavior....

  10. miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2 in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Jialu Li

    Full Text Available The transforming growth factor beta (TGF-β signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colorectal cancer (CRC. The inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway. However, the mechanism by which cancer cells downregulate TGFBR2 is unclear. In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2. Because microRNAs (miRNAs are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target TGFBR2. We identified the specific targeting site of miR-135b in the 3'-untranslated region (3'-UTR of TGFBR2. We further identified an inverse correlation between the levels of miR-135b and TGFBR2 protein, but not mRNA, in CRC tissue samples. By overexpressing or silencing miR-135b in CRC cells, we experimentally validated that miR-135b directly binds to the 3'-UTR of the TGFBR2 transcript and regulates TGFBR2 expression. Furthermore, the biological consequences of the targeting of TGFBR2 by miR-135b were examined using in vitro cell proliferation and apoptosis assays. We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression. Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

  11. Pharmacokinetically Stabilized Cystine Knot Peptides that Bind Alpha-v-Beta-6 Integrin with Single-Digit Nanomolar Affinities for Detection of Pancreatic Cancer (United States)

    Kimura, Richard H.; Teed, Robert; Hackel, Benjamin J.; Pysz, Marybeth A.; Chuang, Courtney Z.; Sathirachinda, Ataya; Willmann, Jürgen K.; Gambhir, Sanjiv S.


    Purpose Detection of pancreatic cancer remains high priority and effective diagnostic tools are needed for clinical applications. Many cancer cells overexpress integrin αvβ6, a cell surface receptor being evaluated as a novel clinical biomarker. Experimental Design To validate this molecular target, several highly stable cystine knot peptides were engineered by directed evolution to bind specifically and with high-affinity (3-6 nM) to integrin αvβ6. The binders don’t cross-react with related integrin αvβ5, integrin α5β1 or tumor-angiogenesis associated integrin, αvβ3. Results Positron emission tomography showed that these disulfide-stabilized peptides rapidly accumulate at tumors expressing integrin αvβ6. Clinically relevant tumor-to-muscle ratios of 7.7 ± 2.4 to 11.3 ± 3.0 were achieved within one hour after radiotracer injection. Minimization of off-target dosing was achieved by reformatting αvβ6-binding activities across various natural and pharmacokinetically-stabilized cystine knot scaffolds with different amino acid content. We demonstrate that a peptide scaffold’s primary sequence directs its pharmacokinetics. Scaffolds with high arginine or glutamic acid content suffered high renal retention of > 75 percent injected dose per gram (%ID/g). Substitution of these amino acids with renally-cleared amino acids, notably serine, led to significant decreases in renal accumulation of < 20 %ID/g 1h post injection (p < 0.05, n=3). Conclusions We have engineered highly stable cystine knot peptides with potent and specific integrin αvβ6 binding activities for cancer detection. Pharmacokinetic engineering of scaffold primary sequence led to significant decreases in off-target radiotracer accumulation. Optimization of binding affinity, specificity, stability and pharmacokinetics will facilitate translation of cystine knots for cancer molecular imaging. PMID:22173551

  12. Evaluation of the geological relationships to gas hydrate formation and stability. Progress report, June 16--September 30, 1988

    Energy Technology Data Exchange (ETDEWEB)

    Krason, J.; Finley, P.


    The summaries of regional basin analyses document that potentially economic accumulations of gas hydrates can be formed in both active and passive margin settings. The principal requirement for gas hydrate formation in either setting is abundant methane. Passive margin sediments with high sedimentation rates and sufficient sedimentary organic carbon can generate large quantities of biogenic methane for hydrate formation. Similarly, active margin locations near a terrigenous sediment source can also have high methane generation potential due to rapid burial of adequate amounts of sedimentary organic matter. Many active margins with evidence of gas hydrate presence correspond to areas subject to upwelling. Upwelling currents can enhance methane generation by increasing primary productivity and thus sedimentary organic carbon. Structural deformation of the marginal sediments at both active and passive sites can enhance gas hydrate formation by providing pathways for migration of both biogenic and thermogenic gas to the shallow gas hydrate stability zone. Additionally, conventional hydrocarbon traps may initially concentrate sufficient amounts of hydrocarbons for subsequent gas hydrate formation.

  13. β受体阻滞剂在慢性心力衰竭治疗中的进展%Research Progress of Beta Receptor Blocker in Treating Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)



    The sympathetic nervous system in the patients with chronic heart failure has strong activity, with the development of disease may cause cardiovascular dysfunction, which has a high mortality. Beta receptor blockers is a potent negative inotropic drugs, was been banned for clinical treatment of chronic heart failure for a long time. But large clinical trials proved that, beta receptor blockers can inhibit nerve endocrine activity in patients with chronic heart failure, so as to prevent the progression of the disease, the curative effect on chronic heart failure is undeniable. In China, many scholars also follow the international pace of research, carried out a large number of clinical researches. The objective of this paper is to explore and analysis beta receptor blockers in treating chronic heart failure..%慢性心力衰竭患者的交感神经系统具有较强的活性,随着病情的发展可引起心血管功能失常,具有较高的死亡率。β受体阻滞剂是一种强效、负性的肌力药,有很长一段时间被禁止用于慢性心力衰竭的临床治疗。但经大量的临床试验证明,β受体阻滞剂能够抑制神经内分泌活性以防止慢性心力衰竭患者的病情发展,对慢性心力衰竭的疗效是不可否认的。在我国,很多学者也紧随国际研究的步伐,开展了大量临床研究,本文针对β受体阻滞剂在慢性心力衰竭治疗的进展问题进行探讨性分析。

  14. Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides (United States)

    Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo


    The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single

  15. Transforming growth factor-beta inhibition reduces progression of early choroidal neovascularization lesions in rats: P17 and P144 peptides.

    Directory of Open Access Journals (Sweden)

    Javier Zarranz-Ventura

    Full Text Available The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β inhibitor peptides (P17 & P144 on early laser-induced choroidal neovascularization (LI-CNV lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control, P17 (IV-17, and P144 (IV-144 groups, whereas intravitreal groups included P17 (IVT-17, P144 (IVT-144, and a mixture of both peptides (IVT-17+144 (with fellow eyes receiving vehicle alone. CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3(rd week in IVT-17 and IVT-144 groups, and also from the 2(nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144 decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising

  16. Influence of the tannic and gallic acids on stability of betacyanins from red beetroot (Beta vulgaris L. crude extract. INFLUÊNCIA DOS ÁCIDOS TÂNICO E GÁLICO NA ESTABILIDADE DE BETACIANINAS DO EXTRATO BRUTO DE BETERRABA VERMELHA (Beta vulgaris L.

    Directory of Open Access Journals (Sweden)



    Full Text Available The use of e natural colorants in the food industry is limited because to its low stability under preparation, processing and storage conditions. Techniques for natural colorant’s stabilization, such as copigmentation, have been used frequently in scientific researches. The betacyanins that belong to the groups of the betalain presents in the red beetroot and are used as colorant in food. Tannic and gallic acids were used in this study as a copigment of betacyanin crude extract from red beetroot (Beta vulgaris L.. Betacyanin stability was investigated with and without tannic and gallic acid under different storage conditions in 70% ethanol extract: concentrations of 0.925g/100mL and 0.462g/100mL, pH values 5.00±0.05 and 6.80±0.05 at temperature of 25±1ºC, in the dark and in the presence of oxygen. Results revealed that pH and tannic and gallic acid addition (p<0.05 increased significantly the betacyanins half-life time. The tannic and gallic acids provided significant increase in stability of the betacyanins pigments at both concentrations evaluated, at pH value of 5.00 ± 0.05, tannic acid being more effective.

    O uso dos corantes naturais na indústria alimentícia é limitado em função de sua baixa estabilidade frente às condições de preparação, processamento e estocagem. Técnicas de estabilização de corantes naturais, tais como a copigmentação, vem encontrando destaque em pesquisas científicas. As betacianinas (coloração vermelha violeta, pertencentes ao grupo de pigmentos naturais denominados betalaínas, são as que predominam na beterraba vermelha (Beta vulgaris L., sendo utilizadas como corante em alimentos. O objetivo do presente trabalho foi avaliar a estabilidade de betacianinas em extrato de beterraba (Beta vulgaris L. etanólico a 70% adicionadas dos ácidos orgânicos tânico e gálico, nas

  17. Research progress on storage stability of pesticide residues%农药残留储存稳定性的研究进展

    Institute of Scientific and Technical Information of China (English)

    卞艳丽; 刘丰茂


    农药残留检测对农产品安全、食品卫生有十分重要的意义。残留试验样品运送到实验室后,需要根据农药的性质以及样品类型确定储存条件和储存时间,保证在储存期内待测物的性质和含量不发生变化,确保分析结果的可靠性和科学性。国内关于农药残留储存稳定性研究的规定和储存稳定性影响机制的研究较少,而国外相关机构均对农药残留储存稳定性做了详细的规定和要求。本文综述了美国环境保护署(United States Environmental Protection Agency, EPA)、经济合作与发展组织(Organization for Economic Cooperation and Development, OECD)及联合国粮食及农业组织(Food and Agriculture Organization, FAO)等机构对农药残留储存稳定性操作指南、不同样品基质中农药残留储存稳定性研究进展和农药残留储存稳定性的影响因素,并对分析样品的储存提出了建议,以期为农药残留储存稳定性的深入研究提供参考和借鉴。%Pesticide residue analysis has great significance for agricultural products’ safety and hygiene. Experimenters should determine storage conditions according to the nature of the pesticides and the type of samples, so as to ensure that the content of analytes do not change during the storage period and the results are reliable and scientific. The domestic provisions seldom conduct the research on storage stability of pesticide residues and its influence mechanism, while abroad institutions have regulations and requirements for storage stability in detail. This review summarized the operation guide for storage stability, research progress of different samples storage stability and factors which influenced the storage stability of the United States Environmental Protection Agency (EPA), Organization for Economic Cooperation and Development (OECD) and Food and Agriculture Organization (FAO), meanwhile how to store the samples was suggested, in order to provide

  18. Research progress on storage stability of pesticide residues%农药残留储存稳定性的研究进展

    Institute of Scientific and Technical Information of China (English)

    卞艳丽; 刘丰茂


    农药残留检测对农产品安全、食品卫生有十分重要的意义。残留试验样品运送到实验室后,需要根据农药的性质以及样品类型确定储存条件和储存时间,保证在储存期内待测物的性质和含量不发生变化,确保分析结果的可靠性和科学性。国内关于农药残留储存稳定性研究的规定和储存稳定性影响机制的研究较少,而国外相关机构均对农药残留储存稳定性做了详细的规定和要求。本文综述了美国环境保护署(United States Environmental Protection Agency, EPA)、经济合作与发展组织(Organization for Economic Cooperation and Development, OECD)及联合国粮食及农业组织(Food and Agriculture Organization, FAO)等机构对农药残留储存稳定性操作指南、不同样品基质中农药残留储存稳定性研究进展和农药残留储存稳定性的影响因素,并对分析样品的储存提出了建议,以期为农药残留储存稳定性的深入研究提供参考和借鉴。%ABSTRACT:Pesticide residue analysis has great significance for agricultural products’ safety and hygiene. Experimenters should determine storage conditions according to the nature of the pesticides and the type of samples, so as to ensure that the content of analytes do not change during the storage period and the results are reliable and scientific. The domestic provisions seldom conduct the research on storage stability of pesticide residues and its influence mechanism, while abroad institutions have regulations and requirements for storage stability in detail. This review summarized the operation guide for storage stability, research progress of different samples storage stability and factors which influenced the storage stability of the United States Environmental Protection Agency (EPA), Organization for Economic Cooperation and Development (OECD) and Food and Agriculture Organization (FAO), meanwhile how to store the samples was suggested, in order to

  19. [Transforming growth factor-beta controls pathogenesis of Crohn disease]. (United States)

    Friess, H; di Mola, F F; Egger, B; Scheuren, A; Kleeff, J; Zimmermann, A; Büchler, M W


    The pathogenetic mechanisms which contribute to the progression of Crohn's disease are still not known. Transforming growth factor-beta (TGF-beta) and its subtypes are multifunctional polypeptides which regulate immunological processes as well as the synthesis of the extracellular matrix and fibrogenesis. In the present study, Crohn's disease tissue samples of 18 patients undergoing intestinal resection were analyzed by Northern blot analysis, in situ hybridization and immunostaining for TGF-beta 1-3 and the TGF-beta receptors type I-III (T beta R-I, T beta R-II, T beta R-III). There was a marked overexpression of TGF-beta 1, TGF-beta 3 and T beta R-II in 94% of the Crohn's disease tissue samples. TGF-beta 2 and T beta R-I ALK5 and T beta R-III were enhanced in 72%, 72% and 82% of the Crohn tissue samples, respectively. In situ hybridization and immunostaining revealed that there was frequent coexpression of TGF-beta with its signaling receptors. Our data indicate that TGF-beta and their receptors seem to be involved in the pathogenesis of Crohn's disease. Their enhanced expression might contribute to the increase in extracellular matrix resulting in fibrosis and subsequently in intestinal obstruction.

  20. TGF-beta as a therapeutic target in high grade gliomas - Promises and challenges

    NARCIS (Netherlands)

    Joseph, Justin V.; Balasubramaniyan, Veerakumar; Walenkamp, Annemiek; Kruyt, Frank A. E.


    Transforming growth factor-beta (TGF-beta) is a cytokine with a key role in tissue homeostasis and cancer. TGF-beta elicits both tumor suppressive and tumor promoting functions during cancer progression, in a wide range of cancers. Here, we review the tumor promoting function of TGF-beta and its pos

  1. Tandem beta-enamino ester formation and cyclization with o-alkynyl anilines catalyzed by InBr3: efficient synthesis of beta-(N-indolyl)-alpha,beta-unsaturated esters. (United States)

    Murai, Kenichi; Hayashi, Shoko; Takaichi, Nobuhiro; Kita, Yasuyuki; Fujioka, Hiromichi


    A tandem reaction providing beta-(N-indolyl)-alpha,beta-unsaturated esters from beta-keto esters and o-alkynyl anilines was developed. Z-Alkenes were selectively formed due to the stability of the beta-enamino ester as an intermediate of the reaction. This reaction includes the intermolecular beta-enamino ester formation and intramolecular cyclization catalyzed by InBr(3).

  2. Structural alterations of transforming growth factor-beta receptor genes in human cervical carcinoma

    NARCIS (Netherlands)

    Chen, TP; De Vries, EGE; Hollema, H; Yegen, HA; Vellucci, VF; Strickler, HD; Hildesheim, A; Reiss, M


    The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-beta (TGF beta)-mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGF beta resistance, w

  3. Cost-Effectiveness of Different Interferon Beta Products for Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: Decision Analysis Based on Long-Term Clinical Data and Switchable Treatments

    Directory of Open Access Journals (Sweden)

    Shekoufeh Nikfar


    Full Text Available Multiple sclerosis (MS is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000. Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF β and their copied biopharmaceuticals (CBPs and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs.Methods:A literature-based Markov model was developed to assess the cost-effectiveness of three INF βs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS. Disease progression transition probabilities for symptom management and INF β therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS. A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER of cost/quality adjusted life year (QALY for all available INF β products (brands, biosimilars and CBPs were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model.Results:ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($ respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913.Conclusions:The Markov

  4. The search for neutrinoless double beta decay

    CERN Document Server

    Gomez-Cadenas, J J; Mezzetto, M; Monrabal, F; Sorel, M


    In the last few years the search for neutrinoless double beta decay has evolved from being almost a marginal activity in neutrino physics to one of the highest priorities for understanding neutrinos and the origin of mass. There are two main reasons for this paradigm shift: the discovery of neutrino oscillations, which clearly established the existence of massive neutrinos; and the existence of an unconfirmed, but not refuted, claim of evidence for neutrinoless double decay in 76Ge. As a consequence, a new generation of experiments, employing different detection techniques and {\\beta}{\\beta} isotopes, is being actively promoted by experimental groups across the world. In addition, nuclear theorists are making remarkable progress in the calculation of the neutrinoless double beta decay nuclear matrix elements, thus eliminating a substantial part of the theoretical uncertainties affecting the particle physics interpretation of this process. In this report, we review the main aspects of the double beta decay pro...

  5. Stability in higher-derivative matter fields theories

    CERN Document Server

    Tretyakov, Petr V


    We discuss possible instabilities in higher-derivative matter fields theories. These theories has two free parameters $\\beta_1$ and $\\beta_4$. By using dynamical system approach we explicitly demonstrate that for stability of Minkowski space in expanding Universe it is need condition $\\beta_4-\\frac{1}{3}\\beta_4$ which is need to avoid tachyon-like instability.

  6. Progress in magnetically stabilized bed and magnetic catalyst%磁稳定床及磁性催化剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    鲁威; 文庆; 袁华; 吴元欣


    The research progress in the application of magnetically stabilized bed ( MSB) in the fields of petrochemical and biology was reviewed. MSB is used in catalytic hydrogenation, dust removal, dry coal separation, biochemical separation, immobilized bioreactors and culture of cells, etc. Compared with the conventional process, this novel reactor combines the advantages of fixed bed reactor and fluidized bed reactor, which can intensify the internal mass and heat transfer and improve the reaction efficiency. The design of magnetic catalyst is the key to the application of the MSB. So far,the magnetic catalysts in MSB are more commonly in coreshell structure with the magnetic core. All these catalysts have excellent magnetic properties and good catalytic performance at lower temperature. The research and development of MSB and magnetic catalyst are promising in catalyst industry.%对磁稳定床及磁性催化剂在石油化工和生物工程等领域的应用进行了归纳总结.磁稳定床已经应用于催化加氢、烟尘净化、干法选煤、生化分离、固定化生物反应器、细胞培养等过程.与传统工艺相比,磁稳定床兼有固定床和流化床的优点,能强化受传质传热限制的反应过程,提高反应效率,在实际应用中显示出独特的优越性.磁性催化剂的设计与开发是磁稳定床应用的关键,目前磁性催化剂以包覆型催化剂为主,其共同特点是具有适宜的磁性和低温反应活性,利于反应操作.磁稳定床及其磁性催化剂的研究开发是催化剂工业发展的一个新方向.

  7. 城市河流形态及稳定性演变研究进展%Progress on Urban Stream Transformation of Critical Forms and Stability Relationships

    Institute of Scientific and Technical Information of China (English)

    尹小玲; 李贵才; 刘堃; 钟愉佳


    Urban river degradation under human impacts has aroused wide attention in the areas of geography science and hydrology. But in domestic academic field there is still a lack of systematic theory study on fluvial geomorphology and process which is the important work in river restoration design. Based on the study of river geomorphology and stabilization for nearly half a century, this paper reviews the research results from the con-tent and method, summarizes the features and reasons about river changes in the process of urbanization, and an-alyzes the advantages and limitations of river classification. In conclusion, urbanization has transformed river landscapes across the Earth' s surface, caused great damage to fluvial equilibrium, and highly altered river natu-ral progress. The main parameters include river enlargement, reductions in sinuosity, an overall increase in drain- age densities, and a tendency for bed material to coarsen. The root cause of these changes is the change of hydro- logic suystem and sediment discharge regiments in that urban construction can induce river aggradation due to soil erosion at the beginning of urbanization; and accompanied by the gradual completion of the construction, channel erosion has been the main source of river sediment; and that hydrological system is upset by a decrease in the perviousness of the catchment, driven by land-use changes. Therefore, scholars have been studying the classification of river evolution on form and stability. In this paper, a summary of existing urban stream classifi-cation systems can be classified primarily into three broad types by synthesizing literature methods: form-based method, process-based method and synthesis method. Form-based method is appropriate for concluding river morphological characteristics, but the classification scheme lacks significant explanation and has a limited basis in channel processes and stability. Process-based method can provide important information at the

  8. AE activity during transient beta drops in high poloidal beta discharges (United States)

    Huang, J.; Gong, X. Z.; Ren, Q. L.; Ding, S. Y.; Qian, J. P.; Pan, C. K.; Li, G. Q.; Heidbrink, W. W.; Garofalo, A. M.; McClenaghan, J.


    Enhanced AE activity has been observed during transient beta drops in high poloidal beta DIII-D discharges with internal transport barriers (ITBs). These drops in beta are believed to be caused by n=1 external kink modes. In some discharges, beta recovers within 200 ms but, in others, beta stays suppressed. A typical discharge has βP 3, qmin 3, and q95 12. The drop in beta affects both fast ions and thermal particles, and a drop is also observed in the density and rotation. The enhanced AE activity follows the instability that causes the beta drop, is largest at the lowest beta, and subsides as beta recovers. MHD stability analysis is planned. A database study of the plasma conditions associated with the collapse will be also presented. Supported in part by the US Department of Energy under DE-FC02-04ER54698, DE-AC05-06OR23100, and by the National Natural Science Foundation of China 11575249, and the National Magnetic Confinement Fusion Program of China No. 2015GB110005.

  9. Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

    DEFF Research Database (Denmark)

    Larsen, Claus Morten; Døssing, M G; Papa, S;


    IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen...

  10. Beta-carotene (United States)

    ... patches on the tongue and mouth called oral leukoplakia. Taking beta-carotene by mouth for up to 12 months seems to decrease symptoms of oral leukoplakia. Osteoarthritis. Beta-carotene taken by mouth may prevent ...

  11. Beta-glucosidases and nucleic acids encoding same

    DEFF Research Database (Denmark)


    and pharmaceuticals. Several enzymes of the newly identified strain are efficient in degradation of lignocellulosic biomasses. In particular one enzyme has been identified and characterised as having improved beta-glucosidase activity. The identified beta-glucosidase has improved thermal stability, while maintaining...

  12. Mucosal tolerance to a combination of ApoB and HSP60 peptides controls plaque progression and stabilizes vulnerable plaque in Apob(tm2SgyLdlr(tm1Her/J mice.

    Directory of Open Access Journals (Sweden)

    Lakshmi Mundkur

    Full Text Available Oral tolerance to auto antigens reduces the development of atherosclerosis in mouse models. However, the effect of immune tolerance to multiple self antigenic peptides in plaque progression and stabilization is not known. We studied the protective effect of mucosal tolerance to peptides from apolipoprotein B (ApoB; 661-680 and heat shock protein 60 (HSP60; 153-163, in combination with diet, in the prevention of atherosclerotic lesion progression and plaque stabilization in ApoB(tm25gyLDLr(tm1Her mice. We found that oral administration of five doses of a combination of ApoB and HSP60 peptides (20 µg/mice/dose induced tolerance to both the peptides and reduced early plaque development by 39.9% better than the individual peptides (ApoB = 28.7%;HSP60 = 26.8%(P<0.001. Oral tolerance to combination of peptides along with diet modification arrested plaque progression by 37.6% which was associated with increases in T-regulatory cell and transforming growth factor-β expression in the plaque and peripheral circulation. Reduced macrophage infiltration and tumor necrosis factor-α expression in the plaque was also observed. Tolerance with continued hypercholesterolemia resulted in 60.8% reduction in necrotic core area suggesting plaque stabilization, which was supported by reduction in apoptosis and increased efferocytosis demonstrated by greater expression of receptor tyrosine kinase Mer (MerTK in the plaque. Tolerance to the two peptides also reduced the expression of matrix metalloproteinase 9, tissue factor, calprotectin, and increased its collagen content. Our study suggests that oral tolerance to ApoB and HSP60 peptide combination induces CD4(+ CTLA4(+ Tregs and CD4(+CD25(+Foxp3(+ Tregs secreting TGF-β, which inhibit pathogenic T cell response to both peptides thus reducing the development and progression of atherosclerosis and provides evidence for plaque stabilization in ApoB(tm25gyLDLr(tm1Her mice.

  13. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward......-looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...

  14. Clinical application value of urinary transforming growth factor-beta 1 in predicting IgA nephropathy progress%尿转化生长因子-β1在预测IgA肾病进展中的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    周金金; 徐家云; 彭霞; 邵叶青


    Objective Through analyzing relevance of urinary transforming growth factor-beta 1(TGF-β1)and clinicopathological characteristics of IgA nephropathy, study clinical significance of urinary TGF- beta 1 in IgAN pathogenesis and progress.Methods Choose 30 cases primary IgAN patients hospitalized in nephrology department of The First Affiliated Hospital of Henan University of Science and Technology from March 2013 to May 2015; and 5 cases healthy control subjects. Test urine TGF - 1 level by ELISA method, and test other clinical indicators including serum creatinine, urine creatinine, 24h urinary protein quantitative. Result 1 urinary TGF- beta 1/ urinary Cr ratio was higher than normal controls of IgAN patients (P<0.05); 2 urinary TGF- beta 1/urinary Cr level of IgAN patients were positively related with pathological grading, 24h urinary protein, CKD classification.Conclusion Urinary TGF- beta 1 level can be used as early molecular biological indicator of IgAN activity and progress.%目的:通过分析IgA肾病(IgAN)尿转化生长因子β1(TGF-β1)与临床病理的相关性,探讨尿TGF-β1在IgAN发病和进展中的临床意义。方法选择2013年3月至2015年5月间在河南科技大学第一附属医院肾内科住院的原发性IgAN患者30例,健康对照者5例,采用ELISA法检测尿TGF-β1水平,同时测定血、尿肌酐,24h尿蛋白定量等临床指标。结果1、IgAN患者尿TGF-β1/尿Cr比值高于正常对照者(P<0.05);2、IgAN患者尿 TGF-β1/尿Cr水平分别与病理分级、24h尿蛋白定量、CKD分期呈正相关。结论尿TGF-β1水平可作为反映IgAN活动和进展的早期分子生物学指标。

  15. Prediction of the Long Term Stability of Polyester-Based Recording Media. First Annual Report, June 1982; Second Annual Report, August 1983; Progress Report, December 1984. (United States)

    Brown, Daniel W.; And Others

    This document comprises three progress reports for a 5-year environmental aging study aimed at establishing the lifetimes of magnetic tapes and the poly(ethylene terephthalate) (PET) base of photographic and electronic film under archival storage conditions. The first annual report (1982) introduces the rationale for the project, provides…

  16. Circulating Levels of MicroRNA from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence That miR-25 Associates to Residual Beta-Cell Function and Glycaemic Control during Disease Progression

    DEFF Research Database (Denmark)

    Nielsen, Lotte B.; Wang, Cheng; Sorensen, Kaspar


    This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRN...... for tissue physiopathology and potential intervention targets....

  17. Betting against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse


    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for......, the return of the BAB factor is low. (4) Increased funding liquidity risk compresses betas toward one. (5) More constrained investors hold riskier assets....... for US equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures. (2) A betting against beta (BAB) factor, which is long leveraged low-beta assets and short high-beta assets, produces significant positive risk-adjusted returns. (3) When funding constraints tighten...

  18. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets........S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...

  19. 纳米混悬剂物理稳定性的研究进展%Progress in Physical Stability of Nanosuspensions

    Institute of Scientific and Technical Information of China (English)

    徐清; 黄琴琴; 王永禄; 李学明


    随着纳米科技的快速发展,纳米混悬剂在药剂学领域日益受到关注.纳米混悬剂是纯药物亚微米颗粒的胶状分散体系,依靠表面活性剂维持稳定.本文综述了纳米混悬剂的物理稳定性问题,包括沉淀、团聚、晶体生长和晶型变化等,概述了纳米混悬剂的稳定机制并探讨了解决其稳定性问题的主要方法.%Nanosuspensions in pharmaceutical field have been increasingly concerned with the rapid development of nanotechnology. Nanosuspensions are colloid dispersion system composed of pure drug sub-micron particles, which depend on surfactants to remain stability. The physical stabilities of nanosuspensions, including sedimentation, agglomeration, crystal growth and crystal transition are summarized in this paper. The mechanism of stability and main solutions of the problems are briefly reviewed.

  20. Research Progress of Light Stabilizer in Polymer Materials%光稳定剂在聚合物材料中的研究进展

    Institute of Scientific and Technical Information of China (English)

    池晓智; 温作杨; 邵晓林


    As the ozone hole mounting, the dangers of exposure to ultraviolet radiation on the surface of the earth for human get widely attention, and the light stabilizer is undoubtedly the most direct and effective method for the prevention and control of ultraviolet harm. Two different types of light stability additives polymer material such as the UV absorber and hindered amine light stabilizers were introduced in detail, and the synergies between those two materials were simply described.%随着臭氧空洞的日益加剧,照射到地球表面的紫外线对人类的危害这一问题被广泛关注,而光稳定剂无疑是最直接有效的防止紫外线危害的方法。本文详细介绍了紫外线吸收剂和受阻胺类光稳定剂两种不同类型的聚合物材料光稳定添加剂,并简单论述了两者之间的协同效应。

  1. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.


    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  2. Imperfect World of $\\beta\\beta$-decay Nuclear Data Sets

    CERN Document Server

    Pritychenko, B


    The precision of double-beta ($\\beta\\beta$) decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for $\\beta\\beta$-decay T$_{1/2}^{2\

  3. Zircons and fluids: An experimental investigation with applications for radioactive waste disposal. Hydrothermal stability of zircons: Progress report, January 1991--December 1991

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, A.K.; Student, J.; Essex, R.


    The long-term stability of nuclear waste forms or barriers is related to changes in physical properties of the material induced through radiation damage and subsequent changes in solubility. Investigations conducted by us on natural zircons (ZrSiO{sub 4}) supports a positive correlation between level of alpha damage and fluid composition to enhanced levels of corrosion. New data are presented on the nature and rate of the solution process. We also present data on our continuing efforts to synthesize and characterize both pure ZrSiO{sub 4} and doped with U, Th, Hf, Dy and P.

  4. 低温相变贮能材料定形技术研究进展%Research Progress in Shape-Stabilizing Technology of Low Temperature Phase Change Materials for Energy Storage

    Institute of Scientific and Technical Information of China (English)

    张艳辉; 邓建国; 黄奕刚


    Low-temperature phase Change materials have been widely applied in the fields of energy conservation and thermal control. The synthesis, compound and shape-stabilizing technology of these materials keep developing and have been a highpoint of material researches. The methods and technologies of preparing shape-stabilized phase change materials are reviewed, and the progress of porous matrix adsorption method, polymer matrix eomposited method, micro-encapsulation technology and other shape-stabilizing technology are introduced in this paper. Three aspects are the focus of micro- encapsulation technology: in-situ polymerization, interfacial polymerization and coacervation. Additionally, the advantages and disadvantages on the preparation methods are analyzed. The prospective application and development in shape-stabilized PCMs were anticipated.%低温相变贮能材料广泛应用于节能和温控领域,其合成、复配及定形技术不断发展,已成为材料研究领域的热点之一。本文综述了低温相变材料的定形方法和技术,介绍了多孔基质吸附法、聚合物基复合法、微胶囊技术以及其它定形技术的国内外研究进展,重点介绍了原位聚合、界面聚合、凝聚法3种微胶囊技术。分析了各种制备方法的优缺点,并指出了制备低温定形相变材料中存在的问题及今后发展方向,最后展望了低温定形相变贮能材料的发展前景。

  5. Ideal MHD beta-limits of poloidally asymmetric equilibria

    Energy Technology Data Exchange (ETDEWEB)

    Todd, A.M.M.; Miller, A.E.; Grimm, R.C.; Okabayashi, M.; Dalhed, H.E. Jr.


    The ideal MHD stability of poloidally asymmetric equilibria, which are typical of a tokamak reactor design with a single-null poloidal divertor is examined. As with symmetric equilibria, stability to non-axisymmetric modes improves with increasing triangularity and ellipticity, and with lower edge safety factor. Pressure profiles optimized with respect to ballooning stability are obtained for an asymmetric shape, resulting in ..beta../sub critical/ approx. = 5.7%. The corresponding value for an equivalent symmetric shape is ..beta../sub critical/ approx. = 6.5%.

  6. Negative Beta Encoder

    CERN Document Server

    Kohda, Tohru; Aihara, Kazuyuki


    A new class of analog-digital (A/D), digital-analog (D/A) converters as an alternative to conventional ones, called $\\beta$-encoder, has been shown to have exponential accuracy in the bit rates while possessing self-correction property for fluctuations of amplifier factor $\\beta$ and quantizer threshold $\

  7. Double beta decay experiments

    CERN Document Server

    Barabash, A S


    The present status of double beta decay experiments is reviewed. The results of the most sensitive experiments are discussed. Proposals for future double beta decay experiments with a sensitivity to the $$ at the level of (0.01--0.1) eV are considered.

  8. Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case report Interferon beta en polineuropatía crónica inflamatoria desmienlinizante: caso clínico

    Directory of Open Access Journals (Sweden)

    Andrés Maria Villa


    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired immune-mediated neuropathy. It presents with a course of progression which may be slow and steady or step-wise or relapsing. Sensory ataxic polyneuropathy may be the only clinical manifestation of this disease. Treatment with interferon beta1a (INF beta1a has been tried with different results in patients who were refractory to other, more conventional, immunomodulatory therapies. Here we report on a patient who had a relapsing form of pure sensory ataxic CIDP and who failed to respond to intravenous human immunoglobulin. He was put on INF beta1a for 3 years. During this period he suffered no relapses while his condition stabilized.La polineuropatía crónica inflamatoria desmielinizante (PCID es una neuropatía inmuno-mediada, que presenta un curso clínico primariamente progresivo o en forma de recaídas. Las manifestaciones sensoriales pueden ser su unica forma de expresión clínica. El tratamiento con interferon beta 1a (IFN beta1a ha sido ensayado en varias oportunidades, con diferentes respuestas terapéuticas, en pacientes refractarios a las terapias inmunomoduladoras convencionales. Nosotros comunicamos un paciente con una forma ataxica recurrente de PCID, que no respondió al tratamiento con inmunoglobulina endovenosa. Posteriormente fue tratado con IFN beta 1 a por tres años. Durante el período de seguimiento no mostró nuevas recaídas y su cuadro neurológico se estabilizó.

  9. Genetics Home Reference: beta thalassemia (United States)

    ... Understand Genetics Home Health Conditions beta thalassemia beta thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Beta thalassemia is a blood disorder that reduces the production ...

  10. Poly(ADP-ribosyl)ation enhances H-RAS protein stability and causes abnormal cell cycle progression in human TK6 lymphoblastoid cells treated with hydroquinone. (United States)

    Liu, Linhua; Ling, Xiaoxuan; Tang, Huanwen; Chen, Jialong; Wen, Qiaosheng; Zou, Fei


    Hydroquinone (HQ), one of the most important benzene-derived metabolites, can induce aberrant cell cycle progression; however, the mechanism of this induction remains unclear. Poly(ADP-ribosyl)ation (PARylation), which is catalysed primarily by poly(ADP-ribose) polymerase-1 (PARP-1), participates in various biological processes, including cell cycle control. The results of the present study show an accumulation in G1 phase versus S phase of TK6 human lymphoblast cells treated with HQ for 48h compared with PBS-treated cells; after 72h of HQ treatment, the cells transitioned from G1 arrest to S phase arrest. We examined the expression of six genes related to the cell cycle or leukaemia to further explore the reason for this phenomenon. Among these genes, H-RAS was found to be associated with this phenomenon because its mRNA and protein expression decreased at 48h and increased at 72h. Experiments for PARP activity induction and inhibition revealed that the observed PARylation was positively associated with H-RAS expression. Moreover, in cells treated with HQ in conjunction with PARP-1 knockdown, expression of the H-RAS protein decreased and the number of cells in G1 phase increased. The degree of poly(ADP-ribosyl) modification of the H-RAS protein increased in cells treated with HQ for 72h, further supporting that changes in PARylation contributed to the rapid alteration of H-RAS protein expression, followed by abnormal progression of the cell cycle. Co-immunoprecipitation (co-IP) assays were employed to determine whether protein complexes were formed by PARP-1 and H-RAS proteins, and the direct interaction between these proteins indicated that PARylation regulated H-RAS expression. As detected by confocal microscopy, the H-RAS protein was found in the nucleus and cytoplasm. To our knowledge, this study is the first to reveal that H-RAS protein can be modified by PARylation.

  11. 天然虾青素提取及其稳定性研究进展%Research Progress on Extraction and Stability of Natural Astaxanthin

    Institute of Scientific and Technical Information of China (English)

    张碧娜; 吕飞; 丁玉庭


    Because of the attractive coloring and excellent physiological function, astaxanthin had attracted a lot of attention.In this article, the extraction technology of astaxanthin and the factors affected its stability as following, own organism, environmental conditions, metal ions, antioxidants and preparation methods were compared and described.%虾青素因其诱人的感官呈色性及优良的生理功能一直备受人们的关注.因此,就有关天然虾青素的提取工艺技术与影响其稳定性的因素,如生物体自身、环境、金属离子、抗氧化剂和制备方法等进行了比对阐述.

  12. Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hee June; Lee, Ji Min; Kim, Hyunkyung; Nam, Hye Jin; Shin, Hi-Jai R.; Kim, Dongha [Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742 (Korea, Republic of); Ko, Enyoung; Noh, Dong-Young [Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Kim, Keun Il [Department of Biological Sciences, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Jung Hwa [Department of Medical Sciences, Inha University, Incheon 402-751 (Korea, Republic of); Baek, Sung Hee, E-mail: [Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742 (Korea, Republic of)


    Research highlights: {yields} CtBP1 as a new binding partner of Bcl3. {yields} Bcl3 stabilizes CtBP1 by inhibiting ubiquitination of CtBP1. {yields} Bcl3 antagonizes CtBP1-mediated apoptotic responses. {yields} Positive correlation between increased Bcl3 and CtBP1 protein levels in breast cancer tissues. -- Abstract: B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.

  13. Rapid synthesis of beta zeolites (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng


    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  14. Indications of progressive desiccation of the Transvaal Lowveld over the past 100 years, and implications for the water stabilization programme in the Kruger National Park

    Directory of Open Access Journals (Sweden)

    U. De V. Pienaar


    Full Text Available All available rainfall statistics recorded for the Kruger National Park area since 1907, coupled with an analysis of all the historical climatological data on hand, appear to confirm the quasi-twenty-year rainfall oscillation in precipitation pattern for the summer rainfall area. This was first pointed out by Tyson & Dyer (1975. The dendrochronological data obtained by Hall (1976 from a study of growth rings of a very old yellowwood tree (Podocarpus falcatus in Natal, also appear to indicate a superimposed, long-term (80-100 years pattern of alternate below- average and above-average rainfall periods. The historical data relating to climate in the park, during the past century or two, seem to bear out such a pattern. If this can be confirmed, it will be an enormous aid not only in wildlife-management planning, but also to agriculturists, demographic planners and others. It would appear that the long, relatively dry rainfall period of 1860-1970, with its concomitant progressive desiccation of the @ area in question, has passed over into the next aboveverage rainfall era. This does not mean that there will be no further cataclysmic droughts during future rainfall trough periods. It is therefore wise to plan ahead to meet such contingencies. The present water distribution pattern in the park (natural plus artificial water is conspicuously still well below that which pertained, during dry seasons, at the turn of the century, when the Sabi and Shingwedzi game reserves were proclaimed. It is the declared policy of the National Parks Board of Trustees to simulate natural regulating mechanisms as closely as possible. In consequence the artificial water-for-game program is a long way from completion. The large numbers of game animals in the park (including dominant species such as elephant Loxodonta africana and buffalo Syncerus coffer can no longer migrate out of the area to escape natural catastrophes (such as the crippling droughts of 1911-1917, the

  15. Progress in use of beta-blockers for cardiovascular diseases%β受体阻滞剂在心血管疾病中的应用进展

    Institute of Scientific and Technical Information of China (English)




  16. The classification , clinical usage and its progress of beta-blocker%β-受体阻滞药的分类、临床应用及其进展

    Institute of Scientific and Technical Information of China (English)

    刘万车; 方立梅; 胡少红; 谷雨; 张冬梅; 刑春阳


    The application of beta-blocker is unfailing for more than forty years, furthermore its indica-tion is magnified continually, which make it play very important role in the treatment of caxdiovascular diseases. In order to master the elassfication , clinical application and the recent research better, we write this overview by summarizeing articles at home and abroad.%β-受体阻滞药的应用40多年来久用不衰,而且适应证不断拓宽,使其在心血管疾病的治疗中起着十分重要的作用,为更好地掌握其分类、临床应用及其进展,本文结合国内外文献作一综述.

  17. Alpha-beta bidirectional associative memories


    María Elena Acevedo Mosqueda; Cornelio Yáñez Márquez


    Most models of Bidirectional associative memories intend to achieve that all trained pattern correspond to stable states; however, this has not been possible. Also, none of the former models has been able to recall all the trained patterns. In this work we introduce a new model of bidirectional associative memory which is not iterative and has no stability problems. It is based on the Alpha-Beta associative memories. This model allows perfect recall of all trained patterns, with no ambiguity ...

  18. Crystalline Morphology, Mechanical Properties and Fatigue Stability of Isotactic Polypropylene in the Presence of Alpha- and Beta-nucleating Agents%聚丙烯结晶形态与力学性能及其疲劳稳定性

    Institute of Scientific and Technical Information of China (English)

    石小丽; 倪清兰; 王飞


    The modification of crystallinity morphology of isotactic polypropylene ( IPP) by using alpha- and beta-nucleating agents was conducted with Haake rheometer at high temperature. The crystalline morphology and mechanical properties of the modified IPP prior to and after dynamic fatigue experiment were investigated with polarized light microscopy, x-rays diffraction and tensile test. Crystalline stress was released and tensile strength was increased slightly during initial fatigue period for alpha-nulceated IPP while no crystalline stress was found, the degree of crystallization was decreased, and tensile strength was increased after short fatigue period for beta-nulceated IPP. The transition under dynamic load was still found for alpha-nulceated IPP but to much less extent for the case of beta-nulceated IPP.%基于Haake转矩流变仪,分别将α和β成核剂熔混到等规聚丙烯中以改变其结晶形态.用偏光显微镜法、X射线衍射法和力学性能测试方法研究了疲劳作用前后α晶和β晶相互转变及其结构性能.实验结果表明:α成核剂在降低球晶尺寸和增加结晶度同时,在晶胞内产生了内应力,在疲劳初期,结晶应力消除、拉伸强度增加,继续疲劳时,结晶度和拉伸强度都下降,疲劳后,β含量相对增加.当β成核剂用量较少时,β晶含量增加,拉伸强度降低;在β晶结晶度适中时,疲劳并不改变晶胞结构与结晶度,表现较好的耐疲劳性;结晶度较高时,疲劳降低了结晶度,但拉伸强度有所增加.

  19. 爆破震动及结构面渐进破坏对边坡稳定性影响%Influence of blasting vibration and structural plane progressive failure on slope stability

    Institute of Scientific and Technical Information of China (English)

    任月龙; 才庆祥; 舒继森; 周伟; 韩流


    为了研究爆破震动及结构面渐进破坏对于边坡稳定性的影响,掌握爆破震动过程中的致损机理及稳定系数变化规律,根据结构面抗剪强度退化机理,明确了渐进破坏过程中抗剪强度变化规律;结合爆破动载荷的作用机理,修正了震动条件下抗滑力、下滑力的计算公式;基于此,推导出了平面和折面滑坡模式的时效稳定系数计算方法,并对哈尔乌素露天矿北端帮边坡稳定性进行研究。结果表明:结构面完好和贯通时的稳定系数分别为1.348和1.173。结构面渐进破坏过程中,边坡稳定系数呈线性递减,且递减的速度与岩体的黏聚力C呈正比;爆破震动作用下,边坡时效稳定系数以初始稳定系数为中心,响应震动加速度上下波动;爆破震动和结构面渐进损伤耦合作用下,边坡时效稳定系数在波动变化的同时呈现整体下滑趋势。%In order to investigate the impact of blasting vibration and structural surface damage on slope stability and the stability coefficient variation and undermining mechanism during blasting pro-cess, the research gets the law of the shear strength variation during under mining process with the deg-radation mechanism for shear strength in structural surface as the basis. In combination with the mecha-nism of blasting dynamic loading, calculation formula of both sliding and sliding resistance forces under the condition of fixed vibration were corrected. The calculation methods of timeliness stability coeffi-cient for planar and folding landslide models are deduced and applied to the study of the north slope stability at Haerwusu Surface Coal Mine. The results show that stability factors are 1.348 and 1.173 for intact structural surface and damaged structural surface respectively. In addition, the slope stability co-efficient decreases linearly during the slope undermining progress while the decreasing speed is propor-tional to the

  20. 丹参注射剂的配伍稳定性研究%Research Progress of Compatibility Stability of Salvia Miltiorrhiza Injection

    Institute of Scientific and Technical Information of China (English)



    目的:为临床合理使用丹参注射剂提供参考。方法:查阅分析近年来国内医药期刊公开发表的有关丹参注射剂与其他药物间的配伍稳定性研究文献。结果:丹参注射剂与某些药物配伍后可能发生理化反应。结论:丹参注射剂应尽可能单独应用。%Objective:To provide the evidence for rational clinical use of salvia miltiorrhiza injection.Methods:The reports on Com-patible stability of salvia miltiorrhiza injection with other drugs in recent years were reviewed.Results:Some physical and chemical reac-tions occurred when salvia miltiorrhiza injection was administered with other drugs simultaneously.Conclusion:Salvia miltiorrhiza injec-tion should be used as a separate application.

  1. Stability evaluation of metal mine goaf based on improved catastrophe progression method%基于改进突变级数法的金属矿采空区稳定性评价

    Institute of Scientific and Technical Information of China (English)

    陈娇; 罗周全; 侯造水


    为了有效、科学地对金属矿采空区的稳定性进行评价,提出基于改进突变级数法的采空区稳定性分析模型。根据改进突变级数法,对影响采空区稳定的9个因素进行多层次分解,并运用主成分分析法确定各层指标的相对重要性,以获得采空区稳定性评价指标体系。为得到最后的评价结果,对数据进行归一化处理,并结合突变理论与模糊数学理论,进行综合量化运算。利用搜集的26组地下金属矿采空区数据,对该评价模型进行训练和检验。研究表明,该评价模型既有效地避免了直接使用难于确定的“权重”概念,又客观地确定了各层指标的相对重要性,其判别结果比较符合实际,为金属矿采空区稳定性评价提供了一种新方法。%In order to evaluate the goaf stability of metal mines effectively and scientifically , based on the improved catastrophe progression method , an integrative identification model for the stability classification of goaf was presen-ted.Nine control factors were selected in the analysis of multi-level objective decomposition ,and their relative im-portance were determined by analyzing measured data using principal component analysis method .According to the catastrophe theory and the fuzzy member function , the data were normalized and the catastrophic affiliated function-al value was calculated , then a catastrophe progression model was obtained to classify the stability classification of goaf .26 typical goaf cases of metal mines were collected to train and test the improved catastrophe progression mod -el.The results showed that the identification model both effectively avoids the direct use of the “weight” concept which is difficult to determine , and objectively determines the relative importance of each layer indicators .It has excellent performance and high prediction accuracy , and can be used to evaluate the stability of metal mine goaf .

  2. 定形相变材料的研究进展%Recent progress in shape-stabilized phase change materials

    Institute of Scientific and Technical Information of China (English)

    汪意; 杨睿; 张寅平; 王馨


      定形相变材料是以聚合物为基体,相变物质分布在聚合物三维网状结构中的一种新型相变材料。定形相变材料在相变过程中表现为宏观固相、微观液相,支撑和力学性能优秀,不易泄漏,因其优良的加工性能和安全性能而受到广泛关注,并表现出了广阔的应用前景。本文综述了定形相变材料的制备、导热和阻燃性能等方面的研究进展,并从实验和模拟两方面综合评价了定形相变材料在建筑节能方面的使用性能,展望了定形相变材料的发展前景。%  Shape-stabilized phase change materials (SSPCM) uses polymer as a matrix with the phase change materials dispersed in the matrix. SSPCM shows a solid state macroscopically and hence possesses some salient features including excellent mechanical properties, good processability and high safety. This paper provides a review on the SSPCM, including preparation, thermal conductivity enhancement and flame retardation. An assessment is then made on the use of the materials with a specific focus on energy saving in buildings.

  3. 虾青素微胶囊化及其稳定性的研究进展%Research Progress on Microencapsulation and Stability of Astaxanthin

    Institute of Scientific and Technical Information of China (English)

    付力丹; 刘頔; 赵晓燕; 毕玉平; 王兴军


    天然虾青素作为一种新型的天然抗氧化剂,其抗氧化能力约为VE的550倍,在许多领域有着广阔的应用价值,如食品、医药等。因虾青素结构中存在较多共轭双键,故易受外界环境的影响而发生降解氧化。针对虾青素这一特性,主要探讨喷雾干燥过程中壁材及干燥温度等因素对虾青素微胶囊包埋效果的影响,并分析了虾青素微胶囊在贮存过程中对外界环境因素的耐受情况;同时对虾青素微胶囊现阶段在食品领域中的应用现状进行了总结,为日后虾青素产品的开发及广泛应用提供新思路。%Natural astaxanthin is a novel powerful antioxidant, whose antioxidant capacity is 550 times higher than Vitamin E. It has been widely applied in food, pharmaceutical industry. The astaxanthin can be easily de-graded by environmental conditions because of its unsaturated double bonds. This paper mainly explored the ef-fect of different conditions in spray drying process on astaxanthin microcapsules, such as wall material and dry-ing temperature etc. It also analyzed the stability of astaxanthin microcapsules during storage. At the same time , the development status of astaxanthin microcapsules in food field was summarized, in order to provide a new idea for the widely exploitation and application of astaxanthin product in the future.

  4. Effect of heating rate on temperature of titanium alloy (. cap alpha. +. beta. ). -->. beta. transformaton

    Energy Technology Data Exchange (ETDEWEB)

    Gridnev, V.N.; Ivasishin, O.M.; Markovskij, P.E. (AN Ukrainskoj SSR, Kiev. Inst. Metallofiziki)


    The effect of doping of two-phase titaniums alloys and morphology of initial structure on the Tsub(t) temperature shift value of (..cap alpha..+..beta..)..--> beta.. transformation depending on heating rate is investigated. It has been found that the Tsub(t) shift occurs in the strictly determined temperature range depending on chemical alloy composition. The Tsub(t) shift is directly proportional to the Ksub(..beta..) coefficient applied as a quantitative alloying characteristic as well as a dimensional factor equal either to the plate thickness or the ..cap alpha..-phase globule diameter depending on the type of initial structure. In the limits of this temperature range the (..cap alpha..+..beta..)..--> beta..-transformation occurs completely according to the diffusion mechanism. The critical heating rate at which maximum permissible Tsub(t) value is attained and above which its stabilization is observed is determined by the same parameters - the alloy doping degree characterized by the Ksub(..beta..) coefficient and the ..cap alpha..-phase crystal dimensions in the initial structure.

  5. Neutrinoless double beta decay

    Indian Academy of Sciences (India)

    Kai Zuber


    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given.

  6. Nonionic emulsion-mediated synthesis of zeolite beta

    Indian Academy of Sciences (India)

    Yuguo Shen; Ying Zhang; Chao Jin; Ying Cao; Wei Gao; Lishan Cui


    Zeolite beta synthesis was first carried out in a newly developed emulsion system containing nonionic polyoxyethylated alkylphenol surfactant, which showed interesting non-conventional features. Compared to the conventional hydrothermal synthesis of zeolite beta, the reported nonionic emulsion system showed a faster nucleation rate. Furthermore, the emulsion system could stabilize the beta product and retarded its further transformation to ZSM-5 even under the high crystallization temperature at 453 K. Additionally, the beta particle size could be tuned by the adoption of different lengths of alkyl chain in the surfactant and cosurfactant. Control experiments showed each emulsion component played a crucial role in the zeolite beta growth. The approach proposed in this paper might be extended to apply for the syntheses of other types of zeolites with particle size under control.

  7. Alpha and Beta Determinations

    CERN Document Server

    Dunietz, Isard


    Because the Bd -> J/psi Ks asymmetry determines only sin(2 beta), a discrete ambiguity in the true value of beta remains. This note reviews how the ambiguity can be removed. Extractions of the CKM angle alpha are discussed next. Some of the methods require very large data samples and will not be feasible in the near future. In the near future, semi-inclusive CP-violating searches could be undertaken, which are reviewed last.

  8. {beta} - amyloid imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.

  9. Beta cell dynamics: beta cell replenishment, beta cell compensation and diabetes. (United States)

    Cerf, Marlon E


    Type 2 diabetes, characterized by persistent hyperglycemia, arises mostly from beta cell dysfunction and insulin resistance and remains a highly complex metabolic disease due to various stages in its pathogenesis. Glucose homeostasis is primarily regulated by insulin secretion from the beta cells in response to prevailing glycemia. Beta cell populations are dynamic as they respond to fluctuating insulin demand. Beta cell replenishment and death primarily regulate beta cell populations. Beta cells, pancreatic cells, and extra-pancreatic cells represent the three tiers for replenishing beta cells. In rodents, beta cell self-replenishment appears to be the dominant source for new beta cells supported by pancreatic cells (non-beta islet cells, acinar cells, and duct cells) and extra-pancreatic cells (liver, neural, and stem/progenitor cells). In humans, beta cell neogenesis from non-beta cells appears to be the dominant source of beta cell replenishment as limited beta cell self-replenishment occurs particularly in adulthood. Metabolic states of increased insulin demand trigger increased insulin synthesis and secretion from beta cells. Beta cells, therefore, adapt to support their physiology. Maintaining physiological beta cell populations is a strategy for targeting metabolic states of persistently increased insulin demand as in diabetes.

  10. Automatic Fiscal Stabilizers

    Directory of Open Access Journals (Sweden)

    Narcis Eduard Mitu


    Full Text Available Policies or institutions (built into an economic system that automatically tend to dampen economic cycle fluctuations in income, employment, etc., without direct government intervention. For example, in boom times, progressive income tax automatically reduces money supply as incomes and spendings rise. Similarly, in recessionary times, payment of unemployment benefits injects more money in the system and stimulates demand. Also called automatic stabilizers or built-in stabilizers.

  11. Research progress of beta-blockers in the treatment of infantile hemangioma%β-受体阻滞剂治疗婴幼儿血管瘤的研究进展

    Institute of Scientific and Technical Information of China (English)

    李忠达; 彭智


    Infantile hemangiomas (IH) are the most common tumors of infancy, with a prevalence of approxi-mately 4~10%of infants. Although the natural history of IH is to spontaneously involute, a significant minority of IH re-quire therapy with the aim to prevent disfigurement, functional impairment, or ulceration. In 2008, propranolol, a non-se-lective beta (β)-blocker, was reported to be highly effective in treating IH. Since that time there have been more than 200 articles published regarding the efficacy and potential toxicity ofβ-blockers, both systemic and topical, for the treatment of IH. Based on these findings,β-blockers appear to be highly effective in treating IH and are well tolerated, though side effects have been reported. When therapy is appropriately monitored,β-blockers have been proven to be a safer and su-perior alternative to systemic steroids. This paper mainly reviews the treatment of IH through beta-blockers in recent years involving the mechanism, side effects, usage and dosage.%婴幼儿血管瘤(IH)是一种最常见的良性肿瘤,在婴幼儿中患病率为4%~10%,虽然有部分IH存在自然消退过程,但少数IH仍需要有效治疗,以防止其对皮肤的损害,导致肢体功能障碍以及发生局部溃疡.自2008年,普萘洛尔,一种非选择性β-受体阻滞剂被报道能高效治疗婴幼儿血管瘤之后,目前有约200篇文献报道β-受体阻滞剂对IH治疗存在全身性、局部性疗效及潜在毒性.基于以上发现,β-受体阻滞剂在治疗IH中产生非常高的疗效并得到了认可.与类固醇比较,即使β-受体阻滞剂在使用过程中产生一定的副作用,如果在治疗过程中得到适当监测,其更加安全与优质.本文主要对近几年来β-受体阻滞剂治疗IH作用机制,不良反应,用法、用量做一综述.

  12. Beta and gamma decay heat measurements between 0.1s-50,000s for neutron fission of {sup 235}U, {sup 238}U and {sup 239}Pu. Progress report, March 1, 1993--January 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Schier, W.A.; Couchell, G.P.


    Decay heat measurements following the fast fission of {sup 238}U are well underway. The He-jet system and spectrometers were moved to the 1 MW research reactor to gain sufficient fast neutron flux for these measurements. On the Van de Graaff accelerator, the He-jet capillary has been shortened so that beta and gamma measurements following the thermal neutron fission of {sup 235}U could be made down to delay times near 0.1 s. Gamma-ray response functions are now well characterized for gamma energies up to 1.5 MeV for our large Nal spectrometer. Such response functions out to high energies are needed to extract energy distributions of our measured gamma spectra. The response function unfolding program, FERD-PC, has been operated successfully with trial spectra. Comparisons of individual fission products for {sup 235}U(n{sub th}f) with ENDF/B-VI at short delay times suggest several improvements to the data base particularly in production probabilities. The new data acquisition and data analysis systems have arrived and will soon be brought on line extending considerably the capabilities of our research group.

  13. Progress report and technology status development of an EG and G Berthold LB-150 alpha/beta particulate monitor for use on the East Tennessee Technology Park Toxic Substances Control Act Incinerator

    Energy Technology Data Exchange (ETDEWEB)

    Shor, J.T.; Singh, S.P.N. [Oak Ridge National Lab., TN (United States). Chemical Technology Div.; Gibson, L.V. Jr. [East Tennessee Technology Park, Oak Ridge, TN (United States). ASO Customer Services Div.


    The purpose of this project was to modify and evaluate a commercially available EG and G Berthold LB-150 alpha-beta radionuclide particulate monitor for the high-temperature and moisture-saturation conditions of the East Tennessee Technology Park (formerly K-25 Site) Toxic Substances Control Act (TSCA) Incinerator stack. The monitor was originally outfitted for operation at gas temperatures of 150 F on the defunct Los Alamos National Laboratory (LANL) controlled air incinerator, and the objective was to widen its operating envelope. A laboratory apparatus was constructed that simulated the effects of water-saturated air at the TSCA Incinerator stack-gas temperatures, 183 F. An instrumented set of heat exchangers was constructed to then condition the gas so that the radionuclide monitor could be operated without condensation. Data were collected under the conditions of the elevated temperatures and humidities and are reported herein, and design considerations of the apparatus are provided. The heat exchangers and humidification equipment performed as designed, the Mylar film held, and the instrument suffered no ill effects. However, for reasons as yet undetermined, the sensitivity of the radionuclide detection diminishes as the gas temperature is elevated, whether the gas is humidified or not. The manufacturer has had no experience with (a) the operation of the monitor under these conditions and (b) any commercial market that might exist for an instrument that operates under these conditions. The monitor was not installed into the radiologically contaminated environment of the TSCA Incinerator stack pending resolution of this technical issue.

  14. Study on the complexation of isoquercitrin with {beta}-cyclodextrin and its derivatives by spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yunlong; Qiao Xiaona; Li Wenchao; Zhou Yehong; Jiao Yong [Research Center of Environmental Science and Engineering, School of Chemistry and Chemical Engineering, Shanxi University, Wu Cheng Road 36, Taiyuan 030006 (China); Yang Cheng [Department of Applied Chemistry, Osaka University, Suita 565-0871 (Japan); Dong Chuan, E-mail: [Research Center of Environmental Science and Engineering, School of Chemistry and Chemical Engineering, Shanxi University, Wu Cheng Road 36, Taiyuan 030006 (China); Inoue, Yoshihisa [Department of Applied Chemistry, Osaka University, Suita 565-0871 (Japan); Shuang, Shaomin, E-mail: [Research Center of Environmental Science and Engineering, School of Chemistry and Chemical Engineering, Shanxi University, Wu Cheng Road 36, Taiyuan 030006 (China)


    The inclusion complexes of isoquercitrin (IQ) with cyclodextrins (CDs) including {beta}-cyclodextrin ({beta}-CD), hydroxypropyl-{beta}-cyclodextrin (HP-{beta}-CD) and dimethyl-{beta}-cyclodextrin (DM-{beta}-CD) have been investigated using the methods of steady-state fluorescence, UV-vis absorption and induced circular dichroism. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was measured in the case of DM-{beta}-CD due to the increased hydrophobicity of the host cavity, followed by HP-{beta}-CD and {beta}-CD. The effect of pH on the complexation process was also quantitatively assessed. IQ exists in different molecular forms depending on pH and {beta}-CDs were most suitable for inclusion of the neutral form of IQ. The phase-solubility diagrams obtained with {beta}-CD, HP-{beta}-CD and DM-{beta}-CD were all classical A{sub L} type. And DM-{beta}-CD provided the best solubility enhancement, 12.3-fold increase compared to 2.8- and 7.5-fold increase for {beta}-CD and HP-{beta}-CD. The apparent stability constants obtained from the solubility data at 25 deg. C were comparable with those obtained from the fluorescence assays. Moreover, {sup 1}H NMR was carried out, which revealed that the IQ favorably inserted into the inner cavity from the chromone part instead of the phenyl part, which was in agreement with molecular modeling studies.

  15. Monomelic amyotrophy with late progression. (United States)

    Rowin, J; Meriggioli, M N; Cochran, E J


    Monomelic amyotrophy is a sporadic juvenile-onset disease that presents with gradual onset of weakness and atrophy in the hand muscles unilaterally. Generally, this disease is considered a 'benign' and non-progressive motor neuron disease, which stabilizes within five years of onset. We discuss a case that illustrates that monomelic amyotrophy may rarely exhibit late clinical progression to the lower extremities after a prolonged period of disease stability.

  16. Directional and Attitude Stability Control Kit (United States)


    and Attitude Stability Control Kit Final Progress Report This report outlines progress on the DARPA M3 Program, project “Directional and Attitude ...2 ABSTRACT Number of Papers published in peer-reviewed journals: Number of Papers published in non peer-reviewed journals: Directional and Attitude ...Stability Control Kit Final Progress Report Report Title This report outlines progress on the DARPA M3 Program, project “Directional and Attitude

  17. Boosted beta regression.

    Directory of Open Access Journals (Sweden)

    Matthias Schmid

    Full Text Available Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1. Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures.

  18. Gastrointestinal hyperplasia with altered expression of DNA polymerase beta.

    Directory of Open Access Journals (Sweden)

    Katsuhiko Yoshizawa

    Full Text Available BACKGROUND: Altered expression of DNA polymerase beta (Pol beta has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol beta over-expression has not yet been evaluated in a mouse model. METHODOLOGY/PRINCIPAL FINDINGS: We have recently developed a novel transgenic mouse model that over-expresses Pol beta. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol beta over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol beta expression. We observed elevated expression of Pol beta in stomach adenomas and thyroid follicular carcinomas, but reduced Pol beta expression in esophageal adenocarcinomas and squamous carcinomas. CONCLUSIONS/SIGNIFICANCE: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation.

  19. Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved beta(2)-microglobulin

    DEFF Research Database (Denmark)

    Heegaard, N.H.H.; Jørgensen, T.J.D.; Rozlosnik, N.;


    beta(2)-Microglobulin (beta(2)m) is the amyloidogenic protein in dialysis-related amyloidosis, but the mechanisms underlying beta(2)m fibrillogenesis in vivo are largely unknown. We study a structural variant of beta(2)M that has been linked to cancer and inflammation and may be present in the ci......beta(2)-Microglobulin (beta(2)m) is the amyloidogenic protein in dialysis-related amyloidosis, but the mechanisms underlying beta(2)m fibrillogenesis in vivo are largely unknown. We study a structural variant of beta(2)M that has been linked to cancer and inflammation and may be present...... in the circulation of dialysis patients. This beta(2)M variant, Delta K58-beta(2)m, is a disulfide-linked two-chain molecule consisting of amino acid residues 1-57 and 59-99 of intact beta(2)m, and we here demonstrate and characterize its decreased conformational stability as compared to wild-type (wt) beta(2)M......, and at 37 degrees C the half-time for unfolding is more than 170-fold faster than at 15 degrees C. Conformational changes are also reflected by a very prominent Congo red binding of Delta K58-beta(2)m at 37 degrees C, by the evolution of thioflavin T fluorescence, and by changes in intrinsic fluorescence...

  20. Noncovalent Interaction Energies in Covalent Complexes: TEM-1 beta-Lactamase and beta-Lactams

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaojun; Minasov, George; Shoichet, Brian K. (NWU)


    The class A {beta}-lactamase TEM-1 is a key bacterial resistance enzyme against {beta}-lactam antibiotics, but little is known about the energetic bases for complementarity between TEM-1 and its inhibitors. Most inhibitors form a covalent adduct with the catalytic Ser70, making the measurement of equilibriumconstants, and hence interaction energies, technically difficult. This study evaluates noncovalent interactions withincovalent complexes by examining the differential stability of TEM-1 and its inhibitor adducts. The thermal denaturation of TEM-1 follows a two-state, reversible model with a melting temperature (T{sub m}) of 51.6 C and a van't Hoff enthalpy of unfolding ({Delta}H{sub VH}) of 146.2 kcal/mol at pH 7.0. The stability of the enzyme changes on forming an inhibitor adduct. As expected, some inhibitors stabilize TEM-1; transition-state analogues increase the T{sub m} by up to 3.7 C(1.7 kcal/mol). Surprisingly, all {beta}-lactam covalent acyl-enzyme complexes tested destabilize TEM-1 significantly relative to the apoenzyme. For instance, the clinically used inhibitor clavulanic acid and the {beta}-lactamase-resistant {beta}-lactams moxalactam and imipenem destabilize TEM-1 by over 2.6 C (1.2 kcal/mol) in their covalent adducts. Based on the structure of the TEM-1/imipenem complex (Maveyraud et al., J Am Chem Soc 1998;120:9748-52), destabilization by moxalactam and imipenem is thought to be caused by a steric clash between the side-chain of Asn132 and the 6(7)-{alpha} group of these {beta}-lactams. To test this hypothesis, the mutant enzyme N132A was made. In contrast with wild-type, the covalent complexes between N132A and both imipenem and moxalactam stabilize the enzyme, consistent with the hypothesis. To investigate the structural bases of this dramatic change instability, the structure of N132A/imipenem was determined by X-ray crystallography. In the complex with N132A, imipenemadopts a very different conformation from that observed in the wild


    Energy Technology Data Exchange (ETDEWEB)



    The long-term prospects for fully exploring three-flavor mixing in the neutrino sector depend upon an ongoing and increased investment in the appropriate accelerator R&D. Two new concepts have been proposed that would revolutionize neutrino experiments, namely the Neutrino Factory and the Beta Beam facility. These new facilities would dramatically improve our ability to test the three-flavor mixing framework, measure CP violation in the lepton sector, and perhaps determine the neutrino mass hierarchy, and, if necessary, probe extremely small values of the mixing angle {theta}{sub 13}. The stunning sensitivity that could be achieved with a Neutrino Factory is described, together with our present understanding of the corresponding sensitivity that might be achieved with a Beta Beam facility. In the Beta Beam case, additional study is required to better understand the optimum Beta Beam energy, and the achievable sensitivity. Neither a Neutrino Factory nor a Beta Beam facility could be built without significant R&D. An impressive Neutrino Factory R&D effort has been ongoing in the U.S. and elsewhere over the last few years and significant progress has been made towards optimizing the design, developing and testing the required accelerator components, and significantly reducing the cost. The recent progress is described here. There has been no corresponding activity in the U.S. on Beta Beam facility design and, given the very limited resources, there is little prospect of starting a significant U.S. Beta Beam R&D effort in the near future. However, the Beta Beam concept is interesting, and progress on its development in Europe should be followed. The Neutrino Factory R&D program has reached a critical stage in which support is required for two crucial international experiments and a third-generation international design study. If this support is forthcoming, a Neutrino Factory could be added to the Neutrino Community's road map in about a decade.

  2. Hereditary and sporadic beta-amyloidoses. (United States)

    Di Fede, Giuseppe; Giaccone, Giorgio; Tagliavini, Fabrizio


    Cerebral amyloidoses are chronic, progressive neurodegenerative diseases that are caused by the aggregation and deposition of misfolded proteins in the central nervous system, and lead to cognitive deficits, stroke, and focal neurological dysfunction including cerebellar and extrapyramidal signs. Among them, beta-amyloidoses are a heterogenous set of conditions characterised by the deposition of beta-amyloid protein in brain parenchyma and/or vessel walls that lead to the development of two main clinico-pathological entities: Alzheimer's disease and cerebral amyloid angiopathy, which may be sporadic or familial, and may also co-exist in the same patient. The aim of this review is to describe the most important differences in the pathways leading to parenchymal and cerebrovascular beta-amyloidoses, and the main clinical, neuropathological and biochemical characteristics of the two conditions. It also discusses the phenotypes associated with a series of familial and sporadic beta-amyloidoses in more detail in order to highlight the clinical and neuropathological features that may help to distinguish the different forms of disease.

  3. Lithium and neuropsychiatric therapeutics: neuroplasticity via glycogen synthase kinase-3beta, beta-catenin, and neurotrophin cascades. (United States)

    Wada, Akihiko


    Mood disorders are not merely attributed to the functional defect of neurotransmission, but also are due to the structural impairment of neuroplasticity. Chronic stress decreases neurotrophin levels, precipitating or exacerbating depression; conversely, antidepressants increase expression of various neurotrophins (e.g., brain-derived neurotrophic factor and vascular endothelial growth factor), thereby blocking or reversing structural and functional pathologies via promoting neurogenesis. Since the worldwide approval of lithium therapy in 1970, lithium has been used for its anti-manic, antidepressant, and anti-suicidal effects, yet the therapeutic mechanisms at the cellular level remain not-fully defined. During the last five years, multiple lines of evidence have shown that the mood stabilization and neurogenesis by lithium are due to the lithium-induced inhibition of glycogen synthase kinase-3beta (GSK-3beta), allowing accumulation of beta-catenin and beta-catenin-dependent gene transcriptional events. Altered levels of GSK-3beta and beta-catenin are associated with various neuropsychiatric and neurodegenerative diseases, while various classical neuropsychiatric drugs inhibit GSK-3beta and up-regulate beta-catenin expression. In addition, evidence has emerged that insulin-like growth factor-I enhances antidepression, anti-anxiety, memory, neurogenesis, and angiogenesis; antidepressants up-regulate expression of insulin-like growth factor-I, while insulin-like growth factor-I up-regulates brain-derived neurotrophic factor expression and its receptor TrkB level, as well as brain-derived neurotrophic factor-induced synaptic protein levels. More importantly, physical exercise and healthy diet raise transport of peripheral circulating insulin-like growth factor I into the brain, reinforcing the expression of neurotrophins (e.g., brain-derived neurotrophic factor) and the strength of cell survival signalings (e.g., phosphoinositide 3-kinase / Akt / GSK-3beta pathway

  4. 尿路感染患儿产ESBL大肠埃希菌的研究进展%Progress of E.coli producing extended spectrum beta-lactameses in children with urinary tract infection

    Institute of Scientific and Technical Information of China (English)



    Urinary tract infections (UTI)is a childhood disease.With the use of extended spectrum antibiotics,resistant strains have increased every year,especially Escherichia coli(E.coli).The mechanisms of drug resistance are as follows:hydrolase,target gene mutations,efflux pumps and membrane permeability change.Of which producing extended-spectrum β-lactamase(ESBL) is increasing.So it presents a huge challenge to clinical antibiotic selection.According to the resistance genes (blaTEM,blaSHV,blaCTX-M,etc.),the ESBL can be classified into different types (TEM type,SHV-type,CTX-M type,etc.).The drug-resistant genes play an important role in spreading and prevalence of the resistance genes.It's necessary to do a review of the currently known genotypes.It is both in favor of scientific research work and providing guidance for clinical work.%尿路感染(urinary tract infection,UTI)是儿童期多发病,随着广谱抗生素的大量使用,耐药菌株逐年增多,尤以大肠埃希菌(Escherichia coli,E.coli)为著.E.coli耐药机制有产生药物水解酶、靶基因突变、主动外排泵和膜通透性的改变等,其中产超广谱β-内酰胺酶(extended spectrum beta-lactamases,ESBL)E.coli日趋增多,给临床抗生素的选择提出了巨大挑战.根据其耐药基因(blaTEM、blaSHV、blaCTX-M等)的不同分为不同类型(TEM型、SHV型、CTX-M型等)的ESBL.各种类型的ESBL对耐药基因的传播和流行起重要的作用,该文对目前已知耐药基因型的现状作一综述.

  5. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.;


    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...

  6. Compact DEMO, SlimCS: design progress and issues (United States)

    Tobita, K.; Nishio, S.; Enoeda, M.; Kawashima, H.; Kurita, G.; Tanigawa, H.; Nakamura, H.; Honda, M.; Saito, A.; Sato, S.; Hayashi, T.; Asakura, N.; Sakurai, S.; Nishitani, T.; Ozeki, T.; Ando, M.; Ezato, K.; Hamamatsu, K.; Hirose, T.; Hoshino, T.; Ide, S.; Inoue, T.; Isono, T.; Liu, C.; Kakudate, S.; Kawamura, Y.; Mori, S.; Nakamichi, M.; Nishi, H.; Nozawa, T.; Ochiai, K.; Ogiwara, H.; Oyama, N.; Sakamoto, K.; Sakamoto, Y.; Seki, Y.; Shibama, Y.; Shimizu, K.; Suzuki, S.; Takahashi, K.; Tanigawa, H.; Tsuru, D.; Yamanishi, T.; Yoshida, T.


    The design progress in a compact low aspect ratio (low A) DEMO reactor, 'SlimCS', and its design issues are reported. The design study focused mainly on the torus configuration including the blanket, divertor, materials and maintenance scheme. For continuity with the Japanese ITER-TBM, the blanket is based on a water-cooled solid breeder blanket. For vertical stability of the elongated plasma and high beta access, the blanket is segmented into replaceable and permanent blankets and a sector-wide conducting shell is arranged inbetween these blankets. A numerical calculation indicates that fuel self-sufficiency can be satisfied when the blanket interior is ideally fabricated. An allowable heat load to the divertor plate should be 8 MW m-2 or lower, which can be a critical constraint for determining a handling power of DEMO.

  7. Beta limits in H-modes and VH-modes in JET

    Energy Technology Data Exchange (ETDEWEB)

    Smeulders, P.; Hender, T.C.; Huysmans, G.; Marcus, F.; Ali-Arshad, S.; Alper, B.; Balet, B.; Bures, M.; Deliyanakis, N.; Esch, H. de; Fshpool, G.; Jarvis, O.N.; Jones, T.T.C.; Ketner, W.; Koenig, R.; Lawson, K.; Lomas, P.; O`Brien, D.; Sadler, G.; Stok, D.; Stubberfield, P.; Thomas, P.; Thomen, K.; Wesson, J. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Nave, M.F. [Universidade Tecnica, Lisbon (Portugal). Inst. Superior Tecnico


    In Hot-ion H- and VH-modes, the highest achieved beta was about 10% below the Troyon value in the best case of discharge 26087. The operational space of the high beta discharges obtained before March 1992 has been explored as function of the parameters H{sub ITER89P}, {beta}{sub n}, q{sub 95}, I{sub p}. Also, a limiting envelope on the fusion reactivity as a function of the average plasma pressure and beta has been observed with R{sub DD} related to {beta}{sub {phi}}{sup 2}.B{sub {phi}}{sup 4}. MHD stability analysis shows that the JET VH modes at the edge are in the second region for ballooning mode stability. The dependence of ballooning stability and the n=1 external kink on the edge current density is analyzed. (authors). 6 figs., 6 refs.

  8. Beta Thalassemia (For Parents) (United States)

    ... had their spleens removed. Slower growth rates. The anemia resulting from beta thalassemia can cause children to grow more slowly and also can lead ... boost production of new red blood cells. Some children with moderate anemia may require an occasional blood transfusion , particularly after ...

  9. Trichoderma .beta.-glucosidase (United States)

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian


    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  10. Roughing up Beta

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

    Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross-section...

  11. Inflammatory Cytokines Stimulate Bone Morphogenetic Protein-2 Expression and Release from Pancreatic Beta Cells

    DEFF Research Database (Denmark)

    Urizar, Adriana Ibarra; Friberg, Josefine; Christensen, Dan Ploug;


    The proinflammatory cytokines interleukin-1 beta (IL-1β) and interferon gamma (IFN-γ) play important roles in the progressive loss of beta-cell mass and function during development of both type 1 and type 2 diabetes. We have recently showed that bone morphogenetic protein (BMP)-2 and -4...

  12. The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

    Energy Technology Data Exchange (ETDEWEB)

    Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen


    Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

  13. The catalytic role of beta effect in barotropization processes

    CERN Document Server

    Venaille, Antoine; Griffies, S M


    The vertical structure of freely evolving, continuously stratified, quasi-geostrophic flow is investigated. We predict the final state organization, and in particular its vertical structure, using statistical mechanics and these predictions are tested against numerical simulations. The key role played by conservation laws in each layer, including the fine-grained enstrophy, is discussed. In general, the conservation laws, and in particular that enstrophy is conserved layer-wise, prevent complete barotropization, i.e., the tendency to reach the gravest vertical mode. The peculiar role of the $\\beta$-effect, i.e. of the existence of planetary vorticity gradients, is discussed. In particular, it is shown that increasing $\\beta$ increases the tendency toward barotropization through turbulent stirring. The effectiveness of barotropisation may be partly parameterized using the Rhines scale $2\\pi E_{0}^{1/4}/\\beta^{1/2}$. As this parameter decreases (beta increases) then barotropization can progress further, because...

  14. Recent Insights into Clostridium perfringens Beta-Toxin

    Directory of Open Access Journals (Sweden)

    Masahiro Nagahama


    Full Text Available Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin.

  15. TGF-beta and osteoarthritis.

    NARCIS (Netherlands)

    Blaney Davidson, E.N.; Kraan, P.M. van der; Berg, W.B. van den


    OBJECTIVE: Cartilage damage is a major problem in osteoarthritis (OA). Growth factors like transforming growth factor-beta (TGF-beta) have great potential in cartilage repair. In this review, we will focus on the potential therapeutic intervention in OA with TGF-beta, application of the growth facto

  16. Dysregulated transforming growth factor-beta in neonatal and adult autoimmune MRL-lpr mice. (United States)

    Kreft, B; Yokoyama, H; Naito, T; Kelley, V R


    Transforming growth factor- beta (TGF- beta) is a cytokine that promotes inflammatory processes and prevents tissue injury. Autoimmune destruction of the kidney in MRL-lpr mice is spontaneous, rapid, fatal and consists of glomerular damage and an influx of lymphocytes surrounding vessels and in the interstitium. In MRL-lpr mice, cytokine dysregulation is apparent in neonates and continues throughout the life span. Circulating levels of tumour necrosis factor (TNF- alpha) and colony stimulating factor-1 (CSF-1) are detected in neonatal mice and progressively increase in proportion to the loss of renal function. We now report elevated intracellular expression of distinct isoforms of TGF- beta (TGF- beta 3, TGF- beta 2, and TGF- beta 1) detected immunohistochemically in MRL-lpr kidneys and other tissues including the liver and thymus. Enhanced TGF- beta 3 and TGF- beta 2 isoforms are detectable in neonatal mice within the renal tubular epithelial cells (TEC) and vascular smooth muscle cells (VSMC). In MRL-lpr mice 4-6 months of age, TGF- beta 2 and TGF- beta 1 are detected in TEC, VSMC, glomerular epithelial cells (GEC) and in perivascular infiltrating cells. By comparison, TGF- beta is minimally detectable in the normal kidneys of age and sex matched MRL(-)+2 or C3H/Fej mice. Paradoxically, in vitro cultured TEC and VSMC from MRL-lpr mice secrete less TGF- beta than TEC and VSMC isolated from MRL(-)+2 or C3H/FeJ mice. TNF- alpha, but not IL-6, CSF-1, or IFN- gamma stimulated the secretion of TGF- beta in TEC and VSMC. Our data demonstrate the dysregulation of TGF- beta isoforms in neonatal and adult MRL-lpr mice prior to and after the onset of autoimmune renal disease. We suggest that TNF- alpha and/or other molecules increase TGF- beta expression in MRL-lpr mice. We speculate that enhanced expression of TGF- beta promotes autoinmune renal injury in MRL-lpr mice.

  17. Stability and Index of the Meet Game on a Lattice


    Joseph Abdou


    We study the stability and the stability index of the meet game form defined on a meet semilattice. Given any active coalition structure, we show that the stability index relative to the equilibrium, to the beta core and to the exact core is a function of the Nakamura number, the depth of the semilattice and its gap function.

  18. Differential regulation of chemoattractant-stimulated beta 2, beta 3, and beta 7 integrin activity. (United States)

    Sadhu, C; Masinovsky, B; Staunton, D E


    Leukocyte adhesion to endothelium and extravasation are dynamic processes that require activation of integrins. Chemoattractants such as IL-8 and FMLP are potent activators of leukocyte integrins. To compare the chemoattractant-stimulated activation of three integrins, alpha 4 beta 7, alpha L beta 2, and alpha V beta 3, in the same cellular context, we expressed an IL-8 receptor (IL-8RA) and FMLP receptor (FPR) in the lymphoid cell line JY. Chemoattractants induced a rapid increase in alpha L beta 2- and alpha V beta 3-dependent JY adhesion within 5 min, and it was sustained for 30 min. In contrast, stimulation of alpha 4 beta 7-dependent adhesion was transient, returning to basal levels by 30 min. The activation profiles of the integrins were similar regardless of whether IL-8 or FMLP was used for induction. We also demonstrate that alpha 4 beta 7-dependent adhesion was uniquely responsive to the F actin-disrupting agent cytochalasin D and the protein kinase C (PKC) inhibitor chelerythrin. While alpha V beta 3- and alpha L beta 2-mediated cell adhesion was significantly reduced by cytochalasin D, alpha 4 beta 7-mediated adhesion was enhanced. Chelerythrin inhibited both the IL-8 and PMA activation of alpha L beta 2 and alpha V beta 3. In contrast, inducible alpha 4 beta 7 activity was unaffected, and basal activity was increased. These findings demonstrate that the mechanism of alpha 4 beta 7 regulation by chemoattractants is different from that of alpha L beta 2 and alpha V beta 3 and that it appears to involve distinct cytoskeletal and PKC dependencies. In addition, PKC activity may be a positive or negative regulator of integrin-dependent adhesion.

  19. The Research Progress on Beet Mosaic and Resistance of Germplasm in Sugar beet (Beta vulgaris L.)%甜菜花叶病及种质资源抗性的研究进展

    Institute of Scientific and Technical Information of China (English)

    丁广洲; 陈丽; 陈连江; 赵春雷; 王希; 张玉霜; 刘娜; 贾海伦; 郭莹莹


    甜菜花叶病是甜菜生产的世界性病害,可经多种蚜虫非持久性传播.花叶病毒侵染甜菜,嫩叶常出现脉间褪绿的明脉现象,发生皱缩;功能叶片会出现明暗相间的绿色斑驳,进而产生花叶,严重的发生坏死,给甜菜生产造成巨大损失.本研究归纳了BtMV病原及种质资源抗性的研究概况,分析了BtMV病原生物学特性、病原基因组及编码蛋白结构功能,病原介体及病毒复制模式,以及BtMV侵染甜菜植株及叶片的结构与微观变化.总结了当前用于甜菜花叶病的检测方法和甜菜种质资源的花叶病抗性与抗病反应的研究进展.提出了当前甜菜抗花叶病需要深入开展的研究论题,并对甜菜抗花叶病分子机理和基因工程育种进行了展望.为该病的深入性研究,特别是基因工程育种提供参考.%Beet mosaic is an aphid transmitted viral disease of sugar beet found worldwide, transmitted by many species of aphids in the non-persistent manner. Infected beets are sometimes stunted, young leaves often show vein-clearing; older leaves show a pronounced light and dark green mottle, and are often puckered. The author concluded the situation of pathogen of Beet Mosaic Virus (BtMV) and germplasm resistance research, analyzed biological characteristics, genome and encoding protein structure function of BtMV pathogen, and studied the pathogen mediator and the virus replication mode; and also studied the structure and microscopic changes of BtMV inflected plants and leaves of sugar beet; summarized the detection methods for beet mosaic and the research progress of beet mosaic germplasm resistance and resistance reflection. The author put forwards the thesis of further research on beet mosaic resistance, and made prospects on molecular mechanics of beet mosaic resistance and genetic engineering breeding. It could be helpful for the disease resistance investigation in agricultural production and shed some light for genetic

  20. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella


    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  1. Beta-thalassemia. (United States)

    Galanello, Renzo; Origa, Raffaella


    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  2. Beta and muon decays

    Energy Technology Data Exchange (ETDEWEB)

    Galindo, A.; Pascual, P.


    These notes represent a series of lectures delivered by the authors in the Junta de Energia Nuclear, during the Spring term of 1965. They were devoted to graduate students interested in the Theory of Elementary Particles. Special emphasis was focussed into the computational problems. Chapter I is a review of basic principles (Dirac equation, transition probabilities, final state interactions.) which will be needed later. In Chapter II the four-fermion punctual Interaction is discussed, Chapter III is devoted to the study of beta-decay; the main emphasis is given to the deduction of the formulae corresponding to electron-antineutrino correlation, electron energy spectrum, lifetimes, asymmetry of electrons emitted from polarized nuclei, electron and neutrino polarization and time reversal invariance in beta decay. In Chapter IV we deal with the decay of polarized muons with radiative corrections. Chapter V is devoted to an introduction to C.V.C. theory. (Author)

  3. Realized Beta GARCH

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Voev, Valeri Radkov


    We introduce a multivariate generalized autoregressive conditional heteroskedasticity (GARCH) model that incorporates realized measures of variances and covariances. Realized measures extract information about the current levels of volatilities and correlations from high-frequency data, which...... is particularly useful for modeling financial returns during periods of rapid changes in the underlying covariance structure. When applied to market returns in conjunction with returns on an individual asset, the model yields a dynamic model specification of the conditional regression coefficient that is known...... as the beta. We apply the model to a large set of assets and find the conditional betas to be far more variable than usually found with rolling-window regressions based exclusively on daily returns. In the empirical part of the paper, we examine the cross-sectional as well as the time variation...

  4. Coroutine Sequencing in BETA

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger;

    In object-oriented programming, a program execution is viewed as a physical model of some real or imaginary part of the world. A language supporting object-oriented programming must therefore contain comprehensive facilities for modeling phenomena and concepts form the application domain. Many ap...... applications in the real world consist of objects carrying out sequential processes. Coroutines may be used for modeling objects that alternate between a number of sequential processes. The authors describe coroutines in BETA...

  5. Magic Baseline Beta Beam

    CERN Document Server

    Agarwalla, Sanjib Kumar; Raychaudhuri, Amitava


    We study the physics reach of an experiment where neutrinos produced in a beta-beam facility at CERN are observed in a large magnetized iron calorimeter (ICAL) at the India-based Neutrino Observatory (INO). The CERN-INO distance is close to the so-called "magic" baseline which helps evade some of the parameter degeneracies and allows for a better measurement of the neutrino mass hierarchy and $\\theta_{13}$.

  6. Thymosin Beta 4 and Thymosin Beta 10 Expression in Hepatocellular Carcinoma (United States)

    Theunissen, W.; Fanni, D.; Nemolato, S.; Di Felice, E.; Cabras, T.; Gerosa, C.; Van Eyken, P.; Messana, I.; Castagnola, M.; Faa, G.


    Thymosin beta 4 (Tβ4) and thymosin beta 10 (Tβ10) are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC). To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30%) and Tβ10 reactivity in 22/23 (96%) cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression. PMID:24704991

  7. Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    W. Theunissen


    Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC. To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30% and Tβ10 reactivity in 22/23 (97% cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.

  8. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis


    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades......, but the mechanisms involved are still not clarified. In this review the information obtained in previous studies is recapitulated together with some of the current attempts to resolve the controversy in the field: identification of the putative progenitor cells, identification of the factors involved...

  9. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel


    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  10. LHCb: $2\\beta_s$ measurement at LHCb

    CERN Multimedia

    Conti, G


    A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

  11. Ideal Stabilization

    CERN Document Server

    Nesterenko, Mikhail


    We define and explore the concept of ideal stabilization. The program is ideally stabilizing if its every state is legitimate. Ideal stabilization allows the specification designer to prescribe with arbitrary degree of precision not only the fault-free program behavior but also its recovery operation. Specifications may or may not mention all possible states. We identify approaches to designing ideal stabilization to both kinds of specifications. For the first kind, we state the necessary condition for an ideally stabilizing solution. On the basis of this condition we prove that there is no ideally stabilizing solution to the leader election problem. We illustrate the utility of the concept by providing examples of well-known programs and proving them ideally stabilizing. Specifically, we prove ideal stabilization of the conflict manager, the alternator, the propagation of information with feedback and the alternating bit protocol.

  12. Nitro-thiocyanobenzoic acid (NTCB) reactivity of cysteines beta100 and beta110 in porcine luteinizing hormone: metastability and hypothetical isomerization of the two disulfide bridges of its beta-subunit seatbelt. (United States)

    Belghazi, Maya; Klett, Danièle; Cahoreau, Claire; Combarnous, Yves


    Luteinizing hormone (LH) like all other glycoprotein hormones is composed of two dissimilar subunits, alpha and beta, that are non-covalently associated. The heterodimer is stabilized by a region of the beta-subunit called the "seatbelt" because it wraps around the alpha-subunit and it is fastened by a disulfide bridge between cysteines beta26 and beta110. Although all 22 cysteines of porcine LH (pLH) are engaged in disulfide bridges, we previously showed that the free cysteine-specific reagent NTCB could react with pLH: it slowly cyanylated two cysteines in pLH and there was a close relationship between NTCB reaction with pLH and association/dissociation kinetics of its subunits. Therefore, cysteines beta26 and beta110 were considered as the best candidates for NTCB reaction. In order to identify the NTCB-reactive cysteines in pLH we have performed a mass spectroscopic analysis of the peptides released after mild basic hydrolysis of S-cyanylated pLH and its subunits. Only cysteines beta100 and beta110 were found to react with NTCB. Since these residues are not linked by a disulfide bridge in the crystallographic 3D structure of gonadotropins, it is proposed that their respective counterparts (Cysbeta93 and beta26) do not react with NTCB either because they are shielded from solvent or because they form a transient bridge. In the first hypothesis, both seatbelt bridges would be independently metastable; in the second one, a fast reversible isomerization between bridges beta26-beta110 and beta93-beta100 would occur. Such a reaction could be catalyzed by the previously recognized intrinsic protein disulfide isomerase (PDI) activity of gonadotropins.

  13. Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1. (United States)

    Murakami, Shigeru; Takashima, Hajime; Sato-Watanabe, Mariko; Chonan, Sumi; Yamamoto, Koji; Saitoh, Masako; Saito, Shiuji; Yoshimura, Hiromitsu; Sugawara, Koko; Yang, Junshan; Gao, Nannan; Zhang, Xinggao


    Transforming growth factor-beta (TGF-beta), a multifunctional cytokine which is involved in extracellular matrix modulation, has a major role in the pathogenesis and progression of fibrotic diseases. We now report the effects of ursolic acid on TGF-beta1 receptor binding and TGF-beta1-induced cellular functions in vitro. Ursolic acid inhibited [(125)I]-TGF-beta1 receptor binding to Balb/c 3T3 mouse fibroblasts with an IC(50) value of 6.9+/-0.8 microM. Ursolic acid dose-dependently recovered reduced proliferation of Minc Mv1Lu cells in the presence of 5 nM of TGF-beta1 and attenuated TGF-beta1-induced collagen synthesis and production in human fibroblasts. Molecular dynamics simulations suggest that ursolic acid may interact with the hydrophobic region of the dimeric interface and thereby inhibit the binding of TGF-beta1 to its receptor. All these findings taken together show that ursolic acid functions as an antagonist for TGF-beta1. This is the first report to show that a small molecule can inhibit TGF-beta1 receptor binding and influence functions of TGF-beta1.

  14. Incisional wound healing in transforming growth factor-beta1 null mice. (United States)

    Koch, R M; Roche, N S; Parks, W T; Ashcroft, G S; Letterio, J J; Roberts, A B


    Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.

  15. Prediction of the martensite start temperature for {beta} titanium alloys as a function of composition

    Energy Technology Data Exchange (ETDEWEB)

    Neelakantan, Suresh [Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, 2629 HS, Delft (Netherlands); Materials Innovation Institute, Kluyverweg 1, 2629 HS, Delft (Netherlands)], E-mail:; Rivera-Diaz-del-Castillo, P.E.J.; Zwaag, Sybrand van der [Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, 2629 HS, Delft (Netherlands)


    A thermodynamics-based model to predict the martensite start temperature of {beta} titanium alloys is presented. The tendency of the {beta} phase to transform into martensite is estimated by applying the Ghosh-Olson approach to martensite nucleation modelling. The energetics and M{sub s} temperature for binary alloys are predicted with good accuracy. A succinct formula predicting M{sub s} temperature in multicomponent {beta} alloys is presented. The new equation is compared to the classical Mo equivalence criterion for assessing {beta} stability.

  16. Experimental Study on the Milling of a Ti Beta 21S

    Institute of Scientific and Technical Information of China (English)


    Ti Beta 21S (Ti-15Mo-2.7Nb-3Al-0.2Si) was devel op ed by TIMET in 1989. It is a metastable beta titanium alloy that offers subs tantial weight reductions over other engineering materials. Compared with common beta Ti alloys, it offers the high specific strength, good cold formability, im proved oxidation resistance, elevated temperature strength, creep resistance, an d thermal stability. Besides the common characters of titanium alloy, such as po or heat diffusivity, low elastic modulus, Ti Beta 21S has ...

  17. Performance of a parallel plate ionization chamber in beta radiation dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Patricia L.; Caldas, Linda V.E., E-mail: patrilan@ipen.b, E-mail: lcaldas@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)


    A homemade parallel plate ionization chamber with graphite collecting electrode, and developed for use in mammography beams, was tested in relation to its usefulness in beta radiation dosimetry at the Calibration Laboratory of IPEN. Characterization tests of this ionization chamber were performed, using the Sr-90 + Y-90, Kr-85 and Pm-147 sources of a beta secondary standard system. The results of saturation, leakage current, stabilization time, response stability, linearity, angular dependence, and calibration coefficients are within the recommended limits of international recommendations that indicate that this chamber may be used for beta radiation dosimetry. (author)

  18. The disintegrin and metalloproteinase ADAM12 contributes to TGF-beta signaling through interaction with the type II receptor

    DEFF Research Database (Denmark)

    Atfi, Azeddine; Dumont, Emmanuelle; Colland, Frédéric;


    Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological processes through two types of Ser/Thr transmembrane receptors: the TGF-beta type I receptor and the TGF-beta type II receptor (TbetaRII). Upon ligand binding, TGF-beta type I receptor activated by TbetaRII propagates...... signals to Smad proteins, which mediate the activation of TGF-beta target genes. In this study, we identify ADAM12 (a disintegrin and metalloproteinase 12) as a component of the TGF-beta signaling pathway that acts through association with TbetaRII. We found that ADAM12 functions by a mechanism...... independent of its protease activity to facilitate the activation of TGF-beta signaling, including the phosphorylation of Smad2, association of Smad2 with Smad4, and transcriptional activation. Furthermore, ADAM12 induces the accumulation of TbetaRII in early endosomal vesicles and stabilizes the Tbeta...

  19. Recent Progress on Spherical Torus Research

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Masayuki [PPPL; Kaita, Robert [PPPL


    The spherical torus or spherical tokamak (ST) is a member of the tokamak family with its aspect ratio (A = R0/a) reduced to A ~ 1.5, well below the normal tokamak operating range of A ≥ 2.5. As the aspect ratio is reduced, the ideal tokamak beta β (radio of plasma to magnetic pressure) stability limit increases rapidly, approximately as β ~ 1/A. The plasma current it can sustain for a given edge safety factor q-95 also increases rapidly. Because of the above, as well as the natural elongation κ, which makes its plasma shape appear spherical, the ST configuration can yield exceptionally high tokamak performance in a compact geometry. Due to its compactness and high performance, the ST configuration has various near term applications, including a compact fusion neutron source with low tritium consumption, in addition to its longer term goal of attractive fusion energy power source. Since the start of the two megaampere class ST facilities in 2000, National Spherical Torus Experiment (NSTX) in the US and Mega Ampere Spherical Tokamak (MAST) in UK, active ST research has been conducted worldwide. More than sixteen ST research facilities operating during this period have achieved remarkable advances in all of fusion science areas, involving fundamental fusion energy science as well as innovation. These results suggest exciting future prospects for ST research both near term and longer term. The present paper reviews the scientific progress made by the worldwide ST research community during this new mega-ampere-ST era.

  20. Deletion of the mitochondrial flavoprotein apoptosis inducing factor (AIF induces beta-cell apoptosis and impairs beta-cell mass.

    Directory of Open Access Journals (Sweden)

    Fabienne T Schulthess

    Full Text Available BACKGROUND: Apoptosis is a hallmark of beta-cell death in both type 1 and type 2 diabetes mellitus. Understanding how apoptosis contributes to beta-cell turnover may lead to strategies to prevent progression of diabetes. A key mediator of apoptosis, mitochondrial function, and cell survival is apoptosis inducing factor (AIF. In the present study, we investigated the role of AIF on beta-cell mass and survival using the Harlequin (Hq mutant mice, which are hypomorphic for AIF. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical evaluation of pancreata from Hq mutant mice displayed much smaller islets compared to wild-type mice (WT. Analysis of beta-cell mass in these mice revealed a greater than 4-fold reduction in beta-cell mass together with an 8-fold increase in beta-cell apoptosis. Analysis of cell cycle dynamics, using BrdU pulse as a marker for cells in S-phase, did not detect significant differences in the frequency of beta-cells in S-phase. In contrast, double staining for phosphorylated Histone H3 and insulin showed a 3-fold increase in beta-cells in the G2 phase in Hq mutant mice, but no differences in M-phase compared to WT mice. This suggests that the beta-cells from Hq mutant mice are arrested in the G2 phase and are unlikely to complete the cell cycle. beta-cells from Hq mutant mice display increased sensitivity to hydrogen peroxide-induced apoptosis, which was confirmed in human islets in which AIF was depleted by siRNA. AIF deficiency had no effect on glucose stimulated insulin secretion, but the impaired effect of hydrogen peroxide on beta-cell function was potentiated. CONCLUSIONS/SIGNIFICANCE: Our results indicate that AIF is essential for maintaining beta-cell mass and for oxidative stress response. A decrease in the oxidative phosphorylation capacity may counteract the development of diabetes, despite its deleterious effects on beta-cell survival.

  1. Rare-earth doped (alpha'/beta')-sialon ceramics

    CERN Document Server

    Gajum, N R


    combination of light and heavy rare-earth (Yb-Nd and Gd-Nd), and then pressureless sintered and compared with the single cation materials. Materials in the as sintered state were composed of a high alpha' sialon content with a minor amount of beta' sialon and 12H A1N polytype indicating that the heavy rare-earth (which is the principal alpha' stabilizer) has a dominant effect although EDAX analysis confirmed the presence of both cations (light and heavy) within the alpha' structure. The research also compared, and developed an understanding of, the thermal stability of alpha'-sialon using single Yb or mixed cations. The Yb single cation alpha'/beta' materials exhibited excellent stability over a range of temperature (1200 - 1600 deg C) and for different periods of time up to 168 hrs. The heat treatments result in the crystallisation of the residual phase as a Yb garnet phase which formed at approx 1300 deg C. The mixed cation alpha'/beta' materials showed some alpha'-beta' transformation. The transformation w...

  2. ATP-promoted amyloidosis of an amyloid beta peptide. (United States)

    Exley, C


    Amyloidosis is implicated in the aetiology of a number of disorders of human health. The factors that influence its instigation and subsequent rate of progress are the subject of a considerable research effort. The peptide fragment A beta(25-35) is amyloidogenic and has proven to be a useful model of the processes involved in amyloidosis. It is demonstrated herein that the assembly of A beta(25-35) into thioflavin T-reactive fibrils and their subsequent rearrangement into advanced glycation endproducts is accelerated by ATP. Aluminium potentiated these effects of ATP, suggesting a possible link with the aetiology of amyloidoses in vivo.

  3. Model of Break-Bone Fever via Beta-Derivatives

    Directory of Open Access Journals (Sweden)

    Abdon Atangana


    Full Text Available Using the new derivative called beta-derivative, we modelled the well-known infectious disease called break-bone fever or the dengue fever. We presented the endemic equilibrium points under certain conditions of the physical parameters included in the model. We made use of an iteration method to solve the extended model. To show the efficiency of the method used, we have presented in detail the stability and the convergence of the method for solving the system (2. We presented the uniqueness of the special solution of system (2 and finally the numerical simulations were presented for various values of beta.

  4. Model of Break-Bone Fever via Beta-Derivatives (United States)

    Atangana, Abdon; Oukouomi Noutchie, Suares Clovis


    Using the new derivative called beta-derivative, we modelled the well-known infectious disease called break-bone fever or the dengue fever. We presented the endemic equilibrium points under certain conditions of the physical parameters included in the model. We made use of an iteration method to solve the extended model. To show the efficiency of the method used, we have presented in detail the stability and the convergence of the method for solving the system (2). We presented the uniqueness of the special solution of system (2) and finally the numerical simulations were presented for various values of beta. PMID:25295263

  5. Progress Report

    DEFF Research Database (Denmark)

    Duer, Karsten


    Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

  6. Simultaneous beta and gamma spectroscopy (United States)

    Farsoni, Abdollah T.; Hamby, David M.


    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  7. Annual Progress report - General Task

    Energy Technology Data Exchange (ETDEWEB)

    Wesnousky, S.G.


    This report provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).{close_quotes} A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing tasks.

  8. Detailed transcriptome atlas of the pancreatic beta cell

    Directory of Open Access Journals (Sweden)

    Eizirik Decio L


    Full Text Available Abstract Background Gene expression patterns provide a detailed view of cellular functions. Comparison of profiles in disease vs normal conditions provides insights into the processes underlying disease progression. However, availability and integration of public gene expression datasets remains a major challenge. The aim of the present study was to explore the transcriptome of pancreatic islets and, based on this information, to prepare a comprehensive and open access inventory of insulin-producing beta cell gene expression, the Beta Cell Gene Atlas (BCGA. Methods We performed Massively Parallel Signature Sequencing (MPSS analysis of human pancreatic islet samples and microarray analyses of purified rat beta cells, alpha cells and INS-1 cells, and compared the information with available array data in the literature. Results MPSS analysis detected around 7600 mRNA transcripts, of which around a third were of low abundance. We identified 2000 and 1400 transcripts that are enriched/depleted in beta cells compared to alpha cells and INS-1 cells, respectively. Microarray analysis identified around 200 transcription factors that are differentially expressed in either beta or alpha cells. We reanalyzed publicly available gene expression data and integrated these results with the new data from this study to build the BCGA. The BCGA contains basal (untreated conditions gene expression level estimates in beta cells as well as in different cell types in human, rat and mouse pancreas. Hierarchical clustering of expression profile estimates classify cell types based on species while beta cells were clustered together. Conclusion Our gene atlas is a valuable source for detailed information on the gene expression distribution in beta cells and pancreatic islets along with insulin producing cell lines. The BCGA tool, as well as the data and code used to generate the Atlas are available at the T1Dbase website (

  9. Trace Carbon in Biomedical Beta-Titanium Alloys: Recent Progress (United States)

    Zhao, D.; Ebel, T.; Yan, M.; Qian, M.


    Owing to their relatively low Young's modulus, high strength, good resistance to corrosion, and excellent biocompatibility, β-titanium (Ti) alloys have shown great potential for biomedical applications. In β-Ti alloys, carbon can exist in the form of titanium carbide (TiC x ) as well as interstitial atoms. The Ti-C binary phase diagram predicts a carbon solubility value of 0.08 wt.% in β-Ti, which has been used as the carbon limit for a variety of β-Ti alloys. However, noticeable grain boundary TiC x particles have been observed in β-Ti alloys containing impurity levels of carbon well below the predicted 0.08 wt.%. This review focuses its attention on trace carbon (≤0.08 wt.%) in biomedical β-Ti alloys containing niobium (Nb) and molybdenum (Mo), and it discusses the nature and precipitation mechanism of the TiC x particles in these alloys.

  10. Beta section Beta: biogeographical patterns of variation and taxonomy.

    NARCIS (Netherlands)

    Letschert, J.P.W.


    In Chapter 1 an account is given of the historical subdivision of the genus Beta and its sections, and the relations of the sections are discussed. Emphasis is given to the taxonomic treatment of wild section Beta by various authors. The Linnaean names B. vulgaris L. and B. maritima L. are lectotypi

  11. Cyclic modular beta-sheets. (United States)

    Woods, R Jeremy; Brower, Justin O; Castellanos, Elena; Hashemzadeh, Mehrnoosh; Khakshoor, Omid; Russu, Wade A; Nowick, James S


    The development of peptide beta-hairpins is problematic, because folding depends on the amino acid sequence and changes to the sequence can significantly decrease folding. Robust beta-hairpins that can tolerate such changes are attractive tools for studying interactions involving protein beta-sheets and developing inhibitors of these interactions. This paper introduces a new class of peptide models of protein beta-sheets that addresses the problem of separating folding from the sequence. These model beta-sheets are macrocyclic peptides that fold in water to present a pentapeptide beta-strand along one edge; the other edge contains the tripeptide beta-strand mimic Hao [JACS 2000, 122, 7654] and two additional amino acids. The pentapeptide and Hao-containing peptide strands are connected by two delta-linked ornithine (deltaOrn) turns [JACS 2003, 125, 876]. Each deltaOrn turn contains a free alpha-amino group that permits the linking of individual modules to form divalent beta-sheets. These "cyclic modular beta-sheets" are synthesized by standard solid-phase peptide synthesis of a linear precursor followed by solution-phase cyclization. Eight cyclic modular beta-sheets 1a-1h containing sequences based on beta-amyloid and macrophage inflammatory protein 2 were synthesized and characterized by 1H NMR. Linked cyclic modular beta-sheet 2, which contains two modules of 1b, was also synthesized and characterized. 1H NMR studies show downfield alpha-proton chemical shifts, deltaOrn delta-proton magnetic anisotropy, and NOE cross-peaks that establish all compounds but 1c and 1g to be moderately or well folded into a conformation that resembles a beta-sheet. Pulsed-field gradient NMR diffusion experiments show little or no self-association at low (

  12. The role of EKLF in human beta-globin gene competition. (United States)

    Wijgerde, M; Gribnau, J; Trimborn, T; Nuez, B; Philipsen, S; Grosveld, F; Fraser, P


    We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knockout mice express the human epsilon and gamma-globin genes normally in embryonic red cells. However, fetal liver erythropoiesis, which is marked by a period of gamma- and beta-gene competition in which the genes are alternately transcribed, exhibits an altered ratio of gamma- to beta-gene transcription. EKLF heterozygous fetal livers display a decrease in the number of transcriptionally active beta genes with a reciprocal increase in the number of transcriptionally active gamma genes. beta-Gene transcription is absent in homozygous knockout fetuses with coincident changes in chromatin structure at the beta promoter. There is a further increase in the number of transcriptionally active gamma genes and accompanying gamma gene promoter chromatin alterations. These results indicate that EKLF plays a major role in gamma- and beta-gene competition and suggest that EKLF is important in stabilizing the interaction between the Locus Control Region and the beta-globin gene. In addition, these findings provide further evidence that developmental modulation of globin gene expression within individual cells is accomplished by altering the frequency and/or duration of transcriptional periods of a gene rather than changing the rate of transcription.

  13. Integration of BETA with Eclipse

    DEFF Research Database (Denmark)

    Andersen, Peter; Madsen, Ole Lehrmann; Enevoldsen, Mads Brøgger


    This paper presents language interoperability issues appearing in order to implement support for the BETA language in the Java-based Eclipse integrated development environment. One of the challenges is to implement plug-ins in BETA and be able to load them in Eclipse. In order to do this, some form...

  14. Measurements of sin 2 $\\beta$

    CERN Document Server

    Tricomi, A


    A review of the most recent measurements of the CP violating parameter sin 2 beta from LEP and CDF is reported. These yield an average value of sin 2 beta =0.91+or-0.35, giving a confidence level that CP violation in the B system has been observed of almost 99%. (10 refs).

  15. Beta decay of Cu-56

    NARCIS (Netherlands)

    Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M


    The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the p

  16. Beta Function and Anomalous Dimensions

    DEFF Research Database (Denmark)

    Pica, Claudio; Sannino, Francesco


    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalou...

  17. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  18. How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study.

    Directory of Open Access Journals (Sweden)

    Zdeněk Kříž

    Full Text Available Progressive cerebral deposition of amyloid beta occurs in Alzheimers disease and during the aging of certain mammals (human, monkey, dog, bear, cow, cat but not others (rat, mouse. It is possibly due to different amino acid sequences at positions 5, 10 and 13. To address this issue, we performed series of 100 ns long trajectories (each trajectory was run twice with different initial velocity distribution on amyloid beta (1-42 with the human and rat amino acid sequence in three different environments: water with only counter ions, water with NaCl at a concentration of 0.15 M as a model of intracellular Na(+ concentration at steady state, and water with NaCl at a concentration of 0.30 M as a model of intracellular Na(+ concentration under stimulated conditions. We analyzed secondary structure stability, internal hydrogen bonds, and residual fluctuation. It was observed that the change in ionic strength affects the stability of internal hydrogen bonds. Increasing the ionic strength increases atomic fluctuation in the hydrophobic core of the human amyloid, and decreases the atomic fluctuation in the case of rat amyloid. The secondary structure analyses show a stable α-helix part between residues 10 and 20. However, C-terminus of investigated amyloids is much more flexible showing no stable secondary structure elements. Increasing ionic strength of the solvent leads to decreasing stability of the secondary structural elements. The difference in conformational behavior of the three amino acids at position 5, 10 and 13 for human and rat amyloids significantly changes the conformational behavior of the whole peptide.

  19. Project 8 Phase II: Improved beta decay electrons reconstruction (United States)

    Guigue, Mathieu; Project 8 Collaboration


    The Project 8 collaboration aims to measure the absolute neutrino mass scale using a cyclotron radiation emission spectroscopy technique on the beta decays of tritium. The second phase of the project will measure a differential spectrum of tritium beta decays and extract the tritium endpoint value with an eV or sub-eV scale precision. Monoenergetic electrons emitted by gaseous 83mKr atoms can be used to determine the coefficient between the cyclotron frequency and the electron energy and to optimize the instrument configuration for the tritium measurement. We present the progress on the processing of the electron cyclotron radiation signal to reconstruct the beta decay spectrum of krypton and tritium.

  20. Stability Functions

    CERN Document Server

    Burns, Daniel; Wang, Zuoqin


    In this article we discuss the role of stability functions in geometric invariant theory and apply stability function techniques to problems in toric geometry. In particular we show how one can use these techniques to recover results of Burns-Guillemin-Uribe and Shiffman-Tate-Zelditch on asymptotic properties of sections of holomorphic line bundles over toric varieties.

  1. Progressive Business

    DEFF Research Database (Denmark)

    Christiansen, Christian O.


    Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015.......Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015....

  2. Computational Studies of Beta Amyloid (Aβ42 with p75NTR Receptor: A Novel Therapeutic Target in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Shine Devarajan


    Full Text Available Alzheimer’s disease is a neurodegenerative disorder characterized by the accumulation of beta amyloid plaques (Aβ which can induce neurite degeneration and progressive dementia. It has been identified that neuronal apoptosis is induced by binding of Aβ42 to pan neurotrophin receptor (p75NTR and gave the possibility that beta amyloid oligomer is a ligand for p75NTR. However, the atomic contact point responsible for molecular interactions and conformational changes of the protein upon binding was not studied in detail. In view of this, we conducted a molecular docking and simulation study to investigate the binding behaviour of Aβ42 monomer with p75NTR ectodomain. Furthermore, we proposed a p75NTR-ectodomain-Aβ42 complex model. Our data revealed that, Aβ42 specifically recognizes CRD1 and CRD2 domains of the receptor and formed a “cap” like structure at the N-terminal of receptor which is stabilized by a network of hydrogen bonds. These findings are supported by molecular dynamics simulation that Aβ42 showed distinct structural alterations at N- and C-terminal regions due to the influence of the receptor binding site. Overall, the present study gives more structural insight on the molecular interactions of beta amyloid protein involved in the activation of p75NTR receptor.

  3. Radioactive decays at limits of nuclear stability

    DEFF Research Database (Denmark)

    Pfützner, M.; Karny, M.; Grigorenko, L. V.


    , and their relative probabilities. When approaching limits of nuclear stability, new decay modes set in. First, beta decays are accompanied by emission of nucleons from highly excited states of daughter nuclei. Second, when the nucleon separation energy becomes negative, nucleons start being emitted from the ground...

  4. Hb Santa Clara (beta 97His-->Asn), a human haemoglobin variant: functional characterization and structure modelling. (United States)

    De Rosa, Maria Cristina; Carelli Alinovi, Cristiana; Schininà, Maria Eugenia; Clementi, Maria Elisabetta; Amato, Antonio; Cappabianca, Maria Pia; Pezzotti, Michela; Giardina, Bruno


    This study examines the functional and structural effects of amino acid substitution at alpha(1)beta(2) interface of Hb Santa Clara (beta 97His-->Asn). We have characterized the variation by a combination of electrospray ionisation mass spectrometry and DNA sequence analysis followed by oxygen-binding experiments. Functional studies outlined an increased oxygen affinity, reduced effect of organic phosphates and a reduced Bohr effect with respect to HbA. In view of the primary role of this interface in the cooperative quaternary transition from the T to R conformational state, a theoretical three-dimensional model of Hb Santa Clara was generated. Structural investigations suggest that replacement of Asn for His beta 97 results in a significant stabilization of the high affinity R-state of the haemoglobin molecule with respect to the low affinity T-state. The role of beta FG4 position has been further examined by computational models of known beta FG4 variants, namely Hb Malmö (beta 97His-->Gln), Hb Wood (beta 97His-->Leu), Hb Nagoya (beta 97His-->Pro) and Hb Moriguchi (beta 97His-->Tyr). These findings demonstrate that, among the various residues at the alpha(1)beta(2) (and alpha(2)beta(1)) intersubunit interface, His beta FG4 contributes significantly to the quaternary constraints that are responsible for the low oxygen affinity of human deoxyhaemoglobin.

  5. 污泥中重金属的稳定化研究进展与去除方法简述%Research Progress of Stabilization of Heavy Metals in Sludge and Their Removal Methods

    Institute of Scientific and Technical Information of China (English)

    刘晓光; 董滨; 戴翎翎; 戴晓虎


    通过“十一五”污水处理厂的建设,我国污泥产量也随之大幅增长,污泥的处理处置已经成为制约社会经济发展的重要问题。国际上的经验表明土地利用是污泥最终处置的主要发展方向,然而污泥中的重金属成为其土地利用的主要障碍。越来越多的研究者意识到,重金属的环境危害不仅仅取决于其总量,更取决于重金属存在形态。目前,Tessier分步提取法作为主流的污泥重金属划分方法,取得了广泛应用,该法将污泥中的重金属分成5种形态,分别为可交换态、碳酸盐结合态、铁锰氧化物结合态、有机结合态和残渣态。本文以此为基础综述了目前国内外主要的污泥重金属稳定和去除方法的原理及研究进展,比较了不同重金属稳定及去除方法的优点与不足,并提出了新的展望。%Through construction of sewage treatment plant during the 11 th Five-Year Plan, sludge production increased a lot. It leads to serious problems of sludge treatment and disposal that is restricting the development of society and economy. According to the experiences abroad, the method of land applications is the trend of the final disposal of sludge. However, heavy metal existence in sludge obstructs the land application. More and more researchers realize that the heavy metal hazard depends not only on the total amount but also the existence form. Presently, as a popular method for dividing the heavy metals in sludge, Tessier' s Step-by-step Extraction is applied widely. It classifies the heavy metals in sludge into five existence forms, i.e. , changeable state, carbonate, Iron-manganese oxide, organic state and residue. In this paper, based on the description above, the mechanism and research progress of present popular stabilization and removal processes are reviewed, and their advantages and disadvantages of different process are compared. The prospects in this respect arc

  6. Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis (United States)

    Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A.; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko


    Patient: Female, 49 Final Diagnosis: Cerebral venous thrombosis Symptoms: Altered mental state • weakness in limbs Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. Care Report: A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient’s thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. Conclusions: Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT. PMID:28228636

  7. Ensuring Stability

    Institute of Scientific and Technical Information of China (English)


    "Stable"will be a key word for China’s economy in 2012.That’s the beat set at the annual Central Economic Work Conference held in Beijing on December 12-14,which reviewed this year’s development and mapped out plans for the next year.Policymakers at the conference decided to keep macroeconomic policies stable,seek a stable and relatively fast economic growth,stabilize consumer prices and maintain social stability in 2012.On the basis of stability,the government will transform the development model,deepen reform and improve people’s livelihood.

  8. First principles theory of disordered alloys and alloy phase stability

    Energy Technology Data Exchange (ETDEWEB)

    Stocks, G.M.; Nicholson, D.M.C.; Shelton, W.A. [and others


    These lecture notes review the LDA-KKR-CPA method for treating the electronic structure and energetics of random alloys and the MF-CF and GPM theories of ordering and phase stability built on the LDA- KKR-CPA description of the disordered phase. Section 2 lays out the basic LDA-KKR-CPA theory of random alloys and some applications. Section 3 reviews the progress made in understanding specific ordering phenomena in binary solid solutions base on the MF-CF and GPM theories of ordering and phase stability. Examples are Fermi surface nesting, band filling, off diagonal randomness, charge transfer, size difference or local strain fluctuations, magnetic effects; in each case, an attempt is made to link the ordering and the underlying electronic structure of the disordered phase. Section 4 reviews calculations of electronic structure of {beta}-phase Ni{sub c}Al{sub 1-c} alloys using a version of the LDA-KKR-CPA codes generalized to complex lattices.

  9. Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint



    Paul J FitzgeraldThe Zanvyl Krieger Mind/Brain Institute, Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USAAbstract: There is growing evidence that the neurotransmitter norepinephrine (NE) and its sister molecule epinephrine (EPI) (adrenaline) affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors) results in lower recurrence, progression, or mortality of ...

  10. Stabilizing Niger

    DEFF Research Database (Denmark)

    Hahonou, Eric Komlavi

    international intervention in Niger. Their main objective is to secure their own strategic, economic and political interests by strengthening the Nigerien authorities through direct intervention and capacity building activities. For western states reinforcing state security institutions and stabilizing elite...

  11. Experiments on double beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Busto, J. [Neuchatel Univ. (Switzerland). Inst. de Physique


    The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

  12. Alterations of expression and regulation of transforming growth factor beta in human cancer prostate cell lines. (United States)

    Blanchère, M; Saunier, E; Mestayer, C; Broshuis, M; Mowszowicz, I


    TGF beta can promote and/or suppress prostate tumor growth through multiple and opposing actions. Alterations of its expression, secretion, regulation or of the sensitivity of target cells can lead to a favorable environment for tumor development. To gain a better insight in TGF beta function during cancer progression, we have used different cultured human prostate cells: preneoplastic PNT2 cells, the androgen-dependent LNCaP and the androgen-independent PC3 and DU145 prostate cancer cell lines. We have studied by specific ELISA assays in conditioned media (CM), the secretion of TGF beta 1 and TGF beta 2 in basal conditions and after hormonal treatment (DHT or E2) and the expression of TGF beta 1 mRNA by Northern blot. We have also compared the effect of fibroblast CM on TGF beta secretion by the different cell types. Compared to PNT2 cells, cancer cell lines secrete lower levels of active TGF beta which are not increased in the presence of fibroblast CM. LNCaP cells respond to androgen or estrogen treatment by a 10-fold increase of active TGF beta secretion while PC3 and DU145 are unresponsive. In conclusion, prostate cancer cell lines have lost part of their ability to secrete and activate TGF beta, and to regulate this secretion through stromal-epithelial interactions. Androgen-sensitive cancer cells may compensate this loss by hormonal regulation.

  13. Dosimetry of {beta} extensive sources; Dosimetria de fuentes {beta} extensas

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E.L.; Lallena R, A.M. [Departamento de Fisica Moderna, Universidad de Granada, E-18071 Granada (Spain)


    In this work, we have been studied, making use of the Penelope Monte Carlo simulation code, the dosimetry of {beta} extensive sources in situations of spherical geometry including interfaces. These configurations are of interest in the treatment of the called cranealfaringyomes of some synovia leisure of knee and other problems of interest in medical physics. Therefore, its application can be extended toward problems of another areas with similar geometric situation and beta sources. (Author)

  14. Evolution of outer membrane beta-barrels from an ancestral beta beta hairpin. (United States)

    Remmert, M; Biegert, A; Linke, D; Lupas, A N; Söding, J


    Outer membrane beta-barrels (OMBBs) are the major class of outer membrane proteins from Gram-negative bacteria, mitochondria, and plastids. Their transmembrane domains consist of 8-24 beta-strands forming a closed, barrel-shaped beta-sheet around a central pore. Despite their obvious structural regularity, evidence for an origin by duplication or for a common ancestry has not been found. We use three complementary approaches to show that all OMBBs from Gram-negative bacteria evolved from a single, ancestral beta beta hairpin. First, we link almost all families of known single-chain bacterial OMBBs with each other through transitive profile searches. Second, we identify a clear repeat signature in the sequences of many OMBBs in which the repeating sequence unit coincides with the structural beta beta hairpin repeat. Third, we show that the observed sequence similarity between OMBB hairpins cannot be explained by structural or membrane constraints on their sequences. The third approach addresses a longstanding problem in protein evolution: how to distinguish between a very remotely homologous relationship and the opposing scenario of "sequence convergence." The origin of a diverse group of proteins from a single hairpin module supports the hypothesis that, around the time of transition from the RNA to the protein world, proteins arose by amplification and recombination of short peptide modules that had previously evolved as cofactors of RNAs.

  15. Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate ({beta}-TCP) on the beagle dog 1-wall periodontal defect model

    Energy Technology Data Exchange (ETDEWEB)

    Anzai, Jun, E-mail: [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Kitamura, Masahiro, E-mail: [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nozaki, Takenori, E-mail: [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagayasu, Toshie, E-mail: [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Terashima, Akio, E-mail: [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Asano, Taiji, E-mail: [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Murakami, Shinya, E-mail: [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan)


    Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontal tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal

  16. Questions Students Ask: Beta Decay. (United States)

    Koss, Jordan; Hartt, Kenneth


    Answers a student's question about the emission of a positron from a nucleus. Discusses the problem from the aspects of the uncertainty principle, beta decay, the Fermi Theory, and modern physics. (YP)

  17. Understanding the influence of MgO and SrO binary doping on the mechanical and biological properties of beta-TCP ceramics. (United States)

    Banerjee, Shashwat S; Tarafder, Solaiman; Davies, Neal M; Bandyopadhyay, Amit; Bose, Susmita


    The objective of this study was to evaluate the influence of MgO and SrO doping on the mechanical and biological properties of beta-tricalcium phosphate (beta-TCP). beta-TCP was doped with two different binary compositions, 0.25 and 1.0wt.% SrO along with 1.0wt.% MgO. MgO and SrO doping increased the beta phase stability at a sintering temperature of 1250 degrees C and marginally decreased the compressive strength of beta-TCP. An in vitro cell-material interaction study, using human fetal osteoblast cells (hFOB), indicated that doped beta-TCP was non-toxic, and MgO/SrO dopants improved cell attachment and growth. beta-TCP implants doped with 1.0wt.% MgO and 1.0wt.% SrO showed good in vivo biocompatibility when tested in male Sprague-Dawley rats for 16 weeks. Histomorphology analysis indicated that MgO/SrO-doped beta-TCP promoted more osteogenesis than pure beta-TCP. In vivo osteocalcin and type I collagen assay also revealed faster bone formation in rats with doped beta-TCP implant compared to rats with pure beta-TCP implant. Low Ca(2+) concentration in the urine of rats with doped beta-TCP implant confirmed slower degradation of MgO/SrO-doped beta-TCP than pure beta-TCP.

  18. Design and production of sintered {beta}-tricalcium phosphate 3D scaffolds for bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Carlos F.L. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Silva, Abilio P. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Lopes, Luis [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Pires, Ines [Instituto de Engenharia Mecanica - Lisboa (IDMEC Lisboa/IST/UTL), Avenida Rovisco Pais, 1049-001 Lisboa (Portugal); Correia, Ilidio J., E-mail: [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)


    The characteristics of sintered {beta}-tricalcium phosphate ({beta}-TCP) scaffolds produced by 3D printing were studied by means of X-ray diffraction, Scanning Electron Microscopy, Fourier transform infrared spectroscopy, uniaxial compression tests and cytotoxicity tests, using human osteoblast cells. The results reported include details of the {beta}-TCP scaffolds' porosity, density, phase stability, mechanical behavior and cytotoxic profile. Collectively, these properties are fundamental for the future application of these scaffolds as bone substitutes for individualized therapy. Highlights: Black-Right-Pointing-Pointer {beta}-Tricalcium phosphate ({beta}-TCP) 3D scaffolds were produced by rapid prototyping. Black-Right-Pointing-Pointer Scaffold properties were assessed by SEM, FTIR, XRD and by mechanical tests. Black-Right-Pointing-Pointer The cytotoxic profile of the scaffolds was characterized by in vitro assays. Black-Right-Pointing-Pointer Scaffolds have good properties for its application as bone substitutes for individualized therapy.

  19. Effect of Addition of Cereal Based Beta-glucan on Technological and Functional Properties of Foods

    Directory of Open Access Journals (Sweden)

    Nihal Şimşekli


    Full Text Available Nowadays usage of dietary fibers in foods has been increasing duo to revealing of health benefits. Beta-glucans found especially in oats and barley, are polysaccharide and source of water-soluble dietary fiber. Positive effects of beta-glucans like healing coronary-heart disease, lowering blood cholesterol level, balancing blood sugar level and preventing obesity, made beta-glucans widespread functional food components for producing various foods. In addition to beneficial physiological effects of beta-glucans, they texturize, gelatinize, emulsify and stabilize the foods. They increase viscosity, replace fat and enhance rheological properties in cereal, meat and dairy products. They are also used to produce packing material depending on their mechanical properties and molecular weights. In this review, effects of addition of cereal based beta-glucans on technological and functional properties of various foods are revealed based on previous studies.

  20. An Investigation of low beta triplet vibrational issues at Fermilab's Collider Detector

    Energy Technology Data Exchange (ETDEWEB)

    Michael W. McGee


    The vibrational aspects of recent disturbances at the low beta focusing quadrupoles, which caused proton beam loss at the Collider Detector at Fermilab (CDF), are discussed. Two low beta focusing quadrupoles are supported by a girder, which is extended over the CDF collision hall pit on each side. The low beta girder has a ledge mount support at an alcove's face and two Invar rods near the opposite end. Forced response measurements were taken on the low beta girder, where the power spectral density (PSD) function was used to obtain RMS displacement. The effects of local excitation due to operating equipment and near-field excitation due to ambient ground motion caused by local traffic are examined. The discussion explores dynamic response characteristics of the low beta quadrupoles and supporting girder using beam loss as the vibrational stability criteria. This paper also presents practical problem-solving approaches for similar accelerator components.

  1. Thermal denaturation of beta-galactosidase and of two site-specific mutants. (United States)

    Edwards, R A; Jacobson, A L; Huber, R E


    The thermal denaturation of wild-type beta-galactosidase and two beta-galactosidases with substitutions at the active site was studied by kinetics, differential scanning calorimetry, electrophoresis, molecular exclusion chromatography, and circular dichroism. From the results, a model is developed for thermal denaturation of beta-galactosidase which includes the reversible dissociation of ligands, reversible formation of an inactive tetramer, irreversible dissociation of the inactive tetramer to inactive monomers, and subsequent aggregation of inactive monomers to dimers and larger aggregates. Under some conditions, partial reversibility of the activity loss could be demonstrated, and several intermediates in the thermal denaturation process were trapped by quenching and observed by electrophoresis and molecular exclusion chromatography. The ligands Mg2+ and phenylethyl thio-beta-D-galactoside increase the stability of beta-galactosidase to heat denaturation by shifting the ligand binding equilibrium according to Le Chatelier's principle, thus decreasing the concentration of the ligand-free tetramer which can proceed to subsequent steps. Circular dichroism results indicated that beta-galactosidase is dominated by beta-sheet with lower amounts of alpha-helix. Large changes in secondary structure begin to occur only after activity has been lost. Single amino acid changes at the active site can have significant effects on thermal stability of beta-galactosidases. Some of the effects result from increased thermal stability of the ligand-free enzyme itself. Other effects result from changes in ligand binding, but the magnitude of the resulting changes in stability is not related to the strength of ligand binding in a simple fashion.

  2. Dynesys 动态固定系统与腰椎相邻节段退变的研究进展%Research progress of Dynesys dynamic stabilization system and lumbar adjacent segment degeneration

    Institute of Scientific and Technical Information of China (English)

    张阳; 李放


      In recent years, the lumbar non-fusion technique remains a hot research topic in spine surgery, and the Dynesys dynamic stabilization system is one of the most widely applied non-fusion techniques clinically. The system is designed to stabilize the operated segments and meanwhile preserve some mobility, so as to prevent the stress concentration of adjacent segments and relieve adjacent segment degeneration. Many clinical studies show that the Dynesys system could have satisfied clinical results, but at present there are still some controversies about the role of the Dynesys dynamic stabilization system in reducing adjacent segment degeneration. The biomechanical and clinical research about the role of the Dynesys system in preventing adjacent segment degeneration is reviewed in this article, to provide clinical evidence.

  3. Beta Function and Anomalous Dimensions

    CERN Document Server

    Pica, Claudio


    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalous dimension of the fermion masses at the infrared fixed point, and the resulting values compare well with the lattice determinations.

  4. Polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Morant, Marc


    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  5. Role of metabolic programming in the pathogenesis of beta-cell failure in postnatal life. (United States)

    Simmons, Rebecca A


    Intrauterine growth retardation (IUGR) has been linked to later development of type 2 diabetes in adulthood. Human studies indicate that individuals who were growth retarded at birth have impaired insulin secretion and insulin resistance. Multiple animal models of IUGR demonstrate impaired beta-cell function and development. We have developed a model of IUGR in the rat that leads to diabetes in adulthood with the salient features of most forms of type 2 diabetes in the human: progressive defects in insulin secretion and insulin action prior to the onset of overt hyperglycemia. Decreased beta-cell proliferation leads to a progressive decline in beta-cell mass. Using this model, we have tested the hypothesis that uteroplacental insufficiency disrupts the function of the electron transport chain in the fetal beta-cell and leads to a debilitating cascade of events: increased production of reactive oxygen species, which in turn damage mitochondrial (mt) mtDNA and causes further production of reactive oxygen species (ROS). The net result is progressive loss of beta-cell function and eventual development of type 2 diabetes in the adult. Studies in the IUGR rat also demonstrate that an abnormal intrauterine environment induces epigenetic modifications of key genes regulating beta-cell development; experiments directly link chromatin remodeling with suppression of transcription. Future research will be directed at elucidating the mechanisms underlying epigenetic modifications in offspring.

  6. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Slobodan M Jankovic


    Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

  7. Shape-controlled Synthesis of Gold Nanoparticles from Gold(III)-chelates of {beta}-diketones

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Subrata [Indian Institute of Technology, Department of Chemistry (India); Pal, Anjali [Indian Institute of Technology, Department of Civil Engineering (India); Ghosh, Sujit Kumar; Nath, Sudip; Panigrahi, Sudipa; Praharaj, Snigdhamayee; Basu, Soumen; Pal, Tarasankar [Indian Institute of Technology, Department of Chemistry (India)], E-mail:


    Chelating ligands with {beta}-diketone skeleton have been employed for the first time as reductant to produce ligand stabilized gold nanoparticles of different shapes out of aqueous HAuCl{sub 4} solutions. Evolution of stable gold nanoparticles happens to be first order with respect to gold particles having rate constants {approx}{approx}10{sup -2} min{sup -1} and subsequent chlorine insertion in the {beta}-diketone skeleton is reported as a general feature. Spherical or triangular or hexagonal particle evolution goes selectively under the influence of different {beta}-diketones in terms of capping and reducing capabilities of the reductants.

  8. Interactions of ceftobiprole with beta-lactamases from molecular classes A to D. (United States)

    Queenan, Anne Marie; Shang, Wenchi; Kania, Malgosia; Page, Malcolm G P; Bush, Karen


    The interactions of ceftobiprole with purified beta-lactamases from molecular classes A, B, C, and D were determined and compared with those of benzylpenicillin, cephaloridine, cefepime, and ceftazidime. Enzymes were selected from functional groups 1, 2a, 2b, 2be, 2d, 2e, and 3 to represent beta-lactamases from organisms within the antibacterial spectrum of ceftobiprole. Ceftobiprole was refractory to hydrolysis by the common staphylococcal PC1 beta-lactamase, the class A TEM-1 beta-lactamase, and the class C AmpC beta-lactamase but was labile to hydrolysis by class B, class D, and class A extended-spectrum beta-lactamases. Cefepime and ceftazidime followed similar patterns. In most cases, the hydrolytic stability of a substrate correlated with the MIC for the producing organism. Ceftobiprole and cefepime generally had lower MICs than ceftazidime for AmpC-producing organisms, particularly AmpC-overexpressing Enterobacter cloacae organisms. However, all three cephalosporins were hydrolyzed very slowly by AmpC cephalosporinases, suggesting that factors other than beta-lactamase stability contribute to lower ceftobiprole and cefepime MICs against many members of the family Enterobacteriaceae.

  9. Inclusion complexes of nabumetone with beta-cyclodextrins: thermodynamics and molecular modelling studies. Influence of sodium perchlorate. (United States)

    Goyenechea, N; Sánchez, M; Vélaz, I; Martín, C; Martínez-Ohárriz, M C; González-Gaitano, G


    Fluorescence, (1)H-NMR and molecular mechanics have been used to study the inclusion complexes of nabumetone (4,6-methoxy-2-naphthyl-butan-2-one; NAB) with beta-cyclodextrin (beta-CD), randomly methylated-beta (M beta-CD) and hydroxypropyl-beta-cyclodextrins (HP beta-CD). The emission spectrum of NAB shows a maximum whose fluorescence intensity increases with the different beta-CDs growing concentrations. This phenomenon allows calculation of the stability constants at 15, 25, 37 and 45 degrees C. The thermodynamic parameters Delta H degrees and Delta S degrees for the inclusion process were obtained from the temperature dependence of the stability constants. Molecular mechanics calculations, together with proton NMR measurements, for the complex with beta-CD prove that the complex can be formed by penetration through any of the rims, with the naphthalene nucleus included and the substituents outside the cavity. The influence of NaClO(4) in the aforementioned complexes has been analysed by spectrofluorimetric measurements. It has been found that the stability constants for the complexes decrease with the salt concentration; the causes are discussed.


    Institute of Scientific and Technical Information of China (English)



    A new algorithm for the stabilization of (possibly turbulent, chaotic) distributed systems, governed by linear or non linear systems of equations is presented. The SPA (Stabilization Parallel Algorithm) is based on a systematic parallel decomposition of the problem (related to arbitrarily overlapping decomposition of domains) and on a penalty argument. SPA is presented here for the case of linear parabolic equations: with distrjbuted or boundary control. It extends to practically all linear and non linear evolution equations, as it will be presented in several other publications.

  11. The GERDA experiment on 0{nu}{beta}{beta} decay

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Kai [Eberhard Karls Universitaet Tuebingen (Germany); Collaboration: GERDA-Collaboration


    The Gerda (Germanium Detector Array) collaboration searches for the neutrinoless double beta decay (0{nu}{beta}{beta}) of {sup 76}Ge. The existence of this decay would give rise to the assumption that the neutrino is a Majorana particle, i.e. its own antiparticle. A measured half-life could be used to determine the effective neutrino mass and hence resolve the neutrino mass hierarchy problem. Germanium diodes, isotopically enriched in {sup 76}Ge, are used as both source and detector. Due to the low rate of this decay (T{sub 1/2}>10{sup 25} y), the experimental background must be reduced to a level of 10{sup -2}counts/(kg y keV) or better in the region around Q{sub {beta}{beta}}. To minimize background from cosmogenically produced secondary particles, a low Z shielding is employed. Thus, the naked diodes are operated in a liquid argon cryostat, which is surrounded by a water tank acting as both passive shield and active muon Cherenkov veto. Gerda started the commissioning runs in 2010 and in November 2011, the first phase of data taking with enriched detectors has begun. In this talk, the first year of the experiment is summarized.

  12. Factors contributing to the breakdown of sodium beta-alumina

    Energy Technology Data Exchange (ETDEWEB)

    Buechele, A.C.


    Clarification of the breakdown process occurring during charge transfer in sodium beta alumina solid electrolytes was derived from: (1) studying the effects of molten sodium contact at 350/sup 0/C on single crystal sodium beta alumina and polycrystalline sodium beta alumina; (2) determination of critical current density by monitoring acoustic emissions accompanying crack growth in sodium/sodium beta alumina/sodium cells subjected to linear current ramping at 1 mA cm/sup -2/ sec/sup -1/; (3) failure analysis conducted on cycled electrolytes, some from commercial sodium/sulfur cells, which had been subjected to up to 703 Ahr cm/sup -2/ of charge transfer. Gray coloration developing in beta aluminas in contact with molten sodium was found to be a consequence of formation, through reduction by sodium, of oxygen vacancies charge compensated by electrons. Electronic conductivity of the electrolyte increases as a result. No second phase formation was detected. Colored electrolytes from sodium/sulfur cells show evidence of a newly recognized degradation mechanism in which fracture occurs when sodium is reduced and deposited internally under pressure as metal in regions where an electronic conductivity gradient exists. Heating colored beta aluminas in air produces reoxidation and bleaching. Kinetics and other properties of the coloration and bleaching processes were determined. Critical current density was found to bear an inverse relation to average electrolyte grain size. Evidence was found in the cycled electrolytes for a slow crack growth mechanism and a progressive mode of degradation advancing from the sulfur electrode interface. Implications of the findings for the construction and operation of sodium/sulfur battery systems are discussed.

  13. Interstrand side chain--side chain interactions in a designed beta-hairpin: significance of both lateral and diagonal pairings. (United States)

    Syud, F A; Stanger, H E; Gellman, S H


    The contributions of interstrand side chain-side chain contacts to beta-sheet stability have been examined with an autonomously folding beta-hairpin model system. RYVEV(D)PGOKILQ-NH2 ((D)P = D-proline, O = ornithine) has previously been shown to adopt a beta-hairpin conformation in aqueous solution, with a two-residue loop at D-Pro-Gly. In the present study, side chains that display interstrand NOEs (Tyr-2, Lys-9, and Leu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In the beta-hairpin conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen bonded pair). This "lateral" juxtaposition of two hydrophobic side chains appears to contribute to beta-hairpin conformational stability, which is consistent with results from other beta-sheet model studies and with statistical analyses of interstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 and Lys-9 also stabilizes the beta-hairpin conformation. Tyr-2/Lys-9 is a "diagonal" interstrand juxtaposition because these residues are not directly across from one another in terms of the hydrogen bonding registry between the strands. This diagonal interaction arises from the right-handed twist that is commonly observed among beta-sheets. Evidence of diagonal side chain-side chain contacts has been observed in other autonomously folding beta-sheet model systems, but we are not aware of other efforts to determine whether a diagonal interaction contributes to beta-sheet stability.

  14. Macroeconomic stability

    DEFF Research Database (Denmark)

    Jespersen, Jesper


    It is demonstrated that full employment and sustainable development not necessarily are conflicting goals. On the other hand macroeconomic stability cannot be obtained without a deliberate labour sharing policy and a shift in the composition of private consumption away from traditional material...

  15. In-trap decay spectroscopy for {beta}{beta} decays

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Thomas


    The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

  16. Analysis of betaS and betaA genes in a Mexican population with African roots. (United States)

    Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha


    To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

  17. Kinetics and thermodynamics of hydrogen absorption and release in {beta}-titanium alloys; Kinetik und Thermodynamik der Wasserstoffaufnahme und -abgabe von {beta}-Titanlegierungen

    Energy Technology Data Exchange (ETDEWEB)

    Decker, M.; Christ, H.J. [Siegen Univ. (Gesamthochschule) (Germany). Inst. fuer Werkstofftechnik


    The work reported was intended to yield results allowing to describe as completely as possible the processes of interaction of {beta}-titanium and hydrogen. Three alloys have been selected for the experiments which suitably differ in stability of the {beta} phase. The characterisation of the hydrogen/metal interactions is primarily based on gravimetric measurements. A method was found to determine the diffusion coefficient of hydrogen, which is a significant variable for quantitative characterisation of the hydrogen absorption rate. (orig./CB) [Deutsch] In der Arbeit wird eine moeglichst vollstaendige Beschreibung der Wechselwirkung von {beta}-Titanlegierungen mit Wasserstoff angestrebt. Hierfuer wird mit drei Legierungen gearbeitet, die sich hinsichtlich der Stabilitaet der {beta}-Phase in sinnvoll abgestufter Weise unterscheiden. Fuer die Charakterisierung der Wasserstoff/Metall-Wechselwirkung wurden insbesondere gravimetrische Messungen eingesetzt. Weiterhin wurde die fuer eine quantitative Beschreibung der Wasserstoffaufnahmegeschwindigkeit wichtige Groesse des Diffusionskoeffizienten von Wasserstoff mit einem Verfahren bestimmt. (orig./MM)

  18. Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Dudas, Jozsef, E-mail: [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)


    Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the


    Energy Technology Data Exchange (ETDEWEB)



    OAK-B135 Advanced tokamak research in DIII-D seeks to optimize the tokamak approach for fusion energy production, leading to a compact, steady state power source. High power density implies operation at high toroidal beta, {beta}{sub T}=

    2{micro}{sub 0}/B{sub T}{sup 2}, since fusion power density increases roughly as the square of the plasma pressure. Steady-state operation with low recirculating power for current drive implies operation at high poloidal beta, {beta}{sub P} =

    2{micro}{sub 0}/{sup 2}, in order to maximize the fraction of self-generated bootstrap current. Together, these lead to a requirement of operation at high normalized beta, {beta}{sub N} = {beta}{sub T}(aB/I), since {beta}{sub P}{beta}{sub T} {approx} 25[(1+{kappa}{sup 2})/2] ({beta}{sub N}/100){sup 2}. Plasmas with high normalized beta are likely to operate near one or more stability limits, so control of MHD stability in such plasmas is crucial.

  20. General Biochemical Characterization of Thermostable Extracellular beta-Amylase from Clostridium thermosulfurogenes. (United States)

    Hyun, H H; Zeikus, J G


    Clostridium thermosulfurogenes, an anaerobic bacterium which ferments starch into ethanol at 62 degrees C, produced an active extracellular amylase and contained intracellular glucoamylase but not pullulanase activity. The extracellular amylase was purified 2.4-fold, and its general physicochemical and catalytic properties were examined. The extracellular amylase was characterized as a beta-amylase (1,4-alpha-d-glucan maltohydrolase) based on demonstration of exocleavage activity and the production of maltose with a beta-anomeric configuration from starch. The beta-amylase activity was stable and optimally active at 80 and 75 degrees C, respectively. The pH optimum for activity and the pH stability range was 5.5 to 6 and 3.5 to 6.5, respectively. The apparent [S](0.5V) and V(max) for beta-amylase activity on starch was 1 mg/ml and 60 U/mg of protein. Similar to described beta-amylase, the enzyme was inhibited by p-chloromercuribenzoate, Cu, and Hg; however, alpha- and beta-cyclodextrins were not competitive inhibitors. The beta-amylase was active and stable in the presence of air or 10% (vol/vol) ethanol. The beta-amylase and glucoamylase activities enabled the organism to actively ferment raw starch in the absence of significant pullulanase or alpha-amylase activity.

  1. Effects of beta-glucan addition to a probiotic containing yogurt. (United States)

    Vasiljevic, T; Kealy, T; Mishra, V K


    This study investigated the effects of addition of beta-glucan from 2 different cereal sources (oat and barley) on growth and metabolic activity of Bifidobacterium animalis ssp. lactis (Bb-12) as determined by plating on a selective medium in yogurt during prolonged cold storage. These yogurt batches were compared to unsupplemented and inulin supplemented controls. All batches were also assessed for syneresis. Oat beta-glucan addition resulted in improved probiotic viability and stability comparable to that of inulin. It also enhanced lactic and propionic acid production. The barley beta-glucan addition suppressed proteolytic activity more than that from oat. These improvements were hindered by greater syneresis caused likely by thermodynamic incompatibility. Small amplitude oscillatory measurements of acidified model mixture of beta-glucan/skim milk solids showed formation of casein gel within the beta-glucan network. Binary mixtures of beta-glucan and skim milk solids had apparent pseudoplastic and non-Newtonian behavior governed mainly by beta-glucan contribution. Above critical concentrations, the mixtures underwent phase separation with the lower phase rich in protein. The phase diagram also showed that the addition of beta-glucan may be possible at or below 0.24 w/w%.

  2. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis. (United States)

    Del Senno, L; Pirastu, M; Barbieri, R; Bernardi, F; Buzzoni, D; Marchetti, G; Perrotta, C; Vullo, C; Kan, Y W; Conconi, F


    Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+)-thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I. Images PMID:2580095

  3. Annual progress Report on research related to our research project “Stabilization of Plutonium in Subsurface Environments via Microbial Reduction and Biofilm Formation” funded by the Environmental Remediation Sciences Division (ERSD)

    Energy Technology Data Exchange (ETDEWEB)

    New, Mary


    The overarching goal of this research project is to investigate and optimize the mechanisms for in situ immobilization of Pu species by naturally-occurring bacteria. Specific research objectives are: (a) investigate the mechanism of bacterial accumulation and immobilization of plutonium species by biofilm formation under aerobic conditions and (b) to demonstrate the direct and indirect stabilization of Pu via dissimilatory reduction by Geobacter metallireducens.

  4. Research Progress in Physiological Functions and Stability of Lycopene%番茄红素的生理功能及保持其稳定性方法的研究进展

    Institute of Scientific and Technical Information of China (English)

    罗金凤; 任美燕; 陈敬鑫; 丁晓雯


    As a natural pigment,lycopene has a variety of physiological activities.Currently,lycopene is a hot research point in the functional food,pharmaceutical,cosmetic fields and others.However,lycopene has a special unsaturated structure and poor stability so that it is easy to degrade and isomerize,which reveals the limitation of lycopene.In this paper,basic properties,physiological functions and stability of lycopene are summarized.Meanwhile,some methods for providing lycopene stability are also proposed with the aim of provide useful information for the application of lycopene.%番茄红素是一种天然的色素,具有多种生理活性,是目前功能食品、医药、化妆品等行业的研究热点。但由于番茄红素具有特殊的不饱和结构,稳定性较差,容易发生降解和异构化,使其在应用中受到了很大的限制。本文主要对番茄红素基本性质、生理功能及稳定性进行综述,并对如何保持番茄红素稳定性的研究提出建议,以期为番茄红素的应用提供可借鉴信息。

  5. Sonic hedgehog acts as a negative regulator of {beta}-catenin signaling in the adult tongue epithelium. (United States)

    Schneider, Fabian T; Schänzer, Anne; Czupalla, Cathrin J; Thom, Sonja; Engels, Knut; Schmidt, Mirko H H; Plate, Karl H; Liebner, Stefan


    Wnt/beta-catenin signaling has been implicated in taste papilla development; however, its role in epithelial maintenance and tumor progression in the adult tongue remains elusive. We show Wnt/beta-catenin pathway activation in reporter mice and by nuclear beta-catenin staining in the epithelium and taste papilla of adult mouse and human tongues. beta-Catenin activation in APC(min/+) mice, which carry a mutation in adenomatous poliposis coli (APC), up-regulates Sonic hedgehog (Shh) and Jagged-2 (JAG2) in the tongue epithelium without formation of squamous cell carcinoma (SCC). We demonstrate that Shh suppresses beta-catenin transcriptional activity in a signaling-dependent manner in vitro and in vivo. A similar regulation and function was observed for JAG2, suggesting that both pathways negatively regulate beta-catenin, thereby preventing SCC formation in the tongue. This was supported by reduced nuclear beta-catenin in the tongue epithelium of Patched(+/-) mice, exhibiting dominant active Shh signaling. At the invasive front of human tongue cancer, nuclear beta-catenin and Shh were increased, suggesting their participation in tumor progression. Interestingly, Shh but not JAG2 was able to reduce beta-catenin signaling in SCC cells, arguing for a partial loss of negative feedback on beta-catenin transcription in tongue cancer. We show for the first time that the putative Wnt/beta-catenin targets Shh and JAG2 control beta-catenin signaling in the adult tongue epithelium, a function that is partially lost in lingual SCC.

  6. Progress in polymer solar cell

    Institute of Scientific and Technical Information of China (English)

    LI LiGui; LU GuangHao; YANG XiaoNiu; ZHOU EnLe


    This review outlines current progresses in polymer solar cell. Compared to traditional silicon-based photovoltaic (PV) technology, the completely different principle of optoelectric response in the polymer cell results in a novel configuration of the device and more complicated photovoltaic generation process. The conception of bulk-heterojunction (BHJ) is introduced and its advantage in terms of morphology is addressed. The main aspects including the morphology of photoactive layer, which limit the efficiency and stability of polymer solar cell, are discussed in detail. The solutions to boosting up both the efficiency and stability (lifetime) of the polymer solar cell are highlighted at the end of this review.

  7. Smart Beta or Smart Alpha

    DEFF Research Database (Denmark)

    Winther, Kenneth Lillelund; Steenstrup, Søren Resen


    Smart beta has become the flavor of the decade in the investment world with its low fees, easy access to rewarded risk premiums, and appearance of providing good investment results relative to both traditional passive benchmarks and actively managed funds. Although we consider it well documented...... that smart beta investing probably will do better than passive market capitalization investing over time, we believe many are coming to a conclusion too quickly regarding active managers. Institutional investors are able to guide managers through benchmarks and risk frameworks toward the same well......-documented smart beta risk premiums and still motivate active managers to avoid value traps, too highly priced small caps, defensives, etc. By constructing the equity portfolios of active managers that resemble the most widely used risk premiums, we show that the returns and risk-adjusted returns measures...

  8. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. (United States)

    Brown, Kimberly A; Pietenpol, Jennifer A; Moses, Harold L


    Transforming growth factor-beta (TGF-beta) is an important growth inhibitor of epithelial cells, and insensitivity to this cytokine results in uncontrolled cell proliferation and can contribute to tumorigenesis. Smad2 and Smad3 are direct mediators of TGF-beta signaling, however little is known about the selective activation of Smad2 versus Smad3. The Smad2 and Smad3 knockout mouse phenotypes and studies comparing Smad2 and Smad3 activation of TGF-beta target genes, suggest that Smad2 and Smad3 have distinct roles in TGF-beta signaling. The observation that TGF-beta inhibits proliferation of Smad3-null mammary gland epithelial cells, whereas Smad3 deficient fibroblasts are only partially growth inhibited, suggests that Smad3 has a different role in epithelial cells and fibroblasts. Herein, the current understanding of Smad2 and Smad3-mediated TGF-beta signaling and their relative roles are discussed, in addition to potential mechanisms for the selective activation of Smad2 versus Smad3. Since alterations in the TGF-beta signaling pathway play an important role in promoting tumorigenesis and cancer progression, methods for therapeutic targeting of the TGF-beta signaling pathway are being pursued. Determining how Smad2 or Smad3 differentially regulate the TGF-beta response may translate into developing more effective strategies for cancer therapy.

  9. The microbial oxidation of (-)-beta-pinene by Botrytis cinerea. (United States)

    Farooq, Afgan; Choudhary, M Iqbal; Tahara, Satoshi; Rahman, Atta-ur; Başer, K Hüsnü Can; Demirci, Fatih


    (-)-beta-pinene, a flavor and fragrance monoterpene is an important constituent of essential oils of many aromatic plants. It was oxidized by a plant-pathogenic fungus, Botrytis cinerea to afford four metabolites characterized as (-)-6a-hydroxy-beta-pinene, (-)-4beta,5beta-dihydroxy-beta-pinene, (-)-2beta,3beta-dihydroxypinane, and (-)-4beta-hydroxy-beta-pinene-6-one by detailed spectroscopic studies along with other known metabolites.

  10. Interaction between bradykinin potentiating nonapeptide (BPP9a) and {beta}-cyclodextrin: A structural and thermodynamic study

    Energy Technology Data Exchange (ETDEWEB)

    Lula, Ivana; De Sousa, Frederico B. [Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG (Brazil); Denadai, Angelo M.L. [Centro Federal de Educacao Tecnologica de Minas Gerais, CEFET-MG, Campus VII, 35.183-006, Timoteo, MG (Brazil); Ferreira de Lima, Guilherme; Duarte, Helio Anderson [Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG (Brazil); Mares Guia, Thiago R. dos [Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); Faljoni-Alario, Adelaide [Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, 05508-900, Sao Paulo, SP (Brazil); Santoro, Marcelo M. [Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); Camargo, Antonio C.M. de [Center for Applied Toxinology CAT-CEPID, Laboratorio Especial de Toxicologia Aplicada, Instituto Butantan, 05503-900, Sao Paulo, SP (Brazil); Santos, Robson A.S. dos [Departamento de Fisiologia e Biofisica, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); and others


    Herein, we demonstrate the physical and chemical characterizations of the supramolecular complex formed between {beta}-cyclodextrin ({beta}CD) and bradykinin potentiating nonapeptide (BPP9a), an endogenous toxin found in Bothrops jararaca. Circular dichroism results indicate a conformational change in the BPP9a secondary structure upon its complexation with {beta}CD. Nuclear magnetic resonance results, mainly from NOESY experiments, and theoretical calculations showed a favorable interaction between the tryptophan residue of BPP9a and the {beta}CD cavity. Thermodynamic inclusion parameters were investigated by isothermal titration calorimetry, demonstrating that {beta}CD/BPP9a complex formation is an exothermic process that results in a reduction in entropy. Additionally, in vitro degradation study of BPP9a against trypsin (37 Degree-Sign C, pH 7.2) showed higher stability of peptide in presence of {beta}CD. This {beta}CD/BPP9a complex, which presents new chemical properties arising from the peptide inclusion process, may be useful as an antihypertensive drug in oral pharmaceutical formulations. Highlights: Black-Right-Pointing-Pointer Cd and NMR showed evidences for the existence of more than one structure in solution. Black-Right-Pointing-Pointer Complexation with {beta}CD reduces the conformational rigidity of the peptide. Black-Right-Pointing-Pointer {beta}CD cavity recognize Trp and/or Pro segments of BPP9a. Black-Right-Pointing-Pointer Interactions involving disaggregation of BPP9a assemblies and binding with {beta}CD.

  11. Neutrinoless double beta decay experiments

    CERN Document Server

    Zuber, K


    The study of neutrinoless double beta decay is of outmost importance for neutrino physics. It is considered to be the gold plated channel to probe the fundamental character of neutrinos and to determine the neutrino mass. From the experimental point about nine different isotopes are explored for the search. After a general introduction follows a short discussion on nuclear matrix element calculations and supportive measurements. The current experimental status of double beta searches is presented followed by a short discussion of the ideas and proposals for large scale experiments.

  12. A {beta} - {gamma} coincidence; Metodo de coincidencias {beta} - {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Agullo, F.


    A {beta} - {gamma} coincidence method for absolute counting is given. The fundamental principles are revised and the experimental part is detailed. The results from {sup 1}98 Au irradiated in the JEN 1 Swimming pool reactor are given. The maximal accuracy is 1 per cent. (Author) 11 refs.

  13. Beta thalassaemia mutations in Turkish Cypriots. (United States)

    Sozuoz, A; Berkalp, A; Figus, A; Loi, A; Pirastu, M; Cao, A


    Using oligonucleotide hybridisation or restriction endonuclease analysis, we have characterised the molecular defect in 94 patients with thalassaemia major and four with thalassaemia intermedia of Turkish Cypriot descent. We found that four mutations, namely beta+ IVS-1 nt 110, beta zero IVS-1 nt, beta+ IVS-1 nt 6, and beta+ IVS-2 nt 745 were prevalent, accounting for 69.9%, 11.7%, 8.7%, and 5.6% respectively of the beta thalassaemia chromosomes. This information may help in the organisation of a large scale prevention programme based on fetal diagnosis of beta thalassaemia by DNA analysis in the Turkish population. PMID:3236356

  14. Tumors from rats given 1,2-dimethylhydrazine plus chlorophyllin or indole-3-carbinol contain transcriptional changes in beta-catenin that are independent of beta-catenin mutation status. (United States)

    Wang, Rong; Dashwood, W Mohaiza; Bailey, George S; Williams, David E; Dashwood, Roderick H


    Tumors induced in the rat by 1,2-dimethylhydrazine (DMH) contain mutations in beta-catenin, but the spectrum of such mutations can be influenced by phytochemicals such as chlorophyllin (CHL) and indole-3-carbinol (I3C). In the present study, we determined the mutation status of beta-catenin in more than 50 DMH-induced colon tumors and small intestine tumors, and compared this with the concomitant expression of beta-catenin mRNA using quantitative real-time RT-PCR analysis. In total, 19/57 (33%) of the tumors harbored mutations in beta-catenin, and 14/19 (74%) of the genetic changes substituted amino acids adjacent to Ser33, a key site for phosphorylation and beta-catenin degradation. These tumors were found to express a 10-fold range of beta-catenin mRNA levels, independent of the beta-catenin mutation status and phytochemical exposure, i.e. CHL or I3C given post-initiation. However, beta-catenin mRNA levels were strongly correlated with mRNA levels of c-myc, c-jun and cyclin D1, which are targets of beta-catenin/Tcf signaling. Tumors with the highest levels of beta-catenin mRNA often had over-expressed beta-catenin protein, and those with lower beta-catenin mRNA typically had low beta-catenin protein expression, but there were exceptions (high beta-catenin mRNA/low beta-catenin protein, or vice versa). We conclude that DMH-induced mutations stabilize beta-catenin protein in tumors, which increase c-myc, c-jun and cyclin D1, but there also can be over-expression of beta-catenin itself at the mRNA level, contributing to high beta-catenin protein levels. Similar findings have been reported in primary human colon cancers and their liver metastases, compared with matched normal-looking tissue. Thus, further studies are warranted on the mechanisms that upregulate beta-catenin at the transcriptional level in human and rodent colon cancers.

  15. 稳定塘处理污水的机理研究及应用研究进展%Mechanism, Application Status and Research Progress of Stabilization Pond for Treatment of Wastewater

    Institute of Scientific and Technical Information of China (English)

    张巍; 许静; 李晓东; 晁雷; 曾华; 赵晓光; 安乐


    Stabilization pond system in wastewater treatment has many advantages. For example, it has low capital investment and operating costs;it is simple to maintain and repair and easy to operate;it can remove the organic matter effectively and without the treatment of sludge. In recent years, it has been paid more and more attention. Its purification process is similar to natural water. This paper summarizes the removal mechanism of organic matter, nitrogen and phosphorus in stabilization pond. The removals of organic matter generally include precipitation and flocculation, the role of anaerobic microorganisms, aerobic microorganisms, plankton and aquatic plants. The removals of nitrogen in stabilization pond primarily through bio-assimilation into their own organic nitrogen, stripping of ammonia nitrogen, formation of biological precipitation, and nitrification/denitrification, etc. The removals of phosphorus involve oxidative decomposition of organic phosphorus in the role of microorganism, bacteria and algae and other organisms absorb inorganic phosphorus to synthesize new cells, and the conversion between soluble and non-soluble phosphorus, they are combined effect of a variety of mechanisms. Aiming at the defects existing in the traditional stabilization pond, people are continuously improved stabilization pond, there have been many new ponds, including high algae pond, aquatic plant pond and aquaculture pond, efficient composite anaerobic pond, ultra-deep anaerobic pond, biological filtration pond and so on. In order to improve the efficiency of wastewater treatment, the researchers also developed a number of combined pond processes, such as UNITANK process + biological stabilization pond combined with traditional biological methods, hydrolytic acidification +stabilization pond process, and baffled aeration biological filter + stabilization pond process, etc. Multistage tandem pond system with the combination of all kinds of ponds, ecological comprehensive pond

  16. Research progress review of solid particles stabilized Pickering emulsion and polymerization%固体颗粒稳定的 Pickering 乳液及其聚合研究述评

    Institute of Scientific and Technical Information of China (English)

    刘瑞雪; 段瑞卿; 岳英英; 张晓静; 方少明


    Recent advances in Pickering emulsion stabilized by solid particles and Pickering emulsion poly-merization were reviewed.It pointed out that the main stability theories of Pickering emulsion were the in-terface theory and the contact angle theory.The influence factors of Pickering emulsion included solid par-ticle concentration,pH value and the type of electrolyte,etc.SiO2 ,Laponite and magnetite had been commonly used as solid stabilizers in Pickering emulsion polymerization.The shortages on Pickering emul-sion research were also pointed out,such as neglecting the influence of electrical properties of solid parti-cles and deficient research on lamellar colloidal particles as Pickering emulsion stabilizer.Preparing the new Pickering emulsion less affected by monomer with stable properties,so as to enrich Pickering emulsion and its joint technology will be the research focus in the future.%综观国内外学者近年对固体颗粒稳定的 Pickering 乳液及其聚合的研究,相关理论有界面理论和接触角理论,对其影响因素的分析主要有固体颗粒浓度、水相 pH 值和水相电解质。研究者已经将SiO2,Laponite 粘土,磁铁矿等一系列无机固体颗粒成功地应用于 Pickering 乳液中,并制备出一系列性能各异的材料,但研究工作仍存在一些不足,如忽略固体颗粒的电性质对 Pickering 乳液的影响,对 Pickering 乳液的片状胶体颗粒稳定剂的研究不系统等。制备受单体影响小、性能稳定的新型 Pick-ering 乳液聚合稳定剂,从而不断丰富 Pickering 乳液及其聚合技术将是未来研究的热点。

  17. Interleukin-1 beta, interleukin-6 and TGF-beta in follicular tissue of impacted third molars. (United States)

    Mesgarzadeh, Ali Hossein; Abolfathi, Ali Akbar; Dastgiri, Saeed; Shaaker, Maghsod; Vatankhah, Amir Mansour; Solehakahnamoiee, Shiva; Darabi, Masoud


    The clinical evaluation and management of impacted third molars remain challenging. The aim of the present study was to investigate possible associations between follicular tissue cytokines and radiographic manifestations of impacted third molar. The population included 72 patients who underwent surgical extraction of impacted third molars. All these patients underwent a preliminary panoramic radiograph. Levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and transforming growth factor beta (TGF-β) in tissue extracts were determined using ELISA. There were no significant differences between bony and tissue impaction as regards IL-1β, IL-6 and TGF-β levels. Moreover, the same results were obtained as far as the amount of pericoronal space and the presence or absence of a history of pericoronitis are concerned. These results suggest that radiographic findings or a history of pericoronitis are not associated with levels of expression of pro-inflammatory cytokines in patients undergoing surgical removal of impacted third molars. However, further studies are needed to address the possibility of variability during disease progression.

  18. Beta Cell Workshop 2013 Kyoto

    DEFF Research Database (Denmark)

    Heller, R Scott; Madsen, Ole D; Nielsen, Jens Høiriis


    The very modern Kyoto International Conference Center provided the site for the 8th workshop on Beta cells on April 23-26, 2013. The preceding workshops were held in Boston, USA (1991); Kyoto, Japan (1994); Helsingør, Denmark (1997); Helsinki, Finland (2003); El Perello, Spain (2006); Peebles...

  19. Estimating $\\beta$-mixing coefficients

    CERN Document Server

    McDonald, Daniel J; Schervish, Mark


    The literature on statistical learning for time series assumes the asymptotic independence or ``mixing' of the data-generating process. These mixing assumptions are never tested, nor are there methods for estimating mixing rates from data. We give an estimator for the $\\beta$-mixing rate based on a single stationary sample path and show it is $L_1$-risk consistent.

  20. Beta-carotene as antioxidant

    NARCIS (Netherlands)

    Bast, A.; Plas, R.M. van der; Berg, H. van den; Haenen, G.R.M.M.


    Objective: Beta-carotene has been shown to exhibit a good radical-trapping antioxidant activity in vitro. We were interested to see if dietary β-carotene in combination with various intake levels for vitamin A would also inhibit lipid peroxidation. Design: Sixty male Wistar rats received vitamin A (

  1. Molecular Dynamics Simulation of Amyloid Beta Dimer Formation

    CERN Document Server

    Urbanc, B; Ding, F; Sammond, D; Khare, S; Buldyrev, S V; Stanley, H E; Dokholyan, N V


    Recent experiments with amyloid-beta (Abeta) peptide suggest that formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depends on their structure, which is governed by assembly dynamics. Due to limitations of current experimental techniques, a detailed knowledge of oligomer structure at the atomic level is missing. We introduce a molecular dynamics approach to study Abeta dimer formation: (1) we use discrete molecular dynamics simulations of a coarse-grained model to identify a variety of dimer conformations, and (2) we employ all-atom molecular mechanics simulations to estimate the thermodynamic stability of all dimer conformations. Our simulations of a coarse-grained Abeta peptide model predicts ten different planar beta-strand dimer conformations. We then estimate the free energies of all dimer conformations in all-atom molecular mechanics simulations with explicit water. We compare the free energies of Abeta(1-42) and Abeta(1-40...

  2. Ozonolysis of alpha-pinene and beta-pinene: kinetics and mechanism. (United States)

    Zhang, Dan; Zhang, Renyi


    A combined quantum-chemical and RRKM/ME (ME--master equation) approach is employed to investigate the structures, energetics, and kinetics of intermediate and stable species, and the yields of stabilized carbonyl oxides and OH radicals from the alpha-pinene and beta-pinene ozonolysis reactions. The cycloaddition of O(3) is highly exothermic, with the reaction energies of 55.1 and 51.1 kcal mol(-1) for alpha- and beta-pinenes, respectively. Cleavage of primary ozonides yields carbonyl oxides with the barrier height of 12.2-17.5 kcal mol(-1). For the prompt reactions of carbonyl oxides from alpha- and beta-pinene ozonolysis, H migration to hydroperoxides represents the dominant pathway over ring closure to dioxiranes. The kinetic calculations indicate a significant portion of stabilization for alpha- and beta-carbonyl oxides. The yields of stabilized carbonyl oxides are estimated to be 0.34 for alpha-pinene and 0.22 for beta-pinene. The applicability of theoretical methods for investigation of oxidation reactions of large hydrocarbon molecules is demonstrated.

  3. Bone morphogenetic protein 4 inhibits insulin secretion from rodent beta cells through regulation of calbindin1 expression and reduced voltage-dependent calcium currents

    DEFF Research Database (Denmark)

    Christensen, Gitte L.; Jacobsen, Maria L. B.; Wendt, Anna


    AIMS/HYPOTHESIS: Type 2 diabetes is characterised by progressive loss of pancreatic beta cell mass and function. Therefore, it is of therapeutic interest to identify factors with the potential to improve beta cell proliferation and insulin secretion. Bone morphogenetic protein 4 (BMP4) expression...

  4. Neutron Beta Decay Studies with Nab

    CERN Document Server

    Baeßler, S; Alonzi, L P; Balascuta, S; Barrón-Palos, L; Bowman, J D; Bychkov, M A; Byrne, J; Calarco, J R; Chupp, T; Vianciolo, T V; Crawford, C; Frlež, E; Gericke, M T; Glück, F; Greene, G L; Grzywacz, R K; Gudkov, V; Harrison, D; Hersman, F W; Ito, T; Makela, M; Martin, J; McGaughey, P L; McGovern, S; Page, S; Penttilä, S I; Počanić, D; Rykaczewski, K P; Salas-Bacci, A; Tompkins, Z; Wagner, D; Wilburn, W S; Young, A R


    Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer.

  5. Balancing needs and means: the dilemma of the beta-cell in the modern world. (United States)

    Leibowitz, G; Kaiser, N; Cerasi, E


    The insulin resistance of type 2 diabetes mellitus (T2DM), although important for its pathophysiology, is not sufficient to establish the disease unless major deficiency of beta-cell function coexists. This is demonstrated by the fact that near-physiological administration of insulin (CSII) achieved excellent blood glucose control with doses similar to those used in insulin-deficient type 1 diabetics. The normal beta-cell adapts well to the demands of insulin resistance. Also in hyperglycaemic states some degree of adaptation does exist and helps limit the severity of disease. We demonstrate here that the mammalian target of rapamycin (mTOR) system might play an important role in this adaptation, because blocking mTORC1 (complex 1) by rapamycin in the nutritional diabetes model Psammomys obesus caused severe impairment of beta-cell function, increased beta-cell apoptosis and progression of diabetes. On the other hand, under exposure to high glucose and FFA (gluco-lipotoxicity), blocking mTORC1 in vitro reduced endoplasmic reticulum (ER) stress and beta-cell death. Thus, according to the conditions of stress, mTOR may have beneficial or deleterious effects on the beta-cell. beta-Cell function in man can be reduced without T2DM/impaired glucose tolerance (IGT). Prospective studies have shown subjects with reduced insulin response to present, several decades later, an increased incidence of IGT/T2DM. From these and other studies we conclude that T2DM develops on the grounds of beta-cells whose adaptation capacity to increased nutrient intake and/or insulin resistance is in the lower end of the normal variation. Inborn and acquired factors that limit beta-cell function are diabetogenic only in a nutritional/metabolic environment that requires high functional capabilities from the beta-cell.

  6. Estrogen Receptor Beta Displays Cell Cycle-Dependent Expression and Regulates the G1 Phase through a Non-Genomic Mechanism in Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Antoni Hurtado


    Full Text Available Background: It is well known that estrogens regulate cell cycle progression, but the specific contributions and mechanisms of action of the estrogen receptor beta (ERβ remain elusive.

  7. Lupeol inhibits proliferation of human prostate cancer cells by targeting beta-catenin signaling. (United States)

    Saleem, Mohammad; Murtaza, Imtiyaz; Tarapore, Rohinton S; Suh, Yewseok; Adhami, Vaqar Mustafa; Johnson, Jeremy James; Siddiqui, Imtiaz Ahmad; Khan, Naghma; Asim, Mohammad; Hafeez, Bilal Bin; Shekhani, Mohammed Talha; Li, Benyi; Mukhtar, Hasan


    Lupeol, a dietary triterpene, was shown to decrease serum prostate-specific antigen levels and inhibit the tumorigenicity of prostate cancer (CaP) cells in vivo. Here, we show that Lupeol inhibits the proliferative potential of CaP cells and delineated its mechanism of action. Employing a focused microarray of human CaP-associated genes, we found that Lupeol significantly modulates the expression level of genes such as ERBB2, tissue inhibitor of metalloproteinases-3, cyclin D1 and matrix metalloproteinase (MMP)-2 that are known to be associated with proliferation and survival. A common feature of these genes is that all of them are known to either regulate or act as downstream target of beta-catenin signaling that is highly aberrant in CaP patients. Lupeol treatment significantly (1) reduced levels of beta-catenin in the cytoplasmic and nuclear fractions, (2) modulated expression levels of glycogen synthase kinase 3 beta (GSK3beta)-axin complex (regulator of beta-catenin stability), (3) decreased the expression level and enzymatic activity of MMP-2 (downstream target of beta-catenin), (4) reduced the transcriptional activation of T Cell Factor (TCF) responsive element (marker for beta-catenin signaling) in pTK-TCF-Luc-transfected cells and (5) decreased the transcriptional activation of MMP-2 gene in pGL2-MMP-2-Luc-transfected cells. Effects of Lupeol treatment on beta-catenin degradation were significantly reduced in CaP cells where axin is knocked down through small interfering RNA transfection and GSK3beta activity is blocked. Collectively, these data suggest the multitarget efficacy of Lupeol on beta-catenin-signaling network thus resulting in the inhibition CaP cell proliferation. We suggest that Lupeol could be developed as an agent for chemoprevention as well as chemotherapy of human CaP.

  8. Shell structure of nuclei far from stability

    CERN Document Server

    Grawe, H


    The experimental status of shell structure studies in medium-heavy nuclei far off the line of beta-stability is reviewed. Experimental techniques, signatures for shell closure and expectations for future investigations are discussed for the key regions around sup 4 sup 8 sup , sup 5 sup 6 Ni, sup 1 sup 0 sup 0 Sn for proton rich nuclei and the neutron-rich N=20 isotones, Ca, Ni and Sn isotopes.

  9. The beta-decay of Al-22

    NARCIS (Netherlands)

    Achouri, NL; Santos, FDO; Lewitowicz, M; Blank, B; Aysto, J; Canchel, G; Czajkowski, S; Dendooven, P; Emsallem, A; Giovinazzo, J; Guillet, N; Jokinen, A; Larid, AM; Longour, C; Perajarvi, K; Smirnova, N; Stanoiu, M


    In an experiment performed at the LISE3 facility of GANIL, we studied the decay of Al-22 produced by the fragmentation of a Ar-36 primary beam. A beta-decay half-life of T-1/2 = 91.1 +/- 0.5ms was measured. The beta-delayed one- and two-proton emission as well as beta-alpha and beta-delayed gamma-de

  10. Traumatic Brain Injury, Microglia, and Beta Amyloid


    Mannix, Rebekah C.; Whalen, Michael J


    Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (A\\(\\beta\\)). Data from both AD and TBI studies suggest that microglia play a central role in A\\(\\beta\\) accumulation after TBI. This paper focuses on the current research on the role of microglia response to A\\(\\beta\\) after TBI.

  11. Ionizing radiation predisposes non-malignant human mammaryepithelial cells to undergo TGF beta-induced epithelial to mesenchymaltransition

    Energy Technology Data Exchange (ETDEWEB)

    Andarawewa, Kumari L.; Erickson, Anna C.; Chou, William S.; Costes, Sylvain; Gascard, Philippe; Mott, Joni D.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen


    Transforming growth factor {beta}1 (TGF{beta}) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGF{beta}, activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGF{beta}-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGF{beta} (0.4 ng/ml), or double-treated. All double-treated (IR+TGF{beta}) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, {beta}-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel{trademark}. Neither radiation nor TGF{beta} alone elicited EMT, even though IR increased chronic TGF{beta} signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGF{beta}-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGF{beta}, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.

  12. The effects of glucagon-like peptide-1 on the beta cell

    DEFF Research Database (Denmark)

    Vilsbøll, Tina


    Type 2 diabetes is a progressive disease characterized by insulin resistance and impaired beta-cell function. Treatments that prevent further beta-cell decline are therefore essential for the management of type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is known...... to stimulate glucose-dependent insulin secretion. Furthermore, GLP-1 appears to have multiple positive effects on beta cells. However, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), which limits the clinical relevance of GLP-1 for the treatment of type 2 diabetes. Two main classes of GLP-1-based...... therapies have now been developed: DPP-4 inhibitors and GLP-1 receptor agonists. Liraglutide and exenatide are examples of GLP-1 receptor agonists that have been developed to mimic the insulinotropic characteristics of endogenous GLP-1. Both have demonstrated improved beta-cell function in patients...

  13. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes? (United States)

    Kahraman, Sevim; Okawa, Erin R; Kulkarni, Rohit N


    Diabetes is a progressive disease affecting millions of people worldwide. There are several medications and treatment options to improve the life quality of people with diabetes. One of the strategies for the treatment of diabetes could be the use of human pluripotent stem cells or induced pluripotent stem cells. The recent advances in differentiation of stem cells into insulin-secreting beta-like cells in vitro make the transplantation of the stem cell-derived beta-like cells an attractive approach for treatment of type 1 and type 2 diabetes. While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases.

  14. Radioiodinated Naphthylalanine Derivatives Targeting Pancreatic Beta Cells in Normal and Nonobese Diabetic Mice (United States)

    Amartey, John K.; Shi, Yufei; Al-Jammaz, Ibrahim; Esguerra, Celestina; Al-Otaibi, Basem; Al-Mohanna, Futwan


    An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P < .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies showed colocalization of insulin and the conjugate radioligand in the pancreas. The results demonstrated that pancreatic uptake is receptor-mediated, and that beta cells are the primary target. PMID:18483609

  15. Information-Selectivity of Beta-Amyloid Pathology in an Associative Memory Model

    Directory of Open Access Journals (Sweden)

    Mark eRowan


    Full Text Available This work updates Ruppin and Reggia's associative neural network model of Alzheimer's disease by simulating beta-amyloid pathology and modelling the progression of beta-amyloid throughout the network according to Small's synaptic scaling theory, leading to a self-reinforcing cascade of damage. Using an information theoretic approach, it is shown that the simulated beta-amyloid pathology initially selectively targets neurons with low contribution to the overall performance of the network, but that it targets neurons with increasingly higher significance to the network as the disease progresses. The results provide a possible explanation for the apparent low correlation between amyloid plaque density and cognitive decline in the early stages of Alzheimer's disease.

  16. Stabilizing the Higgs potential with a Z′

    Energy Technology Data Exchange (ETDEWEB)

    Di Chiara, Stefano; Keus, Venus, E-mail:; Lebedev, Oleg


    Current data point toward metastability of the electroweak vacuum within the Standard Model. We study the possibility of stabilizing the Higgs potential in U(1) extensions thereof. A generic Z′ boson improves stability of the scalar potential in two ways: it increases the Higgs self-coupling, due to a positive contribution to the beta-function of the latter, and it decreases the top quark Yukawa coupling, which again has a stabilizing effect. We determine the range of U(1) charges which leads to a stable electroweak vacuum. In certain classes of models, such stabilization is possible even if the Z′ does not couple to the Higgs and is due entirely to the reduction of the top Yukawa coupling. We also study the effect of the kinetic mixing between the extra U(1) and hypercharge gauge fields.


    NARCIS (Netherlands)



    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These

  18. Beta-lactamases in Enterobacteriaceae in broilers

    NARCIS (Netherlands)

    Dierikx, C.M.


    Resistance to cephalosprins due to the production of extended spectrum beta-lactamases (ESBLs) or plasmid mediated AmpC beta-lactamases is increasingly found in infections in humans outside the hospital. The genes encoding for these beta-lactamases are located on mobile DNA (plasmids), which can be

  19. Higher-Order Beta Matching with Solutions in Long Beta-Eta Normal Form

    DEFF Research Database (Denmark)

    Støvring, Kristian


    up to beta-eta equivalence is a long-standing open problem.We show that higher-order matching up to beta-eta equivalence is decidable if and only if a restricted form of higher-order matching up to beta equivalence is decidable: the restriction is that solutions must be in long beta-eta normal form....

  20. Research Progress in Improving the Cycling Stability of High-Voltage LiNi0.5Mn1.5O4 Cathode in Lithium-Ion Battery (United States)

    Xu, XiaoLong; Deng, SiXu; Wang, Hao; Liu, JingBing; Yan, Hui


    High-voltage lithium-ion batteries (HVLIBs) are considered as promising devices of energy storage for electric vehicle, hybrid electric vehicle, and other high-power equipment. HVLIBs require their own platform voltages to be higher than 4.5 V on charge. Lithium nickel manganese spinel LiNi0.5Mn1.5O4 (LNMO) cathode is the most promising candidate among the 5 V cathode materials for HVLIBs due to its flat plateau at 4.7 V. However, the degradation of cyclic performance is very serious when LNMO cathode operates over 4.2 V. In this review, we summarize some methods for enhancing the cycling stability of LNMO cathodes in lithium-ion batteries, including doping, cathode surface coating, electrolyte modifying, and other methods. We also discuss the advantages and disadvantages of different methods.

  1. Production and some characteristics of beta-glucosidase in Diaporthe (Phomopsis) helianthi. (United States)

    Pericin, D; Jarak, M


    Diaporthe (Phomopsis) helianthi Munt.-Cvet. et al. is an important phytopathogenic fungus which causes stem canker of sunflower. When grown in submerged cultures in the presence of milled wheat chaff as a carbon source this phytopathogen produced extracellular and intracellular beta-glucosidases. The optimum pH of these enzymes was 4.8. The temperature of crude intracellular beta-glucosidase activity was at 60 degrees C, whereas the optimum activity of crude extracellular beta-glucosidase was observed in a wide range of temperature between 40 and 70 degrees C. Although, extracellular and intracellular beta-glucosidase activities had identical pH and similar temperature optima, the thermal stability of the intracellular enzyme was significantly higher.

  2. Preliminary Study of Ideal Operational MHD Beta Limit in HL-2A Tokamak Plasmas

    Institute of Scientific and Technical Information of China (English)

    SHEN Yong; DONG Jiaqi; HE Hongda; A. D. TURNBULL


    Magnetohydrodynamic (MHD) n=1 kink mode with n the toroidal mode number is studied and the operational beta limit, constrained by the mode, is calculated for the equilibrium of HL-2A by using the GATO code. Approximately the same beta limit is obtained for configurations with a value of the axial safety factor q0 both larger and less than 1. Without the stabilization of the conducting wall, the beta limit is found to be 0.821% corresponding to a normalized beta value of βcN=2.56 for a typical HL-2A discharge with a plasma current Ip=0.245 MA, and the scaling of βcN~constant is confirmed.

  3. Deuterium-tritium TFTR plasmas in the high poloidal beta regime

    Energy Technology Data Exchange (ETDEWEB)

    Sabbagh, S.A.; Mauel, M.E.; Navratil, G.A. [Columbia Univ., New York, NY (United States). Dept. of Applied Physics] [and others


    Deuterium-tritium plasmas with enhanced energy confinement and stability have been produced in the high poloidal beta, advanced tokamak regime in TFTR. Confinement enhancement H {triple_bond} {tau}{sub E}/{tau}{sub E ITER-89P} > 4 has been obtained in a limiter H-mode configuration at moderate plasma current I{sub p} = 0.85 {minus} 1.46 MA. By peaking the plasma current profile, {beta}{sub N dia} {triple_bond} 10{sup 8} < {beta}{sub t{perpendicular}} > aB{sub 0}/I{sub p} = 3 has been obtained in these plasma,s exceeding the {beta}{sub N} limit for TFTR plasmas with lower internal inductance, l{sub i}. Fusion power exceeding 6.7 MW with a fusion power gain Q{sub DT} = 0.22 has been produced with reduced alpha particle first orbit loss provided by the increased l{sub i}.

  4. Phospholipase C-beta 2 promotes mitosis and migration of human breast cancer-derived cells. (United States)

    Bertagnolo, Valeria; Benedusi, Mascia; Brugnoli, Federica; Lanuti, Paola; Marchisio, Marco; Querzoli, Patrizia; Capitani, Silvano


    Like most human neoplasm, breast cancer has aberrations in signal transduction elements that can lead to increased proliferative potential, apoptosis inhibition, tissue invasion and metastasis. Due to the high heterogeneity of this tumor, currently, no markers are clearly associated with the insurgence of breast cancer, as well as with its progression from in situ lesion to invasive carcinoma. We have recently demonstrated an altered expression of the beta2 isoform of the phosphoinositide-dependent phospholipase C (PLC) in invasive breast tumors with different histopathological features. In primary breast tumor cells, elevated amounts of this protein are closely correlated with a poor prognosis of patients with mammary carcinoma, suggesting that PLC-beta2 may be involved in the development and worsening of the malignant phenotype. Here we demonstrate that PLC-beta2 may improve some malignant characteristics of tumor cells, like motility and invasion capability, but it fails to induce tumorigenesis in non-transformed breast-derived cells. We also report that, compared with the G(0)/G(1) phases of the cell cycle, the cells in S/G(2)/M phases show high PLC-beta2 expressions that reach the greatest levels during the late mitotic stages. In addition, even if unable to modify the proliferation rate and the expression of cell cycle-related enzymes of malignant cells, PLC-beta2 may promote the G(2)/M progression, a critical event in cancer evolution. Since phosphoinositides, substrates of PLC, are involved in regulating cytoskeleton architecture, PLC-beta2 in breast tumor cells may mediate the modification of cell shape that characterizes cell division, motility and invasion. On the basis of these data, PLC-beta2 may constitute a molecular marker of breast tumor cells able to monitor the progression to invasive cancers and a target for novel therapeutic breast cancer strategies.

  5. Stem cells to pancreatic beta-cells: new sources for diabetes cell therapy. (United States)

    Guo, Tingxia; Hebrok, Matthias


    The number of patients worldwide suffering from the chronic disease diabetes mellitus is growing at an alarming rate. Insulin-secreting beta-cells in the islet of Langerhans are damaged to different extents in diabetic patients, either through an autoimmune reaction present in type 1 diabetic patients or through inherent changes within beta-cells that affect their function in patients suffering from type 2 diabetes. Cell replacement strategies via islet transplantation offer potential therapeutic options for diabetic patients. However, the discrepancy between the limited number of donor islets and the high number of patients who could benefit from such a treatment reflects the dire need for renewable sources of high-quality beta-cells. Human embryonic stem cells (hESCs) are capable of self-renewal and can differentiate into components of all three germ layers, including all pancreatic lineages. The ability to differentiate hESCs into beta-cells highlights a promising strategy to meet the shortage of beta-cells. Here, we review the different approaches that have been used to direct differentiation of hESCs into pancreatic and beta-cells. We will focus on recent progress in the understanding of signaling pathways and transcription factors during embryonic pancreas development and how this knowledge has helped to improve the methodology for high-efficiency beta-cell differentiation in vitro.

  6. Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation

    NARCIS (Netherlands)

    Leuner, K.; Schutt, T.; Kurz, C.; Eckert, S.H.; Schiller, C.; Occhipinti, A.; Mai, S.; Jendrach, M.; Eckert, G.P.; Kruse, S.E.; Palmiter, R.D.; Brandt, U.; Drose, S.; Wittig, I.; Willem, M.; Haass, C.; Reichert, A.S.; Muller, W.E.


    AIMS: Intracellular amyloid beta (Abeta) oligomers and extracellular Abeta plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Abeta production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species (RO

  7. Amyloid-beta Oligomers Relate to Cognitive Decline in Alzheimer's Disease

    NARCIS (Netherlands)

    Jongbloed, W.; Bruggink, K.A.; Kester, M.I.; Visser, P.J.; Scheltens, P.; Blankenstein, M.A.; Verbeek, M.M.; Teunissen, C.E.; Veerhuis, R.


    BACKGROUND: Amyloid-beta (Abeta)-oligomers are neurotoxic isoforms of Abeta and are a potential diagnostic biomarker for Alzheimer's disease (AD). OBJECTIVES: 1) Analyze the potential of Abeta-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large c

  8. Rat beta(3)-adrenoceptor protein expression : antibody validation and distribution in rat gastrointestinal and urogenital tissues

    NARCIS (Netherlands)

    Cernecka, Hana; Pradidarcheep, Wisuit; Lamers, Wouter H.; Schmidt, Martina; Michel, Martin C.


    beta(3)-Adrenoceptors play important roles in the regulation of urogenital and probably gastrointestinal function. However, despite recent progress, their detection at the protein level has remained difficult due to a lack of sufficiently validated selective antibodies. Therefore, we have explored t

  9. Inhibition of AmpC beta-lactamase through a destabilizing interaction in the active site

    Energy Technology Data Exchange (ETDEWEB)

    Trehan, I.; Beadle, B.M.; Shoichet, B.K. (NWU)


    {beta}-Lactamases hydrolyze {beta}-lactam antibiotics, including penicillins and cephalosporins; these enzymes are the most widespread resistance mechanism to these drugs and pose a growing threat to public health. {beta}-Lactams that contain a bulky 6(7){alpha} substituent, such as imipenem and moxalactam, actually inhibit serine {beta}-lactamases and are widely used for this reason. Although mutant serine {beta}-lactamases have arisen that hydrolyze {beta}-lactamase resistant {beta}-lactams (e.g., ceftazidime) or avoid mechanism-based inhibitors (e.g., clavulanate), mutant serine {beta}-lactamases have not yet arisen in the clinic with imipenemase or moxalactamase activity. Structural and thermodynamic studies suggest that the 6(7){alpha} substituents of these inhibitors form destabilizing contacts within the covalent adduct with the conserved Asn152 in class C {beta}-lactamases (Asn132 in class A {beta}-lactamases). This unfavorable interaction may be crucial to inhibition. To test this destabilization hypothesis, we replaced Asn152 with Ala in the class C {beta}-lactamase AmpC from Escherichia coli and examined the mutant enzyme's thermodynamic stability in complex with imipenem and moxalactam. Consistent with the hypothesis, the Asn152 {yields} Ala substitution relieved 0.44 and 1.10 kcal/mol of strain introduced by imipenem and moxalactam, respectively, relative to the wild-type complexes. However, the kinetic efficiency of AmpC N152A was reduced by 6300-fold relative to that of the wild-type enzyme. To further investigate the inhibitor's interaction with the mutant enzyme, the X-ray crystal structure of moxalactam in complex with N152A was determined to a resolution of 1.83 {angstrom}. Moxalactam in the mutant complex is significantly displaced from its orientation in the wild-type complex; however, moxalactam does not adopt an orientation that would restore competence for hydrolysis. Although Asn152 forces {beta}-lactams with 6(7){alpha

  10. Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis. (United States)

    Fernández-Millán, Elisa; Cordero-Herrera, Isabel; Ramos, Sonia; Escrivá, Fernando; Alvarez, Carmen; Goya, Luis; Martín, María Angeles


    We have recently shown that cocoa flavanols may have anti-diabetic potential by promoting survival and function of pancreatic beta-cells in vitro. In this work, we investigated if a cocoa-rich diet is able to preserve beta-cell mass and function in an animal model of type 2 diabetes and the mechanisms involved. Our results showed that cocoa feeding during the prediabetic state attenuates hyperglycaemia, reduces insulin resistant, and increases beta cell mass and function in obese Zucker diabetic rats. At the molecular level, cocoa-rich diet prevented beta-cell apoptosis by increasing the levels of Bcl-xL and decreasing Bax levels and caspase-3 activity. Cocoa diet enhanced the activity of endogenous antioxidant defenses, mainly glutathione peroxidase, preventing thus oxidative injury induced by the pre-diabetic condition and leading to apoptosis prevention. These findings provide the first in vivo evidence that a cocoa-rich diet may delay the loss of functional beta-cell mass and delay the progression of diabetes by preventing oxidative stress and beta-cell apoptosis.

  11. Amino acid preference against beta sheet through allowing backbone hydration enabled by the presence of cation

    CERN Document Server

    Sharley, John N


    It is known that steric blocking by peptide sidechains of hydrogen bonding, HB, between water and peptide groups, PGs, in beta sheets accords with an amino acid intrinsic beta sheet preference. The present observations with Quantum Molecular Dynamics, QMD, simulation with quantum mechanical treatment of every water molecule solvating a beta sheet that would be transient in nature suggest that this steric blocking is not applicable in a hydrophobic region unless a cation is present, so that the amino acid beta sheet preference due to this steric blocking is only effective in the presence of a cation. We observed backbone hydration in a polyalanine and to a lesser extent polyvaline alpha helix without a cation being present, but a cation could increase the strength of these HBs. Parallel beta sheets have a greater tendency than antiparallel beta sheets of equivalent small size to retain regular structure in solvated QMD, and a 4 strand 4 inter-PG HB chain parallel beta sheet was used. Stability was reinforced b...

  12. Spectroscopic characterization of the inclusion complexes of luteolin with native and derivatized beta-cyclodextrin. (United States)

    Jullian, Carolina; Cifuentes, Constanza; Alfaro, Muriel; Miranda, Sebastián; Barriga, Germán; Olea-Azar, Claudio


    The inclusion complexes of Luteolin (LU) with cyclodextrins (CDs) including beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD) and dimethyl-beta-cyclodextrin (DMbetaCD), Scheme 1, have been investigated using the method of steady-state fluorescence. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was obtained in the case of HPbetaCD followed by DMbetaCD and betaCD. Moreover, 1H NMR and 2D NMR were carried out, revealing that LU has different form of inclusion which is in agreement with molecular modeling studies. These models confirm that when LU-betaCD and LU-DMbetaCD complexes are formed, the B-ring is oriented toward the primary rim; however, for LU-HPbetaCD complex this ring is oriented toward the secondary rim. The ESR results showed that the antioxidant activity of luteolin was the order LU-HPbetaCD>LU-DMbetaCD>LU-betaCD>LU, hence the LU-complexes behave are better antioxidants than luteolin free.

  13. The ToI-beta transgenic mouse: a model to study the specific role of NF-kappaB in beta-cells. (United States)

    Eldor, Roy; Baum, Ketty; Abel, Roy; Sever, Dror; Melloul, Danielle


    Type 1 diabetes is characterized by the infiltration of inflammatory cells into pancreatic islets of Langerhans, followed by the selective and progressive destruction of insulin-secreting beta-cells. Islet infiltrating leukocytes secrete cytokines including IL-1beta and IFN-gamma, which contribute to beta-cell death. In vitro evidence suggests that cytokine-induced activation of the transcription factor NF-kappaB is an important component of the signal triggering beta-cell apoptosis. To study the role of NF-kappaB in vivo we generated a transgenic mouse line expressing a degradation-resistant NF-kappaB protein inhibitor (DeltaNIkappaBalpha) and the luciferase gene, acting specifically in beta-cells, in an inducible and reversible manner, by using the tet-on regulation system. Using this new mouse model, termed the ToI-beta mouse (for Tet-Ondelta I kappaB in beta-cells) we have previously shown in vitro, that islets expressing the DeltaNIkappaBalpha protein were resistant to the deleterious effects of IL-1beta and IFN-gamma, as assessed by reduced NO production and beta-cell apoptosis. In vivo, a nearly complete protection against multiple low dose streptozocin-induced diabetes was observed, with reduced intra-islet lymphocytic infiltration. In the present study we demonstrate the tight regulated and reversible expression of the DeltaNIkappaBalpha transgene in the ToI-beta mouse model as well as the effect of its overexpression on glucose metabolism and insulin secretion. The results show a lack of effect of transgene induction on both in vivo glucose tolerance tests and in vitro islet insulin secretion and content. Furthermore, to prove the tight control of induction in the model, luciferase mediated light emission was only detected at constant levels in Dox-treated double transgenic mice or islets as well as in a model of islet transplantation. Upon removal of the inducing stimulus, complete reversal of both NF-kappaB inhibition and luciferase activity were

  14. Pseudosubstrate regulation of the SCF(beta-TrCP) ubiquitin ligase by hnRNP-U

    DEFF Research Database (Denmark)

    Davis, Matti; Hatzubai, Ada; Andersen, Jens S


    . Consequently, hnRNP-U engages a highly neddylated active SCF(beta-TrCP), which dissociates in the presence of a high-affinity substrate, resulting in ubiquitination of the latter. Our study points to a novel regulatory mechanism, which secures the localization, stability, substrate binding threshold...

  15. Design of peptides with alpha,beta-dehydro residues: pseudo-tripeptide N-benzyloxycarbonyl-DeltaLeu-L-Ala-L-Leu-OCH3. (United States)

    Makker, Jyoti; Dey, Sharmistha; Kumar, Pravindra; Singh, Tej P


    The title peptide N-benzyloxycarbonyl-DeltaLeu-L-Ala-L-Leu-OCH(3) [methyl N-(benzyloxycarbonyl)-alpha,beta-dehydroleucyl-L-alanyl-L-leucinate], C(24)H(35)N(3)O(6), was synthesized in the solution phase. The peptide adopts a type II' beta-turn conformation which is stabilized by an intramolecular 4 --> 1 N-H* * *O hydrogen bond. The crystal packing is stabilized by two intermolecular N-H* * *O hydrogen bonds.

  16. Reduced migration from flexible poly(vinyl chloride) of a plasticizer containing beta-cyclodextrin derivative. (United States)

    Yu, Ong Yong; Chung, Jae Woo; Kwak, Seung-Yeop


    The migration of endocrine-disrupting di-(2-ethylhexyl) phthalate (DEHP) poses a serious threat to public health and the environment. In this study, we successfully prepared a plasticizerwith reduced DEHP migration by directly incorporating 2,3,6-per-O-benzoyl-beta-cyclodextrin (Bz-beta-CD) into DEHP. Bz-beta-CD was prepared by esterification between the hydroxyl groups of beta-CD and benzoyl chloride. The presence of this cyclodextrin is expected to facilitate formation of stable complexes through pi-pi association with DEHP molecules. The flexible PVC was prepared with a gelation-fusion process that uses the prepared migration-resistant plasticizer, and its properties (flexibility, thermal stability, and clarity) were evaluated by carrying out DSC and tensile testing, TGA, and haze testing, respectively. No significant changes in the physical properties of the flexible PVC were observed when Bz-beta-CD was added. DEHP migration tests were carried out for the flexible PVC according to the ISO 3826:1993(E) test method, and the quantity of migrated DEHP was then determined with UV-vis spectroscopy. It was found that the addition of Bz-beta-CD decreases the levels of DEHP migration from the flexible PVC samples by almost 40%. We investigated the molecular interaction between Bz-beta-CD and DEHP using molecular mechanics simulations, and we conclude that this reduction in DEHP migration is due to the formation of stabilized pi-pi attractive association and inclusion complexes of Bz-beta-CD and DEHP in flexible PVC.

  17. β-Catenin signaling increases during melanoma progression and promotes tumor cell survival and chemoresistance.

    Directory of Open Access Journals (Sweden)

    Tobias Sinnberg

    Full Text Available Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy.

  18. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis.


    del Senno, L; Pirastu, M; Barbieri, R.; De Bernardi, F.; Buzzoni, D; Marchetti, G.; Perrotta, C; Vullo, C; Kan, Y W; Conconi, F


    Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in...

  19. Stabilizing brokerage. (United States)

    Stovel, Katherine; Golub, Benjamin; Milgrom, Eva M Meyersson


    A variety of social and economic arrangements exist to facilitate the exchange of goods, services, and information over gaps in social structure. Each of these arrangements bears some relationship to the idea of brokerage, but this brokerage is rarely like the pure and formal economic intermediation seen in some modern markets. Indeed, for reasons illuminated by existing sociological and economic models, brokerage is a fragile relationship. In this paper, we review the causes of instability in brokerage and identify three social mechanisms that can stabilize fragile brokerage relationships: social isolation, broker capture, and organizational grafting. Each of these mechanisms rests on the emergence or existence of supporting institutions. We suggest that organizational grafting may be the most stable and effective resolution to the tensions inherent in brokerage, but it is also the most institutionally demanding.

  20. Influence of toroidal effects on the stability of the internal kink mode

    Energy Technology Data Exchange (ETDEWEB)

    Galvao, R.M.O.; Sakanaka, P.H.; Shigueoka, H.


    Using the sigma-stability technique, we study the stability of the internal kink mode in toroidal geometry. We show that there are two unstable regions separated by a stable on in a ..beta..-q/sub c/ stability diagram. In one of these regions toroidal effects are stabilizing and in the other they are destabilizing. Discrepant results of previous analytical theories and experimental results are explained.

  1. Shear viscosity of $\\beta$-stable nuclear matter

    CERN Document Server

    Benhar, Omar


    Viscosity plays a critical role in determining the stability of rotating neutron stars. We report the results of a calculation of the shear viscosity of $\\beta$~-~stable matter, carried out using an effective interaction based on a state-of-the-art nucleon-nucleon potential and the formalism of correlated basis functions. Within our approach the equation of state, determining the proton fraction, and the nucleon-nucleon scattering probability are consistently obtained from the same dynamical model. The results show that, while the neutron contribution to the viscosity is always dominant, above nuclear saturation density the electron contribution becomes appreciable.

  2. Specific Triazine Herbicides Induce Amyloid-beta(42) Production

    NARCIS (Netherlands)

    Portelius, Erik; Durieu, Emilie; Bodin, Marion; Cam, Morgane; Pannee, Josef; Leuxe, Charlotte; Mabondzo, Aloise; Oumata, Nassima; Galons, Herve; Lee, Jung Yeol; Chang, Young-Tae; Stuber, Kathrin; Koch, Philipp; Fontaine, Gaelle; Potier, Marie-Claude; Manousopoulou, Antigoni; Garbis, Spiros D.; Covaci, Adrian; Van Dam, Debby; De Deyn, Peter; Karg, Frank; Flajolet, Marc; Omori, Chiori; Hata, Saori; Suzuki, Toshiharu; Blennow, Kaj; Zetterberg, Henrik; Meijer, Laurent


    Proteolytic cleavage of the amyloid-beta protein precursor (A beta PP) ecretases leads to extracellular release of amyloid-beta (A beta) peptides. Increased production of A beta(42) over A beta(40) and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark. Identifyin

  3. 17-Beta-estradiol inhibits transforming growth factor-beta signaling and function in breast cancer cells via activation of extracellular signal-regulated kinase through the G protein-coupled receptor 30. (United States)

    Kleuser, Burkhard; Malek, Daniela; Gust, Ronald; Pertz, Heinz H; Potteck, Henrik


    Breast cancer development and breast cancer progression involves the deregulation of growth factors leading to uncontrolled cellular proliferation, invasion and metastasis. Transforming growth factor (TGF)-beta plays a crucial role in breast cancer because it has the potential to act as either a tumor suppressor or a pro-oncogenic chemokine. A cross-communication between the TGF-beta signaling network and estrogens has been postulated, which is important for breast tumorigenesis. Here, we provide evidence that inhibition of TGF-beta signaling is associated with a rapid estrogen-dependent nongenomic action. Moreover, we were able to demonstrate that estrogens disrupt the TGF-beta signaling network as well as TGF-beta functions in breast cancer cells via the G protein-coupled receptor 30 (GPR30). Silencing of GPR30 in MCF-7 cells completely reduced the ability of 17-beta-estradiol (E2) to inhibit the TGF-beta pathway. Likewise, in GPR30-deficient MDA-MB-231 breast cancer cells, E2 achieved the ability to suppress TGF-beta signaling only after transfection with GPR30-encoding plasmids. It is most interesting that the antiestrogen fulvestrant (ICI 182,780), which possesses agonistic activity at the GPR30, also diminished TGF-beta signaling. Further experiments attempted to characterize the molecular mechanism by which activated GPR30 inhibits the TGF-beta pathway. Our results indicate that GPR30 induces the stimulation of the mitogen-activated protein kinases (MAPKs), which interferes with the activation of Smad proteins. Inhibition of MAPK activity prevented the ability of E2 from suppressing TGF-beta signaling. These findings are of great clinical relevance, because down-regulation of TGF-beta signaling is associated with the development of breast cancer resistance in response to antiestrogens.

  4. Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. (United States)

    Maestro, Miguel Angel; Cardalda, Carina; Boj, Sylvia F; Luco, Reini F; Servitja, Joan Marc; Ferrer, Jorge


    Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). Herein, we review what we have learnt during recent years concerning the functions of these regulators in the developing and adult pancreas. Mouse studies have revealed that HNF1beta is a critical regulator of a transcriptional network that controls the specification, growth, and differentiation of the embryonic pancreas. HNF1beta mutations in humans accordingly often cause pancreas hypoplasia. By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. HNF4alpha mutations paradoxically also cause in utero and neonatal hyperinsulinism, which later evolves to decreased glucose-induced secretion. Recent studies show that Hnf4alpha deficiency in mice causes not only abnormal insulin secretion, but also an impairment of the expansion of beta-cell mass that normally occurs during pregnancy. In line with this finding, we present data that Hnf1alpha-/- beta-cells expressing SV40 large T antigen show a severe impairment of proliferation and failure to form tumours. Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells.

  5. Future double beta decay experiments

    Energy Technology Data Exchange (ETDEWEB)

    Piquemal, F. [Laboratoire Souterrain de Modane, Modane (France); Centre d' Etudes Nucleaire, Bordeaux-Gradignan (France)


    The search of neutrinoless double beta decay is very challenging because of the expected half-life of the process and the backgrounds from the natural radioactivity. Many projects exist to try to reach a sensitivity of ∼50 meV on the effective neutrino mass corresponding to a mass of isotopes of ∼100 kg. In this article some of the futur projects are presented.

  6. 鱼鳞胶原提取及其热稳定性提高的研究进展%Extraction of fish scale collagen and its thermal stability:research progress

    Institute of Scientific and Technical Information of China (English)

    杜田明; 陈子浩; 唐翔宇; 武继民


    近年来,随着水产加工业的迅速发展,鱼类下脚料中胶原蛋白的提取成为人们的研究热点。鱼鳞胶原具有优于畜禽胶原的低抗原性、低过敏性等特点,且来源广泛、价格低廉。该文综述了鱼鳞胶原提取及其热稳定性改进技术方面的研究进展。%In recent years, researchers have become more interested in fish scrap collagen collection .Fish collagen, thanks to its low antigenic and hypoallergenic properties , is superior to that of higher animals .Meanwhile , fish collagen derives from a wealth of sources and has a moderate price .Based on recent fish collagen extraction and modification , this article summarizeds extraction technologies , such as hot-water, chemistry, bio-enzyme, compound extraction and such modification methods as physical and chemical processes to improve the thermal stability .

  7. Research progress of additives for improving therapeutic peptides and proteins stability in PLGA microspheres%提高PLGA微球载蛋白多肽类药物稳定性添加剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈红丽; 王永学; 郭伟云; 张其清


    Microspheres made of poly-lactic-co-glycolic acid (PLGA) have been frequently proposed as drug delivery systems.A very significant challenge in the development of controlled PLGA releasing systems is the instability of drugs especially therapeutic peptides and proteins.Additional approaches,particularly the use of additives,are needed to optimize PLGA delivery of drugs.This article reviews the effects of additives,especially the effects of stabilizing protein during the preparation of PLGA microsphere and the sustained drug releasing processes.%聚乳酸-羟基乙酸共聚物(PLGA)包裹药物制成微球制剂是近年来药物输送体系的研究热点,但是PLGA包囊药物尤其是蛋白多肽类变性失活问题是研究的难点.改进生产工艺特别是使用添加剂可提高微球中包载药物的稳定性.综述了PLGA微球制备及释放过程中不同添加剂的作用特别是稳定蛋白药物的作用.

  8. Myokardinfarkt und Beta-Blocker

    Directory of Open Access Journals (Sweden)

    Stühlinger H-G


    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  9. Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer’s disease

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Chun Yang; Yufeng Liu; Peng Li; Huiying Yang; Jingxing Dai; Rongmei Qu; Lin Yuan


    Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei-mer’s disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant deg-radative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer’s disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.

  10. CRM 1-mediated degradation and agonist-induced down-regulation of beta-adrenergic receptor mRNAs. (United States)

    Bai, Ying; Lu, Huafei; Machida, Curtis A


    The beta1-adrenergic receptor (beta1-AR) mRNAs are post-transcriptionally regulated at the level of mRNA stability and undergo accelerated agonist-mediated degradation via interaction of its 3' untranslated region (UTR) with RNA binding proteins, including the HuR nuclear protein. In a previous report [Kirigiti et al. (2001). Mol. Pharmacol. 60:1308-1324], we examined the agonist-mediated down-regulation of the rat beta1-AR mRNAs, endogenously expressed in the rat C6 cell line and ectopically expressed in transfectant hamster DDT1MF2 and rat L6 cells. In this report, we determined that isoproterenol treatment of neonatal rat cortical neurons, an important cell type expressing beta1-ARs in the brain, results in significant decreases in beta1-AR mRNA stability, while treatment with leptomycin B, an inhibitor of the nuclear export receptor CRM 1, results in significant increases in beta1-AR mRNA stability and nuclear retention. UV-crosslinking/immunoprecipitation and glycerol gradient fractionation analyses indicate that the beta1-AR 3' UTR recognize complexes composed of HuR and multiple proteins, including CRM 1. Cell-permeable peptides containing the leucine-rich nuclear export signal (NES) were used as inhibitors of CRM 1-mediated nuclear export. When DDT1MF2 transfectants were treated with isoproterenol and peptide inhibitors, only the co-addition of the NES inhibitor reversed the isoproterenol-induced reduction of beta1-AR mRNA levels. Our results suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation and agonist-mediated down-regulation of the beta1-AR mRNAs.

  11. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kover, Karen, E-mail: [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Tasch, James; Hager, Melissa [Kansas City University Medical Biosciences, Kansas City, MO (United States); Clements, Mark; Moore, Wayne V. [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States)


    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  12. Multiple roles of mesenchymal beta-catenin during murine limb patterning. (United States)

    Hill, Theo P; Taketo, Makoto M; Birchmeier, Walter; Hartmann, Christine


    Recently canonical Wnt signaling in the ectoderm has been shown to be required for maintenance of the apical ectodermal ridge (AER) and for dorsoventral signaling. Using conditional gain- and loss-of-function beta-catenin alleles, we have studied the role of mesenchymal beta-catenin activity during limb development. Here, we show that loss of beta-catenin results in limb truncations due to a defect in AER maintenance. Stabilization of beta-catenin also results in truncated limbs, caused by a premature regression of the AER. Concomitantly, in these limbs, the expression of Bmp2, Bmp4 and Bmp7, and of the Bmp target genes Msx1, Msx2 and gremlin, is expanded in the mesenchyme. Furthermore, we found that the expression of Lmx1b, a gene exclusively expressed in the dorsal limb mesenchyme and involved in dorsoventral patterning, is reduced upon loss of beta-catenin activity and is expanded ventrally in gain-of-function limbs. However, the known ectodermal regulators Wnt7a and engrailed 1 are expressed normally. This suggests that Lmx1b is also regulated, in part, by a beta-catenin-mediated Wnt signal, independent of the non-canoncial Wnt7a signaling pathway. In addition, loss of beta-catenin results in a severe agenesis of the scapula. Concurrently, the expression of two genes, Pax1 and Emx2, which have been implicated in scapula development, is lost in beta-catenin loss-of-function limbs; however, only Emx2 is upregulated in gain-of-function limbs. Mesenchymal beta-catenin activity is therefore required for AER maintenance, and for normal expression of Lmx1b and Emx2.

  13. Age-related changes in the expression of 11beta-hydroxysteroid dehydrogenase type 2 in rat Leydig cells.

    Directory of Open Access Journals (Sweden)

    Katerina Georgieva


    Full Text Available Previous studies in rats have shown that the ability of Leydig cells (LCs to produce testosterone significantly declines with age. To address the possible mechanisms by which aging LCs lose their steroidogenic function, we determined the effect of aging on the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD type 2. The enzyme plays a protective role in blunting the suppressive effects of glucocorticoids on LCs steroidogenesis. Our immunohistochemical analysis revealed progressive decline in 11beta-HDS type 2 expression in LCs of the 18 months of age rats and the most significant reduction in 11beta-HSD2 immunoreactivity was evident in the testicular interstitium of 24- month-old rats. The decrease in the 11beta-HDS type 2 immunostaining in LCs during aging coincided with decline in insulin-like 3/relaxin-like factor (INSL3/RLF expression, an independent marker for LCs differentiation status. Concomitant with the age-related decrease of 11beta-HDS type 2 immunoreactivity in the LCs population, the immunoexpression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD, marker for LCs steroidogenic activity, was greatly reduced at 24 months compared to 3-month-old control. Similar pattern of expression exhibited also androgen receptor (AR which is localized in the nuclei of Sertoli cells (SCs, LCs, and peritubular cells. During ages we observed progressive decrease in the immunoreactivity for AR in the testicular types and there was a loss of stage specificity in SCs at age of 24 months. It now seems evident that a variety of factors are likely to be involved in age-related decreases in LCs steroidogenesis, including 11beta-HSD type 2. The observed reduction in 11beta-HSD type 2 expression in aging LCs reflects the decline in their protection ability, opposing the suppressive effect of glucocorticoids on testosterone production.

  14. $\\beta$-particle energy-summing correction for $\\beta$-delayed proton emission measurements

    CERN Document Server

    Meisel, Z; Crawford, H L; Cyburt, R H; Grinyer, G F; Langer, C; Montes, F; Schatz, H; Smith, K


    A common approach to studying $\\beta$-delayed proton emission is to measure the energy of the emitted proton and corresponding nuclear recoil in a double-sided silicon-strip detector (DSSD) after implanting the $\\beta$-delayed proton emitting ($\\beta$p) nucleus. However, in order to extract the proton-decay energy, the measured energy must be corrected for the additional energy implanted in the DSSD by the $\\beta$-particle emitted from the $\\beta$p nucleus, an effect referred to here as $\\beta$-summing. We present an approach to determine an accurate correction for $\\beta$-summing. Our method relies on the determination of the mean implantation depth of the $\\beta$p nucleus within the DSSD by analyzing the shape of the total (proton + recoil + $\\beta$) decay energy distribution shape. We validate this approach with other mean implantation depth measurement techniques that take advantage of energy deposition within DSSDs upstream and downstream of the implantation DSSD.

  15. EDITORIAL: Catalysing progress Catalysing progress (United States)

    Demming, Anna


    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  16. Function of the integrin alpha 6 beta 1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor

    DEFF Research Database (Denmark)

    Shaw, L M; Chao, C; Wewer, U M;


    The involvement of the alpha 6 beta a integrin, a laminin receptor, in breast carcinoma progression needs to be addressed rigorously. We report that a human breast carcinoma cell line, MDA-MB-435, known to be highly invasive and metastatic, expresses three potential integrin laminin receptors...... function that involved expression of a cytoplasmic domain deletion mutant of the beta 4 integrin subunit by cDNA transfection. Stable transfectants of MDA-MB-435 cells that expressed this mutant beta 4 subunit were inhibited dramatically in their ability to adhere and migrate on laminin matrices......, and their capacity to invade Matrigel was reduced significantly. These findings support the hypothesis that alpha 6 beta 1 is important for breast cancer progression. Moreover, this approach is a powerful method that should be useful in assessing the role of alpha 6 beta 1 in other cells....

  17. SIRT1 inhibits proliferation of pancreatic cancer cells expressing pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, by suppression of {beta}-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Srisuttee, Ratakorn; Moon, Jeong [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Choi, Young-Whan [Department of Horticultural Bioscience, Pusan National University, Miryang 627-706 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Oh, Sangtaek [Department of Advanced Fermentation Fusion Science and Technology, Kookmin University, Seoul 136-702 (Korea, Republic of); Chung, Young-Hwa, E-mail: [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer SIRT1 inhibits protein levels of {beta}-catenin and its transcriptional activity. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for the decrease of {beta}-catenin expression. Black-Right-Pointing-Pointer SIRT1-mediated degradation of {beta}-catenin is not required for GSK-3{beta} and Siah-1 but for proteosome. Black-Right-Pointing-Pointer SIRT1 activation inhibits proliferation of pancreatic cancer cells expressing PAUF. -- Abstract: Because we found in a recent study that pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, induces a rapid proliferation of pancreatic cells by up-regulation of {beta}-catenin, we postulated that {beta}-catenin might be a target molecule for pancreatic cancer treatment. We thus speculated whether SIRT1, known to target {beta}-catenin in a colon cancer model, suppresses {beta}-catenin in those pancreatic cancer cells that express PAUF (Panc-PAUF). We further evaluated whether such suppression would lead to inhibition of the proliferation of these cells. The ectopic expression of either SIRT1 or resveratrol (an activator of SIRT1) suppressed levels of {beta}-catenin protein and its transcriptional activity in Panc-PAUF cells. Conversely, suppression of SIRT1 expression by siRNA enhanced {beta}-catenin expression and transcriptional activity. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for reduction of {beta}-catenin. Treatment with MG132, a proteasomal inhibitor, restored {beta}-catenin protein levels, suggesting that SIRT1-mediated degradation of {beta}-catenin requires proteasomal activity. It was reported that inhibition of GSK-3{beta} or Siah-1 stabilizes {beta}-catenin in colon cancer cells, but suppression of GSK-3{beta} or Siah-1 using siRNA in the presence of resveratrol instead diminished {beta}-catenin protein levels in Panc-PAUF cells. This suggests that GSK-3{beta} and Siah-1 are not involved in SIRT1

  18. TGF-beta1 system in Leydig cells. Part II: TGF-beta1 and progesterone, through Smad1/5, are involved in the hyperplasia/hypertrophy of Leydig cells. (United States)

    Gonzalez, Candela R; Gonzalez, Betina; Rulli, Susana B; Dos Santos, Mara L; Mattos Jardim Costa, Guilherme; França, Luiz R; Calandra, Ricardo S; Gonzalez-Calvar, Silvia I


    Several reports indicate that transforming growth factor beta1 (TGF-beta1) participates in the regulation of cell cycle progression. In this work, we analyzed the in vitro effect of TGF-beta1 on Leydig cell proliferation markers and the in vivo effect of this cytokine in Leydig cell hyperplasia/hypertrophy. The in vitro effect of TGF-beta1 (1 ng/ml) plus progesterone (10(-6) M) on purified Leydig cells from 3 week-old mice increased the immunocytochemically detected PCNA and stimulated the phosphorylation of Smad 1/5. Progesterone (10(-6) M) in the presence or absence of TGF-beta1 diminished the ratio Bax/Bcl-2. Morphometric testicular studies of mice treated with progesterone (s.c.) plus TGF-beta1 (intratesticular), showed an increase in interstitial volume and a decrease in tubular volume. Furthermore, the cytoplasmic volume of Leydig cells showed an increment in this experimental group with a diminution in nuclear volume. Thus, it turned out that the administration of progesterone and TGF-beta1 augmented the volume of Leydig cells. These results indicate a clear effect of TGF-beta1 in the hypertrophy/hyperplasia of Leydig cells.

  19. Sequential mutations in the interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor beta-subunit genes are necessary for the complete conversion to growth autonomy mediated by a truncated beta C subunit. (United States)

    Hannemann, J; Hara, T; Kawai, M; Miyajima, A; Ostertag, W; Stocking, C


    An amino-terminally truncated beta C receptor (beta C-R) subunit of the interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor complex mediates factor-independent and tumorigenic growth in two spontaneous mutants of a promyelocytic cell line. The constitutive activation of the JAK2 protein kinase in these mutants confirms that signaling occurs through the truncated receptor protein. Noteworthily, in addition to a 10-kb deletion in the beta C-R subunit gene encoding the truncated receptor, several secondary and independent mutations that result in the deletion or functional inactivation of the allelic beta C-R subunit and the closely related beta IL3-R subunit genes were observed in both mutants, suggesting that such mutations are necessary for the full oncogenic penetrance of the truncated beta C-R subunit. Reversion of these mutations by the expression of the wild-type beta C-R in the two mutants resulted in a fivefold decrease in cloning efficiency of the mutants in the absence of IL3, confirming a functional interaction between the wild-type and truncated proteins. Furthermore, expression of the truncated beta C-R subunit in factor-dependent myeloid cells did not immediately render the cells autonomous but increased the spontaneous frequency to factor-independent growth by 4 orders of magnitude. Implications for both leukemogenic progression and receptor-subunit interaction and signaling are discussed.

  20. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    Directory of Open Access Journals (Sweden)

    Hamid Arazi


    Full Text Available RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated in four weeks resistance training. Before and after the test period fasting blood samples were obtained to determine anabolic (the growth hormone and testosterone and catabolic (cortisol hormones, and fat mass, lean body mass (LBM and muscular strength were measured. Dependent and independent t-tests were used to analyze data.Results:After the training period, there were no significant differen-ces between the groups with respect to fat mass, LBM and anabolic-catabolic hormones. HMB supplementation resulted in a significantly greater strength gain (p≤0.05.Conclusion:Greater increase in strength for HMB group was not accompanied by body composition and basal circulating anabolic-catabolic hormonal changes. It seems that HMB supplementation may have beneficial effects on neurological adaptations of strength gain.

  1. Some aspects of pressure-induced {omega} {yields} {beta} transformation in group IVB elements

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, K D; Jyoti, G; Gupta, Satish C; Sikka, S K [High Pressure Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)


    The {omega} (hexagonal) to {beta} (bcc) transformation in Zr and Hf occurs at 30 and 71 GPa under static pressures. This transition has not been found in Ti up to 87 GPa. On the basis of full-potential linearized augmented plane wave calculations aided with thermal and entropy correction we predict an {omega} {yields} {beta} transition in Ti at around 102 GPa along the 300 K isotherm. In addition to this, we calculate the {omega} {yields} {beta} transitions in Zr and Hf at around 27 and 65 GPa respectively, which are in excellent agreement with the experimental values. The {omega} {yields} {beta} transition pressures, 102, 27 and 65 GPa for Ti, Zr and Hf respectively, do not follow the trend implied by the principle of corresponding states. We have analysed the causes for this anomalous trend. We observe that the {omega} {yields} {beta} transition depends on how the increased d-population due to s-d transfer under pressure is distributed in the different d-substates. For example, at ambient conditions, the bcc phase is unstable and the difference between the average charges in the bcc stabilizing d-t{sub 2g} state and the destabilizing d-e{sub g} state are 0.008, 0.082 and 0.013 for Ti, Zr and Hf respectively. Compression increases this difference and stabilizes the bcc structure when it becomes about 0.1. The charge transfer needed for stabilizing the {beta} structure is highest for Ti followed by Hf and then Zr, in line with the trend in transition pressures.

  2. Abstraction Mechanisms in the BETA Programming Language

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger


    ]) --- covering both data, procedural and control abstractions, substituting constructs like class, procedure, function and type. Correspondingly objects, procedure activation records and variables are all regarded as special cases of the basic building block of program executions: the entity. A pattern thus......The BETA programming language is developed as part of the BETA project. The purpose of this project is to develop concepts, constructs and tools in the field of programming and programming languages. BETA has been developed from 1975 on and the various stages of the language are documented in [BETA...... a]. The application area of BETA is programming of embedded as well as distributed computing systems. For this reason a major goal has been to develop constructs that may be efficiently implemented. Furthermore the BETA language is intended to have a few number of basic but general constructs...

  3. Pediatric heart failure therapy with beta-adrenoceptor antagonists. (United States)

    Foerster, Susan R; Canter, Charles E


    Management of chronic heart failure in pediatrics has been altered by the adult literature showing improvements in mortality and hospitalization rates with the use of beta-adrenoceptor antagonists (beta-blockers) for routine therapy of all classes of ischemic and non-ischemic heart failure. Many pediatric heart failure specialists have incorporated these agents into their routine management of pediatric heart failure related to dilated cardiomyopathy or ventricular dysfunction in association with congenital heart disease. Retrospective and small prospective case series have shown encouraging improvements in cardiac function and symptoms, but interpretation has been complicated by the high rate of spontaneous recovery in pediatric patients. A recently completed pediatric double-blind, randomized, placebo-controlled clinical trial showed no difference between placebo and two doses of carvedilol over a 6-month period of follow-up, with significant improvement of all three groups over the course of evaluation. Experience with adults has suggested that only certain beta-blockers, including carvedilol, bisoprolol, nebivolol, and metoprolol succinate, should be used in the treatment of heart failure and that patients with high-grade heart failure may derive the most benefit. Other studies surmise that early or prophylactic use of these medications may alter the risk of disease progression in some high-risk subsets, such as patients receiving anthracyclines or those with muscular dystrophy. This article reviews these topics using experience as well as data from all the recent pediatric studies on the use of beta-blockers to treat congestive heart failure, especially when related to systolic ventricular dysfunction.

  4. Hanford beta-gamma personnel dosimeter prototypes and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Fix, J.J.; Holbrook, K.L.; Soldat, K.L.


    Upgraded and modified Hanford dosimeter prototypes were evaluated for possible use at Hanford as a primary beta-gamma dosimeter. All prototypes were compatible with the current dosimeter card and holder design, as well as processing with the automated Hanford readers. Shallow- and deep-dose response was determined for selected prototypes using several beta sources, K-fluorescent x rays and filtered x-ray techniques. All prototypes included a neutron sensitive chip. A progressive evaluation of the performance of each of the upgrades to the current dosimeter is described. In general, the performance of the current dosimeter can be upgraded using individual chip sensitivity factors to improve precision and an improved algorithm to minimize bias. The performance of this dosimeter would be adequate to pass all categories of the ANSI N13.11 performance criteria for dosimeter procesors, provided calibration techniques compatible with irradiations adopted in the standard were conducted. The existing neutron capability of the dosimeter could be retained. Better dosimeter performance to beta-gamma radiation can be achieved by modifying the Hanford dosimeter so that four of the five chip positions are devoted to calculating these doses instead of the currently used two chip positions. A neutron sensitive chip was used in the 5th chip position, but all modified dosimeter prototypes would be incapable of discriminating between thermal and epithermal neutrons. An improved low energy beta response can be achieved for the current dosimeter and all prototypes considered by eliminating the security credential. Further improvement can be obtained by incorporating the 15-mil thick TLD-700 chips.

  5. Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. (United States)

    Hasnain, Sumaira Z; Borg, Danielle J; Harcourt, Brooke E; Tong, Hui; Sheng, Yonghua H; Ng, Choa Ping; Das, Indrajit; Wang, Ran; Chen, Alice C-H; Loudovaris, Thomas; Kay, Thomas W; Thomas, Helen E; Whitehead, Jonathan P; Forbes, Josephine M; Prins, Johannes B; McGuckin, Michael A


    In type 2 diabetes, hyperglycemia is present when an increased demand for insulin, typically due to insulin resistance, is not met as a result of progressive pancreatic beta cell dysfunction. This defect in beta cell activity is typically characterized by impaired insulin biosynthesis and secretion, usually accompanied by oxidative and endoplasmic reticulum (ER) stress. We demonstrate that multiple inflammatory cytokines elevated in diabetic pancreatic islets induce beta cell oxidative and ER stress, with interleukin-23 (IL-23), IL-24 and IL-33 being the most potent. Conversely, we show that islet-endogenous and exogenous IL-22, by regulating oxidative stress pathways, suppresses oxidative and ER stress caused by cytokines or glucolipotoxicity in mouse and human beta cells. In obese mice, antibody neutralization of IL-23 or IL-24 partially reduced beta cell ER stress and improved glucose tolerance, whereas IL-22 administration modulated oxidative stress regulatory genes in islets, suppressed ER stress and inflammation, promoted secretion of high-quality efficacious insulin and fully restored glucose homeostasis followed by restitution of insulin sensitivity. Thus, therapeutic manipulation of immune regulators of beta cell stress reverses the hyperglycemia central to diabetes pathology.

  6. The Protective Role of Carnosic Acid against Beta-Amyloid Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    H. Rasoolijazi


    Full Text Available Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer’s disease (AD. Previous studies have demonstrated the role of carnosic acid (CA, an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1–40 was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aβ groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1–40 can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aβ + CA group, in comparison with the Aβ group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus.

  7. DJ-1 Protects Pancreatic Beta Cells from Cytokine- and Streptozotocin-Mediated Cell Death


    Deepak Jain; Gesine Weber; Daniel Eberhard; Mehana, Amir E; Jan Eglinger; Alena Welters; Barbara Bartosinska; Kay Jeruschke; Jürgen Weiss; Günter Päth; Hiroyoshi Ariga; Jochen Seufert; Eckhard Lammert


    A hallmark feature of type 1 and type 2 diabetes mellitus is the progressive dysfunction and loss of insulin-producing pancreatic beta cells, and inflammatory cytokines are known to trigger beta cell death. Here we asked whether the anti-oxidant protein DJ-1 encoded by the Parkinson's disease gene PARK7 protects islet cells from cytokine- and streptozotocin-mediated cell death. Wild type and DJ-1 knockout mice (KO) were treated with multiple low doses of streptozotocin (MLDS) to induce inflam...

  8. Properties of starch subjected to partial gelatinization and beta-amylolysis. (United States)

    Hickman, B Elliot; Janaswamy, Srinivas; Yao, Yuan


    The overall objective of this research is to understand the impact of partial gelatinization and beta-amylase hydrolysis (beta-amylolysis) on the physicochemical properties of starch. Three starches (normal corn, waxy corn, and wheat) were chosen as test examples and thermally treated at 40% moisture content to up to 95 degrees C and then subjected to beta-amylolysis. The enzyme treatment resulted in over 10% maltose yield. Subsequent debranching analysis showed the production of chain stubs as short as having the degree of polymerization of 2 and 3, suggesting a thorough beta-amylolysis at certain branch locations. For starch samples subjected to partial gelatinization, polarized light microscopy shows reduced intensity of birefringence and differential scanning calorimetry shows reduced enthalpy change associated with gelatinization. Both indicate the reduced chain organization due to the treatment. Further, a substantial transformation of initial A-type crystalline structure to B- and V-types upon treatments is noticed from X-ray powder diffraction measurements. In addition, the rapid viscosity analysis (RVA) indicated a drastic viscosity reduction, increased peak temperature, and improved stability of pasting behavior due to hydrothermal treatments and beta-amylolysis. Overall, our results point out the possibility of obtaining modified starches having desirable stable pasting behavior by using a combined partial gelatinization and beta-amylolysis approach.

  9. Is heart rate reduction more important than target dose in chronic heart failure therapy with a beta-blocker?

    Institute of Scientific and Technical Information of China (English)

    Yong-Fang Guo; Yi An


    1 IntroductionBeta-adrenoceptor blocking agents (beta-blockers) are now well established as cornerstone therapy in patients with systolic chronic heart failure (CHF).[1] Clinical data have overwhelmingly proven the beneficial effects of beta-blocker therapy in terms of improving patient prognosis,decreasing requirements for hospitalization,and postponing disease progression.[2-4] However,it remains unclear what the optimal efficacious and safe dose for an individual patient with CHF is,and whether this can simply be inferred from the target dose for each beta-blocking agent as used in the major clinical trials.Beta-blockers are a heterogeneous class of drugs,and due to the polymorphisms of beta-adrenoceptor gene expression,there is marked individual variation in responsiveness to specific agents.[5] If pharmacodynamic markers of responsiveness to beta-blockade (such as heart rate (HR) reduction) are more important than the achievement of a target dose,could they become another potential therapeutic target in beta-blocker therapy? We provide a discussion of the question in this article.

  10. Binding constants of inclusion complexes of nitroimidazoles with {beta}-cyclodextrins in the absence and presence of PVP

    Energy Technology Data Exchange (ETDEWEB)

    Chadha, Renu [University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014 (India)]. E-mail:; Jain, D.V.S. [Depatment of Chemistry, Panjab University, Chandigarh 160014 (India); Aggarwal, Amit [University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014 (India); Singh, Surjit [GND University, Amritsar, Panjab (India); Thakur, Deepika [University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014 (India)


    Thermodynamics of complexation of 5-nitroimidazoles with {beta}-cyclodextrin and its methylated and hydroxypropyl derivatives in water and in 0.25% polyvinylpyrrolidone are determined by solution calorimetry. A 1:1 stoichiometry was established. The equilibrium constant (K) for all the nitroimidazoles fall in the range 1000-1900 M{sup -1} suitable for use of cyclodextrins as drug carriers. The complexation ability is significantly enhanced by methylation of the {beta}-cyclodextrin. The stability constant increased in the order metronidazole < ornidazole < tinidazole < secnidazole. The presence of polyvinylpyrrolidone enhances the stability constants.

  11. Achieving a long-lived high-beta plasma state by energetic beam injection. (United States)

    Guo, H Y; Binderbauer, M W; Tajima, T; Milroy, R D; Steinhauer, L C; Yang, X; Garate, E G; Gota, H; Korepanov, S; Necas, A; Roche, T; Smirnov, A; Trask, E


    Developing a stable plasma state with high-beta (ratio of plasma to magnetic pressures) is of critical importance for an economic magnetic fusion reactor. At the forefront of this endeavour is the field-reversed configuration. Here we demonstrate the kinetic stabilizing effect of fast ions on a disruptive magneto-hydrodynamic instability, known as a tilt mode, which poses a central obstacle to further field-reversed configuration development, by energetic beam injection. This technique, combined with the synergistic effect of active plasma boundary control, enables a fully stable ultra-high-beta (approaching 100%) plasma with a long lifetime.

  12. Progress in Interferometry for LISA at JPL

    CERN Document Server

    Spero, Robert; de Vine, Glenn; Dickson, Jeffrey; Klipstein, William; Ozawa, Tetsuo; McKenzie, Kirk; Shaddock, Daniel; Robison, David; Sutton, Andrew; Ware, Brent


    Recent advances at JPL in experimentation and design for LISA interferometry include the demonstration of Time Delay Interferometry using electronically separated end stations, a new arm-locking design with improved gain and stability, and progress in flight readiness of digital and analog electronics for phase measurements.

  13. Progress in interferometry for LISA at JPL

    Energy Technology Data Exchange (ETDEWEB)

    Spero, Robert; Bachman, Brian; De Vine, Glenn; Dickson, Jeffrey; Klipstein, William; Ozawa, Tetsuo; McKenzie, Kirk; Shaddock, Daniel; Robison, David; Ware, Brent [Jet Propulsion Laboratory (JPL), California Institute of Technology, 4800 Oak Grove Drive Pasadena, CA 91109 (United States); Sutton, Andrew, E-mail: [Centre for Gravitational Physics, The Australian National University, ACT 0200 (Australia)


    Recent advances at JPL in experimentation and design for LISA interferometry include the demonstration of time delay interferometry using electronically separated end stations, a new arm-locking design with improved gain and stability, and progress in flight readiness of digital and analog electronics for phase measurements.

  14. Milk Intolerance, Beta-Casein and Lactose. (United States)

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen


    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  15. Sawtooth crashes at high beta on JET

    Energy Technology Data Exchange (ETDEWEB)

    Alper, B.; Huysmans, G.T.A.; Sips, A.C.C. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Nave, M.F.F. [Universidade Tecnica, Lisbon (Portugal). Inst. Superior Tecnico


    The sawtooth crashes on JET display features which depend on beta. The main observation is a transient bulging of flux surfaces (duration inferior to 30 microsec.), which is predominantly on the low field side and extends to larger radii as beta increases. This phenomenon reaches the plasma boundary when beta{sub N} exceeds 0.5 and in these cases is followed by an ELM within 50 microsec. These sawtooth/ELM events limit plasma performance. Modelling of mode coupling shows qualitative agreement between observations of the structure of the sawtooth precursor and the calculated internal kink mode at high beta. (authors). 6 refs., 5 figs.

  16. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal


    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  17. Learning numerical progressions. (United States)

    Vitz, P C; Hazan, D N


    Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968).

  18. Influence of beta instabilities on the early stages of nucleation and growth of alpha in beta titanium alloys (United States)

    Nag, Soumya

    Microstructural evolution in beta Titanium alloys is an important factor that governs the properties exhibited by them. Intricate understanding of complex phase transformations in these alloys is vital to tailor their microstructures and in turn their properties to our advantage. One such important subject of study is the nucleation and growth of alpha precipitates triggered by the compositional instabilities in the beta matrix, instilled in them during non equilibrium heat treatments. The present work is an effort to investigate such a phenomenon. Here studies have been conducted primarily on two different beta-Titanium alloys of commercial relevance- Ti5553 (Ti-5Al-5Mo-5V-3Cr-0.5Fe), an alloy used in the aerospace industry for landing gear applications and, TNZT (Ti-35Nb-7Zr-5Ta), a potential load bearing orthopedic implant alloy. Apart from the effect of thermal treatment on these alloys, the focus of this work is to study the interplay between different alpha and beta stabilizers present in them. For this, advanced nano-scale characterization tools such as High Resolution STEM, High Resolution TEM, EFTEM and 3D Atom Probe have been used to determine the structure, distribution and composition of the non equilibrium instabilities such as beta' and o, and also to investigate the subsequent nucleation of stable alpha. Thus in this work, very early stages of phase separation via spinodal decomposition and second phase nucleation in titanium alloys are successfully probed at an atomic resolution. For the first time, atomically resolved HRSTEM 'Z'-contrast image is recorded showing modulated structures within the as-quenched beta matrix. Also in the same condition HRTEM results showed the presence of nanoscale alpha regions. These studies are revalidated by conventional selected area diffraction and 3D atom probe reconstruction results. Also TEM dark field and selected are diffraction studies are conducted to understand the effect of quenching and subsequent aging of

  19. Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine [beta]-synthase

    Energy Technology Data Exchange (ETDEWEB)

    Koutmos, Markos; Kabil, Omer; Smith, Janet L.; Banerjee, Ruma (Michigan-Med)


    The catalytic potential for H{sub 2}S biogenesis and homocysteine clearance converge at the active site of cystathionine {beta}-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes {beta}-replacement reactions of either serine or cysteine by homocysteine to give cystathionine and water or H{sub 2}S, respectively. In this study, high-resolution structures of the full-length enzyme from Drosophila in which a carbanion (1.70 {angstrom}) and an aminoacrylate intermediate (1.55 {angstrom}) have been captured are reported. Electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base. Additional stabilizing interactions between active site residues and the catalytic intermediates are observed. Furthermore, the structure of the regulatory 'energy-sensing' CBS domains, named after this protein, suggests a mechanism for allosteric activation by S-adenosylmethionine.

  20. Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. (United States)

    Chesire, Dennis R; Isaacs, William B


    Beta-catenin signaling may contribute to prostate cancer (CaP) progression. Although beta-catenin is known to upregulate T cell factor (TCF) target gene expression in CaP cells, recent evidence demonstrates its capacity to enhance ligand-dependent androgen receptor (AR) function. Thus, we wished to further understand the interaction between these two pathways. We find in both CaP cells (CWR22-Rv1, LAPC-4, DU145) and non-CaP cells (HEK-293, TSU, SW480, HCT-116) that beta-catenin/TCF-related transcription (CRT), as measured by activation of a synthetic promoter and that of cyclin D1, is inhibited by androgen treatment. This inhibition is AR-dependent, as it only occurs in cells expressing AR endogenously or transiently, and is abrogated by AR antagonists. Additional analyses convey that the ligand-dependent nature of CRT suppression depends on transactivation-competent AR in the nucleus, but not on indirect effects stemming from AR target gene expression. Given the recent work identifying an AR/beta-catenin interaction, and from our finding that liganded AR does not prompt gross changes in the constitutive nuclear localization of TCF4 or mutant beta-catenin, we hypothesized that transcription factor (i.e. AR and TCF) competition for beta-catenin recruitment may explain, in part, androgen-induced suppression of CRT. To address this idea, we expressed an AR mutant lacking its DNA-binding domain (DBD). This receptor could not orchestrate ligand-dependent CRT repression, thereby providing support for those recent data implicating the AR DBD/LBD as necessary for beta-catenin interaction. Further supporting this hypothesis, TCF/LEF over-expression counteracts androgen-induced suppression of CRT, and requires beta-catenin binding activity to do so. Interestingly, TCF4 over-expression potently antagonizes AR function; however, this inhibition may occur independently of beta-catenin/TCF4 interaction. These results from TCF4 over-expression analyses, taken together, provide

  1. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi


    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  2. Hypersynchrony despite pathologically reduced beta oscillations in patients with Parkinson's disease: a pharmaco-magnetoencephalography study. (United States)

    Heinrichs-Graham, Elizabeth; Kurz, Max J; Becker, Katherine M; Santamaria, Pamela M; Gendelman, Howard E; Wilson, Tony W


    Parkinson's disease (PD) is a progressive debilitating neurodegenerative disorder clinically manifest by motor, posture and gait abnormalities. Human neurophysiological studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchrony throughout the basal ganglia-thalamic-cortical motor network in PD. Notably, suppression of this pathological beta synchrony by dopamine replacement therapy or deep-brain stimulation has been associated with improved motor function. However, due to the invasive nature of these studies, it remains unknown whether this "pathological beta" is actually stronger than that observed in healthy demographically matched controls. We used magnetoencephalography to investigate neuronal synchrony and oscillatory amplitude in the beta range and lower frequencies during the resting state in patients with PD and a matched group of patients without neurological disease. Patients with PD were studied both in the practically defined drug "OFF" state, and after administration of dopamine replacements. We found that beta oscillatory amplitude was reduced bilaterally in the primary motor regions of unmedicated patients with PD compared with controls. Administration of dopaminergic medications significantly increased beta oscillatory activity, thus having a normalizing effect. Interestingly, we also found significantly stronger beta synchrony (i.e., hypersynchrony) between the primary motor regions in unmedicated patients with PD compared with controls, and that medication reduced this coupling which is in agreement with the intraoperative studies. These results are consistent with the known functionality of the basal ganglia-thalamic-cortical motor circuit and the likely consequences of beta hypersynchrony in the subthalamic nucleus of patients with PD.

  3. Nuclear spectroscopic studies. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Riedinger, L.L.; Sorensen, S.P.


    This report describes progress in the experimental nuclear physics program of the University of Tennessee, Knoxville. It presents findings related to properties of high-spin states, low-energy levels of nuclei far from stability, and high-energy heavy-ion physics, as well as a brief description of the Joint Institute of Heavy Ion Research (a collaboration between the University of Tennessee, Vanderbilt University, and Oak Ridge National Laboratory) and its activities (particularly those of the last few years), and a list of publications. 89 refs., 18 figs., 5 tabs.

  4. Structural Aspects for Evolution of [beta]-Lactamases from Penicillin-Binding Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Meroueh, Samy O.; Minasov, George; Lee, Wenlin; Shoichet, Brian K.; Mobashery, Shahriar (NWU); (UCSF); (Notre)


    Penicillin-binding proteins (PBPs), biosynthetic enzymes of bacterial cell wall assembly, and {beta}-lactamases, resistance enzymes to {beta}-lactam antibiotics, are related to each other from an evolutionary point of view. Massova and Mobashery (Antimicrob. Agents Chemother. 1998, 42, 1-17) have proposed that for {beta}-lactamases to have become effective at their function as antibiotic resistance enzymes, they would have had to undergo structure alterations such that they would not interact with the peptidoglycan, which is the substrate for PBPs. A cephalosporin analogue, 7{beta}-[N-Acetyl-L-alanyl-{gamma}-D-glutamyl-L-lysine]-3-acetoxymethyl-3-cephem-carboxylic acid (compound 6), was conceived and synthesized to test this notion. The X-ray structure of the complex of this cephalosporin bound to the active site of the deacylation-deficient Q120L/Y150E variant of the class C AmpC {beta}-lactamase from Escherichia coli was solved at 1.71 {angstrom} resolution. This complex revealed that the surface for interaction with the strand of peptidoglycan that acylates the active site, which is present in PBPs, is absent in the {beta}-lactamase active site. Furthermore, insertion of a peptide in the {beta}-lactamase active site at a location where the second strand of peptidoglycan in some PBPs binds has effectively abolished the possibility for such interaction with the {beta}-lactamase. A 2.6 ns dynamics simulation was carried out for the complex, which revealed that the peptidoglycan surrogate (i.e., the active-site-bound ligand) undergoes substantial motion and is not stabilized for binding within the active site. These factors taken together disclose the set of structure modifications in the antibiotic resistance enzyme that prevent it from interacting with the peptidoglycan, en route to achieving catalytic proficiency for their intended function.

  5. The pharmacokinetics of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Visser, J; Hefting, N R; Oosting, R; Meijer, D K; Lerk, C F


    Hydroxypropyl-beta-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 micrograms/ml. The pharmacokinetics of beta-cyclodextrin and of hydroxypropyl-beta-cyclodextrin were studied after intravenous adm

  6. The impact of beta-elemene on beta-tubulin of human hepatoma hepg2 cells

    Institute of Scientific and Technical Information of China (English)

    Yuqiu Mao; Liying Ban; Jielin Zhang; Li Hou; Xiaonan Cui


    Objective:The aim of this study was to investigate the impact of beta-elemene injection on the growth and beta-tubulin of human hepatocarcinoma HepG2 cells. Methods:cellproliferation was assessed by MTT assay. cellcycle distribution was detected by flow cytometry (FCM). The mRNA expression of beta-tubulin was measured by RT-PCR. West-ern blot analysis was used to determine protein expression of beta-tubulin and the polymerization of beta-tubulin. Results:Beta-elemene injection inhibited HepG2 cells proliferation in a dose-and time-dependent manner;FCM analysis indicated beta-elemene injection induced cellcycle arrested at S phase. RT-PCR and western-blot analysis showed that beta-elemene injection down-regulated beta-tubulin expression at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusion:Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells, the mechanism might be partly related to the down-regulation of beta-tubulin and inhibition of microtubular polymerization.

  7. Expressions of GSK-3beta, Beta-Catenin and PPAR-Gamma in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhang; Lu Si; Yu Li; Can Mi


    Objective: To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application.Methods: Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues.Results: The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation.Conclusion: Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

  8. Radiation-induced polymerization of {beta}(+)-pinene and synthesis of optically active {beta}(+)/{beta}(-)pinene polymers and copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Franco, E-mail: franco.cataldo@fastwebnet.i [Lupi Chemical Research, Via Casilina 1626/A, 00133 Rome (Italy); Lilla, Edo; Ursini, Ornella [Institute of Chemical Methodologies, CNR, Via Salaria Km. 29300, Monterotondo Stazione 00016, Rome (Italy)


    Poly-{beta}(+)-pinene (pB(+)p) was synthesized with {gamma} irradiation of the monomer {beta}(+)-pinene in bulk under vacuum at 1181 kGy. Also scalemic mixtures of {beta}(+)-pinene and {beta}(-)-pinene were irradiated at 1181 kGy to obtain synthetic copolymers of pB(+)/B(-)p. For comparison also {beta}(-)-pinene was converted into poly-{beta}(-)-pinene (pB(-)p) under the identical conditions adopted for its enantiomer. Furthermore pB(+)p and pB(-)p were also synthesized by thermal processing under the action of a chemical free radical initiator. The optical rotatory dispersion (ORD) of all pBp resins synthesized were accurately studied in the spectral range comprised between 375 and 625 nm and a curious asymmetry in the ORD of pB(+)p versus the ORD of pB(-)p is reported. Furthermore, it is shown that (+)-p-menth-1-ene and (-)-p-menth-1-ene are useful as a model compounds for the pBp resins and for the explanation of the amplification of the optical activity of the {beta}(+)-pinene and {beta}(-)-pinene after their ring-opening polymerization to pB(+)p and pB(-)p. The pBp resins were studied also by FT-IR spectroscopy and by thermal analysis (TGA and DTG).

  9. Imperfect World of beta beta-decay Nuclear Data Sets

    Energy Technology Data Exchange (ETDEWEB)

    Pritychenko, B. [Brookhaven National Lab. (BNL), Upton, NY (United States). NNDC


    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  10. Selective binding of chiral molecules of cinchona alkaloid by beta- and gamma-cyclodextrins and organoselenium-bridged bis(beta-cyclodextrin)s. (United States)

    Liu, Yu; Li, Li; Zhang, Heng-Yi; Fan, Zhi; Guan, Xu-Dong


    The inclusion complexation behavior of chiral members of cinchona alkaloid with beta- and gamma-cyclodextrins (1 and 2) and 6,6(')-trimethylenediseleno-bridged bis(beta-cyclodextrin) (3) was assessed by means of fluorescence and 2D-NMR spectroscopy. The spectrofluorometric titrations have been performed in aqueous buffer solution (pH 7.20) at 25.0 degrees C to determine the stability constants of the inclusion complexation of 1-3 with guest molecules (i.e., cinchonine, cinchonidine, quinine, and quinidine) in order to quantitatively investigate the molecular selective binding ability. The stability constants of the resulting complexes of 2 with guest molecules are larger than that of 1. As a result of cooperative binding, the stability constants of inclusion complexation of dimeric beta-cyclodextrin 3 with cinchonidine and cinchonine are higher than that of parent 1 by factor of 4.5 and 2.4, respectively. These results are discussed from the viewpoint of the size-fit and geometric complementary relationship between the host and guest.

  11. Beta-glucosidase I variants with improved properties

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander


    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  12. Microscopic stability of cold shock protein A examined by NMR native state hydrogen exchange as a function of urea and trimethylamine N-oxide. (United States)

    Jaravine, V. A.; Rathgeb-Szabo, K.; Alexandrescu, A. T.


    Native state hydrogen exchange of cold shock protein A (CspA) has been characterized as a function of the denaturant urea and of the stabilizing agent trimethylamine N-oxide (TMAO). The structure of CspA has five strands of beta-sheet. Strands beta1-beta4 have strongly protected amide protons that, based on experiments as a function of urea, exchange through a simple all-or-none global unfolding mechanism. By contrast, the protection of amide protons from strand beta5 is too weak to measure in water. Strand beta5 is hydrogen bonded to strands beta3 and beta4, both of which afford strong protection from solvent exchange. Gaussian network model (GNM) simulations, which assume that the degree of protection depends on tertiary contact density in the native structure, accurately predict the strong protection observed in strands beta1-beta4 but fail to account for the weak protection in strand beta5. The most conspicuous feature of strand beta5 is its low sequence hydrophobicity. In the presence of TMAO, there is an increase in the protection of strands beta1-beta4, and protection extends to amide protons in more hydrophilic segments of the protein, including strand beta5 and the loops connecting the beta-strands. TMAO stabilizes proteins by raising the free energy of the denatured state, due to highly unfavorable interactions between TMAO and the exposed peptide backbone. As such, the stabilizing effects of TMAO are expected to be relatively independent of sequence hydrophobicity. The present results suggest that the magnitude of solvent exchange protection depends more on solvent accessibility in the ensemble of exchange susceptible conformations than on the strength of hydrogen-bonding interactions in the native structure. PMID:10716181

  13. Dosimetry of low-energy beta radiation

    Energy Technology Data Exchange (ETDEWEB)

    Borg, J.


    Useful techniques and procedures for determination of absorbed doses from exposure in a low-energy {beta} radiation field were studied and evaluated in this project. The four different techniques included were {beta} spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical low-energy {beta} radiation field a moderated spectrum from a {sup 14}C source (E{sub {beta}},{sub max} =156 keV) was chosen for the study. The measured response of a Si(Li) detector to photons (bremsstrahlung) showed fine agreement with the MC calculated photon response, whereas the difference between measured and MC calculated responses to electrons indicates an additional dead layer thickness of about 12 {mu}m in the Si(Li) detector. The depth-dose profiles measured with extrapolation chambers at two laboratories agreed very well, and it was confirmed that the fitting procedure previously reported for {sup 147}Pm depth-dose profiles is also suitable for {beta} radiation from {sup 14}C. An increasing difference between measured and MC calculated dose rates for increasing absorber thickness was found, which is explained by limitations of the EGS4 code for transport of very low-energy electrons (below 10-20 keV). Finally a study of the thermally stimulated exoelectron emission (TSEE) response of BeO thin film dosemeters to {beta} radiation for radiation fields with maximum {beta} energies ranging from 67 keV to 2.27 MeV is reported. For maximum {beta} energies below approximately 500 keV, a decrease in the response amounting to about 20% was observed. It is thus concluded that a {beta} dose higher than about 10 {mu}Gy can be measured with these dosemeters to within 0 to -20% independently of the {beta}energy for E{sub {beta}},{sub max} values down to 67 keV. (au) 12 tabs., 38 ills., 71 refs.


    Institute of Scientific and Technical Information of China (English)

    王家臣; 骆中洲


    In fact, the failure of any slope takes place progressively, but the progressive failure mechanism has not been emphasized sufficently in the present stability analysis of slopes. This paper provides an example of the progressive slope failure which took place at Pingzhuang west surface coal mine and was numbered the 26th slide. The three-dimensional reliability model for progressive slope failure is used to study the failure process of the 26th slide. The outcomes indicate that the progressive failure is indeed the failure mechanism of the slide.

  15. Hyperations, Veblen progressions and transfinite iterations of ordinal functions

    CERN Document Server

    Fernández-Duque, David


    In this paper we introduce hyperations and cohyperations, which are forms of transfinite iteration of ordinal functions. Hyperations are iterations of normal functions. Unlike iteration by pointwise convergence, hyperation preserves normality. The hyperation of a normal function f is a sequence of normal functions so that f^0= id, f^1 = f and for all ordinals \\alpha, \\beta we have that f^(\\alpha + \\beta) = f^\\alpha f^\\beta. These conditions do not determine f^\\alpha uniquely; in addition, we require that the functions be minimal in an appropriate sense. We study hyperations systematically and show that they are a natural refinement of Veblen progressions. Next, we define cohyperations, very similar to hyperations except that they are left-additive: given \\alpha, \\beta, f^(\\alpha + \\beta)= f^\\beta f^\\alpha. Cohyperations iterate initial functions which are functions that map initial segments to initial segments. We systematically study cohyperations and see how they can be employed to define left inverses to h...

  16. Geothermal progress monitor. Progress report No. 1

    Energy Technology Data Exchange (ETDEWEB)


    Progress is reported on the following: electrical uses, direct-heat uses, drilling activities, leases, geothermal loan guarantee program, general activities, and legal, institutional, and regulatory activites. (MHR)

  17. Hydrothermal synthesis of alpha- and beta-HgS nanostructures (United States)

    Galain, Isabel; María, Pérez Barthaburu; Ivana, Aguiar; Laura, Fornaro


    We synthesized HgS nanostructures by the hydrothermal method in order to use them as electron acceptors in hybrid organic-inorganic solar cells. We employed different mercury sources (HgO and Hg(CH3COO)2) and polyvinylpyrrolidone (PVP) or hexadecanethiol (HDT) as stabilizing/capping agent for controlling size, crystallinity, morphology and stability of the obtained nanostructures. We also used thiourea as sulfur source, and a temperature of 180 °C during 6 h. Synthesized nanostructures were characterized by powder X-Ray Diffraction, Diffuse Reflectance Infrared Fourier Transform and Transmission Electron Microscopy. When PVP acts as stabilizing agent, the mercury source has influence on the size -but not in morphology- of the beta-HgS obtained nansostructures. HDT has control over nanostructures' size and depending on the relation Hg:HDT, we obtained a mixture of alpha and beta HgS which can be advantageous in the application in solar cells, due their absorption in different spectral regions. The smallest nanostructures obtained have a mean diameter of 20 nm when using HDT as capping agent. Also, we deposited the aforementioned nanostructures onto flat glass substrates by the spin coating technique as a first approach of an active layer of a solar cell. The depositions were characterized by atomic force microscopy. We obtained smaller particle deposition and higher particle density -but a lower area coverage (5%) - in samples with HDT as capping agent. This work presents promising results on nanostructures for future application on hybrid solar cells. Further efforts will be focused on the deposition of organic-inorganic layers.

  18. Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4

    DEFF Research Database (Denmark)

    Richter, Wito; Day, Peter; Agrawal, Rani


    Beta1- and beta2-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta1AR but not beta2AR signaling, and chronic stimulation of the two receptors has opposing...

  19. Nebivolol : third-generation beta-blockade

    NARCIS (Netherlands)

    de Boer, Rudolf A.; Voors, Adriaan A.; van Veldhuisen, Dirk J.


    Nebivolol is a third generation beta-blocker. It is highly selective for the beta 1-adrenoceptor, and has additional nitric oxide-mediated vasodilating and antioxidant properties, along with a favourable metabolic profile. Nebivolol is well tolerated by patients with hypertension and heart failure.

  20. The beta subunit of casein kinase II

    DEFF Research Database (Denmark)

    Boldyreff, B; Piontek, K; Schmidt-Spaniol, I;


    cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies....

  1. Venus: Geology of Beta Regio rift system (United States)

    Nikishin, A. M.; Borozdin, V. K.; Bobina, N. N.


    Beta Regio is characterized by the existence of rift structures. We compiled new geologic maps of Beta Regio according to Magellan data. There are many large uplifted tesserae on beta upland. These tesserae are partly buried by younger volcanic cover. We can conclude, using these observations, that Beta upland formed mainly due to lithospheric tectonic uplifting and was only partly constructed by volcanism. Theia Mons is the center of the Beta rift system. Many rift belts are distributed radially to Theia Mons. Typical widths of rifts are 40-160 km. Rift valleys are structurally represented by crustal grabens or half-grabens. There are symmetrical and asymmetrical rifts. Many rifts have shoulder uplifts up to 0.5-1 km high and 40-60 km wide. Preliminary analysis for rift valley structural cross sections lead to the conclusion that rifts originated due to 5-10 percent crustal extension. Many rifts traverse Beta upland and spread to the surrounding lowlands. We can assume because of these data that Beta rift system has an active-passive origin. It formed due to regional tectonic lithospheric extension. Rifting was accelerated by upper-mantle hot spot origination under the center of passive extension (under the Beta Regio).

  2. Beta-agonists and animal welfare (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  3. Shielding for beta-gamma radiation. (United States)

    Fletcher, J J


    The build-up factor, B, for lead was expressed as a polynominal cubic function of the relaxation length, mu x, and incorporated in a "general beta-gamma shielding equation." A computer program was written to determine shielding thickness for polyenergetic beta-gamma sources without resorting to the conventional "add-one-HVL" method.

  4. Anti-TGF-beta strategies for the treatment of chronic liver disease. (United States)

    Breitkopf, Katja; Haas, Stephan; Wiercinska, Eliza; Singer, Manfred V; Dooley, Steven


    Permanent alcohol abuse may lead to chronic liver injury with deleterious sequelae such as liver cirrhosis and hepatocellular carcinoma. Mechanisms of fibrogenesis encompass recruitment of inflammatory cells at the site of injury and cytokine mediated activation of hepatic stellate cells (HSC) with accumulation of interstitial collagens. HSC transdifferentiation and accompanying apoptosis result in destruction of liver architecture and are therefore key steps of disease progression. TGF-beta represents the main profibrogenic cytokine in liver fibrosis and other fibroproliferative disorders by inducing extracellular matrix deposition as part of the wound healing response. In parallel, TGF-beta triggers hepatocytes that are strongly responsive for this cytokine, to undergo apoptosis, thereby providing space for HSC proliferation and generation of a collagenous matrix. Anti TGF-beta approaches were established and successfully utilized for the treatment of experimental fibrogenesis. Dominant negative TGF-beta receptors (TbetaR), generated by fusing the Fc domain of human IgG and the N-terminal (extracellular) fragment of TbetaRII (Fc:TbetaRII) were applied to suppress fibrosis. Similarly TGF-beta binding proteins like decorin, antagonistic cytokines such as bone morphogenetic protein-7, hepatocyte growth factor, IL-10, or IFN-gamma were as efficient as camostat mesilate, a protease inhibitor that possibly abrogated proteolytic activation of TGF-beta. Further, our group recently overexpressed Smad7 in bile duct ligation induced liver fibrosis and achieved efficient inhibition of intracellular TGF-beta signaling, thereby counteracting profibrogenic effects in cultured HSC and in vivo. A direct link between the effect of alcohol and TGF-beta exists through reactive oxygen species that are generated in liver cells by alcohol metabolism and represent activators of TGF-beta signaling. Thus, soluble TbetaRII expression reduced experimental fibrogenesis in vitro and in vivo

  5. [Stress hormones liberated by fangotherapy. ACTH and beta-endorphin levels under heat stress]. (United States)

    Giusti, P; Cima, L; Tinello, A; Cozzi, F; Targa, L; Lazzarin, P; Todesco, S


    In 6 healthy subjects submitted to fango therapy in the Euganean thermal baths (Italy), the plasma concentrations of beta-endorphin and ACTH increased transitorily but significantly. These results correlate with the release of these peptides by the pituitary in response to thermal stressing. The analgesic and hypothermic action responsible for good toleration of thermal stress induced by fango therapy, can be explained by this increase in plasma beta-endorphin. The repeated brief increases in plasma beta-endorphin during thermal treatment result in progressive improvement in articular and muscular symptomatology. The results of our study on plasma levels of ACTH confirm that the thermal stress associated with fango therapy activates the pituitary gland. Immunomodulatory effects are discussed.

  6. Beta-glucuronidase in physiology and disease. (United States)

    Basińska, Agnieszka; Floriańczyk, Bolesław


    beta-glucoronidase (EC is a lysosomal enzyme catylysing the decomposition of beta-D-glucoronides--compounds arising as a result of the combination of beta-D-glucoronic acid and a number of compounds both exo- and endogenous, containing hydroxylic, carboxylic, amine, imine or thiol groups. The most common test evaluating the activity of the enzyme is that using phenolphtalein glucoronide as a biosynthetic substrate. The freed aglycons are colorimetrically assayed. The activity of beta-glucoronidase increases in many pathological conditions: liver infammations, cirrhosis of the liver, inflammations of other organs, cholestatic jaundice, tuberculosis, sarcoidosis and also in neoplasms. Many authors point to beta-glucoronidase as a sensitive indicator signalling cell damage.

  7. Precision measurements in 20F beta decay (United States)

    Hughes, Maximilian; Naviliat-Cuncic, Oscar; Voytas, Paul; George, Elizabeth; Paulauskas, Stan; Huyan, Xueying


    Precision measurements of the shape of the beta particle energy spectrum provide a sensitive window to search for new interactions beyond the standard model. The decay of 20F offers an attractive system due to the simple decay scheme for a coincidence measurement. A beam of 20F ions, produced at the National Superconducting Cyclotron Laboratory, was implanted into a beta-detector. A gamma-ray detection system surrounded the beta detector to detect the beta-delayed gammas in coincidence to reduce the background. Preliminary analysis of these data focus on the half-life of 20F due to the statistical inconsistency of previous work. Monte Carlo simulations are ongoing to analyze the shape of the beta energy spectrum. Results of the analysis of the half-life will be presented. Supported by National Science Foundation Grant PHY-1102511.

  8. Ranking Beta Sheet Topologies of Proteins

    DEFF Research Database (Denmark)

    Fonseca, Rasmus; Helles, Glennie; Winter, Pawel


    One of the challenges of protein structure prediction is to identify long-range interactions between amino acids.  To reliably predict such interactions, we enumerate, score and rank all beta-topologies (partitions of beta-strands into sheets, orderings of strands within sheets and orientations...... of paired strands) of a given protein.  We show that the beta-topology corresponding to the native structure is, with high probability, among the top-ranked. Since full enumeration is very time-consuming, we also suggest a method to deal with proteins with many beta-strands. The results reported...... in this paper are highly relevant for ab initio protein structure prediction methods based on decoy generation. The top-ranked beta-topologies can be used to find initial conformations from which conformational searches can be started. They can also be used to filter decoys by removing those with poorly...

  9. Experimental beta-alaninuria induced by (aminooxyacetate.

    Directory of Open Access Journals (Sweden)

    Kurozumi Y


    Full Text Available Experimental beta-alaninuria was induced in rats by injection of (aminooxyacetate (AOA, a potent inhibitor of aminotransferases, in order to elucidate the pathogenesis of hyper-beta-alaninemia. A 27-fold increase of beta-alanine (BALA excretion was induced by subcutaneous injection of 1 5 mg of AOA per kg of body weight. A 13-fold and a 9-fold increase of beta-aminoisobutyric acid (BAIBA and gamma-aminobutyric acid (GABA, respectively, were also induced simultaneously by the AOA injection. Identification of BALA and BAIBA isolated from the rat urine was performed by chromatographic and mass spectrometric analyses. The effects of AOA injection on the tissue levels of these amino acids were also studied. Contents of BALA in the liver and kidney and GABA in the brain increased significantly in response to AOA injection. The present study indicates that BALA transaminase is involved in hyper-beta-alaninemia.

  10. Laminins containing the beta2 chain modulate the precise organization of CNS synapses. (United States)

    Egles, Christophe; Claudepierre, Thomas; Manglapus, Mary K; Champliaud, Marie-France; Brunken, William J; Hunter, Dale D


    Synapses are formed and stabilized by concerted interactions of pre-, intra-, and post-synaptic components; however, the precise nature of the intrasynaptic components in the CNS remains obscure. Potential intrasynaptic components include extracellular matrix molecules such as laminins; here, we isolate beta2-containing laminins, including perhaps laminins 13 (alpha3beta2gamma3) and 14 (alpha4beta2gamma3), from CNS synaptosomes suggesting a role for these molecules in synaptic organization. Indeed, hippocampal synapses that form in vivo in the absence of these laminins are malformed at the ultrastructural level and this malformation is replicated in synapses formed in vitro, where laminins are provided largely by the post-synaptic neuron. This recapitulation of the in vivo function of laminins in vitro suggests that the malformations are a direct consequence of the removal of laminins from the synapse. Together, these results support a role for neuronal laminins in the structural integrity of central synapses.

  11. Proposal for the construction of a High-Beta Tokamak at LASL

    Energy Technology Data Exchange (ETDEWEB)

    Van der Laan, P.C.T.; Freidberg, J.P.; Thomas, K.S.


    The large heating rate inherent to implosion heating allows the rapid generation of high-beta tokamak plasmas. A study of these plasmas in the proposed HBT machine can give information on how MHD equilibrium and stability limit ..beta.. and q. Both a wide current profile and a moderate elongation of the minor cross section should help to raise the permissible peak ..beta.. values in HBT to at least 20 percent. The longer term loss processes occurring in MHD-stable plasmas are to be investigated. The main parameters of HBT are: R = 0.30 m, minor cross section a racetrack of width and height 0.24 m and 0.48 m, B/sub phi/ = 2 T, I/sub phi/ approximately 750 kA.

  12. A Global Model of $\\beta^-$-Decay Half-Lives Using Neural Networks

    CERN Document Server

    Costiris, N; Gernoth, K A; Mavrommatis, E


    Statistical modeling of nuclear data using artificial neural networks (ANNs) and, more recently, support vector machines (SVMs), is providing novel approaches to systematics that are complementary to phenomenological and semi-microscopic theories. We present a global model of $\\beta^-$-decay halflives of the class of nuclei that decay 100% by $\\beta^-$ mode in their ground states. A fully-connected multilayered feed forward network has been trained using the Levenberg-Marquardt algorithm, Bayesian regularization, and cross-validation. The halflife estimates generated by the model are discussed and compared with the available experimental data, with previous results obtained with neural networks, and with estimates coming from traditional global nuclear models. Predictions of the new neural-network model are given for nuclei far from stability, with particular attention to those involved in r-process nucleosynthesis. This study demonstrates that in the framework of the $\\beta^-$-decay problem considered here, ...

  13. Liver cancer-derived hepatitis C virus core proteins shift TGF-beta responses from tumor suppression to epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Serena Battaglia

    Full Text Available BACKGROUND: Chronic hepatitis C virus (HCV infection and associated liver cirrhosis represent a major risk factor for hepatocellular carcinoma (HCC development. TGF-beta is an important driver of liver fibrogenesis and cancer; however, its actual impact in human cancer progression is still poorly known. The aim of this study was to investigate the role of HCC-derived HCV core natural variants on cancer progression through their impact on TGF-beta signaling. PRINCIPAL FINDINGS: We provide evidence that HCC-derived core protein expression in primary human or mouse hepatocyte alleviates TGF-beta responses in terms or growth inhibition or apoptosis. Instead, in these hepatocytes TGF-beta was still able to induce an epithelial to mesenchymal transition (EMT, a process that contributes to the promotion of cell invasion and metastasis. Moreover, we demonstrate that different thresholds of Smad3 activation dictate the TGF-beta responses in hepatic cells and that HCV core protein, by decreasing Smad3 activation, may switch TGF-beta growth inhibitory effects to tumor promoting responses. CONCLUSION/SIGNIFICANCE: Our data illustrate the capacity of hepatocytes to develop EMT and plasticity under TGF-beta, emphasize the role of HCV core protein in the dynamic of these effects and provide evidence for a paradigm whereby a viral protein implicated in oncogenesis is capable to shift TGF-beta responses from cytostatic effects to EMT development.

  14. Plutonium inventories for stabilization and stabilized materials

    Energy Technology Data Exchange (ETDEWEB)

    Williams, A.K.


    The objective of the breakout session was to identify characteristics of materials containing plutonium, the need to stabilize these materials for storage, and plans to accomplish the stabilization activities. All current stabilization activities are driven by the Defense Nuclear Facilities Safety Board Recommendation 94-1 (May 26, 1994) and by the recently completed Plutonium ES&H Vulnerability Assessment (DOE-EH-0415). The Implementation Plan for accomplishing stabilization of plutonium-bearing residues in response to the Recommendation and the Assessment was published by DOE on February 28, 1995. This Implementation Plan (IP) commits to stabilizing problem materials within 3 years, and stabilizing all other materials within 8 years. The IP identifies approximately 20 metric tons of plutonium requiring stabilization and/or repackaging. A further breakdown shows this material to consist of 8.5 metric tons of plutonium metal and alloys, 5.5 metric tons of plutonium as oxide, and 6 metric tons of plutonium as residues. Stabilization of the metal and oxide categories containing greater than 50 weight percent plutonium is covered by DOE Standard {open_quotes}Criteria for Safe Storage of Plutonium Metals and Oxides{close_quotes} December, 1994 (DOE-STD-3013-94). This standard establishes criteria for safe storage of stabilized plutonium metals and oxides for up to 50 years. Each of the DOE sites and contractors with large plutonium inventories has either started or is preparing to start stabilization activities to meet these criteria.

  15. Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin

    DEFF Research Database (Denmark)

    Nybo, Mads; Nielsen, E H; Svehag, S E


    Complement activation (CA) has been reported to play a role in the pathogenesis of Alzheimer's disease (AD). To investigate whether CA may contribute to amyloidogenesis in general, the CA potential of different amyloid fibril proteins was tested. CA induced by A beta preparations containing soluble...... protein, protofilaments and some fibrils or only fibrils in a solid phase system (ELISA) was modest with a slow kinetics compared to the positive delta IgG control. Soluble A beta induced no detectable CA in a liquid phase system (complement consumption assay) while fibrillar A beta caused CA at 200 mg....../ml and higher concentrations. Soluble beta 2-microglobulin (beta 2M) purified from peritoneal dialysates was found to be as potent a complement activator as A beta in both solid and liquid phase systems while beta 2M purified from urine exhibited lower activity, a difference which may be explained...

  16. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;


    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

  17. Painlev\\'e representation of Tracy-Widom$_\\beta$ distribution for $\\beta = 6$

    CERN Document Server

    Rumanov, Igor


    In \\cite{betaFP1}, we found explicit Lax pairs for the soft edge of beta ensembles with even integer values of $\\beta$. Using this general result, the case $\\beta=6$ is further considered here. This is the smallest even $\\beta$, when the corresponding Lax pair and its relation to Painlev\\'e II (PII) have not been known before, unlike cases $\\beta=2$ and $4$. It turns out that again everything can be expressed in terms of the Hastings-McLeod solution of PII. In particular, a second order nonlinear ODE for the logarithmic derivative of Tracy-Widom distribution for $\\beta=6$ involving the PII function in the coefficients, is found, which allows one to compute asymptotics for the distribution function. The ODE is a consequence of a linear system of three ODEs for which the local Painlev\\'e analysis yields series solutions with exponents in the set $4/3$, $1/3$ and $-2/3$.

  18. Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated and nuclear transfer derived bovine pregnancies. (United States)

    Ravelich, S R; Shelling, A N; Wells, D N; Peterson, A J; Lee, R S F; Ramachandran, A; Keelan, J A


    Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.

  19. A Review on Nanofluids: Preparation, Stability Mechanisms, and Applications


    Wei Yu; Huaqing Xie


    Nanofluids, the fluid suspensions of nanomaterials, have shown many interesting properties, and the distinctive features offer unprecedented potential for many applications. This paper summarizes the recent progress on the study of nanofluids, such as the preparation methods, the evaluation methods for the stability of nanofluids, and the ways to enhance the stability for nanofluids, the stability mechanisms of nanofluids, and presents the broad range of current and future applications in var...

  20. Sugar Beet (Beta vulgaris L.)


    Kagami, Hiroyo; Kurata, Masayuki; Matsuhira, Hiroaki; Taguchi, Kazunori; Mikami, Tetsuo; Tamagake, Hideto; Kubo, Tomohiko


    Creating transgenic plants is invaluable for the genetic analysis of sugar beet and will be increasingly important as sugar beet genomic technologies progress. A protocol for Agrobacterium-mediated transformation of sugar beet is described in this chapter. Our protocol is optimized for a sugar beet genotype that performs exceptionally well in tissue culture, including the steps of dedifferentiation, callus proliferation, and regeneration. Because of the infrequent occurrence of such a genotyp...

  1. Influence of the substitution of {beta}-cyclodextrins by cationic groups on the complexation of organic anions

    Energy Technology Data Exchange (ETDEWEB)

    Hbaieb, S. [U.R. Physico-Chimie des Materiaux Solides, Faculte des Sciences de Tunis, Manar II, 2092 Tunis (Tunisia)], E-mail:; Kalfat, R. [U.R. Physico-Chimie des Materiaux Solides, Faculte des Sciences de Tunis, Manar II, 2092 Tunis (Tunisia); Chevalier, Y. [Laboratoire d' Automatique et de Genie des Procedes (LAGEP), UMR 5007 CNRS-Universite Claude Bernard Lyon 1, 69622 Villeurbanne (France)], E-mail:; Amdouni, N. [U.R. Physico-Chimie des Materiaux Solides, Faculte des Sciences de Tunis, Manar II, 2092 Tunis (Tunisia); Parrot-Lopez, H. [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires (ICBMS), UMR 5246 CNRS-Universite Claude Bernard Lyon 1, 69622 Villeurbanne (France)], E-mail:


    The inclusion complexation of the organic anion, dansyl-acid, by cationic derivatives of {beta}-cyclodextrin has been investigated. A series of cationic {beta}-cyclodextrins with various positive charge has been synthesized by selective functionalization of the primary face of {beta}-cyclodextrin with amino groups. The complexes were of the 1:1 stoichiometry; the stability constants (K{sub 11}) have been evaluated from UV-Vis measurements by application of the Benesi-Hildebrand equation. The presence of amino groups increased the complexation ability. {beta}-cyclodextrin fully substituted at the primary face with amino groups showed the strongest inclusion binding ability towards the dansyl-acid guest. The enhanced complexation for anions was ascribed to the cationic amino groups. A simple thermodynamic model of the electrostatic contribution to the complexation is presented.

  2. Parkin protects dopaminergic neurons from excessive Wnt/{beta}-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Rawal, Nina [Laboratory of Molecular Neurobiology, MBB, DBRM, Karolinska Institute, S-17177 Stockholm (Sweden); Corti, Olga [Universite Pierre et Marie Curie-Paris 6, CRICM UMR-S975, Inserm, U975 (France); CNRS, UMR 7225, Paris (France); Sacchetti, Paola [Laboratory of Molecular Neurobiology, MBB, DBRM, Karolinska Institute, S-17177 Stockholm (Sweden); Ardilla-Osorio, Hector [Universite Pierre et Marie Curie-Paris 6, CRICM UMR-S975, Inserm, U975 (France); CNRS, UMR 7225, Paris (France); Sehat, Bita [Cancer Center Karolinska, Karolinska Institute, S-17177 Stockholm (Sweden); Brice, Alexis [Universite Pierre et Marie Curie-Paris 6, CRICM UMR-S975, Inserm, U975 (France); CNRS, UMR 7225, Paris (France); Department of Genetics and Cytogenetics, AP-HP, Groupe Hospitalier Pitie-Salpetriere, Paris (France); Arenas, Ernest, E-mail: [Laboratory of Molecular Neurobiology, MBB, DBRM, Karolinska Institute, S-17177 Stockholm (Sweden)


    Parkinson's disease (PD) is caused by degeneration of the dopaminergic (DA) neurons of the substantia nigra but the molecular mechanisms underlying the degenerative process remain elusive. Several reports suggest that cell cycle deregulation in post-mitotic neurons could lead to neuronal cell death. We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates {beta}-catenin protein levels in vivo. Stabilization of {beta}-catenin in differentiated primary ventral midbrain neurons results in increased levels of cyclin E and proliferation, followed by increased levels of cleaved PARP and loss of DA neurons. Wnt3a signaling also causes death of post-mitotic DA neurons in parkin null animals, suggesting that both increased stabilization and decreased degradation of {beta}-catenin results in DA cell death. These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and {beta}-catenin-induced cell death.

  3. Report on Progress Toward Security and Stability in Afghanistan (United States)


    assistance from ISAF. The TAA effort is now focused on developing ASI capacity to generate and sustain their forces. Advisors interact with...three Afghan domestic election observation groups: Afghanistan Youth National and Social Organization, Transparent Election Foundation of Afghanistan...approximately 40 individuals. The combined operations of the ANSF resulted in the seizures of 18,137 kg of opium, 52 kg morphine , 1,849 kg of heroin, 1,004 kg

  4. Report on Progress Toward Security and Stability in Afghanistan (United States)


    seeking to sell its Amu Darya extraction rights to Tajik or Uzbek investors. The Afghan-Tajik hydrocarbon basin seismic survey is ongoing, with...complete), improvements to the Kandahar medium voltage network (early stages), and installation of Turbine Unit 2 at Kajaki Dam (completion of preparatory

  5. Report on Progress Toward Security and Stability in Afghanistan (United States)


    facilities formerly based in Afghanistan have now been moved to Pakistan, specifically in the border town of Chaman , Baluchistan Province. The...area of Chaman – while reflecting the weakness of the Taliban in Afghanistan, have the potential to have a significant political effect in Afghanistan...patronage networks. Further, several border crossing points, including Weesh Chaman and the Kandahar inland customs depot, still lack the automated

  6. Report on Progress Toward Security and Stability in Afghanistan (United States)


    captured or detained by the KKA. KKA personnel have forensics and investigative training, and are able to exploit intelligence gained during their...enable, preserve, and sustain operations. These items include ballistic guard shacks, small arms and crew-served weapons, ammunition, and equipment...collection, challenges remain in forensics analysis, the logistics involved in maintaining a chain of custody, and the storage of evidence while awaiting

  7. Next year China’s economic progress will maintain stability

    Institute of Scientific and Technical Information of China (English)


    Central Economic Work Conference was held in Beijing from December 12 to December 14.The meeting proposed the general requirements for economic work of 2012.In 2012,the government will continue to carry out proactive fiscal policy and prudent

  8. Report on Progress Toward Security and Stability in Afghanistan (United States)


    marketing efforts resulted in the sale of more than 11.5 UNCLASSIFIED 169 million condoms and oral and injectable contraceptive products, with a...determined. Another key factor in this assessment will be whether a Bilateral Security Agreement (BSA) between the U.S. and Afghanistan is reached...reporting period. Thus far, these attacks have not significantly affected the strong relationship between coalition and ANSF personnel, particularly

  9. Role of dentin MMPs in caries progression and bond stability. (United States)

    Mazzoni, A; Tjäderhane, L; Checchi, V; Di Lenarda, R; Salo, T; Tay, F R; Pashley, D H; Breschi, L


    Dentin can be described as a biological composite with collagen matrix embedded with nanosized hydroxyapatite mineral crystallites. Matrix metalloproteinases (MMPs) and cysteine cathepsins are families of endopeptidases. Enzymes of both families are present in dentin and collectively capable of degrading virtually all extracellular matrix components. This review describes these enzymes and their presence in dentin, mainly focusing on their role in dentin caries pathogenesis and loss of collagen in the adhesive hybrid layer under composite restorations. MMPs and cysteine cathepsins present in saliva, mineralized dentin, and/or dentinal fluid may affect the dentin caries process at the early phases of demineralization. Changes in collagen and noncollagenous protein structure may participate in observed decreases in mechanical properties of caries-affected dentin and reduce the ability of caries-affected dentin to remineralize. These endogenous enzymes also remain entrapped within the hybrid layer during the resin infiltration process, and the acidic bonding agents themselves (irrespective of whether they are etch-and-rinse or self-etch) can activate these endogenous protease proforms. Since resin impregnation is frequently incomplete, denuded collagen matrices associated with free water (which serves as a collagen cleavage reagent for these endogenous hydrolase enzymes) can be enzymatically disrupted, finally contributing to the degradation of the hybrid layer. There are multiple in vitro and in vivo reports showing that the longevity of the adhesive interface is increased when nonspecific enzyme-inhibiting strategies are used. Different chemicals (i.e., chlorhexidine, galardin, and benzalkonium chloride) or collagen cross-linker agents have been successfully employed as therapeutic primers in the bonding procedure. In addition, the incorporation of enzyme inhibitors (i.e., quaternary ammonium methacrylates) into the resin blends has been recently promoted. This review will describe MMP functions in caries and hybrid layer degradation and explore the potential therapeutic role of MMP inhibitors for the development of improved intervention strategies for MMP-related oral diseases.

  10. Role of Dentin MMPs in Caries Progression and Bond Stability


    A. Mazzoni; Tjäderhane, L.; Checchi, V.; Di Lenarda, R.; Salo, T.; Tay, F.R.; Pashley, D.H.; Breschi, L


    Dentin can be described as a biological composite with collagen matrix embedded with nanosized hydroxyapatite mineral crystallites. Matrix metalloproteinases (MMPs) and cysteine cathepsins are families of endopeptidases. Enzymes of both families are present in dentin and collectively capable of degrading virtually all extracellular matrix components. This review describes these enzymes and their presence in dentin, mainly focusing on their role in dentin caries pathogenesis and loss of collag...

  11. Role of Dentin MMPs in Caries Progression and Bond Stability (United States)

    Mazzoni, A.; Tjäderhane, L.; Checchi, V.; Di Lenarda, R.; Salo, T.; Tay, F.R.; Pashley, D.H.


    Dentin can be described as a biological composite with collagen matrix embedded with nanosized hydroxyapatite mineral crystallites. Matrix metalloproteinases (MMPs) and cysteine cathepsins are families of endopeptidases. Enzymes of both families are present in dentin and collectively capable of degrading virtually all extracellular matrix components. This review describes these enzymes and their presence in dentin, mainly focusing on their role in dentin caries pathogenesis and loss of collagen in the adhesive hybrid layer under composite restorations. MMPs and cysteine cathepsins present in saliva, mineralized dentin, and/or dentinal fluid may affect the dentin caries process at the early phases of demineralization. Changes in collagen and noncollagenous protein structure may participate in observed decreases in mechanical properties of caries-affected dentin and reduce the ability of caries-affected dentin to remineralize. These endogenous enzymes also remain entrapped within the hybrid layer during the resin infiltration process, and the acidic bonding agents themselves (irrespective of whether they are etch-and-rinse or self-etch) can activate these endogenous protease proforms. Since resin impregnation is frequently incomplete, denuded collagen matrices associated with free water (which serves as a collagen cleavage reagent for these endogenous hydrolase enzymes) can be enzymatically disrupted, finally contributing to the degradation of the hybrid layer. There are multiple in vitro and in vivo reports showing that the longevity of the adhesive interface is increased when nonspecific enzyme-inhibiting strategies are used. Different chemicals (i.e., chlorhexidine, galardin, and benzalkonium chloride) or collagen cross-linker agents have been successfully employed as therapeutic primers in the bonding procedure. In addition, the incorporation of enzyme inhibitors (i.e., quaternary ammonium methacrylates) into the resin blends has been recently promoted. This review will describe MMP functions in caries and hybrid layer degradation and explore the potential therapeutic role of MMP inhibitors for the development of improved intervention strategies for MMP-related oral diseases. PMID:25535202

  12. Report on Progress Toward Security and Stability in Afghanistan (United States)


    through fiscal year 2010 and has been prepared in coordination with the Secretary of State, the Director of National Intelligence, the Attorney General...During Ramadan, as seen in previous years, insurgent fundraising efforts increase in Islamic nations. Internally, a significant portion of funds are...before the ACU was shut-down in September by order of the Attorney General as a result of the indictment and arrest of Mohammad Zia Salehi. The

  13. Report on Progress Toward Security and Stability in Afghanistan (United States)


    to provide support to ANSF/Afghan Government while conducting snow removal, personnel recovery, and security operations in the Salang Pass avalanche ...15 SAFIRE is surface to air fire. 16 NATO Secret CIDNE database, through 31 March 2010 0 100 200 300 400...processing centers and markets. Since most agricultural production is rainfall dependent, early melting of mountain snow due to warm winter

  14. Report on Progress Toward Security and Stability in Afghanistan (United States)


    and medical kits so soldiers can give self-aid and buddy-aid at the point of injury; the use of Mi-17 helicopters for casualty evacuation; well suited for Afghanistan’s environment. The number of Mi-17s accounts for all operational helicopters (including 10 on loan to the SMW) and...the ANSF’s only night-vision goggle qualified ( NVG ) air assault and fixed-wing ISR capability. The SMW is the only air mobility asset in Afghanistan

  15. Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta(2) agonist and steroid response

    NARCIS (Netherlands)

    Vonk, Judith M.; Postma, Dirkje S.; Maarsingh, Harm; Bruinenberg, Marcel; Koppelman, Gerard H.; Meurs, Herman


    Rationale Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta(2) agonists. Objectives We investigated the association between arginase 1 a

  16. SOX4 Mediates TGF-beta-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition

    NARCIS (Netherlands)

    Vervoort, Stephin J.; Lourenco, Ana Rita; van Boxtel, Ruben; Coffer, Paul J.


    The epithelial to mensenchymal transition program regulates various aspects of embryonic development and tissue homeostasis, but aberrant activation of this pathway in cancer contributes to tumor progression and metastasis. TGF-beta potently induces an epithelial to mensenchymal transition in cancer

  17. PCR-based plasmid typing in Enterococcus faecium strains reveals widely distributed pRE25-, pRUM-, pIP501-and pHT beta-related replicons associated with glycopeptide resistance and stabilizing toxin-antitoxin systems

    DEFF Research Database (Denmark)

    Rosvoll, T.C.S.; Pedersen, T.; Sletvold, H.;


    A PCR-based typing scheme was applied to identify plasmids in an epidemiologically and geographically diverse strain collection of Enterococcus faecium (n=93). Replicon types of pRE25 (n=56), pRUM (n=41), pIP501 (n=17) and pHT beta (n=14) were observed in 83% of the strains, while pS86, pCF10, p......RUM replicons (74%) than non-CC17 strains (2.2% and 35%, respectively). A prevalent genetic linkage between the pRUM-replicon type and axe-txe was demonstrated by cohybridization analyses. The vanA resistance determinant was associated with all four replicon types, but we also confirmed the genetic linkage...... of vanA to unknown transferable replicons. PCR-based replicon typing, linked to the detection of other important plasmid-encoded traits, seems to be a feasible tool for tracing disseminating resistance plasmids stably maintained in various environments....

  18. Highly mesoporous single-crystalline zeolite beta synthesized using a nonsurfactant cationic polymer as a dual-function template

    KAUST Repository

    Zhu, Jie


    Mesoporous zeolites are useful solid catalysts for conversion of bulky molecules because they offer fast mass transfer along with size and shape selectivity. We report here the successful synthesis of mesoporous aluminosilicate zeolite Beta from a commercial cationic polymer that acts as a dual-function template to generate zeolitic micropores and mesopores simultaneously. This is the first demonstration of a single nonsurfactant polymer acting as such a template. Using high-resolution electron microscopy and tomography, we discovered that the resulting material (Beta-MS) has abundant and highly interconnected mesopores. More importantly, we demonstrated using a three-dimensional electron diffraction technique that each Beta-MS particle is a single crystal, whereas most previously reported mesoporous zeolites are comprised of nanosized zeolitic grains with random orientations. The use of nonsurfactant templates is essential to gaining single-crystalline mesoporous zeolites. The single-crystalline nature endows Beta-MS with better hydrothermal stability compared with surfactant-derived mesoporous zeolite Beta. Beta-MS also exhibited remarkably higher catalytic activity than did conventional zeolite Beta in acid-catalyzed reactions involving large molecules. © 2014 American Chemical Society.

  19. Finite-beta effects on the nonlinear evolution of the (m = 1; n = 1) mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, J.A.; Carreras, B.A.; Hicks, H.R.; Lynch, V.E.; Rothe, K.E.


    The stability and evolution of ISX-B-like plasmas are numerically studied using a reduced set of resistive magnetohydrodynamic (MHD) equations. For a sequence of equilibria stable to ideal modes, the n = 1 mode changes from a tearing branch to a pressure-driven branch as ..beta../sup p/ is increased. When this mode is unstable at low beta, it is just the (m = 1;n = 1) tearing mode. Higher n modes also become linearly unstable with increasing ..beta../sub p/; they are essentially pressure driven and have a ballooning character. For low values of beta the instability is best described as a ..beta../sub p/ distortion of the (m = 1;n = 1) tearing mode. This mode drives many other helicities through toroidal and nonlinear couplings. As ..beta../sub p/ is increased, the growth of the m = 1 island slows down in time, going from exponential to linear before reconnection occurs. If ..beta../sub p/ is large enough, the island saturates without reconnection. A broad spectrum of other modes, driven by the (m = 1;n = 1) instability, is produced. These results agree with some observed features of MHD activity in ISX-B.

  20. Scintillation characteristics of phosphich-detector for detection of beta- and gamma-radiations

    CERN Document Server

    Ananenko, A A; Gavrilyuk, V


    The results of the study on the influence of individual peculiarities of the compound scintillation detector structure on the value and stability of the light yield by the gamma- and beta-radiation combined registration are presented. The phosphich detector is manufactured from the sodium iodide monocrystal, activated by thallium, and the scintillation plastic on the polystyrol basis. The comparison of the experimental results with the mathematical modeling data revealed certain regularities of the process of forming the phosphich detector light signal. The recommendations are worked out by means whereof the following characteristics of the scintillation unit: the light yield and its stability, amplitude resolution and the peak-to-valley ratio by the gamma- and beta-radiation registration were improved

  1. RWM Critical Rotation Frequency and Beta Dependence in NSTX (United States)

    Sontag, Aaron; Sabbagh, S. A.; Menard, J. E.; Battaglia, D. J.


    The resistive wall mode (RWM) can be stabilized by maintaining the plasma toroidal rotation frequency (φφ) above a critical rotation frequency (φcrit). Recent experiments on NSTX seek to determine φcrit and rotation profile effects through actively braking plasma rotation by the application of external magnetic fields. Results from these experiments indicate that maintaining φφ at the q = 2 surface above φA/4q^2 is a necessary condition for RWM stability where φA is the local Alfven frequency. This result is in agreement with a theoretical model derived from a drift-kinetic energy principle. Similarity experiments with DIII-D are being performed to examine the aspect ratio dependence of the φcrit scaling. When φφ at the q = 2 surface drops below φcrit, the growth of internal kink/ballooning modes can prevent the RWM from terminating the discharge. A small beta collapse which drops φcrit, accompanies this mode growth allowing a recovery of RWM rotational stabilization while maintaining βN> βN^no-wall.

  2. Calcium phosphate cements: study of the beta-tricalcium phosphate--monocalcium phosphate system. (United States)

    Mirtchi, A A; Lemaitre, J; Terao, N


    The possibility of making cements based on beta-tricalcium phosphate (beta-TCP), a promising bone graft material, was investigated. Upon admixture with water, beta-TCP/monocalcium phosphate monohydrate (MCPM) mixtures were found to set and harden like conventional hydraulic cements. Beta-TCP powders with larger particle size, obtained by sintering at higher temperatures, increased the ultimate strength of the cement. Results show that setting occurs after dissolution of MCPM, as a result of the precipitation of dicalcium phosphate dihydrate (DCPD) in the paste. The ultimate tensile strength of the hardened cement is proportional to the amount of DCPD formed. Upon ageing above 40 degrees C, DCPD transforms progressively into anhydrous dicalcium phosphate (DCP), thereby decreasing the strength. Ageing of the pastes in 100% r.h. results in a decay of the mechanical properties. This can be ascribed to an intergranular dissolution of the beta-TCP aggregates as a result of the pH lowering brought about by the MCPM to DCPD conversion.

  3. Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoactive cannabinoid. (United States)

    Zurier, Robert B; Rossetti, Ronald G; Burstein, Sumner H; Bidinger, Bonnie


    Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, reduces joint tissue damage in rats with adjuvant arthritis. Because interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) are central to the progression of inflammation and joint tissue injury in patients with rheumatoid arthritis, we investigated human monocyte IL-1beta and TNFalpha responses after the addition of AjA to cells in vitro. Peripheral blood and synovial fluid monocytes (PBM and SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AjA (0-30 microM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for mRNA, and supernatants were collected for cytokine assay. Addition of AjA to PBM and SFM in vitro reduced both steady-state levels of IL-1beta mRNA and secretion of IL-1beta in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 microM AjA (Parthritis. Development of nonpsychoactive therapeutically useful synthetic analogs of Cannabis constituents, such as AjA, may help resolve the ongoing debate about the use of marijuana as medicine.

  4. Identification of new pancreatic beta cell targets for in vivo imaging by a systems biology approach. (United States)

    Bouckenooghe, Thomas; Flamez, Daisy; Ortis, Fernanda; Goldman, Serge; Eizirik, Decio L


    Systems biology is an emergent field that aims to understand biological systems at system-level. The increasing power of genome sequencing techniques and ranges of other molecular biology techniques is enabling the accumulation of in-depth knowledge of biological systems. This growing information, properly quantified, analysed and presented, will eventually allow the establishment of a system-based cartography of different cellular populations within the organism, and of their interactions at the tissue and organ levels. It will also allow the identification of specific markers of individual cell types. Systems biology approaches to discover diagnostic markers may have an important role in diabetes. There are presently no reliable ways to quantify beta cell mass (BCM) in vivo, which hampers the understanding of the pathogenesis and natural history of diabetes, and the development of novel therapies to preserve BCM. To solve this problem, novel and specific beta cell biomarkers must be identified to enable adequate in vivo imaging by methods such as Positron Emission Tomography (PET). The ideal biomarker should allow measurements by a minimally invasive technology enabling repeated examinations over time, should identify the early stages of decreased BCM, and should provide information on progression of beta cell loss and eventual responses to agents aiming to arrest or revert beta cell loss in diabetes. The present review briefly describes the "state-of-the-art" in the field, and then proposes a step-by-step systems biology approach for the identification and initial testing of novel candidates for beta cell imaging.

  5. Characterization of the conformational space of a triple-stranded beta-sheet forming peptide with molecular dynamics simulations

    NARCIS (Netherlands)

    Soto, P; Colombo, G


    Molecular dynamics (MD) simulations have been performed on a series of mutants of the 20 amino acid peptide Betanova in order to critically assess the ability of MD simulations to reproduce the folding and stability of small beta-sheet-forming peptides on currently accessible timescales. Simulations

  6. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. (United States)

    Cernea, Simona; Dobreanu, Minodora


    Diabetes is a complex, heterogeneous condition that has beta cell dysfunction at its core. Many factors (e.g. hyperglycemia/glucotoxicity, lipotoxicity, autoimmunity, inflammation, adipokines, islet amyloid, incretins and insulin resistance) influence the function of pancreatic beta cells. Chronic hyperglycaemia may result in detrimental effects on insulin synthesis/secretion, cell survival and insulin sensitivity through multiple mechanisms: gradual loss of insulin gene expression and other beta-cell specific genes; chronic endoplasmic reticulum stress and oxidative stress; changes in mitochondrial number, morphology and function; disruption in calcium homeostasis. In the presence of hyperglycaemia, prolonged exposure to increased free fatty acids result in accumulation of toxic metabolites in the cells ("lipotoxicity"), finally causing decreased insulin gene expression and impairment of insulin secretion. The rest of the factors/mechanisms which impact on the course of the disease are also discusses in detail. The correct assessment of beta cell function requires a concomitant quantification of insulin secretion and insulin sensitivity, because the two variables are closely interrelated. In order to better understand the fundamental pathogenetic mechanisms that contribute to disease development in a certain individual with diabetes, additional markers could be used, apart from those that evaluate beta cell function. The aim of the paper was to overview the relevant mechanisms/factors that influence beta cell function and to discuss the available methods of its assessment. In addition, clinical considerations are made regarding the therapeutical options that have potential protective effects on beta cell function/mass by targeting various underlying factors and mechanisms with a role in disease progression.

  7. TGF-beta1 immobilized tri-co-polymer for articular cartilage tissue engineering. (United States)

    Chou, Cheng-Hung; Cheng, Winston T K; Lin, Chien-Cheng; Chang, Chih-Hung; Tsai, Chien-Chen; Lin, Feng-Huei


    Tri-co-polymer with composition of gelatin, hyaluronic acid and chondroitin-6-sulfate has been used to mimic the cartilage extracellular matrix as scaffold for cartilage tissue engineering. In this study, we try to immobilize TGF-beta1 onto the surface of the tri-co-polymer sponge to suppress the undesired differentiation during the cartilage growth in vitro. The scaffold was synthesized with a pore size in a range of 300-500 microm. TGF-beta1 was immobilized on the surface of the tri-co-polymer scaffold with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as a crosslinking agent. Tri-co-polymer scaffolds with and without TGF-beta1 were seeded with porcine chondrocytes and cultured in a spinner flask for 2, 4, and 6 weeks. The chondrocytes were characterized by the methods of immunohistochemical staining with anti-type II collagen and anti-S-100 protein monoclonal antibody, and RT-PCR. After culturing for 4 weeks, chondrocytes showed positive in S-100 protein, Alcian blue, and type II collagen for the scaffold with TGF-beta1 immobilization. There is no observed type I and type X collagen expression in the scaffolds from the observation of RT-PCR. In addition, the scaffold without TGF-beta1 immobilization, type X collagen, can be detected after cultured for 2 weeks. Type I collagen was progressively expressed after 4 weeks. These results can conclude that TGF-beta1 immobilized scaffold can suppress chondrocytes toward prehypertrophic chondrocytes and osteolineage cells. The tri-co-polymer sponge with TGF-beta1 immobilization should have a great potential in cartilage tissue engineering in the future.

  8. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;


    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators.......The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...

  9. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)


    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  10. CdWO4 crystal scintillators from enriched isotopes for double beta decay experiments

    CERN Document Server

    Poda, D V; Belli, P; Bernabei, R; Boiko, R S; Brudanin, V B; Cappella, F; Caracciolo, V; Castellano, S; Cerulli, R; Chernyak, D M; Danevich, F A; d'Angelo, S; Degoda, V Ya; Di Vacri, M L; Dossovitskiy, A E; Galashov, E N; Incicchitti, A; Kobychev, V V; Konovalov, S I; Kovtun, G P; Laubenstein, M; Mikhlin, A L; Mokina, V M; Nikolaiko, A S; Nisi, S; Podviyanuk, R B; Polischuk, O G; Shcherban, A P; Shlegel, V N; Solopikhin, D A; Tretyak, V I; Umatov, V I; Vasiliev, Ya V; Virich, V D


    Cadmium tungstate crystal scintillators enriched in 106Cd and 116Cd were developed. The produced scintillators exhibit good optical and scintillation properties, and a low level of radioactive contamination. Experiments to search for double beta decay of 106Cd and 116Cd are in progress at the Gran Sasso National Laboratories of the INFN (Italy). Prospects to further improve the radiopurity of the detectors by recrystallization are discussed.

  11. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    Energy Technology Data Exchange (ETDEWEB)

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.; (IIT); (NIH); (UC)


    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  12. Mechanical design and analysis for a low beta squeezed half-wave resonator

    CERN Document Server

    He, Shoubo; Zhang, Shenghu; Yue, Weiming; Zhang, Cong; Wang, Zhijun; Wang, Ruoxu; Xu, Mengxin; Huang, Shichun; Huang, Yulu; Jiang, Tiancai; Wang, Fengfeng; Zhang, Shengxue; Zhao, Hongwei


    A superconducting half-wave resonator (HWR) of frequency=162.5 MHz and {\\beta}=0.09 has been developed at Institute of Modern Physics. Mechanical stability of the low beta HWR cavity is a big challenge in cavity design and optimization. The mechanical deformations of a radio frequency superconducting cavity could be a source of instability, both in continues wave(CW) operation or in pulsed mode. Generally, the lower beta cavities have stronger Lorentz force detuning than that of the higher beta cavities. In this paper, a basic design consideration in the stiffening structure for the detuning effect caused by helium pressure and Lorentz force has been presented. The mechanical modal analysis has been investigated with finite element method(FEM). Based on these considerations, a new stiffening structure has been promoted for the HWR cavity. The computation results concerning the frequency shift show that the low beta HWR cavity with new stiffening structure has low frequency sensitivity coefficient, Lorentz for...


    Directory of Open Access Journals (Sweden)

    Diah Rini Handjari


    Full Text Available Loss of adenomatous polyposis coli (APC function is typically an early event in sporadic colorectal cancer (CRC pathogenesis. The key tumor suppressor function of the APC protein lies in its ability to destabilize free cytoplasmic beta catenin. This lead to the accumulation of nuclear beta catenin, and together with the DNA binding protein Tcf-4, function as a transcriptional activator. Accumulation of stabilized free β-catenin is considered as an early event and perhaps initiating the process in intestinal tumorigenesis. Neoplastic transformation in the CRC associated chronic colitis is considered similar to the adenoma-carcinoma sequence in sporadic CRC. The distinguish feature from the CRC-related colitis is the difference in time and frequency changes. Loss of APC function, regarded as the beginning of a very common event in sporadic CRC, but the CRC associated chronic colitis generally occurs at the end of thedysplasia-carcinoma sequence. This research was conducted to determine the subcellular location of beta catenin expression in chronic colitis, colorectal adenomas and carcinomas that were evaluated by immunohistochemical staining. It can be concluded that beta-catenin is a component that plays a role in the development of the CRC and the subcellular location of beta-catenin can describe its oncogenic activity.

  14. Inclusion complex of butachlor with beta-cyclodextrin: characterization, solubility, and speciation-dependent adsorption. (United States)

    Bian, Haitao; Chen, Jingwen; Cai, Xiyun; Liu, Ping; Liu, Huihui; Qiao, Xianliang; Huang, Liping


    Due to soil adsorption, higher amounts of the herbicide butachlor are necessary to achieve its herbicidal activity, hence increasing its environmental risks. In this study, the effects of beta-cyclodextrin (beta-CD) on solubility and soil adsorption of butachlor were investigated. Formation of a 1:1 stoichiometric inclusion complex between them with an apparent stability constant of 443 L mol(-1) was confirmed in the solution. Fourier transform infrared spectroscopy showed that the (N-CO) amide bond and alkyl ether moiety of butachlor molecule could enter into the cavity of beta-CD, but the double-substituted aromatic ring was excluded because it was larger size than the cavity. Significant enhancing dissolution of butachlor in the inclusion complex occurred in comparison to the free herbicide. The adsorption of butachlor on soil was reduced with an increase of beta-CD concentration because of the formation of the inclusion complex with low adsorption potency. Although the sorption distribution coefficient of complexed butachlor (i.e., butachlor/beta-cyclodextrin inclusion complex) (K(d,c) = 6.14) was about 14% of that of the free herbicide (K(d,f) = 44.54), the proportion of the adsorbed amount of complexed butachlor to the total adsorbed amount rose with the increase of beta-CD concentration. Thus, the adsorption of inclusion complex cannot be neglected in the presence of high concentrations cyclodextrins, although its water solubility was much higher than that of the free herbicide. These results indicate that beta-CD may be used as a formation additive to improve the solubility of butachlor, reduce its adsorption on soil, and increase the availability of butachlor for weeds.

  15. TGF-beta is required for vascular barrier function, endothelial survival and homeostasis of the adult microvasculature.

    Directory of Open Access Journals (Sweden)

    Tony E Walshe

    Full Text Available Pericyte-endothelial cell (EC interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-beta signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-beta signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-beta signaling was inhibited by systemic expression of soluble endoglin (sEng and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-beta signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG. Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-beta signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-beta signaling. These results implicate constitutive TGF-beta signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-beta signaling in vasoproliferative and vascular degenerative retinal diseases.

  16. Dosimetry of Low-Energy Beta Radiation

    DEFF Research Database (Denmark)

    Borg, Jette

    Useful techniques and procedures for derermination of absorbed doses from exposure in a low-energy beta radiation were studied and evaluated. The four techniques included were beta spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical...... low-energy beta radiation field a moderated spectrum from a carbon-14 source was used. The measured responce of a Si(Li) detector to photons (bremsstrahlung) showed fine agreemant with the MC calculated photon response, whereas the difference between measured and MC calculated response to electrons...

  17. Scintillating bolometers for Double Beta Decay search

    CERN Document Server

    Gironi, Luca


    In the field of Double Beta Decay (DBD) searches, the use of high resolution detectors in which background can be actively discriminated is very appealing. Scintillating bolometers containing a Double Beta Decay emitter can largely fulfill this very interesting possibility. In this paper we present the latest results obtained with CdWO4 and CaMoO4 crystals. Moreover we report, for the first time, a very interesting feature of CaMoO4 bolometers: the possibility to discriminate beta-gamma events from those induced by alpha particles thanks to different thermal pulse shape.

  18. Beta-2-mikroglobulin ved medicinske sygdomme

    DEFF Research Database (Denmark)

    Hansen, P B; Olsen, Niels Vidiendal


    -interstitial nephropathy, increased quantities of beta 2M are excreted in the urine. If the rate of glomerular filtration is reduced, serum-beta 2M is increased and this is also the case in persons with increased cell division despite normal renal function. Serum-beta 2M is, therefore, raised in numerous malignant...... must be presumed to be of value not only in the diagnosis of cerebral AIDS and other (latent) CNS infections but also to demonstrate complicating cerebral malignant lymphomata at an early stage....

  19. Silent ischemia and beta-blockade

    DEFF Research Database (Denmark)

    Egstrup, K


    and should also be directed at the other coronary artery risk factors of the patients. The effects of beta-blockers, which reduce the duration and frequency of silent ischemic episodes, is well described. The effect is most pronounced in the morning, when the frequency of ischemia is highest......, and the mechanism of action seems mainly mediated through a reduction in myocardial oxygen demand. beta-Blockers have shown effectiveness in both effort-induced angina and mixed angina, and increased anti-ischemic potency may be achieved by combination therapy with a calcium antagonist. Abrupt withdrawal of beta-blockers...

  20. Electronic structure and driving forces in {beta}-cyclodextrin: Diclofenac inclusion complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bogdan, Diana [National Institute for Research and Development of Isotopic and Molecular Technologies, Donath street 71-103, 400293 Cluj-Napoca (Romania); Morari, C. [National Institute for Research and Development of Isotopic and Molecular Technologies, Donath street 71-103, 400293 Cluj-Napoca (Romania)]. E-mail:


    We investigate the geometry and electronic structure for complexes of {beta}-cyclodextrin with diclofenac using DFT calculations. The effect of solvent is explicitly taken into account. This investigation allows us to draw meaningful conclusions upon the stability of the complex and the nature of the driving forces leading to the complexation process. In particular we emphasize the role of the water, by pointing out the changes in the solvent's electronic structure for different docking geometries.