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Sample records for beta sheet formation

  1. Is beta-pleated sheet the molecular conformation which dictates formation of helicoidal cuticle?

    PubMed

    Iconomidou, V A; Willis, J H; Hamodrakas, S J

    1999-03-01

    Over 100 sequences for cuticular proteins are now available, but there have been no formal analyses of how these sequences might contribute to the helicoidal architecture of cuticle or to the interaction of these proteins with chitin. A secondary structure prediction scheme (Hamodrakas, S.J., 1988. A protein secondary structure prediction scheme for the IBM PC and compatibles. CABIOS 4, 473-477) that combines six different algorithms predicting alpha-helix, beta-strands and beta-turn/loops/coil has been used to predict the secondary structure of chorion proteins and experimental confirmation has established its utility (Hamodrakas, S.J., 1992. Molecular architecture of helicoidal proteinaceous eggshells. In: Case, S.T. (Ed.), Results and Problems in Cell Differentiation, Vol. 19, Berlin-Heidelberg, Springer Verlag, pp. 116-186 and references therein). We have used this same scheme with eight cuticular protein sequences associated with hard cuticles and nineteen from soft cuticles. Secondary structure predictions were restricted to a conserved 68 amino acid region that begins with a preponderance of hydrophilic residues and ends with a 33 amino acid consensus region, first identified by Rebers and Riddiford (Rebers, J.F., Riddiford, L.M., 1988. Structure and expression of a Manduca sexta larval cuticle gene homologous to Drosophila cuticle genes. J. Mol. Biol. 203, 411-423). Both classes of sequences showed a preponderance of beta-pleated sheet, with four distinct strands in the proteins from 'hard' cuticles and three from 'soft'. In both cases, tyrosine and phenylalanine were found on one face within a sheet, an optimal location for interaction with chitin. We propose that this beta-sheet dictates formation of helicoidal cuticle. PMID:10319442

  2. Conformational diversity in prion protein variants influences intermolecular [beta]-sheet formation

    SciTech Connect

    Lee, Seungjoo; Antony, Lizamma; Hartmann, Rune; Knaus, Karen J.; Surewicz, Krystyna; Surewicz, Witold K.; Yee, Vivien C.

    2010-04-19

    A conformational transition of normal cellular prion protein (PrP{sup C}) to its pathogenic form (PrP{sup Sc}) is believed to be a central event in the transmission of the devastating neurological diseases known as spongiform encephalopathies. The common methionine/valine polymorphism at residue 129 in the PrP influences disease susceptibility and phenotype. We report here seven crystal structures of human PrP variants: three of wild-type (WT) PrP containing V129, and four of the familial variants D178N and F198S, containing either M129 or V129. Comparison of these structures with each other and with previously published WT PrP structures containing M129 revealed that only WT PrPs were found to crystallize as domain-swapped dimers or closed monomers; the four mutant PrPs crystallized as non-swapped dimers. Three of the four mutant PrPs aligned to form intermolecular {beta}-sheets. Several regions of structural variability were identified, and analysis of their conformations provides an explanation for the structural features, which can influence the formation and conformation of intermolecular {beta}-sheets involving the M/V129 polymorphic residue.

  3. Amyloid-beta-sheet formation at the air-water interface.

    PubMed

    Schladitz, C; Vieira, E P; Hermel, H; Mhwald, H

    1999-12-01

    An amyloid(1-40) solution rich in coil, turn, and alpha-helix, but poor in beta-sheet, develops monolayers with a high beta-sheet content when spread at the air-water interface. These monolayers are resistant to repeated compression-dilatation cycles and interaction with trifluoroethanol. The secondary structure motifs were detected by circular dichroism (CD) in solution and with infrared reflection-absorption spectroscopy (IRRAS) at the interface. Hydrophobic influences are discussed for the structure conversion in an effort to understand the completely unknown reason for the natural change of the normal prion protein cellular (PrP(C)) into the abnormal prion protein scrapie (PrP(Sc)). PMID:10585952

  4. In situ atomic force microscopy study of Alzheimer's beta-amyloid peptide on different substrates: new insights into mechanism of beta-sheet formation.

    PubMed

    Kowalewski, T; Holtzman, D M

    1999-03-30

    We have applied in situ atomic force microscopy to directly observe the aggregation of Alzheimer's beta-amyloid peptide (Abeta) in contact with two model solid surfaces: hydrophilic mica and hydrophobic graphite. The time course of aggregation was followed by continuous imaging of surfaces remaining in contact with 10-500 microM solutions of Abeta in PBS (pH 7.4). Visualization of fragile nanoscale aggregates of Abeta was made possible by the application of a tapping mode of imaging, which minimizes the lateral forces between the probe tip and the sample. The size and the shape of Abeta aggregates, as well as the kinetics of their formation, exhibited pronounced dependence on the physicochemical nature of the surface. On hydrophilic mica, Abeta formed particulate, pseudomicellar aggregates, which at higher Abeta concentration had the tendency to form linear assemblies, reminiscent of protofibrillar species described recently in the literature. In contrast, on hydrophobic graphite Abeta formed uniform, elongated sheets. The dimensions of those sheets were consistent with the dimensions of beta-sheets with extended peptide chains perpendicular to the long axis of the aggregate. The sheets of Abeta were oriented along three directions at 120 degrees to each other, resembling the crystallographic symmetry of a graphite surface. Such substrate-templated self-assembly may be the distinguishing feature of beta-sheets in comparison with alpha-helices. These studies show that in situ atomic force microscopy enables direct assessment of amyloid aggregation in physiological fluids and suggest that Abeta fibril formation may be driven by interactions at the interface of aqueous solutions and hydrophobic substrates, as occurs in membranes and lipoprotein particles in vivo. PMID:10097098

  5. Liquid Crystal Based Sensor to Detect Beta-Sheet Formation of Peptides

    NASA Astrophysics Data System (ADS)

    Sadati, Monirosadat; Izmitli Apik, Aslin; Abbott, Nicholas L.; de Pablo, Juan J.

    2015-03-01

    Protein aggregation into amyloid fibrils is involved in the progression of Alzheimer's, typeII diabetes and Huntington's diseases. Although larger aggregates remain important for clinical determination, small oligomers are of great interest due to their potentially toxic nature. It is therefore crucial to develop methods that probe the aggregation process at early stages and in the vicinity of biological membranes. Here, we present a simple method that relies on liquid crystalline materials and a Langmuir monolayer at the aqueous-liquid crystal (LC) interface. The approach is based on the LC's specific response to β-sheet structures, which abound in amyloid fibrils. When the system is observed under polarized light, the fibrils formed by amyloidogenic peptides give rise to the formation of elongated and branched structures in the LCs. Moreover, the PolScope measurements prove that the LCs are predominantly aligned along the fibrils when exposed to a β-sheet forming peptide. In contrast, non-amyloidogenic peptides form ellipsoidal domains of irregularly tilted LCs. This method is capable of reporting aggregation at lipid-aqueous interfaces at nanomolar concentrations of the peptide, and much earlier than commonly used fluorescence-based techniques. We thank Prof. Oleg D. Levrentovich and Young-Ki Kim from the Liquid Crystal Institute of Kent State University for the use of their PolScope instrument. This work was partially supported by the Swiss National Science Foundation (P300P2_151342).

  6. Intermediacy of poly(L-proline) II and beta-strand conformations in poly(L-lysine) beta-sheet formation probed by temperature-jump/UV resonance Raman spectroscopy.

    PubMed

    JiJi, Renee D; Balakrishnan, Gurusamy; Hu, Ying; Spiro, Thomas G

    2006-01-10

    Ultraviolet resonance Raman spectroscopy (UVRR) in combination with a nanosecond temperature jump (T-jump) was used to investigate early steps in the temperature-induced alpha-helix to beta-sheet conformational transition of poly(L-lysine) [poly(K)]. Excitation at 197 nm from a tunable frequency-quadrupled Ti:sapphire laser provided high-quality UVRR spectra, containing multiple conformation-sensitive amide bands. Although un-ionized poly(K) (pH 11.6) is mainly alpha-helical below 30 degrees C, there is a detectable fraction (approximately 15%) of unfolded polypeptide, which is mainly in the poly(L-proline) II (PPII) conformation. However, deviations from the expected amide I and II signals indicate an additional conformation, suggested to be beta-strand. Above 30 degrees C un-ionized poly(K) forms a beta-sheet at a rate (minutes) which increases with increasing temperature. A 22-44 degrees C T-jump is accompanied by prompt amide I and II difference signals suggested to arise from a rapid shift in the PPII/beta-strand equilibrium. These signals are superimposed on a subsequently evolving difference spectrum which is characteristic of PPII, although the extent of conversion is low, approximately 2% at the 3 micros time limit of the experiment. The rise time of the PPII signals is approximately 250 ns, consistent with melting of short alpha-helical segments. A model is proposed in which the melted PPII segments interconvert with beta-strand conformation, whose association through interstrand H-bonding nucleates the formation of beta-sheet. The intrinsic propensity for beta-strand formation could be a determinant of beta-sheet induction time, with implications for the onset of amyloid diseases. PMID:16388578

  7. Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to beta-sheet in amyloid fibril formation

    PubMed Central

    Bleiholder, Christian; Dupuis, Nicholas F.; Wyttenbach, Thomas; Bowers, Michael T.

    2010-01-01

    Amyloid cascades leading to peptide ?-sheet fibrils and plaques are central to many important diseases. Recently, intermediate assemblies of these cascades were identified as the toxic agents that interact with the cellular machinery. The location and cause of the transformation from natively unstructured assembly to the beta-sheet oligomers found in all fibrils is important in understanding disease onset and the development of therapeutic agents. Research on this early oligomeric region has largely been unsuccessful since all traditional techniques measure only ensemble average oligomer properties. Here, ion mobility methods are utilized to deduce the peptide self-assembly mechanism. We look at a series of amyloid forming peptides clipped from larger peptides or proteins associated with disease. We provide unambiguous evidence for structural transitions in each of these fibril forming peptide systems establishing the potential of this method for the development of therapeutic agents and drug evaluation. PMID:21258392

  8. Handedness of crossover connections in beta sheets.

    PubMed Central

    Richardson, J S

    1976-01-01

    In a crossover connection, the polypeptide chain leaves one end of a beta sheet, forms a loop of any length and any conformation, and reenters the same beta sheet from the opposite end. Of the 85 examples of crossover connections which occur in the known protein structures, 83 are righthanded and only two are lefthanded. It is proposed that consistent handedness, even in long irregular loops, could be produced by the preferred twist direction of extended chain and the righthandedness of alpha-helices, provided certain conditions hold during the protein folding process. PMID:183204

  9. Handedness of crossover connections in beta sheets.

    PubMed

    Richardson, J S

    1976-08-01

    In a crossover connection, the polypeptide chain leaves one end of a beta sheet, forms a loop of any length and any conformation, and reenters the same beta sheet from the opposite end. Of the 85 examples of crossover connections which occur in the known protein structures, 83 are righthanded and only two are lefthanded. It is proposed that consistent handedness, even in long irregular loops, could be produced by the preferred twist direction of extended chain and the righthandedness of alpha-helices, provided certain conditions hold during the protein folding process. PMID:183204

  10. The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

    SciTech Connect

    Makabe, Koki; Koide, Shohei

    2009-06-17

    Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success of the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.

  11. Pattern formation in floating sheets

    NASA Astrophysics Data System (ADS)

    King, Hunter

    This thesis presents a study of two basic modes of deformation of a thin sheet: wrinkling and crumpling, viewed primarily in the context of an elastic sheet confined by capillary forces on a drop of liquid. First, it provides a brief conceptual background in the relevant physics of thin sheet mechanics and capillarity and introduces the general principles of wrinkling and crumpling. The problem of confining a circular sheet on an increasingly curved spherical drop is presented as a vehicle to explore these principles. At finite curvature, the sheet is seen to wrinkle around its outer edge. At large confinement, characteristic features of crumpling gradually dominate the pattern. The experimental observations in both regimes are analyzed separately. Analysis of images of the sheet in the wrinkled regime yield data for the number and length of the wrinkled zone, as a function of the experimental control parameter, the pressure. The length of the wrinkles is correctly described by a far-from-threshold theory, which describes a limiting regime in thin-sheet mechanics, distinguished by high 'bendability'. The validity of this theory is verified by the data for highly bendable, ultrathin sheets for the first time. The theory is based on the assumption that the wrinkles completely relax compressive stresses and therefore preserve the cylindrical symmetry of the stress field. The emergence of crumpling from the wrinkled shape is explored via evolution of visible features in the sheet as well as gaussian curvature measurements obtained by analyzing height maps from optical profilometry. The emergence of several length scales, increasing asymmetry in curvature distribution, the failure of wrinkle extent prediction and formation of d-cones associated with crumpling are all measured to locate the transition to a crumpled state. The value of gaussian curvature at the center of the sheet appears to follow the cylindrically symmetric prediction over the whole range of the experiment, suggesting that the onset of crumpling events does not affect the global shape of the sheet. Finally, analogous wrinkling and crumpling behavior of particle-laden interfaces is discussed. The spontaneous formation of conical defects in a curved 2D crystal is compared to the crumpling of a sheet on a drop, and insight from thin sheet mechanics is applied to the mysterious wrinkling of particle rafts. Some future directions for measuring wrinkling of sheets on negative curvature surfaces and deformations of fluid interfaces are proposed.

  12. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,

  13. Control of nano-micrometric twist and helical ribbon formation with gemini-oligoalanine via interpeptidic beta-sheet structure formation.

    PubMed

    Brizard, Aurlie; Ahmad, Roni Kiagus; Oda, Reiko

    2007-06-14

    Confinement of anionic oligo-alanine peptides at the surfaces of cationic membrane by ionic interaction can induce their secondary structure formation; such organized peptides reciprocally transfer their chirality to membranes with non-chiral amphiphiles and their supramolecular chiral structures can be tuned both by peptides and amphiphiles structures. PMID:17534515

  14. Beating the Heat - Fast Scanning Melts Silk Beta Sheet Crystals

    PubMed Central

    Cebe, Peggy; Hu, Xiao; Kaplan, David L.; Zhuravlev, Evgeny; Wurm, Andreas; Arbeiter, Daniela; Schick, Christoph

    2013-01-01

    Beta-pleated-sheet crystals are among the most stable of protein secondary structures, and are responsible for the remarkable physical properties of many fibrous proteins, such as silk, or proteins forming plaques as in Alzheimer's disease. Previous thinking, and the accepted paradigm, was that beta-pleated-sheet crystals in the dry solid state were so stable they would not melt upon input of heat energy alone. Here we overturn that assumption and demonstrate that beta-pleated-sheet crystals melt directly from the solid state to become random coils, helices, and turns. We use fast scanning chip calorimetry at 2,000?K/s and report the first reversible thermal melting of protein beta-pleated-sheet crystals, exemplified by silk fibroin. The similarity between thermal melting behavior of lamellar crystals of synthetic polymers and beta-pleated-sheet crystals is confirmed. Significance for controlling beta-pleated-sheet content during thermal processing of biomaterials, as well as towards disease therapies, is envisioned based on these new findings. PMID:23350037

  15. Beating the Heat - Fast Scanning Melts Silk Beta Sheet Crystals

    NASA Astrophysics Data System (ADS)

    Cebe, Peggy; Hu, Xiao; Kaplan, David L.; Zhuravlev, Evgeny; Wurm, Andreas; Arbeiter, Daniela; Schick, Christoph

    2013-01-01

    Beta-pleated-sheet crystals are among the most stable of protein secondary structures, and are responsible for the remarkable physical properties of many fibrous proteins, such as silk, or proteins forming plaques as in Alzheimer's disease. Previous thinking, and the accepted paradigm, was that beta-pleated-sheet crystals in the dry solid state were so stable they would not melt upon input of heat energy alone. Here we overturn that assumption and demonstrate that beta-pleated-sheet crystals melt directly from the solid state to become random coils, helices, and turns. We use fast scanning chip calorimetry at 2,000 K/s and report the first reversible thermal melting of protein beta-pleated-sheet crystals, exemplified by silk fibroin. The similarity between thermal melting behavior of lamellar crystals of synthetic polymers and beta-pleated-sheet crystals is confirmed. Significance for controlling beta-pleated-sheet content during thermal processing of biomaterials, as well as towards disease therapies, is envisioned based on these new findings.

  16. Beating the Heat: Fast Scanning Melts Beta Sheet Crystals

    NASA Astrophysics Data System (ADS)

    Cebe, Peggy; Hu, Xiao; Kaplan, David; Zhuravlev, Evgeny; Wurm, Andreas; Arbeiter, Daniella; Schick, Christoph

    2014-03-01

    Beta-pleated-sheet crystals are among the most stable of protein secondary structures, and are responsible for the remarkable physical properties of many fibrous proteins, such as silk. Previous thinking was that beta-pleated-sheet crystals in the dry solid state would not melt upon input of heat energy alone. Indeed, at conventional heating rates (~1-50 C/min), silk exhibits its glass transition (~175 C), followed by cold crystallization, and then by immediate thermal degradation beginning at about 225 C. Here we demonstrate that beta-pleated-sheet crystals can melt directly from the solid state to become random coils, helices, and turns. We use fast scanning chip calorimetry at 2,000 K/s to avoid thermal degradation, and report the first reversible thermal melting of protein beta-pleated-sheet crystals, exemplified by silk fibroin. The similarity between thermal melting behavior of lamellar crystals of synthetic polymers and beta-pleated-sheet crystals is confirmed. The authors acknowledge support from the National Science Foundation and German Academic Exchange Service DAAD; EZ acknowledges a European Union funded Marie Curie EST fellowship (ADVATEC); XH and DK acknowledge NIH P41 Tissue Engineering Resource Center.

  17. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    SciTech Connect

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.

    2009-07-24

    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.

  18. Determining Beta Sheet Crystallinity in Fibrous Proteins by Thermal Analysis and Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hu, Xiao; Kaplan, David; Cebe, Peggy

    2007-03-01

    We report a study of self-assembled beta pleated sheets in Bombyx mori silk fibroin films using thermal analysis and infrared spectroscopy. Crystallization of beta pleated sheets was effected either by heating the films above the glass transition temperature (Tg) and holding isothermally, or by exposure to methanol. The fractions of secondary structural components including random coils, alpha helices, beta pleated sheets, turns, and side chains, were evaluated using Fourier self-deconvolution (FSD) of the infrared absorbance spectra. As crystalline beta sheets form, the heat capacity increment from the TMDSC trace at Tg is systematically decreased and is linearly well correlated with beta sheet content determined from FSD. This analysis of beta sheet content can serve as an alternative to X-ray methods and may have wide applicability to other crystalline beta sheet forming proteins.

  19. Tape-casting technique can prepare beta-TCP sheets with uniform thickness and flexibility.

    PubMed

    Tanimoto, Yasuhiro; Hayakawa, Tohru; Nemoto, Kimiya

    2005-04-01

    The objective of this study is to propose a new fabrication technology for bone substitutes. In this study, a tape-casting method was used to prepare flexible beta-tricalcium phosphate (beta-TCP) sheets. A beta-TCP slurry containing a binder and plasticizer was used in a doctor blade system. The beta-TCP sheet obtained by this tape-casting method was highly flexible, enabling twisting and free-form shaping. The beta-TCP sheet was approximately 0.21 mm thick. X-ray diffraction and Fourier transform infrared spectrometry revealed that the structure of the beta-TCP component in the sheet is the same as that of the original beta-TCP powder. Observation by field-emission scanning electron microscopy showed that the beta-TCP sheet had a flat, microgranular surface. During the early stages, the tensile stress-strain curves of the beta-TCP sheet showed a nonlinear behavior until reaching the point of final fracture. This result was derived from the ductile property of the prepared beta-TCP sheet. In conclusion, a flexible beta-TCP sheet was easily prepared using a tape-casting technique. Fabrication using tape casting offers the advantages of enabling the preparation of ceramic sheets with precise thickness and not requiring expensive fabrication facilities. PMID:15786445

  20. Aggregation of the amphipathic peptides (AAKA)n into antiparallel beta-sheets.

    PubMed

    Measey, Thomas J; Schweitzer-Stenner, Reinhard

    2006-10-18

    Helical wheel projections of peptides based on the repeating unit Ac-(AAKA)n-NH2 clearly illustrate an amphipathic nature. One should therefore expect these peptides to form helices if the number of residues exceeds a certain threshold value. Indeed, ECD measurements show that Ac-(AAKA)4-NH2 and, to a minor extent, also Ac-(AAKA)3-NH2 exhibit some helical content at millimolar concentrations in aqueous solution. Surprisingly, however, these peptides were found to form hydrogels with an antiparallel beta-sheet conformation at centimolar concentrations. This occurs despite the positively charged lysine side chain which would be expected to inhibit the formation of extended beta-sheet layers. PMID:17031922

  1. Microphase Separation Controlled Beta Sheet Crystallization Kinetics in Silk Fibroin Protein.

    NASA Astrophysics Data System (ADS)

    Hu, Xiao; Lu, Qiang; Kaplan, David; Cebe, Peggy

    2009-03-01

    We investigate the mechanism of isothermal crystallization kinetics of beta-sheet crystals in silk multiblock fibrous proteins. The Avrami analysis kinetic theory, for studies of synthetic polymer crystal growth, is for the first time extended to investigate protein self-assembly in beta-sheet rich Bombyx mori silk fibroin samples, using time-resolved Fourier transform infrared spectroscopy, differential scanning calorimetry and synchrotron real-time wide-angle X-ray scattering. Results indicate formation of beta sheet crystals in silk proteins is different from the 3-D spherulitic crystal growth found in synthetic homopolymers. Observations by scanning electron microscopy support the view that the protein structures vary during the different stages of crystal growth, and show a microphase separation pattern after chymotrypsin enzyme biodegradation. We present a model to explain the crystallization of the multiblock silk fibroin protein, by analogy to synthetic block copolymers. This model could be widely applicable in other proteins with multiblock (i.e., crystallizable and non-crystallizable) domains.

  2. Role of Polyalanine Domains in -Sheet Formation in Spider Silk Block Copolymers

    SciTech Connect

    Rabotyagova, O.; Cebe, P; Kaplan, D

    2010-01-01

    Genetically engineered spider silk-like block copolymers were studied to determine the influence of polyalanine domain size on secondary structure. The role of polyalanine block distribution on {beta}-sheet formation was explored using FT-IR and WAXS. The number of polyalanine blocks had a direct effect on the formation of crystalline {beta}-sheets, reflected in the change in crystallinity index as the blocks of polyalanines increased. WAXS analysis confirmed the crystalline nature of the sample with the largest number of polyalanine blocks. This approach provides a platform for further exploration of the role of specific amino acid chemistries in regulating the assembly of {beta}-sheet secondary structures, leading to options to regulate material properties through manipulation of this key component in spider silks.

  3. Formation of Sprays From Conical Liquid Sheets

    NASA Technical Reports Server (NTRS)

    Peck, Bill; Mansour, N. N.; Koga, Dennis (Technical Monitor)

    1999-01-01

    Our objective is to predict droplet size distributions created by fuel injector nozzles in Jet turbines. These results will be used to determine the initial conditions for numerical simulations of the combustion process in gas turbine combustors. To predict the droplet size distribution, we are currently constructing a numerical model to understand the instability and breakup of thin conical liquid sheets. This geometry serves as a simplified model of the liquid jet emerging from a real nozzle. The physics of this process is difficult to study experimentally as the time and length scales are very short. From existing photographic data, it does seem clear that three-dimensional effects such as the formation of streamwise ligaments and the pulling back of the sheet at its edges under the action of surface tension are important.

  4. Folding dynamics of a family of beta-sheet proteins

    NASA Astrophysics Data System (ADS)

    Rousseau, Denis

    2008-03-01

    Fatty acid binding proteins (FABP) consist of ten anti-parallel beta strands and two small alpha helices. The beta strands are arranged into two nearly orthogonal five-strand beta sheets that surround the interior cavity, which binds unsaturated long-chain fatty acids. In the brain isoform (BFABP), these are very important for the development of the central nervous system and neuron differentiation. Furthermore, BFABP is implicated in the pathogenesis of a variety of human diseases including cancer and neuronal degenerative disorders. In this work, site-directed spin labeling combined with EPR techniques have been used to study the folding mechanism of BFABP. In the first series of studies, we labeled the two Cys residues at position 5 and 80 in the wild type protein with an EPR spin marker; in addition, two singly labeled mutants at positions 5 and 80 in the C80A and C5A mutants, respectively, were also produced and used as controls. The changes in the distances between the two residues were examined by a pulsed EPR method, DEER (Double Electron Electron Resonance), as a function of guanidinium hydrochloride concentration. The results were compared with those from CW EPR, circular dichroism and fluorescence measurements, which provide the information regarding sidechain mobility, secondary structure and tertiary structure, respectively. The results will be discussed in the context of the folding mechanism of the family of fatty acid binding proteins.

  5. Analysis of the factors that stabilize a designed two-stranded antiparallel beta-sheet.

    PubMed

    Espinosa, Juan F; Syud, Faisal A; Gellman, Samuel H

    2002-06-01

    Autonomously folding beta-hairpins (two-strand antiparallel beta-sheets) have become increasingly valuable tools for probing the forces that control peptide and protein conformational preferences. We examine the effects of variations in sequence and solvent on the stability of a previously designed 12-residue peptide (1). This peptide adopts a beta-hairpin conformation containing a two-residue loop (D-Pro-Gly) and a four-residue interstrand sidechain cluster that is observed in the natural protein GB1. We show that the conformational propensity of the loop segment plays an important role in beta-hairpin stability by comparing 1 with (D)P--> N mutant 2. In addition, we show that the sidechain cluster contributes both to conformational stability and to folding cooperativity by comparing 1 with mutant 3, in which two of the four cluster residues have been changed to serine. Thermodynamic analysis suggests that the high loop-forming propensity of the (D)PG segment decreases the entropic cost of beta-hairpin formation relative to the more flexible NG segment, but that the conformational rigidity of (D)PG may prevent optimal contacts between the sidechains of the GB1-derived cluster. The enthalpic favorability of folding in these designed beta-hairpins suggests that they are excellent scaffolds for studying the fundamental mechanisms by which amino acid sidechains interact with one another in folded proteins. PMID:12021448

  6. Current Sheet Formation in the Interstellar Medium

    NASA Astrophysics Data System (ADS)

    Zweibel, Ellen G.; Brandenburg, Axel

    1997-03-01

    There is phenomenological evidence that magnetic reconnection operates in the interstellar medium, and magnetic reconnection is also necessary for the operation of a galactic dynamo. The extremely long ohmic diffusion times of magnetic fields in typical interstellar structures suggest that reconnection occurs in two stages, with thin current layers that have relatively short resistive decay times forming by magnetohydrodynamical processes first, followed by reconnection of the fields in the layers. We propose that ambipolar drift can lead to the formation of these thin sheets in weakly ionized interstellar gas and can delineate the parameter regime in which this occurs by means of a numerical model: we find that the magnetic field cannot be too large and the medium cannot be too diffusive. Both limits are imposed by the requirement that the field be wound up about 1 time by the eddy.

  7. Precise assembly of complex beta sheet topologies from de novo designed building blocks

    PubMed Central

    King, Indigo Chris; Gleixner, James; Doyle, Lindsey; Kuzin, Alexandre; Hunt, John F; Xiao, Rong; Montelione, Gaetano T; Stoddard, Barry L; DiMaio, Frank; Baker, David

    2015-01-01

    Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here, we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followed by amino acid sequence optimization at the newly formed strand-strand, strand-helix, and helix-helix interfaces. Crystal structures of two such designs closely match the computational design models. Searches for similar structures in the SCOP protein domain database yield only weak matches with different beta sheet connectivities. A similar beta sheet fusion mechanism may have contributed to the emergence of complex beta sheets during natural protein evolution. DOI: http://dx.doi.org/10.7554/eLife.11012.001 PMID:26650357

  8. Propagating structure of alzheimer's {beta}-amyloid is parallel {beta}-sheet with residues in exact register.

    SciTech Connect

    Benzinger, T. L. S.; Gregory, D. M.; Burkoth, T. S.; Miller-Auer, H.; Lynn, D. G.; Botto, R. E.; Meredith, S. C.; Chemistry; Univ. of Chicago

    1998-11-10

    The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa {beta}-amyloid (A{beta}) peptide. Crosslinking of A{beta} peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated A{beta}. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the A{beta} peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated A{beta}. Peptides containing a single carbonyl 13C label at Gln15, Lys16, Leu17, or Val18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Angstrom. Analysis of these data establish that this central core of A{beta} consists of a parallel {beta}-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the A{beta} fibril is a hydrogen-bonded, parallel {beta}-sheet defining the long axis of the A{beta} fibril propagation.

  9. Formation and separation of merged liquid sheets developed from the mixing of coaxial swirling liquid sheets

    NASA Astrophysics Data System (ADS)

    Sivakumar, D.; Raghunandan, B. N.

    2003-11-01

    Liquid-liquid coaxial swirl atomizers are used in liquid rocket engines to achieve an efficient mixing between the fuel and oxidizer sprays. The characteristics of the mixed spray are mainly controlled by the flow behavior of merged liquid sheet originating at the contact point of inner and outer swirling liquid sheets. With an intention of identifying various flow regimes of merged liquid sheet at different conditions of inner and outer liquid sheets, we report here a fundamental experimental investigation on the characteristics of merged liquid sheets using water as the experimental liquid. The physical processes involved in the formation and separation of a merged liquid sheet are described from the experimental measurements. For a given outer liquid sheet condition, the merged liquid sheet forms and separates at specific inner liquid sheet flow conditions. At low outer liquid sheet flow conditions with Weber number less than 50, the merged liquid sheet exhibits a self-sustaining periodic separation process, whose frequency increases with increasing inner liquid sheet Weber number for a given outer liquid sheet Weber number. Experimental measurements are presented to show that the dynamics of the contact point plays a major role in governing the characteristics of merged liquid sheets.

  10. Mechanism for the formation of plasmoids and kink waves in the heliospheric current sheet

    SciTech Connect

    Wang, S.; Lee, L.C.; Wei, C.Q.; Akasofu, S.I.

    1987-09-18

    Satellite observations of the heliospheric current sheet indicate that the plasma flow velocity is low at the center of the current sheet and high on the two sides of current sheet. In this paper, we investigate the growth rates and eigenmodes of the sausage, kink, and tearing instabilities in the heliospheric current sheet with the observed sheared flow. These instabilities may lead to the formation of the plasmoids and kink waves in the solar wind. The results show that both the sausage and kink modes can be excited in the heliospheric current sheet with a growth time about 0.05-5 day. Therefore, these modes can grow during the transit of the solar wind from the Sun to the Earth. The sausage mode grows faster than the kink mode for beta at infinity < 1.5, while the streaming kink instability has a higher growth rate for beta at infinity > 1.5. Here beta at infinity is the ratio between the plasma and magnetic pressures away from the current layer. If a finite resistivity is considered, the streaming sausage mode evolves into the streaming tearing mode with the formation of magnetic islands. We suggest that some of the magnetic clouds and plasmoids observed in the solar wind may be associated with the streaming sausage instability. Furthermore, it is found that a large-scale kink wave may develop in the region with a radial distance greater than 0.5-1.5 AU.

  11. Conversion of non-fibrillar {beta}-sheet oligomers into amyloid fibrils in Alzheimer's disease amyloid peptide aggregation

    SciTech Connect

    Benseny-Cases, Nuria; Cocera, Mercedes; Cladera, Josep

    2007-10-05

    A{beta}(1-40) is one of the main components of the fibrils found in amyloid plaques, a hallmark of brains affected by Alzheimer's disease. It is known that prior to the formation of amyloid fibrils in which the peptide adopts a well-ordered intermolecular {beta}-sheet structure, peptide monomers associate forming low and high molecular weight oligomers. These oligomers have been previously described in electron microscopy, AFM, and exclusion chromatography studies. Their specific secondary structures however, have not yet been well established. A major problem when comparing aggregation and secondary structure determinations in concentration-dependent processes such as amyloid aggregation is the different concentration range required in each type of experiment. In the present study we used the dye Thioflavin T (ThT), Fourier-transform infrared spectroscopy, and electron microscopy in order to structurally characterize the different aggregated species which form during the A{beta}(1-40) fibril formation process. A unique sample containing 90 {mu}M peptide was used. The results show that oligomeric species which form during the lag phase of the aggregation kinetics are a mixture of unordered, helical, and intermolecular non-fibrillar {beta}-structures. The number of oligomers and the amount of non-fibrillar {beta}-structures grows throughout the lag phase and during the elongation phase these non-fibrillar {beta}-structures are transformed into fibrillar (amyloid) {beta}-structures, formed by association of high molecular weight intermediates.

  12. Formation of current sheets in magnetic reconnection

    SciTech Connect

    Boozer, Allen H.

    2014-07-15

    An ideal evolution of magnetic fields in three spatial dimensions tends to cause neighboring field lines to increase their separation exponentially with distance ? along the lines, ?(?)=?(0)e{sup ?(?)}. The non-ideal effects required to break magnetic field line connections scale as e{sup ??}, so the breaking of connections is inevitable for ? sufficiently largeeven though the current density need nowhere be large. When the changes in field line connections occur rapidly compared to an Alfvn transit time, the constancy of j{sub ||}/B along the magnetic field required for a force-free equilibrium is broken in the region where the change occurs, and an Alfvnic relaxation of j{sub ||}/B occurs. Independent of the original spatial distribution of j{sub ||}/B, the evolution is into a sheet current, which is stretched by a factor e{sup ?} in width and contracted by a factor e{sup ?} in thickness with the current density j{sub ||} increasing as e{sup ?}. The dissipation of these sheet currents and their associated vorticity sheets appears to be the mechanism for transferring energy from a reconnecting magnetic field to a plasma. Harris sheets, which are used in models of magnetic reconnection, are shown to break up in the direction of current flow when they have a finite width and are in a plasma in force equilibrium. The dependence of the longterm nature of magnetic reconnection in systems driven by footpoint motion can be studied in a model that allows qualitative variation in the nature of that motion: slow or fast motion compared to the Alfvn transit time and the neighboring footpoints either exponentially separating in time or not.

  13. Multi-layer Parallel Beta-Sheet Structure of Amyloid Beta peptide (1-40) aggregate observed by discrete molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Peng, Shouyong; Urbanc, Brigita; Ding, Feng; Cruz, Luis; Buldyrev, Sergey; Dokholyan, Nikolay; Stanley, H. E.

    2003-03-01

    New evidence shows that oligomeric forms of Amyloid-Beta are potent neurotoxins that play a major role in neurodegeneration of Alzheimer's disease. Detailed knowledge of the structure and assembly dynamics of Amyloid-Beta is important for the development of new therapeutic strategies. Here we apply a two-atom model with Go interactions to model aggregation of Amyloid-Beta (1-40) peptides using the discrete molecular dynamics simulation. At temperatures above the transition temperature from an alpha-helical to random coil, we obtain two types of parallel beta-sheet structures, (a) a helical beta-sheet structure at a lower temperature and (b) a parallel beta-sheet structure at a higher temperature, both with inter-sheet distance of 10 A and with free edges which possibly enable further fibrillar elongation.

  14. Dichroic ratios in polarized Fourier transform infrared for nonaxial symmetry of beta-sheet structures.

    PubMed Central

    Marsh, D

    1997-01-01

    The transition moments for the amide bands from beta-sheet peptide structures generally do not exhibit axial symmetry about the director in linearly polarized Fourier transform infrared (FTIR) measurements on oriented systems. The angular dependences of the dichroic ratios of the amide bands are derived for beta-sheet structures in attenuated total reflection (ATR) and polarized transmission experiments on samples that are oriented with respect to the normal to the substrate and are randomly distributed with respect to the azimuthal angle in the plane of the orienting substrate. The orientational distributions of both the beta-strands and the beta-sheets are considered, and explicit expressions are given for the dichroic ratios of the amide I and amide II bands. The dichroic ratio of the amide II band, which is parallel polarized, can yield the orientation of the beta-strands directly, but to specify the orientations of the beta-sheets completely requires measurement of the dichroic ratios of both the amide I and amide II bands, or generally two bands with parallel and perpendicular polarizations. A random distribution in tilt of the planes of the beta-sheets does not give rise to equal dichroic ratios for bands with perpendicular and parallel polarizations, such as the amide I and amide II bands. The results are applied to previous ATR and polarized transmission FTIR measurements on a potassium channel-associated peptide, the Escherichia coli outer membrane protein OmpA, and the E. coli OmpF porin protein in oriented membranes. Images FIGURE 1 FIGURE 3 FIGURE 4 PMID:9168046

  15. Pore formation by beta-2-microglobulin: a mechanism for the pathogenesis of dialysis associated amyloidosis.

    PubMed

    Hirakura, Y; Kagan, B L

    2001-06-01

    Beta-2 microglobulin (beta 2M, molecular weight 10,000) is a 99 residue immune system protein which is part of the MHC Class I complex whose role is to present antigens to T cells. beta 2M serum levels rise dramatically in renal failure, and a syndrome called "dialysis associated amyloidosis" occurs with time in a majority of hemodialysis patients who exhibit beta 2M amyloid deposits in joints, bone and other organs. beta 2M can also induce Ca++ efflux from calvariae, collagenase production, and bone resorption. We report here that beta 2M formed relatively nonselective, long-lived, voltage independent ion channels in planar phospholipid bilayer membranes at physiologically relevant concentrations. The channels were inhibited by Congo red and blocked by zinc suggesting that they exist in an aggregated beta sheet state as is common with other amyloid fibril forming peptides. Multiple single channel conductances were seen suggesting that various oligomers of beta 2M may be capable of forming channel structures. We suggest that beta 2M channel formation may account for some of the pathophysiologic effects seen in dialysis associated amyloidosis. These findings lend further weight to the "channel hypothesis" of amyloid pathogenesis. PMID:11409039

  16. Flanking Polyproline Sequences Inhibit [beta]-Sheet Structure in Polyglutamine Segments by Inducing PPII-like Helix Structure

    SciTech Connect

    Darnell, Gregory; Orgel, Joseph P.R.O.; Pahl, Reinhard; Meredith, Stephen C.

    2008-06-24

    Polyglutamine (poly(Q)) expansion is associated with protein aggregation into {beta}-sheet amyloid fibrils and neuronal cytotoxicity. In the mutant poly(Q) protein huntingtin, associated with Huntington's disease, both aggregation and cytotoxicity may be abrogated by a polyproline (poly(P)) domain flanking the C terminus of the poly(Q) region. To understand structural changes that may occur with the addition of the poly(P) sequence, we synthesized poly(Q) peptides with 3-15 glutamine residues and a corresponding set of poly(Q) peptides flanked on the C terminus by 11 proline residues (poly(Q)-poly(P)), as occurs in the huntingtin sequence. The shorter soluble poly(Q) peptides (three or six glutamine residues) showed polyproline type II-like (PPII)-like helix conformation when examined by circular dichroism spectroscopy and were monomers as judged by size-exclusion chromatography (SEC), while the longer poly(Q) peptides (nine or 15 glutamine residues) showed a {beta}-sheet conformation by CD and defined oligomers by SEC. Soluble poly(Q)-poly(P) peptides showed PPII-like content but SEC showed poorly defined, overlapping oligomeric peaks, and as judged by CD these peptides retained significant PPII-like structure with increasing poly(Q) length. More importantly, addition of the poly(P) domain increased the threshold for fibril formation to {approx} 15 glutamine residues. X-ray diffraction, electron microscopy, and film CD showed that, while poly(Q) peptides with {ge} 6 glutamine residues formed {beta}-sheet-rich fibrils, only the longest poly(Q)-poly(P) peptide (15 glutamine residues) did so. From these and other observations, we propose that poly(Q) domains exist in a 'tug-of-war' between two conformations, a PPII-like helix and a {beta}-sheet, while the poly(P) domain is conformationally constrained into a proline type II helix (PPII). Addition of poly(P) to the C terminus of a poly(Q) domain induces a PPII-like structure, which opposes the aggregation-prone {beta}-sheet. These structural observations may shed light on the threshold phenomenon of poly(Q) aggregation, and support the hypothesized evolution of 'protective' poly(P) tracts adjacent to poly(Q) aggregation domains.

  17. The orientation of beta-sheets in porin. A polarized Fourier transform infrared spectroscopic investigation.

    PubMed Central

    Nabedryk, E; Garavito, R M; Breton, J

    1988-01-01

    The orientation of the protein secondary structures in porin is investigated by Fourier transform infrared (FTIR) linear dichroism of oriented multilayers of porin reconstituted in lipid vesicles. The FTIR absorbance spectrum shows the amide I band at 1,631 cm-1 and several shoulders around 1,675 cm-1 and at 1,696 cm-1 indicative of antiparallel beta-sheets. The amide II is centered around 1,530 cm-1. The main dichroic signals peak at 1,738, 1,698, 1,660, 1,634, and 1,531 cm-1. The small magnitude of the 1,634 cm-1 and 1,531 cm-1 positive dichroism bands demonstrates that the transition moments of the amide I and amide II vibrations are on the average tilted at 47 degrees +/- 3 degrees from the membrane normal. This indicates that the plane of the beta-sheets is approximately perpendicular to the bilayer. From these IR dichroism results and previously reported diffuse x-ray data which revealed that a substantial number of beta-strands are nearly perpendicular to the membrane, a model for the packing of beta-strands in porin is proposed which satisfies both IR and x-ray requirements. In this model, the porin monomer consists of at least two beta-sheet domains, both with their plane perpendicular to the membrane. One sheet has its strands direction lying nearly parallel to the membrane normal while the other sheet has its strands inclined at a small angle away from the membrane plane. PMID:2455547

  18. Probing the nanosecond dynamics of a designed three-stranded beta-sheet with a massively parallel molecular dynamics simulation.

    PubMed

    Voelz, Vincent A; Luttmann, Edgar; Bowman, Gregory R; Pande, Vijay S

    2009-03-01

    Recently a temperature-jump FTIR study of a designed three-stranded sheet showing a fast relaxation time of approximately 140 +/- 20 ns was published. We performed massively parallel molecular dynamics simulations in explicit solvent to probe the structural events involved in this relaxation. While our simulations produce similar relaxation rates, the structural ensemble is broad. We observe the formation of turn structure, but only very weak interaction in the strand regions, which is consistent with the lack of strong backbone-backbone NOEs in previous structural NMR studies. These results suggest that either (D)P(D)P-II folds at time scales longer than 240 ns, or that (D)P(D)P-II is not a well-defined three-stranded beta-sheet. This work also provides an opportunity to compare the performance of several popular forcefield models against one another. PMID:19399235

  19. Captides: Rigid Junctions between Beta Sheets and Small Molecules

    PubMed Central

    Kier, Brandon L.; Andersen, Niels H.

    2014-01-01

    An extensive series of covalently linked small molecule-peptide adducts based on a terminally capped beta hairpin motif is reported. The constructs can be prepared by standard solid-phase fmoc chemistry with 1 to 4 peptide chains linked to small molecule hubs bearing carboxylic acid moieties. The key feature of interest is the precise, buried environment of the small molecule, and its rigid orientation relative to one or more short, but fully structured peptide chain(s). Most of this study employs a minimalist 9 residue captide, a capped ?-turn, but we illustrate general applicability to peptides which can terminate in a beta strand. The non-peptide portion of these adducts can include nearly any molecule bearing one or more carboxylic acid groups. Fold-dependent rigidity sets this strategy apart from currently available bioconjugation methods, which typically engender significant flexibility between peptide and tag. Applications to catalyst enhancement, drug design, higher-order assembly, and FRET calibration rulers are discussed. PMID:24909552

  20. Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers

    PubMed Central

    Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap; Law, Peter; Bryers, James; Varani, Gabriele; Caughey, Byron; Daggett, Valerie

    2014-01-01

    Previous studies suggest that the toxic soluble-oligomeric form of different amyloid proteins share a common backbone conformation, but the amorphous nature of this oligomer prevents its structural characterization by experiment. Based on molecular dynamics simulations we proposed that toxic intermediates of different amyloid proteins adopt a common, nonstandard secondary structure, called ?-sheet. Here we report the experimental characterization of peptides designed to be complementary to the ?-sheet conformation observed in the simulations. We demonstrate inhibition of aggregation in two different amyloid systems, ?-amyloid peptide (A?) and transthyretin, by these designed ?-sheet peptides. When immobilized the ?-sheet designs preferentially bind species from solutions enriched in the toxic conformer compared with non-aggregated, nontoxic species or mature fibrils. The designs display characteristic spectroscopic signatures distinguishing them from conventional secondary structures, supporting ?-sheet as a structure involved in the toxic oligomer stage of amyloid formation and paving the way for novel therapeutics and diagnostics. DOI: http://dx.doi.org/10.7554/eLife.01681.001 PMID:25027691

  1. Blue color formation of cyanobacteria with beta-cyclocitral.

    PubMed

    Harada, Ken-Ichi; Ozaki, Keiko; Tsuzuki, Sayaka; Kato, Hajime; Hasegawa, Masateru; Kuroda, Emilia K; Arii, Suzue; Tsuji, Kiyomi

    2009-11-01

    Volatile compounds, such as beta-cyclocitral, geosmin, and 2-methylisoborneol, from cyanobacteria showed a lytic activity against cyanobacteria. Particularly, beta-cyclocitral caused an interesting color change in the culture broth from green to blue during the lysis process. In the present study, the lytic behavior of various cyanobacteria with beta-cyclocitral was investigated, and a mechanism for the blue color formation was developed. beta-Cyclocitral lysed both the laboratory strains of any genera and bloom samples including many species of cyanobacteria, and caused the characteristic color change from green to blue. beta-Cyclocitral provided a characteristic behavior, such that the absorption maxima of chlorophyll-a and beta-carotene disappeared, but that of phycocyanin still remained after 12 h, which indicated that beta-cyclocitral decomposed chlorophyll-a and beta-carotene rapidly, so that the inherent colors from the tolerant water-soluble pigments became observable in the cultured broth. This phenomenon was confirmed by another experiment using Phormidium (NIES-611), which showed a pink color derived from phycoerythrin. beta-Cyclocitral was more easily oxidized when compared with similar aldehyde compounds, so that the pH of the solution quickly decreased to 4.5. An oxidation product of beta-cyclocitral in water solution was isolated and identified as 2,6,6-trimethylcyclohexene-1-carboxylic acid. This study provides support that beta-cyclocitral derived from cyanobacteria plays an important role in the lysis of cyanobacteria and participates in the blue color formation under natural conditions. PMID:19936836

  2. BetaCore, a designed water soluble four-stranded antiparallel β-sheet protein

    PubMed Central

    Carulla, Natàlia; Woodward, Clare; Barany, George

    2002-01-01

    BetaCore is a designed ∼50-residue protein in which two BPTI-derived core modules, CM I and CM II, are connected by a 22-atom cross-link. At low temperature and pH 3, homo- and heteronuclear NMR data report a dominant folded (`f') conformation with well-dispersed chemical shifts, i, i+1 periodicity, numerous long-range NOEs, and slowed amide hydrogen isotope exchange patterns that is a four-stranded antiparallel β-sheet with nonsymmetrical and specific association of CM I and CM II. BetaCore `f' conformations undergo reversible, global, moderately cooperative, non-two-state thermal transitions to an equilibrium ensemble of unfolded `u' conformations. There is a significant energy barrier between `f' and `u' conformations. This is the first designed four-stranded antiparallel β-sheet that folds in water. PMID:12021452

  3. Thermally Induced Alpha-Helix to Beta-Sheet Transition in Regenerated Silk Fibers and Films

    SciTech Connect

    Drummy,L.; Phillips, D.; Stone, M.; Farmer, B.; Naik, R.

    2005-01-01

    The structure of thin films cast from regenerated solutions of Bombyx mori cocoon silk in hexafluoroisopropyl alcohol (HFIP) was studied by synchrotron X-ray diffraction during heating. A solid-state conformational transition from an alpha-helical structure to the well-known beta-sheet silk II structure occurred at a temperature of approximately 140 degrees C. The transition appeared to be homogeneous, as both phases do not coexist within the resolution of the current study. Modulated differential scanning calorimetry (DSC) of the films showed an endothermic melting peak followed by an exothermic crystallization peak, both occurring near 140 degrees C. Oriented fibers were also produced that displayed this helical molecular conformation. Subsequent heating above the structural transition temperature produced oriented beta-sheet fibers very similar in structure to B. mori cocoon fibers. Heat treatment of silk films at temperatures well below their degradation temperature offers a controllable route to materials with well-defined structures and mechanical behavior.

  4. Alpha-helical, but not beta-sheet, propensity of proline is determined by peptide environment.

    PubMed Central

    Li, S C; Goto, N K; Williams, K A; Deber, C M

    1996-01-01

    Proline is established as a potent breaker of both alpha-helical and beta-sheet structures in soluble (globular) proteins. Thus, the frequent occurrence of the Pro residue in the putative transmembrane helices of integral membrane proteins, particularly transport proteins, presents a structural dilemma. We propose that this phenomenon results from the fact that the structural propensity of a given amino acid may be altered to conform to changes imposed by molecular environment. To test this hypothesis on proline, we synthesized model peptides of generic sequence H2N-(Ser-LyS)2-Ala- Leu-Z-Ala-Leu-Z-Trp-Ala-Leu-Z-(Lys-Ser)3-OH (Z = Ala and/or Pro). Peptide conformations were analyzed by circular dichroism spectroscopy in aqueous buffer, SDS, lysophosphatidylglycerol micelles, and organic solvents (methanol, trifluoroethanol, and 2-propanol). The helical propensity of Pro was found to be greatly enhanced in the membrane-mimetic environments of both lipid micelles and organic solvents. Proline was found to stabilize the alpha-helical conformation relative to Ala at elevated temperatures in 2-propanol, an observation that argues against the doctrine that Pro is the most potent alpha-helix breaker as established in aqueous media. Parallel studies in deoxycholate micelles of the temperature-induced conformational transitions of the single-spanning membrane bacteriophage IKe major coat protein, in which the Pro-containing wild type was compared with Pro30 --> Ala mutant, Pro was found to protect the helix, but disrupt the beta-sheet structure as effectively as it does to model peptides in water. The intrinsic capacity of Pro to disrupt beta-sheets was further reflected in a survey of porins where Pro was found to be selectively excluded from the core of membrane-spanning beta-sheet barrels. The overall data provide a rationale for predicting and understanding the structural consequences when Pro occurs in the context of a membrane. PMID:8692877

  5. Predicting location and structure of beta-sheet regions using stochastic tree grammars

    SciTech Connect

    Mamitsuke, Hiroshi; Abe, Naoki

    1994-12-31

    We describe and demonstrate the effectiveness of a method of predicting protein secondary structures, {Beta}-sheet regions in particular, using a class of stochastic tree grammars as representational language for their amino acid sequence patterns. The family of stochastic tree grammars we use, the Stochastic Ranked Node Rewriting Grammars (SRNRG), is one of the rare families of stochastic grammars that are expressive enough to capture the kind of long-distance dependencies exhibited by the sequences of {Beta}-sheet regions, and at the same time enjoy relatively efficient processing. We applied our method on real data obtained from the HSSP database and the results obtained are encouraging: Using an SRNRG trained by data of a particular protein, our method was actually able to predict the location and structure of {Beta}-sheet regions in a number of different proteins, whose sequences are less than 25 percent homologous to the training sequences. The learning algorithm we use is an extension of the {open_quote}Inside-Outside{close_quote} algorithm for stochastic context free grammars, but with a number of significant modifications. First, we restricted the grammars used to be members of the {open_quote}linear{close_quote} subclass of SPLNRG, and devised simpler and faster algorithms for this subclass. Secondly, we reduced the alphabet size (i.e. the number of amino acids) by clustering them using their physicochemical properties, gradually through the iterations of the learning algorithm. Finally, we parallelized. our parsing algorithm to run on a highly parallel computer, a 32-processor CM-5, and were able to obtain a nearly linear speed-up. We emphasize that our prediction method already goes beyond what is possible by the homology-based approaches. We also stress that our method can predict the structure as well as the location of {Beta}-sheet regions, which was not possible by previous inverse protein folding methods.

  6. Methylated mono- and di(ethylene glycol)-functionalized beta-sheet forming polypeptides.

    PubMed

    Hwang, J; Deming, T J

    2001-01-01

    We have synthesized methylated mono- and di(ethylene glycol)-functionalized polymers of L-serine and L-cysteine that adopt beta-sheet conformations in the solid state: poly(O-(2-(2-methoxyethoxy)ethyl)-L-serine), poly(1); poly(O-(2-(methoxy)ethyl)-L-serine), poly(2); and poly(S-(2-(2-methoxyethoxy)ethoxy)carbonyl-L-cysteine), poly(3). Of these three polymers, only poly(1) was found to be highly soluble in water independent of pH. Circular dichroism analysis of poly(1) in water or trifluoroethanol at 25 degrees C revealed that it is in a random conformation, which was unperturbed by changes in pH, buffer, or temperature. However, addition of methanol or acetonitrile to aqueous solutions of poly(1) resulted in a transition to the beta-sheet conformation, as found in the solid state. The polymers were synthesized by transition metal catalyzed polymerization of amino acid-N-carboxyanhydrides, prepared from the functionalized amino acids and represent a new class of readily processable beta-sheet forming polypeptides. PMID:11749148

  7. Design and biological activity of {beta}-sheet breaker peptide conjugates

    SciTech Connect

    Rocha, Sandra Cardoso, Isabel; Boerner, Hans; Pereira, Maria Carmo; Saraiva, Maria Joao; Coelho, Manuel

    2009-03-06

    The sequence LPFFD (iA{beta}{sub 5}) prevents amyloid-{beta} peptide (A{beta}) fibrillogenesis and neurotoxicity, hallmarks of Alzheimer's disease (AD), as previously demonstrated. In this study iA{beta}{sub 5} was covalently linked to poly(ethylene glycol) (PEG) and the activity of conjugates was assessed and compared to the activity of the peptide alone by in vitro studies. The conjugates were characterized by MALDI-TOF. Competition binding assays established that conjugates retained the ability to bind A{beta} with similar strength as iA{beta}{sub 5}. Transmission electron microscopy analysis showed that iA{beta}{sub 5} conjugates inhibited amyloid fibril formation, which is in agreement with binding properties observed for the conjugates towards A{beta}. The conjugates were also able to prevent amyloid-induced cell death, as evaluated by activation of caspase 3. These results demonstrated that the biological activity of iA{beta}{sub 5} is not affected by the pegylation process.

  8. Formation of sheeting joints in Yosemite National Park, California

    NASA Astrophysics Data System (ADS)

    Martel, S. J.

    2009-04-01

    The formation of sheeting joints (i.e., "exfoliation joints"), opening mode fractures subparallel to the Earth's surface, has been a classic unresolved problem in geology. Diverse new observations and analyses support the hypothesis that sheeting joints develop in response to a near-surface tension induced by compressive stresses parallel to a convex slope (hypothesis 1) rather than the conventional explanation that the joints form as a result of removal of overburden by erosion (hypothesis 2). The opening mode displacements across the joints together with the absence of mineral precipitates within the joints mean that sheeting joints open in response to a near-surface tension normal to the surface (N) rather than a pressurized fluid. An absolute tension must arise in the shallow subsurface if a plot of N as a function of depth normal to the surface (z) has a positive slope at the surface (z=0). The differential equations of static equilibrium require that this slope (derivative) equals k2 P22 + k3 P33 - ?g cosβ, where k2 and k3 are the principal curvatures of the surface, P22 and P33 are the respective surface-parallel normal stresses along the principal curvatures, ? is the material density, g is gravitational acceleration, and β is the slope. This derivative will be positive and sheeting joints can open if the surface-parallel stress in at least one direction is sufficiently compressive (negative) and the curvature in that direction is sufficiently convex (negative). Hypotheses 1 and 2 are being tested using geologic mapping and aerial LIDAR data from Yosemite National Park, California. The abundance of sheeting joints on convex ridges there, where erosion is a local minimum, coupled with their scarcity in the adjacent concave valleys, where erosion is a local maximum, is consistent with hypothesis 1 but inconsistent with hypothesis 2. At several sites with sheeting joints, measurements of the current topographic curvatures and the current surface-parallel stresses, typically about -10 MPa, meet the requirement above. In apparent violation of hypothesis 1, however, sheeting joints occur locally at the bottom of Tenaya Canyon, one of the park's deepest glaciated, U-shaped (concave) canyons in Yosemite. The sheeting joints occur only where the canyon is convex in the downstream direction though, and that is the approximate direction of the most compressive stress based on nearby stress measurements. Apparently the effect of the least compressive stress acting across the valley, which acts to close the joints, is overcome by the effect of the most compressive stress acting along the down-valley convex curvature, which promotes the opening of the joints.

  9. Current Sheets and Prominence Formation in the Solar Atmosphere

    NASA Astrophysics Data System (ADS)

    Cheng, C. Z.; Choe, G. S.

    1998-09-01

    If magnetic field lines in opposite directions expand toward each other to squeeze out the field between them, they come into contact to form an abrupt field reversal (tangential discontinuity) which supports a current sheet. Field line expansion can be caused by the combined pressure gradient and gravity force, the magnetic field pressure gradient force, magnetic fields merging toward each other, or a combination of these effects. In this paper we show that in a quadrupolar magnetic field geometry magnetohydrostatic (MHS) equilibria without null point can be deformed into equilibrium field configurations containing current sheets by changes in forces associated with thermodynamic properties or field line footpoint displacement. The shape of current sheets depends on the pressure distributions and footpoint displacement profiles. These MHS equilibria containing current sheets can evolve into different prominence magnetic field configurations via resistive magnetic reconnection processes to support a higher plasma density at the reconnection site than its surrounding. Examples are given to demonstrate these physical processes. If the plasma pressure (or density) on the photospheric boundary is higher in the lower flux tubes than in the higher tubes in each bipolar arcade, the combined pressure gradient and gravity force pushes magnetic field lines outward from the center of each bipolar arcade. When the plasma temperature increases above a critical value, the enhanced expansion of these arcade fields results in the formation of a current sheet between these two arcades along a separatrix line. Similarly, if the field line footpoints undergo a spatially continuous shearing motion so that the outward gradient force of the sheared magnetic field pressure pushes the field lines of each bipolar arcade into contact, a current sheet of the same shape is formed when the amount of shear is above a critical value. This field configuration can be deformed into a configuration with an X-point through resistive magnetic reconnection. It is expected that an inverse polarity prominence can stably reside above the X-point. If the plasma pressure (or density) on the photospheric boundary is lower in the lower flux tubes than in the higher tubes in each bipolar arcade, the combined pressure gradient and gravity force which pushes down magnetic field lines is reduced when the atmosphere is cooled. When the temperature is decreased below a critical value, the subsequent expansion of field lines due to the magnetic tension force creates a new current sheet configuration with a sharp downward-pointing tip hanging at a distance above the bottom boundary. Resistive magnetic reconnection in this type of current sheet results in a Malville-type field configuration with a magnetic island wrapped in dipped field lines. It is expected that an inverse polarity prominence can stably reside within the magnetic island. Our results suggest that the formation of MHS equilibria containing current sheets and their evolution into prominence magnetic field configurations must be a general process in the solar atmosphere.

  10. CURRENT SHEETS FORMATION IN TANGLED CORONAL MAGNETIC FIELDS

    SciTech Connect

    Rappazzo, A. F.; Parker, E. N. E-mail: parker@oddjob.uchicago.edu

    2013-08-10

    We investigate the dynamical evolution of magnetic fields in closed regions of solar and stellar coronae. To understand under which conditions current sheets form, we examine dissipative and ideal reduced magnetohydrodynamic models in Cartesian geometry, where two magnetic field components are present: the strong guide field B{sub 0}, extended along the axial direction, and the dynamical orthogonal field b. Magnetic field lines thread the system along the axial direction that spans the length L and are line-tied at the top and bottom plates. The magnetic field b initially has only large scales, with its gradient (current) length scale of the order of l{sub b}. We identify the magnetic intensity threshold b/B{sub 0} {approx} l{sub b}/L. For values of b below this threshold, field-line tension inhibits the formation of current sheets, while above the threshold they form quickly on fast ideal timescales. In the ideal case, above the magnetic threshold, we show that current sheets thickness decreases in time until it becomes smaller than the grid resolution, with the analyticity strip width {delta} decreasing at least exponentially, after which the simulations become underresolved.

  11. Role of electrostatic interactions in amyloid beta-protein (A beta) oligomer formation: a discrete molecular dynamics study.

    PubMed

    Yun, Sijung; Urbanc, B; Cruz, L; Bitan, G; Teplow, D B; Stanley, H E

    2007-06-01

    Pathological folding and oligomer formation of the amyloid beta-protein (A beta) are widely perceived as central to Alzheimer's disease. Experimental approaches to study A beta self-assembly provide limited information because most relevant aggregates are quasi-stable and inhomogeneous. We apply a discrete molecular dynamics approach combined with a four-bead protein model to study oligomer formation of A beta. We address the differences between the two most common A beta alloforms, A beta 40 and A beta 42, which oligomerize differently in vitro. Our previous study showed that, despite simplifications, our discrete molecular dynamics approach accounts for the experimentally observed differences between A beta 40 and A beta 42 and yields structural predictions amenable to in vitro testing. Here we study how the presence of electrostatic interactions (EIs) between pairs of charged amino acids affects A beta 40 and A beta 42 oligomer formation. Our results indicate that EIs promote formation of larger oligomers in both A beta 40 and A beta 42. Both A beta 40 and A beta 42 display a peak at trimers/tetramers, but A beta 42 displays additional peaks at nonamers and tetradecamers. EIs thus shift the oligomer size distributions to larger oligomers. Nonetheless, the A beta 40 size distribution remains unimodal, whereas the A beta 42 distribution is trimodal, as observed experimentally. We show that structural differences between A beta 40 and A beta 42 that already appear in the monomer folding, are not affected by EIs. A beta 42 folded structure is characterized by a turn in the C-terminus that is not present in A beta 40. We show that the same C-terminal region is also responsible for the strongest intermolecular contacts in A beta 42 pentamers and larger oligomers. Our results suggest that this C-terminal region plays a key role in the formation of A beta 42 oligomers and the relative importance of this region increases in the presence of EIs. These results suggest that inhibitors targeting the C-terminal region of A beta 42 oligomers may be able to prevent oligomer formation or structurally modify the assemblies to reduce their toxicity. PMID:17307823

  12. Amphiphilic beta-sheet cobra cardiotoxin targets mitochondria and disrupts its network.

    PubMed

    Wang, Chia-Hui; Wu, Wen-guey

    2005-06-01

    Recent advance in understanding the role of toxin proteins in controlling cell death has revealed that pro-apoptotic viral proteins targeting mitochondria contain amphiphilic alpha-helices with pore-forming properties. Herein, we describe that the pore-forming amphiphilic beta-sheet cardiotoxins (or cytotoxins, CTXs) from Taiwan cobra (Naja atra) also target mitochondrial membrane after internalization and act synergistically with CTX-induced cytosolic calcium increase to disrupt mitochondria network. It is suggested that CTX-induced fragmentation of mitochondria play a role in controlling CTX-induced necrosis of myocytes and cause severe tissue necrosis in the victims. PMID:15922335

  13. An exact collisionless equilibrium for the Force-Free Harris Sheet with low plasma beta

    NASA Astrophysics Data System (ADS)

    Allanson, O.; Neukirch, T.; Wilson, F.; Troscheit, S.

    2015-10-01

    We present a first discussion and analysis of the physical properties of a new exact collisionless equilibrium for a one-dimensional nonlinear force-free magnetic field, namely, the force-free Harris sheet. The solution allows any value of the plasma beta, and crucially below unity, which previous nonlinear force-free collisionless equilibria could not. The distribution function involves infinite series of Hermite polynomials in the canonical momenta, of which the important mathematical properties of convergence and non-negativity have recently been proven. Plots of the distribution function are presented for the plasma beta modestly below unity, and we compare the shape of the distribution function in two of the velocity directions to a Maxwellian distribution.

  14. Designing biomaterials exploiting beta-sheet forming peptides self-assembly

    NASA Astrophysics Data System (ADS)

    Saiani, Alberto

    2013-03-01

    The use of non-covalent self-assembly to construct materials has become a prominent strategy in material science offering practical routes for the construction of increasingly functional materials for a variety of applications ranging from electronic to biotechnology. A variety of molecular building blocks can be used for this purpose, one such block that has attracted considerable attention are de-novo designed peptides. The library of 20 natural amino acids offers the ability to play with the intrinsic properties of the peptide such as structure, hydrophobicity, charge and functionality allowing the design of materials with a wide range of properties. The beta-sheet motif is of particular interest as short peptides can be designed to form beta-sheet rich fibres that entangle and consequently form hydrogels. These hydrogels can be further functionalised using specific biological signals or drugs by synthesising functionalised peptides that are incorporated into the hydrogel network during the self-assembling process. This functionalisation approach is very attractive has it does not require any chemistry avoiding therefore the use of additional potentially toxic chemicals. It also offers the possibility to introduce multiple functionalities in a straightforward fashion. The hydrogels can also be made responsive through the use of enzymatic catalysis and/or conjugation with responsive polymers. In this presentation we will discuss the design opportunities offered by these peptides to create new functional biomaterials.

  15. Microphase Separation Controlled beta-Sheet Crystallization Kinetics in Fibrous Proteins

    SciTech Connect

    Hu, X.; Lu, Q; Kaplan, D; Cebe, P

    2009-01-01

    Silk is a naturally occurring fibrous protein with a multiblock chain architecture. As such, it has many similarities with synthetic block copolymers, including the possibility for e-sheet crystallization restricted within the crystallizable blocks. The mechanism of isothermal crystallization kinetics of e-sheet crystals in silk multiblock fibrous proteins is reported in this study. Kinetics theories, such as Avrami analysis which was established for studies of synthetic polymer crystal growth, are for the first time extended to investigate protein self-assembly in e-sheet rich Bombyx mori silk fibroin samples, using time-resolved Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and synchrotron real-time wide-angle X-ray scattering (WAXS). The Avrami exponent, n, was close to 2 for all methods and crystallization temperatures, indicating formation of e-sheet crystals in silk proteins is different from the 3-D spherulitic crystal growth found in synthetic polymers. Observations by scanning electron microscopy support the view that the protein structures vary during the different stages of crystal growth, and show a microphase separation pattern after chymotrypsin enzyme biodegradation. We present a model to explain the crystallization of the multiblock silk fibroin protein, by analogy to block copolymers: crystallization of e-sheets occurs under conditions of geometrical restriction caused by phase separation of the crystallizable and uncrystallizable blocks. This crystallization model could be widely applicable in other proteins with multiblock (i.e., crystallizable and noncrystallizable) domains.

  16. Transition to a beta-sheet-rich structure in spidroin in vitro: the effects of pH and cations.

    PubMed

    Dicko, Cedric; Kenney, John M; Knight, David; Vollrath, Fritz

    2004-11-01

    Unlike man-made fibers, the silks of spiders are spun from aqueous solutions and at atmospheric pressure in a process still poorly understood. The molecular mechanism of this process involves the conversion of a highly concentrated, predominantly disordered silk protein (spidroin) into beta-sheet-rich structures. To help store and transport the spidroins in solution, as well as probably control their conversion, a liquid crystalline arrangement is established in the storage region in the ampulla and persists into the duct. Although it has been suggested that changes in the concentration of hydrogen and metal ions play a role in the formation of the solid thread, there is no reported evidence that these ions influence the secondary structure of native spidroin in solution. Here, we demonstrate that pH values between approximately 3.5 and 4.5 induce a slow change of conformation from the disordered to the beta-sheet-rich form. We also report that Al(3+), K(+), and Na(+) ions induce similar changes in structure, while Ca(2+) and Mg(2+) stabilize the predominantly disorder state of the protein. Cs(+) and Li(+) have no apparent effect. Direct volumetric and spectrophotometric titration showed a pI of 4.22 +/- 0.33 and apparent pK values of 6.74 +/- 0.71 and 9.21 +/- 0.27, suggesting a mechanism for the effect of low pH on the protein and a rationale for the observed reduction in pH in the duct. We discuss the importance of these findings for the spinning process and the active role played by the spider to alter the kinetics of the transition. PMID:15518557

  17. Modulation of aggregate size- and shape-distributions of the amyloid-beta peptide by a designed beta-sheet breaker.

    PubMed

    Nagel-Steger, Luitgard; Demeler, Borries; Meyer-Zaika, Wolfgang; Hochdrffer, Katrin; Schrader, Thomas; Willbold, Dieter

    2010-02-01

    A peptide with 42 amino acid residues (Abeta42) plays a key role in the pathogenesis of the Alzheimer's disease. It is highly prone to self aggregation leading to the formation of fibrils which are deposited in amyloid plaques in the brain of diseased individuals. In our study we established a method to analyze the aggregation behavior of the Abeta peptide with a combination of sedimentation velocity centrifugation and enhanced data evaluation software as implemented in the software package UltraScan. Important information which becomes accessible by this methodology is the s-value distribution and concomitantly also the shape-distribution of the Abeta peptide aggregates generated by self-association. With this method we characterized the aggregation modifying effect of a designed beta-sheet breaker molecule. This compound is built from three head-to-tail connected aminopyrazole moieties and represents a derivative of the already described Tripyrazole. By addition of this compound to a solution of the Abeta42 peptide the maximum of the s-value distribution was clearly shifted to smaller s-values as compared to solutions where only the vehicle DMSO was added. This shift to smaller s-values was stable for at least 7 days. The information about size- and shape-distributions present in aggregated Abeta42 solutions was confirmed by transmission electron microscopy and by measurement of amyloid formation by thioflavin T fluorescence. PMID:19238376

  18. A method to predict edge strands in beta-sheets from protein sequences.

    PubMed

    Guilloux, Antonin; Caudron, Bernard; Jestin, Jean-Luc

    2013-01-01

    There is a need for rules allowing three-dimensional structure information to be derived from protein sequences. In this work, consideration of an elementary protein folding step allows protein sub-sequences which optimize folding to be derived for any given protein sequence. Classical mechanics applied to this system and the energy conservation law during the elementary folding step yields an equation whose solutions are taken over the field of rational numbers. This formalism is applied to beta-sheets containing two edge strands and at least two central strands. The number of protein sub-sequences optimized for folding per amino acid in beta-strands is shown in particular to predict edge strands from protein sequences. Topological information on beta-strands and loops connecting them is derived for protein sequences with a prediction accuracy of 75%. The statistical significance of the finding is given. Applications in protein structure prediction are envisioned such as for the quality assessment of protein structure models. PMID:24688737

  19. A method to predict edge strands in beta-sheets from protein sequences

    PubMed Central

    Guilloux, Antonin; Caudron, Bernard; Jestin, Jean-Luc

    2013-01-01

    There is a need for rules allowing three-dimensional structure information to be derived from protein sequences. In this work, consideration of an elementary protein folding step allows protein sub-sequences which optimize folding to be derived for any given protein sequence. Classical mechanics applied to this system and the energy conservation law during the elementary folding step yields an equation whose solutions are taken over the field of rational numbers. This formalism is applied to beta-sheets containing two edge strands and at least two central strands. The number of protein sub-sequences optimized for folding per amino acid in beta-strands is shown in particular to predict edge strands from protein sequences. Topological information on beta-strands and loops connecting them is derived for protein sequences with a prediction accuracy of 75%. The statistical significance of the finding is given. Applications in protein structure prediction are envisioned such as for the quality assessment of protein structure models. PMID:24688737

  20. Translocation efficiency of apolipoprotein B is determined by the presence of beta-sheet domains, not pause transfer sequences.

    PubMed

    Yamaguchi, Junji; Conlon, Donna M; Liang, John J; Fisher, Edward A; Ginsberg, Henry N

    2006-09-15

    Cotranslational translocation of apoB100 across the endoplasmic reticulum (ER) membrane is inefficient, resulting in exposure of nascent apoB on the cytosolic surface of the ER. This predisposes apoB100 to ubiquitinylation and targeting for proteasomal degradation. It has been suggested that pause transfer sequences (PTS) present throughout apoB cause inefficient translocation. On the other hand, our previous study demonstrated that the translocation efficiency of apoB100 is dependent on the presence of a beta-sheet domain between 29 and 34% of full-length apoB100 (Liang, J.-S., Wu, X., Jiang, H., Zhou, M., Yang, H., Angkeow, P., Huang, L.-S., Sturley, S. L., and Ginsberg, H. N. (1998) J. Biol. Chem. 273, 35216-35221); this region of apoB has no PTS. However, the effects of the beta-sheet domain may require the presence of PTS elsewhere in the N-terminal region of apoB100. To further investigate the roles of PTS and beta-sheet domains in the translocation of apoB100 across the ER, we transfected McArdle RH7777, HepG2, or Chinese hamster ovary cells with human albumin (ALB)/human apoB chimeric cDNA constructs: ALB/B12-17 (two PTS but no beta-sheet), ALB/B29-34 (beta-sheet but no PTS), ALB/B36-41 (two PTS and a beta-sheet), and ALB/B49-54 (neither PTS nor a beta-sheet). ALB/ALB1-40 served as a control. Compared with ALB/ALB1-40, secretion rates of ALB/B12-17, ALB/B29-34, and ALB/B36-41 were reduced. Secretion of ALB/B49-54 was similar to that of ALB/ALB1-40. However, only ALB/B29-34 and ALB/B36-41 had increased proteinase K sensitivity, ubiquitinylation, and increased physical interaction with Sec61alpha. These results indicate that the translocation efficiency of apoB100 is determined mainly by the presence of beta-sheet domains. PTS do not appear to affect translocation, but may affect secretion by other mechanisms. PMID:16854991

  1. Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation

    NASA Astrophysics Data System (ADS)

    Guo, Chinlin

    We studied two particular biomedical systems which exhibit collective molecular behavior. One is clustering of tumor necrosis factor receptor I (TNFR1), and another is β-sheet folding and aggregation. Receptor clustering has been shown to be a crucial step in many signaling events but its biological meaning has not been adequately addressed. Here, via a simple lattice model, we show how cells use this clustering machinery to enhance sensitivity as well as robustness. On the other hand, intracellular deposition of aggregated protein rich in β-sheet is a prominent cytopathological feature of most neurodegenerative diseases. How this aggregation occurs and how it responds to therapy is not completely understood. Here, we started from a reconstruction of the H-bond potential and carry out a full investigation of β-sheet thermodynamics as well as kinetics. We show that β-sheet aggregation is most likely due to molecular stacking and found that the minimal length of an aggregate mutant polymer corresponds well with the number observed in adult Huntington's disease. We have also shown that molecular agents such as dendrimers might fail at high-dose therapy; instead, a potential therapy strategy is to block β-turn formation. Our predictions can be used for future experimental tests and clinical trials.

  2. I. The design, synthesis, and structure of antiparallel beta-sheet and beta-strand mimics. II. The design of a scripted chemistry outreach program to high schools

    NASA Astrophysics Data System (ADS)

    Waldman, Amy Sue

    I. Protein structure is not easily predicted from the linear sequence of amino acids. An increased ability to create protein structures would allow researchers to develop new peptide-based therapeutics and materials, and would provide insights into the mechanisms of protein folding. Toward this end, we have designed and synthesized two-stranded antiparallel beta-sheet mimics containing conformationally biased scaffolds and semicarbazide, urea, and hydrazide linker groups that attach peptide chains to the scaffold. The mimics exhibited populations of intramolecularly hydrogen-bonded beta-sheet-like conformers as determined by spectroscopic techniques such as FTIR, sp1H NMR, and ROESY studies. During our studies, we determined that a urea-hydrazide beta-strand mimic was able to tightly hydrogen bond to peptides in an antiparallel beta-sheet-like configuration. Several derivatives of the urea-hydrazide beta-strand mimic were synthesized. Preliminary data by electron microscopy indicate that the beta-strand mimics have an effect on the folding of Alzheimer's Abeta peptide. These data suggest that the urea-hydrazide beta-strand mimics and related compounds may be developed into therapeutics which effect the folding of the Abeta peptide into neurotoxic aggregates. II. In recent years, there has been concern about the low level of science literacy and science interest among Americans. A declining interest in science impacts the abilities of people to make informed decisions about technology. To increase the interest in science among secondary students, we have developed the UCI Chemistry Outreach Program to High Schools. The Program features demonstration shows and discussions about chemistry in everyday life. The development and use of show scripts has enabled large numbers of graduate and undergraduate student volunteers to demonstrate chemistry to more than 12,000 local high school students. Teachers, students, and volunteers have expressed their enjoyment of The UCI Chemistry Outreach Program to High Schools.

  3. A mixed helix-beta-sheet model of the transmembrane region of the nicotinic acetylcholine receptor.

    PubMed

    Ortells, M O; Lunt, G G

    1996-01-01

    We have modelled the transmembrane region of the alpha 7 nicotinic acetylcholine receptor as a mixed alpha-helical/beta-sheet structure. The model was mainly based on the crystal structure of a pore-forming toxin, heat-labile enterotoxin. This is a pentameric protein having a central pore or channel composed of five alpha-helices, one from each of the 5 B subunits that form this pentamer. The remainder of this structure is beta-sheet, loops and a short alpha-helix, not included in the model. The model uses this channel as a template to build the transmembrane region, from M1 to the middle of M3. The remainder of M3 and M4 were built de novo as alpha-helices. Great consideration was given to labelling data available for the transmembrane region. In general terms, the shape of the model agrees very well with that obtained independently by electron microscopic analysis and the secondary structure predicted by the model is in accord with that estimated independently by Fourier transform infrared spectroscopy. The M2 helical region of the model is only slightly kinked, contrary to what is inferred from electron microscopic analysis, but has the same overall shape and form. On the membrane face of the model, the presence of deep pockets may provide the structural basis for the distinction between annular and non-annular lipid binding sites. Also, the transmembrane region is clearly asymmetric in the direction perpendicular to the membrane, and this may have strong influence on the surrounding lipid composition of each leaflet of the cytoplasmic membrane. PMID:9053903

  4. Reversible hydrogel-solution system of silk with high beta-sheet content.

    PubMed

    Bai, Shumeng; Zhang, Xiuli; Lu, Qiang; Sheng, Weiqin; Liu, Lijie; Dong, Boju; Kaplan, David L; Zhu, Hesun

    2014-08-11

    Silkworm silk has been widely used as a textile fiber, as biomaterials and in optically functional materials due to its extraordinary properties. The β-sheet-rich natural nanofiber units of about 10-50 nm in diameter are often considered the origin of these properties, yet it remains unclear how silk self-assembles into these hierarchical structures. A new system composed of β-sheet-rich silk nanofibers about 10-20 nm in diameter is reported here, where these nanofibers formed into "flowing hydrogels" at 0.5-2% solutions and could be transformed back into the solution state at lower concentrations, even with a high β-sheet content. This is in contrast with other silk processed materials, where significant β-sheet content negates reversibility between solution and solid states. These fibers are formed by regulating the self-assembly process of silk in aqueous solution, which changes the distribution of negative charges while still supporting β-sheet formation in the structures. Mechanistically, there appears to be a shift toward negative charges along the outside of the silk nanofibers in our present study, resulting in a higher zeta potential (above -50 mV) than previous silk materials which tend to be below -30 mV. The higher negative charge on silk nanofibers resulted in electrostatic repulsion strong enough to negate further assembly of the nanofibers. Changing silk concentration changed the balance between hydrophobic interactions and electrostatic repulsion of β-sheet-rich silk nanofibers, resulting in reversible hydrogel-solution transitions. Furthermore, the silk nanofibers could be disassembled into shorter fibers and even nanoparticles upon ultrasonic treatment following the transition from hydrogel to solution due to the increased dispersion of hydrophobic smaller particles, without the loss of β-sheet content, and with retention of the ability to transition between hydrogel and solution states through reversion to longer nanofibers during self-assembly. These reversible solution-hydrogel transitions were tunable with ultrasonic intensity, time, or temperature. PMID:25056606

  5. Singularity formation and nonlinear evolution of a viscous vortex sheet model

    NASA Astrophysics Data System (ADS)

    Sohn, Sung-Ik

    2013-01-01

    We study Dhanak's model [J. Fluid Mech. 269, 265 (1994)], 10.1017/S0022112094001552 of a viscous vortex sheet in the sharp limit, to investigate singularity formations and present nonlinear evolutions of the sheets. The finite-time singularity does not disappear by giving viscosity to the vortex sheet, but is delayed. The singularity in the sharp viscous vortex sheet is found to be different from that of the inviscid sheet in several features. A discontinuity in the curvature is formed in the viscous sheet, similarly as the inviscid sheet, but a cusp in the vortex sheet strength is less sharpened by viscosity. Exponential decay of the Fourier amplitudes is lost by the formation of the singularity, and the amplitudes of high wavenumbers exhibit an algebraic decay, while in the inviscid vortex sheet, the algebraic decay of the Fourier amplitudes is valid from fairly small wavenumbers. The algebraic decay rate of the viscous vortex sheet is approximately -2.5, independent of viscosity, which is the same rate as the asymptotic analysis of the inviscid sheet. Results for evolutions of the regularized vortex sheets show that the roll-up is weakened by viscosity, and the regularization parameter has more significant effects on the fine-structure of the core than does viscosity.

  6. Differential stability of beta-sheets and alpha-helices in beta-lactamase: a high temperature molecular dynamics study of unfolding intermediates.

    PubMed Central

    Vijayakumar, S; Vishveshwara, S; Ravishanker, G; Beveridge, D L

    1993-01-01

    beta-Lactamase, which catalyzes beta-lactam antibiotics, is prototypical of large alpha/beta proteins with a scaffolding formed by strong noncovalent interactions. Experimentally, the enzyme is well characterized, and intermediates that are slightly less compact and having nearly the same content of secondary structure have been identified in the folding pathway. In the present study, high temperature molecular dynamics simulations have been carried out on the native enzyme in solution. Analysis of these results in terms of root mean square fluctuations in cartesian and [phi, psi] space, backbone dihedral angles and secondary structural hydrogen bonds forms the basis for an investigation of the topology of partially unfolded states of beta-lactamase. A differential stability has been observed for alpha-helices and beta-sheets upon thermal denaturation to putative unfolding intermediates. These observations contribute to an understanding of the folding/unfolding processes of beta-lactamases in particular, and other alpha/beta proteins in general. Images FIGURE 1 FIGURE 4 PMID:8312470

  7. Equilibria, Dynamics, and Current Sheet Formation in Magnetically Confined Coronae

    NASA Astrophysics Data System (ADS)

    Rappazzo, A. F.

    2015-12-01

    The dynamics of magnetic fields in closed regions of solar and stellar coronae are investigated with a reduced magnetohydrodynamic (MHD) model in the framework of the Parker scenario for coronal heating. A novel analysis of reduced MHD equilibria shows that their magnetic fields have an asymmetric structure in the axial direction with variation length scale z? ?B0/b, where B0 is the intensity of the strong axial guide field, b that of the orthogonal magnetic field component, and ? the scale of {\\boldsymbol{b}}. Equilibria are then quasi-invariant along the axial direction for variation scales larger than approximatively the loop length z? ? Lz, and increasingly more asymmetric for smaller variation scales z? ? Lz. The critical length z? Lz corresponds to the magnetic field intensity threshold b ?B0/Lz. Magnetic fields stressed by photospheric motions cannot develop strong axial asymmetries. Therefore, fields with intensities below such a threshold evolve quasi-statically, readjusting to a nearby equilibrium, without developing nonlinear dynamics or dissipating energy. But stronger fields cannot access their corresponding asymmetric equilibria hence, they are out of equilibrium and develop nonlinear dynamics. The subsequent formation of current sheets and energy dissipation is necessary for the magnetic field to relax to equilibrium, since dynamically accessible equilibria have variation scales larger than the loop length z? ? Lz, with intensities smaller than the threshold b ? ?B0/Lz. The dynamical implications for magnetic fields of interest to solar and stellar coronae are investigated numerically and the impact on coronal physics discussed.

  8. Hybrid modeling of the formation and structure of thin current sheets in the magnetotail

    SciTech Connect

    Hesse, M.; Winske, D.; Birn, J.

    1996-07-01

    Hybrid simulations are used to investigate the formation of a thin current sheet inside the plasma sheet of a magnetotail-like configuration. The initial equilibrium is subjected to a driving electric field qualitatively similar to what would be expected from solar wind driving. As a result, we find the formation of a raw current sheet, with a thickness of approximately the ion inertial length. The current density inside the current sheet region is supplied largely by the electrons. Ion acceleration in the cross-tail direction is absent due since the driving electric field fails to penetrate into the equatorial region.

  9. Network formation through active migration of human vascular endothelial cells in a multilayered skeletal myoblast sheet.

    PubMed

    Nagamori, Eiji; Ngo, Trung Xuan; Takezawa, Yasunori; Saito, Atsuhiro; Sawa, Yoshiki; Shimizu, Tatsuya; Okano, Teruo; Taya, Masahito; Kino-oka, Masahiro

    2013-01-01

    Autologous transplantation of myoblast sheet has attracted attention as a new technique for curing myocardial infarction. Myoblast sheet has the ability to secret cytokines that improve heart function via the facilitation of angiogenesis on affected part. To mimic the invivo angiogenesis in the myoblast sheet after transplantation, a five-layered cell sheet of human skeletal muscle myoblasts (HSMMs) was overlaid on human umbilical vein endothelial cells (HUVECs) which enables evaluation of dynamic HUVEC behavior. HUVECs existing initially at the bottom of the sheet changed to be a stretched shape and migrated upward compared with the surrounding HSMMs in the sheet. Prolonged incubation resulted in network formation of HUVECs in the middle of the sheet, although non-networked HUVECs continued to migrate to the top of the sheet, which meant the spatial habitation of HUVECs in the cell sheet. Image processing was performed to determine the variation in the extent of network formation at different HUVEC densities. It was found that the extent of formed network depended on the frequency of encounters among HUVECs in the middle of the sheet. The present system, which can evaluate network formation, is considered to be a promising invitro angiogenesis model. PMID:23117213

  10. Structural basis of ARNT PAS-B dimerization: use of a common beta-sheet interface for hetero- and homodimerization.

    PubMed

    Card, Paul B; Erbel, Paul J A; Gardner, Kevin H

    2005-10-28

    The aryl hydrocarbon receptor nuclear translocator (ARNT) is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits to control a variety of biological pathways, some of which are centrally involved in disease initiation and/or progression. One of these is the hypoxia response pathway, which allows eukaryotic cells to respond to low oxygen tension via the formation of a heterodimeric complex between ARNT and another bHLH-PAS protein, the hypoxia-inducible factor alpha (HIF-alpha). We have previously shown that the C-terminal PAS domains of an HIF-alpha isoform (HIF-2alpha) and ARNT interact in vitro, and that mutations in the solvent-exposed beta-sheet surface of the HIF-2alpha domain not only disrupt this interaction, but also greatly attenuate the hypoxia response in living cells. Here, we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. We also show that this domain self-associates in a concentration-dependent manner, and that the interface used in this homodimeric complex is very similar to that used in the formation of heterodimer. In addition, using experimentally derived NMR restraints, we used the program HADDOCK to calculate a low-resolution model of the complex formed in solution by these two PAS domains, and confirm the validity of this model using site-directed spin labeling to obtain long-range distance information in solution. With this information, we propose a model for the mode of multi-PAS domain interaction in bHLH-PAS transcriptional activation complexes. PMID:16181639

  11. Occurrence, Formation and Function of Organic Sheets in the Mineral Tube Structures of Serpulidae (Polychaeta, Annelida)

    PubMed Central

    Vinn, Olev

    2013-01-01

    A scanning electron microscopy study of organic sheets in serpulid tube mineral structures was carried out to discern their function, formation and evolution. The organic sheets may have some taxonomic value in distinguishing the two major clades of serpulids previously identified. The organic sheets in the mineral tube structure occur only in certain taxa belonging to clade A, but not all species in clade A have them. Organic sheets are best developed in genus Spirobranchus. One could speculate that organic sheets have evolved as an adaption to further strengthen the mechanical properties of the tubes in clade A, which contains serpulids with the most advanced mineral tube microstructures. The organic sheets are presumably secreted with at least some mineral phase. PMID:24116035

  12. Occurrence, formation and function of organic sheets in the mineral tube structures of Serpulidae (polychaeta, Annelida).

    PubMed

    Vinn, Olev

    2013-01-01

    A scanning electron microscopy study of organic sheets in serpulid tube mineral structures was carried out to discern their function, formation and evolution. The organic sheets may have some taxonomic value in distinguishing the two major clades of serpulids previously identified. The organic sheets in the mineral tube structure occur only in certain taxa belonging to clade A, but not all species in clade A have them. Organic sheets are best developed in genus Spirobranchus. One could speculate that organic sheets have evolved as an adaption to further strengthen the mechanical properties of the tubes in clade A, which contains serpulids with the most advanced mineral tube microstructures. The organic sheets are presumably secreted with at least some mineral phase. PMID:24116035

  13. Development of the dual scintillator sheet and Phoswich detector for simultaneous Alpha- and Beta-rays measurement

    SciTech Connect

    Seo, B.K.; Kim, G.H.; Park, C.H.; Jung, Y.H.; Jung, C.H.; Lee, K.W.; Han, M.J.

    2007-07-01

    Thin sheet type of ZnS(Ag)/plastic dual scintillator for simultaneous counting of alpha- and beta-particles using a organic and inorganic scintillator widely used in the radiation measurement was manufactured, which could be applicable in the contamination monitoring systems. Counting materials were manufactured by solidification of the scintillator solution which mixed scintillator, solvent, and polymer. Prepared dual scintillator is a counting material which can simultaneously measure the alpha- and beta-particles. It was divided into two parts : an inorganic scintillator layer for alpha-particle detection and an organic one for beta-particle detection. The organic layer was composed of 2,5-diphenyloxazole [PPO] and 1,4,-bis[5-phenyl(oxazolyl)benzene] [POPOP] acting as the scintillator and polysulfone acting as the polymer. The inorganic layer was composed of ZnS(Ag) as scintillator and polysulfone as paste. The ZnS(Ag) scintillator layer was printed onto the organic layer using screen printing method. To estimate the detection ability of the prepared counting materials, alpha-particle emitting nuclide, Am-241, and beta emitting nuclide, Sr/Y-90, were used. The scintillations produced by interaction between radiation and scintillator were measured by photomultiplier tube. The overall counting results reveal that the developed detector is efficient for simultaneous counting of alpha- and beta-particles. For application test, the dual scintillator was fabricated with a Phoswich detector for monitoring the in-pipe alpha and beta contamination. To deploy inside a pipe, two types of Phoswich detectors, sheets and cylinders, were prepared. For in-pipe monitoring, it was found that the cylindrical type was excellent. In the study, polymer composite counting material and Phoswich detectors were prepared using organic and inorganic scintillator for detecting different radiations. In the future, it will be applied to the contamination monitoring system for nuclear decommissioning sites, waste treatment sites, and similar areas. (authors)

  14. [Neutralization of static electricity charged on running vinyl chloride sheet by the use of soft beta-ray sources (author's transl)].

    PubMed

    Itakura, K; Wada, N

    1978-04-01

    The feasibility of 147Pm and 3H beta-ray sources as static eliminator was experimentally investigated. A sheet of vinyl chloride of 0.1 mm in thickness was used as an example of electrified materials. Its surface charge densities before and after beta-ray neutralization were measured as the function of electrostatic charge changing the speed of the sheet and the distance between the beta-ray source and the sheet. With a 147Pm beta-ray source of 200mCi in effective activity, almost complete neutralization was found for the sheet with the charge density less than 6 X 10(-6) C/m2 running at the speed of 0.18 m/s. In the case of the running speed of 0.5 m/s frequently used in industry, the electrostatic charge below 3 X 10(6) C/m2, where corona discharger is not so effective, was also perfectly eliminated. It was found that the optimal distance between the beta-ray source and the sheet was 10 cm in the case of 147Pm. The use of 3H beta-ray source of 1 Ci was not satisfactory. These results demonstrate that 147 Pm beta-ray source operates most efficiently as static eliminator when the charge density of material and/or its moving speed is not high. PMID:663315

  15. Current Sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-frequency Assisted Discharge

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Hallock, Ashley K.; Choueiri, Edgar Y.

    2008-01-01

    Data from an inductive conical theta pinch accelerator are presented to gain insight into the process of inductive current sheet formation in the presence of a preionized background gas produced by a steady-state RF-discharge. The presence of a preionized plasma has been previously shown to allow for current sheet formation at lower discharge voltages and energies than those found in other pulsed inductive accelerator concepts, leading to greater accelerator efficiencies at lower power levels. Time-resolved magnetic probe measurements are obtained for different background pressures and pulse energies to characterize the effects of these parameters on current sheet formation. Indices are defined that describe time-resolved current sheet characteristics, such as the total current owing in the current sheet, the time-integrated total current ('strength'), and current sheet velocity. It is found that for a given electric field strength, maximums in total current, strength, and velocity occur for one particular background pressure. At other pressures, these current sheet indices are considerably smaller. The trends observed in these indices are explained in terms of the principles behind Townsend breakdown that lead to a dependence on the ratio of the electric field to the background pressure. Time-integrated photographic data are also obtained at the same experimental conditions, and qualitatively they compare quite favorably with the time-resolved magnetic field data.

  16. The peculiarities of formation of thin current sheet in the Earth's magnetotail

    NASA Astrophysics Data System (ADS)

    Kropotkin, Alexey; Artemyev, Anton; Malova, Helmi; Domrin, Vladimir

    We investigate the process of self-consistent thinning of magnetotail current sheet in the presence of the evolving magnetic field normal component Bz, which usually decreases during the substorm growth phase. Using PIC codes to describe plasma processes with ions becoming demagnetized and electrons being considered as the cold neutralizing background, we show that the appearance of the self-consistent electric field component inside CS can lead to the current sheet thinning and to the appearance of an extremely thin current sheet with thickness close to the ion gyroradius. Due to particle [ExB] drift during the current sheet evolution, the enhanced trapping of ions near the current sheet central plane takes place. It is shown that the density of quasi-trapped particles around current sheet at the final stage depends on both the value of the initial magnetic field normal component Bz, and the speed of the Bz decrease. If the initial magnetic field normal component is less than about 0.14 of the tangential field at the edges, the trapped plasma density near the current sheet is small. As a result, the above mentioned extremely thin current sheet is formed. In the opposite case, when the initial normal component related to the tangential field is larger than 0.14, the density of trapped particles is much higher, which produces effective thickening of the current sheet. In both cases transient (Speiser) ions are the main current carriers, but in the second case local diamagnetic currents of the trapped plasma perturb the сurrent sheet profile making it thicker. Also trapped particles can be responsible for intense negative currents at the current sheet edges. During the Bz decrease, an additional effect of ion polarization drifts in the Y direction can compete with these negative diamagnetic fields of quasi-trapped ions. Therefore the ion dynamics is probably the general mechanism which contributes to the formation of thin current sheet and its fine structure.

  17. Spontaneous formation of electric current sheets and the origin of solar flares

    NASA Technical Reports Server (NTRS)

    Low, B. C.; Wolfson, R.

    1988-01-01

    It is demonstrated that the continuous boundary motion of a sheared magnetic field in a tenuous plasma with an infinite electrical conductivity can induce the formation of multiple electric current sheets in the interior plasma. In response to specific footpoint displacements, the quadrupolar magnetic field considered is shown to require the formation of multiple electric current sheets as it achieves a force-free state. Some of the current sheets are found to be of finite length, running along separatrix lines of force which separate lobes of magnetic flux. It is suggested that current sheets in the form of infinitely thin magnetic shear layers may be unstable to resistive tearing, a process which may have application to solar flares.

  18. Effects of side-chain orientation on the 13C chemical shifts of antiparallel beta-sheet model peptides.

    PubMed

    Villegas, Myriam E; Vila, Jorge A; Scheraga, Harold A

    2007-02-01

    The dependence of the (13)C chemical shift on side-chain orientation was investigated at the density functional level for a two-strand antiparallel beta-sheet model peptide represented by the amino acid sequence Ac-(Ala)(3)-X-(Ala)(12)-NH(2) where X represents any of the 17 naturally occurring amino acids, i.e., not including alanine, glycine and proline. The dihedral angles adopted for the backbone were taken from, and fixed at, observed experimental values of an antiparallel beta-sheet. We carried out a cluster analysis of the ensembles of conformations generated by considering the side-chain dihedral angles for each residue X as variables, and use them to compute the (13)C chemical shifts at the density functional theory level. It is shown that the adoption of the locally-dense basis set approach for the quantum chemical calculations enabled us to reduce the length of the chemical-shift calculations while maintaining good accuracy of the results. For the 17 naturally occurring amino acids in an antiparallel beta-sheet, there is (i) good agreement between computed and observed (13)C(alpha) and (13)C(beta) chemical shifts, with correlation coefficients of 0.95 and 0.99, respectively; (ii) significant variability of the computed (13)C(alpha) and (13)C(beta) chemical shifts as a function of chi(1) for all amino acid residues except Ser; and (iii) a smaller, although significant, dependence of the computed (13)C(alpha) chemical shifts on chi(xi) (with xi > or = 2) compared to chi(1) for eleven out of seventeen residues. Our results suggest that predicted (13)C(alpha) and (13)C(beta) chemical shifts, based only on backbone (phi,psi) dihedral angles from high-resolution X-ray structure data or from NMR-derived models, may differ significantly from those observed in solution if the dihedral-angle preferences for the side chains are not taken into account. PMID:17180547

  19. Engineering of betabellin-15D: a 64 residue beta sheet protein that forms long narrow multimeric fibrils.

    PubMed

    Lim, A; Saderholm, M J; Makhov, A M; Kroll, M; Yan, Y; Perera, L; Griffith, J D; Erickson, B W

    1998-07-01

    The betabellin target structure is a beta-sandwich protein consisting of two 32 residue beta-sheets packed against one another by interaction of their hydrophobic faces. The 32 residue chain of betabellin-15S (HSLTAKIpkLTFSIAphTYTCAV pkYTAKVSH, where p=DPro, k=DLys, and h=DHis) did not fold in water at pH 6.5. Air oxidation of betabellin-15S provided betabellin-15D, the 64 residue disulfide bridged two-chain molecule, which also remained unfolded in water at pH 6.5. By circular dichroic spectropolarimetry, the extent of beta structure observed for betabellin-15D increased with the pH and ionic strength of the solution and the betabellin-15D concentration. By electron microscopy, in 5.0 mM MOPS and 0.25 M NaCl at pH 6.9, betabellin-15D formed long narrow multimeric fibrils. A molecular model was constructed to show that the dimensions of these betabellin-15D fibrils are consistent with a single row of beta-sandwich molecules joined by multiple intersheet H-bonds. PMID:9684887

  20. The formation of wrinkles in single-layer graphene sheets under nanoindentation

    NASA Astrophysics Data System (ADS)

    Gil, A. J.; Adhikari, S.; Scarpa, F.; Bonet, J.

    2010-04-01

    We investigate the formation of wrinkles and bulging in single-layer graphene sheets using an equivalent atomistic continuum nonlinear hyperelastic theory for nanoindentation and nanopressurization. We show that nonlinear geometrical effects play a key role in the development of wrinkles. Without abandoning the classical tension field membrane theory, we develop an enhanced model based upon the minimization of a relaxed energy functional in conjunction with nonlinear finite hyperelasticity. Formation of wrinkles are observed in rectangular graphene sheets due to the combination of induced membrane tension and edge effects under external pressure.

  1. Beta-D-Allose inhibits fruiting body formation and sporulation in Myxococcus xanthus.

    PubMed

    Chavira, Marielena; Cao, Nga; Le, Karen; Riar, Tanveer; Moradshahi, Navid; McBride, Melinda; Lux, Renate; Shi, Wenyuan

    2007-01-01

    Myxococcus xanthus, a gram-negative soil bacterium, responds to amino acid starvation by entering a process of multicellular development which culminates in the assembly of spore-filled fruiting bodies. Previous studies utilizing developmental inhibitors (such as methionine, lysine, or threonine) have revealed important clues about the mechanisms involved in fruiting body formation. We used Biolog phenotype microarrays to screen 384 chemicals for complete inhibition of fruiting body development in M. xanthus. Here, we report the identification of a novel inhibitor of fruiting body formation and sporulation, beta-d-allose. beta-d-Allose, a rare sugar, is a member of the aldohexose family and a C3 epimer of glucose. Our studies show that beta-d-allose does not affect cell growth, viability, agglutination, or motility. However, beta-galactosidase reporters demonstrate that genes activated between 4 and 14 h of development show significantly lower expression levels in the presence of beta-d-allose. Furthermore, inhibition of fruiting body formation occurs only when beta-d-allose is added to submerged cultures before 12 h of development. In competition studies, high concentrations of galactose and xylose antagonize the nonfruiting response to beta-d-allose, while glucose is capable of partial antagonism. Finally, a magellan-4 transposon mutagenesis screen identified glcK, a putative glucokinase gene, required for beta-d-allose-mediated inhibition of fruiting body formation. Subsequent glucokinase activity assays of the glcK mutant further supported the role of this protein in glucose phosphorylation. PMID:17056749

  2. Hole formation and sheeting in the drainage of thin liquid films

    SciTech Connect

    Bergeron, V.; Jimenez-Laguna, A.I.; Radke, C.J. Univ. of California, Berkeley )

    1992-12-01

    Foam, emulsion, and pseudoemulsion films stabilized by surfactants above the critical micelle concentration exhibit pronounced stepwise thinning or stratification. Dynamic removal of a layer is initiated by the formation and subsequent sheeting of a hole (or holes) at each step of the stratified thinning. We outline a nonlinear hydrodynamic stability analysis which successfully models the dynamics of hole formation and sheeting by accounting for an equilibrium oscillatory structural component in the disjoining pressure isotherm. Initiation of a hole is attributed to the nonlinear growth of a hydrodynamic instability during film thinning under the action of a constant capillary pressure and an oscillatory disjoining pressure. Subsequent growth or sheeting of the hole is explained by outward fluid flow within the inhomogeneous thin film as radial pressure gradients develop from curvature variations and viscous resistance to flow. Qualitative comparison is made between the proposed hydrodynamic theory and experimental observations of thinning events and rates. 32 refs., 6 figs.

  3. I32E and V36K double mutation in beta2-sheet abrogates amyloid beta peptide toxicity.

    PubMed

    Subramanian, Sarada; Mishra, Pradeep Kumar; Bandopadhyay, Debashree

    2010-11-01

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly, wherein, the accumulation of amyloid beta (Abeta) peptide as cytotoxic oligomers leads to neuropathologic changes. Transgenic mice with brain Abeta plaques immunized with aggregated Abeta have reduced amyloid burden and improved cognitive functions. However, such active immunization in humans led to a small but significant occurrence of meningoencephalitis in 6% AD volunteers due to Abeta induced toxicity. In an attempt to develop safer alternative vaccines, the design of a highly soluble peptide homologous to Abeta (Abeta-EK), that has a reduced amyloidogenic potential while maintaining the major immunogenic epitopes of Abeta is reported. More importantly, this homologue has been shown to be non-toxic, as this peptide failed to exert any observable effect on erythrocytes. The results of the present study suggests that immunization with non-toxic Abeta derivative may offer a safer therapeutic approach to AD, instead of using toxic Abeta fibrils. PMID:21117449

  4. Dynamically stable beta-sheets in Cu-initiated misfolding of ?-synuclein

    NASA Astrophysics Data System (ADS)

    Rose, Francis; Hodak, Miroslav; Bernholc, Jerry

    2008-03-01

    The human protein ?-synuclein has been implicated as a central constituent in multiple neurodegenerative diseases. In Parkinson disease it is even thought to be the causative link. ?-synuclein can be stimulated to aggregate into deleterious fibrillar structures by mutation, metal binding, and agitation. In particular, Cu^2+ has been found in high concentrations in neural tissues of Parkinson sufferers. We propose a scenario involving the metal ion Cu^2+ as the misfolding ?-sheet initiator of fibrillogenesis. A model fragment of the metal-bound protein was investigated using DFT to obtain conformational details of the energetically favorable geometries. Feasible ?-sheet structures incorporating the DFT geometries were explored using heuristic ?-sheet guidelines and inverse kinematics. The resulting structures were tested for dynamic stability by simulating the fully solvated protein by classical MD constrained by the DFT geometries. Our results indicate that dynamically stable structures exist and that the metal binding is directly responsible for initiating misfolding.

  5. Bond formation in ultrasonically welded aluminum sheet metal

    NASA Astrophysics Data System (ADS)

    Wilkosz, Daniel Edward

    Ultrasonic welding (USW), a solid state joining technology, has been used to bond aluminum alloys commonly used in the automotive industry. Bonding occurs due to USW's high frequency (20 kHz) in-plane vibration of sample interfaces while being held under moderate clamp pressure normal to the plane of vibration. Vibration and clamp pressure are transmitted into bond formation via contact with a weld-tip. To better understand how weld-tip geometry affected bond formation, experiments were conducted to quantify how tip geometry influenced plastic deformation characteristics between fully welded coupons of 0.9mm thick AA6111-T4 aluminum alloy. Weld-interface microstructure features were documented by optical microscopy and features quantified in a 19 point matrix. Correlation between microstructure features, such as rolling-wakes, and resulting weld bond strengths of more than 3.0kN is made. Weld zone microstructure features appear to result from deformation at and severe migration of the original weld interface during USW. To confirm this hypothesis, intrinsic and extrinsic markers were employed to monitor weld interface deformation characteristics. Various physical and analytical techniques were used in conjunction with these markers to show that joining of "like" and "dislike" aluminum samples is achieved through mechanical mixing of mating interfaces and not by elemental diffusion. It is also hypothesized that severe deformation of the original interface would result in areas of high residual strain within a formed weld zone. To investigate this and the influence that tip geometry may have on residual strain, fully welded samples were annealed at 500C for a controlled period of time and recovery, recrystallization and grain growth characteristics were monitored. In all welds, initial recrystallization and grain growth occurred at the outer ends of weld zones and along weld interfaces where the most turbulent mixing and grain size reduction was observed. Similarity in how all welds responded to annealing indicates that the tip geometries investigated had little influence on resulting weld formation. This claim is further supported by lap-shear failure load data for welds made with these tips being within statistical error of each other.

  6. Research of vacancy defect formation on the surface of two-dimensional boron sheets

    NASA Astrophysics Data System (ADS)

    Boroznina, E. V.; Zhiganova, T. A.; Boroznin, S. V.

    2015-01-01

    Mechanism of vacancy defect formation on the surface of two types of BS: triangular BS (TBS), ?-sheet (?BS) have been calculated within the model of molecular cluster with the use of quantum chemical MNDO scheme. The process of atomic vacancy formation of BS has been modeled by step-by-step abstraction of one central boron atom. Incremental method allowed us to build energy curves for vacancy formation process. The process of vacancy migration on the BS surface has also have been investigated, and more probable paths of migration have been found.

  7. Hydroxyl-rich beta-sheet adhesion to the gold surface in water by first-principle simulations.

    PubMed

    Calzolari, Arrigo; Cicero, Giancarlo; Cavazzoni, Carlo; Di Felice, Rosa; Catellani, Alessandra; Corni, Stefano

    2010-04-01

    Proteins able to recognize inorganic surfaces are of paramount importance for living organisms. Mimicking nature, surface-recognizing proteins and peptides have also been man-made by combinatorial biochemistry. However, to date the recognition mechanisms remain elusive, and the underlying physicochemical principles are still unknown. Selectivity of gold-binding peptides (cysteine-free and rich in hydroxyl amino acids) is particularly puzzling, since the most relevant gold surface, Au(111), is known to be chemically inert and atomically flat. Using atomistic first-principle simulations we show that weak chemical interactions of dative-bond character confer to a prototype secondary structure (an antiparallel beta-sheet made of hydroxyl amino acids) and its hydration layer the capability of discriminating among gold surface sites. Our results highlight the unexpected role of hydration water in this process, suggesting that hydrophilic amino acids and their hydration shell cooperate to contribute to protein-gold surface recognition. PMID:20225820

  8. Multinuclear NMR studies of the flavodoxin from Anabaena 7120:. beta. -sheet structure and the flavin mononucleotide binding site

    SciTech Connect

    Stockman, B.J.

    1989-01-01

    A concerted approach to primary {sup 1}H, {sup 13}C, and {sup 15}N nuclear magnetic resonance assignments in proteins was developed. The method requires enrichment of the protein with {sup 13}C and {sup 15}N. The technique relies on the comparison of data sets from NMR experiments that correlate various nuclei: {sup 13}C({sup 13}C) double quantum correlations, {sup 1}H({sup 13}C) and {sup 1}H({sup 15}N) single bond correlations, and {sup 1}H({sup 13}C) and {sup 1}H({sup 15}N) multiple bond correlations. Comparison of data sets increases the number of resonances that can be assigned and improves assignment confidence. By combined use of these and conventional NMR techniques, sequential assignments were made for the {beta}-sheet and flavin mononucleotide (FMN) binding site residues in flavodoxin from Anabaena 7120. The {beta}-sheet structure was found to be similar to that seen in the crystal structure of Anacystis nidulans flavodoxin. In the FMN binding site, a total of 69 NOEs were identified: eight between protons of FMN, 36 between protons of binding site residues, and 25 between protons of FMN and protein. These constraints were used to determine the localized solution structure of the flavin binding site. The electronic environment and conformation of the protein-bound isoalloxazine ring were investigated by determining chemical shifts and coupling constants for the ring atoms. The carbonyl edge of the flavin ring was found to be slightly polarized by hydrogen bonding to the protein. The xylene ring was found to be nonplanar. The C{sup 6}-N{sup 5} region of the flavin appears to be solvent accessible.

  9. Formation and Reconnection of Three-Dimensional Current Sheets in the Solar Corona

    NASA Technical Reports Server (NTRS)

    Edmondson, J. K.; Antiochos, S. K.; DeVore, C. R.; Zurbuchen, T. H.

    2010-01-01

    Current-sheet formation and magnetic reconnection are believed to be the basic physical processes responsible for much of the activity observed in astrophysical plasmas, such as the Sun s corona. We investigate these processes for a magnetic configuration consisting of a uniform background field and an embedded line dipole, a topology that is expected to be ubiquitous in the corona. This magnetic system is driven by a uniform horizontal flow applied at the line-tied photosphere. Although both the initial field and the driver are translationally symmetric, the resulting evolution is calculated using a fully three-dimensional magnetohydrodynamic (3D MHD) simulation with adaptive mesh refinement that resolves the current sheet and reconnection dynamics in detail. The advantage of our approach is that it allows us to apply directly the vast body of knowledge gained from the many studies of 2D reconnection to the fully 3D case. We find that a current sheet forms in close analogy to the classic Syrovatskii 2D mechanism, but the resulting evolution is different than expected. The current sheet is globally stable, showing no evidence for a disruption or a secondary instability even for aspect ratios as high as 80:1. The global evolution generally follows the standard Sweet- Parker 2D reconnection model except for an accelerated reconnection rate at a very thin current sheet, due to the tearing instability and the formation of magnetic islands. An interesting conclusion is that despite the formation of fully 3D structures at small scales, the system remains close to 2D at global scales. We discuss the implications of our results for observations of the solar corona. Subject Headings: Sun: corona Sun: magnetic fields Sun: reconnection

  10. Probing the Nanosecond Dynamics of a Designed Three-Stranded Beta-Sheet with a Massively Parallel Molecular Dynamics Simulation

    PubMed Central

    Voelz, Vincent A.; Luttmann, Edgar; Bowman, Gregory R.; Pande, Vijay S.

    2009-01-01

    Recently a temperature-jump FTIR study of a designed three-stranded sheet showing a fast relaxation time of ~140 20 ns was published. We performed massively parallel molecular dynamics simulations in explicit solvent to probe the structural events involved in this relaxation. While our simulations produce similar relaxation rates, the structural ensemble is broad. We observe the formation of turn structure, but only very weak interaction in the strand regions, which is consistent with the lack of strong backbone-backbone NOEs in previous structural NMR studies. These results suggest that either DPDP-II folds at time scales longer than 240 ns, or that DPDP-II is not a well-defined three-stranded ?-sheet. This work also provides an opportunity to compare the performance of several popular forcefield models against one another. PMID:19399235

  11. Venus: volcanism and rift formation in Beta regio.

    PubMed

    Campbell, D B; Head, J W; Harmon, J K; Hine, A A

    1984-10-12

    A new high-resolution radar image of Beta Regio, a Venus highland area, confirms the presence of a major tectonic rift system and associated volcanic activity. The lack of identifiable impact craters, together with the apparent superposition of the Theia Mons volcanic structure on the rift system, suggest that at least some of the volcanic activity occurred in relatively recent geologic time. The presence of topographically similar highland areas elsewhere on Venus (Aphrodite Terra, Dali Chasma, and Diana Chasma) suggests that rifting and volcanism are significant processes on Venus. PMID:17814347

  12. Venus - Volcanism and rift formation in Beta Regio

    NASA Technical Reports Server (NTRS)

    Campbell, D. B.; Harmon, J. K.; Hine, A. A.; Head, J. W.

    1984-01-01

    A new high-resolution radar image of Beta Regio, a Venus highland area, confirms the presence of a major tectonic rift system and associated volcanic activity. The lack of identifiable impact craters, together with the apparent superposition of the Theia Mons volcanic structure on the rift system, suggest that at least some of the volcanic activity occurred in relatively recent geologic time. The presence of topographically similar highland areas elsewhere on Venus (Aphrodite Terra, Dali Chasma, and Diana Chasma) suggests that rifting and volcanism are significant processes on Venus.

  13. Venus - Volcanism and rift formation in Beta Regio

    NASA Astrophysics Data System (ADS)

    Campbell, D. B.; Head, J. W.; Harmon, J. K.; Hine, A. A.

    1984-10-01

    A new high-resolution radar image of Beta Regio, a Venus highland area, confirms the presence of a major tectonic rift system and associated volcanic activity. The lack of identifiable impact craters, together with the apparent superposition of the Theia Mons volcanic structure on the rift system, suggest that at least some of the volcanic activity occurred in relatively recent geologic time. The presence of topographically similar highland areas elsewhere on Venus (Aphrodite Terra, Dali Chasma, and Diana Chasma) suggests that rifting and volcanism are significant processes on Venus.

  14. Factors contributing to the formation of sheeting joints: A study of sheeting joints on a dome in Yosemite National Park

    NASA Astrophysics Data System (ADS)

    Mitchell, Kelly J.

    Sheeting joints (shallow, surface-parallel, opening-mode rock fractures) are widespread and have been studied for centuries. They are commonly attributed to removal of overburden by erosion, but erosion alone cannot open a sheeting joint. I test an alternative hypothesis that sheeting joints open in response to surface-parallel compression along a convex topographic surface using field observations, a large-scale fracture map, and analyses of stresses, slopes, and surface-curvatures (derived from aerial laser altimetry data) for a dome along Tenaya Creek in Yosemite National Park. Approximately 90% of the surface of detailed study is convex in at least one direction. Existing stresses and topography there can account for the nature and distribution of sheeting joints on the doubly-convex surfaces. Sheeting joints parallel and constitute the surface where the surface is doubly convex. Elsewhere, sheeting joints daylight, implying the surface has been eroded since the sheeting joints formed. My findings support the hypothesis.

  15. Penicillinase (beta-lactamase) formation by blue-green algae.

    PubMed

    Kushner, D J; Breuil, C

    1977-03-01

    Beta-Lactamase (penicillinase) activity was found in a number of strains of blue-green algea. In some cases, this enzyme permitted algae to overcome the inhibitory effects of penicillin. Production and localization of beta-lactamase were studied in a unicellular species, Coccochloris elabens (strain 7003), and in a filamentous, nitrogen-fixing Anabaena species (strain 7120). When cells were grown in a neutral medium with NaNO3 as N source, the pH rose during growth; at a pH of about 10, most of the enzyme was expressed equally well in intact or disrupted cells. If the pH was kept near neutrality during growth by gassing with CO2 in N2 or by growth under conditions of N2 fixation, the enzyme remained cell-bound and cryptic for most of the growth phase, being measurable only after cells were disrupted. The enzymes from strains 7003 and 7120 had greater activity on benzyl penicillin and other penicillins than on cephalosporins. Some differences were observed in the "substrate proliles" of penicillinases from the two strains against different penicillins. PMID:15530

  16. Formation and Degradation of Beta-casomorphins in Dairy Processing.

    PubMed

    Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

    2015-01-01

    Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from ?-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B ?-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme-linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown. PMID:25077377

  17. Formation and Degradation of Beta-casomorphins in Dairy Processing

    PubMed Central

    Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

    2015-01-01

    Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme–linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown. PMID:25077377

  18. World Sheet Commuting beta-gamma CFT and Non-Relativistic StringTheories

    SciTech Connect

    Kim, Bom Soo

    2007-08-30

    We construct a sigma model in two dimensions with Galilean symmetry in flat target space similar to the sigma model of the critical string theory with Lorentz symmetry in 10 flat spacetime dimensions. This is motivated by the works of Gomis and Ooguri[1] and Danielsson et. al.[2, 3]. Our theory is much simpler than their theory and does not assume a compact coordinate. This non-relativistic string theory has a bosonic matter {beta}{gamma} CFT with the conformal weight of {beta} as 1. It is natural to identify time as a linear combination of {gamma} and {bar {gamma}} through an explicit realization of the Galilean boost symmetry. The angle between {gamma} and {bar {gamma}} parametrizes one parameter family of selection sectors. These selection sectors are responsible for having a non-relativistic dispersion relation without a nontrivial topology in the non-relativistic setup, which is one of the major differences from the previous works[1, 2, 3]. This simple theory is the non-relativistic analogue of the critical string theory, and there are many different avenues ahead to be investigated. We mention a possible consistent generalization of this theory with different conformal weights for the {beta}{gamma} CFT. We also mention supersymmetric generalizations of these theories.

  19. Efficient Traversal of Beta-Sheet Protein Folding Pathways Using Ensemble Models

    NASA Astrophysics Data System (ADS)

    Shenker, Solomon; O'Donnell, Charles W.; Devadas, Srinivas; Berger, Bonnie; Waldispühl, Jérôme

    Molecular Dynamics (MD) simulations can now predict ms-timescale folding processes of small proteins - however, this presently requires hundreds of thousands of CPU hours and is primarily applicable to short peptides with few long-range interactions. Larger and slower-folding proteins, such as many with extended β-sheet structure, would require orders of magnitude more time and computing resources. Furthermore, when the objective is to determine only which folding events are necessary and limiting, atomistic detail MD simulations can prove unnecessary. Here, we introduce the program tFolder as an efficient method for modelling the folding process of large β-sheet proteins using sequence data alone. To do so, we extend existing ensemble β-sheet prediction techniques, which permitted only a fixed anti-parallel β-barrel shape, with a method that predicts arbitrary β-strand/β-strand orientations and strand-order permutations. By accounting for all partial and final structural states, we can then model the transition from random coil to native state as a Markov process, using a master equation to simulate population dynamics of folding over time. Thus, all putative folding pathways can be energetically scored, including which transitions present the greatest barriers. Since correct folding pathway prediction is likely determined by the accuracy of contact prediction, we demonstrate the accuracy of tFolder to be comparable with state-of-the-art methods designed specifically for the contact prediction problem alone. We validate our method for dynamics prediction by applying it to the folding pathway of the well-studied Protein G. With relatively very little computation time, tFolder is able to reveal critical features of the folding pathways which were only previously observed through time-consuming MD simulations and experimental studies. Such a result greatly expands the number of proteins whose folding pathways can be studied, while the algorithmic integration of ensemble prediction with Markovian dynamics can be applied to many other problems.

  20. Formation of self-organized shear structures in thin current sheets

    NASA Astrophysics Data System (ADS)

    Malova, H. V.; Mingalev, O. V.; Grigorenko, E. E.; Mingalev, I. V.; Melnik, M. N.; Popov, V. Yu.; Delcourt, D. C.; Petrukovich, A. A.; Shen, C.; Rong, Z. J.; Zelenyi, L. M.

    2015-06-01

    Self-consistent kinetic (particle-in-cell) model of magnetotail thin current sheet (TCS) is used to understand the formation of self-consistent sheared magnetic structures. It is shown that shear configurations appear in TCS as a result of self-consistent evolution of some initial magnetic perturbation at the current sheet center. Two general shapes of shear TCS components are found as a function of the transverse coordinate: symmetric and antisymmetric. We show that TCS formation goes together with the emergence of field-aligned currents in the center of the current sheet, as a result of north-south asymmetry of quasi-adiabatic ion motions. Ion drift currents can also contribute to the magnetic shear evolution, but their role is much less significant, their contribution depending upon the normal component Bz and the amplitude of the initial perturbation in TCS. Parametric maps illustrating different types of TCS equilibria are presented that show a higher probability of formation of symmetric shear TCS configuration at lower values of the normal magnetic component.

  1. Existing Data Format for Two-Parameter Beta-Gamma Histograms for Radioxenon

    SciTech Connect

    TW Bowyer; TR Heimbigner; JI McIntyre; AD McKinnon; PL Reeder; E Wittinger

    1999-03-23

    There is a need to establish a commonly acceptable format for storing beta-gated coincidence data for stations in the International Monitoring System (IMS) for the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The current aerosol RMS type data format is not applicable for radioxenon in that the current format contains implicit assumptions specific to conventional gamma-ray spectrometry. Some assumptions in the current RMS format are not acceptable for the beta-gated spectra expected from the U.S. Department of Energy PNNL Automated Radioxenon Sampler-Analyzer (ARSA) and other similar systems under use or development from various countries. The RMS data format is not generally applicable for radioxenon measurements in the CTBT for one or more of the following main reasons: 1) The RMS format does not currently support 2-dimensional data. That is, the RMS data format is setup for a simple l-dimensional gamma-ray energy histogram. Current data available from the ARSA system and planned for other radioxenon monitors includes spectral information from gamma-rays and betas/conversion electrons. It is worth noting that the beta/conversion electron energy information will be used to separate the contributions from the different radioxenons. 2) The RMS data format assumes that the conversion between counts and activity can be calculated based (in part) on a simple calibration curve (detector efficiency curve) that depends only on energy of the gamma-ray. In the case of beta-gated gamma-ray spectra and for 2-dimensional spectra, there are generally two detector calibration curves that must be convoluted, the lower energy cutoff for the betas must be considered, and the energy acceptance window must be taken into account to convert counts into activity. . 3) The RMS format has header information that contains aerosol-specific information that allows the activity (Bq) calculated to be converted into a concentration (Bq/SCM). This calculation is performed by dividing the activity calculated (Bq) into number of standard cubic meters of air (SCM) passed through the filters. Most xenon-samplers do not have a 100% collection and transfer efficiency, and these efficiencies should not be assumed constant, so that the total volume flow through the sampler may not be used to convert activity into concentration. There is a pretty straightforward analogy that requires, instead, the total volume of xenon gas measured by the xenon station for the conversion. The following paper describes one possible file format for storing the multi-parameter beta-gamma coincidence spectra generated by the DOE PNNL ARSA sampler. This format proposal was generated as a draft guide to begin discussions.

  2. Swelling and folding as mechanisms of 3D shape formation in thin elastic sheets

    NASA Astrophysics Data System (ADS)

    Dias, Marcelo A.

    We work with two different mechanisms to generate geometric frustration on thin elastic sheets; isotropic differential growth and folding. We describe how controlled growth and prescribing folding patterns are useful tools for designing three-dimensional objects from information printed in two dimensions. The first mechanism is inspired by the possibility to control shapes by swelling polymer films, where we propose a solution for the problem of shape formation by asking the question, what 2D metric should be prescribed to achieve a given 3D shape?', namely the reverse problem. We choose two different types of initial configurations of sheets, disk-like with one boundary and annular with two boundaries. We demonstrate our technique by choosing four examples of 3D axisymmetric shapes and finding the respective swelling factors to achieve the desired shape. Second, we present a mechanical model for a single curved fold that explains both the buckled shape of a closed fold and its mechanical stiffness. The buckling arises from the geometrical frustration between the prescribed crease angle and the bending energy of the sheet away from the crease. This frustration increases as the sheet's area increases. Stiff folds result in creases with constant space curvature while softer folds inherit the broken symmetry of the buckled shape. We extend the application of our numerical model to show the potential to study multiple fold structures.

  3. Current sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-Frequency Assisted Discharge

    NASA Technical Reports Server (NTRS)

    Hallock, Ashley K.; Choueiri, Edgar Y.; Polzin, Kurt A.

    2007-01-01

    The inductive formation of current sheets in a conical theta pinch FARAD (Faraday Accelerator with Radio-frequency Assisted Discharge) thruster is investigated experimentally with time-integrated photography. The goal is to help in understanding the mechanisms and conditions controlling the strength and extent of the current sheet, which are two indices important for FARAD as a propulsion concept. The profiles of these two indices along the inside walls of the conical acceleration coil are assumed to be related to the profiles of the strength and extent of the luminosity pattern derived from photographs of the discharge. The variations of these profiles as a function of uniform back-fill neutral pressure (with no background magnetic field and all parameters held constant) provided the first clues on the nature and qualitative dependencies of current sheet formation. It was found that there is an optimal pressure for which both indices reach a maximum and that the rate of change in these indices with pressure differs on either side of this optimal pressure. This allowed the inference that current sheet formation follows a Townsend-like breakdown mechanism modified by the existence of a finite pressure-dependent radio-frequency-generated electron density background. The observation that the effective location of the luminosity pattern favors the exit-half of the conical coil is explained as the result of the tendency of the inductive discharge circuit to operate near its minimal self-inductance. Movement of the peak in the luminosity pattern towards the upstream side of the cone with increasing pressure is believed to result from the need of the circuit to compensate for the increase in background plasma resistivity due to increasing pressure.

  4. Landscape formation by past continental ice sheets: insights into the subglacial environment

    NASA Astrophysics Data System (ADS)

    Piotrowski, Jan A.

    2014-05-01

    Glaciers and ice sheets are known as most powerful, climatically driven agents of large-scale sediment redistribution and landscape formation in the Earth system. During the Quaternary, repeated waxing and waning of continental ice sheets contributed to profound reshaping of the Earth surface and set the scene for the development of ecosystems in the post-glacial time. Despite the well-established impact of glaciers on the upper lithosphere the specific processes of glacial erosion, transport and deposition and the formation landforms at the ice-bed interface are contentious. In particular, the relative importance of direct ice impact versus the impact of glacial meltwater is highly controversial. Here, we focus on the southern peripheral area of the Scandinavian Ice Sheet hosting thick successions of soft, deformable sediments and examine some spectacular sediment/landform assemblages found nowadays in both terrestrial and marine settings to illustrate the nature of the subglacial processes. In order to decipher the past ice sheet behavior field, experimental and numerical approaches are combined. It is shown that the strength of the coupling between the ice and the bed that controls the response of the substratum to ice overriding and stress propagation depends primarily on the ability of the glacial system to evacuate meltwater from ice-bed interface. Strong coupling, locally enhanced by subglacial permafrost resulted in deeply rooted (100's of meters) glaciotectonic deformation reflected on the surface as ice-shoved hills whereas weak coupling promoted by water accumulating under the ice triggered the formation of deep (100's of meters) tunnel valley networks. Under the arteries of fast-flowing ice known as palaeo-ice streams, remoulding of soft sediments generated mega-scale glacial lineations and drumlins that hold the key to understanding glacier dynamics. The subglacial environment is envisaged as a four-dimensional mosaic of stable and deforming spots transient in time and space whose impact is embedded in the properties of sediment/landform systems.

  5. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    PubMed Central

    Wang, Zhifa; Li, Zhijin; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

    2016-01-01

    To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration. PMID:26848656

  6. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site.

    PubMed

    Wang, Zhifa; Li, Zhijin; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

    2016-01-01

    To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration. PMID:26848656

  7. Calcofluor fluorescence assay for wort beta-glucan in a microplate format

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The widely-used fluorescent (Calcofluor) flow injection analysis method for determining the concentrations of beta-glucans in Congress worts from barley malts is adapted to microplate format. Adaptation of the Calcofluor assay to use widely available fluorescent microplate readers makes the assay m...

  8. Phosphoinositide 3-kinase p85beta regulates invadopodium formation

    PubMed Central

    Cariaga-Martínez, Ariel E.; Cortés, Isabel; García, Esther; Pérez-García, Vicente; Pajares, María J.; Idoate, Miguel A.; Redondo-Muñóz, Javier; Antón, Inés M.; Carrera, Ana C.

    2014-01-01

    ABSTRACT The acquisition of invasiveness is characteristic of tumor progression. Numerous genetic changes are associated with metastasis, but the mechanism by which a cell becomes invasive remains unclear. Expression of p85β, a regulatory subunit of phosphoinositide-3-kinase, markedly increases in advanced carcinoma, but its mode of action is unknown. We postulated that p85β might facilitate cell invasion. We show that p85β localized at cell adhesions in complex with focal adhesion kinase and enhanced stability and maturation of cell adhesions. In addition, p85β induced development at cell adhesions of an F-actin core that extended several microns into the cell z-axis resembling the skeleton of invadopodia. p85β lead to F-actin polymerization at cell adhesions by recruiting active Cdc42/Rac at these structures. In accordance with p85β function in invadopodium-like formation, p85β levels increased in metastatic melanoma and p85β depletion reduced invadopodium formation and invasion. These results show that p85β enhances invasion by inducing cell adhesion development into invadopodia-like structures explaining the metastatic potential of tumors with increased p85β levels. PMID:25217619

  9. Cell autonomous requirement for TGF-beta signaling during odontoblast differentiation and dentin matrix formation.

    PubMed

    Oka, Shoji; Oka, Kyoko; Xu, Xun; Sasaki, Tomoyo; Bringas, Pablo; Chai, Yang

    2007-07-01

    TGF-beta subtypes are expressed in tissues derived from cranial neural crest cells during early mouse craniofacial development. TGF-beta signaling is critical for mediating epithelial-mesenchymal interactions, including those vital for tooth morphogenesis. However, it remains unclear how TGF-beta signaling contributes to the terminal differentiation of odontoblast and dentin formation during tooth morphogenesis. Towards this end, we generated mice with conditional inactivation of the Tgfbr2 gene in cranial neural crest derived cells. Odontoblast differentiation was substantially delayed in the Tgfbr2(fl/fl);Wnt1-Cre mutant mice at E18.5. Following kidney capsule transplantation, Tgfbr2 mutant tooth germs expressed a reduced level of Col1a1 and Dspp and exhibited defects including decreased dentin thickness and absent dentinal tubules. In addition, the expression of the intermediate filament nestin was decreased in the Tgfbr2 mutant samples. Significantly, exogenous TGF-beta2 induced nestin and Dspp expression in dental pulp cells in the developing tooth organ. Our data suggest that TGF-beta signaling controls odontoblast maturation and dentin formation during tooth morphogenesis. PMID:17449229

  10. A density functional theory study of vibrational coupling in the amide I band of beta-sheet models.

    PubMed

    Viswanathan, Raji; Dannenberg, J J

    2008-04-24

    We report the first molecular orbital/density functional theory (DFT) calculations on the vibrational frequencies involved in the amide I band of completely geometrically optimized models for beta-sheet peptides based upon (up to 16) glycine residues. These calculations use the B3LYP/D95** level of DFT. The primary means of vibrational coupling occurs through H bond, rather than through space, interactions, which is consistent with a previous report on alpha-helical polyalanines and H-bonding chains of both formamides and 4-pyridones. We decoupled the C=O stretching vibrations using selected 14C substitutions to probe the coupling mechanism and to determine "natural" frequencies for individual 14C=Os. The intermolecular H-bonding interactions affect the geometries of the amide groups. Those near the center of H-bonding chains have long C=O bonds. The C=O bond lengths correlate with these "natural" frequencies, The frequencies obtained from the DFT calculations are generally more coupled, and the most intense are more red shifted than those calculated by transition dipole coupling (TDC). TDC inverts the order of the shifted frequencies compared to DFT in several cases. PMID:18386875

  11. Formation of thin-current layer embedded in an ion scale current sheet

    NASA Astrophysics Data System (ADS)

    Shinohara, I.; Fujimoto, M.

    2002-12-01

    We have recently found that a quick triggering of magnetic reconnection in an ion-scale current sheet is possible. For the quick triggering of magnetic reconnection, the lower-hybrid drift waves excited at the edges of the current sheet is indispensable. This wave excitation brings about formation of a thin magnetic neutral layer sustained by accelerated electrons, and this thin layer is subject to the quick reconnection. As such, the electron acceleration within the curent sheet is playing a crucial role in making the quick triggering available. We found that the electron acceleration process is strongly coupled with the non-linear evolution of the lower-hybrid drift instability. The inductive electric field, which is generated through change of the current profile, can efficiently accelerate meandering electrons around the magnetic neutral layer. As a result, elctric current in the thin layer is mostly carried by non-adiabatic electrons. We will show results of detailed analyses of this key process for the quick reonnection triggering.

  12. Effect of secondary structure on the potential of mean force for poly-L-lysine in the alpha-Helix and beta-sheet conformations

    SciTech Connect

    Grigsby, J.J.; Blanch, H.W.; Prausnitz, J.M.

    2001-10-30

    Because poly-L-lysine (PLL) can exist in the {alpha}-helix or {beta}-sheet conformation depending on solution preparation and solution conditions, PLL is a suitable candidate to probe the dependence of protein interactions on secondary structure. The osmotic second virial coefficient and weight-average molecular weight are reported from low-angle laser-light scattering measurements for PLL as a function of NaCl concentration, pH, and {alpha}-helix or {beta}-sheet content. Interactions between PLL molecules become more attractive as salt concentration increases due to screening of PLL charge by salt ions and at low salt concentration become more attractive as pH increases due to decreased net charge on PLL. The experimental results show that interactions are stronger for the {beta}-sheet conformation than for the {alpha}-helix conformation. A spherically-symmetric model for the potential of mean force is used to account for specific interactions not described by DLVO theory and to show how differences in secondary structure affect PLL interactions.

  13. Amyloid formation and inhibition of an all-beta protein: A study on fungal polygalacturonase

    NASA Astrophysics Data System (ADS)

    Chinisaz, Maryam; Ghasemi, Atiyeh; Larijani, Bagher; Ebrahim-Habibi, Azadeh

    2014-02-01

    Theoretically, all proteins can adopt the nanofibrillar structures known as amyloid, which contain cross-beta structures. The all-beta folded proteins are particularly interesting in this regard, since they appear to be naturally more predisposed toward this structural arrangement. In this study, methanol has been used to drive the beta-helix protein polygalacturonase (PG), toward amyloid fibril formation. Congo red absorbance, thioflavin T fluorescence, circular dichroism (CD) and transmission electron microscopy have been used to characterize this process. Similar to other all-beta proteins, PG shows a non-cooperative fibrillation mechanism, but the structural changes that are monitored by CD indicate a different pattern. Furthermore, several compounds containing aromatic components were tested as potential inhibitors of amyloid formation. Another protein predominantly composed of alpha-helices (human serum albumin) was also targeted by these ligands, in order to get an insight into their potential anti-aggregation property toward structurally different proteins. Among tested compounds, silibinin and chlorpropamide were able to considerably affect both proteins fibrillation process.

  14. High-Resolution Structure of a Self-Assembly-Competent Form of a Hydrophobic Peptide Captured in a Soluble [beta]-Sheet Scaffold

    SciTech Connect

    Makabe, Koki; Biancalana, Matthew; Yan, Shude; Tereshko, Valentina; Gawlak, Grzegorz; Miller-Auer, Hélène; Meredith, Stephen C.; Koide, Shohei

    2010-02-08

    {beta}-Rich self-assembly is a major structural class of polypeptides, but still little is known about its atomic structures and biophysical properties. Major impediments for structural and biophysical studies of peptide self-assemblies include their insolubility and heterogeneous composition. We have developed a model system, termed peptide self-assembly mimic (PSAM), based on the single-layer {beta}-sheet of Borrelia outer surface protein A. PSAM allows for the capture of a defined number of self-assembly-like peptide repeats within a water-soluble protein, making structural and energetic studies possible. In this work, we extend our PSAM approach to a highly hydrophobic peptide sequence. We show that a penta-Ile peptide (Ile{sub 5}), which is insoluble and forms {beta}-rich self-assemblies in aqueous solution, can be captured within the PSAM scaffold in a form capable of self-assembly. The 1.1-{angstrom} crystal structure revealed that the Ile{sub 5} stretch forms a highly regular {beta}-strand within this flat {beta}-sheet. Self-assembly models built with multiple copies of the crystal structure of the Ile5 peptide segment showed no steric conflict, indicating that this conformation represents an assembly-competent form. The PSAM retained high conformational stability, suggesting that the flat {beta}-strand of the Ile{sub 5} stretch primed for self-assembly is a low-energy conformation of the Ile{sub 5} stretch and rationalizing its high propensity for self-assembly. The ability of the PSAM to 'solubilize' an otherwise insoluble peptide stretch suggests the potential of the PSAM approach to the characterization of self-assembling peptides.

  15. Dissection of the stepwise mechanism to beta-lactam formation and elucidation of a rate-determining conformational change in beta-lactam synthetase.

    PubMed

    Raber, Mary L; Freeman, Michael F; Townsend, Craig A

    2009-01-01

    Clavulanic acid is a widely used beta-lactamase inhibitor whose key beta-lactam core is formed by beta-lactam synthetase. beta-Lactam synthetase exhibits a Bi-Ter mechanism consisting of two chemical steps, acyl-adenylation followed by beta-lactam formation. 32PPi-ATP exchange assays showed the first irreversible step of catalysis is acyl-adenylation. From a small, normal solvent isotope effect (1.38 +/- 0.04), it was concluded that beta-lactam synthesis contributes at least partially to kcat. Site-specific mutation of Lys-443 identified this residue as the ionizable group at pKa approximately 8.1 apparent in the pH-kcat profile that stabilizes the beta-lactam-forming step. Viscosity studies demonstrated that a protein conformational change was also partially rate-limiting on kcat attenuating the observed solvent isotope effect on beta-lactam formation. Adherence to Kramers' theory gave a slope of 1.66 +/- 0.08 from a plot of log(o kcat/kcat) versus log(eta/eta(o)) consistent with opening of a structured loop visible in x-ray data preceding product release. Internal "friction" within the enzyme contributes to a slope of > 1 in this analysis. Correspondingly, earlier in the catalytic cycle ordering of a mobile active site loop upon substrate binding was manifested by an inverse solvent isotope effect (0.67 +/- 0.15) on kcat/Km. The increased second-order rate constant in heavy water was expected from ordering of this loop over the active site imposing torsional strain. Finally, an Eyring plot displayed a large enthalpic change accompanying loop movement (DeltaH approximately 20 kcal/mol) comparable to the chemical barrier of beta-lactam formation. PMID:18955494

  16. Involvement of transforming growth factor-beta in the formation of fibrotic lesions in carcinoid heart disease.

    PubMed Central

    Waltenberger, J.; Lundin, L.; Oberg, K.; Wilander, E.; Miyazono, K.; Heldin, C. H.; Funa, K.

    1993-01-01

    Carcinoid heart disease is a complication of a neuroendocrine carcinoid tumor. Morphologically, it is characterized by the formation of fibrotic plaques with deposition of extracellular matrix in the subendocardium, frequently causing heart valve dysfunction and cardiac failure. Because members of the transforming growth factor-beta (TGF-beta) family are known to stimulate fibroblasts in their production of extracellular matrix, we investigated the expression of the three isoforms of TGF-beta and the binding protein for latent TGF-beta 1 (LTBP) in carcinoid plaques of the right side of the heart, as well as from control tissue, using immunohistochemistry. Tissue specimens were obtained intraoperatively from nine consecutive patients undergoing valve replacement surgery. TGF-beta 1 and TGF-beta 3 were detected in the fibroblasts of all plaques analyzed, whereas TGF-beta 2 was only rarely expressed. The localization of LTBP was partly concordant with that of TGF-beta 1, but the positive staining for LTBP was extracellular. Sections from unaffected heart tissue contained few fibroblasts in the subendocardium, showing only weak or no immunostaining for TGF-beta 1, -beta 2, and -beta 3 and no staining for LTBP. These results suggest that TGF-beta may play a role in the proliferation of fibroblasts and their matrix production in carcinoid heart lesions. Images Figure 1 p75-a Figure 2 PMID:8424467

  17. In vitro peroxidase oxidation induces stable dimers of beta-amyloid (1-42) through dityrosine bridge formation.

    PubMed

    Galeazzi, L; Ronchi, P; Franceschi, C; Giunta, S

    1999-03-01

    beta-amyloid (A beta) is a normal soluble peptide found in the cerebrospinal fluid (CSF) and other biological fluids. A beta fibrils are associated with Alzheimer's disease (AD) senile plaques. We have used purified soluble A beta (1-42) and A beta (12-28) peptides in order to determine the oxidative modification induced in these peptides by exposure to peroxidase and hydrogen peroxide. We have demonstrated that under these in vitro conditions, dimeric forms of A beta (1-42) can be detected by high-resolution polyacrylamide SDS-PAGE electrophoresis. Further experiments performed by reverse-phase high performance liquid chromatography (RP-HPLC), and monitored by fluorescence detection, showed that the dimeric A beta (1-42) forms induced by the peroxidase reaction are the outcomes of dityrosine bridge formation. This cross-link results from the enzyme catalyzed oxidation. During this reaction, phenolic coupling of tyrosine residues of two A beta (1-42) peptides occurs. No detectable peroxidative modifications were observed with the A beta (12-28) peptide which lacks a tyrosine residue. Since oxidative stress is thought to be associated with AD, the experimental model described here can help in understanding the early events leading to chemical, structural and conformational modifications before the conversion of sA beta to amyloid fibrils and eventually the formation of senile plaques in AD. PMID:10211406

  18. Involvement of dopamine receptors and beta-arrestin in metamphetamine-induced inclusions formation in PC12 cells.

    PubMed

    Fornai, Francesco; Lenzi, Paola; Capobianco, Loredana; Iacovelli, Luisa; Scarselli, Pamela; Lazzeri, Gloria; De Blasi, Antonio

    2008-06-01

    Exposure of PC12 cells to metamphetamine (MA) induces the formation of multilamellar structures (whorls) resembling autophagic granules that subsequently develop as intracellular inclusions. These inclusions stain for a variety of antigens belonging to the ubiquitin proteasome pathway. Since MA-induced intracellular bodies require the presence of dopamine in the present study we analyzed the role of dopamine (DA) receptors in producing neuronal inclusions. Moreover, we investigated potential signaling pathways which could lead to ubiquitination in the presence of MA. Based on recent reports that ubiquitination of beta-adrenergic receptors is promoted by beta-arrestin which shuttles proteins from the plasma membrane to the ubiquitin proteasome system we investigated whether beta-arrestin is involved in MA-induced inclusion formation. Our experiments document that (i) beta-arrestin was associated with MA-induced intracellular bodies; (ii) MA induced a rapid and reversible ubiquitination of beta-arrestin; (iii) dopamine antagonists reduced both MA-induced beta-arrestin ubiquitination and intracellular whorls formation; (iv) the number of MA-induced intracellular bodies was reduced in cells transfected with the beta-arrestin dominant negative mutant, betaarrV53D and was increased by the persistently ubiquitinated beta-arrestin-ubiquitin fusion protein. In conclusion, the present study demonstrates the involvement of beta-arrestin in MA-induced intracellular bodies and the participation of dopamine receptors in this process. PMID:18266935

  19. Epithelial Sheet Folding Induces Lumen Formation by Madin-Darby Canine Kidney Cells in a Collagen Gel

    PubMed Central

    Ishida, Sumire; Tanaka, Ryosuke; Yamaguchi, Naoya; Ogata, Genki; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

    2014-01-01

    Lumen formation is important for morphogenesis; however, an unanswered question is whether it involves the collective migration of epithelial cells. Here, using a collagen gel overlay culture method, we show that Madin-Darby canine kidney cells migrated collectively and formed a luminal structure in a collagen gel. Immediately after the collagen gel overlay, an epithelial sheet folded from the periphery, migrated inwardly, and formed a luminal structure. The inhibition of integrin-?1 or Rac1 activity decreased the migration rate of the peripheral cells after the sheets folded. Moreover, lumen formation was perturbed by disruption of apical-basolateral polarity induced by transforming growth factor-?1. These results indicate that cell migration and cell polarity play an important role in folding. To further explore epithelial sheet folding, we developed a computer-simulated mechanical model based on the rigidity of the extracellular matrix. It indicated a soft substrate is required for the folding movement. PMID:25170757

  20. Involvement of acid beta-glucosidase 1 in the salvage pathway of ceramide formation.

    PubMed

    Kitatani, Kazuyuki; Sheldon, Kely; Rajagopalan, Vinodh; Anelli, Viviana; Jenkins, Russell W; Sun, Ying; Grabowski, Gregory A; Obeid, Lina M; Hannun, Yusuf A

    2009-05-01

    Activation of protein kinase C (PKC) promotes the salvage pathway of ceramide formation, and acid sphingomyelinase has been implicated, in part, in providing substrate for this pathway (Zeidan, Y. H., and Hannun, Y. A. (2007) J. Biol. Chem. 282, 11549-11561). In the present study, we examined whether acid beta-glucosidase 1 (GBA1), which hydrolyzes glucosylceramide to form lysosomal ceramide, was involved in PKC-regulated formation of ceramide from recycled sphingosine. Glucosylceramide levels declined after treatment of MCF-7 cells with a potent PKC activator, phorbol 12-myristate 13-acetate (PMA). Silencing GBA1 by small interfering RNAs significantly attenuated acid glucocerebrosidase activity and decreased PMA-induced formation of ceramide by 50%. Silencing GBA1 blocked PMA-induced degradation of glucosylceramide and generation of sphingosine, the source for ceramide biosynthesis. Reciprocally, forced expression of GBA1 increased ceramide levels. These observations indicate that GBA1 activation can generate the source (sphingosine) for PMA-induced formation of ceramide through the salvage pathway. Next, the role of PKCdelta, a direct effector of PMA, in the formation of ceramide was determined. By attenuating expression of PKCdelta, cells failed to trigger PMA-induced alterations in levels of ceramide, sphingomyelin, and glucosylceramide. Thus, PKCdelta activation is suggested to stimulate the degradation of both sphingomyelin and glucosylceramide leading to the salvage pathway of ceramide formation. Collectively, GBA1 is identified as a novel source of regulated formation of ceramide, and PKCdelta is an upstream regulator of this pathway. PMID:19279011

  1. Interchange motion as a transport mechanism for formation of cold-dense plasma sheet

    NASA Astrophysics Data System (ADS)

    Wang, Chih-Ping; Gkioulidou, Matina; Lyons, Larry R.; Xing, Xiaoyan; Wolf, Richard A.

    2014-10-01

    To evaluate whether interchange motion can provide the transport for the formation of the cold-dense plasma sheet in the near-Earth region, we present an event of cold-dense plasma sheet observed by five THEMIS probes after the interplanetary magnetic field turned northward, as well as their comparisons with the simulation results from the Rice Convection Model (RCM) combined with a modified Dungey force-balanced magnetic field solver. The observations of cold-dense plasma at different locations show quite different characteristics: (1) closer to the flank, the appearance is more periodic and exhibits larger fluctuations in plasma moments and magnetic field; (2) further away from the flank, the cold plasma appears later; (3) in the mixture with the cold plasma, the decrease in high-energy particle fluxes becomes less significant further away from the flank; (4) there is energy-dispersion in the cold particles at some locations; and (5) near the magnetopause, the fluctuations have the characteristics of the Kelvin-Helmholtz (K-H) vortices and the colder-denser plasma is likely to have lower entropy. In the RCM simulations, lower entropy plasma consisting of colder-denser ions and electrons was periodically released locally at the outer boundary to represent the plasma created within a K-H vortex. This lower entropy perturbation is interchange unstable and the resulting interchange motion through the magnetosphere-ionosphere coupling pushes the colder-denser plasma radially inward. The simulated particle energy spectrums at different locations qualitatively reproduce the observations, strongly suggesting that the seemingly different characteristics of cold-dense plasma observed by different probes are all a result of the same interchange-related transport mechanism.

  2. Nonlinear evolution of three-dimensional instabilities of thin and thick electron scale current sheets: Plasmoid formation and current filamentation

    SciTech Connect

    Jain, Neeraj; Büchner, Jörg

    2014-07-15

    Nonlinear evolution of three dimensional electron shear flow instabilities of an electron current sheet (ECS) is studied using electron-magnetohydrodynamic simulations. The dependence of the evolution on current sheet thickness is examined. For thin current sheets (half thickness =d{sub e}=c/ω{sub pe}), tearing mode instability dominates. In its nonlinear evolution, it leads to the formation of oblique current channels. Magnetic field lines form 3-D magnetic spirals. Even in the absence of initial guide field, the out-of-reconnection-plane magnetic field generated by the tearing instability itself may play the role of guide field in the growth of secondary finite-guide-field instabilities. For thicker current sheets (half thickness ∼5 d{sub e}), both tearing and non-tearing modes grow. Due to the non-tearing mode, current sheet becomes corrugated in the beginning of the evolution. In this case, tearing mode lets the magnetic field reconnect in the corrugated ECS. Later thick ECS develops filamentary structures and turbulence in which reconnection occurs. This evolution of thick ECS provides an example of reconnection in self-generated turbulence. The power spectra for both the thin and thick current sheets are anisotropic with respect to the electron flow direction. The cascade towards shorter scales occurs preferentially in the direction perpendicular to the electron flow.

  3. Optimum amyloid fibril formation of a peptide fragment suggests the amyloidogenic preference of beta2-microglobulin under physiological conditions.

    PubMed

    Ohhashi, Yumiko; Hasegawa, Kazuhiro; Naiki, Hironobu; Goto, Yuji

    2004-03-12

    Beta(2)-microglobulin (beta(2)m) is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Although full-length beta(2)m readily forms amyloid fibrils in vitro by seed-dependent extension with a maximum at pH 2.5, fibril formation under physiological conditions as detected in patients has been difficult to reproduce. A 22-residue K3 peptide of beta(2)m, Ser(20)-Lys(41), obtained by digestion with Acromobacter protease I, forms amyloid fibrils without seeding. To obtain further insight into the mechanism of fibril formation, we studied the pH dependence of fibril formation of the K3 peptide and its morphology using a ThT fluorescence assay and electron microscopy, respectively. K3 peptide formed amyloid fibrils over a wide range of pH values with an optimum around pH 7 and contrasted with the pH profile of the seed-dependent extension reaction of full-length beta(2)m. This suggests that once the rigid native-fold of beta(2)m is unfolded and additional factors triggering the nucleation process are provided, full-length beta(2)m discloses an intrinsic potential to form amyloid fibrils at neutral pH. The fibril formation was strongly promoted by dimerization of K3 through Cys(25). The morphology of the fibrils varied depending on the fibril formation conditions and the presence or absence of a disulfide bond. Various fibrils had the potential to seed fibril formation of full-length beta(2)m accompanied with a characteristic lag phase, suggesting that the internal structures are similar. PMID:14699107

  4. Use of Geodetic Laser Scanning to Evaluate the Curvature of Bedrock Surfaces in an Investigation of Sheeting Joint Formation

    NASA Astrophysics Data System (ADS)

    Martel, S. J.; Mitchell, K.

    2007-12-01

    We are using aerial and tripod-mounted geodetic laser scanning (GLS) data, together with photography and large-scale geologic mapping, to investigate the formation of sheeting joints in Yosemite National Park. Sheeting joints are opening-mode fractures that form subparallel to the topography, and over broad areas in Yosemite they define the bedrock surface. Rock slabs bounded by sheeting joints superficially resemble the layers of an onion. Our hypothesis is that sheeting joints form where a tensile stress normal to the topographic surface exists in the shallow subsurface. This condition is met where k2 P22 + k3 P33 > γ cosβ, where k2 and k3 are the principal curvatures of the bedrock surface, P22 and P33 are the corresponding normal stresses parallel to the principal stresses, γ is the unit weight of the rock, and β is the slope angle. Sheeting joints are predicted where at least one of the principal curvatures is sufficiently convex (negative) and the corresponding normal stress is sufficiently compressive (negative). We use aerial GLS data with a vertical resolution of ~10 cm and a point spacing of ~1 m to measure the slope and curvature of the bedrock surface at the scale of a ridge or valley. We use tripod-mounted GLS data with a point spacing of ~5 cm, large-scale geologic mapping, and photographs to detect steps between consecutive sheeting joints, with the step height giving the sheet joint spacing. Outcrops hosting sheeting joints have a stair-step appearance with a distinctive curvature signature: high convex curvature at the top of a step, and high concave curvature at the step bottom. Steps between sheeting joints with a spacing of less than a meter or so are difficult to detect using the aerial GLS data. Apparently the interpolation of aerial data onto a grid, necessary for our curvature codes, and the smoothing of gridded data to filter out trees compromises the value of the aerial GLS data in detecting the step edges, even though the vertical resolution of the GLS data should be quite adequate for measuring the step height. A curvature code that does not require gridded data could help detect step edges. The steps can be detected readily with the tripod-mounted GLS data, large-scale geologic mapping, and photographs, which show shadows cast by the steps. Our analyses to date with all the data sets supports our hypothesis for sheet joint formation.

  5. Two distinct β-sheet structures in Italian-mutant amyloid-beta fibrils: a potential link to different clinical phenotypes.

    PubMed

    Hubin, Ellen; Deroo, Stéphanie; Schierle, Gabriele Kaminksi; Kaminski, Clemens; Serpell, Louise; Subramaniam, Vinod; van Nuland, Nico; Broersen, Kerensa; Raussens, Vincent; Sarroukh, Rabia

    2015-12-01

    Most Alzheimer's disease (AD) cases are late-onset and characterized by the aggregation and deposition of the amyloid-beta (Aβ) peptide in extracellular plaques in the brain. However, a few rare and hereditary Aβ mutations, such as the Italian Glu22-to-Lys (E22K) mutation, guarantee the development of early-onset familial AD. This type of AD is associated with a younger age at disease onset, increased β-amyloid accumulation, and Aβ deposition in cerebral blood vessel walls, giving rise to cerebral amyloid angiopathy (CAA). It remains largely unknown how the Italian mutation results in the clinical phenotype that is characteristic of CAA. We therefore investigated how this single point mutation may affect the aggregation of Aβ1-42 in vitro and structurally characterized the resulting fibrils using a biophysical approach. This paper reports that wild-type and Italian-mutant Aβ both form fibrils characterized by the cross-β architecture, but with distinct β-sheet organizations, resulting in differences in thioflavin T fluorescence and solvent accessibility. E22K Aβ1-42 oligomers and fibrils both display an antiparallel β-sheet structure, in comparison with the parallel β-sheet structure of wild-type fibrils, characteristic of most amyloid fibrils described in the literature. Moreover, we demonstrate structural plasticity for Italian-mutant Aβ fibrils in a pH-dependent manner, in terms of their underlying β-sheet arrangement. These findings are of interest in the ongoing debate that (1) antiparallel β-sheet structure might represent a signature for toxicity, which could explain the higher toxicity reported for the Italian mutant, and that (2) fibril polymorphism might underlie differences in disease pathology and clinical manifestation. PMID:26190022

  6. Protein secondary structures (alpha-helix and beta-sheet) at a cellular level and protein fractions in relation to rumen degradation behaviours of protein: a new approach.

    PubMed

    Yu, Peiqiang

    2005-11-01

    Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the alpha-helix and beta-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of beta-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution ( approximately 10 microm). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of alpha-helixes and beta-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P<0.05) the percentage of alpha-helixes (from 47.1 % to 36.1 %: S-FTIR absorption intensity), increased the percentage of beta-sheets (from 37.2 % to 49.8 %: S-FTIR absorption intensity) and reduced the alpha-helix to beta-sheet ratio (from 0.3 to 0.7) in the golden flaxseeds, which indicated a negative effect of the roasting on protein values, utilisation and bioavailability. These results were proved by the Cornell Net Carbohydrate Protein System in situ animal trial, which also revealed that roasting increased the amount of protein bound to lignin, and well as of the Maillard reaction protein (both of which are poorly used by ruminants), and increased the level of indigestible and undegradable protein in ruminants. The present results demonstrate the potential of highly spatially resolved synchrotron-based infrared microspectroscopy to locate 'pure' protein in feed tissues, and reveal protein secondary structures and digestive behaviour, making a significant step forward in and an important contribution to protein nutritional research. Further study is needed to determine the sensitivities of protein secondary structures to various heat-processing conditions, and to quantify the relationship between protein secondary structures and the nutrient availability and digestive behaviour of various protein sources. Information from the present study arising from the synchrotron-based IR probing of the protein secondary structures of protein sources at the cellular level will be valuable as a guide to maintaining protein quality and predicting digestive behaviours. PMID:16277766

  7. Protein Secondary Structures (alpha-helix and beta-sheet) at a Cellular Levle and Protein Fractions in Relation to Rumen Degradation Behaviours of Protein: A New Approach

    SciTech Connect

    Yu,P.

    2007-01-01

    Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the {alpha}-helix and {beta}-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of {beta}-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution ({approx}10 {mu}m). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of {alpha}-helixes and {beta}-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P <0.05) the percentage of {alpha}-helixes (from 47.1% to 36.1%: S-FTIR absorption intensity), increased the percentage of {beta}-sheets (from 37.2% to 49.8%: S-FTIR absorption intensity) and reduced the {alpha}-helix to {beta}-sheet ratio (from 0.3 to 0.7) in the golden flaxseeds, which indicated a negative effect of the roasting on protein values, utilisation and bioavailability. These results were proved by the Cornell Net Carbohydrate Protein System in situ animal trial, which also revealed that roasting increased the amount of protein bound to lignin, and well as of the Maillard reaction protein (both of which are poorly used by ruminants), and increased the level of indigestible and undegradable protein in ruminants. The present results demonstrate the potential of highly spatially resolved synchrotron-based infrared microspectroscopy to locate 'pure' protein in feed tissues, and reveal protein secondary structures and digestive behaviour, making a significant step forward in and an important contribution to protein nutritional research. Further study is needed to determine the sensitivities of protein secondary structures to various heat-processing conditions, and to quantify the relationship between protein secondary structures and the nutrient availability and digestive behaviour of various protein sources. Information from the present study arising from the synchrotron-based IR probing of the protein secondary structures of protein sources at the cellular level will be valuable as a guide to maintaining protein quality and predicting digestive behaviours.

  8. Analysis of Nugget Formation During Resistance Spot Welding on Dissimilar Metal Sheets of Aluminum and Magnesium Alloys

    NASA Astrophysics Data System (ADS)

    Luo, Yi; Li, Jinglong

    2014-10-01

    The nugget formation of resistance spot welding (RSW) on dissimilar material sheets of aluminum and magnesium alloys was studied, and the element distribution, microstructure, and microhardness distribution near the joint interface were analyzed. It was found that the staggered high regions at the contact interface of aluminum and magnesium alloy sheets, where the dissimilar metal melted together, tended to be the preferred nucleation regions of nugget. The main technical problem of RSW on dissimilar metal sheets of aluminum and magnesium alloys was the brittle-hard Al12Mg17 intermetallic compounds distributed in the nugget, with hardness much higher than either side of the base materials. Microcracks tended to generate at the interface of the nugget and base materials, which affected weld quality and strength.

  9. Formation of a very thin current sheet in the near-earth magnetotail and the explosive growth phase of substorms

    NASA Technical Reports Server (NTRS)

    Lee, L. C.; Zhang, L.; Choe, G. S.; Cai, H. J.

    1995-01-01

    A magnetofricional method is used to construct two-dimensional MHD equilibria of the Earth's magnetosphere for a given distribution of entropy functions(S = pV(exp gamma), where p is the plasma pressure and V is the tube volume per unit magnetic flux. It is found that a very thin current sheet with B (sub zeta) is less than 0.5 nu T and thickness less than 1000 km can be formed in the near-earth magnetotail (x is approximately -8 to -20R(sub e) during the growth phase of substorm. The tail current sheets are found to become thinner as the entropy or the entropy gradient increases. It is suggested that the new entropy anti-diffusion instability associated with plasma transport across field lines leads to magnetic field dipolarization and accelerates the formation of thin current sheet, which may explain the observed explosive growth phase of substorms.

  10. Inducing ?-Sheets Formation in Synthetic Spider Silk Fibers by Aqueous Post-Spin Stretching

    PubMed Central

    Hinman, Michael B.; Holland, Gregory P.; Yarger, Jeffery L.; Lewis, Randolph V.

    2012-01-01

    As a promising biomaterial with numerous potential applications, various types of synthetic spider silk fibers have been produced and studied in an effort to produce manmade fibers with mechanical and physical properties comparable to those of native spider silk. In this study, two recombinant proteins based on Nephila clavipes Major ampullate Spidroin 1 (MaSp1) consensus repeat sequence were expressed and spun into fibers. Mechanical test results showed that fiber spun from the higher molecular weight protein had better overall mechanical properties (70 KD versus 46 KD), whereas postspin stretch treatment in water helped increase fiber tensile strength significantly. Carbon-13 solid-state NMR studies of those fibers further revealed that the postspin stretch in water promoted protein molecule rearrangement and the formation of ?-sheets in the polyalanine region of the silk. The rearrangement correlated with improved fiber mechanical properties and indicated that postspin stretch is key to helping the spider silk proteins in the fiber form correct secondary structures, leading to better quality fibers. PMID:21574576

  11. Repetitive formation and decay of current sheets in magnetic loops: An origin of diverse magnetic structures

    SciTech Connect

    Kumar, Dinesh; Bhattacharyya, R.; Smolarkiewicz, P. K.

    2015-01-15

    In this work, evolution of an incompressible, thermally homogeneous, infinitely conducting, viscous magnetofluid is numerically explored as the fluid undergoes repeated events of magnetic reconnection. The initial magnetic field is constructed by a superposition of two linear force-free fields and has similar morphology as the magnetic loops observed in the solar corona. The results are presented for computations with three distinct sets of footpoint geometries. To onset reconnection, we rely on numerical model magnetic diffusivity, in the spirit of implicit large eddy simulation. It is generally expected that in a high Lundquist number fluid, repeated magnetic reconnections are ubiquitous and hence can lead to a host of magnetic structures with considerable observational importance. In particular, the simulations presented here illustrate formations of magnetic islands, rotating magnetic helices and rising flux ropesdepending on the initial footpoint geometry but through the common process of repeated magnetic reconnections. Further, we observe the development of extended current sheets in two case studies, where the footpoint reconnections generate favorable dynamics.

  12. A multimeric quinacrine conjugate as a potential inhibitor of Alzheimer's beta-amyloid fibril formation.

    PubMed

    Dolphin, Gunnar T; Chierici, Sabine; Ouberai, Myriam; Dumy, Pascal; Garcia, Julian

    2008-04-14

    Amyloid formation and accumulation of the amyloid beta-peptide (Abeta) in the brain is associated with Alzheimer's disease (AD) pathogenesis. Therefore, among the therapeutic approaches in development to fight the disease, the direct inhibition of the Abeta self-assembly process is currently widely investigated and is one of the most promising approaches. In this study we investigated the potential of a multimeric display of quinacrine derivatives, as compared to the monomer quinacrine, as a design principal for a novel class of inhibitors against Abeta fibril formation. The presented multimeric conjugate exhibits a cluster of four quinacrine derivatives on a rigid cyclopeptidic scaffold. Herein is reported the synthesis of the conjugate, together with the in vitro inhibitory evaluation of Abeta(1-40) fibrils using the thioflavin T fluorescence assay, and imaging with atomic force microscopy. Our data show that the multimeric compound inhibits Abeta(1-40) fibril formation with an IC(50) value of 20+/-10 microM, which contrasts with the nonactive monomeric analogue. This work suggests that assembling multiple copies of acridine moieties to a central scaffold, for multiple interactions, is a promising strategy for the engineering of inhibitors against Abeta fibril formation. PMID:18330854

  13. Dynamics of beta-amyloid peptide in cholesterol superlattice domain

    NASA Astrophysics Data System (ADS)

    Smirnov, Anton; Zhu, Qing; Vaughn, Mark; Khare, Rajesh; Cheng, K.

    2006-10-01

    Presence of beta-amyloid peptide (beta-A) plagues in membranes of neuron cells is a clinical signature of Alzheimer disease. The onset of beta-A peptide aggregation occurs via a conformational transition from an alpha-helix state to a beta-sheet state. A gradual build-up of beta-A content in the neuronal extracellular space is another characteristic of the beta-A plague formation. Hypothetically, both the pathological conformation and the predominant localization of the beta-A can be a result of specific dynamic characteristics of the interphase between cellular membrane and extracellular milieu. In this study, the beta-A interphase problem has been investigated using a virtual membrane model implemented on the base of GROMACS molecular dynamics simulation package. The detailed folding pattern of beta-A has been examined using a novice interphase model comprised of a cholesterol supperlattice membrane and two water layers.

  14. Biological activities and pore formation of Clostridium perfringens beta toxin in HL 60 cells.

    PubMed

    Nagahama, Masahiro; Hayashi, Shinya; Morimitsu, Shinsuke; Sakurai, Jun

    2003-09-19

    Clostridium perfringens beta toxin is an important agent of necrotic enteritis. Of the 10 cell lines tested, only the HL 60 cell line was susceptible to beta toxin. The toxin induced swelling and lysis of the cell. Treatment of the cells with the toxin resulted in K+ efflux from the cells and Ca2+, Na+, and Cl- influxes. These events reached a maximum just before the cells were lysed by the toxin. Incubation of the cells with the toxin showed the formation of toxin complexes of about 191 and 228 kDa, which were localized in the domains that fulfilled the criteria of lipid rafts. The complex of 228 kDa was observed until 30 min after incubation, and only the complex of 191 kDa was remained after 60 min. Treatment of the cells with methyl-beta-cyclodextrin or cholesterol oxidase blocked binding of the toxin to the rafts and the toxin-induced K+ efflux and swelling. The toxin-induced Ca2+ influx and morphological changes were inhibited by an increase in the hydrodynamic diameter of polyethylene glycols from 200 to 400 and markedly or completely inhibited by polyethylene glycol 600 and 1000. However, these polyethylene glycols had no effect on the toxin-induced K+ efflux. The toxin induced carboxyfluorescein release from phosphatidyl-choline-cholesterol liposomes containing carboxyfluorescein and formed an oligomer with 228 kDa in a dose-dependent manner but did not form an oligomer with the 191-kDa complex. We conclude that the toxin acts on HL 60 cells by binding to lipid rafts and forming a functional oligomer with 228 kDa. PMID:12851396

  15. Formation of High-Beta Plasma and Stable Confinement of Toroidal Electron Plasma in RT-1

    NASA Astrophysics Data System (ADS)

    Saitoh, Haruhiko

    2010-11-01

    The Ring Trap 1 (RT-1) device is a laboratory magnetosphere generated by a levitated superconducting magnet. The goals of RT-1 are to realize stable formation of ultra high-beta plasma suitable for burning advanced fusion fuels, and confinement of toroidal non-neutral plasmas including antimatter particles. RT- 1 has produced high-beta plasma in the magnetospheric configuration. The effects of coil levitation and geomagnetic field compensation [Y. Yano et al., Plasma Fusion Res. 4, 039] resulted drastic improvements of the plasma properties, and a maximum local beta value exceeded 70%. Because plasma is generated by electron cyclotron resonance heating (ECH) in the present experiment, the plasma pressure is mainly due to hot electrons, whose bremsstrahlung was observed with an x-ray CCD camera. The pressure profiles have rather steep gradient near the superconducting coil in the strong field region. The decay rates of magnetic probe and interferometer signals have different time constants, suggesting multiple temperature components. The energy confinement time estimated from the input RF power and stored magnetic energy is on the order of 1s, which is comparable to the decay time constant of the density of hot electron component. Pure electron plasma experiments are also conducted in RT-1. Radial profiles of electrostatic potential and electron density showed that the plasma rigidly rotates in the toroidal direction in the stable confinement phase. Long time confinement of toroidal non- neutral plasma for more than 300s and inward particle diffusion to strong field regions, caused by the activation of the diocotron (Kelvin-Helmholtz) instability, have been realized [Z. Yoshida et al., Phys. Rev. Lett. 104, 235004].

  16. The effect of low levels of dopants upon the formation and properties of beta-phase molybdenum nitride

    SciTech Connect

    Cairns, A.G.; Gallagher, J.G.; Hargreaves, J.S.J.; Mckay, D.; Rico, J.L.; Wilson, K.

    2010-03-15

    The addition of 1 wt% Pd, Au, Ni and Cu dopants has been demonstrated to strongly alter the morphology of beta-phase molybdenum nitride prepared by treatment of MoO{sub 3} with a 3/1 H{sub 2}/N{sub 2} mixture at 750 deg. C. Furthermore, the addition of Pd significantly enhances the surface area and the formation of the nitride phase. It is proposed that the facile formation of molybdenum bronzes in this system is important in this respect. The dopants have also been observed to modify the denitridation characteristics of the beta-phase, with an overall reduction of the proportion of NH{sub 3} formed upon using a 3/1 H{sub 2}/Ar mixture with respect to the undoped sample. - Graphical abstract: Low levels of Pd, Au, Ni and Cu dopant have significant effects upon the morphology, formation and dentitridation characteristics of beta-phase molybdenum nitride.

  17. Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice.

    PubMed

    Sarkar, Sumit; Raymick, James; Ray, Balmiki; Lahiri, Debomoy K; Paule, Merle G; Schmued, Larry

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40 mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain. PMID:26510980

  18. Formation kinetics and structural features of Beta-amyloid aggregates by sedimented solute NMR.

    PubMed

    Bertini, Ivano; Gallo, Gianluca; Korsak, Magdalena; Luchinat, Claudio; Mao, Jiafei; Ravera, Enrico

    2013-09-23

    The accumulation of soluble toxic beta-amyloid (A?) aggregates is an attractive hypothesis for the role of this peptide in the pathology of Alzheimer's disease. We have introduced sedimentation through ultracentrifugation, either by magic angle spinning (in situ) or preparative ultracentrifuge (ex situ), to immobilize biomolecules and make them amenable for solid-state NMR studies (SedNMR). In situ SedNMR is used here to address the kinetics of formation of soluble A? assemblies by monitoring the disappearance of the monomer and the appearance of the oligomers simultaneously. Ex situ SedNMR allows us to select different oligomeric species and to reveal atomic-level structural features of soluble A? assemblies. PMID:23821412

  19. Inhibitory effects of nisin-coated multi-walled carbon nanotube sheet on biofilm formation from Bacillus anthracis spores.

    PubMed

    Dong, Xiuli; McCoy, Eric; Zhang, Mei; Yang, Liju

    2014-12-01

    Multi-walled carbon nanotube (MWCNT) sheet was fabricated from a drawable MWCNT forest and then deposited on poly(methyl methacrylate) film. The film was further coated with a natural antimicrobial peptide nisin. We studied the effects of nisin coating on the attachment of Bacillus anthracis spores, the germination of attached spores, and the subsequent biofilm formation from attached spores. It was found that the strong adsorptivity and the super hydrophobicity of MWCNTs provided an ideal platform for nisin coating. Nisin coating on MWCNT sheets decreased surface hydrophobicity, reduced spore attachment, and reduced the germination of attached spores by 3.5 fold, and further inhibited the subsequent biofilm formation by 94.6% compared to that on uncoated MWCNT sheet. Nisin also changed the morphology of vegetative cells in the formed biofilm. The results of this study demonstrated that the anti-adhesion and antimicrobial effect of nisin in combination with the physical properties of carbon nanotubes had the potential in producing effective anti-biofilm formation surfaces. PMID:25499501

  20. A study of the formation and dynamics of the Earth's plasma sheet using ion composition data

    NASA Technical Reports Server (NTRS)

    Lennartsson, O. W.

    1994-01-01

    Over two years of data from the Lockheed Plasma Composition Experiment on the ISEE 1 spacecraft, covering ion energies between 100 eV/e and about 16 keV/e, have been analyzed in an attempt to extract new information about three geophysical issues: (1) solar wind penetration of the Earth's magnetic tail; (2) relationship between plasma sheet and tail lobe ion composition; and (3) possible effects of heavy terrestrial ions on plasma sheet stability.

  1. Doubling the cross-linking interface of a rationally designed beta roll peptide for calcium-dependent proteinaceous hydrogel formation.

    PubMed

    Dooley, Kevin; Bulutoglu, Beyza; Banta, Scott

    2014-10-13

    We have rationally engineered a stimulus-responsive cross-linking domain based on a repeats-in-toxin (RTX) peptide to enable calcium-dependent formation of supramolecular hydrogel networks. The peptide isolated from the RTX domain is intrinsically disordered in the absence of calcium. In calcium rich environments, the peptide binds Ca(2+) ions and folds into a beta roll (?-roll) secondary structure composed to two parallel ?-sheet faces. Previously, we mutated one of the faces to contain solvent exposed leucine side chains which are localized only in the calcium-bound ?-roll conformation. We demonstrated the ability of this mutant peptide to self-assemble into hydrogels in the presence of calcium with the aid of additional peptide-based cross-linking moieties. Here, we have expanded this approach by engineering both ?-roll faces to contain leucine residues, thereby doubling the cross-linking interface for each monomeric building block. These leucine rich surfaces impart a hydrophobic driving force for self-assembly. Extensive characterization was performed on this double-faced mutant to ensure the retention of calcium affinity and subsequent structural rearrangement similar to that of the wild type domain. We genetically fused an ?-helical leucine zipper capable of forming tetrameric coiled-coil bundles to the peptide and the resulting chimeric protein self-assembles into a hydrogel only in calcium rich environments. Since this new mutant peptide enables cross-linking on both surfaces simultaneously, a higher oligomerization state was achieved. To further investigate the cross-linking capability, we constructed concatemers of the ?-roll with maltose binding protein (MBP), a monomeric globular protein, without the leucine zipper domains. These concatemers show a similar sol-gel transition in response to calcium. Several biophysical techniques were used to probe the structural and mechanical properties of the mutant ?-roll domain and the resulting supramolecular networks including circular dichroism, fluorescence resonance energy transfer, bis-ANS binding, and microrheology. These results demonstrate that the engineered ?-roll peptides can mediate calcium-dependent cross-linking for protein hydrogel formation without the need for any other cross-linking moieties. PMID:25226243

  2. Vitamin C Treatment Promotes Mesenchymal Stem Cell Sheet Formation and Tissue Regeneration by Elevating Telomerase Activity

    PubMed Central

    Wei, F.L.; Qu, C.Y.; Song, T.L.; Ding, G.; Fan, Z.P.; Liu, D.Y.; Liu, Y.; Zhang, C.M.; Shi, S.; Wang, S.L.

    2011-01-01

    Cell sheet engineering has been developed as an alternative approach to improve mesenchymal stem cell-mediated tissue regeneration. In this study, we found that vitamin C (Vc) was capable of inducing telomerase activity in periodontal ligament stem cells (PDLSCs), leading to the up-regulated expression of extracellular matrix type I collagen, fibronectin, and integrin β1, stem cell markers Oct4, Sox2, and Nanog as well as osteogenic markers RUNX2, ALP, OCN. Under Vc treatment, PDLSCs can form cell sheet structures because of increased cell matrix production. Interestingly, PDLSC sheets demonstrated a significant improvement in tissue regeneration compared with untreated control dissociated PDLSCs and offered an effective treatment for periodontal defects in a swine model. In addition, bone marrow mesenchymal stem cell sheets and umbilical cord mesenchymal stem cell sheets were also well constructed using this method. The development of Vc-mediated mesenchymal stem cell sheets may provide an easy and practical approach for cell-based tissue regeneration. PMID:22105792

  3. Maturation induced internalization of beta 1-integrin by Xenopus oocytes and formation of the maternal integrin pool.

    PubMed

    Müller, A H; Gawantka, V; Ding, X; Hausen, P

    1993-07-01

    A pool of beta 1-integrin, ready to be inserted into the cleavage membranes, is present in the cytoplasm of the Xenopus egg, while its plasma membrane is devoid of this membrane protein (Gawantka et al., 1992). The underlying mechanisms that lead to this specific pattern of beta 1-integrin distribution in the egg have been investigated. beta 1-Integrin is present on the oocyte membrane throughout oogenesis. During maturation the oocyte membrane is cleared of beta 1-integrin via internalization of the protein by the oocyte. Synthesis of beta 1-integrin precursor is stimulated moderately in the maturing oocyte. At the same time processing of the precursor into the mature form of beta 1-integrin and its complexing with a putative alpha-chain is greatly accelerated. This way a maternal integrin pool accumulates in the mature oocyte. It is localized in conspicuous yolk free patches which contain large amounts of endoplasmic reticulum, Golgi complexes and smooth vesicles. We suggest that membrane vesicles harbouring the beta 1-integrin are generated in these cytoplasmic regions and that this store of vesicles provides the material source for the rapid membrane formation during cleavage. PMID:7690240

  4. Protonation of a neutral (S)-beta-bisabolene intermediate is involved in (S)-beta-macrocarpene formation by the maize sesquiterpene synthases TPS6 and TPS11.

    PubMed

    Kllner, Tobias G; Schnee, Christiane; Li, Shenghong; Svatos, Ales; Schneider, Bernd; Gershenzon, Jonathan; Degenhardt, Jrg

    2008-07-25

    Terpene synthases are responsible for the large diversity of terpene carbon skeletons found in plants. The unique, carbocationic reaction mechanism of these enzymes can form multiple products from a single prenyl diphosphate substrate. Two maize genes were isolated that encode very similar sesquiterpene synthases, TPS6 and TPS11, which both produce beta-bisabolene, a common monocyclic sesquiterpene, and beta-macrocarpene, an uncommon bicyclic olefin. Investigation of the reaction mechanism showed that the formation of beta-macrocarpene proceeds via a neutral beta-bisabolene intermediate and requires reprotonation by a proton that may ultimately be abstracted from water. This reprotonation is dependent on the pH and the presence of a Mg(2+) cofactor. Mutational analysis of the enzyme demonstrated that a highly conserved tyrosine residue in the active center of the enzymes is important for the protonation process. TPS6 and TPS11 are transcribed both in leaves and roots of maize, but the respective terpene products were only detected in roots. The expression in roots was up-regulated by herbivore damage to the leaves, suggesting a long distance signal transduction cascade between leaves and roots. PMID:18524777

  5. Formation of Sheeting Joints as a Result of Compression Parallel to Convex Surfaces, With Examples from Yosemite National Park, California

    NASA Astrophysics Data System (ADS)

    Martel, S. J.

    2008-12-01

    The formation of sheeting joints has been an outstanding problem in geology. New observations and analyses indicate that sheeting joints develop in response to a near-surface tension induced by compressive stresses parallel to a convex slope (hypothesis 1) rather than by removal of overburden by erosion, as conventionally assumed (hypothesis 2). Opening mode displacements across the joints together with the absence of mineral precipitates within the joints mean that sheeting joints open in response to a near-surface tension normal to the surface rather than a pressurized fluid. Consideration of a plot of this tensile stress as a function of depth normal to the surface reveals that a true tension must arise in the shallow subsurface if the rate of that tensile stress change with depth is positive at the surface. Static equilibrium requires this rate (derivative) to equal P22 k2 + P33 k3 - ρ g cosβ, where k2 and k3 are the principal curvatures of the surface, P22 and P33 are the respective surface- parallel normal stresses along the principal curvatures, ρ is the material density, g is gravitational acceleration, and β is the slope. This derivative will be positive and sheeting joints can open if at least one principal curvature is sufficiently convex (negative) and the surface-parallel stresses are sufficiently compressive (negative). At several sites with sheeting joints (e.g., Yosemite National Park in California), the measured topographic curvatures and the measured surface-parallel stresses of about -10 MPa combine to meet this condition. In apparent violation of hypothesis 1, sheeting joints occur locally at the bottom of Tenaya Canyon, one of the deepest glaciated, U-shaped (concave) canyons in the park. The canyon-bottom sheeting joints only occur, however, where the canyon is convex downstream, a direction that nearly coincides with direction of the most compressive stress measured in the vicinity. The most compressive stress acting along the convex downstream curvature promotes the opening of the joints, whereas the compressive stress acting across the U-shaped valley promotes closure of the joints. Apparently the former more than compensates for the latter. Finally, the abundance of sheeting joints on convex ridges, where erosion is a local minimum, coupled with their scarcity in the adjacent concave valleys, where erosion is a local maximum, is consistent with hypothesis 1 but inconsistent with hypothesis 2.

  6. Solvent effects on self-assembly of beta-amyloid peptide.

    PubMed Central

    Shen, C L; Murphy, R M

    1995-01-01

    beta-amyloid peptide (A beta) is the primary protein component of senile plaques in Alzheimer's disease patients. Synthetic A beta spontaneously assembles into amyloid fibrils and is neurotoxic to cortical cultures. Neurotoxicity has been associated with the degree of peptide aggregation, yet the mechanism of assembly of A beta into amyloid fibrils is poorly understood. In this work, A beta was dissolved in several different solvents commonly used in neurotoxicity assays. In pure dimethylsulfoxide (DMSO), A beta had no detectable beta-sheet content; in 0.1% trifluoroacetate, the peptide contained one-third beta-sheet; and in 35% acetonitrile/0.1% trifluoroacetate, A beta was two-thirds beta-sheet, equivalent to the fibrillar peptide in physiological buffer. Stock solutions of peptide were diluted into phosphate-buffered saline, and fibril growth was followed by static and dynamic light scattering. The growth rate was substantially faster when the peptide was predissolved in 35% acetonitrile/0.1% trifluoroacetate than in 0.1% trifluoroacetate, 10% DMSO, or 100% DMSO. Differences in growth rate were attributed to changes in the secondary structure of the peptide in the stock solvent. These results suggest that formation of an intermediate with a high beta-sheet content is a controlling step in A beta self-assembly. PMID:8527678

  7. Diagnostics of basal conditions - the formation of extensive zones of surface ribs in ice-sheets and streams

    NASA Astrophysics Data System (ADS)

    Hindmarsh, Richard C. A.; Sergienko, Olga V.; Creyts, Timothy T.

    2015-04-01

    Most if not all current predictions of the evolution of ice-streams to changes induced by global change assume static basal conditions. This is a result of current restrictions in the remote sensing of the ice-sheet basal physical environment, which cannot resolve the small-scale phenomena believed to control the basal traction. The search therefore is on for observable structures or features that are the result of the operation of basal processes. Any successful theory of ice-sheet basal processes would need to be able to explain such phenomena associated with or caused by special properties of the basal environment. We present one class of these phenomena, and also present tentative hypotheses as to their formation. Using recent high-resolution observations of the Antarctic and Greenland ice sheets topography, the computed driving stress and the inferred basal traction reveal broad-scale organization in 5-20 km band-like patterns in both quantities. The similarity of patterns on the Greenland and Antarctic ice sheets suggests that the flow of ice sheets is controlled by the same fundamental processes operating at their base, which control ice sheet sliding and are highly variable on relatively short spatial and temporal scales. The formation mechanism for these bands contains information about the operation of the sub-glacial system. There are three possible, non-exclusive causes of these ribs which we examine from a theoretical and evidential point-of-view (i) They are the surface response to similar bands in the basal topography, whose regularity would equally require an explanation in terms of basal processes. (ii) They are translating surface waves in the ice, supported by membrane stress gradients rather than by gradients in the basal resistance. (iii) The ribs are due to the development of a band-like structure in the basal shear stress distribution that is the result of a pattern-forming instability in sub-glacial till and water flow, perhaps related to the formation of sub-glacial landforms.

  8. Inhibition of bacterial cell wall-induced leukocyte recruitment and hepatic granuloma formation by TGF-beta gene transfer.

    PubMed

    Song, X; Zeng, L; Pilo, C M; Zagorski, J; Wahl, S M

    1999-10-01

    Intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats results in dissemination of SCW to the liver, spleen, bone marrow, and peripheral joints. The uptake of SCW by Kupffer cells in the liver initiates a chain of events largely mediated by T lymphocytes and macrophages. Local synthesis and secretion of cytokines and growth factors in response to the persistent SCW lead to the evolution and maintenance of a chronic T cell-dependent granulomatous response and result in granuloma formation and irreversible hepatic fibrosis. In an attempt to impede the development of the chronic granulomatous lesions in the liver, we injected a plasmid DNA encoding TGF-beta 1 i.m. to the SCW animals to determine the effect of TGF-beta 1 gene transfer on the course of liver inflammation and fibrosis. A single injection of plasmid DNA encoding TGF-beta 1 resulted in virtual abolition of the development of the SCW-induced hepatic granuloma formation and matrix expansion. TGF-beta 1 DNA not only reduced key proinflammatory cytokines including TNF-alpha, IL-1 beta, IFN-gamma, and IL-18, but also inhibited both CXC and CC chemokine production, thereby blocking inflammatory cell recruitment and accumulation in the liver. Moreover, TGF-beta 1 gene delivery inhibited its own expression in the liver tissue, which is otherwise up-regulated in SCW-injected animals. Our study suggests that TGF-beta 1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus may provide a new approach to the control of hepatic granulomatous and fibrotic diseases. PMID:10491005

  9. The formation of ice rises, their dynamics and role in the deglaciation of the Antarctic ice sheet

    NASA Astrophysics Data System (ADS)

    Favier, Lionel; Pattyn, Frank

    2015-04-01

    Numerous underwater mountains emerge from the edge of the continental shelf around the Antarctic ice sheet. During the last deglaciation, those features gave birth to ice rises, each being small scale copies of a continental ice sheet characterised by an ice divide and a local flow going outwards embedded within the fringing ice shelves. The well-known millenium-scale stability of ice rises can be strong indicators for the past deglaciation termination. However, the interpretation of physical measurements of an ice rise is not straightforward due to unknown past ice dynamics. Here, using the Bisicles ice-sheet model, we investigate for the first time the formation of an ice rise on top of an underwater mountain during the retreat of an ideal Antarctic-like ice sheet (i.e., including both grounded and floating ice flow). Prior to the retreat, the underwater mountain is barely detectable from the ice surface geometry and velocity. During the ice sheet retreat, induced by an increase of the sea level, an ice divide develops quickly above the underwater mountain. Within a short period of hundreds of years, the ice rise adopts a thousand years stability along with two main features: (i) a shifted upstream position of the ice rise compared to the mountain underneath and (ii) a geometrical asymmetry of the ice rise showing a gentle slope upstream and a steep slope downstream. We also investigate the influence of a non uniform surface mass balance on the migration of the ice divide. Our results provide additional ice dynamical constraints to facilitate numerical reconstructions of the last deglacial history in Antarctica as we demonstrate that ice rises are stable, but transient features of the ice shelf, stabilizing fast outlet flow. The timing of pinning and unpinning therefore becomes crucial in simulating the episodes of slow and fast grounding line retreat, respectively.

  10. Visions of ice sheets in the early Ordovician greenhouse world: Evidence from the Peninsula Formation, Cape Peninsula, South Africa

    NASA Astrophysics Data System (ADS)

    Turner, Brian R.; Armstrong, Howard A.; Holt, Peter

    2011-05-01

    The depositional architecture within the Early Ordovician, Peninsula Formation, South Africa, indicates a three-tier stratal sequence hierarchy comprising likely 4th order autogenic, 3rd order allogenic and 2nd order regressive-transgressive sequence stacking pattern. Based on correlation with the global eustatic sea level curve, we interpret the 3rd order sequences, comprising predominantly lowstand braided fluvial deposits with thin early transgressive system tract marginally marine sandstones, as orbitally induced, glacioeustacy. Eustacy affected sand delivery, base level changes and discharge patterns. The Cape Peninsula lay at ~ 30S during the Early Ordovician yet the primary control on sedimentation was the waxing and waning of ice sheets in the source area. We hypothesize the presence of an Early Ordovician ice sheet of 8-12 10 6 km 3 and a Polar Front at ~ 40S.

  11. Semaphorin 3A blocks the formation of pathologic choroidal neovascularization induced by transforming growth factor beta

    PubMed Central

    Bai, Yujing; Liang, Shuting; Zhao, Min; Huang, Lvzhen; Zhao, Mingwei; Li, Xiaoxin

    2014-01-01

    Objective Choroidal neovascularization (CNV) is a major cause of vision loss in retinal diseases such as age-related macular degeneration (AMD). Previously, we demonstrated that semaphorin3A (Sema3A), which is a chemorepellent guidance molecule, inhibited the formation of retina neovascularization. In the present study, we investigated the antiangiogenic effects of Sema3A on transforming growth factor beta (TGF-?) in vitro and in vivo. Methods Enzyme-linked immunosorbent assays (ELISAs) were used to measure the TGF-? levels in the vitreous humor of patients with AMD and controls. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study, and a laser-induced CNV mouse model was prepared for the in vivo study. The HUVECs were incubated with TGF-? and Sema3A. The proliferation, migration, apoptosis, and tube formation of the cells were then measured using BrdU, Transwell, flow cytometry, and Matrigel assays, respectively, and the SMAD2/3 signaling pathways were analyzed using western blot analysis. The C57BL/6J mouse retina was exposed to a laser to induce choroidal neovascularization (CNV), and Sema3A was injected intravitreously. After 14 days, fundus fluorescein angiography was performed to evaluate the leakage area of the CNV. The vascular endothelial growth factor (VEGF) and TGF-? concentrations in the retina-choroid complex were measured with ELISA. Components of the p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase-1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and SMAD2/3 signaling pathways in the Sema3A-treated groups were analyzed using western blotting. Results In this study, we first verified that the vitreous TGF-? level was higher in patients with neovascular AMD than in the controls. We also showed that Sema3A inhibited TGF-?-induced HUVEC proliferation, migration, and tube formation and inhibited the downstream SMAD2/3 signaling pathway. Sema3A also induced TGF-?-stimulated HUVEC apoptosis and inhibited the response of TGF-? in vitro. In vivo, the TGF-? level was increased in the CNV mouse model. Sema3A not only inhibited laser-induced CNV formation but also inhibited the uptake of VEGF and TGF-?. In the western blot analysis, Sema3A was shown to inhibit the phosphorylation of p38 MAPK, ERK1/2, and JNK and to inhibit the SMAD2/3 signaling pathway after Sema3A treatment in CNV mice. Conclusions Sema3A can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation. PMID:25352735

  12. Numerical model of meltwater retention and firn aquifer formation in Greenland Ice Sheet

    NASA Astrophysics Data System (ADS)

    Liu, X.; Bassis, J. N.

    2014-12-01

    Observations show increasing surface melt and mass loss from the Greenland ice sheet. However, at present considerable uncertainty remains in understanding and predicting, much of the meltwater produced is retained and how much reaches the ocean through surface runoff or by draining through moulins. The potential for the Greenland ice sheet to retain substantial amounts of water has been highlighted by the recent and surprising discovery of a semi-permanent firn aquifer. In this study, we use a numerical model to simulate surface melt and track the meltwater evolution in the snow and firn layer to explore how the firn aquifer forms and their influence on Greenland Ice Sheet mass balance and dynamics. The model is coupled with a surface energy balance model, which computes surface energy and mass balance processes, and a snow-firn model, which simulates snow and ice metamorphic processes and englacial water transport processes. Case studies were carried on the melting part of Greenland Ice Sheet to calibrate and validate the model, driven by in situ AWS stations observational data and ERA-interim downscaled reanalysis data. Model results are used to analyze the conditions on which firn aquifer forms and examine limitations associated with driving a model with coarse scale climate data. We also examine the sensitivity to model results to different parameterization of albedo, densification and water transport.

  13. A novel step in beta-tubulin folding is important for heterodimer formation in Saccharomyces cerevisiae.

    PubMed Central

    Lacefield, Soni; Solomon, Frank

    2003-01-01

    Undimerized beta-tubulin is toxic in the yeast S. cerevisiae. It can arise if levels of beta-tubulin and alpha-tubulin are unbalanced or if the tubulin heterodimer dissociates. We are using the toxicity of beta-tubulin to understand early steps in microtubule morphogenesis. We find that deletion of PLP1 suppresses toxic beta-tubulin formed by disparate levels of alpha- and beta-tubulin. That suppression occurs either when alpha-tubulin is modestly underexpressed relative to beta-tubulin or when beta-tubulin is inducibly and strongly overexpressed. Plp1p does not affect tubulin expression. Instead, a significant proportion of the undimerized beta-tubulin in plp1Delta cells is less toxic than that in wild-type cells. It is also less able to combine with alpha-tubulin to form a heterodimer. As a result, plp1Delta cells have lower levels of heterodimer. Importantly, plp1Delta cells that also lack Pac10, a component of the GimC/PFD complex, are even less affected by free beta-tubulin. Our results suggest that Plp1p defines a novel early step in beta-tubulin folding. PMID:14573467

  14. Structural basis for mechanical force regulation of the adhesin FimH via finger trap-like beta sheet twisting.

    PubMed

    Le Trong, Isolde; Aprikian, Pavel; Kidd, Brian A; Forero-Shelton, Manu; Tchesnokova, Veronika; Rajagopal, Ponni; Rodriguez, Victoria; Interlandi, Gianluca; Klevit, Rachel; Vogel, Viola; Stenkamp, Ronald E; Sokurenko, Evgeni V; Thomas, Wendy E

    2010-05-14

    The Escherichia coli fimbrial adhesive protein, FimH, mediates shear-dependent binding to mannosylated surfaces via force-enhanced allosteric catch bonds, but the underlying structural mechanism was previously unknown. Here we present the crystal structure of FimH incorporated into the multiprotein fimbrial tip, where the anchoring (pilin) domain of FimH interacts with the mannose-binding (lectin) domain and causes a twist in the beta sandwich fold of the latter. This loosens the mannose-binding pocket on the opposite end of the lectin domain, resulting in an inactive low-affinity state of the adhesin. The autoinhibition effect of the pilin domain is removed by application of tensile force across the bond, which separates the domains and causes the lectin domain to untwist and clamp tightly around the ligand like a finger-trap toy. Thus, beta sandwich domains, which are common in multidomain proteins exposed to tensile force in vivo, can undergo drastic allosteric changes and be subjected to mechanical regulation. PMID:20478255

  15. Presence of a glycine-cysteine-rich beta-protein in the oberhautchen layer of snake epidermis marks the formation of the shedding layer.

    PubMed

    Alibardi, Lorenzo

    2014-11-01

    The complex differentiation of snake epidermis largely depends on the variation in the production of glycine-cysteine-rich versus glycine-rich beta-proteins (beta-keratins) that are deposited on a framework of alpha-keratins. The knowledge of the amino acid sequences of beta-proteins in the snake Pantherophis guttatus has allowed the localization of a glycine-cysteine-rich beta-protein in the spinulated oberhautchen layer of the differentiating shedding complex before molting takes place. This protein decreases in the beta-layer and disappears in mesos and alpha-layers. Conversely, while the mRNA for a glycine-rich beta-protein is highly expressed in differentiating beta-cells, the immunolocalization for this protein is low in these cells. This discrepancy between expression and localization suggests that the epitope in glycine-rich beta-proteins is cleaved or modified by posttranslational processes that take place during the differentiation and maturation of the beta-layer. The present study suggests that among the numerous beta-proteins coded in the snake genome to produce epidermal layers with different textures, the glycine-cysteine-rich beta-protein marks the shedding complex formed between alpha- and beta-layers that allows for molting while its disappearance between the beta- and alpha-layers (mesos region for scale growth) is connected to the formation of the alpha-layers. PMID:24817366

  16. Independent formation of DnaseI hypersensitive sites in the murine beta-globin locus control region.

    PubMed

    Bender, M A; Mehaffey, M G; Telling, A; Hug, B; Ley, T J; Groudine, M; Fiering, S

    2000-06-01

    Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals. To analyze the function of individual HSs in the endogenous murine beta-globin LCR, we have used homologous recombination in embryonic stem cells to produce 5 mouse lines, each of which is deficient for 1 of these major HSs. In this report, we demonstrate that deletion of the conserved region of 5'HS 1, 2, 3, 4, or 5/6 abolishes HS formation at the deletion site but has no influence on the formation of the remaining HSs in the LCR. Therefore, in the endogenous murine locus, there is no dominant or initiating site whose formation must precede the formation of the other HSs. This is consistent with the idea that HSs form autonomously. We discuss the implications of these findings for current models of beta-globin regulation. PMID:10828050

  17. Formation of lobate debris aprons on Mars: Assessment of regional ice sheet collapse and debris-cover armoring

    NASA Astrophysics Data System (ADS)

    Fastook, James L.; Head, James W.; Marchant, David R.

    2014-01-01

    Lobate debris aprons (LDA) are lobate-shaped aprons surrounding scarps and isolated massifs that are concentrated in the vicinity of the northern Dichotomy Boundary on Mars. LDAs have been interpreted as (1) ice-cemented talus aprons undergoing viscous flow, (2) local debris-covered alpine-like glaciers, or (3) remnants of the collapse of a regional retreating ice sheet. We investigate the plausibility that LDAs are remnants of a more extensive regional ice sheet by modeling this process. We find that as a regional ice sheet collapses, the surface drops below cliff and massif bedrock margins, exposing bedrock and regolith, and initiating debris deposition on the surface of a cold-based glacier. Reduced sublimation due to debris-cover armoring of the proto-LDA surface produces a surface slope and consequent ice flow that carries the armoring debris away from the rock outcrops. As collapse and ice retreat continue the debris train eventually reaches the substrate surface at the front of the glacier, leaving the entire LDA armored by debris cover. Using a simplified ice flow model we are able to characterize the temperature and sublimation rate that would be necessary to produce LDAs with a wide range of specified lateral extents and thicknesses. We then apply this method to a database of documented LDA parameters (height, lateral extent) from the Dichotomy Boundary region, and assess the implications for predicted climate conditions during their formation and the range of formation times implied by the model. We find that for the population examined here, typical temperatures are in the range of -85 to -40 C and typical sublimation rates lie in the range of 6-14 mm/a. Lobate debris apron formation times (from the point of bedrock exposure to complete debris cover) cluster near 400-500 ka. These results show that LDA length and thickness characteristics are consistent with climate conditions and a formation scenario typical of the collapse of a regional retreating ice sheet and exposure of bedrock cliffs. This scenario helps resolve many of the unusual characteristics of lobate debris aprons (LDA) and lineated valley fill (LVF). For example, the distribution of LVF is very consistent with extensive flow of glacial ice from plateau icefields, and the acquisition of a debris cover in the waning stages of retreat of the regional cover as the bedrock scarps are exposed. The typical concentric development of LDA around massifs is much more consistent with ice sheet retreat than insolation-related local accumulation and flow. We thus conclude that the retreating ice-sheet model is robust and should be investigated and tested in more detail. In addition, these results clearly show that the lobate debris aprons in the vicinity of the Dichotomy Boundary could not have attained temperatures near or above the ice melting point and retained their current shape, a finding that supports subzero temperatures for the last several hundred million years, the age of the LDA surfaces. A further implication is that the LDA ice has been preserved for at least several hundred million years, and could potentially contain the record of the climate of Mars, preserved since that time below a sublimation lag deposit.

  18. Origin of life. Primordial genetics: Information transfer in a pre-RNA world based on self-replicating beta-sheet amyloid conformers.

    PubMed

    Maury, Carl Peter J

    2015-10-01

    The question of the origin of life on Earth can largely be reduced to the question of what was the first molecular replicator system that was able to replicate and evolve under the presumably very harsh conditions on the early Earth. It is unlikely that a functional RNA could have existed under such conditions and it is generally assumed that some other kind of information system preceded the RNA world. Here, I present an informational molecular system that is stable, self-replicative, environmentally responsive, and evolvable under conditions characterized by high temperatures, ultraviolet and cosmic radiation. This postulated pregenetic system is based on the amyloid fold, a functionally unique polypeptide fold characterized by a cross beta-sheet structure in which the beta strands are arranged perpendicular to the fiber axis. Beside an extraordinary structural robustness, the amyloid fold possesses a unique ability to transmit information by a three-dimensional templating mechanism. In amyloidogenesis short peptide monomers are added one by one to the growing end of the fiber. From the same monomeric subunits several structural variants of amyloid may be formed. Then, in a self-replicative mode, a specific amyloid conformer can act as a template and confer its spatially encoded information to daughter molecular entities in a repetitive way. In this process, the specific conformational information, the spatially changed organization, is transmitted; the coding element is the steric zipper structure, and recognition occurs by amino acid side chain complementarity. The amyloid information system fulfills several basic requirements of a primordial evolvable replicator system: (i) it is stable under the presumed primitive Earth conditions, (ii) the monomeric building blocks of the informational polymer can be formed from available prebiotic compounds, (iii) the system is self-assembling and self-replicative and (iv) it is adaptive to changes in the environment and evolvable. PMID:26196585

  19. Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation

    PubMed Central

    Spencer-Segal, Joanna L.; Tsuda, Mumeko C.; Mattei, Larissa; Waters, Elizabeth M.; Romeo, Russell D.; Milner, Teresa A.; McEwen, Bruce S.; Ogawa, Sonoko

    2012-01-01

    Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning. Six hours of estradiol administration increased immunoreactivity for phosphorylated Akt throughout the hippocampal formation, while 48 hours of estradiol increased immunoreactivity for phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB immunoreactivities were abolished in ER alpha and ER beta knockout mice. Estradiol also had distinct effects on immunoreactivity for PSD-95 and BDNF mRNA in ER alpha and beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in several subregions of the hippocampal formation. The different effects of estradiol at 6 and 48 hours indicate that several mechanisms of estrogen receptor signaling contribute to this female hormones influence on hippocampal synaptic plasticity. By further delineating these mechanisms, we will better understand and predict the effects of endogenous and exogenous ovarian steroids on mood, cognition, and other hippocampal-dependent behaviors. PMID:22133892

  20. Beta4 integrin-dependent formation of polarized three-dimensionalarchitecture confers resistance to apoptosis in normal and malignantmammary epithelium

    SciTech Connect

    Weaver, Valerie M.; Lelievre, Sophie; Lakins, Johnathon N.; Chrenek, Micah A.; Jones, Jonathan C.R.; Giancotti, Filippo; Werb, Zena; Bissell, Mina J.

    2002-08-27

    Tumor cells can evade chemotherapy by acquiring resistanceto apoptosis. We investigated the molecular mechanism whereby malignantand nonmalignant mammary epithelial cells become insensitive toapoptosis. We show that regardless of growth status formation ofpolarized, three-dimensional structures driven by basement membraneconfers protection to apoptosis in both nonmalignant and malignantmammary epithelial cells. By contrast, irrespective of their malignantstatus, nonpolarized structures are sensitive to induction of apoptosis.Resistance to apoptosis requires ligation of beta4 integrins, whichregulates tissue polarity, hemidesmosome formation and NFkB activation.Expression of beta4 integrin that lacks the hemidesmosome targetingdomain interferes with tissue polarity and NFkB activation and permitsapoptosis. These results indicate that integrin-induced polarity maydrive tumor cell resistance to apoptosis-inducing agents via effects onNFkB.

  1. The effect of low levels of dopants upon the formation and properties of beta-phase molybdenum nitride

    NASA Astrophysics Data System (ADS)

    Cairns, A. G.; Gallagher, J. G.; Hargreaves, J. S. J.; Mckay, D.; Rico, J. L.; Wilson, K.

    2010-03-01

    The addition of 1 wt% Pd, Au, Ni and Cu dopants has been demonstrated to strongly alter the morphology of beta-phase molybdenum nitride prepared by treatment of MoO 3 with a 3/1 H 2/N 2 mixture at 750 C. Furthermore, the addition of Pd significantly enhances the surface area and the formation of the nitride phase. It is proposed that the facile formation of molybdenum bronzes in this system is important in this respect. The dopants have also been observed to modify the denitridation characteristics of the beta-phase, with an overall reduction of the proportion of NH 3 formed upon using a 3/1 H 2/Ar mixture with respect to the undoped sample.

  2. Thymosin Beta4 Regulates Cardiac Valve Formation Via Endothelial-Mesenchymal Transformation in Zebrafish Embryos

    PubMed Central

    Shin, Sun-Hye; Lee, Sangkyu; Bae, Jong-Sup; Jee, Jun-Goo; Cha, Hee-Jae; Lee, You Mie

    2014-01-01

    Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelialmesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount in situ hybridization. Of the thymosin family members only zTB4 was expressed in the developing heart region. Cardiac valve development at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino-injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube development was observed. The expressions of bone morphogenetic protein (BMP) 4, notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT in developing cardiac valves in zTB4 morphants. EMT marker expression in valve endothelial cells was confirmed after transfection with TB4 siRNA in the presence of transforming growth factor ? (TGF?) by RT-PCR and immunofluorescent assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants, and knockdown of TB4 suppressed TGF-?-induced EMT in ovine valve endothelial cells. Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT. PMID:24732964

  3. Formation of sheet plumes, current coils, and helical magnetic fields in a spherical magnetohydrodynamic dynamo

    SciTech Connect

    Miyagoshi, Takehiro; Kageyama, Akira; Sato, Tetsuya

    2011-07-15

    Aiming at understanding of magnetic field generation process in rapidly rotating stars and planets represented by the Earth, computer simulations of magnetohydrodynamic (MHD) dynamo were performed in a rotating spherical shell geometry. Thermal convection and dynamo process with Ekman number of the order of 10{sup -7} were studied. New structures of convection motion, dynamo-generated electrical current, and magnetic field are found. The flow is organized as a set of thin, sheet-like plumes. The current is made of small-scale coil structure with magnetic flux tubes within each of the coil. These flux tubes are connected each other to form a large scale helical magnetic field structure.

  4. Structure formation during recrystallization of cold-rolled sheet steel 06Kh18ch

    SciTech Connect

    Babitskaya, A.N.; Mishchenko, V.G.; Movshovich, V.S.

    1986-03-01

    The authors determine the optimum recrystallization heat-treatment schedule for cold-rolled steel 06Kh18ch in order to obtain an equilibrium structure. The study was carried out on steel from an industrial melt (C, Mn, Si, P, S, Cr, Ni, Cu, V, and W) and factory reduction. 0.38% ferrocerium, 0.2% Ca, and 0.005% Mg were added to the steel. On the basis of this study the authors conclude that heating to 920-950 degrees C followed by rapid cooling provides the maximum ductility for cold-rolled steel 06Kh18ch sheet.

  5. Engineering stabilising beta-sheet interactions into a conformationally flexible region of the folding transition state of ubiquitin.

    PubMed

    Bofill, Roger; Searle, Mark S

    2005-10-21

    Protein engineering studies suggest that the transition state for the folding of ubiquitin is highly polarised towards the N-terminal part of the sequence and involves a nucleus of residues within the beta-hairpin (residues 1-17) and main alpha-helix (residues 23-34). In contrast, the observation of small phi-values for residues in the C-terminal portion of the sequence (residues 35-76), coupled with a folding topology that results in a much higher contact order, suggests that fast folding of ubiquitin is dependent upon configurational flexibility in the C-terminal part of the polypeptide chain to ensure passage down a relatively smooth folding funnel to the native state. We show that the introduction of a small mini-hairpin motif as an extension of the native 43-50 hairpin stabilises local interactions in the C-terminal part of the sequence, resulting largely in a deceleration of the unfolding kinetics without perturbing the apparent two-state folding mechanism. However, a single-point Leu-->Phe substitution within the engineered hairpin sequence leads to the premature collapse of the denatured ensemble through the stabilisation of non-native interactions and the population of a compact intermediate. Non-linear effects in the kinetic data at low concentrations of denaturant suggest that the collapsed state, which is further stabilised in the presence of cosmotropic salts, may subsequently fold directly to the native state through a "triangular" reaction scheme involving internal rearrangement rather than unfolding and refolding. PMID:16169558

  6. 1-N-glycyl beta-oligosaccharide derivatives as stable intermediates for the formation of glycoconjugate probes.

    PubMed

    Manger, I D; Rademacher, T W; Dwek, R A

    1992-11-10

    Incubation of reducing sugars in ammonium bicarbonate was found to be a simple procedure for the formation of beta-D-glycosylamines of purified complex oligosaccharides in 70-80% yield. These provide valuable intermediates for the synthesis of a wide range of oligosaccharide probes and derivatives by acylation of the 1-amino function. The 1-amino function showed different rates of reactivity with different reagents. In general, interactions with large ring systems such as the fluorophores dansyl chloride and carboxyfluorescein gave 10-20% yields of products, which consisted of mixtures of both anomeric forms, whereas smaller acylating reagents gave near-quantitative yields of the desired beta-D-derivatives. Steric effects may explain differences in reactivity. N-Chloroacetamido derivatives could be obtained in high yield with retention of the beta-anomeric configuration. Subsequent ammonolysis of the chloroacetamido function afforded the corresponding N-glycyl beta-derivatives. The linker thereby introduced retains the amino function, possesses the useful properties of fixed anomeric configuration, improved stability, and uniform reactivity with a variety of reagents, and is structurally analogous to an asparagine side chain. The potential therefore exists for the generation of oligosaccharide derivatives tailored for different applications. PMID:1420188

  7. From Boron Cluster to Two-Dimensional Boron Sheet on Cu(111) Surface: Growth Mechanism and Hole Formation

    PubMed Central

    Liu, Hongsheng; Gao, Junfeng; Zhao, Jijun

    2013-01-01

    As attractive analogue of graphene, boron monolayers have been theoretically predicted. However, due to electron deficiency of boron atom, synthesizing boron monolayer is very challenging in experiments. Using first-principles calculations, we explore stability and growth mechanism of various boron sheets on Cu(111) substrate. The monotonic decrease of formation energy of boron cluster BN with increasing cluster size and low diffusion barrier for a single B atom on Cu(111) surface ensure continuous growth of two-dimensional (2D) boron cluster. During growth process, hexagonal holes can easily arise at the edge of a 2D triangular boron cluster and then diffuse entad. Hence, large-scale boron monolayer with mixed hexagonal-triangular geometry can be obtained via either depositing boron atoms directly on Cu(111) surface or soft landing of small planar BN clusters. Our theoretical predictions would stimulate further experiments of synthesizing boron sheets on metal substrates and thus enrich the variety of 2D monolayer materials. PMID:24241341

  8. Thin current sheet formation in response to the loading and the depletion of magnetic flux during the substorm growth phase

    NASA Astrophysics Data System (ADS)

    Hsieh, M.-S.; Otto, A.

    2015-06-01

    The physics of geomagnetic substorms has been under debate for a long time. Although the growth phase has received less attention than the spectacular expansion phase, the state of the magnetotail at the end of the growth phase, i.e., a thin current sheet (CS) formation is of central importance because it provides the magnetotail conditions for the expansion phase onset. This study investigates CSs evolution during the substorm growth phase. The growth phase physics considered here includes the removal of closed magnetic flux in the near-Earth tail and the addition of magnetic flux into the tail lobes. It is found that two separate CSs evolve at distinct locations in the near-Earth and the midtail region in response to the depletion and the loading of magnetic flux. The relative current densities in the dual-current-sheet configuration depends strongly on whether the depleted or the added magnetic flux dominates. The presented results suggest that substorm expansion onset may be associated only with reconnection onset in the near-Earth CS, while midtail reconnection causes bursty bulk flows or bubbles.

  9. Formation of a long-lived hot field reversed configuration by dynamically merging two colliding high-{beta} compact toroids

    SciTech Connect

    Guo, H. Y.; Binderbauer, M. W.; Barnes, D.; Putvinski, S.; Rostoker, N.; Sevier, L.; Tuszewski, M.; Anderson, M. G.; Andow, R.; Bonelli, L.; Brown, R.; Bui, D. Q.; Bystritskii, V.; Clary, R.; Cheung, A. H.; Conroy, K. D.; Deng, B. H.; Dettrick, S. A.; Douglass, J. D.; Feng, P.

    2011-05-15

    A high temperature field reversed configuration (FRC) has been produced in the newly built, world's largest compact toroid (CT) facility, C-2, by colliding and merging two high-{beta} CTs produced using the advanced field-reversed {theta}-pinch technology. This long-lived, stable merged state exhibits the following key properties: (1) apparent increase in the poloidal flux from the first pass to the final merged state, (2) significantly improved confinement compared to conventional {theta}-pinch FRCs with flux decay rates approaching classical values in some cases, (3) strong conversion from kinetic energy into thermal energy with total temperature (T{sub e} + T{sub i}) exceeding 0.5 keV, predominantly into the ion channel. Detailed modeling using a new 2-D resistive magnetohydrodynamic (MHD) code, LamyRidge, has demonstrated, for the first time, the formation, translation, and merging/reconnection dynamics of such extremely high-{beta} plasmas.

  10. ?-sheet-like formation during the mechanical unfolding of prion protein

    NASA Astrophysics Data System (ADS)

    Tao, Weiwei; Yoon, Gwonchan; Cao, Penghui; Eom, Kilho; Park, Harold S.

    2015-09-01

    Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrPC, whose misfolded form PrPSc can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded ?-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native ?-helical structure to the ?-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ?160-220.

  11. Magnetic neutral sheets in evolving fields. I - General theory. II - Formation of the solar corona

    NASA Technical Reports Server (NTRS)

    Parker, E. N.

    1983-01-01

    The problem of the hydrostatic equilibrium of a large-scale magnetic field embedded in a fluid with infinite electrical conductivity is considered. It is pointed out that a necessary condition for static equilibrium is the invariance of the small-scale pattern in the field along the large-scale direction. A varying topological pattern implies that no fluid pressure distribution exists for which the field is everywhere static. Magnetic neutral sheets form, and dynamical reconnection of the field takes place. It is shown here that the invariance is also a sufficient condition for the existence of a fluid pressure distribution producing static equilibrium. Even in the simplest cases, however, the requirements on the fluid pressure are extreme and, a priori, are unlikely. It is concluded that almost all twisted flux tubes packed together produce dynamical nonequilibrium and dissipation of their twisting. This is the basic effect underlying the long-standing conjecture that the shuffling of the footpoints of the bipolar magnetic fields in the sun is responsible for heating the active corona. Attention is then given to the consequences of this general dynamical dissipation in the magnetic fields that produce the active corona of the sun. The footpoints of the field are continually manipulated by the subphotospheric convection in such a way that the lines of force are continually wrapped and rotated about one another.

  12. On the formation of the tunnel valleys of the southern Laurentide ice sheet

    NASA Astrophysics Data System (ADS)

    Hooke, Roger LeB.; Jennings, Carrie E.

    2006-06-01

    Catastrophic releases of meltwater, produced by basal melting and stored for decades in subglacial reservoirs at high pressure, may have been responsible for eroding the broad, deep tunnel valleys that are common along the margins of some lobes of the southern Laurentide ice sheet. We surmise that these releases began when the high water pressure was transmitted to the margin through the substrate. The water pressure in the substrate at the margin would then have been significantly above the overburden pressure, leading to sapping failure. Headward erosion of a conduit in the substrate (piping) could then tap the stored water, resulting in the outburst. In some situations, development of a siphon may have lowered the reservoir below its overflow level, thus tapping additional water. Following the flood, the seal could have reformed and the reservoir refilled, setting up conditions for another outburst. Order of magnitude calculations suggest that once emptied, a subglacial reservoir could refill in a matter of decades. The amount of water released during several outbursts appears to be sufficient to erode a tunnel valley. We think that tunnel valleys are most likely to have formed in this way where and when the glacier margin was frozen to the bed and permafrost extended from the glacier forefield several kilometers back under the glacier, as reservoirs would then have been larger and more common, and the seal more robust and more likely to reform after an outburst.

  13. Does Long-Term Administration of a Beta-Blocker (Timolol) Induce Fibril-Based Cataract Formation In-vivo?

    PubMed Central

    Nikbakht, Mohammad Reza; Ashrafi-Kooshk, Mohammad Reza; Jaafari, Morteza; Ghasemi, Moosa; Khodarahmi, Reza

    2014-01-01

    Timolol is a non-selective beta-adrenergic receptor antagonist administered for treating glaucoma, heart attacks and hypertension. In the present study, we set out to determine whether or not timolol can provoke cataract formation, thus the influence of timolol on the amyloid-type aggregation of crystallin was investigated. We then provided experimental evidence of crystallin aggregation and its induction by timolol using different spectroscopic measurements. Turbidimetric measurements as well as ThT fluorescence data indicated that timolol induce extent of crystallin amyloid formation. The kinetic of protein aggregation was also changed in presence of increasing concentrations of the drug suggesting that long-term drug administration may contribute to the development of cataract. Since the consequence of timolol-crystallin interaction has yet to be identified, additional data on it may help us to postpone amyloid cataract formation. PMID:25237356

  14. Separation of drug stereoisomers by the formation of. beta. -cyclodextrin inclusion complexes

    SciTech Connect

    Armstrong, D.W.; Ward, T.J.; Armstrong, R.D.; Beesley, T.E.

    1986-05-30

    For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized ..beta..-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as ..beta..-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of ..beta..-cyclodextrin complexes of propanol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of ..beta..-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiometric drugs. 27 references, 3 figures, 2 tables.

  15. Structural Transitions and Oligomerization along Polyalanine Fibril Formation Pathways from Computer Simulations

    PubMed Central

    Phelps, Erin M.; Hall, Carol K.

    2012-01-01

    The results of a computer simulation study of the aggregation kinetics of a large system of model peptides with particular focus on the formation of intermediates are presented. Discontinuous molecular dynamic simulations were used in combination with our intermediate-resolution protein model, PRIME, to simulate the aggregation of a system of 192 polyalanine (KA14K) peptides at a concentration of 5mM and reduced temperature of T* = 0.13 starting from a random configuration and ending in the assembly of a fibrillar structure. The population of various structures, including free monomers, beta sheets, amorphous aggregates, hybrid aggregates, and fibrils, and the transitions between the structures were tracked over the course of thirty independent simulations and averaged together. The aggregation pathway for this system starts with the association of free monomers into small amorphous aggregates that then grow to moderate size by incorporating other free monomers or merging with other small amorphous aggregates. These then rearrange into either small beta sheets or hybrid aggregates formed by association between unstructured chains and beta sheets, both of which grow in size by adding free monomer chains or other small aggregates, one at a time. Fibrillar structures are formed initially either by the stacking of beta sheets, rearrangement of hybrid aggregates or association between beta sheets and hybrid aggregates. They grow by the addition of beta sheets, hybrid aggregates and other small fibrillar structures. The rearrangement of amorphous aggregates into beta sheets is a critical and necessary step in the fibril formation pathway. PMID:22411226

  16. Inhibition of amyloid fibril formation of human amylin by N-alkylated amino acid and alpha-hydroxy acid residue containing peptides.

    PubMed

    Rijkers, Dirk T S; Hppener, Jo W M; Posthuma, George; Lips, Cornelis J M; Liskamp, Rob M J

    2002-09-16

    Amyloid deposits are formed as a result of uncontrolled aggregation of (poly)peptides or proteins. Today several diseases are known, for example Alzheimer's disease, Creutzfeldt-Jakob disease, mad cow disease, in which amyloid formation is involved. Amyloid fibrils are large aggregates of beta-pleated sheets and here a general method is described to introduce molecular mutations in order to achieve disruption of beta-sheet formation. Eight backbone-modified amylin derivatives, an amyloidogenic peptide involved in maturity onset diabetes, were synthesized. Their beta-sheet forming properties were studied by IR spectroscopy and electron microscopy. Modification of a crucial amide NH by an alkyl chain led to a complete loss of the beta-sheet forming capacity of amylin. The resulting molecular mutated amylin derivative could be used to break the beta-sheet thus retarding beta-sheet formation of unmodified amylin. Moreover, it was found that the replacement of this amide bond by an ester moiety suppressed fibrillogenesis significantly. Introduction of N-alkylated amino acids and/or ester functionalities-leading to depsipeptides-into amyloidogenic peptides opens new avenues towards novel peptidic beta-sheet breakers for inhibition of beta-amyloid aggregation. PMID:12298020

  17. Unfolding Simulations of Holomyoglobin from Four Mammals: Identification of Intermediates and ?-Sheet Formation from Partially Unfolded States

    PubMed Central

    Dasmeh, Pouria; Kepp, Kasper P.

    2013-01-01

    Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (Rg ?1.481.51 nm, helicity ?75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable in terrestrial species. At 500 K, heme was lost within 1.03.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD), secondary structure, and ellipticity between 211 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed ?-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations. PMID:24386077

  18. Ectopic bone formation associated with recombinant human bone morphogenetic proteins-2 using absorbable collagen sponge and beta tricalcium phosphate as carriers.

    PubMed

    Kim, Chang-Sung; Kim, Joon-Il; Kim, Jin; Choi, Seong-Ho; Chai, Jung-Kiu; Kim, Chong-Kwan; Cho, Kyoo-Sung

    2005-05-01

    The ectopic bone formation of recombinant human bone morphogenetic protein-2(rhBMP-2) was evaluated using absorbable collagen sponges (ACS) and beta tricalcium phosphate (beta-TCP) as carriers in a rat subcutaneous assay model. Subcutaneous pockets were created on the back of rats. The pockets were implanted with rhBMP-2/ACS, rhBMP-2/beta-TCP, ACS alone, and beta-TCP alone. The rats were sacrificed at 2 or 8 weeks for histological and immunohistochemical evaluation. At 2 weeks, bone formation was evident in both the rhBMP-2/ACS and rhBMP-2/beta-TCP sites. At 8 weeks, the quantity of the new bone with a more advanced stage of remodeling had increased further in the rhBMP-2/beta-TCP sites. However, the newly formed bone observed at 2 weeks was not found in the rhBMP-2/ACS sites. On immunohistochemical observation, osteopontin staining was observed on both the rhBMP-2/ACS (2 weeks) and rhBMP-2/beta-TCP (2 and 8 weeks) sites. Osteocalcin was not detected in any of the samples. The lack of space-providing capacity of ACS may be one of the major factors responsible for its failure to maintain the newly induced bone. Therefore, a carrier for BMPs should provide space for bone formation and maturation during the more advanced healing stages. PMID:15585252

  19. Film formation and paper coating with poly ([beta]-hydroxyalkanoate), a biodegradable latex

    SciTech Connect

    Lauzier, C.A.; Monasterios, C.J.; Saracovan, I.; Marchessault, R.H. ); Ramsay, B.A. )

    1993-05-01

    An aqueous latex of a poly ([beta]-hydroxyalkanoate) (PHA) coated on paper imparted water imperviousness without changing mechanical properties. Hot-pressed films biodegraded faster than solvent cast films. The PHA coating on paper degraded totally in activated sludge within 12 days, leaving the cellulose matrix relatively untouched. Blends of PHA latexes with sodium carboxymethl cellulose, polystyrene latex, carboxylated styrenel butadiene latex, natural rubber latex, carboxylated styrenel butadiene latex; natural rubber latex, and starch powders form satisfactory films at room temperature.

  20. Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

    SciTech Connect

    Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. )

    1991-06-01

    We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

  1. Characterization and bioactivity of tape-cast and sintered TCP sheets.

    PubMed

    Tanimoto, Yasuhiro; Hayakawa, Tohru; Sakae, Toshiro; Nemoto, Kimiya

    2006-03-01

    The purpose of this study was to investigate the influence of sintering temperature on in vivo and in vitro bioactivities of sintered tricalcium phosphate (TCP) sheets prepared by the tape casting technique. Green sheets of beta-TCP prepared by tape casting were sintered for 2 h in a furnace at atmospheric pressure, at five different sintering temperatures: 900, 1000, 1100, 1150, and 1200 degrees C. Measurement of X-ray diffraction and Fourier transform infrared spectrometry showed the presence of alpha-tricalcium phosphate phase in the TCP sheet sintered at 1200 degrees C, in addition to beta-TCP phase. As compared with the other sintered TCP sheet, the TCP sheet sintered at 1200 degrees C demonstrated a lower dissolution rate in phosphate buffered saline solution at 37 degrees C and pH 7.4 over 24 weeks, and more amount of apatite formation in Hanks' balanced salt solution with pH 7.4 was observed. After 4 weeks' implantation of sintered TCP sheets into tibial diaphyses of rabbits, the bone-sheet contact of the TCP sheet sintered at 1200 degrees C was significantly higher than that of the TCP sheet sintered at 900 degrees C. These results indicate that a flat sintered TCP sheet prepared by tape casting is a promising material for a bone substitute. PMID:16278874

  2. Spontaneous Formation of Oligomers and Fibrils in Large-Scale Molecular Dynamics Simulations of A-beta Peptides

    NASA Astrophysics Data System (ADS)

    Hall, Carol

    2013-03-01

    Protein aggregation is associated with serious and eventually-fatal neurodegenerative diseases including Alzheimer's and Parkinson's. While atomic resolution molecular dynamics simulations have been useful in this regard, they are limited to examination of either oligomer formation by a small number of peptides or analysis of the stability of a moderate number of peptides placed in trial or known experimental structures. We describe large scale intermediate-resolution molecular dynamics simulations of the spontaneous formation of fibrils by systems containing large numbers (48) of peptides including A-beta (16-22), and A-beta (17-42) peptides. We trace out the aggregation process from an initial configuration of random coils to proto-filaments with cross- β structures and demonstrate how kinetics dictates the structural details of the fully formed fibril. Fibrillization kinetics depends strongly on the temperature. Nucleation and templated growth via monomer addition occur at and near a transition temperature above which fibrils are unlikely to form. Oligomeric merging and structural rearrangement are observed at lower temperatures. In collaboration with Mookyung Cheon, Iksoo Chang, Pusan University; and David Latshaw, North Carolina State University.

  3. Effects of the Formation of Al x Cu y Gradient Interfaces on Mechanical Property of Steel/Al Laminated Sheets by Introducing Cu Binding-Sheets

    NASA Astrophysics Data System (ADS)

    Wei, Aili; Liu, Xinghai; Shi, Quanxin; Liang, Wei

    2015-07-01

    Steel/Cu/Al laminated sheets were fabricated by two-pass hot rolling to improve the mechanical properties of steel/Al sheets. The bonding properties and deformability of the steel/Cu/Al sheets were studied. Steel/Al and steel/Cu/Al samples were rolled at 350C for 15 min with the first-pass reduction of 40%, and then heated at 600C for 5 min with different reductions. It was found that the steel/Cu/Al samples rolled by the second-pass reduction of 85% could endure the maximum 90 bend cycle times of 45, exhibiting excellent fatigue resistance as well as deformability. The steel/Al samples could only reach the maximum 90 bend cycle times of 20. Furthermore, the scanning electron microscope, energy-dispersive spectrometer, and electron backscattered diffraction results showed that the preferred growth orientations of Cu, Al4Cu9, and Al2Cu on the steel/Cu/Al laminated sheets are {-1, 1, 2} <1, -1, 1>, {1, 0, 0} <0, 1, 0> and {-1, 1, 2} <1, -1, 1> {1, 1, 0} <0, 0, 1>. The orientation relationships between Cu and Al2Cu are {1, 1, 0}(fcc)//{1, 1, 0}(bct) and {1, 1, 1}(fcc)//{1, 1, 1}(bct). The improved bonding property and excellent fatigue resistance as well as deformability were mainly ascribed to the tight combination and consistent deformability across steel, Al, and the transition layers (Cu, Al4Cu9, and Al2Cu).

  4. Formation of alpha and beta tantalum at the variation of magnetron sputtering conditions

    NASA Astrophysics Data System (ADS)

    Nasakina, E. O.; Sevostyanov, M. A.; Mikhaylova, A. B.; Baikin, A. S.; Sergienko, K. V.; Leonov, A. V.; Kolmakov, A. G.

    2016-02-01

    Nano- and microdimensional surface layers of α and β tantalum on flat NiTi, Ti, glass, etc. substrates were created. Structure and composition of samples were defined by SEM, AES and x-ray diffractometry. With increase in deposition time surface layer thickness not linearly increases. The transitional layer provide high adhesion of a surface layer to a substrate. Irrespective of summary sputtering time the β phase is formed in the beginning and at sputtering time more than 20 min on it α tantalum is deposited, while temperature remains below 150°C. Keywords: composite materials, surface layer, tantalum, alpha and beta phase, nitinol, corrosion resistance.

  5. Raman study of the formation of beta silicomolybdic acid supported on silica, prepared by impregnation method

    NASA Astrophysics Data System (ADS)

    Phuc, Nguyen Huu Huy; Ohkita, Hironobu; Mizushima, Takanori; Kakuta, Noriyoshi

    2012-12-01

    Beta silicomolibdic acid/silica (?-SMA, a metastable form of silicomolybdic acid - H4SiMo12O40) forms by the impregnation of fumed silica into molybdenum solution obtained by hydrolyzation of MoO2Cl2. ?-SMA/silica is found to be stable up to 300 C after calcination for 1 h due to the existence of an interlayer MoO3 between silica surface and ?-SMA. Structures of molybdenum species in the preparation process (including precursor solution) were analyzed by Raman spectroscopy and XRD.

  6. Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states.

    PubMed

    Levy, Bruno; Desebbe, Olivier; Montemont, Chantal; Gibot, Sebastien

    2008-10-01

    During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5+/-0.3 in endotoxic shock, 2.1+/-0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (P<0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260+/-40 microM in endotoxic shock, 210+/-30 microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (P<0.05 for all groups). Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability. PMID:18323749

  7. Driving Cartilage Formation in High-Density Human Adipose-Derived Stem Cell Aggregate and Sheet Constructs Without Exogenous Growth Factor Delivery

    PubMed Central

    Dang, Phuong N.; Solorio, Loran D.

    2014-01-01

    An attractive cell source for cartilage tissue engineering, human adipose-derived stem cells (hASCs) can be easily expanded and signaled to differentiate into chondrocytes. This study explores the influence of growth factor distribution and release kinetics on cartilage formation within 3D hASC constructs incorporated with transforming growth factor-β1 (TGF-β1)-loaded gelatin microspheres. The amounts of microspheres, TGF-β1 concentration, and polymer degradation rate were varied within hASC aggregates. Microsphere and TGF-β1 loading concentrations were identified that resulted in glycosaminoglycan (GAG) production comparable to those of control aggregates cultured in TGF-β1-containing medium. Self-assembling hASC sheets were then engineered for the production of larger, more clinically relevant constructs. Chondrogenesis was observed in hASC-only sheets cultured with exogenous TGF-β1 at 3 weeks. Importantly, sheets with incorporated TGF-β1-loaded microspheres achieved GAG production similar to sheets treated with exogenous TGF-β1. Cartilage formation was confirmed histologically via observation of cartilage-like morphology and GAG staining. This is the first demonstration of the self-assembly of hASCs into high-density cell sheets capable of forming cartilage in the presence of exogenous TGF-β1 or with TGF-β1-releasing microspheres. Microsphere incorporation may bypass the need for extended in vitro culture, potentially enabling hASC sheets to be implanted more rapidly into defects to regenerate cartilage in vivo. PMID:24873753

  8. Beta- lactam antibiotics stimulate biofilm formation in non-typeable haemophilus influenzae by up-regulating carbohydrate metabolism.

    PubMed

    Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M; Webster, Paul

    2014-01-01

    Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 g/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended. PMID:25007395

  9. Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

    PubMed Central

    Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M.; Webster, Paul

    2014-01-01

    Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 g/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended. PMID:25007395

  10. Mitochondrial DNA damage in a mouse model of Alzheimer's disease decreases amyloid beta plaque formation

    PubMed Central

    Fukui, Hirokazu; Moraes, Carlos T.

    2014-01-01

    Mitochondrial DNA (mtDNA) damage and the generation of reactive oxygen species have been associated with and implicated in the development and progression of Alzheimer's disease. To study how mtDNA damage affects reactive oxygen species and amyloid beta (A?) pathology in vivo, we generated an Alzheimer's disease mouse model expressing an inducible mitochondrial-targeted endonuclease (Mito-PstI) in the central nervous system. Mito-PstI cleaves mtDNA causing mostly an mtDNA depletion, which leads to a partial oxidative phosphorylation defect when expressed during a short period in adulthood. We found that a mild mitochondrial dysfunction in adult neurons did not exacerbate A? accumulation and decreased plaque pathology. Mito-PstI expression altered the cleavage pathway of amyloid precursor protein without increasing oxidative stress in the brain. These data suggest that mtDNA damage is not a primary cause of Ab accumulation. PMID:23702344

  11. Chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta 1 mRNA inhibits neointima formation in rat carotid artery after balloon injury.

    PubMed

    Ando, Hideyuki; Fukuda, Noboru; Kotani, Motoko; Yokoyama, Shin ichiro; Kunimoto, Satoshi; Matsumoto, Koichi; Saito, Satoshi; Kanmatsuse, Katsuo; Mugishima, Hideo

    2004-01-12

    We designed and synthesized a chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor (TGF)-beta 1 mRNA and found that this ribozyme effectively and specifically inhibited growth of vascular smooth muscle cells. We examined the effects of the chimeric DNA-RNA hammerhead ribozyme targeting TGF-beta 1 mRNA on neointima formation and investigated the underlying mechanism to develop a possible gene therapy for coronary artery restenosis after percutaneous transluminal coronary angioplasty. Expression of mRNAs encoding TGF-beta 1, p27kip1, and connective tissue growth factor (CTGF) in carotid artery increased after balloon injury. Fluorescein-isothiocyanate (FITC)-labeled ribozyme was taken up into the midlayer smooth muscle of the injured carotid artery. Both 2 and 5 mg of ribozyme reduced neointima formation by 65% compared to that of controls. Ribozyme markedly decreased expression of TGF-beta 1 mRNA and protein in injured vessel. Mismatch ribozyme had no effect on expression of TGF-beta 1 mRNA protein in injured vessel. Ribozyme markedly decreased expression of fibronectin, p27kip1, and CTGF mRNAs in injured vessel, whereas a mismatch ribozyme had no effect on these mRNAs. These findings indicate that the chimeric DNA-RNA hammerhead ribozyme targeting TGF-beta 1 mRNA inhibits neointima formation in rat carotid artery after balloon injury with suppression of TGF-beta 1 and inhibition of extracellular matrix and CTGF. In conclusion, the hammerhead ribozyme against TGF-beta 1 may have promise as a therapy for coronary artery restenosis after percutaneous transluminal coronary angioplasty. PMID:14729108

  12. Formation of high-{beta} plasma and stable confinement of toroidal electron plasma in Ring Trap 1

    SciTech Connect

    Saitoh, H.; Yoshida, Z.; Morikawa, J.; Furukawa, M.; Yano, Y.; Kawai, Y.; Kobayashi, M.; Vogel, G.; Mikami, H.

    2011-05-15

    Formation of high-{beta} electron cyclotron resonance heating plasma and stable confinement of pure electron plasma have been realized in the Ring Trap 1 device, a magnetospheric configuration generated by a levitated dipole field magnet. The effects of coil levitation resulted in drastic improvements of the confinement properties, and the maximum local {beta} value has exceeded 70%. Hot electrons are major component of electron populations, and its particle confinement time is 0.5 s. Plasma has a peaked density profile in strong field region [H. Saitoh et al., 23rd IAEA Fusion Energy Conference EXC/9-4Rb (2010)]. In pure electron plasma experiment, inward particle diffusion is realized, and electrons are stably trapped for more than 300 s. When the plasma is in turbulent state during beam injection, plasma flow has a shear, which activates the diocotron (Kelvin-Helmholtz) instability. The canonical angular momentum of the particle is not conserved in this phase, realizing the radial diffusion of charged particles across closed magnetic surfaces. [Z. Yoshida et al., Phys Rev. Lett. 104, 235004 (2010); H. Saitoh et al., Phys. Plasmas 17, 112111 (2010).].

  13. Diet-induced hyperhomocysteinemia increases amyloid-beta formation and deposition in a mouse model of Alzheimer's disease.

    PubMed

    Zhuo, J-M; Portugal, G S; Kruger, W D; Wang, H; Gould, T J; Pratico, D

    2010-03-01

    Hyperhomocysteinemia (HHcy) has been recognized as a risk factor for developing Alzheimer's disease (AD). However, its underlying molecular mechanisms are still elusive. Here we show that HHcy induces an elevation of amyloid beta (Abeta) levels and deposition, as well as behavioral impairments, in a mouse model of AD-like amyloidosis, the Tg2576 mice. This elevation is not associated with significant change of the steady state levels of the Abeta precursor protein (APP), beta- or alpha-secretase pathways, nor with the Abeta catabolic pathways. By contrast, HHcy significantly reduces glycogen synthase kinase 3 (GSK3) Ser21/9 phosphorylation, but not total GSK3 protein levels. Similar results are obtained in brains homogenates from a genetic mouse model of HHcy. In vitro studies show that homocysteine increases Abeta formation, reduces phosphorylated GSK3 levels, without changes in total APP and its metabolism, and these effects are prevented by selective GSK3 inhibition. Overall, these data support a potential link between GSK3 and the pro-amyloidotic effect of HHcy in vivo and in vitro. PMID:19939226

  14. Inhibition of beta-amyloid aggregation by fluorescent dye labels

    SciTech Connect

    Amaro, Mariana; Wellbrock, Thorben; Birch, David J. S.; Rolinski, Olaf J.

    2014-02-10

    The fluorescence decay of beta-amyloid's (Aβ) intrinsic fluorophore tyrosine has been used for sensing the oligomer formation of dye-labelled Aβ monomers and the results compared with previously studied oligomerization of the non-labelled Aβ peptides. It has been demonstrated that two different sized, covalently bound probes 7-diethylaminocoumarin-3-carbonyl and Hilyte Fluor 488 (HLF), alter the rate and character of oligomerization to different extents. The ability of HLF to inhibit formation of highly ordered structures containing beta-sheets was also shown. The implications of our findings for using fluorescence methods in amyloidosis research are discussed and the advantages of this auto-fluorescence approach highlighted.

  15. Hydrogen-1, carbon-13, and nitrogen-15 NMR spectroscopy of Anabaena 7120 flavodoxin: Assignment of. beta. -sheet and flavin binding site resonances and analysis of protein-flavin interactions

    SciTech Connect

    Stockman, B.J.; Krezel, A.M.; Markley, J.L. ); Leonhardt, K.G.; Straus, N.A. )

    1990-10-01

    Sequence-specific {sup 1}H and {sup 13}C NMR assignments have been made for residues that form the five-stranded parallel {beta}-sheet and the flavin mononucleotide (FMN) binding site of oxidized Anabaena 7120 flavodoxin. Interstrand nuclear Overhauser enhancements (NOEs) indicate that the {beta}-sheet arrangement is similar to that observed in the crystal structure of the 70% homologous long-chain flavodoxin from Anacystis nidulans. A total of 62 NOEs were identified: 8 between protons of bound FMN, 29 between protons of the protein in the flavin binding site, and 25 between protons of bound FMN and protons of the protein. These constraints were used to determine the localized solution structure of the FMN binding site. The electronic environment and conformation of the protein-bound flavin isoalloxazine ring were investigated by determining {sup 13}C-{sup 1}H coupling constants. The carbonyl edge of the flavin ring was found to be slightly polarized. The xylene ring was found to be nonplanar. Tyrosine 94, located adjacent to the flavin isoalloxazine ring, was shown to have a hindered aromatic ring flip rate.

  16. Pattern formation in icosahedral virus capsids: the papova viruses and Nudaurelia capensis beta virus.

    PubMed Central

    Marzec, C J; Day, L A

    1993-01-01

    The capsids of the spherical viruses all show underlying icosahedral symmetry, yet they differ markedly in capsomere shape and in capsomere position and orientation. The capsid patterns presented by the capsomere shapes, positions, and orientations of three viruses (papilloma, SV40, and N beta V) have been generated dynamically through a bottom-up procedure which provides a basis for understanding the patterns. A capsomere shape is represented in two-dimensional cross-section by a mass or charge density on the surface of a sphere, given by an expansion in spherical harmonics, and referred to herein as a morphological unit (MU). A capsid pattern is represented by an icosahedrally symmetrical superposition of such densities, determined by the positions and orientations of its MUs on the spherical surface. The fitness of an arrangement of MUs is measured by an interaction integral through which all capsid elements interact with each other via an arbitrary function of distance. A capsid pattern is generated by allowing the correct number of approximately shaped MUs to move dynamically on the sphere, positioning themselves until an extremum of the fitness function is attained. The resulting patterns are largely independent of the details of both the capsomere representation and the interaction function; thus the patterns produced are generic. The simplest useful fitness function is sigma 2, the average square of the mass (or charge) density, a minimum of which corresponds to a "uniformly spaced" MU distribution; to good approximation, the electrostatic free energy of charged capsomeres, calculated from the linearized Poisson-Boltzmann equation, is proportional to sigma 2. With disks as MUs, the model generates the coordinated lattices familiar from the quasi-equivalence theory, indexed by triangulation numbers. Using fivefold MUs, the model generates the patterns observed at different radii within the T = 7 capsid of papilloma and at the surface of SV40; threefold MUs give the T = 4 pattern of Nudaurelia capensis beta virus. In all cases examined so far, the MU orientations are correctly found. Images FIGURE 5 FIGURE 6 FIGURE 8 FIGURE 9 PMID:8312492

  17. Characterization of Sheet Fracture Patterns in Polygonal-Jointed Lavas at Kokostick Butte, OR, and Mazama Ridge, WA: Investigation and Interpretation of Their Formation and Significance

    NASA Astrophysics Data System (ADS)

    Lodge, R. W.; Lescinsky, D. T.

    2006-12-01

    Polygonal joints in lava flows ("columns") are commonly equant leading to a model of formation associated with cooling in an isotropic stress field. This model, however, does not explain rectangular columns, sheet-like fractures, fractures with crosscutting relationships, and fractures with orientations other than perpendicular to the cooling surface. These fracture patterns are often observed at glaciated volcanoes. The presence of preferential fracture orientations suggests an applied stress component likely due to environmental conditions such as the presence of glaciers or flow dynamics such as down-slope settling or flow margin inflation. During this study we investigated the formation and significance of these non-equant fracture patterns to propose a model for their formation. These `abnormal' fracture patterns have not been discussed in the literature and may be important to better understanding the cooling conditions of such lava flows. To test these possibilities we studied Kokostick Butte dacite flow, OR (near South Sister), and Mazama Ridge andesite flow at Mount Rainier, WA. Both of these flows have well developed sheet-like fractures and display evidence of ice-contact during eruption and emplacement. Sheet fractures are long and continuous fractures that have perpendicular connecting fractures forming rectangular columns. The sheet-like fractures are largely parallel to each other on the exposure surface and the connecting fractures vary locally from primary fractures (associated with cooling toward flow interior) to secondary fractures (associated with cooling by water infiltration). Detailed measurements of fracture orientations and spacing were collected at Kokostick Butte and Mazama Ridge to examine the relationship between the sheet fractures and flow geometry. Preliminary results support this relationship and suggest these patterns likely form due to shear associated with small amounts of flow advance by the rapidly cooling lava. Laboratory studies have been undertaken to complement the field observations and measurements. Starch- water experiments have been proven a useful analogue for lava column formation. Various experimental setups involving different mixture thicknesses and compression of the mixture were utilized to simulate the stresses acting during ponding of lava against glacial ice and to produce different fracture morphologies and patterns. Initial results show that compression of the starch slurry results in non-equant fracture patterns with some sheet-like fracturing present.

  18. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing

    PubMed Central

    Masci, Paul P.; Crawford, Ross; Xiao, Yin

    2016-01-01

    Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process. PMID:26909757

  19. Mitochondrial beta-cyanoalanine synthase is essential for root hair formation in Arabidopsis thaliana.

    PubMed

    García, Irene; Castellano, José María; Vioque, Blanca; Solano, Roberto; Gotor, Cecilia; Romero, Luis C

    2010-10-01

    Cyanide is stoichiometrically produced as a coproduct of the ethylene biosynthesis pathway and is detoxified by β-cyanoalanine synthase enzymes. The molecular and phenotypical analysis of T-DNA insertion mutants of the mitochondrial β-cyanoalanine synthase CYS-C1 suggests that discrete accumulation of cyanide is not toxic for the plant and does not alter mitochondrial respiration rates but does act as a strong inhibitor of root hair development. The cys-c1 null allele is defective in root hair formation and accumulates cyanide in root tissues. The root hair defect is phenocopied in wild-type plants by the exogenous addition of cyanide to the growth medium and is reversed by the addition of hydroxocobalamin or by genetic complementation with the CYS-C1 gene. Hydroxocobalamin not only recovers the root phenotype of the mutant but also the formation of reactive oxygen species at the initial step of root hair tip growth. Transcriptional profiling of the cys-c1 mutant reveals that cyanide accumulation acts as a repressive signal for several genes encoding enzymes involved in cell wall rebuilding and the formation of the root hair tip as well as genes involved in ethylene signaling and metabolism. Our results demonstrate that mitochondrial β-cyanoalanine synthase activity is essential to maintain a low level of cyanide for proper root hair development. PMID:20935247

  20. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis.

    PubMed

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A; Confavreux, Christian; Galetta, Steven L; Rudick, Richard A; Lublin, Fred D; Weinstock-Guttman, Bianca; Wynn, Daniel R; Fisher, Elizabeth; Papadopoulou, Athina; Lynn, Frances; Panzara, Michael A; Sandrock, Alfred W

    2010-05-15

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277.5mm(3) versus 525.6mm(3); p<0.001). Compared with IFNbeta-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3mm(3) versus 2210.5mm(3); p<0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p<0.001), and a slower rate of brain atrophy during the second year of therapy (-0.31% versus -0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone. PMID:20236661

  1. Inhibition of islet amyloid polypeptide fibril formation by selenium-containing phycocyanin and prevention of beta cell apoptosis.

    PubMed

    Li, Xiaoling; Ma, Lijuan; Zheng, Wenjie; Chen, Tianfeng

    2014-10-01

    Human islet amyloid polypeptide (hIAPP) fibril is the major constituent of amyloid deposits in pancreatic islets of type 2 diabetes. Misfolding and hIAPP fibril formation are thought to be important in the pathogenesis of diabetes. Studies have showed that selenium-containing phycocyanin (Se-PC) inhibited the fibrillation of hIAPP to form nanoscale particles, which is mainly by interfering with the combination between hIAPP. Small nanoscale oligomers tended to grow into larger nanoparticles and the size of nanoparticles increased with the incubation time. By interfering with the fibrillation of hIAPP and altering the structure, Se-PC alleviated hIAPP-induced cell apoptosis. Meantime, generation of ROS produced during the fibrillation process was inhibited, which was proposed to be the main factor for the hIAPP-cytotoxicity in beta cells. Taken together, Se-PC inhibited hIAPP fibrillation, thus suppressed the formation of ROS to show protective effect on hIAPP mediated cell apoptosis. Our studies provide useful information for our understanding of the interaction mechanisms of Se-PC on hIAPP structure and protective mechanisms on hIAPP cytotoxicity, presenting useful candidate for anti-diabetes drug development. PMID:25034964

  2. Controllable formation of graphene and graphene oxide sheets using photo-catalytic reduction and oxygen plasma treatment

    NASA Astrophysics Data System (ADS)

    Ostovari, Fatemeh; Abdi, Yaser; Ghasemi, Foad

    2012-12-01

    Au/SiO2/Si interdigital electrodes with thickness of 1 ?m were created on silicon substrate. Graphene oxide (GO) sheets hanging from these electrodes were obtained by spin coating of chemically synthesized GO dispersed in water. We used UV-light-induced photo-catalytic activity of titanium oxide nanoparticles to reduce the GO layer. Effects of the photo-induced chemical reduction on the conductivity of the GO were investigated. Also, low power DC plasma was used for oxidation of the sheets. Oxygen bombardment leads to sheets with low electrical conductivity. Measurements show that graphene and GO sheets with the controlled electrical conductivity were obtained by these processes. Scanning electron and atomic force microscopy were used to study the morphology of the TiO2/GO and graphene structures. X-ray diffraction and Raman scattering analysis were used to verify the structural characteristics of the prepared sheets. Analysis showed a gradual increase in the number of C-O bonds on the surface of the graphene layer as a result of increasing the time of plasma bombardment. Based on the Raman spectroscopy, the photo-catalytic activity of TiO2 nanoparticles resulted in a decrease in the number of C-O bonds.

  3. TGF-{beta} signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts

    SciTech Connect

    Luciakova, Katarina; Kollarovic, Gabriel; Kretova, Miroslava; Sabova, Ludmila; Nelson, B. Dean

    2011-08-05

    Highlights: {yields} TGF-{beta} induces the formation of unique nuclear NF1/Smad4 complexes that repress expression of the ANT-2 gene. {yields} Repression is mediated through an NF1-dependent repressor element in the promoter. {yields} The formation of NF1/Smad4 complexes and the repression of ANT2 are prevented by inhibitors of p38 kinase and TGF-{beta} RI. {yields} NF1/Smad complexes implicate novel role for NF1 and Smad proteins in the regulation of growth. -- Abstract: We earlier reported the formation of a unique nuclear NF1/Smad complex in serum-restricted fibroblasts that acts as an NF1-dependent repressor of the human adenine nucleotide translocase-2 gene (ANT2) [K. Luciakova, G. Kollarovic, P. Barath, B.D. Nelson, Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex, Biochem. J. 412 (2008) 123-130]. In the present study, we show that TGF-{beta}, like serum-restriction: (a) induces the formation of NF1/Smad repressor complexes, (b) increases binding of the complexes to the repressor elements (Go elements) in the ANT2 promoter, and (c) inhibits ANT2 expression. Repression of ANT2 by TGF-{beta} is eliminated by mutating the NF1 binding sites in the Go repressor elements. All of the above responses to TGF-{beta} are prevented by inhibitors of TGF-{beta} RI and MAPK p38. These inhibitors also prevent NF1/Smad4 repressor complex formation and repression of ANT2 expression in serum-restricted cells, suggesting that similar signaling pathways are initiated by TGF-{beta} and serum-restriction. The present finding that NF1/Smad4 repressor complexes are formed through TGF-{beta} signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state.

  4. Beta Thalassemia

    MedlinePLUS

    ... chromosomes 11 _ A person with beta thalassemia trait has one abnormal beta globin gene To understand ... one abnormal beta globin gene have beta thalassemia trait (also known as beta thalassemia minor). BETA THALASSEMIA ...

  5. Intermediacy of poly(L-proline) II and ?-strand conformations in poly(L-lysine) ?-sheet formation, probed by temperature-jump/UV resonance Raman spectroscopy

    PubMed Central

    JiJi, Renee D.; Balakrishnan, Gurusamy; Hu, Ying; Spiro, Thomas G.

    2008-01-01

    Ultraviolet resonance Raman spectroscopy (UVRR) in combination with a nanosecond temperature-jump (T-jump) was used to investigate early steps in the temperature induced ?-helix to ?-sheet conformational transition of poly(L-lysine) (poly(K)). Excitation at 197 nm from a tunable frequency-quadrupled Ti:Sapphire laser provided high-quality UVRR spectra, containing multiple conformation-sensitive amide bands. Although unionized poly(K) (pH 11.6) is mainly ?-helical below 30C, there is a detectable fraction (?15 %) of unfolded polypeptide, which is mainly in the polyproline II (PPII) conformation. However, deviations from the expected amide I and II signals indicate an additional conformation, suggested to be ?-strand. Above 30C unionized poly(K) forms ?-sheet at a rate (minutes) which increases with increasing temperature. A 22 44C T-jump is accompanied by prompt amide I and II difference signals suggested to arise from a rapid shift in the PPII/?-strand equilibrium. These signals are superimposed on a subsequently evolving difference spectrum which is characteristic of PPII, although the extent of conversion is low, ? 2 % at the 3 ?s time limit of the experiment. The rise time of the PPII signals is ?250 ns, consistent with melting of short ?-helical segments. A model is proposed in which the melted PPII segments interconvert with ?-strand conformation, whose association through inter-strand H-bonding nucleates the formation of ?-sheet. The intrinsic propensity for ?-strand formation could be a determinant of ?-sheet induction time, with implications for the onset of amyloid diseases. PMID:16388578

  6. Self-assembly and mineralization of genetically modifiable biological nanofibers driven by beta-structure formation

    PubMed Central

    Xu, Hong; Cao, Binrui; George, Anne; Mao, Chuanbin

    2011-01-01

    Bio-inspired mineralization is an innovative approach to the fabrication of bone biomaterials mimicking the natural bone. Bone mineral hydroxylapatite (HAP) is preferentially oriented with c-axis parallel to collagen fibers in natural bone. However, such orientation control is not easy to achieve in artificial bone biomaterials. To overcome the lack of such orientation control, we fabricated a phage-HAP composite by genetically engineering M13 phage, a non-toxic bio-nanofiber, with two HAP-nucleating peptides derived from one of the non-collagenous proteins, Dentin Matrix Protein-1 (DMP1). The phage is a biological nanofiber that can be mass produced by infecting bacteria and is non-toxic to human beings. The resultant HAP-nucleating phages are able to self-assemble into bundles by forming ?-structure between the peptides displayed on their side walls. The ?-structure further promotes the oriented nucleation and growth of HAP crystals within the nanofibrous phage bundles with their c-axis preferentially parallel to the bundles. We proposed that the preferred orientation resulted from the stereochemical matching between the negatively charged amino acid residues within the ?-structure and the positively charged calcium ions on the (001) plane of HAP crystals. The self-assembly and mineralization driven by the ?-structure formation represent a new route for fabricating mineralized fibers that can serve as building blocks in forming bone repair biomaterials and mimic the basic structure of natural bones. PMID:21520924

  7. Beta-hexosaminidase activity of the oral pathogen Tannerella forsythia influences biofilm formation on glycoprotein substrates.

    PubMed

    Roy, Sumita; Phansopa, Chatchawal; Stafford, Prachi; Honma, Kiyonobu; Douglas, C W Ian; Sharma, Ashu; Stafford, Graham P

    2012-06-01

    Tannerella forsythia is an important pathogen in periodontal disease. Previously, we showed that its sialidase activity is key to utilization of sialic acid from a range of human glycoproteins for biofilm growth and initial adhesion. Removal of terminal sialic acid residues often exposes ?-linked glucosamine or galactosamine, which may also be important adhesive molecules. In turn, these residues are often removed by a group of enzymes known as ?-hexosaminidases. We show here that T. forsythia has the ability to cleave glucosamine and galactosamine from model substrates and that this activity can be inhibited by the hexosaminidase inhibitor PugNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino N-phenyl carbamate). We now demonstrate for the first time that ?-hexosaminidase activity plays a role in biofilm growth on glycoprotein-coated surfaces because biofilm growth and initial cell adhesion are inhibited by PugNAc. In contrast, adhesion to siallo-glycoprotein-coated surfaces is unaltered by PugNAc in the absence of sialidase activity (using a sialidase-deficient mutant) or surprisingly on the clinically relevant substrates saliva or serum. These data indicate that ?-hexosaminidase activity has a significant role in biofilm formation in combination with sialidase activity in the biofilm lifestyle of T. forsythia. PMID:22276920

  8. Beta-sheet secondary structure of the trimeric globular domain of C1q of complement and collagen types VIII and X by Fourier-transform infrared spectroscopy and averaged structure predictions.

    PubMed Central

    Smith, K F; Haris, P I; Chapman, D; Reid, K B; Perkins, S J

    1994-01-01

    C1q plays a key role in the recognition of immune complexes, thereby initiating the classical pathway of complement activation. Although the triple-helix conformation of its N-terminal segment is well established, the secondary structure of the trimeric globular C-terminal domain is as yet unknown. The secondary structures of human C1q and C1q stalks and pepsin-extracted human collagen types I, III and IV (with no significant non-collagen-like structure) were studied by Fourier-transform i.r. spectroscopy in 2H2O buffers. After second-derivative calculation to resolve the fine structure of the broad amide I band, the Fourier-transform i.r. spectrum of C1q showed two major bands, one at 1637 cm-1, which is a characteristic frequency for beta-sheets, and one at 1661 cm-1. Both major bands were also detected for Clq in H2O buffers. Only the second major band was observed at 1655 cm-1 in pepsin-digested C1q which contains primarily the N-terminal triple-helix region. The Fourier-transform i.r. spectra of collagen in 2H2O also showed a major band at 1659 cm-1 (and minor bands at 1632 cm-1 and 1682 cm-1). It is concluded that the C1q globular heads contain primarily beta-sheet structure. The C-terminal domains of C1q show approximately 25% sequence identity with the non-collagen-like C-terminal regions of the short-chain collagen types VIII and X. To complement the Fourier-transform-i.r. spectroscopic data, averaged Robson and Chou-Fasman structure predictions on 15 similar sequences for the globular domains of C1q and collagen types VIII and X were performed. These showed a clear pattern of ten beta-strands interspersed by beta-turns and /or loops. Residues thought to be important for C1q-immune complex interactions with IgG and IgM were predicted to be at a surface-exposed loop. Sequence insertions and deletions, glycosylation sites, the free cysteine residue and RGD recognition sequences were also predicted to be at surface-exposed positions. Images Figure 4 PMID:8037678

  9. Formation and evolution of high-plasma-pressure region in the near-Earth plasma sheet: Precursor and postcursor of substorm expansion onset

    NASA Astrophysics Data System (ADS)

    Yao, Y.; Ebihara, Y.; Tanaka, T.

    2015-08-01

    Cause of substorm expansion onset is one of the major problems in the magnetospheric study. On the basis of a global magnetohydrodynamic (MHD) simulation, Tanaka et al. (2010) suggested that formation and evolution of a high-pressure region (HPR) in the near-Earth plasma sheet could result in sudden intensification of the Region 1 field-aligned current and the westward auroral electrojet. In this sense, the formation and evolution of the HPR are a key in understanding the cause of the onset. On 5 April 2009, three probes of the Time History of Events and Macroscale Interactions during Substorms (THEMIS) were located at XGSM~-11 Re around the equator, which provide unique opportunity to investigate the spatial-temporal evolution of the HPR near the substorm expansion onset. Just before the onset, a positive excursion of the plasma pressure appeared at the outermost probe first, followed by the inner ones. Just after the onset, the opposite sequence took place. A positive excursion of the Y component of the current density was observed near the onset by the THEMIS probes and followed by a decrease trend. A similar variation was also found in the MHD simulation. All these features are consistent with the simulation result that a squeeze of the plasma from the plasma sheet results in the formation of the HPR before the onset and that the accumulated plasma spreads outward after the onset. The HPR is shown to be important for the dynamics of the magnetosphere during a substorm.

  10. An RGD spacing of 440 nm is sufficient for integrin alpha V beta 3- mediated fibroblast spreading and 140 nm for focal contact and stress fiber formation

    PubMed Central

    1991-01-01

    The synthetic peptide Gly-Arg-Gly-Asp-Tyr (GRGDY), which contains the RGD sequence of several adhesion molecules, was covalently grafted to the surface of otherwise poorly adhesive glass substrates and was used to determine the minimal number of ligand-receptor interactions required for complete spreading of human foreskin fibroblasts. Well- defined adhesion substrates were prepared with GRGDY between 10(-3) fmol/cm2 and 10(4) fmol/cm2. As the adhesion ligand surface concentration was varied, several distinct morphologies of adherent cells were observed and categorized. The population of fully spread cells at 4 h reached a maximum at 1 fmol/cm2, with no further increases up to 10(4) fmol/cm2. Although maximal cell spreading was obtained at 1 fmol/cm2, focal contacts and stress fibers failed to form at RGD surface concentrations below 10 fmol/cm2. The minimal peptide spacings obtained in this work correspond to 440 nm for spreading and 140 nm for focal contact formation, and are much larger than those reported in previous studies with adsorbed adhesion proteins, adsorbed RGD-albumin conjugates, or peptide-grafted polyacrylamide gels. Vitronectin receptor antiserum specific for integrin alpha V beta 3 blocked cell adhesion and spreading on substrates containing 100 fmol/cm2 of surface- bound GRGDY, while fibronectin receptor antiserum specific for alpha 5 beta 1 did not. Furthermore, alpha V beta 3 was observed to cluster into focal contacts in spread cells, but alpha 5 beta 1 did not. It was thus concluded that a peptide-to-peptide spacing of 440 nm was required for alpha V beta 3-mediated cellular spreading, while 140 nm was required for alpha V beta 3-mediated focal contact formation and normal stress fiber organization in human foreskin fibroblasts; these spacings represent much fewer ligands than were previously thought to be required. PMID:1714913

  11. Anatomy and controlling factors of a Late Cretaceous Aeolian sand sheet: The Marlia and the Adamantina formations, NW Bauru Basin, Brazil

    NASA Astrophysics Data System (ADS)

    Basilici, Giorgio; Fhr Dal'B, Patrick Francisco

    2010-04-01

    Few previous studies have given significant consideration to the palaeosols in aeolian sand sheet sedimentary successions and, mainly, to their palaeoenvironmental and stratigraphic meaning in interaction with the deposits. These themes are considered in this study that deals with the depositional architecture and the factors controlling the construction, accumulation and preservation of an ancient aeolian sand sheet, that forms part of the Adamantina and Marlia formations, in the Bauru Basin (Late Cretaceous, Brazil). In the NW portion of the Bauru Basin, these two units, ca 220 m thick, consist of sandstone, and secondarily of sandy conglomerate and mudstone, and are characterised by vertically alternated palaeosols and deposits. Facies analyses of the deposits and macroscopic characterisation of the palaeosols in 45 outcrops were integrated with laboratory analyses that consisted in descriptions of slabs of rock samples, petrographic analyses, clay mineralogy determination, geochemical analyses of the major oxides, and micromorphological characterisation of the palaeosols. Three architectural elements were recognised: palaeosols, wind-ripple-dominated aeolian sand sheet deposits, and ephemeral river deposits. The palaeosols constitute 66% of the entire sedimentary succession, and consist principally of Aridisols and, subordinately, of Alfisols, Vertisols, and Entisols. The wind-ripple-dominated aeolian sand sheet deposits (25%) are composed of sandstone, organised in translatent climbing wind-ripple strata, and secondarily of sandstone and mudstone deposited by infrequent floods. The ephemeral river deposits (9%) consist of sandy conglomerates 4 m thick and ca 2 km wide. Wind-ripple-dominated aeolian sand sheet deposits formed during relatively dry climate period on an unstable topographic surface of an aeolian sand sheet, where aeolian deposition or erosion prevailed. Palaeosols and ephemeral river deposits formed in a more humid climate period on a stable topographic surface of the aeolian sand sheet. Six bounding surfaces permitted the subdivision of the study formations into genetic geological bodies, revealing different spatial and temporal orders. Two first order surfaces separate mature palaeosol profiles (Aridisols, Alfisols, and Vertisols) from overlying aeolian deposits or other mature palaeosol profiles. A second order surface separates immature palaeosols (Entisols) from overlying aeolian deposits. A third order surface constitutes the channel bottom. A fourth order surface is located at the bottom of flood deposits. A fifth order surface divides translatent wind-ripple. The constructional phase of the aeolian sand sheet occurred during the relatively dry climate period, when the available sediment was supplied from the material originally deposited by rivers and stored during a more humid period (primary supply), and by soil erosion during a drier climate (secondary supply). The accumulation surface was controlled during the drier climate by cemented Bk horizons over Aridisols and by the force of the wind blowing over the other soils or deposits. Otherwise, during the more humid climate, the accumulation surface was a stabilised surface represented by the soil. Preservation was dominated by tectonically induced subsidence and burial.

  12. Intrastriatal injection of interleukin-1 beta triggers the formation of neuromyelitis optica-like lesions in NMO-IgG seropositive rats

    PubMed Central

    2013-01-01

    Background Neuromyelitis optica (NMO) is a severe, disabling disease of the central nervous system (CNS) characterized by the formation of astrocyte-destructive, neutrophil-dominated inflammatory lesions in the spinal cord and optic nerves. These lesions are initiated by the binding of pathogenic aquaporin 4 (AQP4)-specific autoantibodies to astrocytes and subsequent complement-mediated lysis of these cells. Typically, these lesions form in a setting of CNS inflammation, where the bloodbrain barrier is open for the entry of antibodies and complement. However, it remained unclear to which extent pro-inflammatory cytokines and chemokines contribute to the formation of NMO lesions. To specifically address this question, we injected the cytokines interleukin-1 beta, tumor necrosis factor alpha, interleukin-6, interferon gamma and the chemokine CXCL2 into the striatum of NMO-IgG seropositive rats and analyzed the tissue 24 hours later by immunohistochemistry. Results All injected cytokines and chemokines led to profound leakage of immunoglobulins into the injected hemisphere, but only interleukin-1 beta induced the formation of perivascular, neutrophil-infiltrated lesions with AQP4 loss and complement-mediated astrocyte destruction distant from the needle tract. Treatment of rat brain endothelial cells with interleukin-1 beta, but not with any other cytokine or chemokine applied at the same concentration and over the same period of time, caused profound upregulation of granulocyte-recruiting and supporting molecules. Injection of interleukin-1 beta caused higher numbers of blood vessels with perivascular, cellular C1q reactivity than any other cytokine tested. Finally, the screening of a large sample of CNS lesions from NMO and multiple sclerosis patients revealed large numbers of interleukin-1 beta-reactive macrophages/activated microglial cells in active NMO lesions but not in MS lesions with comparable lesion activity and location. Conclusions Our data strongly suggest that interleukin-1 beta released in NMO lesions and interleukin-1 beta-induced production/accumulation of complement factors (like C1q) facilitate neutrophil entry and BBB breakdown in the vicinity of NMO lesions, and might thus be an important secondary factor for lesion formation, possibly by paving the ground for rapid lesion growth and amplified immune cell recruitment to this site. PMID:24252536

  13. Architectural variability of confined turbidite sheet-sands: facies, geometry and infill of associated elementary channels. Examples from the Trois Evchs Basin, Annot Sandstone Formation, SE France

    NASA Astrophysics Data System (ADS)

    Etienne, S.; Mulder, T.; Pace, A.; Bez, M.; Desaubliaux, G.

    2012-04-01

    The worldwide known Annot Sandstone Formation has been considered as a reference of confined siliciclastic turbidite system. This formation crops out in SE France and represents the Upper Eocene to Lower Oligocene gravitary infill of complex foreland basins, developed in front of the Alpine thrusts. This system can be assimilated as a sand-rich turbidite ramp, sourced by multiple fan deltas leading to topographically complex sub-basins. Highly bypassing channelized systems dominate in the most proximal and most confined areas. They distally evolve to relatively less confined areas, in which sedimentary bodies appear to be more continuous and homogenous on a regional scale. These last architectural elements, defined as sheet-sands or depositional lobes, have been the focus of this study in poorly documented areas. From an important dataset made of very high resolution outcrop correlations (gathered mainly in the Trois Evchs and Lauzanier sub-basins), we have quantified the complex distribution of sedimentary facies and structures, grain-size and key surfaces in sand-rich sheets. This was done to understand their variability from depositional event to architectural element scales and to better characterize dimensions and characteristics of their components. Six main types of architectural elements were defined, composed of both channelized and unchannelized elements. Channelized units show a high variability in terms of facies, geometry and patterns of infill that are related to multiple erosional and depositional processes, which will be discussed. We notably relate some evidences of sinuous channels, represented by lateral accretion deposits in the channel complex axis and by low angle cross-bedded facies. We interpret this particular facies as the result of flow deconfinement and overbanks above channel margins. The stratigraphic analysis of elementary objects allows us to propose a genetic model and a spatial distribution model of sheet-sand architectural elements. The latter provides their longitudinal repartition, from proximal vertically stacked internal channels to distal compensating sheets. Those features have not been accurately described in relatively distal sand-rich turbidite deposits so far and this high internal variability necessarily implies heterogeneities both in terms of petrophysical characteristics and reservoir connection. Besides, it also implies reconsidering sedimentary processes involved in these environments. Key Words: Annot Sandstones, Confined Systems, Reservoir Heterogeneities, Turbidite Sheet-sands.

  14. [Beta]-Adrenergic Receptors in the Insular Cortex are Differentially Involved in Aversive vs. Incidental Context Memory Formation

    ERIC Educational Resources Information Center

    Miranda, Maria Isabel; Sabath, Elizabeth; Nunez-Jaramillo, Luis; Puron-Sierra, Liliana

    2011-01-01

    The goal of this research was to determine the effects of [beta]-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the [beta]-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition…

  15. [Beta]-Adrenergic Receptors in the Insular Cortex are Differentially Involved in Aversive vs. Incidental Context Memory Formation

    ERIC Educational Resources Information Center

    Miranda, Maria Isabel; Sabath, Elizabeth; Nunez-Jaramillo, Luis; Puron-Sierra, Liliana

    2011-01-01

    The goal of this research was to determine the effects of [beta]-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the [beta]-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition

  16. Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to ?-sheet in amyloid fibril formation

    NASA Astrophysics Data System (ADS)

    Bleiholder, Christian; Dupuis, Nicholas F.; Wyttenbach, Thomas; Bowers, Michael T.

    2011-02-01

    Amyloid cascades that lead to peptide ?-sheet fibrils and plaques are central to many important diseases. Recently, intermediate assemblies of these cascades were identified as the toxic agents that interact with cellular machinery. The location and cause of the transformation from a natively unstructured assembly to the ?-sheet oligomers found in all fibrils is important in understanding disease onset and the development of therapeutic agents. Largely, research on this early oligomeric region was unsuccessful because all the traditional techniques measure only the average oligomer properties of the ensemble. We utilized ion-mobility methods to deduce the peptide self-assembly mechanism and examined a series of amyloid-forming peptides clipped from larger peptides or proteins associated with disease. We provide unambiguous evidence for structural transitions in each of these fibril-forming peptide systems and establish the potential of this method for the development of therapeutic agents and drug evaluation.

  17. Double Mantle Plume Upwelling—A Possible Formation Mechanism of Beta Plateau and Devana Chasma,Venus

    NASA Astrophysics Data System (ADS)

    Ding, N.

    2009-12-01

    Ning Ding,Zuoxun Zeng,China University of Geosciences,Wuhan,430074,China NingDing.eagle@gmail.com Introduction:Venus represents a‘one plate planet’[1],and the uplift,fractures and volcanism in Beta Regio on Venus are considered to be formed by lithosphere uplift driven by a hot plume[2]. Based on the double peaking saddle landform,we suggest the tectonic pattern of double mantle plume upwelling to interpret the formation mechanism of Beta Plateau and Devana Chasma.We take a physical modeling to validate this possibility. Model:There is no ductile shear in Venus[3],so we use quartz sands to simulate the crust of Venus.We use two wood stickes 1.5cm in diameter rising from the rubber canvas slowly and straight till about half of the model,then falling down slowly and straight.The base is a hard rubber plate,in the center of which,there are two holes 3cm in diameter,and the distance between them is 5cm.The holes are covered by rubber canvas.We use the quartz sands in colours of white, red and black with particle size of 70 mess as the model materials. Result:Fig.1:At the beginning of the wood stickes upwelling,only fine radial cracks are formed above the upwelling from central to outside.With the upwelling continue,surface energy of the fine radial cracks increase and make the cracks unstable,finally,the fine radial cracks connect each other and form a fracture zone.And then the two mantle plume downwelling,the fracture zone is developed to form a chasma at the end. Fig.2:The four profiles all form reverse faults outside and normal faults inside.But the difference is the faults in the middle of the chasma goes deeper than others.It is the pattern of Beta Plateau where the tectonic rising is cut by Devana Chasma zone in the topographic features. Fig.3:From the tow fig., we can see two points similar:a.the elevation is high and distribution area is large around the area of two upwelling and it is high around the area of chasma,but the distribution area is small;b.both of them shows saddle shape and two highland connectting bya chasma. Discussion:Based on the‘Geology Map of V-17’,two highlands of Northern part of Devana Chasma,but the material Unit of North and South highland are different.The material Units of North highland are the oldest unit tt and t,the material Unit of South highland is pl and the material Unit of rift is r are both the youngest unit.From the Magellan SAR mosaic[5],we can clearly see Devana Chasma cut the material Unit of tt and pl.So the two highlands of Northern part of Devana Chasma are simultaneous formed.The younger material Unit of South highland of Northern part of Devana Chasma is because of the volcanic eruption of Theia Mons. Conclusion:The physical modeling validates the model of the double plume upwelling is a possible explanation. Acknowledgements:This research was supported by the National Teaching Bases For Geology(CUG)foundation funded. References:[1]I.López,Icarus2008[2]A.T.Basilevsky,Icarus2007[3]J.C.Aubele,2009,LPSC[4]A.V.Vezolainen,2003,Journalofgeophysicalres5earch[5]http://planetarynames.wr.usgs.gov/images/v17_comp&v29_comp.pdf Fig.1 Fig.2 Fig.3a,3b

  18. Conformational Stability of Fibrillar Amyloid-Beta Oligomers via Protofilament Pair Formation – A Systematic Computational Study

    PubMed Central

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

    2013-01-01

    Amyloid- (A) oligomers play a crucial role in Alzheimer’s disease due to their neurotoxic aggregation properties. Fibrillar A 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 -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 monomers. From that, we propose the following growth mechanism from A 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. PMID:23936224

  19. Utility of tricalcium phosphate and osteogenic matrix cell sheet constructs for bone defect reconstruction

    PubMed Central

    Ueha, Tomoyuki; Akahane, Manabu; Shimizu, Takamasa; Uchihara, Yoshinobu; Morita, Yusuke; Nitta, Naoya; Kido, Akira; Inagaki, Yusuke; Kawate, Kenji; Tanaka, Yasuhito

    2015-01-01

    AIM: To determine the effects of transplanting osteogenic matrix cell sheets and beta-tricalcium phosphate (TCP) constructs on bone formation in bone defects. METHODS: Osteogenic matrix cell sheets were prepared from bone marrow stromal cells (BMSCs), and a porous TCP ceramic was used as a scaffold. Three experimental groups were prepared, comprised of TCP scaffolds (1) seeded with BMSCs; (2) wrapped with osteogenic matrix cell sheets; or (3) both. Constructs were implanted into a femoral defect model in rats and bone growth was evaluated by radiography, histology, biochemistry, and mechanical testing after 8 wk. RESULTS: In bone defects, constructs implanted with cell sheets showed callus formation with segmental or continuous bone formation at 8 wk, in contrast to TCP seeded with BMSCs, which resulted in bone non-union. Wrapping TCP constructs with osteogenic matrix cell sheets increased their osteogenic potential and resulting bone formation, compared with conventional bone tissue engineering TCP scaffolds seeded with BMSCs. The compressive stiffness (mean SD) values were 225.0 95.7, 30.0 11.5, and 26.3 10.6 MPa for BMSC/TCP/Sheet constructs with continuous bone formation, BMSC/TCP/Sheet constructs with segmental bone formation, and BMSC/TCP constructs, respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation was significantly higher than those with segmental bone formation and BMSC/TCP constructs. CONCLUSION: This technique is an improvement over current methods, such as TCP substitution, and is useful for hard tissue reconstruction and inducing earlier bone union in defects. PMID:26131318

  20. Effect of dietary. beta. -carotene, vitamin A and selenium on formation of preneoplastic lesions in rat liver

    SciTech Connect

    Colford, J.; Parker, R.S.

    1986-03-05

    The effect of dietary ..beta..-carotene (BC), retinyl acetate (RA) and sodium selenite on formation of ..gamma..-glutamyltranspeptidase-positive foci in rat liver was investigated. Male Sprague-Dawley rats, 50g, were fed for 16 wks semipurified diets supplemented with either BC (500 mg/kg diet), RA (6400 IU/kg diet for wks 1-7 and 10,000 IU/kg for wks 8-16), 1.8 ppm selenium (Se) or both 1.8 ppm Se and 500 mg/kg BC. The control diet contained 0.1 ppm Se and 3200 IU RA/kg diet. During wks 3-4 rats received 10 intragastric doses of aflatoxin B/sub 1/ (0.4 mg/kg body weight/dose). Preneoplastic foci were quantitated at wk 16. Diet had no significant effect on growth rate or food consumption. None of the treatments resulted in significant differences in the number of foci per cm/sup 2/ liver section, but differences in focal size occurred. RA increased total focal area (mm/sup 2//cm/sup 2/ liver), while Se decreased focal area 5-fold. BC slightly decreased focal area. The combination of BC and Se was not as effective as Se alone. BC, RA, and BC-Se diets yielded equivalent levels of total liver retinol, which exceeded levels in control and Se rats by 30-fold. Livers from BC fed rats contained 4-5 ..mu..g BC/g liver. The different effects of dietary RA and BC on focal development may indicate a role for BC other than as a retinol precursor. The influence of each nutrient on focal size, but not number, implies they act during the post-initiation stage of focal development.

  1. Mechanism of martensite ?'1 single-crystals formation during deformation of beta1-CuZnAl single crystals with oriented distribution of subgrain boundaries

    NASA Astrophysics Data System (ADS)

    Bogdanowicz, W.; Wokulska, Krystyna

    1999-03-01

    (beta) 1-CuZnAl single-crystals were subject to uniaxial tension with subgrain boundaries parallel to the direction of tension. A relation between individual stages of martensite (gamma) '1 single-crystals formation and changes of mechanical stress was determined. The stress was assessed on the basis of diffraction reflexes half-width measurement, measured on a Bond diffractometer, that ensured a precise assessment of even minute changes.

  2. Global MHD simulations of the relative effects of solar wind features on cold dense plasma sheet formation during the August 31 2005 storm

    NASA Astrophysics Data System (ADS)

    Damiano, P. A.; Lotko, W.; Brambles, O. J.; Wiltberger, M. J.; Lyon, J.

    2009-12-01

    The solar wind data for the August 31 2005 storm incorporates a prolonged period of northward Bz followed by a sudden transition to an extended period of southward Bz. This northward to southward transition is one condition that leads to the formation of the cold dense plasma sheet. In addition to this evolution in Bz, the data also exhibits substantial variation in the solar wind By and dynamic pressure. In this study we present results from the Multi-Fluid-Lyon-Fedder-Mobarry (MFLFM) global simulation model of the August 31 storm. A baseline run incorporating the measured solar wind data is contrasted with more controlled simulations where the solar wind By is set to zero and the dynamic pressure is held constant for extended periods of time. The relative influence of these two parameters on the formation and evolution of the cold dense plasma sheet are studied along with the their influence on magnetosphere-ionosphere coupling. Initial results suggest that solar wind By has a stronger influence on the global characteristics of the system within the context of this storm. Additionally, results from a complementary analysis incorporating the effects of ionospheric oxygen outflow are reported.

  3. Efficient triple helix formation by oligodeoxyribonucleotides containing alpha- or beta-2-amino-5-(2-deoxy-D-ribofuranosyl) pyridine residues.

    PubMed Central

    Bates, P J; Laughton, C A; Jenkins, T C; Capaldi, D C; Roselt, P D; Reese, C B; Neidle, S

    1996-01-01

    Triple helices containing C+xGxC triplets are destabilised at physiological pH due to the requirement for base protonation of 2'-deoxycytidine (dC), which has a pKa of 4.3. The C nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (beta-AP) is structurally analogous to dC but is considerably more basic, with a pKa of 5.93. We have synthesised 5'-psoralen linked oligodeoxyribonucleotides (ODNs) containing thymidine (dT) and either beta-AP or its alpha-anomer (alpha-AP) and have assessed their ability to form triplexes with a double-stranded target derived from standard deoxynucleotides (i.e. beta-anomers). Third strand ODNs derived from dT and beta-AP were found to have considerably higher binding affinities for the target than the corresponding ODNs derived from dT and either dC or 5-methyl-2'-deoxycytidine (5-Me-dC). ODNs containing dT and alpha-AP also showed enhanced triplex formation with the duplex target and, in addition are more stable in serum-containing medium than standard oligopyrimidine-derived ODNs or ODNs derived from dT and beta-AP. Molecular modelling studies showed that an alpha-anomeric AP nucleotide can be accommodated within an otherwise beta-anomeric triplex with only minor perturbation of the triplex structure. Molecular dynamics (MD) simulations on triplexes containing either the alpha- or beta-anomer of (N1-protonated) AP showed that in both cases the base retained two standard hydrogen bonds to its associated guanine when the 'A-type' model of the triplex was used as the start-point for the simulation, but that bifurcated hydrogen bonds resulted when the alternative 'B-type' triplex model was used. The lack of a differential stability between alpha-AP- and beta-AP-containing triplexes at pH >7, predicted from the behaviour of the B-type models, suggests that the A-type models are more appropriate. PMID:8932369

  4. A novel pyrrolidine imide catalyzed direct formation of alpha,beta-unsaturated ketones from unmodified ketones and aldehydes.

    PubMed

    Wang, Wei; Mei, Yujiang; Li, Hao; Wang, Jian

    2005-02-17

    A method for direct, stereoselective preparation of (E)-alpha,beta-unsaturated ketones from ketones and aldehydes, promoted by a novel pyrrolidine imide organocatalyst, has been developed in moderate to high yields. Unlike the Claisen-Schmidt condensation and Lewis acid catalyzed tandem aldol-dehydration processes, this method provides mild reaction conditions to access alpha,beta-unsaturated ketones from simple, unmodified ketones. [reaction: see text] PMID:15704904

  5. Inhibitory effect of Bifidobacterium longum cultures on the azoxymethane-induced aberrant crypt foci formation and fecal bacterial beta-glucuronidase.

    PubMed

    Kulkarni, N; Reddy, B S

    1994-12-01

    Epidemiologic and experimental studies suggest that consumption of fermented milk products and lactic bacterial cultures that are used to ferment the dairy products, decrease the incidence of certain types of cancer. The present study was designed to determine the effect of lyophilized cultures of Bifidobacterium longum (B. longum), a lactic bacteria, on the azoxymethane (AOM)-induced preneoplastic lesions such as aberrant crypt foci (ACF) formation in the colon and on fecal bacterial beta-glucuronidase activity in male F344 rats. At 5 weeks of age, groups of animals were fed the AIN-76A (control) and the experimental diets containing 1.5% and 3% lyophilized cultures of B. longum. At 10 weeks of age, all animals received sc injection of AOM dissolved in normal saline at a dose rate of 20 mg/kg body wt, once weekly for 2 weeks. The animals were necropsied 6 weeks after the last AOM injection, and the ACF were visualized under light microscopy in the formalin-fixed, unsectioned methylene blue-stained colons where they were distinguished by their increased size, more prominent epithelial cells, and pericryptal space. The cecal contents were analyzed for bacterial beta-glucuronidase activity. The feeding of lyophilized cultures of B. longum significantly inhibited the ACF formation (53%) and the crypt multiplicity in the colon. A significant decrease in the fecal bacterial beta-glucuronidase was also observed in the animals fed the diets containing Bifidobacterium supplements as compared with control diet. These results demonstrate that B. longum in diet influences the metabolic activity of certain types of intestinal microflora that are involved in the production of beta-glucuronidase. Furthermore, the findings also suggest that B. longum supplements inhibit ACF formation, an early preneoplastic marker of malignant potential in the process of colon carcinogenesis. PMID:7800683

  6. Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-beta stability, oligomerization, and aggregation: amyloid-beta destabilization promotes annular protofibril formation.

    PubMed

    Chen, Wei-Ting; Liao, Yi-Hung; Yu, Hui-Ming; Cheng, Irene H; Chen, Yun-Ru

    2011-03-18

    Abnormally high concentrations of Zn(2+), Cu(2+), and Fe(3+) are present along with amyloid-? (A?) in the senile plaques in Alzheimer disease, where Al(3+) is also detected. A? aggregation is the key pathogenic event in Alzheimer disease, where A? oligomers are the major culprits. The fundamental mechanism of these metal ions on A? remains elusive. Here, we employ 4,4'-Bis(1-anilinonaphthalene 8-sulfonate) and tyrosine fluorescence, CD, stopped flow fluorescence, guanidine hydrochloride denaturation, and photo-induced cross-linking to elucidate the effect of Zn(2+), Cu(2+), Fe(3+), and Al(3+) on A? at the early stage of the aggregation. Furthermore, thioflavin T assay, dot blotting, and transmission electron microscopy are utilized to examine A? aggregation. Our results show that Al(3+) and Zn(2+), but not Cu(2+) and Fe(3+), induce larger hydrophobic exposures of A? conformation, resulting in its significant destabilization at the early stage. The metal ion binding induces A? conformational changes with micromolar binding affinities and millisecond binding kinetics. Cu(2+) and Zn(2+) induce similar assembly of transiently appearing A? oligomers at the early state. During the aggregation, we found that Zn(2+) exclusively promotes the annular protofibril formation without undergoing a nucleation process, whereas Cu(2+) and Fe(3+) inhibit fibril formation by prolonging the nucleation phases. Al(3+) also inhibits fibril formation; however, the annular oligomers co-exist in the aggregation pathway. In conclusion, Zn(2+), Cu(2+), Fe(3+), and Al(3+) adopt distinct folding and aggregation mechanisms to affect A?, where A? destabilization promotes annular protofibril formation. Our study facilitates the understanding of annular A? oligomer formation upon metal ion binding. PMID:21216965

  7. Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation.

    PubMed

    Kleemann, Robert; Gervois, Philippe P; Verschuren, Lars; Staels, Bart; Princen, Hans M G; Kooistra, Teake

    2003-01-15

    C-reactive protein (CRP) is a major acute-phase protein in humans. Elevated plasma CRP levels are a risk factor for cardiovascular disease. CRP is predominantly expressed in hepatocytes and is induced by interleukin-1 (IL-1) and IL-6 under inflammatory situations, such as the acute phase. Fibrates are hypolipidemic drugs that act through the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Fibrates have been shown to reduce elevated CRP levels in humans, but the molecular mechanism is unknown. In this study, we demonstrate that different PPAR-alpha activators suppress IL-1-induced, but not IL-6-induced, expression of CRP in primary human hepatocytes and HuH7 hepatoma cells. Induction of CRP expression by IL-1 occurs at the transcriptional level. Site-directed mutagenesis experiments show that IL-1 induces CRP expression through 2 overlapping response elements, the binding sites for CCAAT-box/enhancer-binding protein-beta (C/EBP-beta) and p50-nuclear factor-kappaB (p50-NFkappaB). Cotransfection of C/EBP-beta and p50-NFkappaB enhances CRP promoter activity, and coimmunoprecipitation experiments indicate that the increase in CRP promoter activity by IL-1 is related to the generation and nuclear accumulation of C/EBP-beta-p50-NFkappaB complexes. Interestingly, PPAR-alpha activators reduce the formation of nuclear C/EBP-beta-p50-NFkappaB complexes, and thereby CRP promoter activity, by 2 mechanisms. First, PPAR-alpha increases IkappaB-alpha expression and thus prevents p50-NFkappaB translocation to the nucleus. Second, fibrates decrease hepatic C/EBP-beta and p50-NFkappaB protein levels in mice in a PPAR-alpha-dependent way. Our findings identify C/EBP-beta and p50-NFkappaB as novel targets for PPAR-alpha and provide a molecular explanation for the reduction of plasma CRP levels by fibrates. PMID:12393563

  8. Calcium ion-induced formation of β-sheet/-turn structure leading to alteration of osteogenic activity of bone morphogenetic protein-2

    PubMed Central

    Zhang, Wenjing; He, Hongyan; Tian, Yu; Gan, Qi; Zhang, Jing; Yuan, Yuan; Liu, Changsheng

    2015-01-01

    Preserving bioactivity of bone morphogenetic protein 2 (BMP-2) still remains a challenge in protein-based therapy. It is not known how Ca2+ released from extracellular matrix or existing in physiological environment influences bioactivity in situ till now. Here, effects of extracellular Ca2+ on conformation and osteogenic bioactivity of recombinant human BMP-2 (rhBMP-2) were investigated systematically. In vitro results indicated that Ca2+ could bind rhBMP-2 rapidly and had no obvious effect on cell behaviors. Low concentration of Ca2+ (0.18 mM) enhanced rhBMP-2-induced osteogenic differentiation, while high Ca2+ concentration (>1.80 mM) exerted negative effect. In vivo ectopic bone formation exhibited similar trend. Further studies by circular dichroism spectroscopy, fluorescence spectroscopy, together with cell culture experiments revealed at low concentration, weak interaction of Ca2+ and rhBMP-2 slightly increased β-sheet/-turn content and facilitated recognition of BMP-2 and BMPRIA. But, high Ca2+ concentration (>1.8 mM) induced formation of Ca-rhBMP-2 complex and markedly increased content of β-sheet/-turn, which led to inhibition binding of rhBMP-2 and BMPRIA and thus suppression of downstream Smad1/5/8, ERK1/2 and p38 mitogen-associated protein kinase signaling pathways. Our work suggests osteogenic bioactivity of BMP-2 can be adjusted via extracellular Ca2+, which should provide guide and assist for development of BMP-2-based materials for bone regeneration. PMID:26212061

  9. Till formation under a soft-bedded palaeo-ice stream of the Scandinavian Ice Sheet, constrained using qualitative and quantitative microstructural analyses

    NASA Astrophysics Data System (ADS)

    Narloch, Włodzimierz; Piotrowski, Jan A.; Wysota, Wojciech; Tylmann, Karol

    2015-08-01

    This study combines micro- and macroscale studies, laboratory experiments and quantitative analyses to decipher processes of till formation under a palaeo-ice stream and the nature of subglacial sediment deformation. Till micromorphology (grain lineations, grain stacks, turbate structures, crushed grains, intraclasts and domains), grain-size and till fabric data are used to investigate a basal till generated by the Vistula Ice Stream of the Scandinavian Ice Sheet during the last glaciation in north-central Poland. A comparison of microstructures from the in situ basal till and laboratory-sheared till experiments show statistical relationships between the number of grain lineations and grain stacks; and between the number of grain lineations and turbate structures. Microstructures in the in situ till document both brittle and ductile styles of deformation, possibly due to fluctuating basal water pressures beneath the ice stream. No systematic vertical and lateral trends are detected in the parameters investigated in the in situ till, which suggests a subglacial mosaic of relatively stable and unstable areas. This situation can be explained by an unscaled space-transgressive model of subglacial till formation whereby at any given point in time different processes operated in different places under the ice sheet, possibly related to the distance from the ice margin and water pressure at the ice-bed interface. A new quantitative measure reflecting the relationship between the number of grain lineations and grain stacks may be helpful in discriminating between pervasive and non-pervasive deformation and constraining the degree of stress heterogeneity within a deformed bed. Independent strain magnitude estimations revealed by a quantitative analysis of micro- and macro-particle data show low cumulative strain in the ice-stream till in the order of 10-102.

  10. Ga(8)Br(8).6NEt(3): formation and structure of donor-stabilized GaBr. A nanoscaled step on the way to beta-gallium?

    PubMed

    Duan, Taike; Henke, Patrick; Stsser, Gregor; Zhang, Qian-Feng; Schnckel, Hansgeorg

    2010-02-01

    Because of their thermodynamic instability, their sophisticated formation, and their high reactivity, only three textbook examples of Al(I)/Ga(I) subhalides have been crystallized so far: Al(4)Br(4), Al(4)I(4), and Ga(8)I(8). Here, we present the formation and structural characterization of molecular Ga(8)Br(8) species. The different structures of Ga(8)I(8) and Ga(8)Br(8) are discussed with regard to their different formation conditions and their different thermodynamic stability based on results from DFT calculations. Structural as well as thermodynamic properties of Ga(8)I(8) and Ga(8)Br(8) are strongly related to the low-temperature modifications beta-Ga and gamma-Ga. Therefore, our fruitful hypothesis about the fundamental relation between structure and energy of a number of metalloid clusters and the corresponding element modifications is now supported by two binary Ga(I)-halide compounds. PMID:20063876

  11. Stability of single sheet GNNQQNY aggregates analyzed by replica exchange molecular dynamics: Antiparallel versus parallel association

    SciTech Connect

    Vitagliano, Luigi; Esposito, Luciana; Pedone, Carlo; De Simone, Alfonso

    2008-12-26

    Protein and peptide aggregation into amyloid plaques is associated with a large variety of neurodegenerative diseases. The definition of the molecular bases of these pathologies is hampered by the transient nature of pre-fibrillar small-oligomers that are considered the toxic species. The ability of the peptide GNNQQNY to form amyloid-like structures makes it a good model to investigate the complex processes involved into amyloid fiber formation. By employing full atomistic replica exchange molecular dynamics simulations, we constructed the free energy surface of small assemblies of GNNQQNY to gain novel insights into the fiber formation process. The calculations suggest that the peptide exhibits a remarkable tendency to form both parallel and antiparallel {beta}-sheets. The data show that GNNQQNY preference for parallel or antiparallel {beta}-sheets is governed by a subtle balance of factors including assemblies' size, sidechain-sidechain interactions and pH. The samplings analysis provides a rationale to the observed trends.

  12. Fibril stability in solutions of twisted Format="TEX"/>-sheet peptides: a new kind of micellization in chiral systems

    NASA Astrophysics Data System (ADS)

    Nyrkova, I. A.; Semenov, A. N.; Aggeli, A.; Boden, N.

    2000-10-01

    The problem of fibril (fibre) formation in chiral systems is explored theoretically being supported by experiments on synthetic de novo 11-mer peptide forming self-assembled -sheet tapes. Experimental data unambiguously indicate that the tapes form fibrils of nearly monodisperse thickness ca. 8-10 nm. Fibril formation and stabilisation are attributed to inter-tape face-to-face attraction and their intrinsic twist, correspondingly. The proposed theory is capable of predicting the fibril aggregation number and its equilibrium twist in terms of molecular parameters of the primary tapes. The suggested novel mechanism of twist stabilisation of finite aggregates (fibrils) is different to the well-known stabilisation of micelles in amphiphilic systems, and it is likely to explain the formation and stability of fibrils in a wide variety of systems including proteinaceous amyloid fibres, sickle-cell hemoglobin fibres responsible for HbS anemia, corkscrew threads found in chromonics in the presence of chiral additives and native cellulose microfibrillar crystallites. The theory also makes it possible to extract the basic molecular parameters of primary tapes (inter-tape attraction energy, helical twist step, elastic moduli) from the experimental data.

  13. FORMATION OF BETA-HYDROXYCARBONYLS FROM THE OH RADICAL-INITIATED REACTIONS OF SELECTED ALKENES (R825252)

    EPA Science Inventory

    beta2.gif" BORDER=0 ALIGN="middle">-Hydroxycarbonyls can be formed from the gas-phase
    reactions of alkenes with the OH radical, both in the presence
    and in the absence of NO. To date, because of analytical
    difficulties, few data have been r...

  14. The Influence of Welding Parameters on the Nugget Formation of Resistance Spot Welding of Inconel 625 Sheets

    NASA Astrophysics Data System (ADS)

    Rezaei Ashtiani, Hamid Reza; Zarandooz, Roozbeh

    2015-09-01

    A 2D axisymmetric electro-thermo-mechanical finite element (FE) model is developed to investigate the effect of current intensity, welding time, and electrode tip diameter on temperature distributions and nugget size in resistance spot welding (RSW) process of Inconel 625 superalloy sheets using ABAQUS commercial software package. The coupled electro-thermal analysis and uncoupled thermal-mechanical analysis are used for modeling process. In order to improve accuracy of simulation, material properties including physical, thermal, and mechanical properties have been considered to be temperature dependent. The thickness and diameter of computed weld nuggets are compared with experimental results and good agreement is observed. So, FE model developed in this paper provides prediction of quality and shape of the weld nuggets and temperature distributions with variation of each process parameter, suitably. Utilizing this FE model assists in adjusting RSW parameters, so that expensive experimental process can be avoided. The results show that increasing welding time and current intensity lead to an increase in the nugget size and electrode indentation, whereas increasing electrode tip diameter decreases nugget size and electrode indentation.

  15. Late Noachian and early Hesperian ridge systems in the south circumpolar Dorsa Argentea Formation, Mars: Evidence for two stages of melting of an extensive late Noachian ice sheet

    NASA Astrophysics Data System (ADS)

    Kress, Ailish M.; Head, James W.

    2015-05-01

    The Dorsa Argentea Formation (DAF), extending from 270°-100° E and 70°-90° S, is a huge circumpolar deposit surrounding and underlying the Late Amazonian South Polar Layered Deposits (SPLD) of Mars. Currently mapped as Early-Late Hesperian in age, the Dorsa Argentea Formation has been interpreted as volatile-rich, possibly representing the remnants of an ancient polar ice cap. Uncertain are its age (due to the possibility of poor crater retention in ice-related deposits), its mode of origin, the origin of the distinctive sinuous ridges and cavi that characterize the unit, and its significance in the climate history of Mars. In order to assess the age of activity associated with the DAF, we examined the ridge populations within the Dorsa Argentea Formation, mapping and characterizing seven different ridge systems (composed of nearly 4,000 ridges covering a total area of ~300,000 km2, with a cumulative length of ridges of ~51,000 km) and performing crater counts on them using the method of buffered crater counting to determine crater retention ages of the ridge populations. We examined the major characteristics of the ridge systems and found that the majority of them were consistent with an origin as eskers, sediment-filled subglacial drainage channels. Ridge morphologies reflect both distributed and channelized esker systems, and evidence is also seen that some ridges form looping moraine-like termini distal to some distributed systems. The ridge populations fall into two age groups: ridge systems between 270° and 0° E date to the Early Hesperian, but to the east, the Promethei Planum and the Chasmata ridge systems date to the Late Noachian. Thus, these ages, and esker and moraine-like morphologies, support the interpretation that the DAF is a remnant ice sheet deposit, and that the esker systems represent evidence of significant melting and drainage of meltwater from portions of this ice sheet, thus indicating at least some regions and/or periods of wet-based glaciation. The Late Noachian and Early Hesperian ages of the ridge systems closely correspond to the ages of valley network/open basin lake systems, representing runoff, drainage and storage of liquid water in non-polar regions of the surface of Mars. Potential causes of such wet-based conditions in the DAF include: 1) top-down melting due to atmospheric warming, 2) enhanced snow and ice accumulation and raising of the melting isotherm to the base of the ice sheet, or 3) basal melting associated with intrusive volcanism (volcano-ice interactions). The early phase of melting is closely correlated in time with valley network formation and thus may be due to global atmospheric warming, while the later phase of melting may be linked to Early Hesperian global volcanism and specific volcano-ice interactions (table mountains) in the DAF. Crater ages indicate that these wet-based conditions ceased by the Late Hesperian, and that further retreat of the DAF to its present configuration occurred largely through sublimation, not melting, thus preserving the extensive ridge systems. MARSIS radar data suggest that significant areas of layered, potentially ice-rich parts of the Dorsa Argentea Formation remain today.

  16. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate.

    PubMed

    Pelletier, Jeffrey C; Lundquist, Joseph T; Gilbert, Adam M; Alon, Nipa; Bex, Frederick J; Bhat, Bheem M; Bursavich, Mattew G; Coleburn, Valerie E; Felix, Luciana A; Green, Daniel M; Green, Paula; Hauze, Diane B; Kharode, Yogendra P; Lam, Ho-Sun; Lockhead, Susan R; Magolda, Ronald L; Matteo, Jeanne J; Mehlmann, John F; Milligan, Colleen; Murrills, Richard J; Pirrello, Jennifer; Selim, Sally; Sharp, Michael C; Unwalla, Ray J; Vera, Matthew D; Wrobel, Jay E; Yaworsky, Paul; Bodine, Peter V N

    2009-11-26

    A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration. PMID:19856966

  17. TGF{beta}-mediated formation of pRb-E2F complexes in human myeloid leukemia cells

    SciTech Connect

    Hu Xiaotang

    2008-05-02

    TGF{beta} is well known for its inhibitory effect on cell cycle G1 checkpoint kinases. However, its role in the control of pRb-E2F complexes is not well established. TGF{beta} inhibits phosphorylation of pRb at several serine and threonine residues and regulates the association of E2F transcription factors with pRb family proteins. Recent studies found that predominantly E2F-4, p130, and histone deacetylase (HDAC) are found to bind to corresponding E2F-responsive promoters in G0/G1 phase. As cells progress through mid-G1, p130-E2F4 complex are replaced by p107-E2F4 followed by activators E2F1, 2, and 3. pRb was not detectable in the promoters containing the E2F-responsive site in cycling cells but was associated with E2F4-p130 complexes or E2F4-p107 complexes during G0/G1 phase. In human myeloid leukemia cell line, MV4-11, TGF{beta} upregulated pRb-E2F-4 and p130-E2F-4, and downregulated p107-E2F-4 complexes. However, pRB-E2F1 and pRb-E2F3 complexes were found in proliferating cells but not in TGF{beta} arrested G1 cells. In addition, electrophoretic gel mobility shift assay (EMSA) could not detect pRb-E2F DNA-binding activities either in S or G1 phase but exhibited the existence of p107-E2F4 in proliferating cells and p130-E2F4 complexes in TGF{beta}-arrested G1 cells, respectively. Our data suggest that p107 and p130, but not pRb, and the repressor E2F, but not activator E2Fs, play a critical role in regulating E2F-responsive gene expression in TGF{beta}-mediated cell cycle control in human myeloid leukemia cells.

  18. Influence of Water Content on the β-Sheet Formation, Thermal Stability, Water Removal, and Mechanical Properties of Silk Materials.

    PubMed

    Yazawa, Kenjiro; Ishida, Kana; Masunaga, Hiroyasu; Hikima, Takaaki; Numata, Keiji

    2016-03-14

    Silk, which has excellent mechanical toughness and is lightweight, is used as a structural material in nature, for example, in silkworm cocoons and spider draglines. However, the industrial use of silk as a structural material has garnered little attention. For silk to be used as a structural material, its thermal processability and associated properties must be well understood. Although water molecules influence the glass transition of silk, the effects of water content on the other thermal properties of silks are not well understood. In this study, we prepared Bombyx mori cocoon raw fibers, degummed fibers, and films with different water contents and then investigated the effects of water content on crystallization, degradation, and water removal during thermal processing. Thermal gravimetric analyses of the silk materials showed that water content did not affect the thermal degradation temperature but did influence the water removal behavior. By increasing the water content of silk, the water molecules were removed at lower temperatures, indicating that the amount of free water in silk materials increased; additionally, the glass transition temperature decreased with increasing water plasticization. Differential scanning calorimetry and wide-angle X-ray scattering of the silk films also suggested that the water molecules in the amorphous regions of the silk films acted as a plasticizer and induced β-sheet crystallization. The plasticizing effect of water was not detected in silk fibers, owing to their lower amorphous content and mobility. The structural and mechanical characterizations of the silk films demonstrated the silk film prepared at RH 97% realized both crystallinity and ductility simultaneously. Thus, the thermal stability, mechanical, and other properties of silk materials are regulated by their water content and crystallinity. PMID:26835719

  19. Overexpression of granulocyte-macrophage colony-stimulating factor induces pulmonary granulation tissue formation and fibrosis by induction of transforming growth factor-beta 1 and myofibroblast accumulation.

    PubMed Central

    Xing, Z.; Tremblay, G. M.; Sime, P. J.; Gauldie, J.

    1997-01-01

    We have previously reported that transfer to rat lung of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene leads to high expression of GM-CSF between days 1 and 4 and granulation tissue formation followed by an irreversible fibrotic response starting from day 12 onward. In the current study, we investigated the underlying mechanisms. We found that GM-CSF overexpression did not enhance production of tumor necrosis factor-alpha in a significant manner at any time after GM-CSF gene transfer. However, the content of transforming growth factor-beta 1 in bronchoalveolar lavage fluid was markedly induced at day 4 and appeared to be maximal around day 7 and remained high at day 12. Macrophages purified from bronchoalveolar lavage fluid 7 days after GM-CSF gene transfer spontaneously released significant quantities of transforming growth factor-beta 1 protein in vitro. After peak transforming growth factor-beta 1 production was the emergence of alpha-smooth muscle actin-rich myofibroblasts. Accumulation of these cells was most prominent at day 12 within the granulation tissues and they were still present in fibrotic areas between days 12 and 24 and diminished markedly afterward. Thus, we provide the first in vivo evidence that tumor necrosis factor-alpha may be dissociated from participation in a fibrotic process in the lung and GM-CSF may play a more direct role in pulmonary fibrogenesis at least in part through its capability to induce transforming growth factor-beta 1 in macrophages and the subsequent emergence of myofibroblast phenotypes. This GM-CSF transgene lung model is useful for a stepwise dissection of both cellular and molecular events involved in pulmonary fibrosis. Images Figure 2 Figure 5 Figure 6 PMID:9006322

  20. The effect of glutamic acid side chain on acidity constant of lysine in beta-sheet: A density functional theory study

    NASA Astrophysics Data System (ADS)

    Sargolzaei, M.; Afshar, M.; Sadeghi, M. S.; Kavee, M.

    2014-07-01

    In this work, the possibility of proton transfer between side chain of lysine and glutamic acid in peptide of Glu--Ala-Lys+ was demonstrated using density functional theory (DFT). We have shown that the proton transfer takes place between side chain of glutamic and lysine residues through the hydrogen bond formation. The structures of transition state for proton transfer reaction were detected in gas and solution phases. Our kinetic studies show that the proton transfer reaction rate in gas phase is higher than solution phase. The ionization constant (p K a) value of lysine residue in peptide was estimated 1.039 which is lower than intrinsic p K a of lysine amino acid.

  1. Proteopedia: Rossmann Fold: A Beta-Alpha-Beta Fold at Dinucleotide Binding Sites

    ERIC Educational Resources Information Center

    Hanukoglu, Israel

    2015-01-01

    The Rossmann fold is one of the most common and widely distributed super-secondary structures. It is composed of a series of alternating beta strand () and alpha helical (a) segments wherein the -strands are hydrogen bonded forming a -sheet. The initial beta-alpha-beta (a) fold is the most conserved segment of Rossmann folds. As this segment

  2. A calorimetric determination of the enthalpy of formation and a description of the defect structure of the ordered beta-phase /Ni, Cu/ /1-x/ Al/x/

    NASA Technical Reports Server (NTRS)

    Henig, E. T.; Lukas, H. L.

    1988-01-01

    In order to describe thermodynamically the defect structure of an ordered B-Hume-Rothery phase, the heat of formation of (Ni,Cu)(1-x)Al(x) was measured at 1100 K as a function of concentration in the range x (sub Al) = 0.4 and 0.55 for three substitution rations x (sub Ni)/x (sub Cu) = infinity; 11; 5. The heat of formation of the NiAl beta-phase is strongly negative. For the stoichiometric composition it is -72.2 kJ/g-atom. On both the nickel-rich side and the aluminum-rich side the magnitude of the enthalpy of formation decreases linearly with concentration. Substitution of nickel for copper decreases the magnitude of the enthalpy of formation over the entire homogeneity range for the phase (Ni,Cu)(1-x)Al(x). The curve for the enthalpy of formation as well as the literature values for the chemical potential of aluminum are described with great accuracy by the disorder model of Wagner-Schottky.

  3. Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the beta subunits.

    PubMed

    Luchsinger, Benjamin P; Rich, Eric N; Gow, Andrew J; Williams, Elizabeth M; Stamler, Jonathan S; Singel, David J

    2003-01-21

    Previous studies of the interactions of NO with human hemoglobin have implied the predominance of reaction channels that alternatively eliminate NO by converting it to nitrate, or tightly complex it on the alpha subunit ferrous hemes. Both channels could effectively quench NO bioactivity. More recent work has raised the idea that NO groups can efficiently transfer from the hemes to cysteine thiols within the beta subunit (cysbeta-93) to form bioactive nitrosothiols. The regulation of NO function, through its chemical position in the hemoglobin, is supported by response to oxygen and to redox agents that modulate the molecular and electronic structure of the protein. In this article, we focus on reactions in which Fe(III) hemes could provide the oxidative requirements of this NO-group transfer chemistry. We report a detailed investigation of the reductive nitrosylation of human met-Hb, in which we demonstrate the production of S-nitroso (SNO)-Hb through a heme-Fe(III)NO intermediate. The production of SNO-Hb is strongly favored (over nitrite) when NO is gradually introduced in limited total quantities; in this situation, moreover, heme nitrosylation occurs primarily within the beta subunits of the hemoglobin tetramer. SNO-Hb can similarly be produced when Fe(II)NO hemes are subjected to mild oxidation. The reaction of deoxygenated hemoglobin with limited quantities of nitrite leads to the production of beta subunit Fe(II)NO hemes, with SNO-Hb produced on subsequent oxygenation. The common theme of these reactions is the effective coupling of heme-iron and NO redox chemistries. Collectively, they establish a connectivity between hemes and thiols in Hb, through which NO is readily dislodged from storage on the heme to form bioactive SNO-Hb. PMID:12524454

  4. Rationally Designed Peptoids Modulate Aggregation of Amyloid-Beta 40

    PubMed Central

    2014-01-01

    Alzheimers disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. Plaques composed of aggregated amyloid-beta protein (A?) accumulate between the neural cells in the brain and are associated with dementia and cellular death. Many strategies have been investigated to prevent A? self-assembly into disease-associated ?-sheet amyloid aggregates; however, a promising therapeutic has not yet been identified. In this study, a peptoid-based mimic of the peptide KLVFF (residues 1620 of A?) was tested for its ability to modulate A? aggregation. Peptoid JPT1 includes chiral, aromatic side chains to induce formation of a stable helical secondary structure that allows for greater interaction between the aromatic side chains and the cross ?-sheet of A?. JPT1 was found to modulate A?40 aggregation, specifically decreasing lag time to ?-sheet aggregate formation as well as the total number of fibrillar, ?-sheet structured aggregates formed. These results suggest that peptoids may be able to limit the formation of A? aggregates that are associated with AD. PMID:24689364

  5. Transforming Growth Factor Beta Signaling Is Essential for the Autonomous Formation of Cartilage-Like Tissue by Expanded Chondrocytes

    PubMed Central

    Tekari, Adel; Luginbuehl, Reto; Hofstetter, Willy; Egli, Rainer J.

    2015-01-01

    Cartilage is a tissue with limited self-healing potential. Hence, cartilage defects require surgical attention to prevent or postpone the development of osteoarthritis. For cell-based cartilage repair strategies, in particular autologous chondrocyte implantation, articular chondrocytes are isolated from cartilage and expanded in vitro to increase the number of cells required for therapy. During expansion, the cells lose the competence to autonomously form a cartilage-like tissue, that is in the absence of exogenously added chondrogenic growth factors, such as TGF-?s. We hypothesized that signaling elicited by autocrine and/or paracrine TGF-? is essential for the formation of cartilage-like tissue and that alterations within the TGF-? signaling pathway during expansion interfere with this process. Primary bovine articular chondrocytes were harvested and expanded in monolayer culture up to passage six and the formation of cartilage tissue was investigated in high density pellet cultures grown for three weeks. Chondrocytes expanded for up to three passages maintained the potential for autonomous cartilage-like tissue formation. After three passages, however, exogenous TGF-?1 was required to induce the formation of cartilage-like tissue. When TGF-? signaling was blocked by inhibiting the TGF-? receptor 1 kinase, the autonomous formation of cartilage-like tissue was abrogated. At the initiation of pellet culture, chondrocytes from passage three and later showed levels of transcripts coding for TGF-? receptors 1 and 2 and TGF-?2 to be three-, five- and five-fold decreased, respectively, as compared to primary chondrocytes. In conclusion, the autonomous formation of cartilage-like tissue by expanded chondrocytes is dependent on signaling induced by autocrine and/or paracrine TGF-?. We propose that a decrease in the expression of the chondrogenic growth factor TGF-?2 and of the TGF-? receptors in expanded chondrocytes accounts for a decrease in the activity of the TGF-? signaling pathway and hence for the loss of the potential for autonomous cartilage-like tissue formation. PMID:25775021

  6. Overexpression of protein kinase C. beta. 1 enhances phospholipase D activity and diacylglycerol formation in phorbol ester-stimulated rat fibroblasts

    SciTech Connect

    Pai, Jinkeon; Pachter, J.A.; Bishop, W.R. ); Weinstein, I.B. )

    1991-01-15

    The authors are using a Rat-6 fibroblast cell line that stably overexpresses the {beta}1 isozyme of protein kinase C (PKC) to study regulation of phospholipid hydrolysis by PKC. Stimulation of control (R6-C1) or overexpressing (R6-PKC3) cells with phorbol ester results in an increase in diacylglycerol (DAG) mass with no increase in inositol phosphates, indicating that DAG is not formed by inositol phospholipid breakdown. A more dramatic DAG increase occurs in R6-PKC3 cells compared to R6-C1 cells. To further define the source of DAG, phosphatidylcholine (PC) pools were labeled with ({sup 3}H)myristic acid or with ({sup 3}H)- or ({sup 32}P)alkyllyso-PC and formation of labeled phosphatidylethanol, an unambiguous marker of phospholipase D activation, was monitored. Phorbol ester-stimulated phosphatidylethanel formation is 5-fold greater in the R6-PKC3 cell line. Formation of radiolabeled phosphatidic acid (PA) is also enhanced by PKC overepression. In cells double-labeled with ({sup 3}H)- and ({sup 32}P)-alkyl-lysoPC, the {sup 3}H/{sup 32}P ratio of PA and PC are identical 15 min after stimulation, suggesting that a phospholipase D mechanism predominates. These results indicate that phospholipase D is regulated by the action of PKC. Enhanced phospholipase D activity may contribute to the growth abnormalities seen in PKC-overexpressing cells.

  7. Long-patch base excision DNA repair of 2-deoxyribonolactone prevents the formation of DNA-protein cross-links with DNA polymerase beta.

    PubMed

    Sung, Jung-Suk; DeMott, Michael S; Demple, Bruce

    2005-11-25

    Oxidized abasic sites are a major form of DNA damage induced by free radical attack and deoxyribose oxidation. 2-Deoxyribonolactone (dL) is a C1'-oxidized abasic site implicated in DNA strand breakage, mutagenesis, and formation of covalent DNA-protein cross-links (DPCs) with repair enzymes such as DNA polymerase beta (polbeta). We show here that mammalian cell-free extracts incubated with Ape1-incised dL substrates under non-repair conditions give rise to DPCs, with a major species dependent on the presence of polbeta. DPC formation was much less under repair than non-repair conditions, with extracts of either polbeta-proficient or -deficient cells. Partial base excision DNA repair (BER) reconstituted with purified enzymes demonstrated that Flap endonuclease 1 (FEN1) efficiently excises a displaced oligonucleotide containing a 5'-terminal dL residue, as would be produced during long-patch (multinucleotide) BER. Simultaneous monitoring of dL repair and dL-mediated DPC formation demonstrated that removal of the dL residue through the combined action of strand-displacement DNA synthesis by polbeta and excision by FEN1 markedly diminished DPC formation with the polymerase. Analysis of the patch size distribution associated with DNA repair synthesis in cell-free extracts showed that the processing of dL residues is associated with the synthesis of >or=2 nucleotides, compared with predominantly single nucleotide replacement for regular abasic sites. Our observations reveal a cellular repair process for dL lesions that avoids formation of DPCs that would threaten the integrity of DNA and perhaps cell viability. PMID:16188889

  8. Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes

    SciTech Connect

    Miklossy, J.; Miller, L.; Qing, H.; Radenovic, A.; Kis, A.; Vileno, B.; Laszlo, F.; Martins, R.N.; Waeber, G.; Mooser, V.; Bosman, F.; Khalili, K.; Darbinian, N.; McGeer, P.L.

    2008-08-25

    Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (A{beta}) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated A{beta}, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. A{beta} was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that A{beta} deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that A{beta} deposits and hyperphosphorylated tau may also occur in other organs than the brain.

  9. Suppression of autophagy and activation of glycogen synthase kinase 3beta facilitate the aggregate formation of tau.

    PubMed

    Kim, Song-In; Lee, Won-Ki; Kang, Sang-Soo; Lee, Sue-Young; Jeong, Myeong-Ja; Lee, Hee Jae; Kim, Sung-Soo; Johnson, Gall V W; Chun, Wanjoo

    2011-04-01

    Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3? has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3?-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3?. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3? in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3?-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation. PMID:21660151

  10. A biased probe analysis of potential well formation in an electron only, low beta Polywell magnetic field

    SciTech Connect

    Carr, Matthew; Khachan, Joe

    2013-05-15

    Orbital limited motion theory has been applied to two biased probes in a low beta Polywell. The cases studied include electron injection, magnetic field scaling, Polywell bias scaling, and radial position profiles. Langmuir's original orbital limited motion results for a monoenergetic electron beam are shown to be in excellent agreement for electron injection into the Polywell. A distribution function is proposed for the electron plasma characteristics in the centre of the magnetic null and confirmed with experimental results. A translational stage was used to measure the radial plasma potential profile. In other experiments, two probes were used to simultaneously measure the profiles in both the null and a position halfway along a corner cusp. The results confirm a radial potential well created by electron trapping in the device. In addition, we present preliminary results of the potential well scaling with the magnetic field, Polywell bias voltage, and the injected beam current. The electron population was found to maintain non-equilibrium in all cases studied.

  11. Inhibition of lignin formation by L-alpha-aminooxy-beta-phenylpropionic acid, an inhibitor of phenylalanine ammonia-lyase.

    PubMed

    Amrhein, N; Frank, G; Lemm, G; Luhmann, H B

    1983-01-01

    Mungbean (Vigna radiata (L.) Wilczek) seedlings grown for 9 days on filter paper soaked with 0.3 to 1 mM L-alpha-aminooxy-beta-phenylpropionic acid (AOPP), a potent inhibitor of L-phenylalanine ammonia-lyase, had a greatly reduced anthocyanin content, and the cell walls of the xylem vessels did not stain with the phloroglucinol/HCl or safranine/astrablue reagents indicating the absence of lignin-like material. Furthermore, vanillin was detectable in nitro-benzene-oxidized lignin preparations only from control seedlings, but not from AOPP-treated seedlings. Scanning electron microscopy of hypocotyl cross sections revealed collapsed xylem vessels in seedlings grown in the presence of AOPP indicating that lignin is required for resistance against the tensile forces in the conducting cells of the xylem. AOPP enhanced the growth of cultured cells of Lonicera prolifera Rehd. while it inhibited the production of extracellular material that gave a positive reaction with phloroglucinol/HCl. PMID:6832164

  12. Study on the Formation and Characterization of the Intermetallics in Friction Stir Welding of Aluminum Alloy to Coated Steel Sheet Lap Joint

    NASA Astrophysics Data System (ADS)

    Das, H.; Ghosh, R. N.; Pal, T. K.

    2014-10-01

    Multimaterial fabrication such as joining of steel and aluminum is currently prominent in a variety of industries. Friction stir welding is a novel solid-state welding process that causes good joint strength between steel and aluminum. However, the phenomenon contributing significant strength at the interface is not yet clear. In the present study, the interface of the friction stir lap-welded aluminum and coated steel sheet having joint strength maximum (71.4 pct of steel base metal) and minimum, respectively, under two parameter combinations, i.e., 1000 rpm 50 mm min-1 and 500 rpm 100 mm min-1, was exclusively characterized by X-ray diffraction, transmission electron microscopy (TEM), concentration profile, and elemental mapping by electron-probe microanalysis. A TEM-assisted EDS study identifies the morphologies of large size Al13Fe4 and small size Fe3Al-type intermetallic compounds at the interface. The diffusion-induced intermetallic growth (thickness) measured from a backscattered image and concentration profile agreed well with the numerically calculated one. The growth of these two phases at 1000 rpm 50 mm min-1 is attributed to the slower cooling rate (~3.5 K/s) with higher diffusion time (44 seconds) along the interface in comparison to the same for 500 rpm 100 mm min-1 with faster cooling rate (~10 K/s) and less diffusion time (13.6 seconds). The formation of thermodynamically stable and hard intermetallic phase Al13Fe4 at 1000 rpm and travel speed 50 mm min-1 in amounts higher than 500 rpm and a travel speed of 100 mm min-1 results in better joint strength, i.e., 71.4 pct, of the steel base metal.

  13. Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and evaluation of its efficacy on peri-implant bone formation.

    PubMed

    Lee, Jae Hyup; Ryu, Mi Young; Baek, Hae-Ri; Seo, Jun-Hyuk; Lee, Kyung-Mee; Lee, Ji-Ho

    2014-10-01

    Dental implant insertion on a site with low bone quality or bone defect should be preceded by a bone graft or artificial bone graft insertion to heal the defect. We generated a beta-tricalcium phosphate (?-TCP) and poloxamer 407-based hydrogel composite and penetration of the ?-TCP/hydrogel composite into the peri-implant area of bone was evaluated by porous bone block experiments. The maximum penetration depth for porous bone blocks and dense bone blocks were 524??m and 464??m, respectively. We report the in-vivo performance of a composite of ?-TCP/hydrogel composite as a carrier of recombinant human bone morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model. Three holes drilled into each tibia of eight male rabbits were (1) grafted with dental implant fixtures; (2) filled with ?-TCP/hydrogel composite (containing 5??g of rhBMP-2), followed by grafting of the dental implant fixtures. Four weeks later, bone-implant contact ratio and peri-implant bone formation were analyzed by radiography, micro-CT and histology of undecalcified specimens. The micro-CT results showed a significantly higher level of trabecular thickness and new bone and peri-implant new bone formation in the experimental treatment compared to the control treatment. Histomorphometry revealed a significantly higher bone-implant contact ratio and peri-implant bone formation with the experimental treatment. The use of ?-TCP/poloxamer 407 hydrogel composite as a carrier of rhBMP-2 significantly promoted new bone formation around the dental implant fixture and it also improved the quality of the new bone formed in the tibial marrow space. PMID:25135209

  14. A Theoretical Model of a Thinning Current Sheet in the Low-? Plasmas

    NASA Astrophysics Data System (ADS)

    Takeshige, Satoshi; Takasao, Shinsuke; Shibata, Kazunari

    2015-07-01

    Magnetic reconnection is an important physical process in various explosive phenomena in the universe. In previous studies, it was found that fast reconnection takes place when the thickness of a current sheet becomes on the order of a microscopic length such as the ion Larmor radius or the ion inertial length. In this study, we investigated the pinching process of a current sheet by the Lorentz force in a low-? plasma using one-dimensional magnetohydrodynamics (MHD) simulations. It is known that there is an exact self-similar solution for this problem that neglects gas pressure. We compared the non-linear MHD dynamics with the analytic self-similar solution. From the MHD simulations, we found that with the gas pressure included the implosion process deviates from the analytic self-similar solution as t\\to {t}0, where t0 is the explosion time when the thickness of a current sheet of the analytic solution becomes 0. We also found that a pair of MHD fast-mode shocks is generated and propagates after the formation of the pinched current sheet as t\\to {t}0. On the basis of the Rankine-Hugoniot relations, we derived the scaling law of the physical quantities with respect to the initial plasma beta in the pinched current sheet. Our study could help us estimate the physical quantities in the pinched current sheet formed in a low-? plasma.

  15. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation.

    PubMed

    Nicole, Olivier; Hadzibegovic, Senka; Gajda, Judyta; Bontempi, Bruno; Bem, Tiaza; Meyrand, Pierre

    2016-01-01

    Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease. PMID:26947247

  16. Analysis of small latent transforming growth factor-beta complex formation and dissociation by surface plasmon resonance. Absence of direct interaction with thrombospondins.

    PubMed

    Bailly, S; Brand, C; Chambaz, E M; Feige, J J

    1997-06-27

    Transforming growth factor-beta (TGFbeta) is a pluripotent regulator of cell growth and differentiation. The growth factor is expressed as a latent complex that must be converted to an active form before interacting with its ubiquitous high affinity receptors. This conversion involves the release of the mature TGFbeta through disruption of the noncovalent interactions with its propeptide or latency associated protein (LAP). Complex formation or dissociation between LAP and TGFbeta plays a very important role in TGFbeta biological activity at different steps. To further characterize the kinetic parameters of this interaction, we have employed surface plasmon resonance biosensor methodology. Using this technique, we observed real time association of LAP with mature TGFbeta1. The complex formation showed an equilibrium Kd around 3-7 nM. Furthermore, we observed dissociation of the complex in the presence of extreme pH, chaotropic agents, or plasmin, confirming their effects on TGFbeta activation. The same approach was used to examine whether latent TGFbeta1 could interact with thrombospondins, previously described as activators of latent TGFbeta. Using this method, we could not detect any direct interaction of thrombospondins with either LAP alone, TGFbeta1 alone, or the small latent TGFbeta1 complex. This suggests that activation of latent TGFbeta1 complex by thrombospondins is through an indirect mechanism. PMID:9195938

  17. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation

    PubMed Central

    Nicole, Olivier; Hadzibegovic, Senka; Gajda, Judyta; Bontempi, Bruno; Bem, Tiaza; Meyrand, Pierre

    2016-01-01

    Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer’s disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer’s disease. PMID:26947247

  18. Nuclear magnetic resonance evidence for the dimer formation of beta amyloid peptide 1-42 in 1,1,1,3,3,3-hexafluoro-2-propanol.

    PubMed

    Shigemitsu, Yoshiki; Iwaya, Naoko; Goda, Natsuko; Matsuzaki, Mizuki; Tenno, Takeshi; Narita, Akihiro; Hoshi, Minako; Hiroaki, Hidekazu

    2016-04-01

    Alzheimer's disease involves accumulation of senile plaques in which filamentous aggregates of amyloid beta (Aβ) peptides are deposited. Recent studies demonstrate that oligomerization pathways of Aβ peptides may be complicated. To understand the mechanisms of Aβ(1-42) oligomer formation in more detail, we have established a method to produce (15)N-labeled Aβ(1-42) suited for nuclear magnetic resonance (NMR) studies. For physicochemical studies, the starting protein material should be solely monomeric and all Aβ aggregates must be removed. Here, we succeeded in fractionating a "precipitation-resistant" fraction of Aβ(1-42) from an "aggregation-prone" fraction by high-performance liquid chromatography (HPLC), even from bacterially overexpressed Aβ(1-42). However, both Aβ(1-42) fractions after 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) treatment formed amyloid fibrils. This indicates that the "aggregation seed" was not completely monomerized during HFIP treatment. In addition, Aβ(1-42) dissolved in HFIP was found to display a monomer-dimer equilibrium, as shown by two-dimensional (1)H-(15)N NMR. We demonstrated that the initial concentration of Aβ during the HFIP pretreatment altered the kinetic profiles of Aβ fibril formation in a thioflavin T fluorescence assay. The findings described here should ensure reproducible results when studying the Aβ(1-42) peptide. PMID:26772162

  19. Sheet of osteoblastic cells combined with platelet-rich fibrin improves the formation of bone in critical-size calvarial defects in rabbits.

    PubMed

    Wang, Zhifa; Hu, Hanqing; Li, Zhijin; Weng, Yanming; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

    2016-04-01

    Techniques that use sheets of cells have been successfully used in various types of tissue regeneration, and platelet-rich fibrin (PRF) can be used as a source of growth factors to promote angiogenesis. We have investigated the effects of the combination of PRF and sheets of mesenchymal stem cells (MSC) from bone marrow on the restoration of bone in critical-size calvarial defects in rabbits to find out whether the combination promotes bony healing. Sheets of MSC and PRF were prepared from the same donor. We then implanted the combined MSC and PRF in critical-size calvarial defects in rabbits and assessed bony restoration by microcomputed tomography (microCT) and histological analysis. The results showed that PRF significantly increased bony regeneration at 8 weeks after implantation of sheets of MSC and PRF compared with sheets of MSC alone (p=0.0048). Our results indicate that the combination of sheets of MSC and PRF increases bone regeneration in critical-size calvarial defects in rabbits, and provides a new way to improve skeletal healing. PMID:26781843

  20. Structural modifications of human beta 2 microglobulin treated with oxygen-derived radicals.

    PubMed Central

    Capeillere-Blandin, C; Delaveau, T; Descamps-Latscha, B

    1991-01-01

    Treatment of human beta 2 microglobulin (beta 2m) with defined oxygen-derived species generated by treatment with gamma-radiation was studied. As assessed by SDS/PAGE, the hydroxyl radicals (.OH) caused the disappearance of the protein band at 12 kDa that represents beta 2m, and cross-linked the protein into protein bands stable to both SDS and reducing conditions. However, when .OH was generated under oxygen in equimolar combination with the superoxide anion radical (O2.-), the high-molecular-mass protein products were less represented, and fragmented derivatives were not obviously detectable. Exposure to .OH alone, or to .OH + O2.- in the presence of O2, induced the formation of beta 2m protein derivatives with a more acidic net electrical charge than the parent molecule. In contrast, O2.- alone had virtually no effect on molecular mass or pI. Changes in u.v. fluorescence during .OH attack indicated changes in conformation, as confirmed by c.d. spectrometry. A high concentration of radicals caused the disappearance of the beta-pleated sheet structure and the formation of a random coil structure. Loss of tryptophan and significant production of dityrosine (2,2'-biphenol type) were noted, exhibiting a clear dose-dependence with .OH alone or with .OH + O2.-. The combination of .OH + O2.- induced a pattern of changes similar to that with .OH alone, but more extensive for c.d. and tryptophan oxidation (2 Trp/beta 2m molecule), and more limited for dityrosine formation. Lower levels of these oxidative agents caused the reproducible formation of species at 18 and 25 kDa which were recognized by antibodies against native beta 2m. These findings provide a model for the protein pattern observed in beta 2m amyloidosis described in the literature. Images Fig. 4. Fig. 5. PMID:1649598

  1. Apolipoprotein E structural requirements for the formation of SDS-stable complexes with beta-amyloid-(1-40): the role of salt bridges.

    PubMed Central

    Bentley, Nicholas M; Ladu, Mary Jo; Rajan, Chandrika; Getz, Godfrey S; Reardon, Catherine A

    2002-01-01

    Of the three major isoforms of human apolipoprotein E (apoE), apoE4 is a risk factor for the development of Alzheimer's disease. Among possible neurologically relevant differences in the properties of apoE3 and apoE4 is the fact that apoE3 forms an SDS-stable complex with beta-amyloid-(1-40) (Abeta40) with greater avidity than does apoE4. This interaction may sequester potentially toxic species of Abeta or facilitate clearance. To understand more about this difference, we examined whether differences in salt bridges between apoE domains influence the capacity of apoE isoforms to form complexes with Abeta. In apoE3 there is a salt bridge between Arg-61 and Asp-65, while in apoE4 there are salt bridges between Arg-61 and Glu-255, and Arg-112 and Glu-109. Mutation of position 112, which is Cys in apoE3 and Arg in apoE4, to Ala or Lys abolished complex formation, while mutant apoE with Ser at this position retained the capacity to form complex. Substituting Ala for Glu-109 had no effect on the ability of either apoE4 or apoE3 to form complexes. On the other hand, substitution of Thr for Arg-61 in apoE3 abolished, and truncation of apoE3 at position 201 substantially lowered, but did not abolish, complex formation. Neither of these mutations within apoE4 had any affect on its complex formation with Abeta. These results suggest that the nature of the cysteine residue in apoE3 and interactions between the N-terminal and C-terminal domains of human apoE are important for the ability of apoE3 to form an SDS-stable complex with Abeta40. PMID:12015813

  2. Molecular basis for amyloid-[beta] polymorphism

    SciTech Connect

    Colletier, Jacques-Philippe; Laganowsky, Arthur; Landau, Meytal; Zhao, Minglei; Soriaga, Angela B.; Goldschmidt, Lukasz; Flot, David; Cascio, Duilio; Sawaya, Michael R.; Eisenberga, David

    2011-10-19

    Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.

  3. Solid-state NMR analysis of the {beta}-strand orientation of the protofibrils of amyloid {beta}-protein

    SciTech Connect

    Doi, Takashi; Masuda, Yuichi; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 ; Irie, Kazuhiro; Akagi, Ken-ichi; Monobe, Youko; Imazawa, Takayoshi; Takegoshi, K.

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer The supramolecular structure of A{beta}42 protofibrils was analyzed by solid-state NMR. Black-Right-Pointing-Pointer The Ala-21 residue in the A{beta}42 protofibrils is included in a slightly disordered {beta}-strand. Black-Right-Pointing-Pointer The A{beta}42 protofibrils do not form intermolecular in-register parallel {beta}-sheets. -- Abstract: Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid {beta}-protein (A{beta}42) in the brain. During the process of fibrillation, the A{beta}42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A{beta}42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A{beta}42 protofibrils was analyzed by {sup 13}C-{sup 13}C rotational resonance experiments in the solid state. Unlike the A{beta}42 fibrils, an intermolecular {sup 13}C-{sup 13}C correlation was not found in the A{beta}42 protofibrils. This result suggests that the {beta}-strands of the A{beta}42 protofibrils are not in an in-register parallel orientation. A{beta}42 monomers would assemble to form protofibrils with the {beta}-strand conformation, then transform into fibrils by forming intermolecular parallel {beta}-sheets.

  4. Streaming sausage, kink and tearing instabilities in a current sheet with applications to the Earth's magnetotail

    SciTech Connect

    Lee, L.C.; Wang, S.; Wei, C.Q.; Tsurutani, B.T.

    1988-07-01

    In this paper, the growth rate and eigenmode structures of the streaming sausage and kink instabilities in a current sheet with a super-Alvenic flow are studied. Based on the linearized compressible profiles of the fastest growing mode which is either the streaming sausage mode or kink mode. The streaming sausage and kink instabilities, similar to the Kelvin-Helmholtz instability, are caused by the sheared plasma flow. The results show that for V/sub 0//sub m/ = 2 V/sub A//sub infinity/ the sausage mode grows faster than the kink mode when ..beta../sub infinity/<1.5. When ..beta../sub infinity/>1.5, the streaming kink instability has a higher growth rate. Here V/sub A//sub infinity/ is the Alfven velocity and ..beta../sub infinity/ is the ratio between the plasma and magnetic pressures far away from the current layer, and V/sub 0//sub m/ is the maximum velocity of plasma flow at the current sheet. In addition, an analytical dispersion equation is obtained for an ideal four-layer model of the current sheet in the incompressible limit. In the presence of a finite resistivity, the mixed sausage-tearing mode or the streaming tearing mode may be excited, which leads to the formation of plasmoids in the magnetotail. As an application to the Earth's magnetotail, where super-Alfvenic plasma flows are observed in the plasma sheet and ..beta../sub infinity/approx. =0.1--0.3 in the lobes, it is suggested that the streaming sausage and streaming tearing instabilities may occur in the magnetotail.

  5. Multi-frequency characterization of radar backscatter and the formation of ice layers in the southeast percolation area of the Greenland ice sheet

    NASA Astrophysics Data System (ADS)

    Miller, J.; Forster, R. R.; Box, J. E.; Long, D. G.

    2012-12-01

    The relationship between radar backscatter and the formation of ice layers in the southeast percolation area of the Greenland ice sheet is explored using two scatterometer data sets, 1999-2009 data acquired from NASA's Ku-band SeaWinds scatterometer on the QuikSCAT satellite (QSCAT), and 2009 data acquired from ESA's C-band advanced scatterometer (ASCAT) on the MetOp satellite, together with 1999-2009 annually dated ice layers from five firn cores acquired during the 2010 and 2011 Arctic Circle Traverse (ACT) campaigns. Snowpack stratigraphy within the southeast percolation area is complex and forms as the result of the seasonal progression of snow accumulation at the surface followed by melt water infiltration. Melt water may be retained in liquid form, or refreeze which creates scattering layers embedded within snow and firn layers at differing depths. Ice layers are created by shallow infiltration and refreezing of melt water at the surface or by downward percolation and lateral infiltration and refreezing of melt water at depth. Ice layers are spatially continuous over large areas and identified in firn core data. Ice pipes, lenses, and glands are created by the downward percolation of melt water at point locations, which subsequently refreezes at depth within percolation channels. Ice pipes, lenses, and glands are spatially discontinuous and rarely identified in firn core data, however, contribute to the microwave response as observed over the large-scale antenna footprint of a satellite- bourne scatterometer. Microwave signatures within this region exhibit what appear to be distinct seasonal responses to melt and refreeze events resulting in the formation of scattering layers within the snowpack, in the form of rapid relative increases and decreases in backscatter measurements followed by a step response in the signal. Two backscatter models identifying both the timing and spatial extent of the given parameter are derived from the observed responses: 1) a melt/refreeze model which estimates the thickness of the wet snow layer, and 2) an ice layer model which estimates increases in the density of the scattering layer. Modeled results using twice-daily 1999-2009 QSCAT enhanced resolution 'slice' data (~5 km) are compared with annually dated firn core ice layers. An approximate sub-annual timing of the formation of the firn core ice layers is established, as well as the large-scale spatial continuity of the ice layers between firn cores. Similarities and differences between firn core ice layer thicknesses and both modeled thickness of the wet snow layer and modeled density increases in the scattering layer are observed and characterized. A second comparison is made between modeled results, using near-daily 2009 QSCAT and ASCAT enhanced resolution 'egg' data (~10 km). Frequency dependent differences linked to the penetration depth are also characterized.

  6. Synergistic Action of Fibroblast Growth Factor-2 and Transforming Growth Factor-beta1 Enhances Bioprinted Human Neocartilage Formation

    PubMed Central

    Cui, Xiaofeng; Breitenkamp, Kurt; Lotz, Martin; DLima, Darryl

    2012-01-01

    Bioprinting as a promising but unexplored approach for cartilage tissue engineering has the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the targeted 3D locations with simultaneous polymerization. This study tested feasibility of using bioprinting for cartilage engineering and examined the influence of cell density, growth and differentiation factors. Human articular chondrocytes were printed at various densities, stimulated transiently with growth factors and subsequently with chondrogenic factors. Samples were cultured for up to 4 weeks to evaluate cell proliferation and viability, mechanical properties, mass swelling ratio, water content, gene expression, ECM production, DNA content, and histology. Bioprinted samples treated with FGF-2/TGF-?1 had the best chondrogenic properties among all groups apparently due to synergistic stimulation of cell proliferation and chondrogenic phenotype. ECM production per chondrocyte in low cell density was much higher than that in high cell seeding density. This finding was also verified by mechanical testing and histology. In conclusion, cell seeding density that is feasible for bioprinting also appears optimal for human neocartilage formation when combined with appropriate growth and differentiation factors. PMID:22508498

  7. Study of formation of deep trapping mechanism by UV, beta and gamma irradiated Eu(3+) activated SrY2O4 and Y4Al2O9 phosphors.

    PubMed

    Dubey, Vikas; Kaur, Jagjeet; Parganiha, Yogita; Suryanarayana, N S; Murthy, K V R

    2016-04-01

    This paper reports the thermoluminescence properties of Eu(3+) doped different host matrix phosphors (SrY2O4 and Y4Al2O9). The phosphor is prepared by high temperature solid state reaction method. The method is suitable for large scale production and fixed concentration of boric acid using as a flux. The prepared samples were characterized by X-ray diffraction technique and the crystallite size calculated by Scherer's formula. The prepared phosphor characterized by Scanning Electron Microscopic (SEM), Fourier Transform Infrared (FTIR), Energy Dispersive X-ray analysis (EDX), thermoluminescence (TL) and Transmission Electron Microscopic (TEM) techniques. The prepared phosphors for different concentration of Eu(3+) ions were examined by TL glow curve for UV, beta and gamma irradiation. The UV 254nm source used for UV irradiation, Sr(90) source was used for beta irradiation and Co(60) source used for gamma irradiation. SrY2O4:Eu(3+)and Y4Al2O9:Eu(3+) phosphors which shows both higher temperature peaks and lower temperature peaks for UV, beta and gamma irradiation. Here UV irradiated sample shows the formation of shallow trap (surface trapping) and the gamma irradiated sample shows the formation of deep trapping. The estimation of trap formation was evaluated by knowledge of trapping parameters. The trapping parameters such as activation energy, order of kinetics and frequency factor were calculated by peak shape method. Here most of the peak shows second order of kinetics. The effect of gamma, beta and UV exposure on TL studies was also examined and it shows linear response with dose which indicate that the samples may be useful for TL dosimetry. Formation of deep trapping mechanism by UV, beta and gamma irradiated Eu(3+) activated SrY2O4 and Y4Al2O9 phosphors is discussed in this paper. PMID:26748019

  8. Interaction between beta-Purothionin and dimyristoylphosphatidylglycerol: a (31)P-NMR and infrared spectroscopic study.

    PubMed Central

    Richard, Julie-Andre; Kelly, Isabelle; Marion, Didier; Pzolet, Michel; Auger, Michle

    2002-01-01

    The interaction of beta-purothionin, a small basic and antimicrobial protein from the endosperm of wheat seeds, with multilamellar vesicles of dimyristoylphosphatidylglycerol (DMPG) was investigated by (31)P solid-state NMR and infrared spectroscopy. NMR was used to study the organization and dynamics of DMPG in the absence and presence of beta-purothionin. The results indicate that beta-purothionin does not induce the formation of nonlamellar phases in DMPG. Two-dimensional exchange spectroscopy shows that beta-purothionin decreases the lateral diffusion of DMPG in the fluid phase. Infrared spectroscopy was used to investigate the perturbations, induced by beta-purothionin, of the polar and nonpolar regions of the phospholipid bilayers. At low concentration of beta-purothionin, the temperature of the gel-to-fluid phase transition of DMPG increases from 24 degrees C to ~33 degrees C, in agreement with the formation of electrostatic interactions between the cationic protein and the anionic phospholipid. At higher protein concentration, the lipid transition is slightly shifted toward lower temperature and a second transition is observed below 20 degrees C, suggesting an insertion of the protein in the hydrophobic core of the lipid bilayer. The results also suggest that the presence of beta-purothionin significantly modifies the lipid packing at the surface of the bilayer to increase the accessibility of water molecules in the interfacial region. Finally, orientation measurements indicate that the alpha-helices and the beta-sheet of beta-purothionin have tilt angles of ~60 degrees and 30 degrees, respectively, relative to the normal of the ATR crystal. PMID:12324425

  9. An experimental study of multiple zonal jet formation in rotating, thermally driven convective flows on a topographic beta-plane

    NASA Astrophysics Data System (ADS)

    Read, P. L.; Jacoby, T. N. L.; Rogberg, P. H. T.; Wordsworth, R. D.; Yamazaki, Y. H.; Miki-Yamazaki, K.; Young, R. M. B.; Sommeria, J.; Didelle, H.; Viboud, S.

    2015-08-01

    A series of rotating, thermal convection experiments were carried out on the Coriolis platform in Grenoble, France, to investigate the formation and energetics of systems of zonal jets through nonlinear eddy/wave-zonal flow interactions on a topographic ?-plane. The latter was produced by a combination of a rigid, conically sloping bottom and the rotational deformation of the free upper surface. Convection was driven by a system of electrical heaters laid under the (thermally conducting) sloping bottom and led to the production of intense, convective vortices. These were observed to grow in size as each experiment proceeded and led to the development of weak but clear azimuthal jet-like flows, with a radial scale that varied according to the rotation speed of the platform. Detailed analyses reveal that the kinetic energy-weighted radial wavenumber of the zonal jets, kJy, scales quite closely either with the Rhines wavenumber as kJy ? 2(?T/2urms)1/2, where urms is the rms total or eddy velocity and ?T is the vorticity gradient produced by the sloping topography, or the anisotropy wavenumber as k J y ? 1 . 25 ( ?T 3 / ? ) 1 / 5 , where ? is the upscale turbulent energy transfer rate. Jets are primarily produced by the direct quasi-linear action of horizontal Reynolds stresses produced by trains of topographic Rossby waves. The nonlinear production rate of zonal kinetic energy is found to be strongly unsteady, however, with fluctuations of order 10-100 times the amplitude of the mean production rate for all cases considered. The time scale of such fluctuations is found to scale consistently with either an inertial time scale, ? p 1 . / ?{ u r m s ? T } , or the Ekman spin-down time scale. Kinetic energy spectra show some evidence for a k-5/3 inertial subrange in the isotropic component, suggestive of a classical Kolmogorov-Batchelor-Kraichnan upscale energy cascade and a steeper spectrum in the zonal mean flow, though not as steep as k-5, as anticipated for fully zonostrophic flow. This is consistent with a classification of all of these flows as marginally zonostrophic, as expected for values of the zonostrophy parameter R? ? 1.6-1.7, though a number of properties related to flow anisotropy were found to vary significantly and systematically within this range.

  10. Alpha, beta-unsaturated lactones 2-furanone and 2-pyrone induce cellular DNA damage, formation of topoisomerase I- and II-DNA complexes and cancer cell death.

    PubMed

    Calderón-Montaño, José Manuel; Burgos-Morón, Estefanía; Orta, Manuel Luis; Pastor, Nuria; Austin, Caroline A; Mateos, Santiago; López-Lázaro, Miguel

    2013-09-12

    The alpha, beta-unsaturated lactones 2-furanone and 2-pyrone are part of the chemical structure of a variety of naturally occurring compounds (e.g., cardenolides, bufadienolides, acetogenins, coumarins, and food-flavoring furanones), some of which have shown anticancer activity and/or DNA damaging effects. Here we report that 2-furanone and 2-pyrone induce cellular DNA damage (assessed by the comet assay and the gamma-H2AX focus assay) and the formation of topoisomerase I- and topoisomerase II-DNA complexes in cells (visualized and quantified in situ by the TARDIS assay). Cells mutated in BRCA2 (deficient in homologous recombination repair) were significantly hypersensitive to the cytotoxic activity of 2-pyrone, therefore suggesting that BRCA2 plays an important role in the repair of DNA damage induced by this lactone. Both lactones were cytotoxic in A549 lung cancer cells at lower concentrations than in MRC5 non-malignant lung fibroblasts. The possible involvement of 2-furanone and 2-pyrone in the anticancer and DNA-damaging activities of compounds containing these lactones is discussed. PMID:23867916

  11. Early Mars climate near the Noachian-Hesperian boundary: Independent evidence for cold conditions from basal melting of the south polar ice sheet (Dorsa Argentea Formation) and implications for valley network formation

    NASA Astrophysics Data System (ADS)

    Fastook, James L.; Head, James W.; Marchant, David R.; Forget, Francois; Madeleine, Jean-Baptiste

    2012-05-01

    Currently, and throughout much of the Amazonian, the mean annual surface temperatures of Mars are so cold that basal melting does not occur in ice sheets and glaciers and they are cold-based. The documented evidence for extensive and well-developed eskers (sediment-filled former sub-glacial meltwater channels) in the south circumpolar Dorsa Argentea Formation is an indication that basal melting and wet-based glaciation occurred at the South Pole near the Noachian-Hesperian boundary. We employ glacial accumulation and ice-flow models to distinguish between basal melting from bottom-up heat sources (elevated geothermal fluxes) and top-down induced basal melting (elevated atmospheric temperatures warming the ice). We show that under mean annual south polar atmospheric temperatures (-100 C) simulated in typical Amazonian climate experiments and typical Noachian-Hesperian geothermal heat fluxes (45-65 mW/m2), south polar ice accumulations remain cold-based. In order to produce significant basal melting with these typical geothermal heat fluxes, the mean annual south polar atmospheric temperatures must be raised from today's temperature at the surface (-100 C) to the range of -50 to -75 C. This mean annual polar surface atmospheric temperature range implies lower latitude mean annual temperatures that are likely to be below the melting point of water, and thus does not favor a "warm and wet" early Mars. Seasonal temperatures at lower latitudes, however, could range above the melting point of water, perhaps explaining the concurrent development of valley networks and open basin lakes in these areas. This treatment provides an independent estimate of the polar (and non-polar) surface temperatures near the Noachian-Hesperian boundary of Mars history and implies a cold and relatively dry Mars climate, similar to the Antarctic Dry Valleys, where seasonal melting forms transient streams and permanent ice-covered lakes in an otherwise hyperarid, hypothermal climate.

  12. Circular dichroism of the parallel beta helical proteins pectate lyase C and E.

    PubMed

    Sieber, V; Jurnak, F; Moe, G R

    1995-09-01

    The pectate lyases, PelC and PelE, have an unusual folding motif, known as a parallel beta-helix, in which the polypeptide chain is coiled into a larger helix composed of three parallel beta-sheets connected by loops having variable lengths and conformations. Since the regular secondary structure consists almost entirely of parallel beta-sheets these proteins provide a unique opportunity to study the effect of parallel beta-helical structure on circular dichroism (CD). We report here the CD spectra of PelC and PelE in the presence and absence of Ca2+, derive the parallel beta-helical components of the spectra, and compare these results with previous CD studies of parallel beta-sheet structure. The shape and intensity of the parallel beta-sheet spectrum is distinctive and may be useful in identifying other proteins that contain the parallel beta-helical folding motif. PMID:8539248

  13. Proteopedia: Rossmann Fold: A Beta-Alpha-Beta Fold at Dinucleotide Binding Sites

    ERIC Educational Resources Information Center

    Hanukoglu, Israel

    2015-01-01

    The Rossmann fold is one of the most common and widely distributed super-secondary structures. It is composed of a series of alternating beta strand (ß) and alpha helical (a) segments wherein the ß-strands are hydrogen bonded forming a ß-sheet. The initial beta-alpha-beta (ßaß) fold is the most conserved segment of Rossmann folds. As this segment…

  14. Beta experiment

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser doppler velocimeter (LDV) system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. A Doppler signal generator was used in mapping the coherent sensitive focal volume of a focused LDV system. System calibration data was analyzed during the flight test activity scheduled for the Beta system. These analyses were performed to determine the acceptability of the Beta measurement system's performance.

  15. Enhanced tumor formation in cyclin D1 x transforming growth factor beta1 double transgenic mice with characterization by magnetic resonance imaging.

    PubMed

    Deane, Natasha G; Lee, Haakil; Hamaamen, Jalal; Ruley, Anna; Washington, M Kay; LaFleur, Bonnie; Thorgeirsson, Snorri S; Price, Ronald; Beauchamp, R Daniel

    2004-02-15

    Transgenic mice that overexpress cyclin D1 protein in the liver develop liver carcinomas with high penetrance. Transforming growth factor beta (TGF-beta) serves as either an epithelial cell growth inhibitor or a tumor promoter, depending on the cellular context. We interbred LFABP-cyclin D1 and Alb-TGF-beta1 transgenic mice to produce cyclin D1/TGF-beta1 double transgenic mice and followed the development of liver tumors over time, characterizing cellular and molecular changes, tumor incidence, tumor burden, and tumor physiology noninvasively by magnetic resonance imaging. Compared with age-matched LFABP-cyclin D1 single transgenic littermates, cyclin D1/TGF-beta1 mice exhibited a significant increase in tumor incidence. Tumor multiplicity, tumor burden, and tumor heterogeneity were higher in cyclin D1/TGF-beta1 mice compared with single transgenic littermates. Characteristics of cyclin D1/TGF-beta1 livers correlated with a marked induction of the peripheral periductal oval cell/stem cell compartment of the liver. A number of cancerous lesions from cyclin D1/TGF-beta1 mice exhibited unique features such as ductal plate malformations and hemorrhagic nodules. Some lesions were contiguous with the severely diseased background liver and, in some cases, replaced the normal architecture of the entire organ. Cyclin D1/TGF-beta1 lesions, in particular, were associated with malignant features such as areas of vascular invasion by hepatocytes and heterogeneous hyperintensity of signal on T2-weighted magnetic resonance imaging. These findings demonstrate that TGF-beta1 promotes stem cell activation and tumor progression in the context of cyclin D1 overexpression in the liver. PMID:14973059

  16. Effect of formation and state of interface on joint strength in friction stir spot welding for advanced high strength steel sheets

    NASA Astrophysics Data System (ADS)

    Taniguchi, Koichi; Matsushita, Muneo; Ikeda, Rinsei; Oi, Kenji

    2014-08-01

    The tensile shear strength and cross tension strength of friction stir spot welded joints were evaluated in the cases of lap joints of 270 N/mm2 grade and 980 N/mm2 grade cold rolled steel sheets with respect to the stir zone area, hardness distribution, and interface condition between the sheets. The results suggested that both the tensile shear strength and cross tension strength were based on the stir zone area and its hardness in both grades of steel. The "hook" shape of the interface also affected the joint strength. However, the joining that occurred across the interfaces had a significant influence on the value of the joint strength in the case of the 270 N/mm2 grade steel.

  17. Glacial landforms on German Bank, Scotian Shelf: evidence for Late Wisconsinan ice-sheet dynamics and implications for the formation of De Geer moraines

    USGS Publications Warehouse

    Todd, Brian J.; Valentine, Page C.; Longva, Oddvar; Shaw, John

    2007-01-01

    The extent and behaviour of the southeast margin of the Laurentide Ice Sheet in Atlantic Canada is of significance in the study of Late Wisconsinan ice sheet-ocean interactions. Multibeam sonar imagery of subglacial, ice-marginal and glaciomarine landforms on German Bank, Scotian Shelf, provides evidence of the pattern of glacial-dynamic events in the eastern Gulf of Maine. Northwest-southeast trending drumlins and megaflutes dominate northern German Bank. On southern German Bank, megaflutes of thin glacial deposits create a distinct northwest-southeast grain. Lobate regional moraines (>10km long) are concave to the northwest, up-ice direction and strike southwest-northeast, normal to the direction of ice flow. Ubiquitous, overlying De Geer moraines (

  18. Ferrous-iron-induced oxidation in chicken liver slices as measured by hemichrome formation and thiobarbituric acid-reactive substances: effects of dietary vitamin E and beta-carotene.

    PubMed

    Andersen, H J; Chen, H; Pellett, L J; Tappel, A L

    1993-07-01

    Hemichrome formation in chicken liver slices was determined by employing a Heme Protein Spectra Analysis Program (HPSAP) on the visible spectrum of the liver tissue. Relative hemichrome formation (RHF) in liver tissue exposed to ferrous iron for 1 h at 37 degrees C could be predicted according to the general catalytic equation RHF = k.[Fe2+]/(Ap + [Fe2+]), with k = 132 +/- 30, where the factor Ap represents the additive antioxidative potential in the liver tissue. RHF in Fe2+ exposed liver slices incubated at 37 degrees C for 1 h correlated significantly with formation of thiobarbituric acid-reactive substances (TBARS) (r = .77, P < .0001). RHF was found to decrease significantly with increasing vitamin E concentration in liver tissue exposed to ferrous iron (1 h, 37 degrees C). However, the influence of beta-carotene on RHF in ferrous-iron exposed liver slices (1 h, 37 degrees C) was less evident, as the concentration of Fe2+ was found to be decisive for whether beta-carotene acted as an antioxidant or a prooxidant under the conditions in question. Results in the liver slice model system regarding the effect of vitamin E and beta-carotene on iron overload were supported in a subsequent in vivo iron injection experiment with chicks. These observations indicate that RHF is a sensitive marker for ferrous-iron-induced oxidative damage in the present tissue slice system. PMID:8359710

  19. The formation mechanism of a textured ceramic of thermoelectric [Ca2CoO3](0.62)[CoO2] on beta-Co(OH)2 templates through in situ topotactic conversion.

    PubMed

    Itahara, Hiroshi; Seo, Won-Seon; Lee, Sujeong; Nozaki, Hiroshi; Tani, Toshihiko; Koumoto, Kunihito

    2005-05-01

    We investigated the formation mechanism of thermoelectric [Ca(2)CoO(3)](0.62)[CoO(2)] (CCO) on beta-Co(OH)(2) templates with maintained orientations by identifying the intermediate phases and specifying the relationship between their crystallographic orientations. We mixed beta-Co(OH)(2) templates with the complementary reactant CaCO(3) and prepared a compact by tape casting, with the developed (001) plane of the templates aligned along the casting plane. High-temperature XRD of the compact revealed that beta-Co(OH)(2) decomposed into Co(3)O(4) by 873 K, and Co(3)O(4) reacted with CaO to form CCO by 1193 K via the formation of the newly detected intermediate phase beta-Na(x)()CoO(2)-type Ca(x)()CoO(2) at 913-973 K. Pole figure measurements and SEM and TEM observations revealed that the relationship between the crystallographic planes was (001) beta-Co(OH)(2)//{111} Co(3)O(4)//(001) Ca(x)()CoO(2)//(001) CCO. The crystal structures of the four materials possess the common CoO(2) layer (or similar), which is composed of edge-sharing CoO(6) octahedra, parallel to the planes. The cross-sectional HRTEM analysis of an incompletely reacted specimen showed transient lattice images from Ca(x)()CoO(2) into CCO, in which every other CoO(2) layer of Ca(x)()CoO(2) was preserved. Thus, it was demonstrated that a textured CCO ceramic is produced through a series of in situ topotactic conversion reactions with a preserved CoO(2) layer of its template. PMID:15853344

  20. IO SUBSYSTEM 1 BETA

    Energy Science and Technology Software Center (ESTSC)

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/outputmore » library for finite element analysis, preprocessing, post processing, and translation programs.« less

  1. Liquid sheet radiator apparatus

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L. (Inventor)

    1990-01-01

    An external flow, liquid sheet radiator apparatus adapted for space applications has as its radiating surface a thin stable liquid sheet formed by fluid flow through a very narrow slit affixed to the sheet generator. As a result of surface tension forces, the sheet has a triangular shape and is collected into a simply designed collector positioned at the apex of the triangle. The specific power for the liquid sheet is virtually the same as the droplet sheet specific power.

  2. Near-earth Thin Current Sheets and Birkeland Currents during Substorm Growth Phase

    SciTech Connect

    Sorin Zaharia; C.Z. Cheng

    2003-04-30

    Two important phenomena observed during the magnetospheric substorm growth phase are modeled: the formation of a near-Earth (|X| {approx} 9 R{sub E}) thin cross-tail current sheet, as well as the equatorward shift of the ionospheric Birkeland currents. Our study is performed by solving the 3-D force-balance equation with realistic boundary conditions and pressure distributions. The results show a cross-tail current sheet with large current (J{sub {phi}} {approx} 10 nA/m{sup 2}) and very high plasma {beta} ({beta} {approx} 40) between 7 and 10 R{sub E}. The obtained region-1 and region-2 Birkeland currents, formed on closed field lines due to pressure gradients, move equatorward and become more intense (J{sub {parallel}max} {approx} 3 {micro}A/m{sup 2}) compared to quiet times. Both results are in agreement with substorm growth phase observations. Our results also predict that the cross-tail current sheet maps into the ionosphere in the transition region between the region-1 and region-2 currents.

  3. Maternal antioxidants prevent beta cell apoptosis and promote formation of dual hormone-expressing endocrine cells in male offspring following fetal and neonatal nicotine exposure

    PubMed Central

    BRUIN, Jennifer E; WOYNILLOWICZ, Amanda K; HETTINGA, Bart P; TARNOPOLSKY, Mark A; MORRISON, Katherine M; GERSTEIN, Hertzel C; HOLLOWAY, Alison C

    2013-01-01

    Aim Fetal and neonatal nicotine exposure causes beta cell oxidative stress and apoptosis in neonates, leading to adult-onset dysglycemia. The goal of this study was to determine whether an antioxidant intervention could prevent nicotine-induced beta cell loss. Methods Nulliparous female Wistar rats received daily subcutaneous injections of either saline or nicotine bitartrate (1.0 mg/kg/d) for 2 weeks prior to mating until weaning. Nicotine-exposed dams received either normal chow or diet containing antioxidants (1000 IU/kg vitamin E, 0.25% w/w coenzyme Q10 and 0.1% w/w alpha-lipoic acid) during mating, pregnancy and lactation; saline-exposed dams received normal chow. Pancreas tissue was collected from male offspring at 3 weeks of age to measure beta cell fraction, apoptosis, proliferation and the presence of cells co-expressing insulin and glucagon. Results The birth weight of the offspring born to nicotine-exposed dams receiving dietary antioxidants was significantly reduced. Most interestingly, the antioxidant intervention to nicotine-exposed dams prevented the beta cell loss and apoptosis observed in nicotine exposed male offspring whose mothers did not receive antioxidants. Male pups born to nicotine-treated mothers receiving antioxidants also had a trend towards increased beta cell proliferation and a significant increase in islets containing insulin/glucagon bi-hormonal cells relative to the other two treatment groups. Conclusion This study demonstrates that exposure to maternal antioxidants protects beta cells from the damaging effects of nicotine thus preserving beta cell mass. PMID:22385833

  4. MESSENGER and Venus Express Observations of the Near-tail of Venus: Magnetic Flux Transport, Current Sheet Structure, and Flux Rope Formation

    NASA Technical Reports Server (NTRS)

    Slavin, James A.; Boardsen, S. A.; Sarantos, M.; Acuna, M. H.; Anderson, B. J.; Barabash, S.; Benna, M.; Fraenz, M.; Gloeckler, G.; Gold, R. E.; Ho, G. C.; Korth, H.; Krimigis, S. M.; McNutt, R. L., Jr.; Raines, J. M.; Solomon, S. C.; Zhang, T.-L.; Zurbuchen, T. H.

    2008-01-01

    At 23:08 UT on 5 June 2007 the MESSENGER spacecraft reached its closest approach altitude (338 km) during its second flyby of Venus en route to its 2011 orbit insertion at Mercury. Whereas no measurements were collected during MESSENGER'S first Venus flyby in October 2006, the Magnetometer (MAG) and the Energetic Particle and Plasma Spectrometer (EPPS) operated successfully throughout this second encounter. Venus provides the solar system's best example to date of a solar wind - ionosphere planetary interaction. We present MESSENGER observations of the near-tail of Venus with emphasis on determining the time scales for magnetic flux transport, the structure of the cross-tail current sheet at very low altitudes (approx. 300 to 1000 km), and the nature and origin of a magnetic flux rope observed in the current sheet. The availability of the simultaneous Venus Express upstream measurements provides a unique opportunity to examine the influence of solar wind plasma and interplanetary magnetic field conditions on this planet's solar wind interaction at solar minimum.

  5. Electron Diffraction Evidence for the Ordering of Excess Nickel Atoms by Relation to Stoichiometry in Nickel-Rich Beta'-Nial Formation of a Nickel-Aluminum (Ni2al) Superlattices

    NASA Technical Reports Server (NTRS)

    Reynaud, F.

    1988-01-01

    In electron diffraction patterns of nickel-rich beta-NiAl alloys, many anomalies are observed. One of these is the appearance of diffuse intensity maxima between the reflexions of the B2 structure. This is explained by the short-range ordering of the excess nickel atoms on the simple cubic sublattice occupied only by aluminum atoms in the stoichiometric, perfectly ordered NiAl alloy. After annealing Ni 37.5 atomic percent Al and Ni 37.75 atomic percent Al for 1 week at 300 and 400 C, the diffuse intensity maxima transformed into sharp superstructure reflexions. These reflexions are explained by the formation of the four possible variants of an ordered hexagonal superstructure corresponding to the Ni2Al composition. This structure is closely related to the Ni2Al3 structure (same space group) formed by the ordering of vacancies on the nickel sublattice in aluminum-rich beta-NiAl alloys.

  6. Secondary structure formation in peptide amphiphile micelles

    NASA Astrophysics Data System (ADS)

    Tirrell, Matthew

    2012-02-01

    Peptide amphiphiles (PAs) are capable of self-assembly into micelles for use in the targeted delivery of peptide therapeutics and diagnostics. PA micelles exhibit a structural resemblance to proteins by having folded bioactive peptides displayed on the exterior of a hydrophobic core. We have studied two factors that influence PA secondary structure in micellar assemblies: the length of the peptide headgroup and amino acids closest to the micelle core. Peptide length was systematically varied using a heptad repeat PA. For all PAs the addition of a C12 tail induced micellization and secondary structure. PAs with 9 amino acids formed beta-sheet interactions upon aggregation, whereas the 23 and 30 residue peptides were displayed in an apha-helical conformation. The 16 amino acid PA experienced a structural transition from helix to sheet, indicating that kinetics play a role in secondary structure formation. A p53 peptide was conjugated to a C16 tail via various linkers to study the effect of linker chemistry on PA headgroup conformation. With no linker the p53 headgroup was predominantly alpha helix and a four alanine linker drastically changed the structure of the peptide headgroup to beta-sheet, highlighting the importance of hydrogen boding potential near the micelle core.

  7. Gender-related effects of 17-{beta}-estradiol and B-hexachlorocyclohexane on liver tumor formation in medaka (Oryzias latipes)

    SciTech Connect

    Cooke, J.B.; Hinton, D.E.

    1994-12-31

    When medaka were acutely exposed to diethylnitrosamine (DEN), greater incidence of hepatocarcinoma was seen in female versus male fish. This is possibly related to elevated female endogenous estrogens, which increase liver weight and production of vitellogenin. To examine roles of estrogens in tumor modulation, 21-day old medaka were exposed to DEN (200 ppm for 24 hr.), then fed purified diets containing the estrogenic compound {beta}-hexachlorocyclohexane ({beta}-HCH) or 17-{beta}estradiol (E2) for 6 months. Incidences of basophilic preneoplastic foci of cellular alteration in females receiving DEN and 0.01, 0.1, or 1.0 ppm E2 were three times the incidences in similarly-treated males. Also, incidences of basophilic foci in DEN + 0.1 ppm E2 males were significantly increased over DEN-only males and were equal to incidences in DEN-only females. Liver weights and hepatosomatic indices of males given 0.1 ppm E2 were not significantly different than females fed control diet. Females fed 0.01-10.0 ppm {beta}-HCH after DEN had 4--5 times greater incidences of basophilic foci as males. Gender-related effects on kinetics of growth rates and volumes of foci are being examined.

  8. Molecular contortionism - on the physical limits of serpin 'loop-sheet' polymers.

    PubMed

    Huntington, James A; Whisstock, James C

    2010-08-01

    Members of the serpin (serine protease inhibitor) superfamily fold into a metastable conformation that is crucial for proper function. As a consequence, serpins are susceptible to mutations that cause misfolding and the intracellular accumulation of pathogenic polymers. The mechanism of serpin polymerisation remains to be resolved, however, over the past two decades the 'loop-sheet' hypothesis has gained wide acceptance. In this mechanism the reactive centre loop of one serpin monomer inserts into the beta-sheet A of another (in trans), in a manner similar to what is seen for reactive centre loop-cleaved and latent conformations (in cis). The hypothesis has been refined in response to certain experimental data, but it has proved difficult to assess the various propositions without creating molecular models. Here we evaluate the loop-sheet mechanism by creating models of pentamers of the archetypal serpin alpha(1)-antitrypsin. We conclude that an inescapable consequence of the loop-sheet mechanism is polymer compaction and rigidity, properties that are inconsistent with the 'beads-on-a-string' morphology of polymers obtained from human tissue. The recent crystal structure of a domain-swapped serpin dimer suggests an alternative mechanism that is consistent with known polymer properties, including the requirement of partial unfolding to induce polymer formation in vitro, and polymerisation from a folding intermediate in vivo. PMID:20731544

  9. Experimental Study of Lower-hybrid Drift Turbulence in a Reconnecting Current Sheet

    SciTech Connect

    Carter, T. A.; Yamada, M.; Ji, H.; Kulsrud, R. M.; Trintchouck, F.

    2002-06-18

    The role of turbulence in the process of magnetic reconnection has been the subject of a great deal of study and debate in the theoretical literature. At issue in this debate is whether turbulence is essential for fast magnetic reconnection to occur in collisionless current sheets. Some theories claim it is necessary in order to provide anomalous resistivity, while others present a laminar fast reconnection mechanism based on the Hall term in the generalized Ohm's law. In this work, a thorough study of electrostatic potential fluctuations in the current sheet of the Magnetic Reconnection Experiment (MRX) [M. Yamada et al., Phys. Plasmas 4, 1936 (1997)] was performed in order to ascertain the importance of turbulence in a laboratory reconnection experiment. Using amplified floating Langmuir probes, broadband fluctuations in the lower hybrid frequency range (fLH approximately 5-15 MHz) were measured which arise with the formation of the current sheet in MRX. The frequency spectrum, spatial amplitude profile, and spatial correlation characteristics of the measured turbulence were examined carefully, finding consistency with theories of the lower-hybrid drift instability (LHDI). The LHDI and its role in magnetic reconnection has been studied theoretically for decades, but this work represents the first detection and detailed study of the LHDI in a laboratory current sheet. The observation of the LHDI in MRX has provided the unique opportunity to uncover the role of this instability in collisionless reconnection. It was found that: (1) the LHDI fluctuations are confined to the low-beta edge of current sheets in MRX; (2) the LHDI amplitude does not correlate well in time or space with the reconnection electric field, which is directly related to the rate of reconnection; and (3) significant LHDI amplitude persists in high collisionality current sheets where the reconnection rate is classical. These findings suggest that the measured LHDI fluctuations do not play an essential role in determining the reconnection rate in MRX.

  10. Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro.

    PubMed Central

    Kirschner, D A; Inouye, H; Duffy, L K; Sinclair, A; Lind, M; Selkoe, D J

    1987-01-01

    Progressive amyloid deposition in senile plaques and cortical blood vessels may play a central role in the pathogenesis of Alzheimer disease. We have used x-ray diffraction and electron microscopy to study the molecular organization and morphology of macromolecular assemblies formed by three synthetic peptides homologous to beta protein of brain amyloid: beta-(1-28), residues 1-28 of the beta protein; [Ala16]beta-(1-28), beta-(1-28) with alanine substituted for lysine at position 16; and beta-(18-28), residues 18-28 of the beta protein. beta-(1-28) readily formed fibrils in vitro that were similar in ultrastructure to the in vivo amyloid and aggregated into large bundles resembling those of senile plaque cores. X-ray patterns from partially dried, oriented pellets showed a cross-beta-conformation. A series of small-angle, equatorial maxima were consistent with a tubular fibril having a mean diameter of 86 A and a wall composed of pairs of cross-beta-pleated sheets. The data may also be consistent with pairs of cross-beta-sheets that are centered 71-A apart. [Ala16]beta-(1-28) formed beta-pleated sheet assemblies that were dissimilar to in vivo fibrils. The width of the 10-A spacing indicated stacks of about six sheets. Thus, substitution of the uncharged alanine for the positively charged lysine in the beta-strand region enhances the packing of the sheets and dramatically alters the type of macromolecular aggregate formed. beta-(18-28) formed assemblies that had even a greater number of stacked sheets, approximately equal to 24 per diffracting domain as indicated by the sharp intersheet reflection. Our findings on these homologous synthetic assemblies help to define the specific sequence that is required to form Alzheimer-type amyloid fibrils, thus providing an in vitro model of age-related cerebral amyloidogenesis. Images PMID:3477820

  11. Assessing the role of precursor cyclones on the formation of extreme Greenland blocking episodes and their impact on summer melting across the Greenland ice sheet

    NASA Astrophysics Data System (ADS)

    McLeod, Jordan T.; Mote, Thomas L.

    2015-12-01

    A 30 year climatology of North Atlantic cyclones from 1979 to 2008 is examined within the context of extreme Greenland blocking and accelerated surface melting across the Greenland ice sheet (GrIS). A distinct class of North Atlantic cyclones, known as precursor cyclones, was identified as any extratropical cyclones originating to the west of Greenland blocks prior to the peak of blocking intensity. Composite map analysis reveals that precursor cyclones contributed to a significant intensification of extreme Greenland blocking episodes (GBEs) through the process of upper level wave amplification. Across all seasons, most extreme GBEs are associated with multiple precursor cyclones prior to peaking in intensity, and a majority of these cyclones have continental rather than oceanic origins. Over both the western and eastern sectors of Greenland, daily meltwater production simulated by the Modle Atmosphrique Rgional regional climate model is greater during extreme GBEs accompanied by precursor cyclones compared to extreme GBEs lacking a precursor cyclone. Based on an analysis of air parcel trajectories and North Atlantic SST anomalies, enhanced surface melting during the summer, particularly over southern and western Greenland, is strongly linked to the combination of vigorous adiabatic warming generated by subsiding air within the blocking anticyclones and warm air advection supplied by the precursor cyclones. With the increased frequency of extreme GBEs accompanied by precursor cyclones observed during a strong positive phase of the Atlantic Multidecadal Oscillation, recent long-term increases in GrIS surface melting can be partially attributed to the interaction of these atmospheric and oceanic processes.

  12. Minimalist design of water-soluble cross-[beta] architecture

    SciTech Connect

    Biancalana, Matthew; Makabe, Koki; Koide, Shohei

    2010-08-13

    Demonstrated successes of protein design and engineering suggest significant potential to produce diverse protein architectures and assemblies beyond those found in nature. Here, we describe a new class of synthetic protein architecture through the successful design and atomic structures of water-soluble cross-{beta} proteins. The cross-{beta} motif is formed from the lamination of successive {beta}-sheet layers, and it is abundantly observed in the core of insoluble amyloid fibrils associated with protein-misfolding diseases. Despite its prominence, cross-{beta} has been designed only in the context of insoluble aggregates of peptides or proteins. Cross-{beta}'s recalcitrance to protein engineering and conspicuous absence among the known atomic structures of natural proteins thus makes it a challenging target for design in a water-soluble form. Through comparative analysis of the cross-{beta} structures of fibril-forming peptides, we identified rows of hydrophobic residues ('ladders') running across {beta}-strands of each {beta}-sheet layer as a minimal component of the cross-{beta} motif. Grafting a single ladder of hydrophobic residues designed from the Alzheimer's amyloid-{beta} peptide onto a large {beta}-sheet protein formed a dimeric protein with a cross-{beta} architecture that remained water-soluble, as revealed by solution analysis and x-ray crystal structures. These results demonstrate that the cross-{beta} motif is a stable architecture in water-soluble polypeptides and can be readily designed. Our results provide a new route for accessing the cross-{beta} structure and expanding the scope of protein design.

  13. Spontaneous imbibition experiment in newspaper sheets.

    PubMed

    Miranda, A M; Menezes-Sobrinho, I L; Couto, M S

    2010-02-26

    We study the behavior of an ink-paper interface in a spontaneous imbibition experiment as a function of time and paper orientation. To characterize the interface roughness the growth beta and Hurst H exponents (calculated using the root mean square interface width W) and the H{q} scaling exponent (calculated using the qth order height-height correlation function) are used. Our results indicate that the values of H and H{q} depend on the orientation of the paper sheets, while beta does not, and that the interface exhibits a multiaffine character during all its evolution. PMID:20366951

  14. Conformation transition of betaA in solution and on surface of lipid bilayer

    NASA Astrophysics Data System (ADS)

    Qiu, Liming; Reay, Andrew; Zhu, Qing; Vaughn, Mark; Cheng, Kwan

    2007-10-01

    Beta amyloid (betaA) is a 39 to 43 residue peptide generated by a proteolytic cleavage of a large transmembrane amyloid precursor protein in neuronal membranes. The misfolding and self-aggregation of betaA, as well as its interactions with neuronal membranes, have been linked to the early onset of pathogenesis of Alzheimer disease. The secondary structure conformational transition of betaA from an alpha-helix to beta-sheet in some key regions of the peptide represents an important signature of the complex misfolding behavior of betaA. Using all-atom molecular dynamics simulations, the conformation changes of betaA in solution and on the surface of lipid bilayer containing nanodomains of cholesterol have been studied. Our results indicated that the appearance of beta-sheet structures depends strong on the initial structures of betaA and the arrangement of cholesterol molecules in the lipid bilayer.

  15. In-situ time-of-flight neutron diffraction of ErD2 (beta phase) formation during D2 loading.

    SciTech Connect

    Browning, James Frederick; Llobet, Anna; Snow, Clark Sheldon; Rodriguez, Mark Andrew; Wixom, Ryan R.

    2008-06-01

    In an effort to better understand the structural changes occurring during hydrogen loading of erbium target materials, we have performed D{sub 2} loading of erbium metal (powder) with simultaneous neutron diffraction analysis. This experiment tracked the conversion of Er metal to the {alpha} erbium deuteride (solid-solution) phase and then on to the {beta} (fluorite) phase. Complete conversion to ErD{sub 2.0} was accomplished at 10 Torr D{sub 2} pressure with deuterium fully occupying the tetrahedral sites in the fluorite lattice. Increased D{sub 2} pressure (up to 500 Torr at 450 C) revealed {approx}10 % deuterium occupation of the octahedral sites. Subsequent vacuum pumping of the sample at 450 C removed octahedral site occupancy while maintaining tetrahedral deuterium occupancy, thereby yielding stoichiometric ErD{sub 2.0} {beta} phase.

  16. Dual folding pathways of an alpha/beta protein from all-atom ab initio folding simulations.

    PubMed

    Lei, Hongxing; Wang, Zhi-Xiang; Wu, Chun; Duan, Yong

    2009-10-28

    Successful ab initio folding of proteins with both alpha-helix and beta-sheet requires a delicate balance among a variety of forces in the simulation model, which may explain that the successful folding of any alpha/beta proteins to within experimental error has yet to be reported. Here we demonstrate that it is an achievable goal to fold alpha/beta proteins with a force field emphasizing the balance between the two major secondary structures. Using our newly developed force field, we conducted extensive ab initio folding simulations on an alpha/beta protein full sequence design (FSD) employing both conventional molecular dynamics and replica exchange molecular dynamics in combination with a generalized-Born solvation model. In these simulations, the folding of FSD to the native state with high population (>64.2%) and high fidelity (C(alpha)-Root Mean Square Deviation of 1.29 A for the most sampled conformation when compared to the experimental structure) was achieved. The folding of FSD was found to follow two pathways. In the major pathway, the folding started from the formation of the helix. In the minor pathway, however, folding of the beta-hairpin started first. Further examination revealed that the helix initiated from the C-terminus and propagated toward the N-terminus. The formation of the hydrophobic contacts coincided with the global folding. Therefore the hydrophobic force does not appear to be the driving force of the folding of this protein. PMID:19894980

  17. Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.

    PubMed Central

    Ushikubo, S.; Aoyama, T.; Kamijo, T.; Wanders, R. J.; Rinaldo, P.; Vockley, J.; Hashimoto, T.

    1996-01-01

    Mitochondrial trifunctional protein (TP) is an enzyme complex with three activities: enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase. Studies on defects in this enzyme in patients with TP deficiency suggest that there are two types of defect. Patients in group 1 have normal amount of cross-reacting material by immunoblot and lack only long-chain 3-hydroxyacyl-CoA dehydrogenase activity. Patients in group 2 have a trace amount of cross-reacting material, with all three activities being low. We identified three patients in group 2, and analysis was made at the cDNA level. In patient 2, there was a heterozygous 71-bp deletion at position 110-180 in the alpha-subunit. In patients 1 and 3, there was an abnormal beta-subunit; patient 1 had an A-788-to-G substitution, and patient 3 had G-182-to-A and G-740-to-A substitutions in each of separate alleles. This is the first demonstration of disease-causing mutations in the beta-subunit. cDNA-expression experiments in patients' fibroblasts, using a vaccinia virus system, and gel filtration analysis, using patients' fibroblasts, revealed that the existence of both normal alpha- and beta-subunits, and possibly their association, are important for stabilizing TP and that A-788-to-G substitution on the beta-subunit in patient 1 seems to interfere with the association, the result being a rapid decomposition of TP. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8651282

  18. Formation of gamma(sup prime)-Ni3Al via the Peritectoid Reaction: gamma + beta (+ Al2O3)=gamma(sup prime)(+ Al2O3)

    NASA Technical Reports Server (NTRS)

    Copeland, Evan

    2008-01-01

    The activities of Al and Ni were measured using multi-cell Knudsen effusion-cell mass spectrometry (multi-cell KEMS), over the composition range 8-32 at.%Al and temperature range T=1400-1750 K in the Ni-Al-O system. These measurements establish that equilibrium solidification of gamma(sup prime)-Ni3Al-containing alloys occurs by the eutectic reaction, L (+ Al2O3)=gamma + Beta(+ Al2O3), at 1640 +/- 1 K and a liquid composition of 24.8 +/- 0.2 at.%al (at an unknown oxygen content). The {gamma + Beta (+Al2O3} phase field is stable over the temperature range 1633-1640 K, and gamma(sup prime)-Ni3Al forms via the peritectoid, gamma + Beta (+ Al2O3)=gamma(sup prime) (+ Al2O3), at 1633 +/- 1 K. This behavior is consistent with the current Ni-Al phase diagram and a new diagram is proposed. This new Ni-Al phase diagram explains a number of unusual steady-state solidification structures reported previously and provides a much simpler reaction scheme in the vicinity of the gamma(sup prime)-Ni2Al phase field.

  19. Formation of gamma'-Ni3Al via the Peritectoid Reaction: gamma plus beta (+Al2O3) equals gamma'(+Al2O3)

    NASA Technical Reports Server (NTRS)

    Copland, Evan

    2008-01-01

    The activities of Al and Ni were measured using multi-cell Knudsen effusion-cell mass spectrometry (multi-cell KEMS), over the composition range 8 - 32 at.%Al and temperature range T = 1400 - 1750 K in the Ni-Al-O system. These measurements establish that equilibrium solidification of gamma'-Ni3Al-containing alloys occurs by the eutectic reaction, L (+ Al2O3) = gamma + beta (+ Al2O3), at 1640 plus or minus 1 K and a liquid composition of 24.8 plus or minus 0.2 at.%Al (at an unknown oxygen content). The {gamma + beta + Al2O3} phase field is stable over the temperature range 1633 - 1640 K, and gamma'-Ni3Al forms via the peritectiod, gamma + beta (+ Al2O3) = gamma'(+ Al2O3), at 1633 plus or minus 1 K. This behavior is inconsistent with the current Ni-Al phase diagram and a new diagram is proposed. This new Ni-Al phase diagram explains a number of unusual steady state solidification structures reported previously and provides a much simpler reaction scheme in the vicinity of the gamma'-Ni3Al phase field.

  20. Protein Complex of Drosophila ATRX/XNP and HP1a Is Required for the Formation of Pericentric Beta-heterochromatin in Vivo*

    PubMed Central

    Emelyanov, Alexander V.; Konev, Alexander Y.; Vershilova, Elena; Fyodorov, Dmitry V.

    2010-01-01

    ATRX belongs to the family of SWI2/SNF2-like ATP-dependent nucleosome remodeling molecular motor proteins. Mutations of the human ATRX gene result in a severe genetic disorder termed X-linked α-thalassemia mental retardation (ATR-X) syndrome. Here we perform biochemical and genetic analyses of the Drosophila melanogaster ortholog of ATRX. The loss of function allele of the Drosophila ATRX/XNP gene is semilethal. Drosophila ATRX is expressed throughout development in two isoforms, p185 and p125. ATRX185 and ATRX125 form distinct multisubunit complexes in fly embryo. The ATRX185 complex comprises p185 and heterochromatin protein HP1a. Consistently, ATRX185 but not ATRX125 is highly concentrated in pericentric beta-heterochromatin of the X chromosome in larval cells. HP1a strongly stimulates biochemical activities of ATRX185 in vitro. Conversely, ATRX185 is required for HP1a deposition in pericentric beta-heterochromatin of the X chromosome. The loss of function allele of the ATRX/XNP gene and mutant allele that does not express p185 are strong suppressors of position effect variegation. These results provide evidence for essential biological functions of Drosophila ATRX in vivo and establish ATRX as a major determinant of pericentric beta-heterochromatin identity. PMID:20154359

  1. Copper(II) inhibits the formation of amylin amyloid in vitro.

    PubMed

    Ward, Benjamin; Walker, Karen; Exley, Christopher

    2008-02-01

    The amyloidogenic peptide amylin is found associated with pancreatic islet beta-cells and is implicated in the aetiology of type-2 diabetes mellitus. We have used fluorimetry and transmission electron microscopy to investigate in vitro the influence of Al(III), Fe(III), Zn(II) and Cu(II) on amylin amyloid formation under near-physiological conditions. Cu(II) at 10.0 microM inhibited amylin of 0.4 and 2.0 microM from forming amyloid fibrils while the same concentration of either Al(III) or Zn(II) promoted the formation of beta-pleated sheet structures. If amylin amyloid is cytotoxic to beta-cells then Cu(II) should protect against the degeneration of the islets in type-2 diabetes mellitus. PMID:18022240

  2. Molecular structures of magnesium dichloride sheets and nanoballs.

    PubMed

    Luhtanen, Tommi N P; Linnolahti, Mikko; Pakkanen, Tapani A

    2004-07-12

    The structures and relative stabilities of (MgCl(2))(n)() sheetlike clusters and nanoballs were studied by quantum chemical methods. The sheets as discrete molecules were studied up to Mg(100)Cl(200). Their stabilities increase systematically as a function of the size of the sheet. Periodic ab initio calculations were performed for (001) monolayer sheets of alpha- and beta-MgCl(2), beta-sheet being slightly favored. Nanoballs were constructed from Archimedean polyhedra, producing tetrahedral, octahedral, and icosahedral symmetries, and were studied up to Mg(60)Cl(120). Nanoballs prefer to take the shape of truncated cuboctahedron (Mg(48)Cl(96)). Comparisons to sheetlike clusters and periodic calculations suggest that magnesium dichloride nanoballs are stable. PMID:15236562

  3. Superfund fact sheet: Exposure pathways. Fact sheet

    SciTech Connect

    Not Available

    1992-09-01

    The fact sheet describes exposure pathways, the different manners in which people can be exposed to hazardous materials. Explanations of several pathways involving surface waters, ground water, air, soil, and the food chain are given. The fact sheet is one in a series providing reference information about Superfund issues and is intended for readers with no formal scientific training.

  4. Structural Biology Fact Sheet

    MedlinePLUS

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  5. Zika Virus Fact Sheet

    MedlinePLUS

    ... 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts Zika virus Fact sheet Updated 18 March 2016 Key facts ... last for 2-7 days. Potential complications of Zika virus disease During large outbreaks in French Polynesia and ...

  6. MHD Ballooning Instability in the Plasma Sheet

    SciTech Connect

    C.Z. Cheng; S. Zaharia

    2003-10-20

    Based on the ideal-MHD model the stability of ballooning modes is investigated by employing realistic 3D magnetospheric equilibria, in particular for the substorm growth phase. Previous MHD ballooning stability calculations making use of approximations on the plasma compressibility can give rise to erroneous conclusions. Our results show that without making approximations on the plasma compressibility the MHD ballooning modes are unstable for the entire plasma sheet where beta (sub)eq is greater than or equal to 1, and the most unstable modes are located in the strong cross-tail current sheet region in the near-Earth plasma sheet, which maps to the initial brightening location of the breakup arc in the ionosphere. However, the MHD beq threshold is too low in comparison with observations by AMPTE/CCE at X = -(8 - 9)R(sub)E, which show that a low-frequency instability is excited only when beq increases over 50. The difficulty is mitigated by considering the kinetic effects of ion gyrorad ii and trapped electron dynamics, which can greatly increase the stabilizing effects of field line tension and thus enhance the beta(sub)eq threshold [Cheng and Lui, 1998]. The consequence is to reduce the equatorial region of the unstable ballooning modes to the strong cross-tail current sheet region where the free energy associated with the plasma pressure gradient and magnetic field curvature is maximum.

  7. Polyalanine and Abeta Aggregation Kinetics: Probing Intermediate Oligomer Formation and Structure Using Computer Simulations

    NASA Astrophysics Data System (ADS)

    Phelps, Erin Melissa

    2011-12-01

    The aggregation of proteins into stable, well-ordered structures known as amyloid fibrils has been associated with many neurodegenerative diseases. Amyloid fibrils are long straight, and un-branched structures containing several proto-filaments, each of which exhibits "cross beta structure," -- ribbon-like layers of large beta sheets whose strands run perpendicular to the fibril axis. It has been suggested in the literature that the pathway to fibril formation has the following steps: unfolded monomers associate into transient unstable oligomers, the oligomers undergo a rearrangement into the cross-beta structure and form into proto-filaments, these proto-filaments then associate and grow into fully formed fibrils. Recent experimental studies have determined that the unstable intermediate structures are toxic to cells and that their presence may play a key role in the pathogenesis of the amyloid diseases. Many efforts have been made to determine the structure of intermediate oligomer aggregates that form during the fibrillization process. The goal of this work is to provide details about the structure and formation kinetics of the unstable oligomers that appear in the fibril formation pathway. The specific aims of this work are to determine the steps in the fibril formation pathway and how the kinetics of fibrillization changes with variations in temperature and concentration. The method used is the application of discontinuous molecular dynamics to large systems of peptides represented with an intermediate resolution model, PRIME, that was previously developed in our group. Three different peptide sequences are simulated: polyalanine (KA14K), Abeta17-40, and Abeta17-42; the latter two are truncated sequences of the Alzheimer's peptide. We simulate the spontaneous assembly of these peptide chains from a random initial configuration of random coils. We investigate aggregation kinetics and oligomer formation of a system of 192 polyalanine (KA14K) chains over a variety of temperatures and concentrations. The fibril formation pathway has the following steps: free monomers associate into small amorphous aggregates, those small amorphous aggregates grow, the amorphous aggregates rearrange into beta-sheets, and finally the beta-sheets stack into small fibrillar structures. The rate of fibril formation increases as concentration increases and temperature decreases; this faster fibril formation is the combination of several effects, including increased amorphous aggregate formation from free monomers, increased amorphous aggregate rearrangement into beta-sheets, and increased stacking into small fibrils. There is a competition between enthalpy and entropy that determine the behavior of the final structure in the system. At low temperature, enthalpy is dominant and the system produces multiple large fibrils, while at high temperature entropy is dominant and the system produces one or no large fibrils. As temperature increases and concentration decreases the intermediate structures that form, such as beta-sheets and large independent amorphous aggregates, are more stabilized which leads to slower fibril formation and fewer chains in the large final fibrillar structure. We study the formation of beta-sheets and small fibrillar structures for both Abeta17-40 and Abeta17-42 to determine the difference between the two sequences in aggregation kinetics and oligomer structure as a function of temperature. We observe that at low temperatures, both Abeta17-40 and Abeta17-42 form large amorphous aggregates with a small amount of beta-sheet character, at intermediate temperatures the peptides form a mixture of beta-sheets and fibrils that are surrounded by amorphous aggregates, and at high temperatures the peptides form small amorphous aggregates or remain isolated as free monomers. Abeta 17-42 forms fibrils over a larger temperature range than Abeta 17-40. The structure of the beta-sheets changes as temperature increases through the range conducive to fibril formation. Abeta17-42 goes through the transition from predominantly intra-strand hydrogen bonds to predominantly inter-strand hydrogen bonds in the beta-sheet structure at a higher temperature than Abeta17-40.

  8. The iA{beta}5p {beta}-breaker peptide regulates the A{beta}(25-35) interaction with lipid bilayers through a cholesterol-mediated mechanism

    SciTech Connect

    Vitiello, Giuseppe; CSGI , Florence ; Grimaldi, Manuela; D'Ursi, Anna Maria; D'Errico, Gerardino; CSGI , Florence

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer iA{beta}5p shows a significant tendency to deeply penetrates the hydrophobic core of lipid membrane. Black-Right-Pointing-Pointer A{beta}(25-35) locates in the external region of the membrane causing a re-positioning of CHOL. Black-Right-Pointing-Pointer iA{beta}5p withholds cholesterol in the inner hydrophobic core of the lipid membrane. Black-Right-Pointing-Pointer iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane. -- Abstract: Alzheimer's disease is characterized by the deposition of aggregates of the {beta}-amyloid peptide (A{beta}) in the brain. A potential therapeutic strategy for Alzheimer's disease is the use of synthetic {beta}-sheet breaker peptides, which are capable of binding A{beta} but unable to become part of a {beta}-sheet structure, thus inhibiting the peptide aggregation. Many studies suggest that membranes play a key role in the A{beta} aggregation; consequently, it is strategic to investigate the interplay between {beta}-sheet breaker peptides and A{beta} in the presence of lipid bilayers. In this work, we focused on the effect of the {beta}-sheet breaker peptide acetyl-LPFFD-amide, iA{beta}5p, on the interaction of the A{beta}(25-35) fragment with lipid membranes, studied by Electron Spin Resonance spectroscopy, using spin-labeled membrane components (either phospholipids or cholesterol). The ESR results show that iA{beta}5p influences the A{beta}(25-35) interaction with the bilayer through a cholesterol-mediated mechanism: iA{beta}5p withholds cholesterol in the inner hydrophobic core of the bilayer, making the interfacial region more fluid and capable to accommodate A{beta}(25-35). As a consequence, iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane, which is the first step of the {beta}-amyloid aggregation process.

  9. Spot welding of steel and aluminum using insert sheet

    SciTech Connect

    Oikawa, H.; Saito, T.; Yoshimura, T.

    1994-12-31

    Automobile industries have been increasingly interested in the use of aluminum and thus joining of steel and aluminum becomes of importance. The joining of the two types of metal raises a problem of brittle welds caused by the formation of intermetallic compounds. The authors solved the problem by using an insert sheet. This paper deals with the resistance spot welding of steel and aluminum sheets using insert sheets. The insert sheet used in the present development was a steel/aluminum clad sheet of the 0.8 mm thickness with 50% steel and 50% aluminum. The clad sheet was produced by warm rolling of steel and aluminum with a direct resistance heating process. Steel to be warm rolled was of EDDQ of the 0.4 mm thickness and aluminum was of JIS A1050 of 0.6 mm thickness. The mechanical properties of the insert clad sheets were in between those of the steel sheets and the aluminum sheets, while the clad sheets showed much better formability than the aluminum sheets. Resistance spot welding was conducted for 0.8 mm thick EDDQ steel sheets and 1.0 mm thick aluminum alloy (AL-5.5%Mg) sheets under the welding force of 1.96 kN, welding current ranging between 4.2 and 20.1 kA, and welding time from 0.5 to 10 cycles. The steel was spot welded to the steel side of the insert sheet while the aluminum was welded to the aluminum side. What the authors investigated were the applicable welding current range, nugget diameter, tensile shear strength, U-tension strength, and macro- and microstructures. In conclusion, steel sheets can be spot welded to aluminum sheets without difficulty by using clad sheets as insert materials while the strength level of the dissimilar metal spot welds is close to that of aluminum joints.

  10. Protein purification with novel porous sheets containing derivatized cellulose.

    PubMed

    Manganaro, J L; Goldberg, B S

    1993-01-01

    Novel porous sheets containing commercially available cellulosic ion exchange media of several different functionalities in a PVC matrix have been prepared and evaluated. The advantages of these materials are resistance to alkali, clean in place procedures and low nonspecific binding. These sheets thus provide well-known and well-characterized particulate chromatographic media in a porous sheet format. The porous sheet format permits use of short, squat geometries (stacked sheets) as well as tolerance of high pressure gradients. The net result is the ability to handle much higher flow rates (10-fold or greater) than achievable by comparable cellulosic packed columns of the neat particulate media. Chromatographic separation of natural egg white proteins by a linear salt gradient on a single sheet of 1.3-mm thickness was demonstrated. In addition, a very significant advantage of the porous sheet format is that it permits the fabrication of devices which are not possible with particulate media. An example of such a device is the Acti-Mod Spiral Module. In the spiral module a spiral flow channel is formed by wrapping the porous sheet material around a mandrel. Embossed ribbing in the porous sheet provides channel spacing. The small open channel accommodates high flow rates of biological suspensions while the porous sheet walls selectively remove components of the suspension. PMID:7763697

  11. Effect of Strand Symmetry on the Nanostructure and Material Properties in Beta-Hairpin Peptide Hydrogels

    NASA Astrophysics Data System (ADS)

    Hule, Rohan; Pochan, Darrin; Nagarkar, Radhika; Schneider, Joel

    2007-03-01

    Hydrogels have been established as promising biomaterials for applications such as scaffolds for tissue engineering, controlled drug delivery and cell encapsulation. De novo designed beta hairpin peptides, capable of undergoing self assembly and hydrogel formation, were investigated that contain asymmetric beta strand arms surrounding a turn sequence. The stimuli responsive self assembly of the hydrogels occurs via an intramolecular folding and strand interdigitation mechanism. CD and FTIR indicate a beta sheet secondary structure. WAXS shows a fibril structure reminiscent of the cross beta spine. SANS has been employed to globally quantify the local structure as being rod-like. Modification of the strand registry results in fibrils with non-twisting, laminated vs. twisted nanostructure. Fibril dimensions as measured by TEM and AFM corroborate the interdigitated assembly. Bulk material properties of these hydrogels studied using oscillatory rheology vary significantly for the different morphologies. Differences in the peptide registry that drive hydrogel nanostructure and the consequent material properties can be potentially utilized for usage in specific biomaterial applications.

  12. Improving the medical take sheet

    PubMed Central

    Reed, Oliver

    2014-01-01

    The GMC states that Trainees in hospital posts must have well organised handover arrangements, ensuring continuity of patient care[1]. In the Belfast City Hospital throughout the day there can be multiple new medical admissions. These can be via the GP Unit, transfers for tertiary care, and transfers due to bed shortages in other hospitals. Over the course of 24 hours there can be up to four medical SHOs and three registrars that fill in the take sheet. Due to the variety of admission routes and number of doctors looking after the medical take information can be lost during handover between SHOs. In the current format there is little room to write and key and relevant information on the medical take sheet about new and transferring patients. I felt that this handover sheet could be improved. An initial questionnaire demonstrated that 47% found the old proforma easy to use and 28.2% felt that it allowed them to identify sick patients. 100% of SHOs and Registrars surveyed felt that it could be improved from its current form. From feedback from my colleagues I created a new template and trialled it in the hospital. A repeat questionnaire demonstrated that 92.3% of responders felt the new format had improved medical handover and that 92.6% felt that it allowed safe handover most of the time/always. The success of this new proforma resulted in it being implemented on a permanent basis for new medical admissions and transfers to the hospital.

  13. Internal hydrogen embrittlement of high-strength beta-alpha titanium alloys

    NASA Astrophysics Data System (ADS)

    Hayes, Sean Paul

    Potential problems and uncertainties are associated with the complex nature of fracture in solution treated and aged (STA) beta-titanium (beta-Ti) alloys, as well as the potential for long-term alloy degradation due to hydrogen embrittlement. This research characterizes the effects of predissolved hydrogen and microstructural conditions on the fracture resistance of two solution treated and aged (STA) high strength beta-titanium alloys, Low Cost Beta (LCB) and Ti-15-3, in sheet form. Rising-CMOD fracture test results demonstrate that STA beta-Ti alloys are severely embrittled at room temperature and a slow displacement rate above a relatively low threshold hydrogen concentration. Hydrogen concentrations of 400 and 500 wppm reduce the threshold stress intensity at the onset of hydrogen cracking to 50% of the air fracture toughness in STA LCB, and Ti-15-3, respectively. Significant embrittlement for both alloys is triggered at concentrations in excess of 750 wppm, with reductions in threshold stress intensity to an asymptotic value equal to 25% of the air fracture toughness. Reductions in crack growth resistance with increasing hydrogen concentrations are accompanied by significant increases in subcritical crack growth rates. Changes in fracture mode are concurrent with reduced in fracture resistance. With increasing hydrogen concentration, the fracture mode changes from microvoid coalescence to transgranular hydrogen-assisted alpha/beta interface cracking. Two mechanisms of internal hydrogen embrittlement in STA metastable beta-Ti alloys, bond decohesion and hydride formation are proposed to occur at alpha/beta interfaces. A critical isothermal aging time must be exceeded to render Ti-15-3 susceptible to internal hydrogen embrittlement. This is attributed to a critical alpha volume fraction and the associated stress and hydrogen concentration. The internal hydrogen embrittlement of STA Ti-15-3 is a time dependent phenomenon. Experimental results and crack tip strain rate calculations demonstrate that embrittlement will persist in STA Ti-15-3 to loading rates of approximately 0.5 MPa?m/s. As such, hydrogen redistribution to the crack tip is a critical component of internal hydrogen embrittlement. Local transport of hydrogen in intra-alpha beta to susceptible alpha/beta interfaces, and possibly growth kinetics of gamma-TiH2, in the fracture process zone are consistent with the observed kinetics and appear to govern the time dependence.

  14. Do parallel beta-helix proteins have a unique fourier transform infrared spectrum?

    PubMed Central

    Khurana, R; Fink, A L

    2000-01-01

    Several polypeptides have been found to adopt an unusual domain structure known as the parallel beta-helix. These domains are characterized by parallel beta-strands, three of which form a single parallel beta-helix coil, and lead to long, extended beta-sheets. We have used ATR-FTIR (attenuated total reflectance-fourier transform infrared spectroscopy) to analyze the secondary structure of representative examples of this class of protein. Because the three-dimensional structures of parallel beta-helix proteins are unique, we initiated this study to determine if there was a corresponding unique FTIR signal associated with the parallel beta-helix conformation. Analysis of the amide I region, emanating from the carbonyl stretch vibration, reveals a strong absorbance band at 1638 cm(-1) in each of the parallel beta-helix proteins. This band is assigned to the parallel beta-sheet structure. However, components at this frequency are also commonly observed for beta-sheets in many classes of globular proteins. Thus we conclude that there is no unique infrared signature for parallel beta-helix structure. Additional contributions in the 1638 cm(-1) region, and at lower frequencies, were ascribed to hydrogen bonding between the coils in the loop/turn regions and amide side-chain interactions, respectively. A 13-residue peptide that forms fibrils and has been proposed to form beta-helical structure was also examined, and its FTIR spectrum was compared to that of the parallel beta-helix proteins. PMID:10653812

  15. Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: analysis by x-ray diffraction.

    PubMed Central

    Inouye, H.; Fraser, P. E.; Kirschner, D. A.

    1993-01-01

    To elucidate the relation between amyloid fibril formation in Alzheimer disease and the primary structure of the beta/A4 protein, which is the major component of the amyloid, we have been investigating the ability of peptides sharing sequences with beta/A4 to form fibrils in vitro. In previous studies we focused on the macroscopic morphology of the assemblies formed by synthetic peptides corresponding in sequence to different regions of this protein. In the present study we analyze the x-ray diffraction patterns obtained from these assemblies. All specimens showed wide angle reflections that could be indexed by an orthogonal lattice of beta-crystallites having unit cell dimensions a = 9.4 A, b = 7 A, and c = 10 A, where a refers to hydrogen bonding direction, b to polypeptide chain direction, and c to intersheet direction. Given the amino acid sequence of beta/A4 as NH2-DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIAT-COOH, we found that, based on their orientation and assembly, the analogues could be classified into three groups: Group A, residues 19-28, 13-28, 12-28, 11-28, 9-28, 1-28, 1-38, 1-40, 6-25, 11-25 and 34-42; Group B, residues 18-28, 17-28, and 15-28; and Group C, residues 22-35 and 26-33. For Groups A and C, the sharpest reflections were (h00), indicating that the assemblies were fibrillar, i.e., elongated in a single direction. Lateral alignment of the crystallites in Group A account for its cross-beta pattern, in which the hydrogen bonding (H-bonding) direction is the fiber (rotation) axis. By comparison, the beta-crystallites of Group C had no preferential orientation, thus giving circular scattering. For Group B, the sharpest reflections were (h0l) on the meridian, indicating that the assemblies were plate-like, i.e., extended in two directions. A series of equatorial Bragg reflections having a 40 A period indicated regular stacking of the plates, and the rotation axis was normal to the surface of the plates. Of the Group A peptides, the analogues 11-28 and 6-25 showed intensity maxima on the equator as well as on higher layer lines, indicating that the beta-crystallites are highly ordered relative to one another in the axial, H-bonding direction. This sampling of the layer lines by a larger period (60 A) suggests that the beta-crystallites are arrayed either in cylindrical or small restricted crystalline lattices. Consistent with its electron microscopic images, we modeled the structure as a tube with five or six f,-crystallites constituting the wall and with the individual crystallite, which either rotates freely or is restricted, made of five or fewer beta-pleated sheets. For the Group B peptides, the electron density projection along the b-axis was calculated from the observed intensities using phase combinations from fl-keratin.Amino acid side-chain positions were apparent and, when refined as 4-A-diameter spheres, led to a substantial decrease in the R-factors.For peptide 18-28 the electron density peaks, which are thought to correspond to side chains, were centered 3.3 A from the peptide backbone, whereas for peptides 17-28 and 15-28, these peaks were centered 1 A or more further from the backbone. Peaks having high electron density faced peaks having lower density, suggesting a favorable stereochemical arrangement of the residues. Thus, our analysis of the fiber x-ray patterns from beta/A4 peptides shows the organization of the beta-crystallites that form the wall of the amyloid fibrils as well as possible side-chain interactions. Images FIGURE 1 PMID:8457674

  16. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    SciTech Connect

    Feng, Ying; Tsinghua University School of Medicine, Haidian District, Beijing 100084 ; Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min; Sun, Gui-yuan; Liu, Rui-tian

    2009-12-25

    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.

  17. Formation of filamentous tau aggregations in transgenic mice expressing V337M human tau.

    PubMed

    Tanemura, K; Akagi, T; Murayama, M; Kikuchi, N; Murayama, O; Hashikawa, T; Yoshiike, Y; Park, J M; Matsuda, K; Nakao, S; Sun, X; Sato, S; Yamaguchi, H; Takashima, A

    2001-12-01

    Formation of neurofibrillary tangles (NFTs) is the most common feature in several neurodegenerative diseases, including Alzheimer's disease (AD). Here we report the formation of filamentous tau aggregations having a beta-sheet structure in transgenic mice expressing mutant human tau. These mice contain a tau gene with a mutation of the frontotemporal dementia parkinsonism (FTDP-17) type, in which valine is substituted with methionine residue 337. The aggregation of tau in these transgenic mice satisfies all histological criteria used to identify NFTs common to human neurodegenerative diseases. These mice, therefore, provide a preclinical model for the testing of therapeutic drugs for the treatment of neurodegenerative disorders that exhibit NFTs. PMID:11741399

  18. W-Band Sheet Beam Klystron Design

    SciTech Connect

    Scheitrum, G.; Caryotakis, G.; Burke, A.; Jensen, A.; Jongewaard, E.a Krasnykh, A.; Neubauer, M.; Phillips, R.; Rauenbuehler, K.; /SLAC

    2011-11-11

    Sheet beam devices provide important advantages for very high power, narrow bandwidth RF sources like accelerator klystrons [1]. Reduced current density and increased surface area result in increased power capabi1ity, reduced magnetic fields for focusing and reduced cathode loading. These advantages are offset by increased complexity, beam formation and transport issues and potential for mode competition in the ovennoded cavities and drift tube. This paper will describe the design issues encountered in developing a 100 kW peak and 2 kW average power sheet beam k1ystron at W-band including beam formation, beam transport, circuit design, circuit fabrication and mode competition.

  19. Kinetic Studies of Inhibition of the Aβ(1–42) Aggregation Using a Ferrocene-tagged β-Sheet Breaker Peptide

    PubMed Central

    Zhang, Lin; Yagnik, Gargey; Peng, Yong; Wang, Jianxiu; Xu, H. Howard; Hao, Yuanqiang; Liu, You-Nian; Zhou, Feimeng

    2013-01-01

    The aggregation of amyloidogenic proteins/peptides has been closely linked to the neuropathology of several important neurological disorders. In Alzheimer's disease (AD), amyloid beta (Aβ) peptides and their aggregation are believed to be at least partially responsible for the etiology of AD. The aggregate-inflicted cellular toxicity can be inhibited by short peptides whose sequence are homologous to segments of the Aβ(1–42) peptide responsible for β-sheet stacking (referred to as the β-sheet breaker peptides). Herein a water-soluble ferrocene (Fc)-tagged β-sheet breaker peptide (Fc-KLVFFK6) is used as an electrochemical probe for kinetic studies of the inhibition of the Aβ(1–42) fibrillation process and for determination of the optimal concentration of β-sheet breaker peptide for efficient inhibition. Our results demonstrated that Fc-KLVFFK6 interacts with the Aβ aggregates instantaneously in solution, and sub-stoichiometric amount of Fc-KLVFFK6 is sufficient to inhibit the formation of the Aβ oligomers and fibrils and to reduce the toxicity of Aβ(1–42). The interaction between Fc-KLVFFK6 and Aβ(1–42) follows a pseudo-first-order reaction, with a rate constant of 1.89 ± 0.05 × 10−4 s−1. Tagging β-sheet breaker peptides with a redox label facilitates design, screening, and rational use of peptidic inhibitors for impeding/altering Aβ aggregation. PMID:23232068

  20. Formation of fast shocks by magnetic reconnection in the solar corona

    SciTech Connect

    Hsieh, M. H.; Tsai, C. L.; Ma, Z. W.; Lee, L. C.

    2009-09-15

    Reconnections of magnetic fields over the solar surface are expected to generate abundant magnetohydrodynamic (MHD) discontinuities and shocks, including slow shocks and rotational discontinuities. However, the generation of fast shocks by magnetic reconnection process is relatively not well studied. In this paper, magnetic reconnection in a current sheet is studied based on two-dimensional resistive MHD numerical simulations. Magnetic reconnections in the current sheet lead to the formation of plasma jets and plasma bulges. It is further found that the plasma bulges, the leading part of plasma jets, in turn lead to the generation of fast shocks on flanks of the bulges. The simulation results show that during the magnetic reconnection process, the plasma forms a series of structures: plasma jets, plasma bulges, and fast shocks. As time increases, the bulges spread out along the current sheet ({+-}z direction) and the fast shocks move just ahead of the bulges. The effects of initial parameters {rho}{sub s}/{rho}{sub m}, {beta}{sub {infinity}}, and t{sub rec} on the fast shock generation are also examined, where {rho}{sub s}/{rho}{sub m} is the ratio of plasma densities on two sides of the initial current sheet, {beta}{sub {infinity}}=P{sub {infinity}}/(B{sub {infinity}}{sup 2}/2{mu}{sub 0}), P{sub {infinity}} is the plasma pressure and B{sub {infinity}} is the magnetic field magnitude far from the current sheet, and t{sub rec} is the reconnection duration. In the asymmetric case with {rho}{sub s}/{rho}{sub m}=2, {beta}{sub {infinity}}=0.01 and t{sub rec}=1000, the maximum Alfven Mach number of fast shocks (M{sub A1max}) is M{sub A1max} congruent with 1.1, where M{sub A1}=V{sub n1}/V{sub A1}, and V{sub n1} and V{sub A1} are, respectively, the normal upstream fluid velocity and the upstream Alfven speed in the fast shocks frame. As the density ratio {rho}{sub s}/{rho}{sub m} (=1-8) and plasma beta {beta}{sub {infinity}} (=0.0001-1) increase, M{sub A1max} varies slightly. For the case with a large plasma beta {beta}{sub {infinity}} (=5), the fast shock is very weak. As the reconnection duration t{sub rec} increases, the bulges lead to generation of fast shocks with a higher M{sub A1max}. The present results can be applied to the mechanism of coronal heating by fast shocks.

  1. Beta Thalassemia (For Parents)

    MedlinePLUS

    ... decreases the ability of red blood cells to transport oxygen around the body. continue Types of Beta ... untreated. Complications of beta thalassemia major include: Excess iron. Kids who have beta thalassemia can end up ...

  2. Complex formation of beta-cyclodextrin in aqueous media with poly(N,N-dimethylacrylamide)containing pendent perfluorooctanesulfonamido groups. Final Report, September 15, 1998 - September 14, 1999

    SciTech Connect

    Dr. Thieo Hogen-Esch

    1999-11-01

    The effect of time on the viscosity of solutions of 0.50--1.0 weight % polyacrylamide copolymers containing 2-(N-ethylperfluorooctanesulfonamido)ethyl acrylate (FOSA) comonomer units was monitored at constant shear rates varying from 0.60 to 3.0 sec{sup {minus}1}. The viscosities decreased to a plateau over a period of about thirty minutes. The copolymer solutions sheared at much higher shear rates of 24 sec{sup {minus}1} showed pronounced shear thinning but regained most of their original viscosities after standing for 20 minutes. Heating the solutions less than one hour caused an increase in the low shear viscosity whereas longer heating times decreased solution viscosities presumably due to hydrolysis of the acrylate groups. Addition of beta-cyclodextrin to solutions of the hydrophobically modified polyacrylamide resulted in sharply decreased copolymer viscosities at cyclodextrin concentrations on the order of about 10{sup {minus}3} M. The above is consistent with competitive hydrophobic association of the perfluorocarbon groups of the copolymer with the cyclodextrin disrupting the mutual association of the perfluorocarbon groups.

  3. Perforating Thin Metal Sheets

    NASA Technical Reports Server (NTRS)

    Davidson, M. E.

    1985-01-01

    Sheets only few mils thick bonded together, punched, then debonded. Three-step process yields perforated sheets of metal. (1): Individual sheets bonded together to form laminate. (2): laminate perforated in desired geometric pattern. (3): After baking, laminate separates into individual sheets. Developed for fabricating conductive layer on blankets that collect and remove ions; however, perforated foils have other applications - as conductive surfaces on insulating materials; stiffeners and conductors in plastic laminates; reflectors in antenna dishes; supports for thermal blankets; lightweight grille cover materials; and material for mockup of components.

  4. Signaling through the TGF Beta-Activin Receptors ALK4/5/7 Regulates Testis Formation and Male Germ Cell Development

    PubMed Central

    Stringer, Jessica M.; van den Bergen, Jocelyn A.; Wilhelm, Dagmar; Sinclair, Andrew H.; Western, Patrick S.

    2013-01-01

    The developing testis provides an environment that nurtures germ cell development, ultimately ensuring spermatogenesis and fertility. Impacts on this environment are considered to underlie aberrant germ cell development and formation of germ cell tumour precursors. The signaling events involved in testis formation and male fetal germ cell development remain largely unknown. Analysis of knockout mice lacking single Tgf? family members has indicated that Tgf?'s are not required for sex determination. However, due to functional redundancy, it is possible that additional functions for these ligands in gonad development remain to be discovered. Using FACS purified gonadal cells, in this study we show that the genes encoding Activin's, TGF?'s, Nodal and their respective receptors, are expressed in sex and cell type specific patterns suggesting particular roles in testis and germ cell development. Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGF? signaling is required for testis cord formation during the critical testis-determining period. We also show that signaling through the Activin/NODAL receptors, ALK4 and ALK7 is required for promoting differentiation of male germ cells and their entry into mitotic arrest. Finally, our data demonstrate that Nodal is specifically expressed in male germ cells and expression of the key pluripotency gene, Nanog was significantly reduced when signaling through ALK4/5/7 was blocked. Our strategy of inhibiting multiple Activin/NODAL/TGF? receptors reduces the functional redundancy between these signaling pathways, thereby revealing new and essential roles for TGF? and Activin signaling during testis formation and male germ cell development. PMID:23342175

  5. Bile acids of marsupials. 2. Hepatic formation of vulpecholic acid (1 alpha,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic acid) from chenodeoxycholic acid in a marsupial, Trichosurus vulpecula (Lesson).

    PubMed

    St Pyrek, J; Lee, S P; Thomsen, L; Tasman-Jones, C; Leydon, B

    1991-09-01

    Free vulpecholic acid (1 alpha,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic) is the major biliary component of the Australian opossum (Trichosurus vulpecula), accompanied only by a few percent of its taurine conjugate. In order to exclude a microbial involvement in its formation (i.e., secondary origin) four sets of experiments were performed. It was found that a) the level of vulpecholic acid remained unchanged in the bile of opossums fed with neomycin and kanamycin for 7 days prior to bile collection; b) it also remained unchanged after long bile drainage; c) in opossums prepared with biliary cannula, intraportally injected [24-14C]chenodeoxycholic acid was transformed to [24-14C]vulpecholic acid; and d) in a similar experiment, the detectable transformation of [1 alpha,2 alpha-3H2]cholesterol to vulpecholic acid was observed. In experiment c) 28-66% of the administered radioactivity was secreted in 2 h in the form of free biliary vulpecholic and chenodeoxycholic acids. Only a trace amount of the corresponding taurine conjugates (approximately 0.4%) was formed. Moreover, rapidly declining specific radioactivity of the unconjugated chenodeoxycholic acid indicated its probable participation in the native formation of vulpecholic acid. PMID:1753212

  6. Silicon sheet surface studies

    NASA Technical Reports Server (NTRS)

    Danyluk, S.

    1984-01-01

    Several activities were performed in the area of silicon sheet surface studies. An interferometry technique was developed for measuring residual stresses in short, thin silicon sheets. Simulation of abrasion of silicon by diamond and by scrating and indentation tests was carried out. The wear rate in silicon was correlated with a wear model.

  7. Magnetic nonequilibrium and current sheet formation

    NASA Technical Reports Server (NTRS)

    Vainshtein, S. I.; Parker, E. N.

    1986-01-01

    This paper investigates the equilibrium of a cluster of long, straight, twisted magnetic flux tubes extending in the z-direction in a highly conducting fluid, subject to the boundary condition that the cluster is surrounded by a uniform pressure P. It is shown that there is equilibrium only for axial symmetry, i.e., only for a single twisted flux tube. Any more complicated cluster of twisted tubes is subject to nonequilibrium reconnection of the transverse component of the field. The example provides another perspective on the general absence of equilibrium, and consequent rapid dissipation, of any magnetic field subject to random small-scale internal strains, such as the fields extending outward from the convective zones of stars.

  8. Beta structures of alternating polypeptides and their possible prebiotic significance

    NASA Technical Reports Server (NTRS)

    Brack, A.; Orgel, L. E.

    1975-01-01

    A survey of the commonest amino acids formed in prebiotic conditions suggests that the earliest form of genetic coding may have specified polypeptides with a strong tendency to form stable beta-sheet structures. Poly(Val-Lys), like other polypeptides in which hydrophobic and hydrophilic residues alternate, tends to form beta structures. It is shown that bilayers with a hydrophobic interior and a hydrophilic exterior may be present in aqueous solution.

  9. Cereal beta-glucans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereal beta-glucans occur predominantly in oats and barley, but can be found in other cereals. Beta-glucan structure is a mixture of single beta-1,3-linkages and consecutive beta-1,4-linkages, and cellotriosyl and cellotetraosyl units typically make up 90-95% of entire molecule. Lichenase can hydr...

  10. Magnetohydrodynamic bending waves in a current sheet

    NASA Technical Reports Server (NTRS)

    Musielak, Z. E.; Suess, S. T.

    1988-01-01

    The physical properties of MHD bending waves in an isothermal, compressible, low-beta, three-dimensional current sheet of finite thickness in which the magnetic field direction and strength varies are considered. The case of the wavenumber (k) to circular frequency ratio being greater than the Alfven velocity outside the layer (V sub A) corresponds to one-sided surface waves, and it is suggested that the heliospheric current sheet ripples are not this type of bending wave. The case of k/omega of less than V sub A describes the interaction of freely and obliquely propagating MHD waves with the layer, while the case of k/omega = V sub A describes an Alfven wave propagating parallel to but having no interaction with the layer.

  11. Nuclear Data Sheets for A = 193

    SciTech Connect

    Achterberg, E.; Capurro, O.A.; Marti, G.V.; Vanin, V.R.; Castro, R.M.

    2006-01-15

    The present revision of the properties for the nuclides belonging to the A = 193 mass chain contains many improvements, corrections and additions to the material presented in previous evaluations (1998Ar07, Nucl. Data Sheets 83, 921 (1998); 1990Sh30, Nucl, Data Sheets 61, 519 (1990)). Among these are measurement results for quadrupole moments, angular distribution coefficients, half-lives and g-factors, for both previously known and new transitions and levels. In addition, major changes to the previously known status of this mass chain consist in the inclusion of data for new superdeformed bands in {sup 193}Pb, and the creation of level schemes for {sup 193}Bi, {sup 193}Po and {sup 193}At. The latter were previously unavailable, except for a very limited attempt in the case of {sup 193}Po, which was not confirmed in later work. Furthermore, the {sup 193}Os beta decay was re-evaluated in order to account for new absolute intensity measurements.

  12. Current status of liquid sheet radiator research

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Calfo, Frederick D.; Mcmaster, Matthew S.

    1993-01-01

    Initial research on the external flow, low mass liquid sheet radiator (LSR), has been concentrated on understanding its fluid mechanics. The surface tension forces acting at the edges of the sheet produce a triangular planform for the radiating surface of width, W, and length, L. It has been experimentally verified that (exp L)/W agrees with the theoretical result, L/W = (We/8)exp 1/2, where We is the Weber number. Instability can cause holes to form in regions of large curvature such as where the edge cylinders join the sheet of thickness, tau. The W/tau limit that will cause hole formation with subsequent destruction of the sheet has yet to be reached experimentally. Although experimental measurements of sheet emissivity have not yet been performed because of limited program scope, calculations of the emissivity and sheet lifetime is determined by evaporation losses were made for two silicon based oils; Dow Corning 705 and Me(sub 2). Emissivities greater than 0.75 are calculated for tau greater than or equal to 200 microns for both oils. Lifetimes for Me(sub 2) are much longer than lifetimes for 705. Therefore, Me(sub 2) is the more attractive working fluid for higher temperatures (T greater than or equal to 400 K).

  13. A comparison of two different methods for formation of the beta phase in nanocomposites based on vinylidene fluoride-hexafluoropropylene copolymer

    NASA Astrophysics Data System (ADS)

    Borisova, Lyudmila; Kiryakova, Dimitrina; Atanassov, Atanas

    2014-06-01

    Nanocomposite materials based on vinylidene fluoride-hexafluoropropylene copolymer and organically modified montmorillonite Cloisite15A were prepared by two different methods: melt mixing and co-precipitation. The changes taking place in crystalline structure, tensile strength, thermal behavior and the formation of piezoelectric b-phase as a result of the polymer system dissolution in dimethyl sulfoxide were studied. The technological specificity of each method has certain effect on the properties of the obtained nanocomposites. The highest content of b-phase 95 % was achieved by co-precipitation from the solution of vinylidene fluoride-hexafluoropropylene copolymer in dimethyl sulfoxide and 6 mass % content of Cloisite15A. Despite the common view that the use of solvents and prolonged technological procedure lead to overall higher expenses, the obtained nanocomposites could be promising for the preparation of new piezo-materials.

  14. Emittance Measurements for a Thin Liquid Sheet Flow

    NASA Technical Reports Server (NTRS)

    Englehart, Amy N.; McConley, Marc W.; Chubb, Donald L.

    1996-01-01

    The Liquid Sheet Radiator (LSR) is an external flow radiator that uses a triangular-shaped flowing liquid sheet as the radiating surface. It has potentially much lower mass than solid wall radiators such as pumped loop and heat pipe radiators, along with being nearly immune to micrometeoroid penetration. The LSR has an added advantage of simplicity. Surface tension causes a thin (100-300 microns) liquid sheet to coalesce to a point, causing the sheet flow to have a triangular shape. Such a triangular sheet is desirable since it allows for simple collection of the flow at a single point. A major problem for all external flow radiators is the requirement that the working fluid be of very low (approx. 10(sup -8) torr) vapor pressure to keep evaporative losses low. As a result, working fluids are limited to certain oils (such as used in diffusion pumps) for low temperatures (300-400 K) and liquid metals for higher temperatures. Previous research on the LSR has been directed at understanding the fluid mechanics of thin sheet flows and assessing the stability of such flows, especially with regard to the formation of holes in the sheet. Taylor studied extensively the stability of thin liquid sheets both theoretically and experimentally. He showed that thin sheets in a vacuum are stable. The latest research has been directed at determining the emittance of thin sheet flows. The emittance was calculated from spectral transmittance data for the Dow Corning 705 silicone oil. By experimentally setting up a sheet flow, the emittance was also determined as a function of measurable quantities, most importantly, the temperature drop between the top of the sheet and the temperature at the coalescence point of the sheet. Temperature fluctuations upstream of the liquid sheet were a potential problem in the analysis and were investigated.

  15. Molecular characterization of alpha-keratins in comparison to associated beta-proteins in soft-shelled and hard-shelled turtles produced during the process of epidermal differentiation.

    PubMed

    Dalla Valle, L; Michieli, F; Benato, F; Skobo, T; Alibardi, L

    2013-11-01

    The tough corneous layer in the carapace and plastron of hard-shelled turtles derives from the accumulation of keratin-associated beta-proteins (KAbetaPs, formerly called beta-keratins) while these proteins are believed to be absent in soft-shelled turtles. Our bioinformatics and molecular study has instead shown that the epidermis of the soft-shelled turtle Apalone spinifera expresses beta-proteins like or even in higher amount than in the hard-shelled turtle Pseudemys nelsoni. The analysis of a carapace cDNAs library has allowed the identification and characterization of three alpha-keratins of type I and of ten beta-proteins (beta-keratins). The acidic alpha-keratins probably combine with the basic beta-proteins but the high production of beta-proteins in A. spinifera is not prevalent over that of alpha-keratin so that their combination does not determine the formation of hard corneous material. Furthermore the presence of a proline and cisteine in the beta-sheet region of beta-proteins in A. spinifera may be unsuited to form hard masses of corneous material. The higher amount of beta-proteins over alpha-keratins instead occurs in keratinocytes of the hard and inflexible epidermis of P. nelsoni determining the deposition of hard corneous material. The study suggests that the hardness of the corneous layer derives not exclusively from the interactions between alpha-keratins with KAbetaPs but also from the different dynamic of accumulation and loss of corneocytes in the corneous layer of the hard shelled turtles where a prevalent accumulation and piling of corneocytes takes place versus the soft shelled turtle where a rapid turnover of the stratum corneum occurs. PMID:23794440

  16. The comparative effectiveness of demineralized bone matrix, beta-tricalcium phosphate, and bovine-derived anorganic bone matrix on inflammation and bone formation using a paired calvarial defect model in rats

    PubMed Central

    Khoshzaban, Ahad; Mehrzad, Shahram; Tavakoli, Vida; Keshel, Saeed Heidari; Behrouzi, Gholam Reza; Bashtar, Maryam

    2011-01-01

    Background In this study, the effectiveness of Iranian Tissue Bankproduced demineralized bone matrix (ITB-DBM), beta-tricalcium phosphate (?TCP), and Bio-Oss (Geistlich Pharma AG, Wolhusen, Switzerland) were evaluated and compared with double controls. The main goal was to measure the amount of new bone formation in the center of defects created in rat calvaria. Another goal was to compare the controls and evaluate the effects of each treatment material on their adjacent untreated (control) defects. Methods In this study, 40 male Wistar rats were selected and divided into four groups, In each group, there were ten rats with two defects in their calvarias; one of them is considered as control and the other one was treated with ITB-DBM (group 1), BIO-OSS (group2), and ?TCP (group 3), respectively. But in group 4, both defects were considered as control. The amount of inflammation and new bone formation were evaluated at 4 and 10 weeks. In the first group, one defect was filled with ITB-DBM; in the second group, one defect was filled with Bio-Oss; in the third group, one defect was filled with ?TCP; and in the fourth group, both defects were left unfilled. Zeiss microscope (Carl Zeiss AG, Oberkochen, Germany) and Image Tool (version 3.0; University of Texas Health Science Center at San Antonio, San Antonio, TX) software were used for evaluation. SPSS Statistics (IBM Corp, Somers, NY) was used for statistical analysis. Results Maximum bone formation at 4 and 10 weeks were observed in the ITB-DBM group (46.960% 4.366%, 94.970% 0.323%), which had significant difference compared with the other groups (P < 0.001). Ranking second was the Bio-Oss group and third, the ?TCP group. Bone formation in the group with two unfilled defects was much more significant than in the other controls beside the Bio-Oss and ?TCP after 10 weeks (29.1 2.065, 29.05 1.649), while this group had the least bone formation compared with the other controls at week 4 (2.100% 0.758%, 1.630% 0.668%, P < 0.001). Conclusion Overall, the ITB-DBM group showed the best results, although the results for other experimental groups were unfavorable. The authors conclude that human DBM (ITB-DBM) should be offered as an alternative for bone regeneration in animals, such as horses, as well as in humans, especially for jaw reconstruction. In relation to bone regeneration in control defects, the effect of experimental material on controls was apparent during the initial weeks. PMID:23674917

  17. Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum.

    PubMed

    Weber, Michael E; Clark, Peter U; Ricken, Werner; Mitrovica, Jerry X; Hostetler, Steven W; Kuhn, Gerhard

    2011-12-01

    The timing of the last maximum extent of the Antarctic ice sheets relative to those in the Northern Hemisphere remains poorly understood. We develop a chronology for the Weddell Sea sector of the East Antarctic Ice Sheet that, combined with ages from other Antarctic ice-sheet sectors, indicates that the advance to and retreat from their maximum extent was within dating uncertainties synchronous with most sectors of Northern Hemisphere ice sheets. Surface climate forcing of Antarctic mass balance would probably cause an opposite response, whereby a warming climate would increase accumulation but not surface melting. Our new data support teleconnections involving sea-level forcing from Northern Hemisphere ice sheets and changes in North Atlantic deep-water formation and attendant heat flux to Antarctic grounding lines to synchronize the hemispheric ice sheets. PMID:22144623

  18. Interhemispheric ice-sheet synchronicity during the last glacial maximum

    USGS Publications Warehouse

    Weber, Michael E.; Clark, Peter U.; Ricken, Werner; Mitrovica, Jerry X.; Hostetler, Steven W.; Kuhn, Gerhard

    2011-01-01

    The timing of the last maximum extent of the Antarctic ice sheets relative to those in the Northern Hemisphere remains poorly understood. We develop a chronology for the Weddell Sea sector of the East Antarctic Ice Sheet that, combined with ages from other Antarctic ice-sheet sectors, indicates that the advance to and retreat from their maximum extent was within dating uncertainties synchronous with most sectors of Northern Hemisphere ice sheets. Surface climate forcing of Antarctic mass balance would probably cause an opposite response, whereby a warming climate would increase accumulation but not surface melting. Our new data support teleconnections involving sea-level forcing from Northern Hemisphere ice sheets and changes in North Atlantic deep-water formation and attendant heat flux to Antarctic grounding lines to synchronize the hemispheric ice sheets.

  19. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    SciTech Connect

    Nintasen, Rungrat; Multidisciplinary Cardiovascular Research Center , University of Leeds, Leeds LS2 9JT; Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University ; Riches, Kirsten; Mughal, Romana S.; Multidisciplinary Cardiovascular Research Center , University of Leeds, Leeds LS2 9JT ; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Multidisciplinary Cardiovascular Research Center , University of Leeds, Leeds LS2 9JT ; Porter, Karen E.

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-{alpha} induced SV neointima formation, increased SMC proliferation and migration, impaired SV-EC migration and increased expression of adhesion molecules. E2 exerted distinct cell-type and function-specific modulation, the mechanisms underlying which are worthy of further detailed study.

  20. Microcomponent sheet architecture

    DOEpatents

    Wegeng, R.S.; Drost, M.K..; McDonald, C.E.

    1997-03-18

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation. 14 figs.

  1. Liquid sheet radiator

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; White, K. Alan, III

    1987-01-01

    A new external flow radiator concept, the liquid sheet radiator (LSR), is introduced. The LSR sheet flow is described and an expression for the length/width (l/w), ratio is presented. A linear dependence of l/w on velocity is predicted that agrees with experimental results. Specific power for the LSR is calculated and is found to be nearly the same as the specific power of a liquid droplet radiator, (LDR). Several sheet thicknesses and widths were experimentally investigated. In no case was the flow found to be unstable.

  2. Microcomponent sheet architecture

    DOEpatents

    Wegeng, Robert S. (Richland, WA); Drost, M. Kevin (Richland, WA); McDonald, Carolyn E. (Richland, WA)

    1997-01-01

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation.

  3. Forced crumpling of self-avoiding elastic sheets

    NASA Astrophysics Data System (ADS)

    Vliegenthart, G. A.; Gompper, G.

    2006-03-01

    Thin elastic sheets are important materials across length scales ranging from mesoscopic (polymerized membranes, clay platelets, virus capsids) to macroscopic (paper, metal foils). The crumpling of such sheets by external forces is characterized by the formation of a complex pattern of folds. We have investigated the role of self-avoidance, the fact that the sheets cannot self-intersect, for the crumpling process by large-scale computer simulations. At moderate compression, the force-compression relations of crumpled sheets for both self-avoiding and phantom sheets are found to obey universal power-law behaviours. However, self-avoiding sheets are much stiffer than phantom sheets and, for a given compression, develop many more folds. Moreover, self-avoidance is relevant already at very small volume fractions. The fold-length distribution for crumpled sheets is determined, and is found to be well-described by a log-normal distribution. The stiffening owing to self-avoidance is reflected in the changing nature of the sheet-to-sheet contacts from line-like to two-dimensionally extended with increasing compression.

  4. Mechanism of inactivation of alanine racemase by beta, beta, beta-trifluoroalanine

    SciTech Connect

    Faraci, W.S.; Walsh, C.T.

    1989-01-24

    The alanine racemases are a group of PLP-dependent bacterial enzymes that catalyze the racemization of alanine, providing D-alanine for cell wall synthesis. Inactivation of the alanine racemases from the Gram-negative organism Salmonella typhimurium and Gram-positive organism Bacillus stearothermophilus with beta, beta, beta-trifluoroalanine has been studied. The inactivation occurs with the same rate constant as that for formation of a broad 460-490-nm chromophore. Loss of two fluoride ions per mole of inactivated enzyme and retention of (1-/sup 14/C)trifluoroalanine label accompany inhibition, suggesting a monofluoro enzyme adduct. Partial denaturation (1 M guanidine) leads to rapid return of the initial 420-nm chromophore, followed by a slower (t1/2 approximately 30 min-1 h) loss of the fluoride ion and /sup 14/CO/sub 2/ release. At this point, reduction by NaB/sub 3/H/sub 4/ and tryptic digestion yield a single radiolabeled peptide. Purification and sequencing of the peptide reveals that lysine-38 is covalently attached to the PLP cofactor. A mechanism for enzyme inactivation by trifluoroalanine is proposed and contrasted with earlier results on monohaloalanines, in which nucleophilic attack of released aminoacrylate on the PLP aldimine leads to enzyme inactivation. For trifluoroalanine inactivation, nucleophilic attack of lysine-38 on the electrophilic beta-difluoro-alpha, beta-unsaturated imine provides an alternative mode of inhibition for these enzymes.

  5. New hydrolysis products of the beta-lactam antibiotic amoxicillin, their pH-dependent formation and search in municipal wastewater.

    PubMed

    Hirte, Kristin; Seiwert, Bettina; Schrmann, Gerrit; Reemtsma, Thorsten

    2016-01-01

    Amoxicillin (AMX) is a widespread ?-lactam-antibiotic and, together with some of its transformation products (TPs) originating from hydrolysis, a known environmental contaminant. To shed light on the abiotic degradation of AMX and the stability of its known TPs, laboratory hydrolysis experiments of AMX were carried out at pH 3, 7 and 11. Not only the rate of hydrolysis but also the pattern of TPs was strongly pH-dependent. The time courses of the obtained transformation products were analyzed by UPLC-HR-QToF-MS. AMX penicilloic acid (TP 1), AMX 2',5'-diketopiperazine (TP 2), AMX penilloic acid (TP 3) and 3-(4-hydroxyphenyl)pyrazinol (TP 4) were found at neutral pH. Surprisingly, the first three were not stable but transformed into 23 yet unknown TPs within three to four weeks. Seven TPs were tentatively identified, based on their product ion spectra and, where possible, confirmed with reference standards, e.g. penicillamine disulfide, 2-[amino(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid and dehydrocarboxylated amoxicillin penilloic acid. Analysis of samples from municipal wastewater treatment plants confirmed these findings with TP 1 being the dominant TP in the influent and a shift towards TP 2, TP 3 and TP 4 in the effluents. The lab experiments predicted up to 13 consecutive TPs from TP 1, TP 2 and TP 3 under neutral conditions. Their detection from surface waters will be difficult, because their large number and slow formation kinetics will lead to comparatively low environmental concentrations. Nevertheless the abiotic degradation of TP 1, TP 2 and TP 3 to further TPs needs to be considered in future studies of the environmental fate of amoxicillin. PMID:26613181

  6. In silico and in vitro studies to elucidate the role of Cu2+ and galanthamine as the limiting step in the amyloid beta (1-42) fibrillation process.

    PubMed

    Hernndez-Rodrguez, Maricarmen; Correa-Basurto, Jos; Benitez-Cardoza, Claudia G; Resendiz-Albor, Aldo Arturo; Rosales-Hernndez, Martha C

    2013-10-01

    The formation of fibrils and oligomers of amyloid beta (A?) with 42 amino acid residues (A? 1-42 ) is the most important pathophysiological event associated with Alzheimer's disease (AD). The formation of A? fibrils and oligomers requires a conformational change from an ?-helix to a ?-sheet conformation, which is encouraged by the formation of a salt bridge between Asp 23 or Glu 22 and Lys 28. Recently, Cu(2+) and various drugs used for AD treatment, such as galanthamine (Reminyl() ), have been reported to inhibit the formation of A? fibrils. However, the mechanism of this inhibition remains unclear. Therefore, the aim of this work was to explore how Cu(2+) and galanthamine prevent the formation of A?1-42 fibrils using molecular dynamics (MD) simulations (20 ns) and in vitro studies using fluorescence and circular dichroism (CD) spectroscopies. The MD simulations revealed that A?1-42 acquires a characteristic U-shape before the ?-helix to ?-sheet conformational change. The formation of a salt bridge between Asp 23 and Lys 28 was also observed beginning at 5 ns. However, the MD simulations of A? 1-42 in the presence of Cu(2+) or galanthamine demonstrated that both ligands prevent the formation of the salt bridge by either binding to Glu 22 and Asp 23 (Cu(2+) ) or to Lys 28 (galanthamine), which prevents A? 1-42 from adopting the U-characteristic conformation that allows the amino acids to transition to a ?-sheet conformation. The docking results revealed that the conformation obtained by the MD simulation of a monomer from the 1Z0Q structure can form similar interactions to those obtained from the 2BGE structure in the oligomers. The in vitro studies demonstrated that A? remains in an unfolded conformation when Cu(2+) and galanthamine are used. Then, ligands that bind Asp 23 or Glu 22 and Lys 28 could therefore be used to prevent ? turn formation and, consequently, the formation of A? fibrils. PMID:23904252

  7. Avian Fact Sheet

    SciTech Connect

    NWCC Wildlife Work Group

    2004-12-01

    OAK-B135 After conducting four national research meetings, producing a document guiding research: Metrics and Methods for Determining or Monitoring Potential Impacts on Birds at Existing and Proposed Wind Energy Sites, 1999, and another paper, Avian Collisions with Wind Turbines: A Summary of Existing Studies and Comparisons to Other Sources of Avian Collision Mortality in the United States, 2001, the subcommittee recognized a need to summarize in a short fact sheet what is known about avian-wind interaction and what questions remain. This fact sheet attempts to summarize in lay terms the result of extensive discussion about avian-wind interaction on land. This fact sheet does not address research conducted on offshore development. This fact sheet is not intended as a conclusion on the subject; rather, it is a summary as of Fall/Winter 2002.

  8. Global ice sheet modeling

    SciTech Connect

    Hughes, T.J.; Fastook, J.L.

    1994-05-01

    The University of Maine conducted this study for Pacific Northwest Laboratory (PNL) as part of a global climate modeling task for site characterization of the potential nuclear waste respository site at Yucca Mountain, NV. The purpose of the study was to develop a global ice sheet dynamics model that will forecast the three-dimensional configuration of global ice sheets for specific climate change scenarios. The objective of the third (final) year of the work was to produce ice sheet data for glaciation scenarios covering the next 100,000 years. This was accomplished using both the map-plane and flowband solutions of our time-dependent, finite-element gridpoint model. The theory and equations used to develop the ice sheet models are presented. Three future scenarios were simulated by the model and results are discussed.

  9. Sheet electron beam tester

    NASA Astrophysics Data System (ADS)

    Spear, Alexander Grenbeaux

    The DARPA HiFIVE project uses a pulsed electron sheet beam gun to power a traveling wave tube amplifier operating at 220 GHz. Presented is a method for characterizing the high current density 0.1 mm by 1 mm sheet electron beam. A tungsten tipped probe was scanned through the cross section of the sheet electron beam inside of a vacuum vessel. The probe was controlled with sub-micron precision using stepper motors and LabView computer control while boxcar averaging hardware sampled the pulsed beam. Matlab algorithms were used to interpret the data, calculate beam dimensions and current density, and create 2-dimensional cross section images. Full characterization of two separate HiFIVE sheet electron guns was accomplished and is also presented.

  10. Biodiesel Basics (Fact Sheet)

    SciTech Connect

    Not Available

    2014-06-01

    This fact sheet provides a brief introduction to biodiesel, including a discussion of biodiesel blends, which blends are best for which vehicles, where to buy biodiesel, how biodiesel compares to diesel fuel in terms of performance, how biodiesel performs in cold weather, whether biodiesel use will plug vehicle filters, how long-term biodiesel use may affect engines, biodiesel fuel standards, and whether biodiesel burns cleaner than diesel fuel. The fact sheet also dismisses the use of vegetable oil as a motor fuel.

  11. Energy information sheets

    SciTech Connect

    1995-07-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  12. Early Events in the Amyloid Formation of the A546T Mutant of Transforming Growth Factor Beta Induced Protein (TGFBIp) in Corneal Dystrophies Compared to the Non-Fibrillating R555W and R555Q Mutants

    PubMed Central

    Koldsø, Heidi; Andersen, Ole Juul; Nikolajsen, Camilla Lund; Scavenius, Carsten; Sørensen, Charlotte S.; Underhaug, Jarl; Runager, Kasper; Nielsen, Niels Chr.; Enghild, Jan J.; Schiøtt, Birgit

    2016-01-01

    The human transforming growth factor beta induced protein (TGFBIp) is involved in several types of corneal dystrophies where protein aggregation and amyloid fibril formation severely impairs vision. Most disease-causing mutations are located in the last of four homologous fasciclin-1 (FAS1) domains of the protein, and it has been shown that when isolated, the fourth FAS1 domain (FAS1–4) mimics the behavior of full-length TGFBIp. In this study, we use molecular dynamics simulations and principal component analysis to study the wild type FAS1–4 domain along with three disease-causing mutations (R555W, R555Q, and A546T) to decipher any internal difference in dynamical properties of the domains that may explain their varied stabilities and aggregation properties. In addition, we use a protein-protein docking method in combination with chemical cross-linking experiments and mass spectrometry of the cross-linked species to obtain information about interaction faces between identical FAS1–4 domains. The results show that the pathogenic mutations A546T and R555W affect the packing in the hydrophobic core of FAS1–4 in different directions. We further show that the FAS1–4 monomers associate using their β-rich regions consistent with peptides observed to be part of the amyloid fibril core in lattice corneal dystrophy patients. PMID:26305369

  13. Effects of mutations in the {beta} subunit hinge domain on ATP synthase F{sub 1} sector rotation: Interaction between Ser 174 and Ile 163

    SciTech Connect

    Kashiwagi, Sachiko; Iwamoto-Kihara, Atsuko; Kojima, Masaki; Nonaka, Takamasa; Futai, Masamitsu Nakanishi-Matsui, Mayumi

    2008-01-11

    A complex of {gamma}, {epsilon}, and c subunits rotates in ATP synthase (F{sub o}F{sub 1}) coupling with proton transport. Replacement of {beta}Ser174 by Phe in {beta}-sheet4 of the {beta} subunit ({beta}S174F) caused slow {gamma} subunit revolution of the F{sub 1} sector, consistent with the decreased ATPase activity [M. Nakanishi-Matsui, S. Kashiwagi, T. Ubukata, A. Iwamoto-Kihara, Y. Wada, M. Futai, Rotational catalysis of Escherichia coli ATP synthase F1 sector. Stochastic fluctuation and a key domain of the {beta} subunit, J. Biol. Chem. 282 (2007) 20698-20704]. Modeling of the domain including {beta}-sheet4 and {alpha}-helixB predicted that the mutant {beta}Phe174 residue undergoes strong and weak hydrophobic interactions with {beta}Ile163 and {beta}Ile166, respectively. Supporting this prediction, the replacement of {beta}Ile163 in {alpha}-helixB by Ala partially suppressed the {beta}S174F mutation: in the double mutant, the revolution speed and ATPase activity recovered to about half of the levels in the wild-type. Replacement of {beta}Ile166 by Ala lowered the revolution speed and ATPase activity to the same levels as in {beta}S174F. Consistent with the weak hydrophobic interaction, {beta}Ile166 to Ala mutation did not suppress {beta}S174F. Importance of the hinge domain [phosphate-binding loop (P-loop)/{alpha}-helixB/loop/{beta}-sheet4, {beta}Phe148-{beta}Gly186] as to driving rotational catalysis is discussed.

  14. Absorption of Beta Particles in Different Materials: An Undergraduate Experiment

    ERIC Educational Resources Information Center

    La Rocca, Paola; Riggi, Francesco

    2009-01-01

    The absorption of beta rays from a radioactive source in different materials was investigated by the use of a simple setup based on a Geiger counter and a set of absorber sheets. The number of electrons traversing the material was measured as a function of its thickness. Detailed GEANT simulations were carried out to reproduce the obtained…

  15. Absorption of Beta Particles in Different Materials: An Undergraduate Experiment

    ERIC Educational Resources Information Center

    La Rocca, Paola; Riggi, Francesco

    2009-01-01

    The absorption of beta rays from a radioactive source in different materials was investigated by the use of a simple setup based on a Geiger counter and a set of absorber sheets. The number of electrons traversing the material was measured as a function of its thickness. Detailed GEANT simulations were carried out to reproduce the obtained

  16. Ferulic acid destabilizes preformed {beta}-amyloid fibrils in vitro

    SciTech Connect

    Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito . E-mail: m-yamada@med.kanazawa-u.ac.jp

    2005-10-21

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fA{beta} formation from A{beta} and destabilizes preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependently inhibited fA{beta} formation from amyloid {beta}-peptide, as well as their extension. Moreover, it destabilized preformed fA{beta}s. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.

  17. beta-Hexachlorocyclohexane (beta-HCH)

    Integrated Risk Information System (IRIS)

    beta - Hexachlorocyclohexane ( beta - HCH ) ; CASRN 319 - 85 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asses

  18. A Logical OR Redundancy within the Asx-Pro-Asx-Gly Type 1 {Beta}-Turn Motif

    SciTech Connect

    Lee, Jihun; Dubey, Vikash Kumar; Longo, Lian M.; Blaber, Michael

    2008-04-19

    Turn secondary structure is essential to the formation of globular protein architecture. Turn structures are, however, much more complex than either {alpha}-helix or {beta}-sheet, and the thermodynamics and folding kinetics are poorly understood. Type I {beta}-turns are the most common type of reverse turn, and they exhibit a statistical consensus sequence of Asx-Pro-Asx-Gly (where Asx is Asp or Asn). A comprehensive series of individual and combined Asx mutations has been constructed within three separate type I 3:5 G1 bulge {beta}-turns in human fibroblast growth factor-1, and their effects on structure, stability, and folding have been determined. The results show a fundamental logical OR relationship between the Asx residues in the motif, involving H-bond interactions with main-chain amides within the turn. These interactions can be modulated by additional interactions with residues adjacent to the turn at positions i + 4 and i + 6. The results show that the Asx residues in the turn motif make a substantial contribution to the overall stability of the protein, and the Asx logical OR relationship defines a redundant system that can compensate for deleterious point mutations. The results also show that the stability of the turn is unlikely to be the prime determinant of formation of turn structure in the folding transition state.

  19. Beta-carotene

    MedlinePLUS

    ... cancer in men. Special precautions & warnings: Pregnancy and breast-feeding: Beta-carotene is LIKELY SAFE when taken by ... not recommended for general use during pregnancy and breast-feeding. Smoking: In people who smoke, beta-carotene supplements ...

  20. Low-Temperature Forming of Beta Titanium Alloys

    NASA Technical Reports Server (NTRS)

    Kaneko, R. S.; Woods, C. A.

    1983-01-01

    Low cost methods for titanium structural fabrication using advanced cold-formable beta alloys were investigated for application in a Mach 2.7 supersonic cruise vehicle. This work focuses on improving processing and structural efficiencies as compared with standard hot formed and riveted construction of alpha-beta alloy sheet structure. Mechanical property data and manufacturing parameters were developed for cold forming, brazing, welding, and processing Ti-15V-3Cr-3Sn-3Al sheet, and Ti-3Al-8V-6Cr-4Zr on a more limited basis. Cost and structural benefits were assessed through the fabrication and evaluation of large structural panels. The feasibility of increasing structural efficiency of beta titanium structure by selective reinforcement with metal matrix composite was also explored.

  1. Spontaneous formation of polyglutamine nanotubes with molecular dynamics simulations.

    PubMed

    Laghaei, Rozita; Mousseau, Normand

    2010-04-28

    Expansion of polyglutamine (polyQ) beyond the pathogenic threshold (35-40 Gln) is associated with several neurodegenerative diseases including Huntington's disease, several forms of spinocerebellar ataxias and spinobulbar muscular atrophy. To determine the structure of polyglutamine aggregates we perform replica-exchange molecular dynamics simulations coupled with the optimized potential for effective peptide forcefield. Using a range of temperatures from 250 to 700 K, we study the aggregation kinetics of the polyglutamine monomer and dimer with chain lengths from 30 to 50 residues. All monomers show a similar structural change at the same temperature from alpha-helical structure to random coil, without indication of any significant beta-strand. For dimers, by contrast, starting from random structures, we observe spontaneous formation of antiparallel beta-sheets and triangular and circular beta-helical structures for polyglutamine with 40 residues in a 400 ns 50 temperature replica-exchange molecular dynamics simulation (total integrated time 20 micros). This approximately 32 A diameter structure reorganizes further into a tight antiparallel double-stranded approximately 22 A nanotube with 22 residues per turn close to Perutz' model for amyloid fibers as water-filled nanotubes. This diversity of structures suggests the existence of polymorphism for polyglutamine with possibly different pathways leading to the formation of toxic oligomers and to fibrils. PMID:20441310

  2. Effect of initial stagger selection on the handedness of Amyloid beta helical fibrils

    SciTech Connect

    Ghattyvenkatakrishna, Pavan K; Cheng, Xiaolin; Uberbacher, Edward C

    2013-01-01

    Various structural models for Amyloid $\\beta$ fibrils derived from a variety of experimental techniques are currently available. However, this data cannot differentiate between the relative position of the two arms of the $\\beta$ hairpin called the stagger. Amyloid fibrils of various heirarchical levels form left--handed helices composed of $\\beta$ sheets. However it is unclear if positive, negative and neutral staggers all form the macroscopic left--handed helices. Studying this is important since the success of computational approaches to develop drugs for amyloidic diseases will depend on selecting the physiologically relevant structure of the sheets. To address this issue we have conducted extensive molecular dynamics simulations of Amyloid$\\beta$ sheets of various staggers and show that only negative staggers generate the experimentally observed left--handed helices while positive staggers generate the incorrect right--handed helices. The implications of this result extend in to all amyloidic--aggregation type diseases.

  3. BetaSearch: a new method for querying ?-residue motifs

    PubMed Central

    2012-01-01

    Background Searching for structural motifs across known protein structures can be useful for identifying unrelated proteins with similar function and characterising secondary structures such as ?-sheets. This is infeasible using conventional sequence alignment because linear protein sequences do not contain spatial information. ?-residue motifs are ?-sheet substructures that can be represented as graphs and queried using existing graph indexing methods, however, these approaches are designed for general graphs that do not incorporate the inherent structural constraints of ?-sheets and require computationally-expensive filtering and verification procedures. 3D substructure search methods, on the other hand, allow ?-residue motifs to be queried in a three-dimensional context but at significant computational costs. Findings We developed a new method for querying ?-residue motifs, called BetaSearch, which leverages the natural planar constraints of ?-sheets by indexing them as 2D matrices, thus avoiding much of the computational complexities involved with structural and graph querying. BetaSearch exhibits faster filtering, verification, and overall query time than existing graph indexing approaches whilst producing comparable index sizes. Compared to 3D substructure search methods, BetaSearch achieves 33 and 240 times speedups over index-based and pairwise alignment-based approaches, respectively. Furthermore, we have presented case-studies to demonstrate its capability of motif matching in sequentially dissimilar proteins and described a method for using BetaSearch to predict ?-strand pairing. Conclusions We have demonstrated that BetaSearch is a fast method for querying substructure motifs. The improvements in speed over existing approaches make it useful for efficiently performing high-volume exploratory querying of possible protein substructural motifs or conformations. BetaSearch was used to identify a nearly identical ?-residue motif between an entirely synthetic (Top7) and a naturally-occurring protein (Charcot-Leyden crystal protein), as well as identifying structural similarities between biotin-binding domains of avidin, streptavidin and the lipocalin gamma subunit of human C8. PMID:22839199

  4. Beta-amyloidbased immunotherapy as a treatment of Alzheimers disease.

    PubMed

    Solomon, Beka

    2007-05-01

    The pathology of Alzheimer's disease shows a significant correlation between beta-amyloid peptide conformation and the clinical severity of dementia. For many years efforts have been focused on the development of inhibitors of beta-amyloid formation and its related neurotoxic effects. A new concept has been developed which shows that site-directed antibodies may modulate formation of beta-amyloid. The performance of anti-beta-amyloid antibodies in transgenic mice models of Alzheimer's disease showed that they are delivered to the central nervous system, preventing in vivo formation of beta-amyloid. Moreover, those antibodies dissolve beta-amyloid plaques and protect the mice from learning and age-related memory deficits. Experimental active immunization with beta-amyloid (1-42) in humans was stopped in phase II of their clinical trials. However, several new preparations, able to provide antibodies against beta-amyloid by either active or passive routes, have been formulated and have reached clinical testing. The data presented support the hypothesis that beta-amyloid peptide plays a central role in Alzheimer's disease, and antibodies which modulate beta-amyloid conformation may lead to immunotherapy of the disease. PMID:17724499

  5. Poking a floating sheet

    NASA Astrophysics Data System (ADS)

    Davidovitch, Benny; Huang, Jiangshui; Menon, Narayanan; Russell, Thomas P.; Vella, Dominic

    2014-03-01

    Poking of liquid surface leads to a simple deformation of the surface, whose characteristic scale is nothing but the capillary length. In contrast, the poking of a circular solid sheet floating on a liquid bath demonstrates a surprisingly complex phenomenology, with numerous distinct length scales that are determined by the capillary length as well as by the poking amplitude and the stretching modulus of the sheet. The fundamental physical mechanism that underlies this complex response is intimately related to the emergence of an highly anisotropic stress, whose radial component is tensile and its hoop component is asymptotically compression-free. In this talk I will discuss the various parameter regimes that describe this problem and will identify the characteristic patterns of the poked sheet in these regimes. Experimental results will be presented and compared to theoretical predictions.

  6. The heliospheric current sheet

    NASA Astrophysics Data System (ADS)

    Smith, Edward J.

    2001-08-01

    The heliospheric current sheet (HCS) is the boundary between open oppositely directed magnetic field lines which commonly originate as the outward extension of the solar magnetic dipole. The dipole tilt, the rotation of the Sun, and the outward propagation of the solar wind cause peaks and valleys in the current sheet which spiral outward. The HCS extends throughout the heliosphere to the greatest distances reached by Pioneer and Voyager. It serves as a magnetic equator, and solar wind parameters including speed, temperature, density, and composition vary with distance from the HCS. Extrapolated back to the Sun, especially near solar minimum, the HCS corresponds to the low-latitude streamer belt. Both features are closely related to a neutral line obtained by extrapolating photospheric magnetic fields to a source surface at several solar radii. The current sheet and sector structure persist throughout the solar cycle including solar maximum. At 1 AU the width of the HCS is approximately 10,000 km while a surrounding plasma sheet is thicker by a factor of ~30. The field inside the HCS does not simply decrease to a null and then reappear with the opposite sense. Instead, the field rotates at nearly constant magnitude from one polarity to the other. In spite of theoretical expectations that fields on opposite sides of the HCS will merge or reconnect, there is little evidence that such is occurring. Many scientific questions remain unanswered. What are the global properties of the HCS near solar maximum, and how faithfully are they reproduced by source surface models? Are multiple HCS crossings caused by waves on the current sheet or by multiple current sheets? What is the effect of coronal mass ejections on the HCS and vice versa?

  7. Energy information sheets

    SciTech Connect

    Not Available

    1993-12-02

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the general public. Written for the general public, the EIA publication Energy Information Sheets was developed to provide information on various aspects of fuel production, prices, consumption and capability. The information contained herein pertains to energy data as of December 1991. Additional information on related subject matter can be found in other EIA publications as referenced at the end of each sheet.

  8. Curved cap corrugated sheet

    NASA Technical Reports Server (NTRS)

    Davis, R. C.; Bales, T. T.; Royster, D. M.; Jackson, L. R. (inventors)

    1984-01-01

    The report describes a structure for a strong, lightweight corrugated sheet. The sheet is planar or curved and includes a plurality of corrugation segments, each segment being comprised of a generally U-shaped corrugation with a part-cylindrical crown and cap strip, and straight side walls and with secondary corrugations oriented at right angles to said side walls. The cap strip is bonded to the crown and the longitudinal edge of said cap strip extends beyond edge at the intersection between said crown and said side walls. The high strength relative to weight of the structure makes it desirable for use in aircraft or spacecraft.

  9. TGF-beta signaling.

    PubMed Central

    Savage-Dunn, Cathy

    2005-01-01

    TGF-beta superfamily ligands play fundamental roles in the development and physiology of diverse animal species. Genetic and genomic analyses in the model organism Caenorhabditis elegans have contributed to the understanding of TGF-beta-related signal transduction mechanisms. In this chapter, I describe the currently characterized TGF-beta-related signals and signal transduction cassettes in C. elegans. Homology searches of the genome identify five TGF-beta-related genes, for which functions have been identified for three. Two of the TGF-beta-related genes, daf-7 and dbl-1, function through conventional signaling pathways. These signaling pathways are comprised of ser/thr kinase receptors, Smads, and transcription co-factors. A third TGF-beta-related gene, unc-129, functions in axonal guidance using novel signaling mechanisms. Thus, TGF-beta-related signaling in C. elegans proceeds via both conserved and novel paradigms that can inform studies in other animal systems. PMID:18050404

  10. Formation of an active form of the interleukin-2/15 receptor beta-chain by insertion of the intracisternal A particle in a radiation-induced mouse thymic lymphoma and its role in tumorigenesis.

    PubMed

    Ukai, Hideki; Ishii-Oba, Hiroko; Ukai-Tadenuma, Maki; Ogiu, Toshiaki; Tsuji, Hideo

    2003-06-01

    Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin-2 receptor (IL-2R) induces tumorigenic transformation, constitutively active IL-2R in tumors has not been reported. We searched for genomic alteration of the IL-2/15R beta-subunit gene (IL-2/15R beta) in cytokine-independent cell lines established from radiation-induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the IL-2/15R beta alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The IAP-IL2/15R beta chimeric gene expressed chimeric mRNA in which IAP-coding Gag-Pol mRNA was fused to IL-2/15R beta mRNA and coded for Gag-Pol-IL-2/15R beta chimeric protein. Forced expression of the Gag-Pol-IL-2/15R beta chimeric cDNA in a mouse cytotoxic T-cell line (CTLL-2) converted IL-2-dependent cell growth to IL-2-independent growth, suggesting that the chimeric protein activates some of the IL-2 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag-Pol-IL-2/15R beta chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c-myc protein. These results suggest that the Gag-Pol-IL-2/15R beta is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c-myc. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL-2-independent autonomous growth potential. PMID:12766910

  11. 71. PALMDALE WATER COMPANY, EASTWOOD MULTIPLEARCHED DAM: STRESS SHEET, SHEET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    71. PALMDALE WATER COMPANY, EASTWOOD MULTIPLE-ARCHED DAM: STRESS SHEET, SHEET 3; DECEMBER 20, 1918. Littlerock Water District files. - Little Rock Creek Dam, Little Rock Creek, Littlerock, Los Angeles County, CA

  12. 46. HANDRAILING, DETAILS TYPE 'B' (Sheet 12 of 14 sheets), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. HANDRAILING, DETAILS TYPE 'B' (Sheet 12 of 14 sheets), April 5, 1932 - West End-North Side Bridge, Spanning Ohio River, approximately 1 mile downstream from confluence of Monongahela & Allegheny rivers, Pittsburgh, Allegheny County, PA

  13. 5. Historic American Buildings Survey Taken from drawing sheet, SHEET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey Taken from drawing sheet, SHEET #21, Showing the house as restored since Survey. (Dormer windows omitted as not authentic) - Samuel des Marest House, River Road, New Milford, Bergen County, NJ

  14. Solar wind double ions beams and the heliospheric current sheet

    NASA Technical Reports Server (NTRS)

    Hammond, C. M.; Feldman, W. C.; Phillips, J. L.; Goldstein, B. E.; Balogh, A.

    1995-01-01

    Double ion beams are often observed in the solar wind, but little work has been done in relating these beams to structures within the solar wind. Double ion beams are observed as beams of a given ion species and charge state occurring at two different energies. We use the three-dimensional ion plasma instrument on board the Ulysses spacecraft to look for evidence of such beams associated with the heliospheric current sheet. In a subset chosen independently of plasma parameters consisting of 8 of cover 47 crossings of the current sheet made during the inecliptic phase of the Ulysses mission we find that these double ion beams are always present on either side of the current sheet. The double beams are present in both the proton and helium species. The secondary beam typically has a higher helium abundance, which suggests that these beams are formed in the helium-rich corona rather than in interplanetary space. The double beams are not present in the interior of the current sheet. Neither collisions nor effects of plasma beta can account for the disappearance of the double beams inside the current sheet in all eight cases. We postulate that these beams are formed by reconnection occurring near the Sun in the boundary region between the open field lines of the coronal holes and the closed field line region of the heliospheric current sheet. Such a scenario would be consistent with previous X ray measurements which suggect that reconnection is occurring in this region.

  15. Prediction of beta-strand packing interactions using the signature product.

    PubMed

    Brown, W Michael; Martin, Shawn; Chabarek, Joseph P; Strauss, Charlie; Faulon, Jean-Loup

    2006-02-01

    The prediction of beta-sheet topology requires the consideration of long-range interactions between beta-strands that are not necessarily consecutive in sequence. Since these interactions are difficult to simulate using ab initio methods, we propose a supplementary method able to assign beta-sheet topology using only sequence information. We envision using the results of our method to reduce the three-dimensional search space of ab initio methods. Our method is based on the signature molecular descriptor, which has been used previously to predict protein-protein interactions successfully, and to develop quantitative structure-activity relationships for small organic drugs and peptide inhibitors. Here, we show how the signature descriptor can be used in a Support Vector Machine to predict whether or not two beta-strands will pack adjacently within a protein. We then show how these predictions can be used to order beta-strands within beta-sheets. Using the entire PDB database with ten-fold cross-validation, we have achieved 74.0% accuracy in packing prediction and 75.6% accuracy in the prediction of edge strands. For the case of beta-strand ordering, we are able to predict the correct ordering accurately for 51.3% of the beta-sheets. Furthermore, using a simple confidence metric, we can determine those sheets for which accurate predictions can be obtained. For the top 25% highest confidence predictions, we are able to achieve 95.7% accuracy in beta-strand ordering. [Figure: see text]. PMID:16365772

  16. Algal Biofuels Fact Sheet

    SciTech Connect

    2009-10-27

    This fact sheet provides information on algal biofuels, which are generating considerable interest around the world. They may represent a sustainable pathway for helping to meet the U.S. biofuel production targets set by the Energy Independence and Security Act of 2007.

  17. Quick Information Sheets. 1988.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    The Trace Center gathers and organizes information on communication, control, and computer access for handicapped individuals. The information is disseminated in the form of brief sheets describing print, nonprint, and organizational resources and listing addresses and telephone numbers for ordering or for additional information. This compilation…

  18. Quick Information Sheets.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    This compilation of "Trace Quick Sheets" provides descriptions, prices, and ordering information for products and services that assist with communication, control, and computer access for disabled individuals. Product descriptions or product sources are included for: adaptive toys and toy modifications; head pointers, light pointers, and…

  19. GED Testing Fact Sheet

    ERIC Educational Resources Information Center

    GED Testing Service, 2009

    2009-01-01

    This GED Testing fact sheet provides information on: (1) GED[R] Tests; (2) Versions and Editions of the GED Tests; (3) Earning a Credential; (4) GED Testing Service[R]; (5) History of the GED Tests; (6) Who Accepts the GED Credential; (7) Public/Private Partnership of GEDTS; (8) Renowned GED Credential Recipients; (9) GED Testing Numbers for 2008;

  20. Quick Information Sheets.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    This compilation of "Trace Quick Sheets" provides descriptions, prices, and ordering information for products and services that assist with communication, control, and computer access for disabled individuals. Product descriptions or product sources are included for: adaptive toys and toy modifications; head pointers, light pointers, and

  1. Insulation Fact Sheet.

    ERIC Educational Resources Information Center

    Conservation and Renewable Energy Inquiry and Referral Service (DOE), Silver Spring, MD.

    Heating and cooling account for 50-70% of the energy consumed in the average American home. Heating water accounts for another 20%. A poorly insulated home loses much of this energy, causing drafty rooms and high energy bills. This fact sheet discusses how to determine if your home needs more insulation, the additional thermal resistance (called…

  2. Ethanol Myths Fact Sheet

    SciTech Connect

    2009-10-27

    Ethanol is a clean, renewable fuel that is helping to reduce our nation’s dependence on oil and can offer additional economic and environmental benefits in the future. This fact sheet is intended to address some common misconceptions about this important alternative fuel.

  3. Ethanol Basics (Fact Sheet)

    SciTech Connect

    Not Available

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  4. Latent TGF-[beta] structure and activation

    SciTech Connect

    Shi, Minlong; Zhu, Jianghai; Wang, Rui; Chen, Xing; Mi, Lizhi; Walz, Thomas; Springer, Timothy A.

    2011-09-16

    Transforming growth factor (TGF)-{beta} is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-{beta}1 requires the binding of {alpha}v integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-{beta} binding proteins. Crystals of dimeric porcine proTGF-{beta}1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between {alpha}v{beta}6 integrin and the prodomain is insufficient for TGF-{beta}1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-{beta} family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.

  5. Polio - Fact Sheet for Parents

    MedlinePLUS

    ... 6 through 18 months 4 through 6 years Fact Sheet for Parents Printer friendly version[2 pages] ... receive their vaccines according to the recommended schedule. Fact Sheets for Parents Diseases and the Vaccines that ...

  6. Graphene oxide strongly inhibits amyloid beta fibrillation

    NASA Astrophysics Data System (ADS)

    Mahmoudi, Morteza; Akhavan, Omid; Ghavami, Mahdi; Rezaee, Farhad; Ghiasi, Seyyed Mohammad Amin

    2012-11-01

    Since amyloid beta fibrillation (A?F) plays an important role in the development of neurodegenerative diseases, we investigated the effect of graphene oxide (GO) and their protein-coated surfaces on the kinetics of A? fibrillation in the aqueous solution. We showed that GO and their protein-covered surfaces delay the A?F process via adsorption of amyloid monomers. Also, the large available surface of GO sheets can delay the A?F process by adsorption of amyloid monomers. The inhibitory effect of the GO sheet was increased when we increase the concentration from 10% (in vitro; stimulated media) to 100% (in vivo; stimulated media). Conclusion: our results revealed that GO and their surface proteins inhibit A?F by decreasing the kinetic reaction.Since amyloid beta fibrillation (A?F) plays an important role in the development of neurodegenerative diseases, we investigated the effect of graphene oxide (GO) and their protein-coated surfaces on the kinetics of A? fibrillation in the aqueous solution. We showed that GO and their protein-covered surfaces delay the A?F process via adsorption of amyloid monomers. Also, the large available surface of GO sheets can delay the A?F process by adsorption of amyloid monomers. The inhibitory effect of the GO sheet was increased when we increase the concentration from 10% (in vitro; stimulated media) to 100% (in vivo; stimulated media). Conclusion: our results revealed that GO and their surface proteins inhibit A?F by decreasing the kinetic reaction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr31657a

  7. Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Weber, M. E.; Clark, P. U.; Ricken, W.; Mitrovica, J. X.; Hostetler, S. W.; Kuhn, G.

    2012-04-01

    The timing of the last maximum extent of the Antarctic ice sheets relative to those in the Northern Hemisphere remains poorly understood because only a few findings with robust chronologies exist for Antarctic ice sheets. We developed a chronology for the Weddell Sea sector of the East Antarctic ice sheet that, combined with ages from other Antarctic ice-sheet sectors, indicates the advance to their maximum extent at 29 -28 ka, and retreat from their maximum extent at 19 ka was nearly synchronous with Northern Hemisphere ice sheets (Weber, M.E., Clark, P. U., Ricken, W., Mitrovica, J. X., Hostetler, S. W., and Kuhn, G. (2011): Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum. - Science, 334, 1265-1269, doi: 10.1126:science.1209299). As for the deglaciation, modeling studies suggest a late ice-sheet retreat starting around 14 ka BP and ending around 7 ka BP with a large impact of an unstable West Antarctic Ice Sheet (WAIS) and a small impact of a stable East Antarctic Ice Sheet (EAIS). However, the Weddell Sea sites studied here, as well as sites from the Scotia Sea, provide evidence that specifically the EAIS responded much earlier, possibly provided a significant contribution to the last sea-level rise, and was much more dynamic than previously thought. Using the results of an atmospheric general circulation we conclude that surface climate forcing of Antarctic ice mass balance would likely cause an opposite response, whereby a warming climate would increase accumulation but not surface melting. Furthermore, our new data support teleconnections involving a sea-level fingerprint forced from Northern Hemisphere ice sheets as indicated by gravitational modeling. Also, changes in North Atlantic Deepwater formation and attendant heat flux to Antarctic grounding lines may have contributed to synchronizing the hemispheric ice sheets.

  8. Modeling the alpha-helix to beta-hairpin transition mechanism and the formation of oligomeric aggregates of the fibrillogenic peptide Abeta(12-28): insights from all-atom molecular dynamics simulations.

    PubMed

    Simona, Fabio; Tiana, Guido; Broglia, Ricardo A; Colombo, Giorgio

    2004-12-01

    In this paper, all-atom molecular dynamics simulations in explicit solvent are used to investigate the structural and dynamical determinants of the alpha-helical to beta-hairpin conformational transition of the 12-28 fragment from the full length Abeta Alzheimer's peptide. The transition from alpha-helical to beta-structure requires the peptide to populate intermediate beta-bend geometries in which several mainly hydrophobic interactions are partially formed. This is followed by the sudden collapse to ordered beta-hairpin structures and the simultaneous disruption of the hydrophobic side-chain interactions with a consequent increase in solvent exposure. The solvent exposure of hydrophobic side-chains belonging to a sequence of five consecutive residues in the beta-hairpin defines a possible starting point for the onset of the aggregation mechanisms. Several different conformations of model oligomeric (dimeric and tetrameric) aggregates are then investigated. These simulations show that while hydrophobic contacts are important to bring together different monomers with a beta-hairpin like conformation, more specific interactions such as hydrogen-bonding and coulombic interactions, should be considered necessary to provide further stabilization and ordering to the nascent fibrillar aggregates. PMID:15530822

  9. Fast Light-Sheet Scanner

    NASA Technical Reports Server (NTRS)

    Hunter, William W., Jr.; Humphreys, William M., Jr.; Bartram, Scott M.

    1995-01-01

    Optomechanical apparatus maintains sheet of pulsed laser light perpendicular to reference axis while causing sheet of light to translate in oscillatory fashion along reference axis. Produces illumination for laser velocimeter in which submicrometer particles entrained in flow illuminated and imaged in parallel planes displaced from each other in rapid succession. Selected frequency of oscillation range upward from tens of hertz. Rotating window continuously shifts sheet of light laterally while maintaining sheet parallel to same plane.

  10. Raman and AFM study of gamma irradiated plastic bottle sheets

    SciTech Connect

    Ali, Yasir; Kumar, Vijay; Dhaliwal, A. S.; Sonkawade, R. G.

    2013-02-05

    In this investigation, the effects of gamma irradiation on the structural properties of plastic bottle sheet are studied. The Plastic sheets were exposed with 1.25MeV {sup 60}Co gamma rays source at various dose levels within the range from 0-670 kGy. The induced modifications were followed by micro-Raman and atomic force microscopy (AFM). The Raman spectrum shows the decrease in Raman intensity and formation of unsaturated bonds with an increase in the gamma dose. AFM image displays rough surface morphology after irradiation. The detailed Raman analysis of plastic bottle sheets is presented here, and the results are correlated with the AFM observations.

  11. Origami folding of polymer sheets by inkjet printing

    NASA Astrophysics Data System (ADS)

    Liu, Ying; Shaw, Brandi; Dickey, Michael D.; Genzer, Jan

    2015-03-01

    In analogy to the ancient Japanese art of paper folding (Origami), self-folding is an attractive strategy to induce the formation of three-dimensional (3D) objects with well-defined shapes and dimensions using conventional two-dimensional (2D) patterning techniques, such as lithography and inkjet printing. Self-folding can be applied in the areas of reconfigurable devices, actuators, and sensors. Here we demonstrate a simple method for self-folding of polymer sheets utilizing localized light absorption on selected areas of the pre-strained polymer sheet. The ink is patterned via a desktop printer and it defines the location of the `hinge' on the sheet. The inked areas on the 2D sheet absorb light preferentially, thus causing the polymer sheet to fold locally in the inked areas. The temperature gradients through the depth of the sheet induce localized shrinkage and the sheet folds within seconds. This patterned polymer sheets act as shape memory materials which can be programmed to fold into various 3D structures based on the nature of the light source, the shape and size of the ink patterns, and ink property. By controlling the aforementioned parameters we achieve a complete control of the time and degree of folding, which ultimately govern the final 3D shape of the folded object.

  12. Beginning Child Care Fact Sheets.

    ERIC Educational Resources Information Center

    Tweedie, Pat

    These six fact sheets from Child Care Aware are designed to help parents ease their children's transition to child care. The first fact sheet, "Before Your Child's First Day," discusses tips such as: (1) "prepare your child"; (2) read and look at picture books about child care; and (3) "prepare yourself." The second fact sheet, "First Day Tips,"

  13. The Physics of Ice Sheets

    ERIC Educational Resources Information Center

    Bassis, J. N.

    2008-01-01

    The great ice sheets in Antarctica and Greenland are vast deposits of frozen freshwater that contain enough to raise sea level by approximately 70 m if they were to completely melt. Because of the potentially catastrophic impact that ice sheets can have, it is important that we understand how ice sheets have responded to past climate changes and…

  14. The Physics of Ice Sheets

    ERIC Educational Resources Information Center

    Bassis, J. N.

    2008-01-01

    The great ice sheets in Antarctica and Greenland are vast deposits of frozen freshwater that contain enough to raise sea level by approximately 70 m if they were to completely melt. Because of the potentially catastrophic impact that ice sheets can have, it is important that we understand how ice sheets have responded to past climate changes and

  15. Skill Sheets for Agricultural Mechanics.

    ERIC Educational Resources Information Center

    Iowa State Univ. of Science and Technology, Ames. Dept. of Agricultural Education.

    This set of 33 skill sheets for agricultural mechanics was developed for use in high school and vocational school agricultural mechanics programs. Some sheets teach operational procedures while others are for simple projects. Each skill sheet covers a single topic and includes: (1) a diagram, (2) a step-by-step construction or operational…

  16. Characterization of Hydrogels Formed via Intramolecular Folding and Consequent Self-Assembly of Beta-HAIRPIN Peptides

    NASA Astrophysics Data System (ADS)

    Ozbas, Bulent; Pakstis, Lisa; Pochan, Darrin J.; Rajagopal, Karthikan; Gill, Juliana; Schneider, Joel P.

    2003-03-01

    Stimuli-responsive and biocompatible networks formed via self-assembly serve great opportunities in tissue engineering and drug delivery applications. In this work we present the formation of hydrogels via the intramolecular folding and consequent self-assembly of 20 aminoacid long beta-Hairpin peptide molecules. These hairpin molecules are amphiphilic in nature with an alternating sequence of hydrophobic valine and hydrophilic lysine amino acids. These molecules are found to form hydrogels with a unique microstructure and nanostructure at different physical condition at low peptide concentrations ( 1 wt %). However, gelation is observed at high pH values ( 9) and at high salt concentrations ( 150 mM) where beta-sheet secondary structure due to hairpin folding is observed. The intimate relationship between beta-Hairpin molecule turn sequence and the consequent materials properties will be discussed. LSCM data reveals that hydrogel structure is heterogeneous at the microscale with water channels in the order of 10 ?m. Cryo-TEM technique shows that the network is consists of interconnected fibrillar/tubular networks. The viscoelastic properties of the hydrogels, as measured by rheology. Importantly, the gel is also reversible with pH, returning to a viscosity of water with a drop in pH that unfolds, and disassembles, the hairpin molecules.

  17. The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.

    PubMed

    Baker, Jillian G

    2005-02-01

    Beta-adrenoceptor antagonists ("beta-blockers") are one of the most widely used classes of drugs in cardiovascular medicine (hypertension, ischaemic heart disease and increasingly in heart failure) as well as in the management of anxiety, migraine and glaucoma. Where known, the mode of action in cardiovascular disease is from antagonism of endogenous catecholamine responses in the heart (mainly at beta1-adrenoceptors), while the worrisome side effects of bronchospasm result from airway beta2-adrenoceptor blockade. The aim of this study was to determine the selectivity of beta-antagonists for the human beta-adrenoceptor subtypes. (3)H-CGP 12177 whole cell-binding studies were undertaken in CHO cell lines stably expressing either the human beta1-, beta2- or the beta3-adrenoceptor in order to determine the affinity of ligands for each receptor subtype in the same cell background. In this study, the selectivity of well-known subtype-selective ligands was clearly demonstrated: thus, the selective beta1 antagonist CGP 20712A was 501-fold selective over beta2 and 4169-fold selective over beta3; the beta2-selective antagonist ICI 118551 was 550- and 661-fold selective over beta1 and beta3, respectively, and the selective beta3 compound CL 316243 was 10-fold selective over beta2 and more than 129-fold selective over beta1. Those beta2-adrenoceptor agonists used clinically for the treatment of asthma and COPD were beta2 selective: 29-, 61- and 2818-fold for salbutamol, terbutaline and salmeterol over beta1, respectively. There was little difference in the affinity of these ligands between beta1 and beta3 adrenoceptors. The clinically used beta-antagonists studied ranged from bisoprolol (14-fold beta1-selective) to timolol (26-fold beta2-selective). However, the majority showed little selectivity for the beta1- over the beta2-adrenoceptor, with many actually being more beta2-selective. This study shows that the beta1/beta2 selectivity of most clinically used beta-blockers is poor in intact cells, and that some compounds that are traditionally classed as "beta1-selective" actually have higher affinity for the beta2-adrenoceptor. There is therefore considerable potential for developing more selective beta-antagonists for clinical use and thereby reducing the side-effect profile of beta-blockers. PMID:15655528

  18. Luminescence Chronology for the Formation of Glacial Lake Calgary, Southern Alberta, Canada: Age Constraints for the Initiation of the Late Pleistocene Retreat of the Laurentide Ice Sheet from its Western Margin

    NASA Astrophysics Data System (ADS)

    Munyikwa, K.; Rittenour, T. M.

    2014-12-01

    Glacial Lake Calgary in southern Alberta, Canada, was a Late Pleistocene proglacial lake that formed along the southwest margin of the Laurentide Ice Sheet (LIS), dammed by the retreating ice sheet margin. Attempts to constrain the age of the lake using radiocarbon methods have been hampered by the lack of datable organic material. In an effort to apply an alternative chronometer, this study uses two optically stimulated luminescence (OSL) dating approaches to date fine grained sand and silt that were deposited in the lake during its existence. OSL dating determines the depositional ages of sediments by measuring the energy from ionizing radiation that is stored in mineral grains such as quartz and feldspar. Dividing the stored energy, also referred to as the paleodose, by the rate at which the dose accumulated, allows an age to be ascertained. In one method applied in this study, the paleodose stored in the feldspar component of the sediment is determined using normalized infrared stimulated luminescence signals acquired using a portable OSL reader. In the second method, blue optically stimulated luminescence signals obtained from quartz separates from the sediment by employing a regular OSL reader and standard protocols are used to determine the paleodose. After correcting the feldspar data for anomalous fading, the age results from the two dating approaches are compared. The ages signify a time period by which the LIS had retreated from the study area and, hence, serve as constraints for the initiation of the retreat of the ice sheet from its western limit. Advantages and limitations of the dating methods are briefly discussed. Constraining the chronology of the retreat of the LIS from western Canada allows for a better understanding of the driving forces behind ice sheet retreat. Secondly, assigning a temporal scale to the postglacial evolution of the environment of the region permits a better insight into the dynamics of the physical and biological environments of the time. Thirdly, the region is at the heart of the ice-free corridor that was ostensibly used by early humans to migrate southwards to populate the Americas ca. 16 ka ago. Hence, an improved deglaciation chronology would allow a more comprehensive evaluation of this concept.

  19. SHEET PLASMA DEVICE

    DOEpatents

    Henderson, O.A.

    1962-07-17

    An ion-electron plasma heating apparatus of the pinch tube class was developed wherein a plasma is formed by an intense arc discharge through a gas and is radially constricted by the magnetic field of the discharge. To avoid kink and interchange instabilities which can disrupt a conventional arc shortiy after it is formed, the apparatus is a pinch tube with a flat configuration for forming a sheet of plasma between two conductive plates disposed parallel and adjacent to the plasma sheet. Kink instabilities are suppressed by image currents induced in the conductive plates while the interchange instabilities are neutrally stable because of the flat plasma configuration wherein such instabilities may occur but do not dynamically increase in amplitude. (AEC)

  20. Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine.

    PubMed

    Miller, M T; Bachmann, B O; Townsend, C A; Rosenzweig, A C

    2001-08-01

    The enzyme beta-lactam synthetase (beta-LS) catalyzes the formation of the beta-lactam ring in clavulanic acid, a clinically important beta-lactamase inhibitor. Whereas the penicillin beta-lactam ring is generated by isopenicillin N synthase (IPNS) in the presence of ferrous ion and dioxygen, beta-LS uses ATP and Mg2+ as cofactors. According to sequence alignments, beta-LS is homologous to class B asparagine synthetases (AS-Bs), ATP/Mg2+-dependent enzymes that convert aspartic acid to asparagine. Here we report the first crystal structure of a beta-LS. The 1.95 A resolution structure of Streptomyces clavuligerus beta-LS provides a fully resolved view of the active site in which substrate, closely related ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP) and a single Mg2+ ion are present. A high degree of substrate preorganization is observed. Comparison to Escherichia coli AS-B reveals the evolutionary changes that have taken place in beta-LS that impede interdomain reaction, which is essential in AS-B, and that accommodate beta-lactam formation. The structural data provide the opportunity to alter the synthetic potential of beta-LS, perhaps leading to the creation of new beta-lactamase inhibitors and beta-lactam antibiotics. PMID:11473258

  1. Clean Cities Fact Sheet

    SciTech Connect

    Not Available

    2004-01-01

    This fact sheet explains the Clean Cities Program and provides contact information for all coalitions and regional offices. It answers key questions such as: What is the Clean Cities Program? What are alternative fuels? How does the Clean Cities Program work? What sort of assistance does Clean Cities offer? What has Clean Cities accomplished? What is Clean Cities International? and Where can I find more information?

  2. Topographical atlas sheets

    USGS Publications Warehouse

    Wheeler, George Montague

    1876-01-01

    The following topographical atlas sheets, accompanying Appendix J.J. of the Annual Report of the Chief of Engineers, U.S. Army-being Annual Report upon U. S. Geographical Surveys-have been published during the fiscal year ending June 30, 1876, and are a portion of the series projected to embrace the territory of the United States lying west of the 100th meridian.

  3. Silicon sheet surface studies

    NASA Technical Reports Server (NTRS)

    Danyluk, S.

    1985-01-01

    Results of the program are presented on developing an understanding of the basic mechanisms of abrasion and wear of silicon and on the nondestructive measurement of residual stresses in sheet silicon. Experiments were conducted at various temperatures and in the presence of various fluids. In abrasive wear, it was shown that dislocations, microtwins, and cracks are generated beneath the contact surface. Residual stresses in ribbon by the edge defined film growth process were measured by use of a shadow moire interferometry technique.

  4. Biomolecular Science (Fact Sheet)

    SciTech Connect

    Not Available

    2012-04-01

    A brief fact sheet about NREL Photobiology and Biomolecular Science. The research goal of NREL's Biomolecular Science is to enable cost-competitive advanced lignocellulosic biofuels production by understanding the science critical for overcoming biomass recalcitrance and developing new product and product intermediate pathways. NREL's Photobiology focuses on understanding the capture of solar energy in photosynthetic systems and its use in converting carbon dioxide and water directly into hydrogen and advanced biofuels.

  5. High Beta Tokamaks

    SciTech Connect

    Cowley, S.

    1998-11-14

    Perhaps the ideal tokamak would have high {beta} ({beta} {approx}> 1) and classical confinement. Such a tokamak has not been found, and we do not know if one does exist. We have searched for such a possibility, so far without success. In 1990, we obtained analytic equilibrium solutions for large aspect ratio tokamaks at {beta} {approx} {Omicron}(1) [1]. These solutions and the extension at high {beta} poloidal to finite aspect ratio [2] provided a basis for the study of high {beta} tokamaks. We have shown that these configurations can be stable to short scale MHD modes [3], and that they have reduced neoclassical transport [4]. Microinstabilities (such as the {del}T{sub i} mode) seem to be stabilized at high {beta} [5] - this is due to the large local shear [3] and the magnetic well. We have some concerns about modes associated with the compressional branch which may appear at high {beta}. Bill Dorland and Mike Kotschenreuther have studied this issue and our concerns may be unfounded. It is certainly tantalizing, especially given the lowered neoclassical transport values, that these configurations could have no microinstabilities and, one could assume, no anomalous transport. Unfortunately, while this work is encouraging, the key question for high {beta} tokamaks is the stability to large scale kink modes. The MHD {beta} limit (Troyon limit) for kink modes at large aspect ratio is problematically low. There is ample evidence from computations that the limit exists. However, it is not known if stable equilibria exist at much higher {beta}--none have been found. We have explored this question in the asymptotic high {beta} poloidal limit. Unfortunately, we are unable to find stable equilibrium and also unable to show that they don't exist. The results of these calculations will be published when a more definitive answer is found.

  6. Plastic bronchitis in beta thalassemia minor

    PubMed Central

    Yadav, Makaresh; Tirpude, Sneha; Joshi, Jyotsna M.

    2013-01-01

    Plastic bronchitis is a rare pulmonary disorder associated with various conditions like cystic fibrosis, asthma, pulmonary infection and characterized by formation and expectoration of cast which assumes the shape of the bronchial tree. We report a case of a 33-year-old woman with beta thalassemia minor who developed plastic bronchitis. PMID:24049256

  7. Hypoglycemia Reduces Vascular Endothelial Growth Factor A Production by Pancreatic Beta Cells as a Regulator of Beta Cell Mass*

    PubMed Central

    Xiao, Xiangwei; Guo, Ping; Chen, Zean; El-Gohary, Yousef; Wiersch, John; Gaffar, Iljana; Prasadan, Krishna; Shiota, Chiyo; Gittes, George K.

    2013-01-01

    VEGF-A expression in beta cells is critical for pancreatic development, formation of islet-specific vasculature, and Insulin secretion. However, two key questions remain. First, is VEGF-A release from beta cells coupled to VEGF-A production in beta cells? Second, how is the VEGF-A response by beta cells affected by metabolic signals? Here, we show that VEGF-A secretion, but not gene transcription, in either cultured islets or purified pancreatic beta cells, was significantly reduced early on during low glucose conditions. In vivo, a sustained hypoglycemia in mice was induced with Insulin pellets, resulting in a significant reduction in beta cell mass. This loss of beta cell mass could be significantly rescued with continuous delivery of exogenous VEGF-A, which had no effect on beta cell mass in normoglycemic mice. In addition, an increase in apoptotic endothelial cells during hypoglycemia preceded an increase in apoptotic beta cells. Both endothelial and beta cell apoptosis were prevented by exogenous VEGF-A, suggesting a possible causative relationship between reduced VEGF-A and the loss of islet vasculature and beta cells. Furthermore, in none of these experimental groups did beta cell proliferation and islet vessel density change, suggesting a tightly regulated balance between these two cellular compartments. The average islet size decreased in hypoglycemia, which was also prevented by exogenous VEGF-A. Taken together, our data suggest that VEGF-A release in beta cells is independent of VEGF-A synthesis. Beta cell mass can be regulated through modulated release of VEGF-A from beta cells based on physiological need. PMID:23378532

  8. Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives

    PubMed Central

    Šneideris, Tomas; Baranauskienė, Lina; Cannon, Jonathan G.; Rutkienė, Rasa; Meškys, Rolandas

    2015-01-01

    A range of diseases is associated with amyloid fibril formation. Despite different proteins being responsible for each disease, all of them share similar features including beta-sheet-rich secondary structure and fibril-like protein aggregates. A number of proteins can form amyloid-like fibrils in vitro, resembling structural features of disease-related amyloids. Given these generic structural properties of amyloid and amyloid-like fibrils, generic inhibitors of fibril formation would be of interest for treatment of amyloid diseases. Recently, we identified five outstanding inhibitors of insulin amyloid-like fibril formation among the pool of 265 commercially available flavone derivatives. Here we report testing of these five compounds and of epi-gallocatechine-3-gallate (EGCG) on aggregation of alpha-synuclein and beta-amyloid. We used a Thioflavin T (ThT) fluorescence assay, relying on halftimes of aggregation as the measure of inhibition. This method avoids large numbers of false positive results. Our data indicate that four of the five flavones and EGCG inhibit alpha-synuclein aggregation in a concentration-dependent manner. However none of these derivatives were able to increase halftimes of aggregation of beta-amyloid. PMID:26421240

  9. Dynamics of dikes versus cone sheets in volcanic systems

    NASA Astrophysics Data System (ADS)

    Galland, Olivier; Burchardt, Steffi; Hallot, Erwan; Mourgues, Régis; Bulois, Cédric

    2015-04-01

    Igneous sheet intrusions of various shapes, such as dikes and cone sheets, coexist as parts of complex volcanic plumbing systems likely fed by common sources. How they form is fundamental regarding volcanic hazards, but yet no dynamic model simulates and predicts satisfactorily their diversity. Here we present scaled laboratory experiments that reproduced dikes and cone sheets under controlled conditions (Galland et al., 2014). Our models show that their formation is governed by a dimensionless ratio (Π1), which describes the shape of the magma source, and a dynamic dimensionless ratio (Π2), which compares the viscous stresses in the flowing magma to the host-rock strength. Plotting our experiments against these two numbers results in a phase diagram evidencing a dike and a cone-sheet field, separated by a sharp transition that fits a power law. This result shows that dikes and cone sheets correspond to distinct physical regimes of magma emplacement in the crust. For a given host-rock strength, cone sheets preferentially form when the source is shallow, relative to its lateral extent, or when the magma influx velocity (or viscosity) is high. Conversely, dikes form when the source is deep compared to its size, or when magma influx rate (or viscosity) is low. Both dikes and cone sheets may form from the same source, the shift from one regime to the other being then controlled by magma dynamics, i.e., different values of Π2. The extrapolated empirical dike-to-cone sheet transition is in good agreement with the occurrence of dikes and cone sheets in various natural volcanic settings. Galland, O., Burchardt, S., Hallot, E., Mourgues, R., Bulois, C., 2014. Dynamics of dikes versus cone sheets in volcanic systems. Journal of Geophysical Research: Solid Earth, 2014JB011059, 10.1002/2014jb011059.

  10. Finite /beta/ stellarators

    SciTech Connect

    Bauer, F.; Betancourt, O.L.; Garabedian, P.R.; Shohet, J.L.

    1981-12-01

    A fully three-dimensional computer code based on an ideal magnetohydrodynamic model has been used to find stellarator configurations with finite critical values of the plasma parameter /beta/. It is established that the WISTOR-U torsatron designed at the University of Wisconsin and the Heliotron E experiment constructed at Kyoto University have average /beta/ limits near 5 percent. 10 refs.

  11. Beta-Carotene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beta-carotene is a pigment that occurs naturally in many photosynthetic plants and organisms and one of the most abundant carotenoids found in human blood. The richest dietary sources of beta-carotene are yellow, orange, and leafy green fruits and vegetables, such as carrots, spinach, sweet potatoes...

  12. Investigations of B- and beta-hematin.

    PubMed

    Blauer, G; Akkawi, M

    1997-05-01

    The preparation from ferriprotoporphyrin IX (FP) in aqueous acid medium of the related pigments beta- and B-hematin [see G. Blauer and M. Akkawi, Biochem. Mol. Biol. Int. 35, 231 (1995)] is presented under different conditions. Both pigments are characterized by infrared spectra which differ in the range of 1600-1700 cm-1 in their strong bands with absorption peaks measured at 1648 +/- 2 cm-1 for B-hematin and at 1663 +/- 1 cm-1 for beta-hematin. The pH dependence of B-hematin formation at 37 degrees C and at different concentrations of acetic acid and FP exhibits a maximum yield near pH 4. The formation of beta-hematin at 70 degrees C shows high yield in 6 M acetic acid or in the presence of 0.028 M trichloroacetate at pH 4.6. The dependence of the yield of the pigments on the time and temperature of incubation, concentration of FP, and the presence of different electrolytes was investigated. Both B- and beta-hematin are either insoluble or very slightly soluble in different solvents at room temperature, and appear to dissociate into regular FP in strongly alkaline aqueous medium. In the presence of different quinoline-based drugs, the formation of both B- and beta-hematin at pH 4-5 is inhibited. Under certain conditions, the effect of added carboxylic acids on pigment formation is suggested to be due, at least in part, to the prevention of initial hydrogen bonding among FP carboxyl groups. For both B- and beta-hematin, branched and cyclic macromolecular structures are proposed involving linkages between an FP iron and a side-chain carboxylate group of another FP, in addition to hydrogen bonds between FP carboxyl groups. B- and beta-hematin are assumed to differ in molecular weight and the extent of bond formation. Possible mechanisms for beta-hematin production from B-hematin and certain relations between the synthetic pigments and the malaria pigment are suggested. PMID:9112763

  13. Synchrotron-based Infrared and X-ray Imaging Shows Focalized Accumulation of Cu and Zn Co-localized With Beta-amyloid Deposits in Alzheimer's Disease

    SciTech Connect

    Miller,L.; Wang, Q.; Telivala, T.; Smith, R.; Lanzirotti, A.; Miklossy, J.

    2006-01-01

    Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains 'hot spots' of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The 'hot spots' of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD.

  14. Rapid synthesis of beta zeolites

    SciTech Connect

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

    2015-08-18

    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.

  15. Conversion of rice husk ash to zeolite beta.

    PubMed

    Prasetyoko, Didik; Ramli, Zainab; Endud, Salasiah; Hamdan, Halimaton; Sulikowski, Bogdan

    2006-01-01

    White rice husk ash (RHA), an agriculture waste containing crystalline tridymite and alpha-cristobalite, was used as a silica source for zeolite Beta synthesis. The crystallization of zeolite Beta from RHA at 150 degrees C in the presence of tetraethylammonium hydroxide was monitored by XRD, FTIR and (29)Si MAS NMR techniques. It was found that zeolite Beta started to form after 12h and the complete crystallization of zeolite Beta phase was achieved after 2d. XRD, (29)Si MAS NMR and solid yield studies indicate that the transformation mechanism of silica present in RHA to zeolite Beta involves dissolution of the ash, formation of an amorphous aluminosilicate after 6h of crystallization, followed by dissolution in the mother liquor and final transformation to pure zeolite Beta crystals. PMID:16274981

  16. Ribbed moraine formation

    NASA Astrophysics Data System (ADS)

    Httestrand, Clas; Kleman, Johan

    Ribbed (Rogen) moraines are conspicuous landforms found in interior parts of formerly glaciated areas. Two major theories for ribbed moraine formation have been suggested in recent years: (i) the shear and stack theory, which explains ribbed moraine formation by shearing and stacking of till slabs or englacially entrained material during compressive flow, followed by basal melt-out of transverse moraine ridges, and (ii) the fracturing theory, according to which ribbed moraines form by fracturing of frozen pre-existing till sheets, at the transition from cold- to warm-based conditions under deglaciating ice sheets. In this paper, we present new data on the distribution of ribbed moraines and their close association with areas of frozen-bed conditions under ice sheets. In addition, we show examples of ribbed moraine ridges that fit together like a jig-saw puzzle. These observations indicate that fracturing and extension of a pre-existing till sheet may be a predominant process in ribbed moraine formation. In summary, we conclude that all described characteristics of ribbed moraines are compatible with the fracturing theory, while the shear and stack theory is hampered by an inability to explain many conspicuous features in the distribution pattern and detailed morphology of ribbed moraines. One implication of the fracturing theory is that the distribution of ribbed moraines can be used to reconstruct the extent of areas that underwent a change from frozen-bed to thawed-bed conditions under former ice sheets.

  17. Double-beta decay

    SciTech Connect

    Moe, M.K.; Rosen, S.P.

    1989-11-01

    In a double-beta event, two neutrons decay simultaneouly into two protons, two beta rays (electrons) and two antineutrinos. Experimentalists are now searching for another form of double-beta decay, one that does not produce neutrinos or antineutrinos. If such an event is found, it could unravelone of nature's great mysteries: What, if anything, is the mass of the neutrino According to the Standard Model, the neutrino accompanying a negative beta ray is the distinct antiparticle of the one accompanying a positive beta ray. The theories that go beyond the Standard Model and assign a mass to the neutrino, however, predict that the particle emitted with a negative beta ray should be the same as the one emitted with a positive ray. In other words, the neutrino would be its own antiparticle. How can we tell whether these predictions are right Double-beta decay is the ideal process in which to seek an answer to this question. If the neutrino has mass and is its own antiparticle, then the neutrino emitted in the first stage of the process might be reaborbed in the second, yielding a form of decay in which no neutrinos materialize. 8 figs.

  18. Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes.

    PubMed Central

    Kapur, V; Majesky, M W; Li, L L; Black, R A; Musser, J M

    1993-01-01

    Streptococcal pyrogenic exotoxin B (SPE B), a conserved extracellular cysteine protease expressed by the human pathogenic bacterium Streptococcus pyogenes, was purified and shown to cleave inactive human interleukin 1 beta precursor (pIL-1 beta) to produce biologically active IL-1 beta. SPE B cleaves pIL-1 beta one residue amino-terminal to the site where a recently characterized endogenous human cysteine protease acts. IL-1 beta resulting from cleavage of pIL-1 beta by SPE B induced nitric oxide synthase activity in vascular smooth muscle cells and killed of the human melanoma A375 line. Two additional naturally occurring SPE B variants cleaved pIL-1 beta in a similar fashion. By demonstrating that SPE B catalyzes the formation of biologically active IL-1 beta from inactive pIL-1 beta, our data add a further dimension to an emerging theme in microbial pathogenesis that bacterial and viral virulence factors act directly on host cytokine pathways. The data also contribute to an enlarging literature demonstrating that microbial extracellular cysteine proteases are important in host-parasite interactions. Images Fig. 1 Fig. 2 Fig. 4 PMID:7689226

  19. Movement of a loop in domain 3 of aerolysin is required for channel formation.

    PubMed

    Rossjohn, J; Raja, S M; Nelson, K L; Feil, S C; van der Goot, F G; Parker, M W; Buckley, J T

    1998-01-13

    Aerolysin is a channel-forming toxin that must oligomerize in order to become insertion-competent. Modeling based on the crystal structure of the proaerolysin dimer and electron microscopic images of the oligomer indicated that a loop in domain 3 must move away from the beta-sheet that forms the main body of the protein before oligomerization can proceed. In order to determine if movement actually occurs, strategically located amino acids in the loop and in the sheet were replaced with cysteines by site-directed mutagenesis. A double mutant was produced in which the new cysteines, at position 253 on the loop and position 300 in the sheet, were close enough together to allow formation of a disulfide bridge. The double mutant was unable to oligomerize, and it was completely inactive, showing not only that the bridge had formed but also that movement of the loop was essential for formation of the oligomer. The existence of the bridge was confirmed by X-ray crystallography. The reduced form of the protein and the single mutants T253C and A300C were as active as wild type, indicating that the amino acid replacements themselves had no functional consequences. Labeling studies using an environment-sensitive fluorescent sulfhydryl-reactive probe confirmed that the structure of the protein changes in the loop region as a consequence of proteolytic activation of proaerolysin, a step which also must precede oligomerization. PMID:9425098

  20. Tyrosine residues 654 and 670 in {beta}-cat enin are crucial in regulation of Met-{beta}-catenin interactions

    SciTech Connect

    Zeng, Gang; Apte, Udayan; Micsenyi, Amanda; Bell, Aaron; Monga, Satdarshan P.S. . E-mail: smonga@pitt.edu

    2006-11-01

    {beta}-catenin, a key component of the canonical Wnt pathway, is also regulated by tyrosine phosphorylation that regulates its association to E-cadherin. Previously, we reported its association with the hepatocyte growth factor (HGF) receptor Met at the membrane. HGF induced Met-{beta}-catenin dissociation and nuclear translocation of {beta}-catenin, which was tyrosine-phosphorylation-dependent. Here, we further investigate the Met-{beta}-catenin interaction by selectively mutating several tyrosine residues, alone or in combination, in {beta}-catenin. The mutants were subcloned into FLAG-CMV vector and stably transfected into rat hepatoma cells, which were treated with HGF. All single or double-mutant-transfected cells continued to show HGF-induced nuclear translocation of FLAG-{beta}-catenin except the mutations affecting 654 and 670 simultaneously (Y654/670F), which coincided with the lack of formation of {beta}-catenin-TCF complex and DNA synthesis, in response to the HGF treatment. In addition, the Y654/670F-transfected cells also showed no phosphorylation of {beta}-catenin or dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine residues in {beta}-catenin are crucial in HGF-mediated {beta}-catenin translocation, activation and mitogenesis.

  1. {alpha}-Lipoic acid exhibits anti-amyloidogenicity for {beta}-amyloid fibrils in vitro

    SciTech Connect

    Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito . E-mail: m-yamada@med.kanazawa-u.ac.jp

    2006-03-24

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of {alpha}-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 {sup o}C in vitro. LA and DHLA dose-dependently inhibited fA{beta} formation from amyloid {beta}-protein, as well as their extension. Moreover, they destabilized preformed fA{beta}s. LA and DHLA could be key molecules for the development of therapeutics for AD.

  2. Ice sheets and nitrogen.

    PubMed

    Wolff, Eric W

    2013-07-01

    Snow and ice play their most important role in the nitrogen cycle as a barrier to land-atmosphere and ocean-atmosphere exchanges that would otherwise occur. The inventory of nitrogen compounds in the polar ice sheets is approximately 260 Tg N, dominated by nitrate in the much larger Antarctic ice sheet. Ice cores help to inform us about the natural variability of the nitrogen cycle at global and regional scale, and about the extent of disturbance in recent decades. Nitrous oxide concentrations have risen about 20 per cent in the last 200 years and are now almost certainly higher than at any time in the last 800 000 years. Nitrate concentrations recorded in Greenland ice rose by a factor of 2-3, particularly between the 1950s and 1980s, reflecting a major change in NOx emissions reaching the background atmosphere. Increases in ice cores drilled at lower latitudes can be used to validate or constrain regional emission inventories. Background ammonium concentrations in Greenland ice show no significant recent trend, although the record is very noisy, being dominated by spikes of input from biomass burning events. Neither nitrate nor ammonium shows significant recent trends in Antarctica, although their natural variations are of biogeochemical and atmospheric chemical interest. Finally, it has been found that photolysis of nitrate in the snowpack leads to significant re-emissions of NOx that can strongly impact the regional atmosphere in snow-covered areas. PMID:23713125

  3. Ice sheets and nitrogen

    PubMed Central

    Wolff, Eric W.

    2013-01-01

    Snow and ice play their most important role in the nitrogen cycle as a barrier to landatmosphere and oceanatmosphere exchanges that would otherwise occur. The inventory of nitrogen compounds in the polar ice sheets is approximately 260 Tg N, dominated by nitrate in the much larger Antarctic ice sheet. Ice cores help to inform us about the natural variability of the nitrogen cycle at global and regional scale, and about the extent of disturbance in recent decades. Nitrous oxide concentrations have risen about 20 per cent in the last 200 years and are now almost certainly higher than at any time in the last 800 000 years. Nitrate concentrations recorded in Greenland ice rose by a factor of 23, particularly between the 1950s and 1980s, reflecting a major change in NOx emissions reaching the background atmosphere. Increases in ice cores drilled at lower latitudes can be used to validate or constrain regional emission inventories. Background ammonium concentrations in Greenland ice show no significant recent trend, although the record is very noisy, being dominated by spikes of input from biomass burning events. Neither nitrate nor ammonium shows significant recent trends in Antarctica, although their natural variations are of biogeochemical and atmospheric chemical interest. Finally, it has been found that photolysis of nitrate in the snowpack leads to significant re-emissions of NOx that can strongly impact the regional atmosphere in snow-covered areas. PMID:23713125

  4. Modelling of the Turbulent Plasma Sheet for Different Geomagnetic Conditions

    NASA Astrophysics Data System (ADS)

    Stepanova, M. V.; Antonova, E. E.

    2009-12-01

    Recent studies has been shown the importance of turbulent processes for the development of self-consistent approach for the dynamics of the magnetosphere of the Earth, in particular, for the analysis of the stability of turbulent plasma sheet. Fluctuations of the plasma bulk velocity were deduced from the measurements on board Interball/Tail, Cluster, Geotail, and Themis satellites. It was found that the plasma sheet flow generally appears to be strongly turbulent, i.e. dominated by fluctuations that are unpredictable. Corresponding eddy-diffusion coefficients were derived using the autocorrelation time and rms velocity. Variations of eddy-diffusion coefficients and particle density across and along the plasma sheet were studied, determining the characteristic values of eddy diffusion and of particle density as well as the thickness of the plasma sheet. The results obtained have been used for direct verification of the Antonova and Ovchinnikov (1996, 1998, 1999) theory of the plasma sheet formation, according to which a compact and comparatively stable turbulent plasma sheet can be formed when the regular plasma transport related to the regular dawn-dusk electric field across the plasma sheet is compensated by the eddy diffusion turbulent transport. When the turbulent fluctuations act to expand the plasma sheet, the large-scale electrostatic dawn-dusk electric field counteracts to compress it, similarly to the case of the laboratory pinch which is compressed by the induction electric field. When the expansion and compression compensate each other, a stationary structure is formed. Our results have shown that this theory reproduces the dynamics of the turbulent plasma sheet, including its thickness, within the accuracy of parameters used.

  5. Transmembrane pores formed by synthetic p-octiphenyl beta-barrels with internal carboxylate clusters: regulation of ion transport by pH and Mg(2+)- complexed 8-aminonaphthalene-1,3,6-trisulfonate.

    PubMed

    Das, Gopal; Matile, Stefan

    2002-04-16

    Design, synthesis, and study of a synthetic barrel-stave supramolecule with p-octiphenyl "staves," beta-sheet "hoops," and hydrophobic exterior as well as internal carboxylate clusters are reported. Ion transport experiments indicate the formation of transmembrane pores at 5 < pH < 7 with nanomolar activity. Blockage of dye efflux from spherical bilayers by external Mg(OAc)(2) and internal 8-aminonaphthalene-1,3,6-trisulfonate is suggestive for weakly cooperative (n = 1.16) formation of aspartate-Mg(2+)-8-aminonaphthalene-1,3,6-trisulfonate complexes within the barrel-stave supramolecule (K(D) = 2.9 mM). Corroborative evidence from structural studies by circular dichroism spectroscopy is provided and discussed with emphasis of the importance of internal charge repulsion for pore formation and future applications toward binding and catalysis within supramolecular synthetic pores. PMID:11891277

  6. 17. INTAKE PIER, BRIDGE STRESS SHEET, SHEET 8 OF 117, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. INTAKE PIER, BRIDGE STRESS SHEET, SHEET 8 OF 117, 1920. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

  7. Laminated sheet composites reinforced with modular filament sheet

    NASA Technical Reports Server (NTRS)

    Reece, O. Y.

    1968-01-01

    Aluminum and magnesium composite sheet laminates reinforced with low density, high strength modular filament sheets are produced by diffusion bonding and explosive bonding. Both processes are accomplished in normal atmosphere and require no special tooling or cleaning other than wire brushing the metal surfaces just prior to laminating.

  8. Method for heating a glass sheet

    DOEpatents

    Boaz, Premakaran Tucker (Livonia, MI)

    1998-01-01

    A method for heating a glass sheet includes the steps of heating a glass sheet to a first predetermined temperature and applying microwave energy to the glass sheet to heat the glass sheet to at least a second predetermined temperature to allow the glass sheet to be formed.

  9. Method for heating a glass sheet

    DOEpatents

    Boaz, P.T.

    1998-07-21

    A method for heating a glass sheet includes the steps of heating a glass sheet to a first predetermined temperature and applying microwave energy to the glass sheet to heat the glass sheet to at least a second predetermined temperature to allow the glass sheet to be formed. 5 figs.

  10. High beta multipoles

    SciTech Connect

    Prager, S C

    1982-05-01

    Multipoles are being employed as devices to study fusion issues and plasma phenomena at high values of beta (plasma pressure/magnetic pressure) in a controlled manner. Due to their large volume, low magnetic field (low synchrotron radiation) region, they are also under consideration as potential steady state advanced fuel (low neutron yield) reactors. Present experiments are investigating neoclassical (bootstrap and Pfirsch-Schlueter) currents and plasma stability at extremely high beta.

  11. Evolution of the thin current sheet in a substorm observed by Geotail

    NASA Astrophysics Data System (ADS)

    Asano, Y.; Mukai, T.; Hoshino, M.; Saito, Y.; Hayakawa, H.; Nagai, T.

    2003-05-01

    Time evolution of a thin current sheet during a substorm is studied in the near-Earth magnetotail of X = -15 RE. Specifically, we study the thickness of the current sheet and its dynamical structure. Using the Geotail plasma data, we obtain the electric current density directly from both ion and electron velocity moments, and the thickness of the current sheet is evaluated from the Ampre's law with the pressure balance of the plasma sheet. It is found that the averaged thickness of the highly fluctuating current sheet becomes as thin as the ion inertial scale during the late growth phase and the early expansion phase. The current sheet temporally forms a double-peaked current sheet in which the current density becomes the largest away from the neutral sheet. We also found that the intense current is mainly carried by electrons, contrary to the ion-dominated diamagnetic current caused by the higher ion temperature than the electron one. We discuss that the Hall electric field plays an important role on the formation of the double-peaked current sheet. The Hall electric field toward the neutral sheet causes the electron dominated current sheet by enhancing the dawnward drift for both ion and electron.

  12. Atomic structure of Beta-tantalum nanocrystallites.

    PubMed

    Tillmann, Karsten; Thust, Andreas; Gerber, Andreas; Weides, Martin P; Urban, Knut

    2005-12-01

    The structural properties of beta-phase tantalum nanocrystallites prepared by room temperature magnetron sputter deposition on amorphous carbon substrates are investigated at atomic resolution. For these purposes spherical aberration-corrected high-resolution transmission electron microscopy is applied in tandem with the numerical retrieval of the exit-plane wavefunction as obtained from a through-focus series of experimental micrographs. We demonstrate that recent improvements in the resolving power of electron microscopes enable the imaging of the atomic structure of beta-tantalum with column spacings of solely 0.127 nm with directly interpretable contrast features. For the first time ever, we substantiate the existence of grain boundaries of 30 degrees tilt type in beta-Ta whose formation may be well explained by atomic agglomeration processes taking place during sputter deposition. PMID:17481332

  13. [Clip Sheets from BOCES. Opportunities. Health. Careers. = Oportunidades. Salud. Una Camera En...

    ERIC Educational Resources Information Center

    State Univ. of New York, Geneseo. Coll. at Geneseo. Migrant Center.

    This collection of 83 clip sheets, or classroom handouts, was created to help U.S. migrants learn more about health, careers, and general "opportunities" including education programs. They are written in both English and Spanish and are presented in an easily understandable format. Health clip-sheet topics include the following: Abuse; AIDS;…

  14. Reduced immunogenicity of beta-lactoglobulin by conjugation with acidic oligosaccharides.

    PubMed

    Hattori, Makoto; Miyakawa, Shunpei; Ohama, Yukie; Kawamura, Hiroyuki; Yoshida, Tadashi; To-o, Kenji; Kuriki, Takashi; Takahashi, Koji

    2004-07-14

    Bovine beta-lactoglobulin (beta-LG) was conjugated with the acidic oligosaccharides, alginic acid oligosaccharide (ALGO) and phosphoryl oligosaccharides (POs) by the Maillard reaction to reduce the immunogenicity of beta-LG. The molar ratios of beta-LG to ALGO and POs in the conjugates were 1:6 and 1:8. The carbohydrate-binding sites in the beta-LG-ALGO conjugate were partially identified to be (60)Lys, (77)Lys, (100)Lys, (138)Lys, and (141)Lys. The isoelectric point of each conjugate was lower than that of beta-LG. CD spectra indicated that the secondary structure of beta-LG was almost maintained after conjugation. The results of fluorescence studies indicated that the conformation around Trp had not changed in each conjugate and that the surface of each conjugate was covered with a saccharide chain. Structural analyses with monoclonal antibodies indicated that the conformation around (8)Lys-(19)Trp (beta-sheet, random coil, short helix) in the conjugates had changed, whereas the native structure was maintained around (15)Val-(29)Ile (beta-sheet) and (125)Thr-(135)Lys (alpha-helix). The beta-LG-ALGO and beta-LG-POs conjugates maintained 77 and 70% of the retinol binding activity of beta-LG. Conjugation with ALGO and POs substantially enhanced the thermal stability of beta-LG. The anti-beta-LG antibody response was markedly reduced after immunization with both conjugates in BALB/c, C57BL/6, and C3H/He mice. B cell epitopes of beta-LG and the conjugate recognized in these mice were determined with 15-mer multipin peptides, and the linear epitope profiles of the conjugates were found to be similar to those of beta-LG, whereas the antibody response to each epitope was dramatically reduced. In particular, effective reduction of the antibody response was observed in the vicinity of the carbohydrate-binding sites. Conjugation of beta-LG with these acidic oligosaccharides was effective in reducing the immunogenicity of beta-LG. The conjugates obtained in this study are edible, so they would be very useful for food application. PMID:15237965

  15. Active volcanism beneath the West Antarctic ice sheet and implications for ice-sheet stability

    USGS Publications Warehouse

    Blankenship, D.D.; Bell, R.E.; Hodge, S.M.; Brozena, J.M.; Behrendt, John C.; Finn, C.A.

    1993-01-01

    IT is widely understood that the collapse of the West Antarctic ice sheet (WAIS) would cause a global sea level rise of 6 m, yet there continues to be considerable debate about the detailed response of this ice sheet to climate change1-3. Because its bed is grounded well below sea level, the stability of the WAIS may depend on geologically controlled conditions at the base which are independent of climate. In particular, heat supplied to the base of the ice sheet could increase basal melting and thereby trigger ice streaming, by providing the water for a lubricating basal layer of till on which ice streams are thought to slide4,5. Ice streams act to protect the reservoir of slowly moving inland ice from exposure to oceanic degradation, thus enhancing ice-sheet stability. Here we present aerogeophysical evidence for active volcanism and associated elevated heat flow beneath the WAIS near the critical region where ice streaming begins. If this heat flow is indeed controlling ice-stream formation, then penetration of ocean waters inland of the thin hot crust of the active portion of the West Antarctic rift system could lead to the disappearance of ice streams, and possibly trigger a collapse of the inland ice reservoir.

  16. Plasma Relaxation Dynamics Moderated by Current Sheets

    NASA Astrophysics Data System (ADS)

    Dewar, Robert; Bhattacharjee, Amitava; Yoshida, Zensho

    2014-10-01

    Ideal magnetohydrodynamics (IMHD) is strongly constrained by an infinite number of microscopic constraints expressing mass, entropy and magnetic flux conservation in each infinitesimal fluid element, the latter preventing magnetic reconnection. By contrast, in the Taylor-relaxed equilibrium model all these constraints are relaxed save for global magnetic flux and helicity. A Lagrangian is presented that leads to a new variational formulation of magnetized fluid dynamics, relaxed MHD (RxMHD), all static solutions of which are Taylor equilibrium states. By postulating that some long-lived macroscopic current sheets can act as barriers to relaxation, separating the plasma into multiple relaxation regions, a further generalization, multi-relaxed MHD (MRxMHD), is developed. These concepts are illustrated using a simple two-region slab model similar to that proposed by Hahm and Kulsrud--the formation of an initial shielding current sheet after perturbation by boundary rippling is calculated using MRxMHD and the final island state, after the current sheet has relaxed through a reconnection sequence, is calculated using RxMHD. Australian Research Council Grant DP110102881.

  17. Preformed {beta}-amyloid fibrils are destabilized by coenzyme Q{sub 10} in vitro

    SciTech Connect

    Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu; Yamada, Masahito . E-mail: m-yamada@med.kanazawa-u.ac.jp

    2005-04-29

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fA{beta} formation from A{beta} and destabilize preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q{sub 10} (CoQ{sub 10}) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ{sub 10} with NDGA and Myr. CoQ{sub 10} dose-dependently inhibited fA{beta} formation from amyloid {beta}-peptide (A{beta}), as well as their extension. Moreover, it destabilized preformed fA{beta}s. The anti-amyloidogenic effects of CoQ{sub 10} were slightly weaker than those of NDGA and Myr. CoQ{sub 10} could be a key molecule for the development of therapeutics for AD.

  18. Silicone Coating on Polyimide Sheet

    NASA Technical Reports Server (NTRS)

    Park, J. J.

    1985-01-01

    Silicone coatings applied to polyimide sheeting for variety of space-related applications. Coatings intended to protect flexible substrates of solar-cell blankets from degradation by oxygen atoms, electrons, plasmas, and ultraviolet light in low Earth orbit and outer space. Since coatings are flexible, generally useful in forming flexible laminates or protective layers on polyimide-sheet products.

  19. Communication Fact Sheets for Parents.

    ERIC Educational Resources Information Center

    Stremel, Kathleen; Bixler, Betsy; Morgan, Susanne; Layton, Kristen

    This booklet contains 28 fact sheets on communication written primarily for parents and families with a child who is deaf-blind. They attempt to address fundamental but complex issues related to the communication needs of children with vision and hearing impairments. Each fact sheet targets a specific area, including: (1) communication; (2)

  20. Development of measurement technique for carbon atoms employing vacuum ultraviolet absorption spectroscopy with a microdischarge hollow-cathode lamp and its application to diagnostics of nanographene sheet material formation plasmas

    SciTech Connect

    Takeuchi, Wakana; Sasaki, Hajime; Takashima, Seigo; Kato, Satoru; Hiramatsu, Mineo; Hori, Masaru

    2009-06-01

    This study describes the development of a compact measurement technique for absolute carbon (C) atom density in processing plasmas, using vacuum ultraviolet absorption spectroscopy (VUVAS) employing a high-pressure CO{sub 2} microdischarge hollow-cathode lamp (C-MHCL) as the light source. The characteristics of the C-MHCL as a resonance line source of C atoms at 165.7 nm for VUVAS measurements of the absolute C atom density are reported. The emission line profile of the C-MHCL under typical operating conditions was estimated to be the Voigt profile with a DELTAnu{sub L}/DELTAnu{sub D} value of 2.5, where DELTAnu{sub L} is the Lorentz width and DELTAnu{sub D} is the Doppler width. In order to investigate the behavior of C and H atoms in the processing plasma used for the fabrication of two-dimensional nanographene sheet material, measurements of the atom densities were carried out using the VUVAS technique. The H atom density increased with increasing pressure, while the C atom density was almost constant at 5x10{sup 12} cm{sup -3}. The density ratio of C to H atoms in the plasma was found to influence the morphology of carbon nanowalls (CNWs). With increasing H/C density ratio, the growth rate decreased and the space between the walls of the CNWs became wider.

  1. Hyperspectral light sheet microscopy.

    PubMed

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O; Huisken, Jan

    2015-01-01

    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5?nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos. PMID:26329685

  2. Hyperspectral light sheet microscopy

    NASA Astrophysics Data System (ADS)

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O.; Huisken, Jan

    2015-09-01

    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos.

  3. Hyperspectral light sheet microscopy

    PubMed Central

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O.; Huisken, Jan

    2015-01-01

    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5?nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos. PMID:26329685

  4. The quantitative inspection of iron aluminide green sheet using transient thermography

    SciTech Connect

    Watkins, Michael L.; Hinders, Mark K.; Scorey, Clive; Winfree, William

    1999-12-02

    The recent development of manufacturing techniques for the fabrication of thin iron aluminide, FeAl, sheet requires advanced quantitative methods for on-line inspection. An understanding of the mechanisms responsible for flaws and the development of appropriate flaw detection methods are key elements in an effective quality management system. The first step in the fabrication of thin FeAl alloy sheet is the formation of a green sheet, either by cold rolling or tape casting FeAl powder mixed with organic binding agents. The finished sheet is obtained using a series of process steps involving binder elimination, densification, sintering, and annealing. Non-uniformities within the green sheet are the major contributor to material failure in subsequent sheet processing and the production of non-conforming finished sheet. Previous work has demonstrated the advantages of using active thermography to detect the flaws and heterogeneity within green powder composites (1)(2)(3). The production environment and physical characteristics of these composites provide for unique challenges in developing a rapid nondestructive inspection capability. Thermography is non-contact and minimizes the potential damage to the fragile green sheet. Limited access to the material also demands a one-sided inspection technique. In this paper, we will describe the application of thermography for 100% on-line inspection within an industrial process. This approach is cost competitive with alternative technologies, such as x-ray imaging systems, and provides the required sensitivity to the variations in material composition. The formation of green sheet flaws and their transformation into defects within intermediate and finished sheet products will be described. A green sheet conformance criterion will be presented which would significantly reduce the probability of processing poor quality green sheet which contributes to higher waste and inferior bulk alloy sheet.

  5. The quantitative inspection of iron aluminide green sheet using transient thermography

    NASA Astrophysics Data System (ADS)

    Watkins, Michael L.; Hinders, Mark K.; Scorey, Clive; Winfree, William

    1999-12-01

    The recent development of manufacturing techniques for the fabrication of thin iron aluminide, FeAl, sheet requires advanced quantitative methods for on-line inspection. An understanding of the mechanisms responsible for flaws and the development of appropriate flaw detection methods are key elements in an effective quality management system. The first step in the fabrication of thin FeAl alloy sheet is the formation of a green sheet, either by cold rolling or tape casting FeAl powder mixed with organic binding agents. The finished sheet is obtained using a series of process steps involving binder elimination, densification, sintering, and annealing. Non-uniformities within the green sheet are the major contributor to material failure in subsequent sheet processing and the production of non-conforming finished sheet. Previous work has demonstrated the advantages of using active thermography to detect the flaws and heterogeneity within green powder composites (1)(2)(3). The production environment and physical characteristics of these composites provide for unique challenges in developing a rapid nondestructive inspection capability. Thermography is non-contact and minimizes the potential damage to the fragile green sheet. Limited access to the material also demands a one-sided inspection technique. In this paper, we will describe the application of thermography for 100% on-line inspection within an industrial process. This approach is cost competitive with alternative technologies, such as x-ray imaging systems, and provides the required sensitivity to the variations in material composition. The formation of green sheet flaws and their transformation into defects within intermediate and finished sheet products will be described. A green sheet conformance criterion will be presented which would significantly reduce the probability of processing poor quality green sheet which contributes to higher waste and inferior bulk alloy sheet.

  6. Solubility enhancement of celecoxib using beta-cyclodextrin inclusion complexes.

    PubMed

    Rawat, Swati; Jain, Sanjay K

    2004-03-01

    Celecoxib has very low water solubility. It forms a complex with beta-cyclodextrin (betaCD) both in aqueous and in solid state. It was observed that due to formation of the inclusion complex, the solubility and dissolution rate of celecoxib were enhanced. The formation of 1:1 complex with betaCD in solution was confirmed by phase solubility and spectral shift studies. The apparent stability constants calculated by these techniques were 881.5 and 341.5 M(-1), respectively. The solid inclusion complexes of celecoxib and betaCD were prepared by the kneading method using different molar proportions of betaCD, and formation of solid inclusion complexes of celecoxib and betaCD at different molar ratios were confirmed by differential scanning calorimetry. Enhancement of dissolution rates with increasing quantity of betaCD in the complex was observed. It was also observed that the complexes exhibit higher dissolution rates than the pure drug and physical mixture. PMID:15018983

  7. Ganges Chasma Sand Sheet

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site]

    Our topic for the weeks of April 4 and April 11 is dunes on Mars. We will look at the north polar sand sea and at isolated dune fields at lower latitudes. Sand seas on Earth are often called 'ergs,' an Arabic name for dune field. A sand sea differs from a dune field in two ways: 1) a sand sea has a large regional extent, and 2) the individual dunes are large in size and complex in form.

    Today's sand sheet is located in the Ganges Chasma portion of Valles Marineris. As with yesterday's image, note that the dune forms are seen only at the margin and that the interior of the sand sheet at this resolution appears to completely lack dune forms.

    Image information: VIS instrument. Latitude -6.4, Longitude 310.7 East (49.3 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  8. Antiangiogenic effect of dual/selective alpha(5)beta(1)/alpha(v)beta(3) integrin antagonists designed on partially modified retro-inverso cyclotetrapeptide mimetics.

    PubMed

    Gentilucci, Luca; Cardillo, Giuliana; Spampinato, Santi; Tolomelli, Alessandra; Squassabia, Federico; De Marco, Rossella; Bedini, Andrea; Baiula, Monica; Belvisi, Laura; Civera, Monica

    2010-01-14

    Recent evidence highlighted the role of alpha(5)beta(1) integrin in angiogenesis and in regulating alpha(v)beta(3) integrin function. As a consequence, selective alpha(5)beta(1) integrin inhibitors or dual alpha(5)beta(1)/alpha(v)beta(3) integrin inhibitors are considered promising candidates for the development of cancer therapeutic agents. In this paper, we describe the synthesis and pharmacological characterization of a minilibrary of cyclotetrapeptide mimetics containing a PMRI Arg-Gly-Asp sequence. In particular, c[(R)-betaPhepsi(NHCO)Asppsi(NHCO)Gly-Arg] (3) displayed a good activity in inhibiting the alpha(v)beta(3) integrin-mediated cell adhesion of fibronectin or vitronectin, as well as the adhesion of fibronectin to the alpha(5)beta(1) integrin. Interestingly, the diastereomeric compound c[(S)-betaPhepsi(NHCO)Asppsi(NHCO)Gly-Arg] (2) maintained a good efficacy in inhibiting alpha(5)beta(1) integrin while gaining a certain selectivity over alpha(v)beta(3) integrin. These two integrin antagonists significantly inhibited bFGF-induced human endothelial cell tube formation at submicromolar concentrations. Conformational analysis and Molecular Docking calculations suggest that the different alpha(5)beta(1) versus alpha(v)beta(3) selectivity of 2 and 3 can be rationalized on the basis of the alternative display of the aromatic side chain adjacent to Asp. PMID:20055426

  9. Vitamin and Mineral Supplement Fact Sheets

    MedlinePLUS

    ... DRI Tool Daily Value (DV) Tables Vitamin and Mineral Supplement Fact Sheets A - E | F - L | M - S | ... Information Botanical Dietary Supplements: Background Information Vitamin and Mineral Fact Sheets Botanical Supplement Fact Sheets Frequently Asked ...

  10. Stem cell approaches for diabetes: towards beta cell replacement

    PubMed Central

    2011-01-01

    Stem cells hold great promise for pancreatic beta cell replacement therapy for diabetes. In type 1 diabetes, beta cells are mostly destroyed, and in type 2 diabetes beta cell numbers are reduced by 40% to 60%. The proof-of-principle that cellular transplants of pancreatic islets, which contain insulin-secreting beta cells, can reverse the hyperglycemia of type 1 diabetes has been established, and there is now a need to find an adequate source of islet cells. Human embryonic stem cells can be directed to become fully developed beta cells and there is expectation that induced pluripotent stem (iPS) cells can be similarly directed. iPS cells can also be generated from patients with diabetes to allow studies of the genomics and pathogenesis of the disease. Some alternative approaches for replacing beta cells include finding ways to enhance the replication of existing beta cells, stimulating neogenesis (the formation of new islets in postnatal life), and reprogramming of pancreatic exocrine cells to insulin-producing cells. Stem-cell-based approaches could also be used for modulation of the immune system in type 1 diabetes, or to address the problems of obesity and insulin resistance in type 2 diabetes. Herein, we review recent advances in our understanding of diabetes and beta cell biology at the genomic level, and we discuss how stem-cell-based approaches might be used for replacing beta cells and for treating diabetes. PMID:21951399

  11. Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity.

    PubMed

    Rajagopalan, Nandhakishore; Pung, Yuh Fen; Zhu, Yi Zhun; Wong, Peter Tsun Hon; Kumar, Prakash P; Kini, R Manjunatha

    2007-11-01

    Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a partial cDNA library from the mRNA of Ophiophagus hannah (king cobra) venom gland tissue and identified five new genes encoding proteins belonging to the three-finger toxin family of snake venom proteins. We have isolated and characterized one of these beta-sheet containing proteins with a mass of 7012.43 +/- 0.91 Da from the venom. The protein was nonlethal up to a dose of 10 mg/kg when injected intraperitoneally into Swiss albino mice. However, it induces labored breathing and death at a dose of 100 mg/kg. It does not show any hemolytic or anticoagulant activity. It caused a dose-dependent decrease of heart rate in vivo (anesthetized Sprague-Dawley rats) and also ex vivo (Langendorff isolated rat heart). This is in contrast to classical cardiotoxins from snake venom that increase the heart rate in animals. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a binding affinity (Ki) of 5.3 and 2.3 microM toward beta1 and beta2 subtypes, respectively, to bring about its effect, and hence, it was named as beta-cardiotoxin. This is the first report of a natural exogenous beta-blocker. PMID:17616557

  12. Amyloid formation of native folded protein induced by peptide-based graft copolymer.

    PubMed

    Koga, Tomoyuki; Taguchi, Kazuhiro; Kogiso, Masaki; Kobuke, Yoshiaki; Kinoshita, Takatoshi; Higuchi, Masahiro

    2002-11-01

    We report here that a native folded holo-myoglobin, when incubated with a synthetic amyloidogenic peptide in aqueous solutions, forms fibrils. These fibrils took a cross-beta form (inter-strand spacing: 4.65 A and inter-sheet spacing: 10.65 A) and bound the amyloidophilic dye Congo red as did the authentic amyloid fibrils. In contrast such fibril formation of myoglobin did not occur in the absence of the peptide. These results suggest the possibility that inter-molecular interaction of native protein with the amyloidogenic peptide trigger the amyloid formation even for the non-pathogenic native protein like myoglobin, which itself exists as a globular form, under certain conditions. PMID:12417301

  13. Penguin Fact Sheet.

    ERIC Educational Resources Information Center

    Flotsam and Jetsam: A Newsletter for Massachusetts Marine Educators, 1985

    1985-01-01

    Presents factual information on penguins using an outline format. Includes descriptions of physical characteristics, behavioral mechanisms, geographical distribution, and physiological processes. Provides separate bibliographies for teachers and students. (ML)

  14. Current sheet bifurcations observed by Cluster during plasma sheet flapping

    NASA Astrophysics Data System (ADS)

    Runov, A.; Sergeev, V.; Baumjohann, W.; Nakamura, R.; Balogh, A.; Klecker, B.; Reme, H.; Sauvaud, J.-A.; Andre, M.

    2003-04-01

    We examined the structure of the tail current sheet at XGSM-19~R_E using fast flapping oscillation. It was found that during 1055 -1107 UT on 29 August 2001 and 2220 - 2235 UT on 26 September 2001, following substorm intensifications, the flapping current sheet displayed a clearly bifurcated structure with current density peaks at |B_x|0.5~B_L and a pronounced broad current density minimum in between. In both cases the bifurcation was associated with the current sheet flapping in the Y-Z plane, with very large tilts (exceeding 45o). The origins of current bifurcation and of severe flapping motions are discussed.

  15. Amyloid Beta as a Modulator of Synaptic Plasticity

    PubMed Central

    Parihar, Mordhwaj S; Brewer, Gregory J

    2011-01-01

    Alzheimer’s disease is associated with synapse loss, memory dysfunction and pathological accumulation of amyloid beta in plaques. However, an exclusively pathological role for amyloid beta is being challenged by new evidence for an essential function of amyloid beta at the synapse. Amyloid beta protein exists in different assembly states in the central nervous system and plays distinct roles ranging from synapse and memory formation to memory loss and neuronal cell death. Amyloid beta is present in the brain of symptom-free people where it likely performs important physiological roles. New evidence indicates that synaptic activity directly evokes the release of amyloid beta at the synapse. At physiological levels, amyloid beta is a normal, soluble product of neuronal metabolism that regulates synaptic function beginning early in life. Monomeric amyloid beta 40 and 42 are the predominant forms required for synaptic plasticity and neuronal survival. With age, some assemblies of amyloid beta are associated with synaptic failure and Alzheimer’s disease pathology, possibly targeting the N-methyl-D-aspartic acid (NMDA) receptor through the α7-nicotinic acetylcholine receptor (α7-nAChR), mitochondrial amyloid-β alcohol dehydrogenase (ABAD) and cyclophilin D. But emerging data suggests a distinction between age effects on the target response in contrast to the assembly state or the accumulation of the peptide. Both aging and beta amyloid independently decrease neuronal plasticity. Our laboratory has reported that amyloid beta, glutamate and lactic acid are each increasingly toxic with neuron age. The basis of the age-related toxicity partly resides in age-related mitochondrial dysfunction and an oxidative shift in mitochondrial and cytoplasmic redox potential. In turn, signaling through phosphorylated extracellular signal-regulated protein kinases (pERK) is affected along with an age-independent increase in phosphorylated cAMP response element-binding protein (pCREB) This review examines the long-awaited functional impact of amyloid beta on synaptic plasticity. PMID:20847424

  16. Boosted Beta Regression

    PubMed Central

    Schmid, Matthias; Wickler, Florian; Maloney, Kelly O.; Mitchell, Richard; Fenske, Nora; Mayr, Andreas

    2013-01-01

    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. PMID:23626706

  17. Transient Surface Tension of an Expanding Liquid Sheet.

    PubMed

    Marmottant; Villermaux; Clanet

    2000-10-01

    We address the problem of dynamic surface tension using measurements of sheet diameters that results from the impact of a liquid jet of diameter d(0) on a small disk of diameter d(i) (d(i)/d(0) approximately 4). At low velocities, the sheet diameter D is related to d(0) by the Weber number We, constructed with the liquid density rho, the jet velocity u(0), and the surface tension sigma at the rim: D/d(0)=18 We=18 [rho u(0)(2)/(sigma/d(0))]. This relation expresses the equilibrium between inertial forces and surface tension forces at the sheet rim. When a surfactant has been dissolved in the bulk of the liquid prior to the formation of the initial jet, the rim surface tension, and therefore the sheet diameter, depends on the amount of surfactant adsorbed at the rim. This amount is fixed by a competition between surface formation induced by radial extension and repopulation of the liquid interface in surfactant. The experimental setup proposed here provides a method to measure dynamic surface tension from sheet diameter measurements and symmetrically to monitor the adsorption of a surfactant on a liquid surface. The available adsorption time ranges from 10 to 100 ms. Experimental data obtained with two surfactants are in agreement with a model of a diffusion-controlled adsorption at the interface. Copyright 2000 Academic Press. PMID:10998285

  18. Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia

    PubMed Central

    Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

    2015-01-01

    The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering. PMID:25755694

  19. Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia.

    PubMed

    Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

    2015-01-01

    The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering. PMID:25755694

  20. Hypoxia Created Human Mesenchymal Stem Cell Sheet for Prevascularized 3D Tissue Construction.

    PubMed

    Zhang, Lijun; Xing, Qi; Qian, Zichen; Tahtinen, Mitchell; Zhang, Zhaoqiang; Shearier, Emily; Qi, Shaohai; Zhao, Feng

    2016-02-01

    3D tissue based on human mesenchymal stem cell (hMSC) sheets offers many interesting opportunities for regenerating multiple types of connective tissues. Prevascularizing hMSC sheets with endothelial cells (ECs) will improve 3D tissue performance by supporting cell survival and accelerating integration with host tissue. It is hypothesized that hypoxia cultured hMSC sheets can promote microvessel network formation and preserve stemness of hMSCs. This study investigates the vascularization of hMSC sheets under different oxygen tensions. It is found that the HN condition, in which hMSC sheets formed under physiological hypoxia (2% O2 ) and then cocultured with ECs under normoxia (20% O2 ), enables longer and more branched microvessel network formation. The observation is corroborated by higher levels of angiogenic factors in coculture medium. Additionally, the hypoxic hMSC sheet is more uniform and less defective, which facilitates fabrication of 3D prevascularized tissue construct by layering the prevascularized hMSC sheets and maturing in rotating wall vessel bioreactor. The hMSCs in the 3D construct still maintain multilineage differentiation ability, which indicates the possible application of the 3D construct for various connective tissues regeneration. These results demonstrate that hypoxia created hMSC sheets benefit the microvessel growth and it is feasible to construct 3D prevascularized tissue construct using the prevascularized hMSC sheets. PMID:26663707

  1. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair.

    PubMed Central

    Pierce, G. F.; Tarpley, J. E.; Yanagihara, D.; Mustoe, T. A.; Fox, G. M.; Thomason, A.

    1992-01-01

    Recombinant platelet-derived growth factor (BB homodimer, rPDGF-BB), transforming growth factor beta 1 (rTGF-beta 1), and basic fibroblast growth factor (rbFGF) can accelerate healing of soft tissues. However, little information is available characterizing the components of wound matrix induced by these growth factors and the molecular mechanisms underlying accelerated repair and wound maturation. In this study, the composition, quantity, and rate of extracellular matrix deposition within growth factor-treated lapine ear excisional wounds were analyzed at different stages of healing using specific histochemical and immunohistochemical stains, coupled with image analysis techniques. Single application of optimal concentrations of each growth factor accelerated normal healing by 30% (P less than 0.0003); rPDGF-BB markedly augmented early glycosaminoglycan (GAG) and fibronectin deposition, but induced significantly greater levels of collagen later in the repair process, compared with untreated wounds rTGF-beta 1 treatment led to rapidly enhanced collagen synthesis and maturation, without increased GAG deposition. In contrast, rbFGF treatment induced a predominantly angiogenic response in wounds, with a marked increase in endothelia and neovessels (P less than 0.0001), and increased wound collagenolytic activity (P less than 0.03). rbFGF-treated wounds did not evolve into collagen-containing scars and continued to accumulate only provisional matrix well past wound closure. These results provide new evidence that growth factors influence wound repair via different mechanisms: 1) rPDGF-BB accelerates deposition of provisional wound matrix; 2) rTGF-beta 1 accelerates deposition and maturation of collagen; and 3) rbFGF induces a profound monocellular angiogenic response which may lead to a marked delay in wound maturation, and the possible loss of the normal signal(s) required to stop repair. These results suggest that specific growth factors may selectively regulate components of the repair response by differing mechanisms, offering the potential for targeted therapeutic intervention. Images Figure 4 Figure 4 Figure 7 PMID:1376557

  2. Inviscid Edge Receeding of an Initially Stationary Two-Dimensional Fluid Sheet

    NASA Astrophysics Data System (ADS)

    Song, Museok

    2002-11-01

    A two-dimensional numerical method for inviscid two-fluid flows with evolution of density interface is developed, and an initially stationary two-dimensional fluid sheet surrounded by another fluid is studied. The interface between two fluids is modeled as a vortex sheet, and the flow field with the evolution of interface is solved by using vortex-in-cell/front-tracking method. The edge of the sheet is pulled back into the sheet due to surface tension and a blob is formed at the edge. This blob and fluid sheet are connected by a thin neck. In the inviscid limit, such process of the blob and neck formation is examined in detail and their kinematic characteristics are summarized with dimensionless parameters. The edge recedes at V = 1.06 ( ? / ? H )^0.5 and the capillary wave propagating into the fluid sheet needs to be considered for better understanding of the edge receding.

  3. Theoretical modeling of the plasma-assisted catalytic growth and field emission properties of graphene sheet

    NASA Astrophysics Data System (ADS)

    Sharma, Suresh C.; Gupta, Neha

    2015-12-01

    A theoretical modeling for the catalyst-assisted growth of graphene sheet in the presence of plasma has been investigated. It is observed that the plasma parameters can strongly affect the growth and field emission properties of graphene sheet. The model developed accounts for the charging rate of the graphene sheet; number density of electrons, ions, and neutral atoms; various elementary processes on the surface of the catalyst nanoparticle; surface diffusion and accretion of ions; and formation of carbon-clusters and large graphene islands. In our investigation, it is found that the thickness of the graphene sheet decreases with the plasma parameters, number density of hydrogen ions and RF power, and consequently, the field emission of electrons from the graphene sheet surface increases. The time evolution of the height of graphene sheet with ion density and sticking coefficient of carbon species has also been examined. Some of our theoretical results are in compliance with the experimental observations.

  4. Synthesis of akageneite (beta-FeOOH)/reduced graphene oxide nanocomposites for oxidative decomposition of 2-chlorophenol by Fenton-like reaction.

    PubMed

    Xiao, Feng; Li, Wentao; Fang, Liping; Wang, Dongsheng

    2016-05-01

    In this work, the composite of reduced graphene oxide and akageneite (Ak/rGO) was synthesised by co-precipitating and reduction processes. The morphological and structural features of the synthesized composites (Ak/rGO) were characterized by XRD, SEM, BET, FTIR, Zeta potential and XPS. The results revealed that (1) beta-FeOOH was successfully loaded on the reduced graphene oxide (rGO); (2) the presence of strong interfacial interactions (FeOC bonds) between rGO and beta-FeOOH was observed; (3) the reduction of graphene oxide may be inhabited in the formation process of beta-FeOOH, producing rGO sheets rather than rGO sphere. In the heterogeneous Fenton-like reaction, the degradation rate constants of 2-chlorophenol (2-CP) increased 2-5 times after the addition of rGO probably due to the FeOC bond. The increase of the content of rGO could contribute to the removal of 2-CP, due to the synergy of catalysis and 2-CP adsorption towards Ak/rGO. In this study, the Ak/rGO composite has exhibited great potential and significant prospects for environmental application. PMID:26808238

  5. Microcomponent chemical process sheet architecture

    DOEpatents

    Wegeng, Robert S. (Richland, WA); Drost, M. Kevin (Richland, WA); Call, Charles J. (Pasco, WA); Birmingham, Joseph G. (Richland, WA); McDonald, Carolyn Evans (Richland, WA); Kurath, Dean E. (Benton County, WA); Friedrich, Michele (Prosser, WA)

    1998-01-01

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one chemical process unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation.

  6. Microcomponent chemical process sheet architecture

    DOEpatents

    Wegeng, R.S.; Drost, M.K.; Call, C.J.; Birmingham, J.G.; McDonald, C.E.; Kurath, D.E.; Friedrich, M.

    1998-09-22

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one chemical process unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation. 26 figs.

  7. Selectively reflective transparent sheets

    NASA Astrophysics Data System (ADS)

    Wach, Rmi; Florescu, Marian; Sweeney, Stephen J.; Clowes, Steven K.

    2015-08-01

    We investigate the possibility to selectively reflect certain wavelengths while maintaining the optical properties on other spectral ranges. This is of particular interest for transparent materials, which for specific applications may require high reflectivity at pre-determined frequencies. Although there exist currently techniques such as coatings to produce selective reflection, this work focuses on new approaches for mass production of polyethylene sheets which incorporate either additives or surface patterning for selective reflection between 8 to 13 ? m. Typical additives used to produce a greenhouse effect in plastics include particles such as clays, silica or hydroxide materials. However, the absorption of thermal radiation is less efficient than the decrease of emissivity as it can be compared with the inclusion of Lambertian materials. Photonic band gap engineering by the periodic structuring of metamaterials is known in nature for producing the vivid bright colors in certain organisms via strong wavelength-selective reflection. Research to artificially engineer such structures has mainly focused on wavelengths in the visible and near infrared. However few studies to date have been carried out to investigate the properties of metastructures in the mid infrared range even though the patterning of microstructure is easier to achieve. We present preliminary results on the diffuse reflectivity using FDTD simulations and analyze the technical feasibility of these approaches.

  8. The metabolism of [4-14C]5-androstene-3 beta, 17 beta-diol by normal human skin in vitro.

    PubMed

    Faredin, I; Tth, I

    1975-01-01

    Healthy female and male abdominal skin slices were incubated with [4-14C]5-androstene-3 beta, 17 beta-diol. With a reverse isotope dilution method the following metabolites were isolated and identified: 5 alpha-androstane-3,17-dione, 4-androstene-3, 17-dione, 5 alpha-dihydrotestosterone, dehydroepiandrosterone, androsterone, testosterone, 7-keto-5-androstene-3beta, 17 beta-diol, 7 alpha-hydroxydehydroepiandrosterone sulphate and 5-androstene-3 beta, 17 beta-diol-3-sulphate. The amounts of the metabolites formed showed that [4-14C]5-androstene-3 beta, 17 beta-diol was metabolized in different ways by healthy female and male abdominal skin slices. In female skin the main direction of metabolism leads to the formation of androgenic steroids, while in male skin the main biosynthetic route is the C7-oxidation of the substrate. The fact that 5-androstene-3beta, 17 beta-diol is transformed to a considerable extent to testosterone and 5 alpha-dihydrotestosterone proves that in human skin 5-androstene-3 beta, 1m beta-diol is a better precursor of the androgenic steroids than dehydroepiandrosterone or 4-androstene-3, 17-dione. PMID:1235221

  9. The presence of a novel protein in calf serum that recognizes beta amyloid in the formalin-fixed section.

    PubMed Central

    Kanemaru, K.; Hasegawa, M.; Shimada, H.; Ihara, Y.

    1990-01-01

    Here we report on a monoclonal antibody, H6-33, that labels various beta-amyloid plaques, including diffuse plaques in the formalin-fixed, paraffin-embedded section from the brain affected with Alzheimer's disease (AD), without formic acid pretreatment. H6-33 also labels some neurofibrillary tangles and all kuru plaques in Gerstmann-Sträussler-Scheinker disease. In sharp contrast, H6-33 did not stain beta amyloid in the leptomeningeal vessel. For specific staining, H6-33 required the presence of fetal calf serum and it was necessary for beta amyloid to be formalin fixed. These results suggest that a novel protein in the calf serum, CSX, binds formalin-fixed beta amyloid, followed by H6-33 binding. The detection of beta amyloid by CSX was nullified by formic acid pretreatment of the tissue section. In accordance with this, CSX reacted only with a polymer form of synthetic beta peptide after fixation, but not with native beta-protein or beta-peptide monomer. These observations strongly suggest that 1) meningovascular beta amyloid should have a beta-pleated sheet structure somewhat dissimilar to that of beta-amyloid cores; and 2) most, if not all, of beta-protein immunoreactivities of diffuse plaques in AD sections are presumably derived from small amounts of amyloid fibrils scattered in the normal-looking neurohil. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1698030

  10. Ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations.

    PubMed

    Bush, L M; Johnson, C C

    2000-06-01

    Although research and development of new penicillins have declined, penicillins continue to be essential antibiotics for the treatment and prophylaxis of infectious diseases. The most recent additions are the ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations. This article reviews the spectrum of activity, toxicity, pharmacokinetics, and clinical uses of the ureidopenicillins, and the beta-lactam/beta-lactamase inhibitor combination agents. PMID:10829263

  11. SEER Cancer Stat Fact Sheets

    Cancer.gov

    Cancer Statistical Fact Sheets are summaries of common cancer types developed to provide an overview of frequently-requested cancer statistics including incidence, mortality, survival, stage, prevalence, and lifetime risk.

  12. Analysis of a Sheet Silicate.

    ERIC Educational Resources Information Center

    Adams, J. M.; Evans, S.

    1980-01-01

    Describes a student project in analytical chemistry using sheet silicates. Provides specific information regarding the use of phlogopite in an experiment to analyze samples for silicon, aluminum, magnesium, iron, potassium, and fluoride. (CS)

  13. Measurements and Characterization (Fact Sheet)

    SciTech Connect

    Not Available

    2011-06-01

    Capabilities fact sheet for the National Center for Photovoltaics: Measurements and Characterization that includes scope, core competencies and capabilities, and contact/web information for Analytical Microscopy, Electro-Optical Characterization, Surface Analysis, and Cell and Module Performance.

  14. Deep Space 1 (fact sheet)

    NASA Technical Reports Server (NTRS)

    Fisher, D. K.

    1998-01-01

    Exerting less force than does a single sheet of paper resting in your hand, Deep Space 1's ion propulsion system will slowly, yet continuously accelerate the spacecraft well beyond speeds attainable by conventional chemical propulsion.

  15. Concentrating Solar Power (Fact Sheet)

    SciTech Connect

    Not Available

    2010-08-01

    Fact sheet describing the overall capabilities of the NREL CSP Program: collector/receiver characterization, advanced reflector and absorber materials, thermal storage and advanced heat transfer fluids, and CSP modeling and analysis.

  16. A facile liquid phase exfoliation method to prepare graphene sheets with different sizes expandable graphite

    SciTech Connect

    Zhou, Keqing; Shi, Yongqian; Jiang, Saihua; Song, Lei; Hu, Yuan; Gui, Zhou

    2013-09-01

    Graphical abstract: - Highlights: This study presented a novel method for the production of high-quality graphene sheets through the exfoliation of Li-intercalated EG with sonication. The quality of the graphene sheets produced from different sizes EG was compared for the first time and the formation mechanism was discussed. The graphene sheets obtained from the small size EG have less layers than the large size EG. - Abstract: In this work, graphene sheets suspension were synthesized directly from expandable graphite (EG) via an intercalation and exfoliation pathway using n-butyl lithium as the intercalating agent, water and N,N-dimethylformamide (DMF) as the exfoliating agent. The quality of the graphene sheets produced from different sizes EG was compared and the formation mechanism was discussed. The formation of the graphene sheets and its formation mechanism were confirmed by transmission electron microscopy (TEM), high-resolution TEM (HRTEM), selected area electron diffraction (SAED), Raman spectroscopy measurement, inductively coupled plasma atomic emission spectrometry (ICP-AES) and thermogravimetric analysis (TGA). The graphene sheets obtained from the small size EG have less layers than the large size EG.

  17. Tracking debris disks within the Beta Pictoris Moving Group

    NASA Astrophysics Data System (ADS)

    Debes, J.

    2014-09-01

    Beta Pictoris represents a stunning example of a young planetary system with a debris disk, moving through local space with a host of other co-eval companion stars. These fellow travelers provide additional understanding for placing the Beta Pictoris disk into a proper context with regards to planet formation throughout the galaxy and our own Solar System. I will review the members of the Beta Pictoris moving group and catalog the latest results regarding the presence and understanding of debris disks around these other systems. Since these stars are close and very young, they represent an excellent opportunity for understanding the structure, composition, and grain properties of debris disks.

  18. State Fact Sheets (Women)

    MedlinePLUS

    ... V ( IL , IN , MI , MN , OH , WI ) Region VI ( AR , LA , NM , OK , TX ) Region VII ( IA , KS , MO , NE ) Region VIII ( CO , MT , ND , SD , UT , WY ) Region IX ( AZ , CA , HI , NV ) Region X ( AK , ID , OR , WA ) These reports are provided in PDF format, available free from Adobe Acrobat. Download a ...

  19. Energy information sheets, July 1998

    SciTech Connect

    1998-07-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  20. Energy information sheets, September 1996

    SciTech Connect

    1996-09-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  1. Beta limits for torsatrons

    SciTech Connect

    Bauer, F.; Betancourt, O.; Garabedian, P.; Shohet, J.L.

    1981-01-01

    An ideal magnetohydrodynamic equilibrium and stability code is used to study ballooning modes in torsatrons. The most dangerous modes turn out to be those with low poloidal and toroidal wave numbers. Beta limits for equilibrium and stability are determined for an l = 2 ultimate torsatron with large l = 1 and l = 3 sidebands.

  2. beta-Propiolactone

    Integrated Risk Information System (IRIS)

    beta - Propiolactone ; CASRN 57 - 57 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  3. beta-Chloronaphthalene

    Integrated Risk Information System (IRIS)

    beta - Chloronaphthalene ; CASRN 91 - 58 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcin

  4. Trichoderma .beta.-glucosidase

    DOEpatents

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

    2006-01-03

    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.

  5. Applied Beta Dosimetry

    SciTech Connect

    Rich, B.L.

    1986-01-01

    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. Osteoblast-like cell proliferation on tape-cast and sintered tricalcium phosphate sheets.

    PubMed

    Tanimoto, Yasuhiro; Shibata, Yo; Kataoka, Yu; Miyazaki, Takashi; Nishiyama, Norihiro

    2008-03-01

    The influence of sintering temperature on the in vitro proliferation of osteoblast-like cells to sintered tricalcium phosphate (TCP) sheets prepared by tape-casting was investigated. Green sheets of tape-cast beta-TCP were sintered for 2h in a furnace at atmospheric pressure at five different sintering temperatures: 900, 1000, 1100, 1150 and 1200 degrees C. The number of osteoblast-like (MC3T3-E1) cells deposited onto TCP sheets was counted after cell cultivation for 1week and was found to have increased with increasing sintering temperature. The TCP sheets sintered at 900 degrees C exhibited a significantly lower cell number than TCP sheets sintered at 1000, 1100, 1150 and 1200 degrees C. In the attenuated total reflection infrared spectra, the peaks around 900-1150cm(-1), corresponding to the P-O vibration mode of the phosphate group, gradually decreased and shifted to lower wavenumbers with increasing sintering temperature. Meanwhile, the zeta potential of TCP sintered at 900 degrees C showed a highly negative charge when compared with the other groups. This would suggest that the higher solubility of the TCP sheets sintered at 900 degrees C exerted the higher negative charge obtained from zeta potential measurement. Within the limitations of this study, it was indicated that osteoblast-like cell proliferation increased with increasing sintering temperature. The biological stability of the sintered TCP sheet surface was considered to have affected cell proliferation. PMID:18054299

  7. Magnetic Reconnection in the Solar Wind at Current Sheets Associated with Extremely Small Field Shear Angles

    NASA Astrophysics Data System (ADS)

    Gosling, J. T.; Phan, T. D.

    2012-12-01

    Using Wind 3-s plasma and magnetic field data, we have identified three reconnection exhausts within a large magnetic flux rope embedded within an interplanetary coronal mass ejection in the solar wind on 19 October 1998. These exhausts were associated with current sheets having local field shear angles ranging from 4.1 to 9.3 degrees, the smallest field shear angles (strongest guide fields) yet associated with identified reconnection exhausts in a space plasma. They were observed in plasma characterized by extremely low (<0.01) proton beta and very high (281 - 383 km/s) Alfvn speed. The very low external plasma beta in these events minimized the effect of diamagnetic drift of the X-line and thus allowed reconnection to occur in a sustained fashion. And, the very high external Alfvn speed translated into sufficiently fast (> 10 km/s) exhaust jets that could be adequately resolved by the Wind 3DP plasma experiment. Thin, very small field shear-angle current sheets are common in the solar wind, but typically are not associated with particularly low plasma beta or particularly high Alfvn speeds. On the other hand, small field shear angle current sheets must also be dominant in topologically complex environments such as the solar corona where the plasma beta is often less than 0.01 and the Alfvn speed is high. Our observations thus suggest that reconnection at thin, low field shear angle current sheets should commonly occur in the corona, and lend some credence to models that suggest that reconnection at low field shear angle current sheets contributes substantially to coronal heating.

  8. Surface behavior and lipid interaction of Alzheimer beta-amyloid peptide 1-42: a membrane-disrupting peptide.

    PubMed

    Ambroggio, Ernesto E; Kim, Dennis H; Separovic, Frances; Barrow, Colin J; Barnham, Kevin J; Bagatolli, Luis A; Fidelio, Gerardo D

    2005-04-01

    Amyloid aggregates, found in patients that suffer from Alzheimer's disease, are composed of fibril-forming peptides in a beta-sheet conformation. One of the most abundant components in amyloid aggregates is the beta-amyloid peptide 1-42 (Abeta 1-42). Membrane alterations may proceed to cell death by either an oxidative stress mechanism, caused by the peptide and synergized by transition metal ions, or through formation of ion channels by peptide interfacial self-aggregation. Here we demonstrate that Langmuir films of Abeta 1-42, either in pure form or mixed with lipids, develop stable monomolecular arrays with a high surface stability. By using micropipette aspiration technique and confocal microscopy we show that Abeta 1-42 induces a strong membrane destabilization in giant unilamellar vesicles composed of palmitoyloleoyl-phosphatidylcholine, sphingomyelin, and cholesterol, lowering the critical tension of vesicle rupture. Additionally, Abeta 1-42 triggers the induction of a sequential leakage of low- and high-molecular-weight markers trapped inside the giant unilamellar vesicles, but preserving the vesicle shape. Consequently, the Abeta 1-42 sequence confers particular molecular properties to the peptide that, in turn, influence supramolecular properties associated to membranes that may result in toxicity, including: 1), an ability of the peptide to strongly associate with the membrane; 2), a reduction of lateral membrane cohesive forces; and 3), a capacity to break the transbilayer gradient and puncture sealed vesicles. PMID:15681641

  9. Cryosphere: Warming ocean erodes ice sheets

    NASA Astrophysics Data System (ADS)

    Kusahara, Kazuya

    2016-01-01

    Antarctic ice sheets are a key player in sea-level rise in a warming climate. Now an ice-sheet modelling study clearly demonstrates that an Antarctic ice sheet/shelf system in the Atlantic Ocean will be regulated by the warming of the surrounding Southern Ocean, not by marine-ice-sheet instability.

  10. FDTD modeling of thin impedance sheets

    NASA Technical Reports Server (NTRS)

    Luebbers, Raymond J.; Kunz, Karl S.

    1991-01-01

    Thin sheets of resistive or dielectric material are commonly encountered in radar cross section calculations. Analysis of such sheets is simplified by using sheet impedances. In this paper it is shown that sheet impedances can be modeled easily and accurately using Finite Difference Time Domain (FDTD) methods.

  11. The effect of tachykinin neuropeptides on amyloid {beta} aggregation

    SciTech Connect

    Flashner, Efrat; Raviv, Uri; Friedler, Assaf

    2011-04-01

    Research highlights: {yields} Mechanistic explanation of how tachykinin neuropeptides reduce A{beta}-induced neurotoxicity. {yields} Biophysical studies suggest that tachykinins do not modulate the distribution of A{beta} oligomeric states, but rather may incorporate into the fibrils. {yields} A possible strategy to inhibit toxicity of amyloid fibrils. -- Abstract: A hallmark of Alzheimer's disease is production of amyloid {beta} peptides resulting from aberrant cleavage of the amyloid precursor protein. Amyloid {beta} assembles into fibrils under physiological conditions, through formation of neurotoxic intermediate oligomers. Tachykinin peptides are known to affect amyloid {beta} neurotoxicity in cells. To understand the mechanism of this effect, we studied how tachykinins affect A{beta}(1-40) aggregation in vitro. Fibrils grown in the presence of tachykinins exhibited reduced thioflavin T (ThT) fluorescence, while their morphology, observed in transmission electron microscopy (TEM), did not alter. Cross linking studies revealed that the distribution of low molecular weight species was not affected by tachykinins. Our results suggest that there may be a specific interaction between tachykinins and A{beta}(1-40) that allows them to co-assemble. This effect may explain the reduction of A{beta}(1-40) neurotoxicity in cells treated with tachykinins.

  12. Beta-2 Microglobulin Tumor Marker

    MedlinePLUS

    ... limited. Home Visit Global Sites Search Help? Beta-2 Microglobulin Tumor Marker Share this page: Was this page helpful? Also known as: B2M; B 2 M; β2-Microglobulin; Thymotaxin Formal name: Beta 2 ...

  13. Interferon Beta-1b Injection

    MedlinePLUS

    Interferon beta-1b injection is used to reduce episodes of symptoms in patients with relapsing-remitting multiple ... and problems with vision, speech, and bladder control). Interferon beta-1b is in a class of medications ...

  14. Manufacturing Laboratory (Fact Sheet)

    SciTech Connect

    Not Available

    2011-10-01

    This fact sheet describes the purpose, lab specifications, applications scenarios, and information on how to partner with NREL's Manufacturing Laboratory at the Energy Systems Integration Facility. The Manufacturing Laboratory at NREL's Energy Systems Integration Facility (ESIF) focuses on developing methods and technologies that will assist manufacturers of hydrogen and fuel cell technologies, as well as other renewable energy technologies, to scale up their manufacturing capabilities to volumes that meet DOE and industry targets. Specifically, the manufacturing activity is currently focused on developing and validating quality control techniques to assist manufacturers of low temperature and high temperature fuel cells in the transition from low to high volume production methods for cells and stacks. Capabilities include initial proof-of-concept studies through prototype system development and in-line validation. Existing diagnostic capabilities address a wide range of materials, including polymer films, carbon and catalyst coatings, carbon fiber papers and wovens, and multi-layer assemblies of these materials, as well as ceramic-based materials in pre- or post-fired forms. Work leading to the development of non-contact, non-destructive techniques to measure critical dimensional and functional properties of fuel cell and other materials, and validation of those techniques on the continuous processing line. This work will be supported by materials provided by our partners. Looking forward, the equipment in the laboratory is set up to be modified and extended to provide processing capabilities such as coating, casting, and deposition of functional layers, as well as associated processes such as drying or curing. In addition, continuous processes are used for components of organic and thin film photovoltaics (PV) as well as battery technologies, so synergies with these important areas will be explored.

  15. FDTD modeling of thin impedance sheets

    NASA Technical Reports Server (NTRS)

    Luebbers, Raymond; Kunz, Karl

    1991-01-01

    Thin sheets of resistive or dielectric material are commonly encountered in radar cross section calculations. Analysis of such sheets is simplified by using sheet impedances. It is shown that sheet impedances can be modeled easily and accurately using Finite Difference Time Domain (FDTD) methods. These sheets are characterized by a discontinuity in the tangential magnetic field on either side of the sheet but no discontinuity in tangential electric field. This continuity, or single valued behavior of the electric field, allows the sheet current to be expressed in terms of an impedance multiplying this electric field.

  16. Younger Dryas interval and outflow from the Laurentide ice sheet

    USGS Publications Warehouse

    Moore, T.C., Jr.; Walker, J.C.G.; Rea, David K.; Lewis, C.F.M.; Shane, L.C.K.; Smith, A.J.

    2000-01-01

    A boxmodel of the Great Lakes is used to estimate meltwater flow into the North Atlantic between 8000 and 14,000 calendar years B.P. Controls on the model include the oxygen isotopic composition of meltwaters and lake waters as measured in the shells of ostracodes. Outflow rates are highest when oxygen isotopic values of the lake waters are most negative, denoting a maximum glacial meltwater component. Flow rates reach maximum values before the onset of the Younger Dryas and after it ends. These maxima appear to be correlative with the major meltwater pulses MWP 1A and 1B. Although the resumption of North Atlantic Deep Water formation may be tied to the reduction in ice sheet melting, neither the onset nor the end of the Younger Dryas, as recorded in the Greenland Ice Sheet Project (GISP2) records, appear tied to maxima in meltwater outflow from the Laurentide ice sheet. Copyright 2000 by the American Geophysical Union.

  17. Dynamic of Current Sheets and Their Associated Particle Energization

    SciTech Connect

    Li, Hui; Guo, Fan; Makwan, Kirit; Li, Xiaocan; Zhandrin, Vladimir; Daughton, William Scott

    2015-08-19

    Magnetic reconnection in current sheets has relevance to Earth's magnetosphere, solar flares, high-energy astrophysics (pulsar wind nebula (e.g. Crab Nebula), gamma-ray bursts, black hole jets), and laboratory plasma/fusion. Data are shown for several cases with varying values of configuration energy Ec and β. Several conclusions were drawn: Depending on the “configuration energy”, the formation, shape, and lifetime of current sheets can vary. Plasma condition (configuration, β, driving, etc.) strongly affect the efficiency of particle acceleration. For low β and general “configuration energy”, particle heating is expected. For low β, large and long-lived current sheets, it is possible to produce highly non-thermal particles via collisionless plasmoid reconnection.

  18. Misleading Betas: An Educational Example

    ERIC Educational Resources Information Center

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael

    2012-01-01

    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the

  19. Mechanism of reconstitution of the apo beta 2 subunit and the alpha 2 apo beta 2 complex of tryptophan synthase with pyridoxal 5'-Phosphate: kinetic studies.

    PubMed

    Bartholmes, P; Balk, H; Kirschner, K

    1980-09-16

    The mechanism of pryidoxal 5'-phosphate (PLP) binding to both the alpha apo beta 2 complex and the apo beta 2 subunit of tryptophan synthase was investigated by rapid mixing experiments. Absorption and fluorescence changes were used to monitor the binding reaction directly. Reduction with sodium borohydride provided the rate of formation of the internal aldimine with the lysine amino group of the enzyme, and substrate turnover monitored the rate of formation of active enzyme. The alpha 2 apo beta 2 complex binds PLP in a sequence of three steps of decreasing rate: formation of a noncovalent complex, which isomerizes to an enzymically inactive internal aldimine, followed by formation of an active alpha 2 holo beta 2 complex. The two binding sites appear to bind PLP independently. The apo beta 2 subunit binds PLP cooperatively in a sequence of three steps of decreasing rate: formation of a noncovalent complex, which isomerizes to an enzymically inactive internal aldimine, followed by the formation of the enzymically active holo beta 2 subunit. Taken together with kinetic studies of pyridoxine phosphate binding [Tschopp, J., & Kirschner, K. (1980) Biochemistry (second paper of three in this issue)], the rate data of the apo beta 2 subunit are shown to be consistent with the concerted mechanism. The difference between the values of the isomerization rate constants of bound PLP and bound PNP appear to result from the covalent internal aldimine, which is formed with PLP but not with PNP. PMID:6996721

  20. Global ice-sheet system interlocked by sea level

    SciTech Connect

    Denton, G.H.; Hughes, T.J.; Karlen, W.

    1986-01-01

    Denton and Hughes postulated that sea level linked a global ice-sheet system with both terrestrial and grounded marine components during later Quaternary ice ages. Summer temperature changes near Northern Hemisphere melting margins initiated sea-level fluctuations that controlled marine components in both polar hemispheres. It was further proposed that variations of this ice-sheet system amplified and transmitted Milankovitch summer half-year insolation changes between 45 and 75/sup 0/N into global climatic changes. New tests of this hypothesis implicate sea level as a major control of the areal extent of grounded portions of the Antarctic Ice Sheet. But factors other than areal changes of the grounded Antarctic Ice Sheet may have strongly influenced Southern Hemisphere climate and terminated the last ice age simultaneously in both polar hemispheres. Atmospheric carbon dioxide linked to high-latitude oceans is the most likely candidate, but another potential influence was high-frequency climatic oscillations. It is postulated that variations in atmospheric carbon dioxide acted through an Antarctic ice shelf linked to the grounded ice sheet to produce and terminate Southern Hemisphere ice-age climate. It is further postulated that Milankovitch summer insolation combined with a warm-high frequency oscillation caused marked recession of Northern Hemisphere ice-sheet melting margins and the North Atlantic polar front about 14,000 /sup 14/C yr B.P. This permitted renewed formation of North Atlantic Deep Water, which could well have controlled atmospheric carbon dioxide. Combined melting and consequent sea-level rise from the three warming factors initiated irreversible collapse of the interlocked global ice-sheet system, which was at its largest but most vulnerable configuration.