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

SciTech Connect

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.

Lee, Seungjoo; Antony, Lizamma; Hartmann, Rune; Knaus, Karen J.; Surewicz, Krystyna; Surewicz, Witold K.; Yee, Vivien C. (Case Western); (Cleveland Clinic)



Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.  

PubMed Central

Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie). Although the formation of PrPSc from the cellular prion protein (PrPC) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in PrPSc synthesis. To assess this possibility, we purified both PrPC and PrPSc by using nondenaturing procedures and determined the secondary structure of each. Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were confirmed by circular dichroism measurements. In contrast, the beta-sheet content of PrPSc was 43% and the alpha-helix 30% as measured by FTIR. As determined in earlier studies, N-terminally truncated PrPSc derived by limited proteolysis, designated PrP 27-30, has an even higher beta-sheet content (54%) and a lower alpha-helix content (21%). Neither PrPC nor PrPSc formed aggregates detectable by electron microscopy, while PrP 27-30 polymerized into rod-shaped amyloids. While the foregoing findings argue that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, we cannot eliminate the possibility that an undetected chemical modification of a small fraction of PrPSc initiates this process. Since PrPSc seems to be the only component of the "infectious" prion particle, it is likely that this conformational transition is a fundamental event in the propagation of prions. Images Fig. 1 Fig. 4

Pan, K M; Baldwin, M; Nguyen, J; Gasset, M; Serban, A; Groth, D; Mehlhorn, I; Huang, Z; Fletterick, R J; Cohen, F E



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

PubMed Central

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.

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



Singular points of protein beta-sheets.  

PubMed Central

Protein beta-sheets can be regarded as surfaces. Two surfaces can be connected along a common edge to form a larger surface, or two edges of a surface can coalesce to form a closed sheet such as a beta-barrel. Singular points are locations where these connections are not perfect. In protein beta-sheets, a singular point is characterized by a residue separating two beta-ladders. In this paper, we study the singular points of protein beta-sheets from the surface topologic viewpoint, summarize our search results from the protein structural data in the Protein Data Bank, and present examples where singular points are near the active sites and may contribute to forming the proper relative positions of catalytic residues.

Liu, W. M.; Chou, K. C.



Sequence specificity, statistical potentials, and three-dimensional structure prediction with self-correcting distance geometry calculations of beta-sheet formation in proteins.  

PubMed Central

A statistical analysis of a representative data set of 169 known protein structures was used to analyze the specificity of residue interactions between spatial neighboring strands in beta-sheets. Pairwise potentials were derived from the frequency of residue pairs in nearest contact, second nearest and third nearest contacts across neighboring beta-strands compared to the expected frequency of residue pairs in a random model. A pseudo-energy function based on these statistical pairwise potentials recognized native beta-sheets among possible alternative pairings. The native pairing was found within the three lowest energies in 73% of the cases in the training data set and in 63% of beta-sheets in a test data set of 67 proteins, which were not part of the training set. The energy function was also used to detect tripeptides, which occur frequently in beta-sheets of native proteins. The majority of native partners of tripeptides were distributed in a low energy range. Self-correcting distance geometry (SECODG) calculations using distance constraints sets derived from possible low energy pairing of beta-strands uniquely identified the native pairing of the beta-sheet in pancreatic trypsin inhibitor (BPTI). These results will be useful for predicting the structure of proteins from their amino acid sequence as well as for the design of proteins containing beta-sheets.

Zhu, H.; Braun, W.



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

SciTech Connect

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.

Makabe, Koki; Koide, Shohei (UC)



Toxicity of non-abeta component of Alzheimer's disease amyloid, and N-terminal fragments thereof, correlates to formation of beta-sheet structure and fibrils.  


The non-Abeta component of Alzheimer's disease amyloid (NAC) and its precursor alpha-synuclein have been linked to amyloidogenesis in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Previously we have shown that NAC forms beta-sheet structures and fibrils [El-Agnaf, O.M.A., Bodles, A.M., Guthrie, D.J.S., Harriott, P. & Irvine, G.B. (1998) Eur. J. Biochem. 258, 157-163]. As a measure of their neurotoxic potential we have examined the ability of fresh and aged NAC and fragments thereof to inhibit the reduction of the redox dye 3-(4, 5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide by rat pheochromocytoma PC12 cells. Micromolar concentrations of NAC and fragments thereof display varying degrees of toxicity. On immediate dissolution and after an incubation period for 3 days at 37 degrees C the full-length peptide and fragments NAC(3-18) and NAC(1-18) scrambled sequence [NAC(1-18 s)] were toxic, whereas fragments NAC(1-13) and NAC(6-14) were not. CD indicates that NAC(3-18) and NAC(1-18 s) exhibit beta-sheet secondary structure in aqueous solution, whereas NAC(1-13) and NAC(6-14) do not. NAC(3-18) aggregates, as indicated by concentration of peptide remaining in solution after 3 days measured by an HPLC assay, and forms fibrils, as determined by electron microscopy. However, although some fibrils were detected for NAC(1-18 s) it does not come out of solution to a significant degree. Fragments NAC(1-13) and NAC(6-14) form few fibrils and remain in solution. These findings indicate that the ability of the central region of NAC to form beta-sheet secondary structures is important for determining the toxicity of the peptide. This contrasts with what has been reported previously for most Abeta peptides as their toxicity appears to require the peptide to have formed fibrillary aggregates as well as displaying beta-sheet. These results suggest that an intermediate, which exhibits beta-sheet structure, may be responsible for the toxic properties of NAC and provides further evidence for the role of NAC in the pathogenesis of AD, PD and DLB. PMID:10759841

Bodles, A M; Guthrie, D J; Harriott, P; Campbell, P; Irvine, G B



Transmuting alpha helices and beta sheets.  


Protein architecture involves two main secondary structural classes: alpha helices and beta sheets. Some natural proteins alter their fold in response to changes in solution conditions or as a consequence of mutation. Here, we discuss recent attempts to induce such conformational changes by design: specifically, the motivation and success of efforts to change one protein fold into a different one in response to the 'Paracelsus Challenge'. The results of such efforts may provide a better understanding of the processes that underlie conformational plasticity in proteins. PMID:9377709

Dalal, S; Balasubramanian, S; Regan, L



Amyloid Beta Mediates Memory Formation  

ERIC Educational Resources Information Center

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,…

Garcia-Osta, Ana; Alberini, Cristina M.



Length dependence of the coil <--> beta-sheet transition in a membrane environment.  


The most abundant structural element in protein aggregates is the beta-sheet. Designed peptides that fold into a beta-sheet structure upon binding to lipid membranes are useful models to elucidate the thermodynamic characteristics of the random coil <-->beta-structure transition. Here, we examine the effect of strand length on the random coil <--> beta-sheet transition of the (KIGAKI)n peptide with the total chain length varying between 7 and 30 amino acids. The beta-sheet content of the peptides in the presence and absence of membranes was measured with circular dichroism spectroscopy. The peptides were titrated with small unilamellar lipid vesicles, and the thermodynamic binding parameters were determined with isothermal titration calorimetry (ITC). Membrane binding includes at least two processes, namely (i) the transfer of the peptide from the aqueous phase to the lipid surface and (ii) the conformational change from a random coil conformation to a beta-sheet structure. CD spectroscopy and ITC analysis demonstrate that beta-sheet formation depends cooperatively on the peptide chain length with a distinct increase in beta-structure for n > 10-12. Binding to the lipid membrane is an entropy-driven process as the binding enthalpy is always endothermic. The contribution of the beta-sheet folding reaction to the overall process was determined with analogues of the KIGAKI repeat where two adjacent amino acids were replaced by their D-enantiomers. The folding reaction for peptides with n >or= 12 is characterized by a negative free folding energy of DeltaG(degree)beta approximately equal -0.15 kcal/mol per amino acid residue. The folding step proper is exothermic with DeltaH(degree)(beta) approximately equal -0.2 to -0.6 kcal/mol per residue and counteracted by a negative entropy term TDeltaS(degree)(beta) = -0.1 to -0.5 kcal/mol per residue, depending on the chain length (18 beta-sheet formation is unfavorable with DeltaG(degree)beta approximately +0.08 kcal/mol per residue. Small changes of environmental parameters like pH or temperature can thus be anticipated to have profound effects on aggregation reactions, leading to amyloid fibril formation. PMID:18163629

Meier, Matthias; Seelig, Joachim



Beating the Heat - Fast Scanning Melts Silk Beta Sheet Crystals  

PubMed Central

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.

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



Beating the Heat - Fast Scanning Melts Silk Beta Sheet Crystals  

NASA Astrophysics Data System (ADS)

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.

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



4,4(')-Dianilino-1,1(')-binaphthyl-5,5(')-disulfonate: report on non-beta-sheet conformers of Alzheimer's peptide beta(1-40).  


The venerable fluorescent probe of protein hydrophobic regions, 4,4(')-dianilino-1,1(')-binaphthyl-5,5(')-disulfonate (bis-ANS), unexpectedly increases in fluorescence with soluble beta(1-40) in acidic buffer solutions but reacts weakly with amyloid fibrils while other hydrophobic probes react with the fibrils. CD analysis correlates reaction with the probe with random coil/mixed conformations and alpha-helical forms of beta(1-40) in buffer solutions but less so with soluble beta-sheet forms or amyloid fibrils. The kinetics of the fluoroalcohol-induced interconversion of conformers can be followed by changes in bis-ANS fluorescence. Formation of the beta-sheet form in aqueous buffer is limited by a slow component (minutes) while fluoroalcohol-promoted changes between beta-sheet and alpha-helix occur over seconds. Variants of beta(1-40) such as beta(1-42) or the Dutch E22Q mutation of beta(1-40) and fragments beta(1-28), beta(12-28), beta(10-20 amide), and beta(10-35 amide) react with bis-ANS under conditions that do not support fibril formation. Primary amino acid sequence is important as beta(1-11) does not cause bis-ANS fluorescence while beta(1-16) does, but hydrophobicity is not as beta(25-35) and beta(15-20 amide) are unreactive. bis-ANS is a useful biophysical tool for characterizing particular, but not all, soluble Abeta conformations distinct from the fibrillar form of amyloid peptides detected by Thioflavin T. PMID:12127075

LeVine, Harry



Nonlinear current sheet formation in ideal plasmas  

NASA Technical Reports Server (NTRS)

We present a numerical study of the formation of current sheets in ideal plasmas. First we confirm the development of singular current sheets in a one-dimensional model. In a second step we extend the analysis to two-dimensional equilibria. Here it is found that the resulting structures are quiet insensitive to the boundary conditions. For the special case of a magnetotail like equilibrium it will be shown that the resulting current distribution provides a possibility to understand the onset of a localized anomalous resistivity from a macroscopic point of view. Furthermore, the resulting structures provide an explanation for the dramatic decrease of the thickness of the current sheet in the magnetotail prior to the onset of geomagnetic substorms.

Voge, A.; Schindler, K.; Otto, A.



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

SciTech Connect

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.

Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.; (IIT); (NIH); (UC)



Formation of Sprays From Conical Liquid Sheets  

NASA Technical Reports Server (NTRS)

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.

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



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

NASA Astrophysics Data System (ADS)

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.

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



Cooperative deformation of hydrogen bonds in beta-strands and beta-sheet nanocrystals  

Microsoft Academic Search

Beta-sheet protein domains are stabilized by weak hydrogen bonds, yet materials such as silk---whose ultimate tensile strength is controlled primarily by this secondary structure---can exceed the ultimate tensile strength of steel. Earlier work has suggested that this is because hydrogen bonds deform cooperatively within small protein domains to reach the maximum strength. Here we study the atomistic mechanism of this

Zhao Qin; Markus J. Buehler



Folding dynamics of a family of beta-sheet proteins  

NASA Astrophysics Data System (ADS)

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.

Rousseau, Denis



Cooperative deformation of hydrogen bonds in beta-strands and beta-sheet nanocrystals  

NASA Astrophysics Data System (ADS)

Beta-sheet protein domains are stabilized by weak hydrogen bonds, yet materials such as silk—whose ultimate tensile strength is controlled primarily by this secondary structure—can exceed the ultimate tensile strength of steel. Earlier work has suggested that this is because hydrogen bonds deform cooperatively within small protein domains to reach the maximum strength. Here we study the atomistic mechanism of this concerted deformation mechanism by applying an elastic structural model, used to solve the deformation field of the chemical bonds in beta-sheet nanostructures under stretching and thereby identify the number of hydrogen bonds that deform cooperatively. Through this analysis, we predict the optimal beta-strand and beta-sheet nanocrystal size associated with reaching the maximum usage of hydrogen bonds under loading applied per unit material volume. Our results, albeit based on a simple model and analytical equations, quantitatively agree with results based on experimental and molecular-dynamics studies and provide physical insight into the underlying molecular mechanisms of weak bond cooperativity. A comparison with the size of hydrogen bond clusters in biology reveals excellent agreement with the cluster sizes predicted by our analysis, suggesting that perhaps the confinement of hydrogen bonds into nanoscale elements is a universal biological design paradigm that turns weakness to strength. The parameters used in this study could be modified and applied to other protein and polymer structures, which imply potential applications of our model in understanding the physics of deformation and failure in a broader range of biological and polymer materials, as well as in de novo biomaterial design.

Qin, Zhao; Buehler, Markus J.



Amyloid beta mediates memory formation  

PubMed Central

The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid ? (1–42) peptide (A?[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, endogenous A? in normal hippocampi mediates learning and memory formation. Furthermore, hippocampal injection of picomolar concentrations of exogenous A?(1–42) enhances memory consolidation. Correlative data suggest that A? peptides may exert their function via nicotinic acethylcoline receptors. Hence, A? peptides, including A?(1–42), play an important physiological role in hippocampal memory formation.

Garcia-Osta, Ana; Alberini, Cristina M.



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

SciTech Connect

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.

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



Current Sheet Formation and Reconnection Dynamics in the Solar Corona  

Microsoft Academic Search

Current sheet formation is a necessary consequence of the evolution of the multi-polar magnetic field topologies that are ubiquitous throughout the solar corona. We present a very high-resolution study of 3D MHD current sheet formation and the resulting reconnection dynamics in an environment appropriate for the corona. The initial field consists of a translationally invariant, potential field with a null-point

Justin K. Edmondson; S. K. Antiochos; C. DeVore; T. H. Zurbuchen



Beating the heat--fast scanning melts silk beta sheet crystals.  


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

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



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

SciTech Connect

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.

Benseny-Cases, Nuria; Cocera, Mercedes [Unitat de Biofisica, Departament de Bioquimica i de Biologia Molecular, i Centre d'Estudis Biofisics, Facultat de Medicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Cladera, Josep [Unitat de Biofisica, Departament de Bioquimica i de Biologia Molecular, i Centre d'Estudis Biofisics, Facultat de Medicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain)], E-mail:



Average electric wave spectra in the plasma sheet: Dependence on ion density and ion beta  

SciTech Connect

Using 4 months of tail data obtained by the ELF/MF spectrum analyzer and the plasma instrument on board the AMPTE/IRM satellite, more than 50,000 ten-second-averaged electric wave spectra were analyzed in order to establish typical spectra for periods of high and low ion density and high and low ion {beta}. The general spectral slope of the spectra in the plasma sheet follows an f{sup {minus}2} law. Ion {beta} has a stronger influence on the spectral form than the ion density. Highest average spectral densities are obtained in the low-{beta} plasma sheet boundary layer, where the spectrum is that of broadband electrostatic noise extending to frequencies near and above the upper hybrid frequency. Lowest wave intensities are encountered in the high-{beta} inner central plasma sheet. The outer central plasma sheet has generally low wave intensities and is dominated by electron cyclotron odd half-harmonics and electron regions of the plasma sheet while higher odd half-harmonics dominate the low-{beta} and low-density inner central plasma sheet.

Baumjohann, W.; Treumann, R.A. (Max-Planck-Inst. fuer Physik und Astrophysik, Garching (West Germany)); LaBelle, J. (Dartmouth College, Hanover, NH (United States))



Spangle formation in galvanized sheet steel coatings  

Microsoft Academic Search

Very large grains, termed “spangles,” are produced on galvanized sheet steel coatings when lead is added to the zinc bath.\\u000a The spangles have been attributed to melt undercooling prior to solidification. The present results indicate this is not the\\u000a case, undercooling being less than 1 ?C. The spangle diameter is shown to be dependent on the alloy addition to the

F. A. Fasoyinu; F. Weinberg



On spontaneous formation of current sheets: Untwisted magnetic fields  

SciTech Connect

This is a study of the spontaneous formation of electric current sheets in an incompressible viscous fluid with perfect electrical conductivity, governed by the magnetohydrodynamic Navier-Stokes equations. Numerical solutions to two initial value problems are presented for a three-dimensional, periodic, untwisted magnetic field evolving, with no change in magnetic topology under the frozen-in condition and at characteristic fluid Reynolds numbers of the order of 500, from a nonequilibrium initial state with the fluid at rest. The evolution converts magnetic free energy into kinetic energy to be all dissipated away by viscosity so that the field settles into a minimum-energy, static equilibrium. The solutions demonstrate that, as a consequence of the frozen-in condition, current sheets must form during the evolution despite the geometric simplicity of the prescribed initial fields. In addition to the current sheets associated with magnetic neutral points and field reversal layers, other sheets not associated with such magnetic features are also in evidence. These current sheets form on magnetic flux surfaces. This property is used to achieve a high degree of the frozen-in condition in the simulations, by describing the magnetic field entirely in terms of the advection of its flux surfaces and integrating the resulting governing equations with a customized version of a general-purpose high-resolution (viz., nonoscillatory) hydrodynamical simulation code EULAG [J. M. Prusa et al., Comput. Fluids 37, 1193 (2008)]. Incompressibility imposes the additional global constraint that the flux surfaces must evolve with no change in the spatial volumes they enclose. In this approach, current sheet formation is demonstrated graphically by the progressive pressing together of suitably selected flux surfaces until their separation has diminished below the minimal resolved distance on a fixed grid. The frozen-in condition then fails in the simulation as the field reconnects through an effecting numerical resistivity. The principal results are related to the Parker theory of current-sheet formation and dissipation in the solar corona.

Bhattacharyya, R. [Udaipur Solar Observatory, Physical Research Laboratory, Dewali, Bari Road, Udaipur-313001 (India); National Center for Atmospheric Research, P.O. Box 3000, Boulder, Colorado 80307 (United States); Low, B. C.; Smolarkiewicz, P. K. [National Center for Atmospheric Research, P.O. Box 3000, Boulder, Colorado 80307 (United States)



Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic [beta]-Sheet Mimics  

SciTech Connect

Protein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. {beta}-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from A{beta} and tau were incorporated into macrocycles, thereby restraining them to {beta}-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which {beta}-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a variety of sheet-to-sheet pairing angles, offering a structural explanation for the heterogeneity of amyloid oligomers.

Liu, Cong; Sawaya, Michael R.; Cheng, Pin-Nan; Zheng, Jing; Nowick, James S.; Eisenberg, David (UCI); (UCLA)



Mechanical energy transfer and dissipation in fibrous beta-sheet-rich proteins  

NASA Astrophysics Data System (ADS)

Mechanical properties of structural protein materials are crucial for our understanding of biological processes and disease states. Through utilization of molecular simulation based on stress wave tracking, we investigate mechanical energy transfer processes in fibrous beta-sheet-rich proteins that consist of highly ordered hydrogen bond (H-bond) networks. By investigating four model proteins including two morphologies of amyloids, beta solenoids, and silk beta-sheet nanocrystals, we find that all beta-sheet-rich protein fibrils provide outstanding elastic moduli, where the silk nanocrystal reaches the highest value of ?40GPa . However, their capacities to dissipate mechanical energy differ significantly and are controlled strongly by the underlying molecular structure of H-bond network. Notably, silk beta-sheet nanocrystals feature a ten times higher energy damping coefficient than others, owing to flexible intrastrand motions in the transverse directions. The results demonstrate a unique feature of silk nanocrystals, their capacity to simultaneously provide extreme stiffness and energy dissipation capacity. Our results could help one to explain the remarkable properties of silks from an atomistic and molecular perspective, in particular its great toughness and energy dissipation capacity, and may enable the design of multifunctional nanomaterials with outstanding stiffness, strength, and impact resistance.

Xu, Zhiping; Buehler, Markus J.



Current Sheet Formation in the Interstellar Medium: Erratum  

NASA Astrophysics Data System (ADS)

In the paper "Current Sheet Formation in the Interstellar Medium" by Ellen G. Zweibel and Axel Brandenburg (ApJ, 478, 563 [1997]), the address given for Dr. Brandenburg is incorrect. It should be Department of Mathematics, University of Newcastle, Newcastle upon Tyne, NE1 7RU, England, UK. His e-mail address is

Zweibel, Ellen G.; Brandenburg, Axel



Formation of thin current sheets in a quasistatic magnetotail model  

NASA Astrophysics Data System (ADS)

Observations suggest that thin current sheets forming in the near-Earth magnetotail late in substorm growth phases may be a crucial part of substorm evolution. In a simple theoretical model the current density was shown to become singular for suitable external perturbations. Here, we address the same problem in a more realistic model based on the adiabatic MHD - theory developed by Schindler and Birn [1982]. We show that under suitable conditions the formation of a thin current sheet in the near-Earth tail is an intrinsic aspect of flux transfer to the magnetotail. The mechanism is based on the strong variation of flux tube volume with the magnetic flux function.

Wiegelmann, T.; Schindler, K.


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

SciTech Connect

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.

Darnell, Gregory; Orgel, Joseph P.R.O.; Pahl, Reinhard; Meredith, Stephen C. (IIT); (UC)



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

PubMed Central

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:

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



Current Sheet Formation in the Solar Corona---Topological Considerations  

NASA Astrophysics Data System (ADS)

An outstanding problem in solar physics has been to understand how the solar corona, with its temperature of millions of degrees, can be so much hotter than the underlying photosphere, which is typically of only a few thousand degrees. A simple model has been proposed for the heating of low-?, low resistivity plasmas, such as the solar corona, which possess highly tangled magnetic fields, and which evolve very slowly from external stresses compared to a typical Alfven crossing time. These plasmas are considered to evolve ``quasi-statically,'' i.e. arbitrarily close to equilibrium at all stages in their evolution. In the model, the heating has been assumed to result from the formation of regions of intense electrical current, or current sheets. A key ingredient in this model has been the topological restrictions imposed on current sheets, owing to the fact that the low-? property constrains current to flow only along the magnetic field lines. Assuming that the most probable sites for the formation of current sheets are closed loops of magnetic field, an estimate has been made of the statistical properties of current sheets. The special role of magnetic neutral points has been considered, and the implications for coronal heating have been discussed.

Albright, B. J.; Cowley, S. C.



Laminated Morphology of Nontwisting beta-Sheet Fibrilis Constructed via Peptide Self-Assembly  

SciTech Connect

A synthetic peptide has been de novo designed that self-assembles into {beta}-sheet fibrils exhibiting a nontwisted, stacked morphology. The stacked morphology is constituted by 2.5 nm wide filaments that laterally associate to form flat fibril laminates exceeding 50 nm in width and micrometers in length. The height of each fibril is limited to the length of exactly one peptide monomer in an extended {beta}-strand conformation, approximately 7 nm. Once assembled, these highly ordered, 2-D structures are stable over a wide range of pH and temperature and exhibit characteristics similar to those of amyloid fibrils. Furthermore, the rate of assembly and degree of fibril lamination can be controlled with kinetic parameters of pH and temperature. Finally, the presence of a diproline peptide between two {beta}-sheet-forming strands in the peptide sequence is demonstrated to be an important factor in promoting the nontwisting, laminated fibril morphology.

Lamm,M.; Rajagopal, K.; Schneider, J.; Pochan, D.



Fibril aggregation inhibitory activity of the beta-sheet breaker peptides: a molecular docking approach.  


In the present study, we used a molecular docking as a rapid, interactive method to study the inhibition of fibrillogenesis process by beta-sheet breaker peptide (BSB) (Ac-L(1)-V(2)-(NMet)F(3)-F(4)-A(5)-NH(2)). Our aim was to find the complex (Abeta:BSB) that blocks the aggregation of the fibrils, and to identify the binding sequences for the small peptides on Abeta(1-42). An NMR structure solved by Lührs et al. in 2005 was used to study the interaction of BSB with the amyloid aggregated forms. From our preliminary step-by-step docking studies, the L(17)-D(23) sequence seems to be one of the most common active sites of Abeta(1-42), and critical in amyloid fibril formation. We note that a single molecule of BSB does not influence the interaction between the two fibrils, while a little excess of BSB (two molecules) with respect to the amyloid does not completely block but undoubtedly obstructs the aggregation process. PMID:19090016

Chini, Maria Giovanna; Scrima, Mario; D'Ursi, Anna Maria; Bifulco, Giuseppe



Formation of sheeting joints in Yosemite National Park, California  

NASA Astrophysics Data System (ADS)

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.

Martel, S. J.



Magnetic Nulls and Current Sheet Formation in the Solar Corona  

NASA Astrophysics Data System (ADS)

An outstanding problem in solar physics has been to understand how the solar corona can be so much hotter than the underlying photosphere. Most contemporary coronal heating models require that magnetic energy be transformed into heat through the generation of small scale current structures in the corona. This work is no exception; a simple model is proposed for the heating of low-?, low resistivity plasmas, such as the solar corona, which possess highly tangled magnetic fields, and which respond to external stresses very slowly compared to a typical Alfven crossing time. In the model, the plasma is considered to evolve ``quasi-statically,'' i.e. arbitrarily close to equilibrium at all stages in its evolution. The heating is assumed to follow from the formation of current sheets, which are sheet-like regions of very high current density. These current sheets must satisfy stringent topological requirements, however. Special attention is given to the role of magnetic nulls, or points where the magnetic field vanishes, in determining where current sheets can form in the coronal plasma and where enhanced heating can occur.

Albright, Brian; Cowley, Steven



Current Sheets Formation and Relaxation of Coronal Magnetic Fields  

NASA Astrophysics Data System (ADS)

We investigate the relaxation of magnetic fields in closed regions of solar and stellar coronae, extending to further topologies our previous work (Rappazzo, A.F. & Parker, E.N., ApJL, 773, L2 (2013)). The dynamical evolution is integrated with the equations of reduced magnetohydrodynamics (RMHD) apt to model a plasma embedded in a strong guide field B0 extended along the axial direction, where the dynamical field is the orthogonal component b. Dissipative and ideal simulations are carried out in Cartesian geometry: 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 in a motionless photosphere. The magnetic field b initially has only large scales, and is not in equilibrium. We show that the magnetic relaxation leads to the formation of current sheets when the intensity of the magnetic field b is beyond a critical value b_c. For values of b below this threshold (b < b_c), line-tying and field-line tension inhibit the formation of current sheets, while above the threshold (b > b_c) 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 ? decreasing at least exponentially, after which the simulations become under-resolved.

Rappazzo, A. F.



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

SciTech Connect

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.

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



Current Sheets Formation in Tangled Coronal Magnetic Fields  

NASA Astrophysics Data System (ADS)

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 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 b . We identify the magnetic intensity threshold b/B 0 ~ l 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 ? decreasing at least exponentially, after which the simulations become underresolved.

Rappazzo, A. F.; Parker, E. N.



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

SciTech Connect

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.

Rocha, Sandra [LEPAE, Chemical Engineering Department, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal)], E-mail:; Cardoso, Isabel [Molecular Neurobiology Unit, Institute for Molecular and Cell Biology, Rua do Campo Alegre 823, 4150-180 Porto (Portugal); Boerner, Hans [Max Planck Institute of Colloids and Interfaces, 14424 Potsdam (Germany); Pereira, Maria Carmo [LEPAE, Chemical Engineering Department, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Saraiva, Maria Joao [Molecular Neurobiology Unit, Institute for Molecular and Cell Biology, Rua do Campo Alegre 823, 4150-180 Porto (Portugal); ICBAS, University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto (Portugal); Coelho, Manuel [LEPAE, Chemical Engineering Department, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal)



Mutational analysis of the folding transition state of the C-terminal domain of ribosomal protein L9: a protein with an unusual beta-sheet topology.  


The C-terminal domain of ribosomal protein L9 (CTL9) is a 92-residue alpha-beta protein which contains an unusual three-stranded mixed parallel and antiparallel beta-sheet. The protein folds in a two-state fashion, and the folding rate is slow. It is thought that the slow folding may be caused by the necessity of forming this unusual beta-sheet architecture in the transition state for folding. This hypothesis makes CTL9 an interesting target for folding studies. The transition state for the folding of CTL9 was characterized by phi-value analysis. The folding of a set of hydrophobic core mutants was analyzed together with a set of truncation mutants. The results revealed a few positions with high phi-values (> or = 0.5), notably, V131, L133, H134, V137, and L141. All of these residues were found in the beta-hairpin region, indicating that the formation of this structure is likely to be the rate-limiting step in the folding of CTL9. One face of the beta-hairpin docks against the N-terminal helix. Analysis of truncation mutants of this helix confirmed its importance in folding. Mutations at other sites in the protein gave small phi-values, despite the fact that some of them had major effects on stability. The analysis indicates that formation of the antiparallel hairpin is critical and its interactions with the first helix are also important. Thus, the slow folding is not a consequence of the need to fully form the unusual three-stranded beta-sheet in the transition state. Analysis of the urea dependence of the folding rates indicates that mutations modulate the unfolded state. The folding of CTL9 is broadly consistent with the nucleation-condensation model of protein folding. PMID:17240985

Li, Ying; Gupta, Ruchi; Cho, Jae-Hyun; Raleigh, Daniel P



The N-terminal region of non-A beta component of Alzheimer's disease amyloid is responsible for its tendency to assume beta-sheet and aggregate to form fibrils.  


Examination of the N-terminal sequence of non-A beta component of Alzheimer's Disease amyloid (NAC) revealed a degree of similarity to regions crucial for aggregation and toxicity of three other amyloidogenic proteins, namely amyloid beta peptide (A beta), prion protein (PrP) and islet amyloid polypeptide (IAPP), leading us to believe that this might be the part of the molecule responsible for causing aggregation. Secondary structure prediction analysis of NAC indicated that the N-terminal half was likely to form a beta-structure whereas the C-terminal half was likely to form an alpha-helix. NAC in solution altered from random coil to beta-sheet structure upon ageing, a process that has previously been shown to lead to fibril formation. To delineate the region of NAC responsible for aggregation we synthesised two fragments, NAC-(1-18)-peptide and NAC-(19-35)-peptide, and examined their physicochemical properties. Upon incubation, solutions of NAC-(1-18)-peptide became congophilic and aggregated to form fibrils of diameter 5-10 nm, whereas NAC-(19-35)-peptide did not bind Congo Red and remained in solution. Circular dichroism spectroscopy was used to study the secondary structure of NAC and the two fragments. In trifluoroethanol/water mixtures, NAC and NAC-(19-35)-peptide adopted alpha-helical structure but NAC-(1-18)-peptide did not. NAC-(1-18)-peptide and NAC formed beta-sheet in acetonitrile/water mixtures more readily than did NAC-(19-35)-peptide. CD spectra of NAC or NAC-(1-18)-peptide in aqueous solution indicate the formation of beta-sheet on ageing. We propose that the N-terminal region of NAC is the principal determinant of aggregation. Our results indicate that NAC resembles A beta, and other amyloidogenic proteins, in that aggregation is dependent upon beta-sheet development. These results lend support to a role for NAC in the development of neurodegenerative disease. PMID:9851705

El-Agnaf, O M; Bodles, A M; Guthrie, D J; Harriott, P; Irvine, G B



Determinants of strand register in antiparallel beta-sheets of proteins.  

PubMed Central

Antiparallel beta-sheets present two distinct environments to inter-strand residue pairs: beta(A,HB) sites have two backbone hydrogen bonds; whereas at beta(A,NHB) positions backbone hydrogen bonding is precluded. We used statistical methods to compare the frequencies of amino acid pairs at each site. Only approximately 10% of the 210 possible pairs showed occupancies that differed significantly between the two sites. Trends were clear in the preferred pairs, and these could be explained using stereochemical arguments. Cys-Cys, Aromatic-Pro, Thr-Thr, and Val-Val pairs all preferred the beta(A,NHB) site. In each case, the residues usually adopted sterically favored chi1 conformations, which facilitated intra-pair interactions: Cys-Cys pairs formed disulfide bonds; Thr-Thr pairs made hydrogen bonds; Aromatic-Pro and Val-Val pairs formed close van der Waals contacts. In contrast, to make intimate interactions at a beta(A,HB) site, one or both residues had to adopt less favored chi1 geometries. Nonetheless, pairs containing glycine and/or aromatic residues were favored at this site. Where glycine and aromatic side chains combined, the aromatic residue usually adopted the gauche conformation, which promoted novel aromatic ring-peptide interactions. This work provides rules that link protein sequence and tertiary structure, which will be useful in protein modeling, redesign, and de novo design. Our findings are discussed in light of previous analyses and experimental studies.

Hutchinson, E. G.; Sessions, R. B.; Thornton, J. M.; Woolfson, D. N.



Strength limit of entropic elasticity in beta-sheet protein domains  

NASA Astrophysics Data System (ADS)

Elasticity and strength of individual beta-sheet protein domains govern key biological functions and the mechanical properties of biopolymers including spider silk, amyloids, and muscle fibers. The worm-like-chain (WLC) model is commonly used to describe the entropic elasticity of polypeptides and other biomolecules. However, force spectroscopy experiments have shown pronounced deviations from the ideal WLC behavior, leading to controversial views about the appropriate elastic description of proteins at nanoscale. Here we report a simple model that explains the physical mechanism that leads to the breakdown of the WLC idealization in experiments by using only two generic parameters of the protein domain, the H-bond energy and the protein backbone’s persistence length. We show that a rupture initiation condition characterized by the free energy release rate of H-bonds characterizes the limit of WLC entropic elasticity of beta-sheet protein domains and the onset of rupture. Our findings reveal that strength and elasticity are coupled and cannot be treated separately. The predictions of the model are compared with atomic force microscopy experiments of protein rupture.

Keten, Sinan; Buehler, Markus J.



Designing biomaterials exploiting beta-sheet forming peptides self-assembly  

NASA Astrophysics Data System (ADS)

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.

Saiani, Alberto



Transthyretin Sequesters Amyloid beta Protein and Prevents Amyloid Formation  

Microsoft Academic Search

The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (Abeta) in the brain and cerebrovasculature. However, the Abeta is found in a soluble form in cerebrospinal fluid in healthy individuals and patients with Alzheimer disease. We postulate that sequestration of Abeta precludes amyloid formation. Failure to sequester Abeta in Alzheimer disease may result in amyloidosis.

Alexander L. Schwarzman; Luisa Gregori; Michael P. Vitek; Sergey Lyubski; Warren J. Strittmatter; Jan J. Enghilde; Ramaninder Bhasin; Josh Silverman; Karl H. Weisgraber; Patricia K. Coyle; Michael G. Zagorski; Joseph Talafous; Moises Eisenberg; Ann M. Saunders; Allen D. Roses; Dmitry Goldgaber



A mechanism of adsorption of beta-nicotinamide adenine dinucleotide on graphene sheets: experiment and theory.  


Beta-nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) play major roles in the development of electrochemical enzyme biosensors and biofuel cells. Unfortunately, the oxidation of NADH at carbon electrodes suffers from passivation of the electrodes and a decrease in passing currents. Here, we investigate experimentally and theoretically the reasons for such passivation. High-resolution X-ray photoelectron spectroscopy (HR-XPS), voltammetry, and amperometry show that adsorption occurs on the edges and "edge-like" defects of graphene sheets. HR-XPS and ab initio molecular dynamics show that the adsorption of NAD(+) molecules on the edges of graphene happens due to interaction with oxygen-containing groups such as carboxylic groups, while graphene edges substituted only with hydrogen are prone to passivation. PMID:19746361

Pumera, Martin; Scipioni, Roberto; Iwai, Hideo; Ohno, Takahisa; Miyahara, Yuji; Boero, Mauro



Complex formation between copper. beta. -diketonates and polyoxypropylene glycols  

SciTech Connect

The complex formation between copper (II) dipivaloylmethanate Cu(dpm)/sub 2/ and copper (II) hexafluoroacetylacetonate Cu(hfacac)/sub 2/ and polyoxypropylene glycols (PPG) with molecular masses of 200 and 1050 was studied by spectrophotometry in the visible region and by ESR. The compositions of the complexes (1:1) and the thermodynamic parameters of complex formation were determined. In complexing power Cu(dpm)/sub 2/ is inferior to Cu(hfacac)/sub 2/. Complex formation between Cu(hfacac)/sub 2/ and PPG is accompanied by structural changes in the ..beta..-diketonate.

Nizel'skii, Y.N.; Ishchenko, S.S.



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)

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.

Waldman, Amy Sue


Multiple native-like conformations trapped via self-association-induced hydrophobic collapse of the 33-residue beta-sheet domain from platelet factor 4.  

PubMed Central

Native platelet factor 4 (PF4) (70 residues) has a hydrophobic three-stranded anti-parallel beta-sheet domain on to which is folded an amphipathic C-terminal alpha-helix and an aperiodic N-terminal domain. The 33-amino acid beta-sheet domain from PF4 (residues 23-55) has been synthesized and studied by c.d. and n.m.r. At 10 degrees C and low concentration, peptide 23-55 appears to exist in aqueous solution in a random-coil distribution of highly flexible conformational states. Some preferred conformation, however, is observed, particularly within a relatively stable chain reversal from Leu-45 to Arg-49. As the peptide concentration and/or temperature is increased, a new conformational state(s) appears and intensifies as slowly exchanging (600 MHz 1H-n.m.r. chemical-shift time scale) random-coil resonances disappear. Hill plots of the concentration-dependence indicated mostly tetramer formation as found in native PF4. Although apparent resonance linewidths in aggregate state(s) are of the order of 100 Hz, sequence-specific assignments for most resonances could be made. N.m.r./nuclear Overhauser effect structural analysis indicates the formation of multiple native-like anti-parallel beta-sheet conformations, kinetically trapped via subunit-association-induced hydrophobic collapse and stabilized by low-dielectric electrostatic interactions among/between Gly-28 and Lys-50 in opposing subunits. Results are discussed in terms of protein folding. Images Figure 9

Ilyina, E; Mayo, K H



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

NASA Technical Reports Server (NTRS)

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 which is qualitatively similar to what would be expected from solar wind driving. As a result, a new current sheet with the thickness of approximately the ion inertial length is formed. The current density inside the current sheet region is supplied largely by the electrons. Ion acceleration in the cross-tail direction is absent as the driving electric field fails to penetrate into the equatorial region.

Hesse, Michael; Winske, Dan; Birn, Joachim



Fibrillar oligomers nucleate the oligomerization of monomeric amyloid beta but do not seed fibril formation.  


Soluble amyloid oligomers are potent neurotoxins that are involved in a wide range of human degenerative diseases, including Alzheimer disease. In Alzheimer disease, amyloid beta (Abeta) oligomers bind to neuronal synapses, inhibit long term potentiation, and induce cell death. Recent evidence indicates that several immunologically distinct structural variants exist as follows: prefibrillar oligomers (PFOs), fibrillar oligomers (FOs), and annular protofibrils. Despite widespread interest, amyloid oligomers are poorly characterized in terms of structural differences and pathological significance. FOs are immunologically related to fibrils because they react with OC, a conformation-dependent, fibril-specific antibody and do not react with antibodies specific for other types of oligomers. However, fibrillar oligomers are much smaller than fibrils. FOs are soluble at 100,000 x g, rich in beta-sheet structures, but yet bind weakly to thioflavin T. EPR spectroscopy indicates that FOs display significantly more spin-spin interaction at multiple labeled sites than PFOs and are more structurally similar to fibrils. Atomic force microscopy indicates that FOs are approximately one-half to one-third the height of mature fibrils. We found that Abeta FOs do not seed the formation of thioflavin T-positive fibrils from Abeta monomers but instead seed the formation of FOs from Abeta monomers that are positive for the OC anti-fibril antibody. These results indicate that the lattice of FOs is distinct from the fibril lattice even though the polypeptide chains are organized in an immunologically identical conformation. The FOs resulting from seeded reactions have the same dimensions and morphology as the initial seeds, suggesting that the seeds replicate by growing to a limiting size and then splitting, indicating that their lattice is less stable than fibrils. We suggest that FOs may represent small pieces of single fibril protofilament and that the addition of monomers to the ends of FOs is kinetically more favorable than the assembly of the oligomers into fibrils via sheet stacking interaction. These studies provide novel structural insight into the relationship between fibrils and FOs and suggest that the increased toxicity of FOs may be due to their ability to replicate and the exposure of hydrophobic sheet surfaces that are otherwise obscured by sheet-sheet interactions between protofilaments in a fibril. PMID:20018889

Wu, Jessica W; Breydo, Leonid; Isas, J Mario; Lee, Jerome; Kuznetsov, Yurii G; Langen, Ralf; Glabe, Charles



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

PubMed Central

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.

Vinn, Olev



Effect of Process Variables on Transformation-Texture Development in Ti-6Al-4V Sheet Following Beta Heat Treatment  

NASA Astrophysics Data System (ADS)

The effect of preheat time, prestrain, cooling rate, and concurrent deformation during cooling on the preferential selection of hcp alpha variants during the decomposition of the high-temperature, bcc beta phase in two-phase titanium alloys was established using Ti-6Al-4V sheet material. For this purpose, sheet tension samples were pre-soaked in the beta phase field for 0 or 10 minutes (to vary the beta grain size), subjected to a prestrain of 0 or 0.1, and cooled at a rate of 11 or 155 K/min (11 or 155 °C/min) under conditions comprising free ends, fixed ends, or concurrent deformation at a strain rate between ~10-5 and 3 × 10-4 s-1. Electron-backscatter diffraction was used to determine the orientations of the alpha variants so formed, from which the underlying high-temperature, beta-grain microstructure and orientations were reconstructed. These measurements revealed that the parent beta texture changed due to grain growth during preheating. A comparison of the alpha- and beta-phase textures indicated that preferential variant selection was most noticeable under conditions involving a slow cooling rate especially when prestrain or concurrent straining was imposed.

Semiatin, S. L.; Kinsel, K. T.; Pilchak, A. L.; Sargent, G. A.



Chondrule formation by current sheets in protoplanetary disks  

SciTech Connect

We numerically explore where, when and if magnetorotational instability in protoplanetary disks can produce current sheets that could form chondrules. Results are tested against astronomical, meteoritic, thermodynamic, and experimental evidence. Theories of protoplanetary disk evolution require that the viscosity of the differentially rotating disk (the resistance of the disk to shear forces) be sufficient for stellar accretion on timescales of 106 years. With only molecular (frictional) viscosity, accretion takes 103 times longer. Vertical turbulent convection cannot provide the needed viscosity. The leading mechanisms for disk viscosity are (a) gravitational instability, which would drive density waves in the disk, and (b) coupling of the disk rotation to its magnetic field. In cold disk regions with a high mass density, gravitational instabilities could occur, and drive chondrule-forming shocks. Alternatively, magnetorotational instability (MRI) is predicted to occur in regions of the disk where the gas is ionized enough to couple to magnetic fields. Like spiral density waves, MRI effectively transfers angular momentum outward in the disk. The MRI also produces magnetic field gradients. In weakly ionized regions where neutral particles can slip through ions (i.e.-where ambipolar diffusion occurs), magnetic field gradients are predicted to grow steeper with time, producing sheets of strong electrical current. We propose that these current sheets could melt chondrule precursors. Unlike mechanisms involving accumulation and dissipation of charge (nebular 'lightning', e.g.-[11]), the MRI is driven by the abundant energy of the differential rotation of the disk itself. Furthermore, current sheets are predicted to occur in different regions over the lifetime of the disk. Which disk regions make current sheets, when, and where might they form chondrules? Because current sheet thermal profiles are qualitatively similar to those of shocks, our results are testable against meteoritic evidence by techniques analogous to those used by [6].

Ebel, D.S.; Joung, M.K.R.; McLow, M.-M. (AMNH); (Columbia)



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  

Microsoft Academic Search

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,

Amy Sue Waldman



Cooperative alpha-helix formation of beta-lactoglobulin and melittin induced by hexafluoroisopropanol.  


Alcohols denature the native state of proteins, and also stabilize the alpha-helical conformation in unfolded proteins and peptides. Among various alcohols, trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) are often used because of their high potential to induce such effects. However, the reason why TFE and HFIP are more effective than other alcohols is unknown. Using CD, we studied the effects of TFE and HFIP as well as reference alcohols, i.e., methanol, ethanol, and isopropanol, on the conformation of bovine beta-lactoglobulin and the bee venom melittin at pH 2. Upon addition of alcohols, beta-lactoglobulin exhibited a transformation from the native state, consisting of beta-sheets, to the alpha-helical state, whereas melittin folded from the unfolded state to the alpha-helical state. In both cases, the order of effectiveness of alcohols was shown to be: HFIP > TFE > isopropanol > ethanol > methanol. The alcohol-induced transitions were analyzed assuming a two-state mechanism to obtain the m value, a measure of the dependence of the free energy change on alcohol concentration. Comparison of the m values indicates that the high potential of TFE can be explained by the additive contribution of constituent groups, i.e., F atoms and alkyl group. On the other hand, the high potential of HFIP is more than that expected from the additive effects, suggesting that the cooperative formation of micelle-like clusters of HFIP is important. PMID:9041644

Hirota, N; Mizuno, K; Goto, Y



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

NASA Technical Reports Server (NTRS)

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.

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



Benchmarking the thermodynamic analysis of water molecules around a model beta sheet.  


Water molecules play a vital role in biological and engineered systems by controlling intermolecular interactions in the aqueous phase. Inhomogeneous fluid solvation theory provides a method to quantify solvent thermodynamics from molecular dynamics or Monte Carlo simulations and provides an insight into intermolecular interactions. In this study, simulations of TIP4P-2005 and TIP5P-Ewald water molecules around a model beta sheet are used to investigate the orientational correlations and predicted thermodynamic properties of water molecules at a protein surface. This allows the method to be benchmarked and provides information about the effect of a protein on the thermodynamics of nearby water molecules. The results show that the enthalpy converges with relatively little sampling, but the entropy and thus the free energy require considerably more sampling to converge. The two water models yield a very similar pattern of hydration sites, and these hydration sites have very similar thermodynamic properties, despite notable differences in their orientational preferences. The results also predict that a protein surface affects the free energy of water molecules to a distance of approximately 4.0 Å, which is in line with previous work. In addition, all hydration sites have a favorable free energy with respect to bulk water, but only when the water-water entropy term is included. A new technique for calculating this term is presented and its use is expected to be very important in accurately calculating solvent thermodynamics for quantitative application. PMID:22457119

Huggins, David J



Ballooning instability-induced plasmoid formation in near-Earth plasma sheet  

NASA Astrophysics Data System (ADS)

The formation of plasmoids in the near-Earth magnetotail is believed to be a key element of the substorm onset process. Previous work has identified a new scenario in MHD simulations where the nonlinear evolution of a ballooning instability is able to induce the formation of plasmoids in a generalized Harris sheet with finite normal magnetic component. In present work, we further examine this novel mechanism for plasmoid formation and explore its implications in the context of substorm onset trigger problem. For that purpose, we adopt the generalized Harris sheet as a model proxy to the near-Earth region of magnetotail during the substorm growth phase. In this region the magnetic component normal to the neutral sheet Bn is weak but nonzero. The magnetic field lines are closed, and there are no Xlines. Simulation results indicate that in the higher Lundquist number regime S?104, the linear axial tail mode, which is also known as "two-dimensional resistive tearing mode," is stabilized by the finite Bn, hence cannot give rise to the formation of X lines or plasmoids by itself. On the other hand, the linear ballooning mode is unstable in the same region and regime, and its nonlinear development leads to the formation of a series of plasmoid structures in the near-Earth and middle magnetotail regions of plasma sheet. This new scenario of plasmoid formation suggests a critical role of ballooning instability in the near-Earth plasma sheet in triggering the onset of a substorm expansion.

Zhu, P.; Raeder, J.



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

NASA Technical Reports Server (NTRS)

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.

Low, B. C.; Wolfson, R.



Formation and Properties of Magnetic Island Plasmoids in Large-Scale Current Sheets During CME Eruptions  

NASA Astrophysics Data System (ADS)

We present the continued analysis of the high-resolution 2.5D MHD simulations of sympathetic magnetic breakout eruptions from a pseudostreamer source region. We examine the generation of X- and O-type null points during the current sheet tearing and their evolution as reconnection progresses. There are three large-scale current sheets that we investigate in detail over the course of the simulation. We examine the properties of reconnection occurring within these current sheets including evolution of the current sheet lengths, Lundquist number, and reconnection rates. We also quantify the statistical and spectral properties of the fluctuations in the current sheets resulting from the resistive tearing and magnetic island plasmoid formation including the distribution of magnetic island width, flux content, and mass. We show that the temporal evolution of the spectral index of the magnetic energy density in our current sheets appears to reflect the transition from the linear to non-linear phase of the instability. Our results are in excellent agreement with recent dedicated reconnection simulations even though our current sheetsformation, growth, and dynamics are both dictated by and in turn, govern the global evolution of sequential, sympathetic CME eruptions.

Lynch, Benjamin J.; Edmondson, Justin K



Effect of planar anisotropy on wrinkle formation tendencies in curved sheets  

Microsoft Academic Search

Wrinkle formation tendencies in the form of short-wavelength shallow buckling modes are investigated for sheet materials exhibiting planar anisotropy. The critical state for the onset of these short-wavelength shallow modes are determined from plastic bifurcation theory. A local analysis is performed by considering the current deformed state of a sheet element in a doubly-curved, biaxial plane stress state. The planar

P. Tu?cu; K. W. Neale; P. D. Wu; S. R. MacEwen



On the possibility of electric-current sheets in dense formation  

SciTech Connect

This is a mathematical study of the formation of tangential discontinuities, or current sheets, in a magnetic field evolving in an electrically perfectly conducting fluid in response to deformation of its domain, an effect first treated by Hahm and Kulsrud [Phys. Fluids 28, 2412 (1985)]. Explicit examples are presented of three-dimensional, untwisted fields, anchored to the boundary, that cannot assume a force-free state in the absence of current sheets. The underlying physics of this process is as described by the Parker theory of spontaneous current sheets, namely, that for most continuous magnetic fields in complex three-dimensional geometry, there is an incompatibility between the preservation of field topology and point-by-point force balance to achieve equilibrium. This incompatibility is removed through discontinuous plasma displacements that produce magnetic tangential discontinuities. In contrast to the twisted magnetic fields central to the Parker theory, fixing the connectivity between the anchored magnetic footpoints alone is sufficient to lead to current-sheet formation in untwisted fields. This mode of sheet formation may produce spatially dense multitudes of sheets to heat a plasma throughout its macroscopic volume such as implied by several phenomena in the solar corona.

Low, B. C. [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, Colorado 80307 (United States) and Institute for Advanced Studies, Nanyang Technological University (Singapore)



Forced reconnection and current sheet formation in Taylor's model  

SciTech Connect

The problem of forced reconnection in Taylor's model, first investigated by Hahm and Kulsrud (Phys. Fluids {bold 28}, 2412 (1985)), is revisited. After the linear phases A, B, and C, described by Hahm and Kulsrud, the plasma enters a nonlinear phase W with a current sheet, described by Waelbroeck (Phys. Fluids B {bold 1}, 2380 (1989)). After the W phase, the plasma passes into the Rutherford regime. The reconnected flux at the separatrix increases monotonically from zero to its asymptotic value in the Rutherford regime. Analytical expressions for the reconnected flux and the island width are given.

Wang, X.; Bhattacharjee, A. (Department of Applied Physics, Columbia University, New York, New York 10027 (United States))



Transport characteristics of a beta sheet breaker peptide across excised bovine nasal mucosa.  


The purpose of the present study was to investigate the permeation characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised bovine nasal mucosa using an Ussing chamber model. The influence of various absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS), cetrimidum, sodium caprate, Na(2)EDTA, polycarbophil (PCP), the thiomer conjugate polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was evaluated. Additionally, the influence of temperature and pH on the transport rate as well as the stability of the peptide drug against enzymatic degradation were investigated in vitro. The effective permeability coefficient (P(eff)) of BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 +/- 0.44)* 10-5, while in the presence of sodium caprate (0.5%) a P(eff) of (9.58 +/- 1.82)*10-5 was achieved. Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate > Na(2)EDTA > poly-L-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease in the absorption of BSB was determined. Na2EDTA reduced the enzymatic degradation of BSB when exposed to a nasal tissue homogenate by more than the half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5) did not lead to an increased transcellular transport. Permeation studies carried out at 4 degrees C compared to 37 degrees C demonstrated a temperature dependent permeation behaviour suggesting an additional active carrier mediated transport. The results obtained within these studies should facilitate the development of a nasal delivery system for AS 602704 for the treatment of Alzheimer's disease. PMID:17192253

Greimel, Alexander; Bernkop-Schnürch, Andreas; Del Curto, Maria Dorly; D'Antonio, Mauro



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

SciTech Connect

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)

Seo, B.K.; Kim, G.H.; Park, C.H.; Jung, Y.H.; Jung, C.H.; Lee, K.W. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Han, M.J. [Kyungil Univ. (Korea, Republic of)



Current Sheet Formation and Self-Organization in Turbulent Plasmas  

NASA Astrophysics Data System (ADS)

Self-Organization can be defined as the process by which a physical system, in the course of its evolution, changes its spatial structure, the form of its equations of motion, or key coefficients in those equations. A turbulent magnetohydrodynamic (MHD) fluid can exhibit self-organization, so defined. A turbulent MHD fluid with collisional resistivity has a low rate of dissipation of turbulent energy. However, as the turbulence develops, it forms thin current sheets in which the current density increases exponentially. When the electron drift speed becomes comparable to or exceeds the ion acoustic speed, plasma instabilities can enhance the resistivity, and thus the dissipation rate. In turbulent evolution of this kind, an MHD fluid can transform itself from a low dissipation to a high dissipation state. Calculations show that it is plausible that turbulence in the solar corona could exhibit this behavior.

Spangler, Steven



Venus' Atla and Beta Regiones: Formation of Chasmata and Coronae  

NASA Astrophysics Data System (ADS)

Two likely areas of current tectonic and volcanic activity on Venus are Atla and Beta Regiones. Both are marked by pronounced topographic and geoid highs and each lies at the intersection of multiple rifts, i.e. the chasmata system. These regiones may be surface expressions of mantle upwellings. We examine the distribution, style, and attitude of coronae with respect to the two geoid highs. Coronae -- circular features unique to Venus -- could be caused by individual rising diapirs. Unlike Earth, Venus shows little evidence of horizontal motion, resulting in juxtaposition of coronae of all ages. Furthermore, there is little erosion to modify features. In our analysis, we use the three-tiered classification (based on the interior morphology) of 394 coronae, hence termed domal, circular, and calderic. These differing styles may reflect different stages in the evolution of a corona: from domal (youngest, possibly still active) features, progressing through increasing degrees of collapse to the calderic coronae. Comparing locations of these features shows the domal coronae average higher elevations, and calderic at lower elevations, with circular in between. Similar comparisons of other characteristics of the coronae, such as size, elongation, or dip, also show the progression from domal through calderic to circular. Both Atla and Beta are ringed by many coronae, but neither has coronae at or near their crests even within 20 m of their geoid highs. Coronae do occur in many rift segments, yet none occurs at or near these intersection points. Perhaps just as remarkable, Atla has a partial ring of four domal coronae, all within a 10-m geoid range of each other, whereas Beta has a partial ring of 6 or so calderic coronae between three and four 10-m contours from its crest. In both instances, the rings parallel geoid contour lines. These are the nearest coronae of their type to the crests. If corona formation is contemporaneous with the uplift process at Atla and Beta, and if the domal are younger than the calderic coronae, then Atla Regio is a recent feature and more active than Beta. This is in agreement with an independent assessment with modified craters. We use stratigraphy, crater modification, and relative tilt of craters and coronae to further test the timing of events implied in our model.

Stoddard, P. R.; Jurdy, D. M.



Effects of line-tying on magnetohydrodynamic instabilities and current sheet formation  

SciTech Connect

An overview of some recent progress on magnetohydrodynamic stability and current sheet formation in a line-tied system is given. Key results on the linear stability of the ideal internal kink mode and resistive tearing mode are summarized. For nonlinear problems, a counterexample to the recent demonstration of current sheet formation by Low and Janse [Astrophys. J. 696, 821 (2009)] is presented, and the governing equations for quasistatic evolution of a boundary driven, line-tied magnetic field are derived. Some open questions and possible strategies to resolve them are discussed.

Huang Yimin; Bhattacharjee, A. [Space Science Center, Center for Magnetic Self-Organization in Laboratory and Astrophysical Plasmas, and Center for Integrated Computation and Analysis of Reconnection and Turbulence, University of New Hampshire, Durham, New Hampshire 03824 (United States); Zweibel, Ellen G. [Department of Physics, Department of Astronomy, and Center for Magnetic Self-Organization in Laboratory and Astrophysical Plasmas, University of Wisconsin, Madison, Wisconsin 53706 (United States)



Relating thin current sheet formation and tail reconnection to substorm development  

SciTech Connect

Observations and simulations have demonstrated the important role of thin current sheet formation and magnetic reconnection in the course of substorms. We discuss new results on the formation of thin current sheets, obtained both within MHD and kinetic theory. They demonstrate when kinetic effects become important and indicate the possibility of a catastrophic onset of substorm dynamics and the potential association with arc brightening. MHD simulations show the role of reconnection in the buildup of the substorm current wedge and the influence of the underlying configuration on the quasi-static and dynamic evolution.

Birn, J. (Joachim); Schindler, K.



Current sheet formation and nonideal behavior at three-dimensional magnetic null points  

SciTech Connect

The nature of the evolution of the magnetic field, and of current sheet formation, at three-dimensional (3D) magnetic null points is investigated. A kinematic example is presented that demonstrates that for certain evolutions of a 3D null (specifically those for which the ratios of the null point eigenvalues are time-dependent), there is no possible choice of boundary conditions that renders the evolution of the field at the null ideal. Resistive magnetohydrodynamics simulations are described that demonstrate that such evolutions are generic. A 3D null is subjected to boundary driving by shearing motions, and it is shown that a current sheet localized at the null is formed. The qualitative and quantitative properties of the current sheet are discussed. Accompanying the sheet development is the growth of a localized parallel electric field, one of the signatures of magnetic reconnection. Finally, the relevance of the results to a recent theory of turbulent reconnection is discussed.

Pontin, D. I.; Bhattacharjee, A.; Galsgaard, K. [Space Science Center and Center for Magnetic Self-Organization, University of New Hampshire, Durham, New Hampshire 03824 (United States); Niels Bohr Institute, University of Copenhagen, Copenhagen (Denmark)




Microsoft Academic Search

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

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



Formation and Reconnection of Three-dimensional Current Sheets in the Solar Corona  

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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 interchange reconnection at the boundaries between coronal holes and helmet streamers in the Sun's corona. We investigate these processes for a magnetic configuration consisting of a uniform background field and an embedded line dipole, a

Justin K. Edmondson; S. K. Antiochos; C. DeVore; M. Velli; T. H. Zurbuchen



Bond formation in ultrasonically welded aluminum sheet metal  

NASA Astrophysics Data System (ADS)

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 500°C 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.

Wilkosz, Daniel Edward


Coronal heating and nanoflares: current sheet formation and heating  

NASA Astrophysics Data System (ADS)

Aims: Solar photospheric footpoint motions can produce strong, localised currents in the corona. A detailed understanding of the formation process and the resulting heating is important in modelling nanoflares, as a mechanism for heating the solar corona. Methods: A 3D MHD simulation is described in which an initially straight magnetic field is sheared in two directions. Grid resolutions up to 5123 were used and two boundary drivers were considered; one where the boundaries are continuously driven and one where the driving is switched off once a current layer is formed. Results: For both drivers a twisted current layer is formed. After a long time we see that, when the boundary driving has been switched off, the system relaxes towards a lower energy equilibrium. For the driver which continuously shears the magnetic field we see a repeating cycle of strong current structures forming, fragmenting and decreasing in magnitude and then building up again. Realistic coronal temperatures are obtained.

Bowness, R.; Hood, A. W.; Parnell, C. E.



Formation and stability of the self-consistent one-dimensional tail current sheet  

SciTech Connect

The paper investigates the formation, the structure, and the stability of self-consistent one-dimensional current sheets in which the ions carry most of the current and momentum (the occurrence of which was suggested by observations of Mitchell et al., 1990; and Sergeev et al., 1990). Results of the analysis showed that, for the case of a cold current sheet, the characteristic thickness lamba equals to about (Bz/B0) exp 4/3 c/omega(p0), where Bz is the normal field component, B0 is the asymptotic magnitude of the reversing field, and c/omega(p0)is the collisionless ion skin depth based on lobe density. A two-dimensional self-consistent dynamical simulation model is developed, which demonstrates that these idealized current sheets are unstable to kink perturbations driven by the anisotropic pressure distribution produced by the chaotic nature of the particle orbits in a field-reversal region. 32 refs.

Pritchett, P.L.; Coroniti, F.V. (California Univ., Los Angeles (United States))



Estradiol improves cerebellar memory formation by activating estrogen receptor beta.  


Learning motor skills is critical for motor abilities such as driving a car or playing piano. The speed at which we learn those skills is subject to many factors. Yet, it is not known to what extent gonadal hormones can affect the achievement of accurate movements in time and space. Here we demonstrate via different lines of evidence that estradiol promotes plasticity in the cerebellar cortex underlying motor learning. First, we show that estradiol enhances induction of long-term potentiation at the parallel fiber to Purkinje cell synapse, whereas it does not affect long-term depression; second, we show that estradiol activation of estrogen receptor beta receptors in Purkinje cells significantly improves gain-decrease adaptation of the vestibulo-ocular reflex, whereas it does not affect general eye movement performance; and third, we show that estradiol increases the density of parallel fiber to Purkinje cell synapses, whereas it does not affect the density of climbing fiber synapses. We conclude that estradiol can improve motor skills by potentiating cerebellar plasticity and synapse formation. These processes may be advantageous during periods of high estradiol levels of the estrous cycle or pregnancy. PMID:17913916

Andreescu, Corina E; Milojkovic, Bogdan A; Haasdijk, Elize D; Kramer, Piet; De Jong, Frank H; Krust, Andrée; De Zeeuw, Chris I; De Jeu, Marcel T G



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

NASA Technical Reports Server (NTRS)

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

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




SciTech Connect

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 (3D) magnetohydrodynamic 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 directly apply the vast body of knowledge gained from the many studies of two-dimensional (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.

Edmondson, J. K. [NASA Jet Propulsion Laboratory, Pasadena, CA 91109 (United States); Antiochos, S. K. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); DeVore, C. R. [Naval Research Laboratory, Washington, DC 20375 (United States); Zurbuchen, T. H., E-mail: jkedmond@umich.ed [Department of Atmospheric, Oceanic, and Space Science, University of Michigan, Ann Arbor, MI 48105 (United States)



Formation and Reconnection of Three-dimensional Current Sheets in the Solar Corona  

NASA Astrophysics Data System (ADS)

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 (3D) magnetohydrodynamic 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 directly apply the vast body of knowledge gained from the many studies of two-dimensional (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.

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



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

NASA Astrophysics Data System (ADS)

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 interchange reconnection at the boundaries between coronal holes and helmet streamers in 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.

Edmondson, Justin K.; Antiochos, S. K.; DeVore, C.; Velli, M.; Zurbuchen, T. H.



Average electric wave spectra in the plasma sheet - Dependence on ion density and ion beta  

Microsoft Academic Search

Using 4 months of tail data obtained by the ELF\\/MF spectrum analyzer and the plasma instrument on board the AMPTE\\/IRM satellite, more than 50,000 ten-second-averaged electric wave spectra were analyzed in order to establish typical spectra for periods of high and low ion density and high and low ion beta. Highest average spectral densities are obtained in the low-beta plasma

Wolfgang Baumjohann; Rudolf A. Treumann; J. Labelle



Martensite formation, strain rate sensitivity, and deformation behavior of type 304 stainless steel sheet  

Microsoft Academic Search

The strain and strain rate dependence of the deformation behavior of Type 304 stainless steel sheet was evaluated by constant\\u000a temperature tensile testing in the temperature range of ?80 C to 160 C. The strain rate sensitivity, strain hardening rate,\\u000a and ductility reflected the compctition of two strengthening mechanisms: strain-induced transformation of austenite to martensite\\u000a and dislocation substructure formation. At

G. L. Huang; Dk. Matlock; G. Krauss



Mechanism of IAPP amyloid fibril formation involves an intermediate with a transient ?-sheet  

PubMed Central

Amyloid formation is implicated in more than 20 human diseases, yet the mechanism by which fibrils form is not well understood. We use 2D infrared spectroscopy and isotope labeling to monitor the kinetics of fibril formation by human islet amyloid polypeptide (hIAPP or amylin) that is associated with type 2 diabetes. We find that an oligomeric intermediate forms during the lag phase with parallel ?-sheet structure in a region that is ultimately a partially disordered loop in the fibril. We confirm the presence of this intermediate, using a set of homologous macrocyclic peptides designed to recognize ?-sheets. Mutations and molecular dynamics simulations indicate that the intermediate is on pathway. Disrupting the oligomeric ?-sheet to form the partially disordered loop of the fibrils creates a free energy barrier that is the origin of the lag phase during aggregation. These results help rationalize a wide range of previous fragment and mutation studies including mutations in other species that prevent the formation of amyloid plaques.

Buchanan, Lauren E.; Dunkelberger, Emily B.; Tran, Huong Q.; Cheng, Pin-Nan; Chiu, Chi-Cheng; Cao, Ping; Raleigh, Daniel P.; de Pablo, Juan J.; Nowick, James S.; Zanni, Martin T.



Incorporation of conformationally constrained beta-amino acids into peptides.  


The use of norbornene units to induce the formation of beta-sheet and beta-turn type structures in peptides is discussed. The norbornene unit is readily prepared by a desymmetrization reaction and is easily incorporated into a peptide chain. Depending upon the exact nature of the norbornene unit, it is possible to form structures which resemble parallel beta-sheets, antiparallel beta-sheets or beta-turns. Similar peptide analogues incorporating a cis-2-amino-cyclopropane carboxylic acid unit can also be prepared. As an illustration of the application of this chemistry, a short, asymmetric synthesis of conformationally constrained metalloprotease inhibitors is presented. PMID:10946995

North, M



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

Microsoft Academic Search

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

Kelly J. Mitchell



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

Microsoft Academic Search

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

S. J. Martel



His26 Protonation in Cytochrome c Triggers Microsecond ?-sheet Formation and Heme Exposure: Implications for Apoptosis  

PubMed Central

Cytochrome c unfolds locally and reversibly upon heating at pH 3. UV resonance Raman (UVRR) spectra reveal that instead of producing unordered structure, unfolding converts turns and some helical elements to ?-sheet. It also disrupts the Met80-heme bond, and was earlier shown to induce peroxidase activity. Aromatic residues that are H-bonded to a heme propionate (Trp59 and Tyr48) alter their orientation, indicating heme displacement. T-jump/UVRR measurements give time constants of 0.2, 3.9 and 67 µs for successive phases of ?-sheet formation and concomitant reorientation of Trp59. UVRR spectra reveal protonation of histidines, and specifically of His26, whose H-bond to Pro44 anchors the 40s ? loop; this loop is known to be the least stable ‘foldon’ in the protein. His26 protonation is proposed to disrupt its H-bond with Pro44, triggering the extension of a short ?-sheet segment at the ‘neck’ of the 40s ? loop into the loop itself and back into the 60’s and 70’s helices. The secondary structure change displaces the heme via H-bonds from residues in the growing ?-sheet, thereby exposing it to exogenous ligands, and inducing peroxidase activity. This unfolding mechanism may play a role in cardiolipin peroxidation by cyt c during apoptosis.

Balakrishnan, Gurusamy; Hu, Ying; Spiro, Thomas G.



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

NASA Astrophysics Data System (ADS)

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.

Piotrowski, Jan A.



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

NASA Technical Reports Server (NTRS)

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.

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



pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; implications for the control of beta-sheet A and polymerization.  


Neuroserpin is a member of the serpin superfamily. Point mutations in the neuroserpin gene underlie the autosomal dominant dementia, familial encephalopathy with neuroserpin inclusion bodies. This is characterized by the retention of ordered polymers of neuroserpin within the endoplasmic reticulum of neurons. pH has been shown to affect the propensity of several serpins to form polymers. In particular, low pH favors the formation of polymers of both alpha(1)-antitrypsin and antithrombin. We report here opposite effects in neuroserpin, with a striking resistance to polymer formation at acidic pH. Mutation of specific histidine residues showed that this effect is not attributable to the shutter domain histidine as would be predicted by analogy with other serpins. Indeed, mutation of the shutter domain His338 decreased neuroserpin stability but had no effect on the pH dependence of polymerization when compared with the wild-type protein. In contrast, mutation of His119 or His138 reduced the polymerization of neuroserpin at both acidic and neutral pH. These residues are at the lower pole of neuroserpin and provide a novel mechanism to control the opening of beta-sheet A and hence polymerization. This mechanism is likely to have evolved to protect neuroserpin from the acidic environment of the secretory granules. PMID:19953505

Belorgey, Didier; Hägglöf, Peter; Onda, Maki; Lomas, David A



A statistical study of current-sheet formation above solar active regions based on selforganized criticality  

NASA Astrophysics Data System (ADS)

We treat flaring solar active regions as physical systems having reached the self-organized critical state. Their evolving magnetic configurations in the low corona may satisfy an instability criterion, related to the excession of a specific threshold in the curl of the magnetic field. This imposed instability criterion implies an almost zero resistivity everywhere in the solar corona, except in regions where magnetic-field discontinuities and. hence, local currents, reach the critical value. In these areas, current-driven instabilities enhance the resistivity by many orders of magnitude forming structures which efficiently accelerate charged particles. Simulating the formation of such structures (thought of as current sheets) via a refined SOC cellular-automaton model provides interesting information regarding their statistical properties. It is shown that the current density in such unstable regions follows power-law scaling. Furthermore, the size distribution of the produced current sheets is best fitted by power laws, whereas their formation probability is investigated against the photospheric magnetic configuration (e.g. Polarity Inversion Lines, Plage). The average fractal dimension of the produced current sheets is deduced depending on the selected critical threshold. The above-mentioned statistical description of intermittent electric field structures can be used by collisional relativistic test particle simulations, aiming to interpret particle acceleration in flaring active regions and in strongly turbulent media in astrophysical plasmas. The above work is supported by the Hellenic National Space Weather Research Network (HNSWRN) via the THALIS Programme.

Dimitropoulou, M.; Isliker, H.; Vlahos, L.; Georgoulis, M.; Anastasiadis, A.; Toutountzi, A.



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

SciTech Connect

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.

Stockman, B.J.



Dynamics of current sheet formation and reconnection in two-dimensional coronal loops  

SciTech Connect

Current sheet formation and magnetic reconnection in a two-dimensional coronal loop with an X-type neutral line are simulated numerically using compressible, resistive magnetohydrodynamic equations. Numerical results in the linear and nonlinear regimes are shown to be in good agreement with a recent analytical theory [X. Wang and A. Bhattacharjee, Astrophys. J. {bold 420}, 415 (1994)]. The topological constraint imposed by helicity-conserving reconnection is discussed. It is found numerically that helicity-conserving reconnection causes the initial X-point structure of the loop to change to Y points, with current sheets at the separatrices encompassing the Y points. Implications for observations are discussed. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

Ma, Z.W.; Ng, C.S.; Wang, X.; Bhattacharjee, A. [Department of Physics and Astronomy, University of Iowa, Iowa City, Iowa 52242 (United States)] [Department of Physics and Astronomy, University of Iowa, Iowa City, Iowa 52242 (United States)



Reduction of Postoperative Scar Formation With Silicone Sheeting: 2 Case Studies  

PubMed Central

Elective surgeries account for millions of acquired scars annually. Many of these scars can be problematic, being aesthetically unpleasant and causing discomfort. Silicone gel sheeting has been shown to be efficacious for the prevention and treatment of problematic scars. By wound hydration, along with other factors, silicone dressings are thought to decrease scarring. However, we found the usual treatment was commonly started after epithelialization of the incision site. The current standard of care in wound healing is to promote a moist wound environment to ensure quick epithelialization and decrease excessive scar formation. With that standard in mind, after foot surgery was performed on 2 patients, silicone sheeting was applied immediately in order to compare its effects with those of standard moist wound healing (XEROFORM Petrolatum Gauze).

Moore, Kirsten A.; Silbernagel, BoniJo



The palladium assisted transfer reduction of. alpha. ,. beta. -unsaturated nitroalkenes to oximes using ammonium formate  

SciTech Connect

{alpha},{beta}-Unsaturated nitroalkenes are readily reduced to the corresponding oximes in good yields using ammonium formate in the presence of palladium. The reactions occur rapidly at room temperature in a solvent system of methanol and tetrahydrofuran.

Kabalka, G.W.; Pace, R.D.; Wadgaonkar, P.P. (Univ. of Tennessee, Knoxville (United States))



Mechanical activation and cement formation of beta-tricalcium phosphate.  


The reactivity of acid base cements forming hydroxyapatite (HA) such as, tetracalcium phosphate, and dicalcium phosphate anhydride or dicalcium phosphate dihydrate, is normally adjusted by altering the particle size and hence the specific surface area of the compounds. Amorphous calcium phosphates, prepared by precipitation from supersaturated solutions, can also react to form apatitic cements since they are thermodynamic unstable with respect to HA and have a setting reaction more independent of particle size. In this report we show for the first time that prolonged high-energy ball milling of beta-tricalcium phosphate (beta-TCP), led to mechanically induced phase transformation from the crystalline to the amorphous state. The process increased the thermodynamic solubility of the beta-TCP compared to the unmilled material by up to nine times and accelerated the normally slow reaction with water. By using a 2.5% Na(2)HPO(4) solution setting times were reduced to 5-16min rather than hours. X-ray diffraction analyses indicated that the amorphous fraction within the materials was responsible for the primary setting reaction and hardening of the cements, while the crystalline fraction remained unreacted and converted only slowly to HA. Mechanically activated beta-TCP cements were produced with compressive and diametral tensile strengths of up to 50 and 7MPa respectively. The effect of preparation and setting parameters on the physical and chemical properties of mechanically activated beta-TCP cement was investigated. PMID:12853242

Gbureck, U; Grolms, O; Barralet, J E; Grover, L M; Thull, R



Contrasting roles for beta1, beta2 and beta3-adrenoceptors in memory formation in the chick.  


Noradrenaline plays distinct roles in the modulation and consolidation of memory for one-trial, discriminated, avoidance learning in the chick. We have previously shown that activation of beta2-, beta3- and alpha1-adrenoceptors (ARs) by injection into the multimodal forebrain association region (intermediate medial hyperstriatum ventrale [IMHV] or intermediate medial mesopallium [IMM]) is involved in the consolidation of memory 30 min after training and that activation of alpha2-ARs in the caudate putamen plays a role in the reinforcement of memory leading to consolidation in the IMM (IMHV). In this paper we provide evidence that noradrenaline acts at beta1-ARs in the basal ganglia (lobus parolfactorius or medial striatum) in short-term memory processing immediately post-training and demonstrate inhibition of memory by selective AR antagonists at particular times in the sequential memory processing sequence after training. These results support separate roles for beta2- and beta3-ARs in memory consolidation. Our studies suggest that, as a consequence of the learning experience, noradrenaline acts in different brain regions and at different times in memory processing, to enhance memory through distinct populations of ARs. PMID:15680689

Gibbs, M E; Summers, R J



Entrainment of prefrontal Beta oscillations induces an endogenous echo and impairs memory formation.  


Brain oscillations across all frequency bands play a key role for memory formation [1-4]. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (?18 Hz) has been shown to be central for encoding of verbal memories [5-8]. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. PMID:24684933

Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin



Generation of Alzheimer beta Amyloid Protein in the Trans-Golgi Network in the Apparent Absence of Vesicle Formation  

Microsoft Academic Search

beta -amyloid protein (Abeta ) formation was reconstituted in permeabilized neuroblastoma cells expressing human Alzheimer beta -amyloid precursor protein (beta APP) harboring the Swedish double mutation associated with familial early-onset Alzheimer disease. Permeabilized cells were prepared following metabolic labeling and incubation at 20 degrees C, a temperature that allows beta APP to accumulate in the trans-Golgi network (TGN) without concomitant

Huaxi Xu; David Sweeney; Rong Wang; Gopal Thinakaran; Amy C. Y. Lo; Sangram S. Sisodia; Paul Greengard; Sam Gandy



A Molecular Model of Alzheimer Amyloid beta Peptide Fibril Formation  

Microsoft Academic Search

Polymerization of the amyloid beta (Ab) peptide into protease-resistant fibrils is a significant step in the pathogenesis of Alzheimer's disease. It has not been pos- sible to obtain detailed structural information about this process with conventional techniques because the peptide has limited solubility and does not form crys- tals. In this work, we present experimental results lead- ing to a

Lars O. Tjernberg; David J. E. Callaway; Agneta Tjernbergi; Solveig Hahne; Christina Lilliehook; Lars Terenius; Johan Thyberg; Christer Nordstedt



Interepithelial signaling with nephric duct is required for the formation of overlying coelomic epithelial cell sheet.  


In most organs of the body, epithelial tissues are supported by their own basement membrane and underlying stroma, the latter being regarded as a complex of amorphous cells, extracellular matrices, and soluble factors. We demonstrate here that an epithelial tube can serve as a component of stroma that supports the formation of epithelial cell sheet derived from a different origin. During development of the mesonephros in chicken embryos, the intermediate mesoderm (IMM), which contains the Wolffian duct (WD) and its associated tubules, is overlain by a sheet of epithelial cells derived from lateral plate (coelomic) mesoderm. We describe that in normal embryos, epitheliogenesis of IMM tubes and the adjacent coelomic cell sheet proceed in a coordinated manner. When the WD was surgically ablated, the overlying coelomic epithelium exhibited aberrant morphology accompanied by a punctated basement membrane. Furthermore, the WD-ablated coelomic epithelium became susceptible to latent external stress; electroporation of Rac1 resulted in epithelial-to-mesenchymal transitions (EMTs) within the coelomic epithelium. The distorted coelomic epithelium was rescued by implanting fibronectin-producing cells in place of the WD, suggesting that fibronectin provided by WD has an important role acting interepithelially. This notion was corroborated further by directly visualizing a translocation of EGFP-tagged fibronectin from fibronectin-producing to -receiving epithelia in vivo. Our findings provide a novel insight into interepithelial signaling that also might occur in adult tissues to protect against EMT and suggest a possible new target for anticancer therapeutic strategy. PMID:24753584

Yoshino, Takashi; Saito, Daisuke; Atsuta, Yuji; Uchiyama, Chihiro; Ueda, Shinya; Sekiguchi, Kiyotoshi; Takahashi, Yoshiko



Beta thalassemia and energy consumption in hemoglobin A1C formation: a model.  


Hemoglobin (Hb) A1C is the nonenzymatic glycated product of the Hb beta chain at the valine terminal residue. Recently, the nature of energy-consuming reaction in HbA1C formation was reported, and this was proposed as an underlying pathophysiology for poor nutritional status, muscle loss, and functional impairment in poor-control diabetic patients. Here, the author focuses on energy change in HbA1C formation in the case of beta thalassemia. According to this study, the energy range required for any type of beta thalassemia is greater than that required for normal Hb. Hence, it might be expressed that beta thalassemia did significantly increase complications due to energy consumption during HbA1C formation in poor-control diabetic cases. PMID:17825760

Wiwanitkit, Viroj



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


Beta(2)-microglobulin (beta(2)m) is the amyloidogenic protein in dialysis-related amyloidosis, but the mechanisms underlying beta(2)m fibrillogenesis in vivo are largely unknown. We study a structural variant of beta(2)m that has been linked to cancer and inflammation and may be present in the circulation of dialysis patients. This beta(2)m variant, DeltaK58-beta(2)m, is a disulfide-linked two-chain molecule consisting of amino acid residues 1-57 and 59-99 of intact beta(2)m, and we here demonstrate and characterize its decreased conformational stability as compared to wild-type (wt) beta(2)m. Using amide hydrogen/deuterium exchange monitored by mass spectrometry, we show that DeltaK58-beta(2)m has increased unfolding rates compared to wt-beta(2)m and that unfolding is highly temperature dependent. The unfolding rate is 1 order of magnitude faster in DeltaK58-beta(2)m than in wt-beta(2)m, and at 37 degrees C the half-time for unfolding is more than 170-fold faster than at 15 degrees C. Conformational changes are also reflected by a very prominent Congo red binding of DeltaK58-beta(2)m at 37 degrees C, by the evolution of thioflavin T fluorescence, and by changes in intrinsic fluorescence. After a few days at 37 degrees C, in contrast to wt-beta(2)m, DeltaK58-beta(2)m forms well-defined high molecular weight aggregates that are detected by size-exclusion chromatography. Atomic force microscopy after seeding with amyloid-beta(2)m fibrils under conditions that induce minimal fibrillation in wt-beta(2)m shows extensive amyloid fibrillation in DeltaK58-beta(2)m samples. The results highlight the instability and amyloidogenicity under near physiological conditions of a slightly modified beta(2)m variant generated by limited proteolysis and illustrate stages of amyloid formation from early conformational variants to overt fibrillation. PMID:15766269

Heegaard, Niels H H; Jørgensen, Thomas J D; Rozlosnik, Noémi; Corlin, Dorthe B; Pedersen, Jesper S; Tempesta, Anna G; Roepstorff, Peter; Bauer, Rogert; Nissen, Mogens H



Beta-galactosidase from Lactobacillus pentosus: purification, characterization and formation of galacto-oligosaccharides.  


A novel heterodimeric beta-galactosidase with a molecular mass of 105 kDa was purified from crude cell extracts of the soil isolate Lactobacillus pentosus KUB-ST10-1 using ammonium sulphate fractionation followed by hydrophobic interaction and affinity chromatography. The electrophoretically homogenous enzyme has a specific activity of 97 U(oNPG)/mg protein. The K(m), k(cat) and k(cat)/K(m) values for lactose and o-nitrophenyl-beta-D-galactopyranoside (oNPG) were 38 mM, 20 s(-1), 530 M(-1).s(-1) and 1.67 mM, 540 s(-1), 325 000 M(-1).s(-1), respectively. The temperature optimum of beta-galactosidase activity was 60-65 degrees C for a 10-min assay, which is considerably higher than the values reported for other lactobacillal beta-galactosidases. Mg(2+) ions enhanced both activity and stability significantly. L. pentosus beta-galactosidase was used for the production of prebiotic galacto-oligosaccharides (GOS) from lactose. A maximum yield of 31% GOS of total sugars was obtained at 78% lactose conversion. The enzyme showed a strong preference for the formation of beta-(1-->3) and beta-(1-->6) linkages, and the main transgalactosylation products identified were the disaccharides beta-D-Galp-(1-->6)-D-Glc, beta-D-Galp-(1-->3)-D-Glc, beta-D-Galp-(1-->6)-D-Gal, beta-D-Galp-(1-->3)-D-Gal, and the trisaccharides beta-D-Galp-(1-->3)-D-Lac, beta-D-Galp-(1-->6)-D-Lac. PMID:20669255

Maischberger, Thomas; Leitner, Elisabeth; Nitisinprasert, Sunee; Juajun, Onladda; Yamabhai, Montarop; Nguyen, Thu-Ha; Haltrich, Dietmar



Existing Data Format for Twp-Parameter Beta-Gamma Histograms for Radioxenon.  

National Technical Information Service (NTIS)

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 ...

AD McKinnon E Wittinger JI McIntyre PL Reeder TR Heimbigner



Formation and transport of sheet-electron beams and multibeam configurations for high-power microwave devices  

NASA Astrophysics Data System (ADS)

Sheet electron beams and configurations with multiple electron beams have the potential to make possible higher power sources of microwave radiation due to their ability to transport high currents, at reduced current densities, through a single RF interaction circuit. Possible microwave device applications using sheet electron beams include sheet-beam klystrons, rectangular grating circuits, and planar FELs. Historically, implementation of sheet beams in microwave devices has been discouraged by their susceptibility to the diocotron instability in solenoidal focusing systems. However, recent theoretical and numerical studies have shown that stable transport of sheet beams is possible in periodically cusped magnetic (PCM) fields. The use of an offset-pole PCM configuration has been shown analytically to provide side- fields for 2D focusing of the beam, and this has been recently verified with PIC code simulations. We will present further theoretical studies of sheet and multibeam transport and discuss results from an experimental investigation of the formation, stability and transport of PCM-focused sheet electron beams. This includes a laboratory method of forming an elliptical sheet beam using magnetic quadrupole pair and a round-beam Pierce gun.

Basten, Mark A.; Booske, Jon H.; Anderson, Jim; Scharer, John E.



Pulling geometry defines the mechanical resistance of a beta-sheet protein.  


Proteins show diverse responses when placed under mechanical stress. The molecular origins of their differing mechanical resistance are still unclear, although the orientation of secondary structural elements relative to the applied force vector is thought to have an important function. Here, by using a method of protein immobilization that allows force to be applied to the same all-beta protein, E2lip3, in two different directions, we show that the energy landscape for mechanical unfolding is markedly anisotropic. These results, in combination with molecular dynamics (MD) simulations, reveal that the unfolding pathway depends on the pulling geometry and is associated with unfolding forces that differ by an order of magnitude. Thus, the mechanical resistance of a protein is not dictated solely by amino acid sequence, topology or unfolding rate constant, but depends critically on the direction of the applied extension. PMID:12923573

Brockwell, David J; Paci, Emanuele; Zinober, Rebecca C; Beddard, Godfrey S; Olmsted, Peter D; Smith, D Alastair; Perham, Richard N; Radford, Sheena E



Effect of initial textures on texture formation in AA 3004 sheets during continuous confined strip shearing and subsequent annealing  

Microsoft Academic Search

The effect of initial textures on the texture formation during continuous confined strip shearing (CCSS) and subsequent annealing\\u000a was investigated in AA 3004 sheets. The CCSS tools were designed to provide a constant shear strain of the order of 0.5 per\\u000a pass while preserving the original sheet shape. During the CCSS deformation, the initial texture disappeared, and shear texture\\u000a components

Hoon-Dong Kim; Moo-Young Huh; No-Jin Park; Young-Hoon Chung



Formation and antimicrobial activity of complexes of beta-cyclodextrin and some antimycotic imidazole derivatives.  


Complex formation between beta-cyclodextrin and six antimycotic imidazole derivatives has been studied. The solubility of all drugs was increased in the presence of beta-cyclodextrin. The smallest increase (approx. 5-fold) was observed for miconazol, and the largest increase (approx. 160-fold) was observed for bifonazol. Apparent 1:1-complex constants were measured and found to decrease in the order: bifonazol greater than ketoconazol greater than tioconazol greater than miconazol greater than itraconazol greater than clotrimazol. The complexes appeared to possess a low, if any, antimicrobial activity. Measurement of inhibition zone sizes, with four test organisms was used to study the release of the antimycotic drugs from topical preparations. The antimycotic drugs were more readily released from topical preparations containing beta-cyclodextrin than from the same vehicles without beta-cyclodextrin. The rationale of beta-cyclodextrin addition to antimycotic topical preparations is discussed. PMID:3393422

Van Doorne, H; Bosch, E H; Lerk, C F



The formation and dynamics of a blob on free and wall sheets induced by a drop impact on surfaces  

NASA Astrophysics Data System (ADS)

A physical model for describing an inviscid motion of free and wall liquid sheets induced by drop impact is presented. This model takes into account the formation of thick borders at the edge of a spreading drop, and the influence of advancing and receding contact angles on the dynamics of blob formation and motion. It has been shown that the blob motion on a free liquid sheet is described by a universal relationship (independent of the Weber number) in terms of dimensionless blob coordinates at both advancing and receding stages. For the case of blob formation and motion on a wall sheet at high Weber numbers, only the advancing stage is described by a universal relationship. The receding stage depends on the ratio of advancing and receding contact angles, but not on the Weber number. At the instant when the drop is at its maximum extension, the blob speed becomes equal to the liquid sheet velocity and the total kinetic energy of the drop is greater than zero. It is shown that the ratio of the instantaneous capillary wavelength to the sheet thickness is a constant 2.619 for a free sheet, when the capillary wave propagates away from the blob.

Fedorchenko, Alexander I.; Wang, An-Bang



Regulation of formation of the intracellular beta-galactosidase activity of Aspergillus nidulans.  


The regulation of formation of the single intracellular beta-galactosidase activity of Aspergillus nidulans was investigated. beta-Galactosidase was not formed during growth on glucose or glycerol, but was rapidly induced during growth on lactose or D-galactose. L-Arabinose, and -- with lower efficacy -- D-xylose also induced beta-galactosidase activity. Addition of glucose to cultures growing on lactose led to a rapid decrease in beta-galactosidase activity. In contrast, in cultures growing on D-galactose, addition of glucose decreased the activity of beta-galactosidase only slightly. Glucose inhibited the uptake of lactose, but not of D-galactose, and required the carbon catabolite repressor CreA for this. In addition, CreA also repressed the formation of basal levels of beta-galactosidase and partially interfered with the induction of beta-galactosidase by D-galactose, L-arabinose, and D-xylose. D-Galactose phosphorylation was not necessary for beta-galactosidase induction, since induction by D-galactose occurred in an A. nidulans mutant defective in galactose kinase, and by the non-metabolizable D-galactose analogue fucose in the wild-type strain. Interestingly, a mutant in galactose-1-phosphate uridylyl transferase produced beta-galactosidase at a low, constitutive level even on glucose and glycerol and was no longer inducible by D-galactose, whereas it was still inducible by L-arabinose. We conclude that biosynthesis of the intracellular beta-galactosidase of A. nidulans is regulated by CreA, partially repressed by galactose-1-phosphate uridylyl transferase, and induced by D-galactose and L-arabinose in independent ways. PMID:12471499

Fekete, Erzsébet; Karaffa, Levente; Sándor, Erzsébet; Seiboth, Bernhard; Biró, Sándor; Szentirmai, Attila; Kubicek, Christian P



Formation of aminosuccinyl derivative from beta-phenacyl aspartyl peptides catalyzed by sodium thiophenoxide.  


In the solid-phase synthesis of cholecystokinin 30-33, Trp-Met-Asp-Phe- amide, the beta-phenacyl ester was used to protect the beta-carboxyl of aspartyl residue. The ester was cleaved, on the solid support, with a 1 M solution of sodium thiophenoxide in DMF, prior to ammonolysis. The product, after purification by countercurrent distribution, was identified as a mixture of isoasparaginyl and aspartyl peptides. A study of the deprotection step, with sodium thiophenoxide, on a model peptide (t-butyloxycarbonyl-beta-phenacyl-aspartyl-phenylalanineamide) showed the rapid formation of the aminosuccinyl derivative, catalyzed by this reagent. PMID:7118398

Gaudreau, P; Morell, J L; Gross, E



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

Microsoft Academic Search

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

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



C. elegans STAT cooperates with DAF-7/TGF-beta signaling to repress dauer formation.  


The DAF-7/TGF-beta pathway in C. elegans interprets environmental signals relayed through amphid neurons and actively inhibits dauer formation during reproductive developmental growth . In metazoans, the STAT pathway interprets external stimuli through regulated tyrosine phosphorylation, nuclear translocation, and gene expression , but its importance for developmental commitment, particularly in conjunction with TGF-beta, remains largely unknown. Here, we report that the nematode STAT ortholog STA-1 accumulated in the nuclei of five head neuron pairs, three of which are amphid neurons involved in dauer formation . Moreover, sta-1 mutants showed a synthetic dauer phenotype with selected TGF-beta mutations. sta-1 deficiency was complemented by reconstitution with wild-type protein, but not with a tyrosine mutant. Canonical TGF-beta signaling involves the DAF-7/TGF-beta ligand activating the DAF-1/DAF-4 receptor pair to regulate the DAF-8/DAF-14 Smads . Interestingly, STA-1 functioned in the absence of DAF-7, DAF-4, and DAF-14, but it required DAF-1 and DAF-8. Additionally, STA-1 expression was induced by TGF-beta in a DAF-3-dependent manner, demonstrating a homeostatic negative feedback loop. These results highlight a role for activated STAT proteins in repression of dauer formation. They also raise the possibility of an unexpected function for DAF-1 and DAF-8 that is independent of their normal upstream activator, DAF-7. PMID:16401427

Wang, Yaming; Levy, David E



Low cost fabrication of sheet structure using a new beta titanium alloy, Ti-15V-3Cr-3Al-3Sn  

NASA Technical Reports Server (NTRS)

Development efforts have been undertaken to improve the processing and structural efficiencies of advanced cold-formable beta Ti alloys, using the standard, hot-formed and rivetted construction of Ti-6Al-4V sheet structures as a basis for comparison. Ti-15V-3Cr-3Al-3Sn (Ti-15-3) beta alloy is formable, brazable and weldable in the solution-treated condition, and after aging displays mechanical properties suitable for postulated service in the -65 to 600 F temperature range. A novel methodology using cold-formed Ti-15-3 stringers and Ti-6Al-4V face sheets that are joined by means of an out-of-furnace isothermal brazing process, followed by low temperature aging, can reduce production costs by as much as 28 per cent. Structural efficiency has been demonstrated in room and elevated temperature crippling tests of small skin-stringer assemblies.

Kaneko, R. S.; Davis, G. W.; Woods, C. A.; Royster, D. M.



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

SciTech Connect

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.

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



The intact human acetylcholinesterase C-terminal oligomerization domain is alpha-helical in situ and in isolation, but a shorter fragment forms beta-sheet-rich amyloid fibrils and protofibrillar oligomers.  


A 14-residue fragment of the C-terminal oligomerization domain, or T-peptide, of human acetylcholinesterase (AChE) shares sequence homology with the amyloid-beta peptide implicated in Alzheimer's disease and can spontaneously self-assemble into classical amyloid fibrils under physiological conditions [Greenfield, S. A., and Vaux, D. J. (2002) Neuroscience 113, 485-492; Cottingham, M. G., Hollinshead, M. S., and Vaux, D. J. (2002) Biochemistry 41, 13539-13547]. Here we demonstrate that the conformation of this AChE(586-599) peptide, both before and after fibril formation, is different from that of a longer peptide, T(40), corresponding to the entire 40-amino acid T-peptide (residues 575-614 of AChE). This peptide is prone to homomeric hydrophobic interactions, consistent with its role in AChE subunit assembly, and possesses an alpha-helical structure which protects against the development of the beta-sheet-rich amyloidogenic conformation favored by the shorter constituent AChE(586-599) fragment. Using a conformation-sensitive monoclonal antibody raised against the alpha-helical T(40) peptide, we demonstrate that the conformation of the T-peptide domain within intact AChE is antigenically indistinguishable from that of the synthetic T(40) peptide. A second monoclonal antibody raised against the fibrillogenic AChE(586-599) fragment recognizes not only beta-sheet amyloid aggregates but also SDS-resistant protofibrillar oligomers. A single-antibody sandwich ELISA confirms that such oligomers exist at micromolar peptide concentrations, well below that required for formation of classical amyloid fibrils. Epitope mapping with this monoclonal antibody identifies a region near the N-terminus of the peptide that remains accessible in oligomer and fibril alike, suggesting a model for the arrangement of subunits within AChE(586-599) protofibrils and fibrils. PMID:12962511

Cottingham, Matthew G; Voskuil, Jan L A; Vaux, David J T



Lagrangian Simulations of Current Sheet Formation During Relaxation of an Unstable Line-Tied Equilibrium  

NASA Astrophysics Data System (ADS)

Our recent theory, based on reduced MHD equations, predicts the formation of current sheets (tangential discontinuities) in an ideal line-tied plasma when an unstable equilibrium relaxes to a state of minimum energy [C. S. Ng and A. Bhattacharjee, Phys. Plasmas 5, 4028 (1998)]. This mechanism has important implications for the heating of the solar corona, first envisioned by E. N. Parker. Testing of this prediction using conventional Eulerian simulations is subjected to the intrinsic numerical difficulty that the magnetic field line mapping is not kept fixed explicitly, as required by the line-tied condition. In fact, field line mapping can change substantially by reconnection due to numerical resistivity. To overcome this obstacle, we have developed a Lagrangian relaxation algorithm to simulate the evolution of an unstable equilibrium by following the movement of magnetic field lines explicitly. Preliminary simulation results will be presented.

Lin, Liwei; Ng, C. S.; Bhattacharjee, A.



Stability of formate species on beta-Ga2O3.  


Gallia (gallium oxide) has been proved to enhance the performance of metal catalysts in a variety of catalytic reactions involving methanol, CO and H(2). The presence of formate species as key intermediates in some of these reactions has been reported, although their role is still a matter of debate. In this work, a combined theoretical and experimental approach has been carried out in order to characterize the formation of such formate species over the gallium oxide surface. Infrared spectroscopy experiments of CO adsorption over H(2) (or D(2)) pretreated beta-Ga(2)O(3) revealed the formation of several formate species. The beta-Ga(2)O(3) (100) surface was modelled by means of periodic DFT calculations. The stability of said species and their vibrational mode assignments are discussed together with the formate interconversion barriers. A possible mechanism is proposed based on the experimental and theoretical results: first CO inserts into surface (monocoordinate) hydroxyl groups leading to monocoordinate formate; this species might evolve to the thermodynamically most stable dicoordinate formate, or might transfer hydrogen to the surface oxidizing to CO(2) creating an oxygen vacancy and a hydride group. The barrier for the first step, CO insertion, is calculated to be significantly higher than that of the monocoordinate formate conversion steps. Monocoordinate formates are thus short-lived intermediates playing a key role in the CO oxidation reaction, while bidentate formates are mainly spectators. PMID:19224041

Calatayud, M; Collins, S E; Baltanás, M A; Bonivardi, A L



The roles of TGF-beta1 gene transfer on collagen formation during Achilles tendon healing.  


Collagen content and cross-linking are believed to be major determinants of tendon structural integrity and function. The current study aimed to investigate the effects of transforming growth factor (TGF)-beta1 on the collagen content and cross-linking of Achilles tendons, and on the histological and biomechanical changes occurring during Achilles tendon healing in rabbits. Bone marrow-derived mesenchymal stem cells (BMSCs) transfected with the TGF-beta1 gene were surgically implanted into experimentally injured Achilles tendons. Collagen proteins were identified by immunohistochemical staining and fiber bundle accumulation was revealed by Sirius red staining. Achilles tendons treated with TGF-beta1-transfected BMSCs showed higher concentrations of collagen I protein, more rapid matrix remodeling, and larger fiber bundles. Thus TGF-beta1 can promote mechanical strength in healing Achilles tendons by regulating collagen synthesis, cross-link formation, and matrix remodeling. PMID:19345669

Hou, Yu; Mao, ZeBing; Wei, XueLei; Lin, Lin; Chen, LianXu; Wang, HaiJun; Fu, Xin; Zhang, JiYing; Yu, ChangLong



A revised set of potentials for beta-turn formation in proteins.  

PubMed Central

Three thousand eight hundred ninety-nine beta-turns have been identified and classified using a nonhomologous data set of 205 protein chains. These were used to derive beta-turn positional potentials for turn types I' and II' for the first time and to provide updated potentials for formation of the more common types I, II, and VIII. Many of the sequence preferences for each of the 4 positions in turns can be rationalized in terms of the formation of stabilizing hydrogen bonds, preferences for amino acids to adopt a particular conformation in phi, psi space, and the involvement of turn types I' and II' in beta-hairpins. Only 1,632 (42%) of the turns occur in isolation; the remainder have at least 1 residue in common with another turn and have hence been classified as multiple turns. Several types of multiple turn have been identified and analyzed.

Hutchinson, E. G.; Thornton, J. M.



The beta-sheets of proteins, the biosynthetic relationships between amino acids, and the origin of the genetic code.  


Two forces are generally hypothesised as being responsible for conditioning the origin of the organization of the genetic code: the physicochemical properties of amino acids and their biosynthetic relationships (relationships between precursor and product amino acids). If we assume that the biosynthetic relationships between amino acids were fundamental in defining the genetic code, then it is reasonable to expect that the distribution of physicochemical properties among the amino acids in precursor-product relationships cannot be random but must, rather, be affected by some selective constraints imposed by the structure of primitive proteins. Analysis shows that measurements representing the 'size' of amino acids, e.g. bulkiness, are specifically associated to the pairs of amino acids in precurso-product relationships. However, the size of amino acids cannot have been selected per se but, rather, because it reflects the beta-sheets of proteins which are, therefore, identified as the main adaptive theme promoting the origin of genetic code organization. Whereas there are no traces of the alpha-helix in the genetic code table. The above considerations make it necessary to re-examine the relationship linking the hydrophilicity of the dinucleoside monophosphates of anticodons and the polarity and bulkiness of amino acids. It can be concluded that this relationship seems to be meaningful only between the hydrophilicity of anticodons and the polarity of amino acids. The latter relationship is supposed to have been operative on hairpin structures, ancestors of the tRNA molecule. Moreover, it is on these very structures that the biosynthetic links between precursor and product amino acids might have been achieved, and the interaction between the hydrophilicity of anticodons and the polarity of amino acids might have had a role in the concession of codons (anticodons) from precursors to products. PMID:9008882

Di Giulio, M



Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia.  


In Alzheimer's disease, microglia cluster around beta-amyloid deposits, suggesting that these cells are important for amyloid plaque formation, maintenance and/or clearance. We crossed two distinct APP transgenic mouse strains with CD11b-HSVTK mice, in which nearly complete ablation of microglia was achieved for up to 4 weeks after ganciclovir application. Neither amyloid plaque formation and maintenance nor amyloid-associated neuritic dystrophy depended on the presence of microglia. PMID:19838177

Grathwohl, Stefan A; Kälin, Roland E; Bolmont, Tristan; Prokop, Stefan; Winkelmann, Georg; Kaeser, Stephan A; Odenthal, Jörg; Radde, Rebecca; Eldh, Therese; Gandy, Sam; Aguzzi, Adriano; Staufenbiel, Matthias; Mathews, Paul M; Wolburg, Hartwig; Heppner, Frank L; Jucker, Mathias



Mutational analysis of designed peptides that undergo structural transition from ? helix to ? sheet and amyloid fibril formation  

Microsoft Academic Search

Background: Conformational alteration and fibril formation of proteins have a key role in a variety of amyloid diseases. A simplified model peptide would lead to a better understanding of underlying mechanisms whereby protein misfolding and aggregation occur. Recently, we reported the design of peptides that undergo a self-initiated structural transition from an ? helix to a ? sheet and form

Yuta Takahashi; Akihiko Ueno; Hisakazu Mihara



Carbon Nanotube Inhibits the Formation of ?-Sheet-Rich Oligomers of the Alzheimer's Amyloid-?(16-22) Peptide  

PubMed Central

Alzheimer's disease is associated with the abnormal self-assembly of the amyloid-? (A?) peptide into toxic ?-rich aggregates. Experimental studies have shown that hydrophobic nanoparticles retard A? fibrillation by slowing down the nucleation process; however, the effects of nanoparticles on A? oligomeric structures remain elusive. In this study, we investigate the conformations of A?(16-22) octamers in the absence and presence of a single-walled carbon nanotube (SWCNT) by performing extensive all-atom replica exchange molecular-dynamics simulations in explicit solvent. Our simulations starting from eight random chains demonstrate that the addition of SWCNT into A?(16-22) solution prevents ?-sheet formation. Simulation starting from a prefibrillar ?-sheet octamer shows that SWCNT destabilizes the ?-sheet structure. A detailed analysis of the A?(16-22)/SWCNT/water interactions reveals that both the inhibition of ?-sheet formation and the destabilization of prefibrillar ?-sheets by SWCNT result from the same physical forces: hydrophobic and ?-stacking interactions (with the latter playing a more important role). By analyzing the stacking patterns between the Phe aromatic rings and the SWCNT carbon rings, we find that short ring–centroid distances mostly favor parallel orientation, whereas large distances allow all other orientations to be populated. Overall, our computational study provides evidence that SWCNT is likely to inhibit A?(16-22) and full-length A? fibrillation.

Li, Huiyu; Luo, Yin; Derreumaux, Philippe; Wei, Guanghong



Effects of salt concentration on formation and dissociation of beta-lactoglobulin/pectin complexes.  


The formation and dissociation of beta-lactoglobulin/pectin complexes at various sodium chloride concentrations (CNaCl) have been studied by turbidimetric titration. An increase of CNaCl up to 0.1 M shifts the critical pHphi1, which designates the formation of beta-lactoglobulin/pectin coacervates, to higher pH values, whereas further increase of CNaCl from 0.1 to 0.8 M decreases pHphi1 values. These salt effects can be explained in terms of a salt-enhanced effect at lower salt concentrations or a salt-reduced effect at higher salt concentrations, respectively. On the other hand, the value of pHphi2, which corresponds to the dissociation of beta-lactoglobulin/pectin coacervates, tends to have smaller pH values when CNaCl increases from 0.1 to 0.3 M. No observable pHphi2 values are found at CNaCl higher than 0.3 M. The disappearance of pHphi2 is mainly attributed to the strong self-aggregation capability of beta-lactoglobulin at higher CNaCl. The aggregation of beta-lactoglobulin at high CNaCl is reversible, as suggested by the atomic force microscopy results. PMID:17979233

Wang, Xiaoyong; Wang, Yu-Wen; Ruengruglikit, Chada; Huang, Qingrong



The formation mechanism of the beta-TCP phase in synthetic fluorohydroxyapatite with different fluorine contents.  


Synthetic hydroxyapatite (HAP) and fluorohydroxyapatite (F(x)AP) products may form the beta-tricalcium phosphate (beta-TCP) phase in a calcination process. The beta-TCP phase has a greater tendency for degradation in vivo than HAP and F(x)AP. Hence, controlling the content of the beta-TCP phase in the apatite is a pivotal factor to affect their lifetime and stability in vivo. It is particularly important to explore the formation mechanism of the beta-TCP phase in synthetic apatite. In this work, F(x)AP products with a chemical composition of Ca(10)(PO(4))(6)(OH)(2-x)F(x) are synthesized, with x = 0, 0.4, 0.8, 1.2, 1.6 and 2.0, using a precipitation method and a calcination process. The effect of fluorine substitution for hydroxyl is investigated by using x-ray diffraction analysis, Fourier transform infrared spectroscopy, and thermogravimetry and differential thermal analysis. The results show that addition of fluorine forms F(x)AP that exhibits high thermal stability. The beta-TCP phase produced as a result of the structural refinement by heat treatment is gradually reduced and dramatically suppressed with the fluorine content. PMID:20644239

Zhao, Hua; Wang, Fuping; Chen, Xiangqun; Wei, Zhaodong; Yu, Dezhen; Jiang, Zhaohua



Nano-beta-tricalcium phosphates synthesis and biodegradation: 2. Biodegradation and apatite layer formation on nano-beta-TCP synthesized via microwave treatment.  


The degradation and/or apatite layer precipitation ability of porous beta-tricalcium phosphate (beta-TCP) samples treated and untreated with microwave radiation during synthesis is investigated. Microwave heating was used to accelerate the formation of CDHA with the Ca/P ratio 1.5 in a shorter processing time which later forms beta-TCP at around 650 degrees C. Soaking in simulated body fluid (SBF) for several periods (4, 8, 12, 24, 36, 48, 60 and 72 h) is performed in a cumulative manner. The deposition of an apatite layer is followed through diffuse reflected FT-IR, SEM and EDS. A microwave-treated sample having a smaller particle size than its parent induces the formation of a homogeneous carbonated apatite layer on its surface. On the other hand, the parent beta-TCP sample exhibited less ability to induce Ca-P formation after being soaked in SBF. The formation of an apatite layer is attributed to the increase in surface area consequent to reduced particle and grain sizes besides the presence of a minor amount of hydroxyapatite phase in the microwave-treated beta-TCP sample. The results prove that it is possible to control the biodegradation and apatite layer formation on sintered beta-TCP porous disks through controlling the particle size. PMID:20526025

Abdel-Fattah, Wafa I; Elkhooly, Tarek A



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

NASA Technical Reports Server (NTRS)

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.

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



Biosynthesis of streptothricin F. 5. Formation of. beta. -lysine by Streptomyces L-1689-23  

SciTech Connect

The formation of the ..beta..-lysine moiety of streptothricin F has been studied by feeding to Streptomyces L-1689-23 ..cap alpha..-(3-/sup 13/C,/sup 15/N)-, ..cap alpha..-((3RS)-/sup 2/H/sub 2/)-, ..cap alpha..-((3R)-/sup 2/H)-, and ..cap alpha..-((3S)-/sup 2/H)lysine and ..beta..-((2S)-/sup 2/H)lysine. From the analysis of either the /sup 13/C NMR or /sup 2/H NMR spectrum of the derived antibiotics, it has been determined that the ..cap alpha..-nitrogen migrates to C-3 with inversion of configuration by an intramolecular process, and the 3-pro-R hydrogen migrates to C-2 with inversion of configuration by a process that is substantially or completely intermolecular. The very high degree of incorporation of labeled ..beta..-lysine indicates it is probably an intermediate in the biosynthesis of streptothricin F.

Thiruvengadam, T.K. (Univ. of Connecticut, Storrs); Gould, S.J.; Aberhart, D.J.; Lin, H.J.



Formation of {beta}-hydroxycarbonyls from the OH radical-initiated reactions of selected alkenes  

SciTech Connect

{beta}-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 reported for the formation of this class of compound from the reactions of the OH radical with alkenes. The authors have determined that {beta}-hydroxy-ketones can be readily analyzed by gas chromatography, and in this work they have shown that in 1 atm of air the {beta}-hydroxyalkoxy radicals formed in the reactions of the OH radical with trans-2-butene, trans-3-hexene, 1-butene, and {alpha}-pinene in the presence of NO primarily decompose rather than react with O{sub 2}. Rate constant ratios k{sub d}/k{sub 0{sub 2}} (or lower limits thereof), where k{sub d} and k{sub 0{sub 2}} are respectively the rate constants for the decomposition and the reaction with 0{sub 2} of the intermediate {beta}-hydroxyalkoxy radicals, have been obtained for the reactions of the CH{sub 3}CH(O)CH-(OH)CH{sub 3}, CH{sub 3}CH{sub 2}CH(O)CH{sub 2}OH, and CH{sub 3}CH{sub 2}CH(O)CH(OH)CH{sub 2}-CH{sub 3} radicals at 296 {+-} 2 K and atmospheric pressure. Using the O{sub 3} reactions with the alkenes to generate OH radicals, the reactions of the OH radical to generate OH radicals, the reactions of the OH radical with trans-2-butene, trans-3-hexene, and {alpha}-pinene in the absence of NO lead to the formation of the expected {beta}-hydroxycarbonyls and (at least for trans-2-butene) the {alpha},{beta}-diol.

Aschmann, S.M.; Arey, J.; Atkinson, R.



Interactive desktop analysis of high resolution simulations: application to turbulent plume dynamics and current sheet formation  

NASA Astrophysics Data System (ADS)

The ever increasing processing capabilities of the supercomputers available to computational scientists today, combined with the need for higher and higher resolution computational grids, has resulted in deluges of simulation data. Yet the computational resources and tools required to make sense of these vast numerical outputs through subsequent analysis are often far from adequate, making such analysis of the data a painstaking, if not a hopeless, task. In this paper, we describe a new tool for the scientific investigation of massive computational datasets. This tool (VAPOR) employs data reduction, advanced visualization, and quantitative analysis operations to permit the interactive exploration of vast datasets using only a desktop PC equipped with a commodity graphics card. We describe VAPORs use in the study of two problems. The first, motivated by stellar envelope convection, investigates the hydrodynamic stability of compressible thermal starting plumes as they descend through a stratified layer of increasing density with depth. The second looks at current sheet formation in an incompressible helical magnetohydrodynamic flow to understand the early spontaneous development of quasi two-dimensional (2D) structures embedded within the 3D solution. Both of the problems were studied at sufficiently high spatial resolution, a grid of 5042 by 2048 points for the first and 15363 points for the second, to overwhelm the interactive capabilities of typically available analysis resources.

Clyne, John; Mininni, Pablo; Norton, Alan; Rast, Mark



Anti-A beta 1-11 antibody binds to different beta-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers.  


Different strategies proposed as therapy for Alzheimer disease (AD) have aimed to reduce the level of toxic forms of A beta peptide in the brain. Here, we directly analyze the therapeutic utility of the polyclonal anti-A beta(1-11) antibody induced in 3xTg-AD mice vaccinated with the second generation prototype epitope vaccine. Substoichiometric concentrations of purified anti-A beta(1-11) antibody prevented aggregation of A beta(42) and induced disaggregation of preformed A beta(42) fibrils down to nonfilamentous and nontoxic species. Anti-A beta(1-11) antibody delayed A beta(42) oligomer formation but ultimately appeared to stabilize nonfibrillar conformations, including oligomer-like assemblies. The reduced oligomer-mediated cytotoxicity observed upon preincubation of A beta oligomers with the anti-A beta(1-11) antibody in the absence of oligomer disaggregation suggests a possible oligomer rearrangement in the presence of the antibody. These in vitro observations suggest that preventive vaccination may protect from AD or may delay the onset of the disease, whereas therapeutic vaccination cannot disrupt the toxic oligomers and may only minimally alleviate preexisting AD pathology. PMID:17545160

Mamikonyan, Grigor; Necula, Mihaela; Mkrtichyan, Mikayel; Ghochikyan, Anahit; Petrushina, Irina; Movsesyan, Nina; Mina, Erene; Kiyatkin, Anatoly; Glabe, Charles G; Cribbs, David H; Agadjanyan, Michael G



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

NASA Astrophysics Data System (ADS)

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.

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



Structure formation and miscibility of sheets from PBT and LCP blends  

Microsoft Academic Search

Sheets from blends containing poly(butylene terephthalate) (PBT) and liquid crystalline polymer (LCP) were prepared using a twin-screw extruder. The LCP used is a copolymer composed of 20 mol % ethylene terephalate (PET) and 80 mol % p-hydroxybenzoic acid (PHB). Thermal behavior, viscoelastic properties, and structure of the sheets of various compositions were investigated by using differential scanning calorimetry (DSC), dynamic

K. Qi; K. Nakayama



Role of primary structure and disulfide bond formation in beta-lactamase secretion.  

PubMed Central

Plasmid pBR322-encoded beta-lactamase was shown to contain a single disulfide bond, which caused the protein to migrate faster in sodium dodecyl sulfate-polyacrylamide gels than the fully reduced form. A similar difference in mobility of the in vitro synthesized precursor before and after reduction indicates that it also contained a disulfide bond. Formation of the disulfide bond in vivo, however, occurred concomitant with processing. In vivo accumulation of the precursor by inhibition of secretion did not allow disulfide bond formation to occur. This result is consistent with post-translational translocation of the precursor. Synthesis of a fragment of beta-lactamase lacking the carboxy terminus was obtained by insertion of a foreign DNA segment into the PstI site of bla. Processing and secretion of the protein did not appear to be greatly affected, indicating that the carboxy terminus is not required for secretion. Images

Pollitt, S; Zalkin, H



Dissecting the structural determinants for the difference in mechanical stability of silk and amyloid beta-sheet stacks.  


Stacking of ?-sheets results in a protein super secondary structure with remarkable mechanical properties. ?-Stacks are the determinants of a silk fiber's resilience and are also the building blocks of amyloid fibrils. While both silk and amyloid-type crystals are known to feature a high resistance against rupture, their structural and mechanical similarities and particularities are yet to be fully understood. Here, we systematically compare the rupture force and stiffness of amyloid and spider silk poly-alanine ?-stacks of comparable sizes using Molecular Dynamics simulations. We identify the direction of force application as the primary determinant of the rupture strength; ?-sheets in silk are orientated along the fiber axis, i.e. the pulling direction, and consequently require high forces in the several nanoNewton range for shearing ?-strands apart, while ?-sheets in amyloid are oriented vertically to the fiber, allowing a zipper-like rupture at sub-nanoNewton forces. A secondary factor rendering amyloid ?-stacks softer and weaker than their spider silk counterparts is the sub-optimal side-chain packing between ?-sheets due to the sequence variations of amyloid-forming proteins as opposed to the perfectly packed poly-alanine ?-sheets of silk. Taken together, amyloid fibers can reach the stiffness of silk fibers in spite of their softer and weaker ?-sheet arrangement as they are missing a softening amorphous matrix. PMID:23633029

Xiao, Senbo; Xiao, Shijun; Gräter, Frauke



RNA binding mediates the local cooperativity between the beta-sheet and the C-terminal tail of the human U1A RBD1 protein.  


Pairwise coupling theory is applied here to determine the energetic interactions between two elements of the N-terminal RNA binding domain (RBD) of the human U1A protein. The novel application of the theory to this system incorporates both measurements of protein stability and RNA binding to define thermodynamic cycles. In this first example of the application, two regions of the protein are selected for study: tyrosine 13, one of the conserved aromatic residues on the surface of the beta-sheet, and the C-terminal tail of the RBD. The six initial pairwise coupling free energies derived from this system describe the communication between these positions, both in the free and RNA-bound states of the protein. The results show that in the absence of RNA, these two elements of the protein act independently. However, when RNA is bound, there is indirect coupling between Tyr13 and the tail, mediated through the RNA. Subsequent thermodynamic cycles involving additional perturbations to the C-terminal tail further define the communication between the C terminus and the beta-sheet. This work demonstrates the general applicability of the pairwise coupling theory to protein:nucleic acid interactions, and illustrates the necessity of such analyses to describe the network of energetic interactions that comprise RNA recognition by this RBD. PMID:9466924

Kranz, J K; Hall, K B



The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment.  


An alpha-helical II-III loop segment of the dihydropyridine receptor activates the ryanodine receptor calcium-release channel. We describe a novel manipulation in which this agonist's activity is increased by modifying its surface structure to resemble that of a toxin molecule. In a unique system, native beta-sheet scorpion toxins have been reported to activate skeletal muscle ryanodine receptor calcium channels with high affinity by binding to the same site as the lower-affinity alpha-helical dihydropyridine receptor segment. We increased the alignment of basic residues in the alpha-helical peptide to mimic the spatial orientation of active residues in the scorpion toxin, with a consequent 2-20-fold increase in the activity of the alpha-helical peptide. We hypothesized that, like the native peptide, the modified peptide and the scorpion toxin may bind to a common site. This was supported by (i) similar changes in ryanodine receptor channel gating induced by the native or modified alpha-helical peptide and the beta-sheet toxin, a 10-100-fold reduction in channel closed time, with a < or = 2-fold increase in open dwell time and (ii) a failure of the toxin to further activate channels activated by the peptides. These results suggest that diverse structural scaffolds can present similar conformational surface properties to target common receptor sites. PMID:12429019

Green, Daniel; Pace, Suzi; Curtis, Suzanne M; Sakowska, Magdalena; Lamb, Graham D; Dulhunty, Angela F; Casarotto, Marco G



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

SciTech Connect

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.

Lennartsson, O.W.



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

NASA Technical Reports Server (NTRS)

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.

Lennartsson, O. W.



Multi modes for the vortex sheet-tube trans- formation process and viscoelastic effect  

Microsoft Academic Search

Primary elements which constitute the turbulent flow field are the vortex sheets and the vortex tubes (1, 2). The vortex tubes are often formed by rolling-up of the vortex sheets. It is generally considered that this rolling-up is attributable to the Kelvin-Helmholtz instability, e.g. (3). The aim of the present study is to reveal the details of the process for

Kiyosi Horiuti; Yohei Takagi; Syouji Abe


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)

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 - ? g cos?, 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 ? 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.

Martel, S. J.



Solution structure and dynamics of an open beta-sheet, glycolytic enzyme, monomeric 23.7 kDa phosphoglycerate mutase from Schizosaccharomyces pombe.  


The structure and backbone dynamics of a double labelled (15N,13C) monomeric, 23.7 kD phosphoglycerate mutase (PGAM) from Schizosaccharomyces pombe have been investigated in solution using NMR spectroscopy. A set of 3125 NOE-derived distance restraints, 148 restraints representing inferred hydrogen bonds and 149 values of (3)J(HNHalpha) were used in the structure calculation. The mean rmsd from the average structure for all backbone atoms from residues 6-205 in the best 21 calculated structures was 0.59 A. The core of the enzyme includes an open, twisted, six-stranded beta-sheet flanked by four alpha-helices and a short 3(10)-helix. An additional smaller domain contains two short antiparallel beta-strands and a further pair of alpha-helices. The C(alpha) atoms of the S. pombe PGAM may be superimposed on their equivalents in one of the four identical subunits of Saccharomyces cerevisiae PGAM with an rmsd of 1.34 A (0.92 A if only the beta-sheet is considered). Small differences between the two structures are attributable partly to the deletion in the S. pombe sequence of a 25 residue loop involved in stabilising the S. cerevisiae tetramer. Analysis of 15N relaxation parameters indicates that PGAM tumbles isotropically with a rotational correlation time of 8.7 ns and displays a range of dynamic features. Of 178 residues analysed, only 77 could be fitted without invoking terms for fast internal motion or chemical exchange, and out of the remainder, 77 required a chemical exchange term. Significantly, 46 of the slowly exchanging (milli- to microsecond) residues lie in helices, and these account for two-thirds of all analysed helix residues. On the contrary, only one beta-sheet residue required an exchange term. In contrast to other analyses of backbone dynamics reported previously, residues in slow exchange appeared to correlate with architectural features of the enzyme rather than congregating close to ligand binding sites. PMID:11237600

Uhrínová, S; Uhrín, D; Nairn, J; Price, N C; Fothergill-Gilmore, L A; Barlow, P N



Involvement of Streptococcus gordonii Beta-Glucoside Metabolism Systems in Adhesion, Biofilm Formation, and In Vivo Gene Expression  

Microsoft Academic Search

Streptococcus gordonii genes involved in beta-glucoside metabolism are induced in vivo on infected heart valves during experimental endocarditis and in vitro during biofilm formation on saliva-coated hydroxyapatite (sHA). To determine the roles of beta-glucoside metabolism systems in biofilm formation, the loci of these induced genes were analyzed. To confirm the function of genes in each locus, strains were constructed with

Ali O. Kilic; Lin Tao; Yongshu Zhang; Yu Lei; Ali Khammanivong; Mark C. Herzberg



Nanofibers formed through pi...pi stacking of the complexes of glucosyl-C2-salicyl-imine and phenylalanine: characterization by microscopy, modeling by molecular mechanics, and interaction by alpha-helical and beta-sheet proteins.  


This paper deals with the self-assembly of the 1:1 complex of two different amphiphiles, namely, a glucosyl-salicyl-imino conjugate (L) and phenylalanine (Phe), forming nanofibers over a period of time through pi...pi interactions. Significant enhancement observed in the fluorescence intensity of L at approximately 423 nm band and the significant decrease observed in the absorbance of the approximately 215 nm band are some characteristics of this self-assembly. Matrix-assisted laser desorption ionization/time of flight titration carried out at different time intervals supports the formation of higher aggregates. Atomic force microscopy (AFM), transmission electron microscopy, and scanning electron miscroscopy results showed the formation of nanofibers for the solutions of L with phenylalanine. In dynamic light scattering measurements, the distribution of the particles extends to a higher diameter range over time, indicating a slow kinetic process of assembly. Similar spectral and microscopy studies carried out with the control molecules support the role of the amino acid moiety over the simple -COOH moiety as well as the side chain phenyl moiety in association with the amino acid, in the formation of these fibers. All these observations support the presence of pi...pi interactions between the initially formed 1:1 complexes leading to the fiber formation. The aggregation of 1:1 complexes leading to fibers followed by the formation of bundles has been modeled by molecular mechanics studies. Thus the fiber formation with L is limited to phenylalanine and not to any other naturally occurring amino acid and hence a polymer composed of two different biocompatible amphiphiles. AFM studies carried out between the fiber forming mixture and proteins resulted in the observation that only BSA selectively adheres to the fiber among the three alpha-helical and two beta-sheet proteins studied and hence may be of use in some medical applications. PMID:20521836

Acharya, Amitabha; Ramanujam, Balaji; Mitra, Atanu; Rao, Chebrolu P



Involvement of Streptococcus gordonii Beta-Glucoside Metabolism Systems in Adhesion, Biofilm Formation, and In Vivo Gene Expression  

PubMed Central

Streptococcus gordonii genes involved in beta-glucoside metabolism are induced in vivo on infected heart valves during experimental endocarditis and in vitro during biofilm formation on saliva-coated hydroxyapatite (sHA). To determine the roles of beta-glucoside metabolism systems in biofilm formation, the loci of these induced genes were analyzed. To confirm the function of genes in each locus, strains were constructed with gene inactivation, deletion, and/or reporter gene fusions. Four novel systems responsible for beta-glucoside metabolism were identified, including three phosphoenolpyruvate-dependent phosphotransferase systems (PTS) and a binding protein-dependent sugar uptake system for metabolizing multiple sugars, including beta-glucosides. Utilization of arbutin and esculin, aryl-beta-glucosides, was defective in some mutants. Esculin and oligochitosaccharides induced genes in one of the three beta-glucoside metabolism PTS and in four other genetic loci. Mutation of genes in any of the four systems affected in vitro adhesion to sHA, biofilm formation on plastic surfaces, and/or growth rate in liquid medium. Therefore, genes associated with beta-glucoside metabolism may regulate S. gordonii in vitro adhesion, biofilm formation, growth, and in vivo colonization.

Kilic, Ali O.; Tao, Lin; Zhang, Yongshu; Lei, Yu; Khammanivong, Ali; Herzberg, Mark C.



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

PubMed Central

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.

Liu, Hongsheng; Gao, Junfeng; Zhao, Jijun



Calcium/calmodulin kinase kinase beta has a male-specific role in memory formation.  


The calcium/calmodulin (CaM) kinase cascade regulates gene transcription, which is required for long-term memory formation. Previous studies with Camkk2 null mutant mice have shown that in males calcium/calmodulin kinase kinase beta (CaMKKbeta) is required for spatial memory formation and for activation of the transcription factor cyclic AMP-responsive element binding protein (CREB) in the hippocampus by spatial training. Here we show that CaMKKbeta is not required for spatial memory formation in female mice as female Camkk2 null mutants were not impaired in spatial memory formation and they had the same level of hippocampal CREB phosphorylation after spatial training as female wild-type mice. Furthermore, we show that male but not female Camkk2 null mutants were impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Finally, a transcriptional analysis of male Camkk2 null mutants led to the identification of a gene, glycosyl phosphatidyl-inositol anchor attachment protein 1 (GAA1), whose hippocampal mRNA expression was up-regulated by spatial and contextual training in male but not in female wild-type mice. Taken together, we conclude that CaMKKbeta has a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation. PMID:17207577

Mizuno, K; Antunes-Martins, A; Ris, L; Peters, M; Godaux, E; Giese, K P



Beta-sheet breaker peptide inhibitor of Alzheimer's amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma.  


Short synthetic peptides homologous to the central region of Abeta but bearing proline residues as beta-sheet blockers have been shown in vitro to bind to Abeta with high affinity, partially inhibit Abeta fibrillogenesis, and redissolve preformed fibrils. While short peptides have been used extensively as therapeutic drugs in medicine, two important problems associated with their use in central nervous system diseases have to be addressed: (a) rapid proteolytic degradation in plasma, and (b) poor blood-brain barrier (BBB) permeability. Recently, we have demonstrated that the covalent modification of proteins with the naturally occurring polyamines significantly increases their permeability at the BBB. We have extended this technology to iAbeta11, an 11-residue beta-sheet breaker peptide that inhibits Abeta fibrillogenesis, by covalently modifying this peptide with the polyamine, putrescine (PUT), and evaluating its plasma pharmacokinetics and BBB permeability. After a single intravenous bolus injection in rats, both 125I-YiAbeta11 and 125I-PUT-YiAbeta11 showed rapid degradation in plasma as determined by trichloroacetic acid (TCA) precipitation and paper chromatography. By switching to the all D-enantiomers of YiAbeta11 and PUT-YiAbeta11, significant protection from degradation by proteases in rat plasma was obtained with only 1.9% and 5.7% degradation at 15 min after intravenous bolus injection, respectively. The permeability coefficient x surface area product at the BBB was five- sevenfold higher in the cortex and hippocampus for the 125I-PUT-D-YiAbeta11 compared to the 125I-D-YiAbeta11, with no significant difference in the residual plasma volume. In vitro assays showed that PUT-D-YiAbeta11 retains its ability to partially inhibit Abeta fibrillogenesis and dissolve preformed amyloid fibrils. Because of its five- to sevenfold increase in permeability at the BBB and its resistance to proteolysis in the plasma, this polyamine-modified beta-sheet breaker peptide may prove to be an effective inhibitor of amyloidogenesis in vivo and, hence, an important therapy for Alzheimer's disease. PMID:10363910

Poduslo, J F; Curran, G L; Kumar, A; Frangione, B; Soto, C



beta-Amyloid Neurotoxicity Requires Fibril Formation and is Inhibited by Congo Red  

Microsoft Academic Search

beta-Amyloid (betaA) is normally produced as a nontoxic soluble peptide. In Alzheimer disease, betaA aggregates and accumulates in the brain as inert diffuse plaques or compact plaques associated with neurodegenerative changes. To determine the relationship of neurotoxicity to the physical state of betaA, we created (i) nonamyloidogenic amorphous aggregates of betaA [amorphous betaA (Am-betaA)] analogous to diffuse plaques and (ii)

Alfredo Lorenzo; Bruce A. Yankner



Alpha- and beta- aspartyl peptide ester formation via aspartimide ring opening.  


The undesirable reaction of aspartimide formation has been proved to occur under both acid and base conditions in solid-phase peptide synthesis and is dependent on the beta-carboxyl protecting group, the acid or base used during the synthesis, as well as the peptide sequence. The hydrolysis of aspartimide-containing peptides, especially during HPLC purification, yields a mixture of alpha- and beta-aspartyl peptides that can not be purified easily. A previous study demonstrated that treatment of aspartimide-containing peptides with methanol in the presence of 2% diisopropylethylamine in solution leads to alpha- and beta-aspartyl peptide methyl esters. Taking advantage of these results and aiming at elucidating the optimal conditions for aspartimide ring opening, the effect of different types and concentrations of alcohols (primary and secondary) and bases (diisopropylethylamine, collidine, 4-pyrrolidinopyridine, 1-methyl-2-pyrrolidone, piperidine and KCN) was tested at various temperatures and reaction times. The best results were obtained with a combination of a primary alcohol and diisopropylethylamine, while aspartimide ring opening by secondary alcohols occurred only at high temperatures. The optimal conditions were also applied to solid-phase peptide synthesis. PMID:15884102

Stathopoulos, Panagiotis; Papas, Serafim; Kostidis, Sarantos; Tsikaris, Vassilios



Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation.  


Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen



Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation  

PubMed Central

Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration.

Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen



Different roles of protein kinase C-beta and -delta in arachidonic acid cascade, superoxide formation and phosphoinositide hydrolysis.  

PubMed Central

In contrast with protein kinase C (PKC)-beta, PKC-delta is exclusively detectable in the membrane fraction of liver macrophages. After long-term treatment with phorbol 12-myristate 13-acetate (PMA) PKC-beta is depleted faster (within 3 h) than PKC-delta (> 7h). Simultaneously, pretreatment with PMA for 3 h inhibits the PMA- and zymosan-induced generation of superoxide and the PMA-induced formation of prostaglandin (PG) E2, whereas a preincubation of more than 7 h is required to affect the zymosan-induced release of PGE2 and inositol phosphates. These results support an involvement of PKC-beta in the PMA-induced activation of the arachidonic acid cascade and in superoxide formation and imply an involvement of PKC-delta in zymosan-induced phosphoinositide hydrolysis and PGE2 formation. Two phorbol ester derivates, sapintoxin A (SAPA) and 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA), which have been previously reported to activate preferentially PLC-beta but not PKC-delta in vitro [Ryves, Evans, Olivier, Parker and Evans (1992) FEBS Lett. 288, 5-9], induce the formation of PGE2 and superoxide, down-regulate PKC-delta and potentiate inositol phosphate formation in parallel SAPA, but not DOPPA, down-regulates PKC-beta and inhibits the PMA-induced formation of eicosanoids and superoxide. Images Figure 1 Figure 2 Figure 5

Duyster, J; Schwende, H; Fitzke, E; Hidaka, H; Dieter, P



Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.  


Alzheimer's disease (AD) involves amyloid beta (Abeta) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential Abeta binding, we investigated whether its efficacy in AD models could be explained by effects on Abeta aggregation. Under aggregating conditions in vitro, curcumin inhibited aggregation (IC(50) = 0.8 microM) as well as disaggregated fibrillar Abeta40 (IC(50) = 1 microM), indicating favorable stoichiometry for inhibition. Curcumin was a better Abeta40 aggregation inhibitor than ibuprofen and naproxen, and prevented Abeta42 oligomer formation and toxicity between 0.1 and 1.0 microM. Under EM, curcumin decreased dose dependently Abeta fibril formation beginning with 0.125 microM. The effects of curcumin did not depend on Abeta sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small beta-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD. PMID:15590663

Yang, Fusheng; Lim, Giselle P; Begum, Aynun N; Ubeda, Oliver J; Simmons, Mychica R; Ambegaokar, Surendra S; Chen, Pingping P; Kayed, Rakez; Glabe, Charles G; Frautschy, Sally A; Cole, Gregory M



Plasma sheet/magnetosheath plasma mixing and LLBL formation(INTERBALL/TAIL probe observations)  

NASA Astrophysics Data System (ADS)

On the basis of plasma, energetic particle and magnetic field measurements the low latitude boundary layer (LLBL) of the Earth's magnetosphere is studied. LLBL is formed due to the mixing of magnetosheath and plasma sheet plasma but the conditions leading to such mixing are not well investigated till now. The mixing process is studied on the base of INTERBALL/Tail probe observations. The variations of the fluxes of ions (measured by CORALL instrument), electrons (measured by ELECTON instrument) and particles with energies more then 25 keV measured by DOK-2 instrument) are analyzed for the number of cases when the satellite intersects LLBL, plasma sheet and its boundaries. The variations of the magnetic field are compared with the variations of particle fluxes. The thickness of the region containing plasma from LLBL is estimated. The stress balance across the analyzed boundary is discussed.

Rossolenko, S. S.; Antonova, E. E.; Yermolaev, Yu. I.; Kirpichev, I. P.; Lutsenko, V. N.


The effect of Mg vapor source on the formation of MgO whiskers and sheets  

NASA Astrophysics Data System (ADS)

By using different Mg vapor sources, different diameters of MgO whiskers and sheets were obtained via different growth mechanisms. When the Mg vapor was generated by carbothermal reduction of MgO and C powder, small MgO nanowhiskers (50 nm in diameter) and nanosheets (700 nm in width and 60-80 nm in thickness) were formed via vapor-liquid-solid (VLS) and vapor-solid (VS) processes. When the Mg vapor was generated by thermal evaporation of Mg powder, large MgO whiskers (0.6-2 ?m in diameter) and sheets (2.4 ?m in width and 1.5 ?m in thickness) were formed, and the growth process was dominated by the VS mechanism. Experimental results suggested that the difference of Mg vapor concentration in the reaction tube is possibly responsible for the difference of the size and growth mechanism of the products.

Chen, Yongjun; Li, Jianbao; Han, Yongsheng; Yang, Xiaozhan; Dai, Jinhui



Characteristics of chip formation in the micro-drilling of multi-material sheets  

Microsoft Academic Search

In order to meet the requirements of electronic product miniaturisation, the use of thinner and smaller printed circuit boards (PCBs) will be required. To achieve this, many more micro-holes must be drilled in a smaller area than before. PCBs are anisotropic multi-material sheets consisting of a dielectric layer (resin\\/glass fibre cloth) and a high purity metal conductor (copper foil). It

Lijuan Zheng; Chengyong Wang; Lipeng Yang; Yuexian Song; Lianyu Fu


Double layer formation during current sheet disruptions in a reconnection experiment  

NASA Technical Reports Server (NTRS)

When the current density in the center of a neutral sheet is increased to a critical value spontaneous current disruptions are observed. The release of stored magnetic field energy results in a large inductive voltage pulse which drops off inside the plasma in the form of a potential double layer. Particles are energized, microinstabilities are generated, the plasma is thinned, and the current flow is redirected. These laboratory observations qualitatively support recent models of magnetic substorms and solar flares.

Stenzel, R. L.; Gekelman, W.; Wild, N.



Formation of liquid sheets by deposition of droplets on a surface.  


Experiments were done to observe the coalescence of highly viscous liquid droplets (87 wt% glycerin-in-water solutions) deposited onto a flat, solid steel plate. Droplets were deposited sequentially in straight lines or square droplet arrays. Droplet center-to-center distance was varied and the final dimensions of lines and sheets measured from photographs. When overlapping droplets were deposited surface tension forces pulled impacting droplets towards those already on the surface, a phenomena known as drawback. A dimensionless drawback index, quantifying the extent of droplet displacement, was calculated from experimental measurements for different values of droplet overlap. At large overlaps droplets deposited in a line or square array coalesced to form a circular film. When the droplet center-to-center distance increased, leading to less interaction, long, thin lines and square sheets were formed. As overlap was further decreased lines and sheets became discontinuous. A simple model was developed to predict the conditions under which rupture occurred. The lowest droplet overlap ratio (defined as droplet overlap distance divided by droplet spread diameter) at which a continuous liquid film could be formed was ?=0.293. At large overlap ratios (?>0.6) droplets deposited in a square array formed a circular film. The minimum thickness of a continuous film formed by coalescence of droplets was shown to vary from 5% to 70% of the initial droplet diameter while increasing impact Weber and Reynolds number reduced the film thickness. PMID:24461848

Dalili, Alireza; Chandra, Sanjeev; Mostaghimi, Javad; Fan, H T Charles; Simmer, Joseph C



Targets of TGF-beta signaling in Caenorhabditis elegans dauer formation.  


Caenorhabditis elegans dauer formation is controlled by multiple environmental factors. The chemosensory neuron ASI regulates dauer formation by secretion of DAF-7/TGF-beta, but the molecular targets of the DAF-7 ligand are incompletely defined and the cellular targets are unknown. We genetically characterized and cloned a putative transducer of DAF-7 signaling called daf-14 and found that it encodes a Smad protein. DAF-14 Smad has a highly unusual structure completely lacking the N-terminal domain found in all other Smad proteins known to date. daf-14 genetically interacts with daf-8, which encodes another Smad, and the interaction suggests partial functional redundancy between these two Smad proteins. We also studied the cellular targets of DAF-7 signaling by studying the sites of action of daf-14 and daf-4, the putative receptor for DAF-7. daf-14::gfp is expressed in multiple tissues that are remodeled during dauer formation. However, analysis of mosaics generated by free duplication loss and tissue-specific expression constructs indicate cell-nonautonomous function of daf-4, arguing against direct DAF-7 signaling to tissues throughout the animal. Instead, these experiments suggest the nervous system as a target of DAF-7 signaling and that the nervous system in turn regulates dauer formation by other tissues. PMID:10625546

Inoue, T; Thomas, J H



Double-stranded helical twisted beta-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids.  


Gramicidin S is a nonribosomally synthesized cyclic decapeptide antibiotic with twofold symmetry (Val-Orn-Leu-D-Phe-Pro)(2); a natural source is Bacillus brevis. Gramicidin S is active against Gram-positive and some Gram-negative bacteria. However, its haemolytic toxicity in humans limits its use as an antibiotic to certain topical applications. Synthetically obtained gramicidin S was crystallized from a solution containing water, methanol, trifluoroacetic acid and hydrochloric acid. The structure was solved and refined at 0.95 A resolution. The asymmetric unit contains 1.5 molecules of gramicidin S, two trifluoroacetic acid molecules and ten water molecules located and refined in 14 positions. One gramicidin S molecule has an exact twofold-symmetrical conformation; the other deviates from the molecular twofold symmetry. The cyclic peptide adopts an antiparallel beta-sheet secondary structure with two type II' beta-turns. These turns have the residues D-Phe and Pro at positions i + 1 and i + 2, respectively. In the crystals, the gramicidin S molecules line up into double-stranded helical channels that differ from those observed previously. The implications of the supramolecular structure for several models of gramicidin S conformation and assembly in the membrane are discussed. PMID:17327677

Llamas-Saiz, Antonio L; Grotenbreg, Gijsbert M; Overhand, Mark; van Raaij, Mark J



Dynamics of beta-amyloid peptide in cholesterol superlattice domain  

NASA Astrophysics Data System (ADS)

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.

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



Alzheimer beta-amyloid homodimers facilitate A beta fibrillization and the generation of conformational antibodies.  


We reported previously that stabilized beta-amyloid peptide dimers were derived from mutant amyloid precursor protein with a single cysteine in the ectodomain juxtamembrane position. In vivo studies revealed that two forms of SDS-stable A beta homodimers exist, species ending at A beta 40 and A beta 42. The phenomenon of the transformation of the initially deposited 42-residue beta-amyloid peptide into the amyloid fibrils of Alzheimer's disease plaques remains to be explained in physical terms, i.e. energetically and structurally. We therefore performed spectroscopic analyses revealing that engineered dimeric peptides ending at residue 42 displayed a much more pronounced beta-structural transition than corresponding monomers. Specifically, the single chemically induced dimerization of A beta peptides significantly increased the beta-sheet content by a factor of 2. The C-terminal residues Ile-41 and Ala-42 of dimeric forms further increased the beta-sheet content by roughly one-third. In contrast to A beta 42, the beta-sheet content of the alpha- and gamma-secretase-generated p3 fragments did not necessarily correlate with the tendency to form fibrils, although p3/17-42 had a pronounced thread forming character with fibril lengths of up to 2.5 microM. Electron microscopic images show that forms of p3/17-42 generated smaller granular particles than forms ending at residue 40. We discuss these findings in terms of A beta 1-42 dimers representing paranuclei, which self-aggregate into ribbon-like ordered fibrils by elongation. Based on A beta 42 dimer-specific titers of a polyclonal antiserum we propose that the A beta homodimer represents a nidus for plaque formation and a well defined novel therapeutic target. PMID:12840025

Schmechel, Ariane; Zentgraf, Hanswalter; Scheuermann, Stefan; Fritz, Guenter; Pipkorn, Rüdiger; Reed, Jennifer; Beyreuther, Konrad; Bayer, Thomas A; Multhaup, Gerd



Design study of the geometry of the blanking tool to predict the burr formation of Zircaloy-4 sheet  

NASA Astrophysics Data System (ADS)

In this work, we investigated factors that influence burr formation for zircaloy-4 sheet used for spacer grids of nuclear fuel roads. Factors we considered are geometric factors of punch. We changed clearance and velocity in order to consider the failure parameters, and we changed shearing angle and corner radius of L-shaped punch in order to consider geometric factors of punch. First, we carried out blanking test with failure parameter of GTN model using L-shaped punch. The tendency of failure parameters and geometric factors that affect burr formation by analyzing sheared edges is investigated. Consequently, geometric factor's influencing on the burr formation is also high as failure parameters. Then, the sheared edges and burr formation with failure parameters and geometric factors is investigated using FE analysis model. As a result of analyzing sheared edges with the variables, we checked geometric factors more affect burr formation than failure parameters. To check the reliability of the FE model, the blanking force and the sheared edges obtained from experiments are compared with the computations considering heat transfer.

Ha, Jisun; Lee, Hyungyil; Kim, Dongchul; Kim, Naksoo



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

PubMed Central

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.

Shen, C L; Murphy, R M



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

SciTech Connect

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.

Miyagoshi, Takehiro [Japan Agency for Marine-Earth Science and Technology, Yokohama 236-0001 (Japan); Kageyama, Akira [Graduate School of System Informatics, Kobe University, Kobe 657-8501 (Japan); Sato, Tetsuya [Graduate School of Simulation Studies, University of Hyogo, Kobe 650-0047 (Japan)



Heparin strongly enhances the formation of beta2-microglobulin amyloid fibrils in the presence of type I collagen.  


The tissue specificity of fibrillar deposition in dialysis-related amyloidosis is most likely associated with the peculiar interaction of beta2-microglobulin (beta2-m) with collagen fibers. However, other co-factors such as glycosaminoglycans might facilitate amyloid formation. In this study we have investigated the role of heparin in the process of collagen-driven amyloidogenesis. In fact, heparin is a well known positive effector of fibrillogenesis, and the elucidation of its potential effect in this type of amyloidosis is particularly relevant because heparin is regularly given to patients subject to hemodialysis to prevent blood clotting. We have monitored by atomic force microscopy the formation of beta2-m amyloid fibrils in the presence of collagen fibers, and we have discovered that heparin strongly accelerates amyloid deposition. The mechanism of this effect is still largely unexplained. Using dynamic light scattering, we have found that heparin promotes beta2-m aggregation in solution at pH 6.4. Morphology and structure of fibrils obtained in the presence of collagen and heparin are highly similar to those of natural fibrils. The fibril surface topology, investigated by limited proteolysis, suggests that the general assembly of amyloid fibrils grown under these conditions and in vitro at low pH is similar. The exposure of these fibrils to trypsin generates a cleavage at the C-terminal of lysine 6 and creates the 7-99 truncated form of beta2-m (DeltaN6beta2-m) that is a ubiquitous constituent of the natural beta2-m fibrils. The formation of this beta2-m species, which has a strong propensity to aggregate, might play an important role in the acceleration of local amyloid deposition. PMID:18056266

Relini, Annalisa; De Stefano, Silvia; Torrassa, Silvia; Cavalleri, Ornella; Rolandi, Ranieri; Gliozzi, Alessandra; Giorgetti, Sofia; Raimondi, Sara; Marchese, Loredana; Verga, Laura; Rossi, Antonio; Stoppini, Monica; Bellotti, Vittorio



A study of multi-ligand beta-lactoglobulin complex formation.  


Beta-lactoglobulin (?-LG), the principal whey protein, possesses multiple sites for binding ligands. Most studies of ?-LG-ligand interactions have focused on the formation and dissociation of protein complexes with single ligands, such as ?-tocopherol, resveratrol or folic acid. In this study, the possibility of a plurality of bioactive compounds binding simultaneously to ?-LG was analysed using protein intrinsic fluorescence quenching. It was found that ?-LG could bind two or three ligands simultaneously, although the sequence in which the ligands were added affected binding affinity. The impact of binding to ?-LG on physicochemical properties of these three ligands is discussed in view of fluorescence spectroscopy and high performance liquid chromatography results. The data obtained in this study suggest the feasibility of developing ?-LG-based carriers of a plurality of active compounds. PMID:25038674

Zhang, Jie; Liu, Xiaoming; Subirade, Muriel; Zhou, Peng; Liang, Li



Magnetic Relaxation, Current Sheets, and Structure Formation in an Extremely Tenuous Fluid Medium  

NASA Astrophysics Data System (ADS)

The process of relaxation of a unidirectional magnetic field in a highly conducting tenuous fluid medium is considered. Null points of the field play a critical role in this process. During an initial stage of relaxation, variations in magnetic pressure are eliminated, and current sheets build up in the immediate neighborhood of null points. This initial phase is followed by a long diffusive phase of slow algebraic decay of the field, during which fluid is continuously sucked into the current sheets, leading to exponential growth of fluid density and concentration of mass around the null points, which show a tendency to cluster. Ultimately, this second phase of algebraic decay gives way to a final period of exponential decay of the field. The peaks of density at the null points survive as a fossil relic of the decay process. Numerical solution of the governing equations provides convincing confirmation of this three-stage scenario. Generalizations to two- and three-dimensional fields are briefly considered.

Bajer, K.; Moffatt, H. K.



WW: An isolated three-stranded antiparallel beta-sheet domain that unfolds and refolds reversibly; evidence for a structured hydrophobic cluster in urea and GdnHCl and a disordered thermal unfolded state.  

PubMed Central

The objective of this study was to evaluate the suitability of the WW domain as a desirable model system to understand the folding and stability of an isolated three-stranded antiparallel beta-sheet structure. The WW domain was subjected to thermal and chaotropic denaturation/reconstitution utilizing a variety of biophysical methods. This three-stranded sheet folds reversibly and cooperatively utilizing both urea and GdnHCl as denaturants; however, the denatured state retains structure in the form of a hydrophobic cluster involving at least one aromatic side chain. In contrast to chaotropic denaturation, thermal denaturation appears to be more complete and may be a two state process. The suitability of the WW domain for future studies aimed at understanding the kinetics and thermodynamics of antiparallel beta-sheet folding clearly emerges from this initial study. The most exciting and significant result in this manuscript is the finding that the chaotropic denatured state of WW has a hydrophobic cluster as discerned by near-UV CD evidence. The role that the denatured state plays in the folding and stability of a three-stranded beta-sheets, and its capacity for preventing aggregation may be particularly important and is the subject of ongoing studies.

Koepf, E. K.; Petrassi, H. M.; Sudol, M.; Kelly, J. W.



Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of beta-hematin formation, and antiplasmodial activity.  


Comparison of 19 aminoquinolines supports the hypothesis that chloroquine and related antimalarials act by complexing ferriprotoporphyrin IX (Fe(III)PPIX), inhibiting its conversion to beta-hematin (hemozoin) and hence its detoxification. The study suggests that a basic amino side chain is also essential for antiplasmodial activity. 2- And 4-aminoquinolines are unique in their strong affinity for Fe(III)PPIX, and attachment of side chains to the amino group has relatively little influence on the strength of complex formation. Association with Fe(III)PPIX is necessary, but not sufficient, for inhibiting beta-hematin formation. Presence of a 7-chloro group in the 4-aminoquinoline ring is a requirement for beta-hematin inhibitory activity, and this is also unaffected by side chains attached to the amino group. In turn, beta-hematin inhibitory activity is necessary, but not sufficient, for antiplasmodial activity as the presence of an aminoalkyl group attached to the 4-amino-7-chloroquinoline template is essential for strong activity. We thus propose that the 4-aminoquinoline nucleus of chloroquine and related antimalarials is responsible for complexing Fe(III)PPIX, the 7-chloro group is required for inhibition of beta-hematin formation, and the basic amino side chain is required for drug accumulation in the food vacuole of the parasite. PMID:10649984

Egan, T J; Hunter, R; Kaschula, C H; Marques, H M; Misplon, A; Walden, J



Using statistical mean state dynamics to understand jet and zonon formation in beta-plane turbulence  

NASA Astrophysics Data System (ADS)

Zonal jets and associated non-zonal structures, such as nonlinearly modified Rossby waves (zonons) and vortices, are prominent features of beta-plane turbulence and also play a central role in determining the statistical mean turbulent state. Understanding the emergence and equilibration of these large scale coherent structures and their coexistence with turbulence in planetary atmospheres constitutes a fundamental theoretical problem. Stochastic Structural Stability Theory (S3T) provides a framework for understanding turbulence based on the statistical mean state dynamics closed at second order. In order to elucidate coherent structure dynamics, predictions for formation and equilibration of zonal and non-zonal structures made using S3T will be compared with results of simulations made using the associated quasi-linear and nonlinear models. S3T will be shown to accurately predict the bifurcation structure associated with coherent structure formation as well as their finite amplitude equilibrium and their ultimate breakdown as a function of parameters. The physical mechanism by which jets and zonons form as linear S3T instabilities and the finite amplitude regime of jet and non-zonal structure coexistence in S3T and nonlinear simulations will be described.

Farrell, B.; Ioannou, P.; Constantinou, N.



Kelvin-Helmholtz vortices around the magnetotail and cold plasma sheet formation: Insight as a multiscale phenomenon  

NASA Astrophysics Data System (ADS)

The magnetopause of the Earth's magnetosphere is a key region in magnetospheric physics, especially in the sense of multiscale coupling from global large-scale phenomena to microscale physics. The velocity shear across the magnetopause is believed to cause Kelvin-Helmholtz instability (KHI) on both the dawn and dusk sides when the interplanetary magnetic field (IMF) points northward; magnetic reconnection and some secondary instabilities are likely to occur in the vortical structure induced by KHI and to play a significant role in solar wind entry across the magnetopause as well as plasma mixing there. This is a manifestation of multiscale coupling; that is, large-scale KH instability may induce micro-scale phenomenon in the rolled-up vortices and resultant formation of the cold plasma sheet in a wide region of the near-Earth magnetotail. Here we show a nice simultaneous measurement of solar wind entry associated with KHI on both sides of the magnetosphere under prolonged northward IMF. In the event that we have found, Cluster on the dawnside and Geotail on the duskside had an opportunity to stay around the magnetopause simultaneously on the opposite side to each other for more than several hours. Proton distribution function on the magnetosphere side of the magnetopause presents dawn-dusk asymmetry, which means that different plasma mixing processes are actually taking place on both sides. Using the Grad-Shafranov reconstruction (GSR) technique that can visualize ambient plasma and field around spacecraft, we clarify that vortical structures due to KHI indeed developed on both sides. These observations and reconstruction analysis suggest that vortical structures induced by KHI result in dawn-dusk asymmetry of plasma mixing around the magnetopause and formation of the cold plasma sheet in a wide region of the near-Earth magnetotail.

Nishino, Masaki N.; Hasegawa, Hiroshi; Fujimoto, Masaki; Mukai, Toshifumi; Saito, Yoshifumi; Reme, Henri; Retino, Alessandro; Nakamura, Rumi; Lucek, Elizabeth


Formation of silicon hydride using hyperthermal negative hydrogen ions (H -) extracted from an argon-seeded hydrogen sheet plasma source  

NASA Astrophysics Data System (ADS)

An E × B probe (a modified Wien filter) is constructed to function both as a mass spectrometer and ion implanter. The device, given the acronym EXBII selects negative hydrogen ions (H -) from a premixed 10% argon-seeded hydrogen sheet plasma. With a vacuum background of 1.0 × 10 -6 Torr, H - extraction ensues at a total gas feed of 1.8 mTorr, 0.5 A plasma discharge. The EXBII is positioned 3 cm distance from the sheet core as this is the region densely populated by cold electrons ( Te ˜ 2 eV, Ne ˜ 3.4 × 10 11 cm -3) best suited for H - formation. The extracted H - ions of flux density ˜0.26 A/m 2 are segregated, accelerated to hyperthermal range (<100 eV) and subsequently deposited into a palladium-coated 1.1 × 1.1 cm 2, n-type Si (1 0 0) substrate held at the rear end of the EXBII, placed in lieu of its Faraday cup. The palladium membrane plays the role of a catalyst initiating the reaction between Si atoms and H - ions simultaneously capping the sample from oxidation and other undesirable adsorbents. AFM and FTIR characterization tests confirm the formation of SiH 2. Absorbance peaks between 900-970 cm -1 (bending modes) and 2050-2260 cm -1 (stretching modes) are observed in the FTIR spectra of the processed samples. It is found that varying hydrogen exposure time results in the shifting of wavenumbers which may be interpreted as changes in the frequencies of vibration for SiH 2. These are manifestations of chemical changes accompanying alterations in the force constant of the molecule. The sample with longer exposure time exhibits an additional peak at 2036 cm -1 which are hydrides of nano-crystalline silicon.

Fernandez, Marcedon S.; Blantocas, Gene Q.; Ramos, Henry J.



A partially folded intermediate species of the beta-sheet protein apo-pseudoazurin is trapped during proline-limited folding.  


The folding of apo-pseudoazurin, a 123-residue, predominantly beta-sheet protein with a complex Greek key topology, has been investigated using several biophysical techniques. Kinetic analysis of refolding using far- and near-ultraviolet circular dichroism (UV CD) shows that the protein folds slowly to the native state with rate constants of 0.04 and 0.03 min(-1), respectively, at pH 7.0 and at 15 degrees C. This process has an activation enthalpy of approximately 90 kJ/mole and is catalyzed by cyclophilin A, indicating that folding is limited by trans-cis proline isomerization, presumably around the Xaa-Pro 20 bond that is in the cis isomer in the native state. Before proline isomerization, an intermediate accumulates during folding. This species has a substantial signal in the far-UV CD, a nonnative signal in the near-UV CD, exposed hydrophobic surfaces (judged by 1-anilino naphthalenesulphonate binding), a noncooperative denaturation transition, and a dynamic structure (revealed by line broadening on the nuclear magnetic resonance time scale). We compare the properties of this intermediate with partially folded states of other proteins and discuss its role in folding of this complex Greek key protein. PMID:11369860

Reader, J S; Van Nuland, N A; Thompson, G S; Ferguson, S J; Dobson, C M; Radford, S E



Pulmonary surfactant-associated polypeptide C in a mixed organic solvent transforms from a monomeric alpha-helical state into insoluble beta-sheet aggregates.  

PubMed Central

In the 35-residue pulmonary surfactant-associated lipopolypeptide C (SP-C), the stability of the valyl-rich alpha-helix comprising residues 9-34 has been monitored by circular dichroism, nuclear magnetic resonance, and Fourier transform infrared spectroscopy in both a mixed organic solvent and in phospholipid micelles. The alpha-helical form of SP-C observed in freshly prepared solutions in a mixed solvent of CHCl3/CH3OH/0.1 M HCl 32:64:5 (v/v/v) at 10 degrees C undergoes within a few days an irreversible transformation to an insoluble aggregate that contains beta-sheet secondary structure. Hydrogen exchange experiments revealed that this conformational transition proceeds through a transition state with an Eyring free activation enthalpy of about 100 kJ mol(-1), in which the polypeptide segment 9-27 largely retains a helical conformation. In dodecylphosphocholine micelles, the helical form of SP-C was maintained after seven weeks at 50 degrees C. The alpha-helical form of SP-C thus seems to be the thermodynamically most stable state in this micellar environment, whereas its presence in freshly prepared samples in the aforementioned mixed solvent is due to a high kinetic barrier for unfolding. These observations support a previously proposed pathway for in vivo synthesis of SP-C through proteolytic processing from a 21-kDa precursor protein.

Szyperski, T.; Vandenbussche, G.; Curstedt, T.; Ruysschaert, J. M.; Wuthrich, K.; Johansson, J.



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

NASA Technical Reports Server (NTRS)

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.

Parker, E. N.



Mechanisms of joint and microstructure formation in high power ultrasonic spot welding 6111 aluminium automotive sheet  

Microsoft Academic Search

Resistance spot welding (RSW) is difficult to apply to aluminium automotive alloys. High power ultrasonic spot welding (HP-USW) is a new alternative method which is extremely efficient, using ?2% of the energy of RSW. However, to date there have been few studies of the mechanisms of bond formation and the material interactions that take place with this process. Here, we

D. Bakavos; P. B. Prangnell



Formation of nanocrystalline surface layers by annealing and their role in filiform corrosion of aluminum sheet  

Microsoft Academic Search

Annealing of specific rolled aluminum alloys at temperatures above 300 C causes a significant increase in the filiform corrosion susceptibility of the painted substrate. As demonstrated for a selected substrate (AA8006), the increased susceptibility is related to the formation of a thin, (electro-)chemically active nanocrystalline layer at the surface as a result of the annealing treatment. The corrosion resistance is

Ha?kon Leth-Olsen; J. H. Nordlien; K. Nisancioglu



Reconnection and Current Sheet Formation in Line-Tied Magnetic Flux Tubes: Energetics and Stability  

NASA Astrophysics Data System (ADS)

Line-tied magnetic fields play a central role in Parker's model of coronal heating [E. N. Parker, Astrophys. J., 174, 499, 1972]. Our previous result [C. S. Ng and A. Bhattacharjee, Phys. Plasmas, 5, 4028, 1998] shows that this model can be realized if a line-tied magnetic equilibrium produced by a smooth footpoint mapping becomes unstable and relaxes to a state with current sheets, leading to magnetic reconnection and heating. A flux-tube tectonics model driven by random footpoint motion [E. R. Priest, J. F. Heyvaerts, and A. M. Title, Astrophys. J., 576, 533, 2002] is revisited. It is shown that if the magnetic field is driven to a statistically steady state, a large current density inversely proportional to the square root of resistivity can fill the whole volume and thus results in a heating rate independent of resistivity. However, the field structures are likely to become unstable and reconnect before they can reach the statistically steady state. The three-dimensional line-tied island coalescence instability -- a possible instability in such systems -- is studied with numerical simulations. Magnetic reconnection in this configuration, which contains neither magnetic nulls nor closed field lines, is discussed. A generalization of the concept of quasi-separatrix layers and a new criterion for the detection of such layers is developed. The new criterion is shown to correlate strongly with reconnection sites. Scaling results from higher resolution simulations will be discussed. This research is supported by a National Science Foundation grant AST-0434322 and by the National Aeronautics and Space Administration.

Ng, C.; Bhattacharjee, A.



A High-Beta, Supersonic Plasma Flow and Shock Formation in Magnetic Channels  

NASA Astrophysics Data System (ADS)

Plasma acceleration and shock wave formation are investigated in the HITOP device of Tohoku University. A high-beta(>50%), and highly-ionized(>50%), flowing He-plasma is produced quasi-steadily(1ms) by an MPD arc jet and is injected into a cylindrical vacuum chamber (diameter: 0.8m, length: 3.3m) along various axial magnetic channels. Axial profiles of an ion acoustic Mach number Mi are measured by a Mach probe and a spectroscopic method. It is found that Mi is almost unity in a uniform magnetic field and Mi increases up to 3 in a diverging magnetic field. When a magnetic bump is added in the diverging field, a shock wave with a sudden decrease in Mi and increase in density is observed near the inlet of the bump region. The subsonic plasma flow is re-accelerated in the converging field. Mi attains to unity near the magnetic throat and increases up to 3 in the diverging region. The bump field works as a magnetic Laval nozzle. These phenomena are quite similar to those in a compressible gas flow through a conventional Laval nozzle.

Inutake, Masaaki; Ando, Akira; Hattori, Kunihiko; Yoshinuma, Mikirou; Imasaki, Atsushi; Yagai, Tsuyoshi; Tobari, Hiroyuki; Murakami, Fumitake; Ashino, Masashi



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

PubMed Central

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.

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



Beta Sheet 2 - Alpha Helix C Loop of Cytochrome P450 Reductase Serves as a Docking Site for Redox Partners  

PubMed Central

As a promiscuous redox partner, the biological role of cytochrome P450 reductase (CPR) depends significantly on protein-protein interactions. We tested a hypothesized CPR docking site by mutating D113, E115, and E116 to alanine and assaying activity toward various electron acceptors as a function of ionic strength. Steady-state cytochrome c studies demonstrated the mutations improved catalytic efficiency and decreased the impact of ionic strength on catalytic parameters when compared to wild type. Based on activity toward 7-ethoxy-4-trifluoro-methylcoumarin, CYP2B1 and CPR favored formation of an active CYP2B1·CPR complex and inactive (CYP2B1)2·CPR complex until higher ionic strength whereby only the binary complex was observed. The mutations increased dissociation constants only for the binary complex and suppressed the ionic strength effect. Studies with a non-binding substrate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) suggest changes in activity toward cytochrome c and CYP2B1 reflect alterations in the route of electron transfer caused by the mutations. Electrostatic modeling of catalytic and binding parameters confirmed the importance of D113 and especially the double mutant E115 and E116 as mediators in forming charge-charge interactions between CPR and complex partners.

Jang, Hyun-Hee; Jamakhandi, Arvind P.; Sullivan, Shane Z.; Yun, Chul-Ho; Hollenberg, Paul F.; Miller, Grover P.



Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment.  


Chicken embryo fibroblasts (CEFs) localize beta-actin mRNA to their lamellae, a process important for the maintenance of cell polarity and motility. The localization of beta-actin mRNA requires a cis localization element (zipcode) and involves zipcode binding protein 1 (ZBP1), a protein that specifically binds to the zipcode. Both localize to the lamellipodia of polarized CEFs. ZBP1 and its homologues contain two NH2-terminal RNA recognition motifs (RRMs) and four COOH-terminal hnRNP K homology (KH) domains. By using ZBP1 truncations fused to GFP in conjunction with in situ hybridization analysis, we have determined that KH domains three and four were responsible for granule formation and cytoskeletal association. When the NH2 terminus was deleted, granules formed by the KH domains alone did not accumulate at the leading edge, suggesting a role for the NH2 terminus in targeting transport granules to their destination. RNA binding studies were used to show that the third and fourth KH domains, not the RRM domains, bind the zipcode of beta-actin mRNA. Overexpression of the four KH domains or certain subsets of these domains delocalized beta-actin mRNA in CEFs and inhibited fibroblast motility, demonstrating the importance of ZBP1 function in both beta-actin mRNA localization and cell motility. PMID:12507992

Farina, Kim L; Huttelmaier, Stefan; Musunuru, Kiran; Darnell, Robert; Singer, Robert H



beta-Galactosidase from Lactobacillus plantarum WCFS1: biochemical characterization and formation of prebiotic galacto-oligosaccharides.  


Recombinant beta-galactosidase from Lactobacillus plantarum WCFS1, homologously over-expressed in L. plantarum, was purified to apparent homogeneity using p-aminobenzyl 1-thio-beta-d-galactopyranoside affinity chromatography and subsequently characterized. The enzyme is a heterodimer of the LacLM-family type, consisting of a small subunit of 35kDa and a large subunit of 72kDa. The optimum pH for hydrolysis of its preferred substrates o-nitrophenyl-beta-d-galactopyranoside (oNPG) and lactose is 7.5 and 7.0, and optimum temperature for these reactions is 55 and 60 degrees C, respectively. The enzyme is most stable in the pH range of 6.5-8.0. The K(m), k(cat) and k(cat)/K(m) values for oNPG and lactose are 0.9mM, 92s(-1), 130mM(-1)s(-1) and 29mM, 98s(-1), 3.3mM(-1)s(-1), respectively. The L. plantarum beta-galactosidase possesses a high transgalactosylation activity and was used for the synthesis of prebiotic galacto-oligosaccharides (GOS). The resulting GOS mixture was analyzed in detail, and major components were identified by using high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) as well as capillary electrophoresis. The maximal GOS yield was 41% (w/w) of total sugars at 85% lactose conversion (600mM initial lactose concentration). The enzyme showed a strong preference for the formation of beta-(1-->6) linkages in its transgalactosylation mode, while beta-(1-->3)-linked products were formed to a lesser extent, comprising approximately 80% and 9%, respectively, of the newly formed glycosidic linkages in the oligosaccharide mixture at maximum GOS formation. The main individual products formed were beta-d-Galp-(1-->6)-d-Lac, accounting for 34% of total GOS, and beta-d-Galp-(1-->6)-d-Glc, making up 29% of total GOS. PMID:20385377

Iqbal, Sanaullah; Nguyen, Thu-Ha; Nguyen, Tien Thanh; Maischberger, Thomas; Haltrich, Dietmar



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

PubMed Central

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.

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



Lipid-specific ?-sheet formation in a mussel byssus protein domain.  


Intrinsically disordered proteins (IDP) or regions (IDR) can adopt multiple conformational states, depending on the interaction partners they encounter. This enables proteins or individual domains to fulfill multiple functions. Here, we analyzed the flank sequences of preCol-NG, one of three collagenous proteins of a mussel byssus thread governing its mechanical performance. preCol-NG comprises a collagen domain and nonrepetitive termini enclosing specific flank regions characterized by tandem repeats known from silk proteins, protein elastomers, and plant cell wall-associated proteins. We recombinantly produced a protein mimicking the M. galloprovincialis preCol-NG C-terminal flank region. The protein was intrinsically unfolded in solution, even at elevated temperatures. However, upon contact with small unilamellar vesicles (SUVs) reversible ?-structure formation occurred, reminiscent of partitioning-folding coupling. This behavior of preCol-NG flank domains likely impacts byssogenesis and sheds new light on a distinct mechanism of how fibrous protein materials might be achieved by lipid-induced self-assembly in nature. PMID:23947342

Heim, Markus; Elsner, Martina B; Scheibel, Thomas



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

PubMed Central

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.

Phelps, Erin M.; Hall, Carol K.



Beta-lactoglobulin/folic acid complexes: formation, characterization, and biological implication.  


Beta-lactoglobulin (beta-LG), the major whey protein in bovine milk, binds to a wide range of compounds. Folic acid (FA) is a synthetic form of the B group vitamin known as folates, which are essential cofactors for a variety of physiological processes. The interaction of beta-LG with FA was studied using fluorescence spectroscopy to determine the FA binding constant and mode and the influence of the protein on FA photodegradation. At < or = 20 microM FA, which may be the critical self-association concentration, the binding constant and number are 2.0 (+/-0.6) x 10(6) M(-1) and 1.30 (+/-0.03) when excited at 280 nm and 4.3 (+/-2.2) x 10(5) M(-1) and 1.17 (+/-0.04) at 295 nm, as determined by protein intrinsic fluorescence. FA binds to the surface of beta-LG, possibly in the groove between the alpha-helix and the beta-barrel. Fluorescence analysis of the pterin portion of FA shows that complexation with beta-LG improves FA photostability. It is suggested that beta-LG complexes could be used as an effective carrier of FA in functional foods. PMID:20411963

Liang, Li; Subirade, Muriel



Analysis of amide bond formation with an alpha-hydroxy-beta-amino acid derivative, 3-amino-2-hydroxy-4-phenylbutanoic acid, as an acyl component: byproduction of homobislactone.  


In the synthesis of peptidomimetics containing alpha-hydroxy-beta-amino acid, the coupling of this N(beta)-protected beta-amino acid with amine components was generally performed without the protection of its alpha-hydroxyl group. However, the formation of dipeptides in low yield was often observed when sterically hindered amine components were used. Boc-Apns-OH [Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid, allophenylnorstatine] (6), which is one of such beta-amino acid derivatives, is intensively employed as a core structure in the development of HIV-1 protease inhibitors. There have been no precise studies, to date, that have examined amide bond formation with alpha-hydroxy-beta-amino acid derivatives as an acyl component. To determine the cause of this low-yield reaction, we studied the amide bond formation focusing on the activation step of N(beta)-protected alpha-hydroxy-beta-amino acid by using a model coupling reaction between 6 and H-Dmt-OR [Dmt: (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid] (7). A significant amount of homobislactone 9 was formed through the activation of the carboxyl group of 6 to the benzotriazole-type active esters such as OBt and OAt. In addition, this homobislactone formation was markedly increased in the presence of a catalytic amount of a base, which exhibited good correlation with the low yield of the amide bond formation, suggesting that homobislactone formation is one major reason for the low yield of the amide bond formation. Moreover, homobislactones were also formed in other derivatives of the N(beta)-protected alpha-hydroxy-beta-amino acid, suggesting a common feature of this type of amino acids. The use of a strong activation method like EDC--HOAt without base addition enhanced amide bond formation, although a small amount of homobislactone may be formed during the coupling reaction. PMID:11485480

Hayashi, Y; Kinoshita, Y; Hidaka, K; Kiso, A; Uchibori, H; Kimura, T; Kiso, Y



Efficient 3'-end formation of human beta-globin mRNA in vivo requires sequences within the last intron but occurs independently of the splicing reaction.  

PubMed Central

The second intron (betaIVS-II) of the human beta-globin gene is essential for the accumulation of stable cytoplasmic mRNA and is implicated in promoting efficient 3'-end formation. This report presents quantitative comparisons between betaIVS-II mutants at physiological levels of expression from within a natural chromatin context in vivo which further defines it's function. In marked contrast to a beta-globin gene lacking a second intron, two mutants defective in splicing (small size or a splice donor mutation), still undergo essentially normal levels of 3'-end formation and in the absence of exon skipping. Therefore, 3' cleavage of beta-globin transcripts requires the presence of betaIVS-II sequences, but not the splicing reaction. The placement of betaIVS-II in the IVS-I position did not reduce the efficiency of 3' cleavage indicating that the distance between the necessary element(s) in this intron and the polyadenylation recognition site is not a crucial factor. Subsequent placement of betaIVS-I in the intron II position, reduced the efficiency of 3'-end formation to only 16% of normal. A direct replacement of intron II by the heterologous introns betaIVS-I or alpha-globin IVS-II, only partially substitute (16 and 30% respectively) for betaIVS-II. Hybrid introns show that efficient 3'-end formation is strongly enhanced by the presence of the terminal 60 nt of betaIVS-II. These data imply that the last intervening sequence of multiple intron containing genes is a principal determinant of the efficiency of 3'-end formation and may act as a post-transcriptional regulatory step in gene expression.

Antoniou, M; Geraghty, F; Hurst, J; Grosveld, F



Formation and self-healing' of magnetic islands in finite-[beta] Helias equilibria  

SciTech Connect

The behavior of finite-pressure-induced magnetic islands is numerically analyzed for three-dimensional magnetohydrostatic equilibria of the Helias configuration by using a three- dimensional equilibrium code. It is found that an island chain is generated on the 5/6 rational surface, when such a surface appears in the plasma region of the finite-[beta] equilibrium. The island chain, however, is not so dangerous as to destroy the plasma confinement even if it appears in a vanishingly small shear region. Thus, a high [beta] equilibrium with clear magnetic surfaces can be realized. Moreover, it is definitely confirmed that the finite pressure effect sometimes exhibits an unexpectedly good aspect, namely, that the vacuum islands are removed as [beta] increases, which can be called self-healing' of islands. This property can be explained by the numerically discovered fact that the phases of islands induced by the finite-pressure effect are always locked in the same phase regardless of [beta].

Hayashi, T.; Sato, T. (National Institute for Fusion Science, Furocho, Nagoya 464-01 (Japan)); Merkel, P.; Nuehrenberg, J.; Schwenn, U. (Max-Planck-Institut fuer Plasmaphysik, IPP-EURATOM Association, D-8046 Garching bei Muenchen (Germany))



Respiration-gated formation of gamma and beta neural assemblies in the mammalian olfactory bulb.  


A growing body of data suggests that information coding can be achieved not only by varying neuronal firing rate, but also by varying spike timing relative to network oscillations. In the olfactory bulb (OB) of a freely breathing anaesthetized mammal, odorant stimulation induces prominent oscillatory local field potential (LFP) activity in the beta (10-35 Hz) and gamma (40-80 Hz) ranges, which alternate during a respiratory cycle. At the same time, mitral/tufted (M/T) cells display respiration-modulated spiking patterns. Using simultaneous recordings of M/T unitary activities and LFP activity, we conducted an analysis of the temporal relationships between M/T cell spiking activity and both OB beta and gamma oscillations. We observed that M/T cells display a respiratory pattern that pre-tunes instantaneous frequencies to a gamma or beta regime. Consequently, M/T cell spikes become phase-locked to either gamma or beta LFP oscillations according to their frequency range and respiratory pattern. Our results suggest that slow respiratory dynamics pre-tune M/T cells to a preferential fast rhythm (beta or gamma) such that a spike-LFP coupling might occur when units and oscillation frequencies are in a compatible range. This double-coupling process might define two complementary beta- and gamma-neuronal assemblies along the course of a respiratory cycle. PMID:19291223

Cenier, Tristan; David, François; Litaudon, Philippe; Garcia, Samuel; Amat, Corine; Buonviso, Nathalie



pH as a trigger of peptide beta-sheet self-assembly and reversible switching between nematic and isotropic phases.  


The hierarchical self-assembly of rationally designed synthetic peptides into beta-sheet tapes, ribbons, fibrils, and fibers opens up potentially useful routes to soft-solidlike materials such as hydrogels, organogels, or liquid crystals. Here, it is shown how incorporation of Glu (-CH(2)CH(2)COOH) or Orn (-CH(2)CH(2)CH(2)NH(2)) into the primary structure of an 11 amino acid peptide enables self-assembly to be rapidly (seconds) and reversibly controlled by simply changing pH. Solutions of monomeric peptide, typically at concentrations in excess of 0.003 v/v, can be switched within seconds to, for example, nematic gel states comprised of interconnected orientationally ordered arrays of fibrils or vice versa. This is to be compared with the lyophilized peptide dissolution route to nematic fluids and gels which is impracticably long, taking many hours or even days. An important design principle, that stabilization of fibrillar dispersions requires of the order of one unit of net positive or negative charge per peptide molecule, is first demonstrated and then used to design an 11 amino acid peptide P(11)-3 (CH(3)CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Gln-Gln-Gln-NH(2)) whose self-assembly behavior is independent of pH (1 < pH < 10). pH control is then incorporated by appropriately positioning Glu or Orn side chains so that the peptide-peptide free energy of interaction in the tapelike substructure is strongly influenced by direct electrostatic forces between gamma-COO(-) in Glu(-) or delta-NH(3)(+) in Orn(+), respectively. This design principle is illustrated by the behavior of two peptides: P(11)-4 (CH(3)CO-Gln-Gln-Arg-Phe-Glu-Trp-Glu-Phe-Glu-Gln-Gln-NH(2)) which can be switched from its nematic to its isotropic fluid state by increasing pH and P(11)-5 (CH(3)CO-Gln-Gln-Orn-Phe-Orn-Trp-Orn-Phe-Gln-Gln-Gln-NH(2)) designed to exhibit the converse behavior. Acid-base titrations of fibrillar dispersions reveal deprotonation of the gamma-COOH of Glu or of the delta-NH(3)(+) of Orn(+) occurs over wide bands of up to 5 pH units, a feature of polyelectrolytes. The values of the energy parameters controlling self-assembly can therefore be smoothly and continuously varied by changing pH. This enables isotropic fluid-to-nematic transitions to be triggered by relatively small additions of acid or base, typically 1 part in 10(3) by volume of 1 M HCl or NaOH. PMID:12904028

Aggeli, Amalia; Bell, Mark; Carrick, Lisa M; Fishwick, Colin W G; Harding, Richard; Mawer, Peter J; Radford, Sheena E; Strong, Andrew E; Boden, Neville



Global Simulations of Differentially Rotating Magnetized Disks: Formation of Low-beta Filaments and Structured Coronae.  


We present the results of three-dimensional global magnetohydrodynamic simulations of the Parker-shearing instability in a differentially rotating torus initially threaded by toroidal magnetic fields. An equilibrium model of a magnetized torus is adopted as an initial condition. When beta0=Pgas&solm0;Pmag approximately 1 at the initial state, magnetic flux buoyantly escapes from the disk and creates looplike structures similar to those in the solar corona. Inside the torus, the growth of nonaxisymmetric magnetorotational (or Balbus & Hawley) instability generates magnetic turbulence. Magnetic field lines are tangled on a small scale, but on a large scale they show low azimuthal wavenumber spiral structure. After several rotation periods, the system oscillates around a state with beta approximately 5. We found that magnetic pressure-dominated (beta<1) filaments are created in the torus. The volume filling factor of the region in which betabeta regions may lead to violent flaring activities in accretion disks and in galactic gas disks. PMID:10702134

Machida; Hayashi; Matsumoto



Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro.  


Previous studies have indicated that MD-fraction (MDF), in which the active component is beta 1,6-glucan with beta 1,3-branches, has anti-tumor activity as an oral agent and acts as an immune adjuvant. Since some other beta glucans appear to promote mobilization of hematopoietic stem cells, the effects of a beta glucan extract from the Maitake mushroom "MD-fraction" on hematopoietic stem cells were examined in a colony forming assay. Here we report for the first time that MDF has a dose response effect on mouse bone marrow cells (BMC) hematopoiesis in vitro. Using the Colony Forming Unit (CFU) assay to detect formation of granulocyte-macrophage (CFU-GM) colonies, and the XTT cytotoxicitiy assay to measure BMC viability, the data showed that the addition of MDF significantly enhanced the development of CFU-GM in a dose range of 50-100 microg/ml (p<0.004). The mechanism of action included significant increase of nonadherent BMC viability, which was observed at MDF doses of 12.5-100 microg/ml (p<0.005). In the presence of Doxorubicin (DOX), MDF promoted BMC viability and protected CFU-GM from DOX induced toxicity. In addition, MDF treatment promoted the recovery of CFU-GM colony formation after BMC were pretreated with DOX. These studies provided the first evidence that MDF acts directly in a dose dependent manner on hematopoietic BMC and enhances BMC growth and differentiation into colony forming cells. PMID:14975363

Lin, Hong; She, Yu-Hong; Cassileth, Barrie R; Sirotnak, Frank; Cunningham Rundles, Susanna



Nanospace-confined formation of flattened Sn sheets in pre-seeded graphenes for lithium ion batteries.  


Flattened Sn sheets are prepared from the pre-seeded Sn salt in the interlayer nanospace of a graphene membrane, which acts as a template to shape Sn crystals and prevent the aggregation. The sandwich structure clamping Sn sheets accommodates the volume change during charge/discharge. We show that the hybrid possesses excellent rate performance and cycling stability as an anode for lithium ion batteries. PMID:24993388

Li, Zhengjie; Lv, Wei; Zhang, Chen; Qin, Jiwen; Wei, Wei; Shao, Jiao-Jing; Wang, Da-Wei; Li, Baohua; Kang, Feiyu; Yang, Quan-Hong



Metal-sheet-beam formation using an impregnated electrode-type liquid-metal ion source with a linear array of emission points  

NASA Astrophysics Data System (ADS)

High current and sheet-shaped metal beams are required in ion implanters which utilize a mass separator. The present paper describes the profiles of the ion beams extracted from the impregnated electrode-type liquid-metal ion source with linear array of emission points (array source) and the formation of the sheet beams with a rectangular lens system. The experimental results indicated that the profiles of the extracted beamlet of array source without use of lens system have smaller divergences along the parallel direction with respect to the ion emission array. Since it has been clarified that the beamlet was convergent along the parallel direction, the focusing lens system was designed so as to converge the ion beam along the perpendicular direction. The profiles of the converged beams were also measured. As a result, it was found that the sheet beams were successfully formed and the thickness of the sheet-shaped beam is found to be about 2 mm. The present results demonstrated that this type of ion source could be utilized in a practical implanter.

Gotoh, Yasuhito; Ishikawa, Junzo; Tsuji, Hiroshi; Fukayama, Norihisa; Ogata, Yasushi



Triggers for ?-sheet formation at the hydrophobic-hydrophilic interface: high concentration, in-plane orientational order, and metal ion complexation.  


Amyloid formation plays a causative role in neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Soluble peptides form ?-sheets that subsequently rearrange into fibrils and deposit as amyloid plaques. Many parameters trigger and influence the onset of the ?-sheet formation. Early stages are recently discussed to be cell-toxic. Aiming at understanding various triggers such as interactions with hydrophobic-hydrophilic interfaces and metal ion complexation and their interplay, we investigated a set of model peptides at the air-water interface. We are using a general approach to a variety of diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes that are connected to amyloid formation. Surface sensitive techniques combined with film balance measurements have been used to assess the conformation of the peptides and their orientation at the air-water interface (IR reflection-absorption spectroscopy). Additionally, the structures of the peptide layers were characterized by grazing incidence X-ray diffraction and X-ray reflectivity. The peptides adsorb to the air-water interface and immediately adopt an ?-helical conformation. This helical intermediate transforms into ?-sheets upon further triggering. The factors that result in ?-sheet formation are dependent on the peptide sequence. In general, the interface has the strongest effect on peptide conformation compared to high concentrations or metal ions. Metal ions are able to prevent aggregation in bulk but not at the interface. At the interface, metal ion complexation has only minor effects on the peptide secondary structure, influencing the in-plane structure that is formed in two dimensions. At the air-water interface, increased concentrations or a parallel arrangement of the ?-helical intermediates are the most effective triggers. This study reveals the role of various triggers for ?-sheet formation and their complex interplay. Our main finding is that the hydrophobic-hydrophilic interface largely governs the conformation of peptides. Therefore, the present study implies that special care is needed when interpreting data that may be affected by different amounts or types of interfaces during experimentation. PMID:22011020

Hoernke, Maria; Falenski, Jessica A; Schwieger, Christian; Koksch, Beate; Brezesinski, Gerald



Secondary product formation by cultures of Beta vulgaris and Nicotiana rustica transformed with Agrobacterium rhizogenes  

Microsoft Academic Search

‘Hairy root’ cultures of Beta vulgaris and Nicotiana rustica were established after roots were induced on plants following infection with Agrobacterium rhizogenes. The transformed cultures of B. vulgaris and N. rustica synthesised their characteristic secondary products, the betalain pigments and nicotine alkaloids respectively, at levels comparable with those of in vivo roots from the same variety. Betalains were entirely retained

J. D. Hamill; A. J. Parr; R. J. Robins; M. J. C. Rhodes



Separation of Drug Stereoisomers by the Formation of beta Cyclodextrin Inclusion Complexes  

Microsoft Academic Search

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

Daniel W. Armstrong; Timothy J. Ward; R. Douglas Armstrong; Thomas E. Beesley



The selective formation of graphene ranging from two-dimensional sheets to three-dimensional mesoporous nanospheres  

NASA Astrophysics Data System (ADS)

This research presents a template-free solvothermal method which offers selective preparation of graphene ranging from two-dimensional sheets to 3-dimensional nanospheres. The thus prepared nanospheres have size-defined mesopores with a huge surface area and, after doping with nitrogen, exhibited stronger electrocatalytic activity toward oxygen reduction than commercial Pt/C catalysts.This research presents a template-free solvothermal method which offers selective preparation of graphene ranging from two-dimensional sheets to 3-dimensional nanospheres. The thus prepared nanospheres have size-defined mesopores with a huge surface area and, after doping with nitrogen, exhibited stronger electrocatalytic activity toward oxygen reduction than commercial Pt/C catalysts. Electronic supplementary information (ESI) available: Detailed experimental procedures, HRTEM, TGA and mass spectroscopy data, Raman spectra, additional synthetic results at different reaction temperatures and results with graphene sheets. See DOI: 10.1039/c4nr00935e

Wang, Jian; Jin, Huile; He, Yuhua; Lin, Dajie; Liu, Aili; Wang, Shun; Wang, Jichang



Roles of magnetic reconnection and buoyancy in the formation of dipolarization fronts: three-dimensional particle simulations of two-dimensional current sheet equilibria  

NASA Astrophysics Data System (ADS)

Unsteady magnetic reconnection in the magnetosphere and in the solar corona involves the formation of localized ejecta, such as the magnetotail dipolarization fronts (DFs) and coronal supra-arcade downflowing loops (SADLs). Both DFs and SADLs move in the direction opposite to the initial magnetic field stretching with a speed comparable to the Alfven speed. However, the DF scales are comparable to the ion gyro radius and therefore their analysis requires kinetic theory and simulations. Recent kinetic theory and PIC simulations of 2D magnetotail equilibria revealed two possible mechanisms of the DF formation, namely mutual attraction of parallel current filaments in thin current sheets causing magnetic reconnection via the tearing instability and magnetic buoyancy resulting in the ballooning-interchange instability. Both mechanisms are most efficient in the geometries with accumulation of magnetic flux at the tailward end of a thin current sheet. To understand the roles of magnetic reconnection and buoyancy in the formation and evolution of DFs we perform 3D PIC simulations of 2D current sheets, where two magnetotails are separated by an equilibrium X-line. To justify modeling the long terrestrial magnetotail in a relatively small simulation box: Lx x Ly x Lz= 40d x 20d x 5d (d is the ion inertial length; GSM coordinate system is used) open boundary conditions are employed in the x-direction. The magnetotail parts of the 2D equilibrium include regions of accumulated magnetic flux, consistent with the Geotail observations of similar signatures prior to substorm onset. We investigate which of the mechanisms is responsible for the formation of DF-like structures in 3D configurations and discuss their subsequent motion and structure. Simulations are compared with recent THEMIS observations of DFs and ballooning-interchange oscillations in the magnetotail, as well as SDO observations of solar flares.

Knizhnik, K.; Sitnov, M. I.; Swisdak, M. M.



An improved medium for adventitious shoot formation and callus induction in Beta vulgaris L. in vitro  

Microsoft Academic Search

Six sugarbeet (Beta vulgaris L.) lines (GWI-248, SPB-11, MonoHy 55, SMS-1, EL45 and FC607) were tested for regeneration. Shoot cultures were initiated in vitro from naked, sterilized embryos obtained from mature seed. Excised petioles from cultured shoots were plated on Gamborg's B5 medium and four modified Murashige and Skoog (MS) media. A medium containing MS inorganic salts supplemented with 0.4

A. H. Freytag; S. C. Anand; A. P. Rao-Arelli; L. D. Owens



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

Microsoft Academic Search

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 (IFN?-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300mg (n=589) or placebo (n=582) intravenously every 4weeks plus IFN?-1a 30µg intramuscularly once weekly. Annual

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



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

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.

Stockman, B.J.; Krezel, A.M.; Markley, J.L. (Univ. of Wisconsin, Madison (USA)); Leonhardt, K.G.; Straus, N.A. (Univ. of Toronto, Ontario (Canada))



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

NASA Astrophysics Data System (ADS)

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-? 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.

Hall, Carol



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

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.

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))



Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP.  


Type 2 diabetes mellitus (T2DM) is characterized by an approximately 60% deficit in beta-cell mass, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) forms oligomers, leading to either amyloid fibrils or toxic oligomers in an aqueous solution in vitro. Either application of hIAPP on or overexpression of hIAPP in cells induces apoptosis. It remains controversial whether the fibrils or smaller toxic oligomers induce beta-cell apoptosis. Rifampicin prevents hIAPP amyloid fibril formation and has been proposed as a potential target for prevention of T2DM. We examined the actions of rifampicin on hIAPP amyloid fibril and toxic oligomer formation as well as its ability to protect beta-cells from either application of hIAPP or endogenous overexpression of hIAPP (transgenic rats and adenovirus-transduced beta-cells). We report that rifampicin (Acocella G. Clin Pharmacokinet 3: 108-127, 1978) prevents hIAPP fibril formation, but not formation of toxic hIAPP oligomers (Bates G. Lancet 361: 1642-1644, 2003), and does not protect beta-cells from apoptosis induced by either overexpression or application of hIAPP. These data emphasize that toxic hIAPP oligomers, rather than hIAPP fibrils, initiate beta-cell apoptosis and that screening tools to identify inhibitors of amyloid fibril formation are likely to be less useful than those that identify inhibitors of toxic oligomer formation. Finally, rifampicin and related molecules do not appear to be useful as candidates for prevention of T2DM. PMID:16849627

Meier, Juris J; Kayed, Rakez; Lin, Chia-Yu; Gurlo, Tatyana; Haataja, Leena; Jayasinghe, Sajith; Langen, Ralf; Glabe, Charles G; Butler, Peter C



Inhibition of beta-amyloid aggregation by fluorescent dye labels  

NASA Astrophysics Data System (ADS)

The fluorescence decay of beta-amyloid's (A?) intrinsic fluorophore tyrosine has been used for sensing the oligomer formation of dye-labelled A? monomers and the results compared with previously studied oligomerization of the non-labelled A? 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.

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



A kinetic study of the formation of beta-cyclodextrin complexes with monomolecular films of fatty acids and glycerides spread at the air/water interface.  


The kinetics of formation of inclusion complexes between beta-cyclodextrin and monolayers of one-, two- and three-chained lipid molecules, namely, oleic acid (OA), monoolein (MO), diolein (DO) and triolein (TO), was investigated at various pH using three independent dynamic methods. The formation and solubilization of soluble inclusion beta-CD/OA and beta-CD/MO complexes was detected by measuring the decrease of the surface area and surface pressure of the OA and MO monolayers in the presence of beta-CD within a wide range of concentrations. A third approach, describing the dilatational properties of the monolayers, influenced by the formation and solubilization of the complexes, was developed. Using the three above-mentioned independent methods, the rate constants of formation (k1) and dissociation (k2) of beta-CD/OA and beta-CD/MO, were determined. We observed that solubilization flux i s for OA monolayer increases with pH and at pH 11 reached a value, which is closed to the diffusion flux iD and the process thus becomes diffusion controlled. For MO monolayer no significant effects of pH was observed above pH 6. The surface pressure (Deltapi)--area per molecule (A) and surface potential (DeltaV)--area per molecule (A) isotherms and rheological properties of DO and TO monolayers were measured in the presence or absence of beta-CD. DO and TO form water-insoluble complexes with beta-CD, as visualized by AFM images. PMID:15784322

Alahverdjieva, Veneta; Ivanova, Margarita; Verger, Robert; Panaiotov, Ivan



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

NASA Astrophysics Data System (ADS)

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.

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



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

PubMed Central

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 µg/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.

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



Formation of silicon hydride using hyperthermal negative hydrogen ions (H ?) extracted from an argon-seeded hydrogen sheet plasma source  

Microsoft Academic Search

An E×B probe (a modified Wien filter) is constructed to function both as a mass spectrometer and ion implanter. The device, given the acronym EXBII selects negative hydrogen ions (H?) from a premixed 10% argon-seeded hydrogen sheet plasma. With a vacuum background of 1.0×10?6Torr, H? extraction ensues at a total gas feed of 1.8mTorr, 0.5A plasma discharge. The EXBII is

Marcedon S. Fernandez; Gene Q. Blantocas; Henry J. Ramos



Formation of silicon hydride using hyperthermal negative hydrogen ions (H-) extracted from an argon-seeded hydrogen sheet plasma source  

Microsoft Academic Search

An E × B probe (a modified Wien filter) is constructed to function both as a mass spectrometer and ion implanter. The device, given the acronym EXBII selects negative hydrogen ions (H-) from a premixed 10% argon-seeded hydrogen sheet plasma. With a vacuum background of 1.0 × 10-6 Torr, H- extraction ensues at a total gas feed of 1.8 mTorr,

Marcedon S. Fernandez; Gene Q. Blantocas; Henry J. Ramos



Formation of high-Beta plasmas in various modes of operation in TPE-2  

NASA Astrophysics Data System (ADS)

Confinement and stability properties of high-beta plasmas in a toroidal screw pinch machine with an elliptic minor cross-section and a small aspect ratio is discussed. Plasma diagnostics and data analysis, and results obtained in the usual mode of operation are discussed. Results of the matched screw-pinch mode are presented. In this mode, the bias field and predischarge current are combined with the power-crowbar circuits in such a way that Bt and Ip increase almost simultaneously to their maximum values in 0.5 msec at a nearly constant value of qI at the wall. For both modes, the time evolution of a typical discharge is shown.

Oomens, A. A. M.; Hayase, H.; Hirota, I.; Kiyama, H.; Kiyama, S.; Maejima, Y.; Sato, Y.; Yahagi, E.; Kito, M.



Formation of hydrogel particles by thermal treatment of beta-lactoglobulin-chitosan complexes.  


Molecular complexes based on proteins and ionic polysaccharides have considerable potential for encapsulation of functional food components, but their widespread utilization is limited because their structure is highly sensitive to pH and ionic strength. We have investigated the possibility of creating stable hydrogel particles by thermal treatment of protein (beta-lactoglobulin) and cationic polysaccharide (chitosan) mixtures. Mixed solutions of beta-lactoglobulin (0.5 wt %) and chitosan (0.1 wt %) were prepared at various pH's (3-8) and were heated (80 degrees C for 20 min). Prior to heating, the biopolymer mixtures formed molecular complexes at pH values where there was an electrostatic attraction between the protein and the polysaccharide: soluble complexes at pH 4.5; complex coacervates at pH 5.0 and 5.5; precipitates at pH>5.5. After heating, relatively small (d approximately 140 nm) and cationic (zeta>+20 mV) hydrogel particles were formed at pH 4.5, but much larger aggregates were formed at pH 5.0 and higher (d>1000 nm). The thermally treated hydrogel particles formed at pH 4.5 maintained their initial particle size when the pH was subsequently adjusted within the range pH 3-5, but they aggregated when the pH was adjusted to >pH 5 because of a reduction in the magnitude of their electrical charge. This study suggests that hydrogel particles can be formed by heating mixed protein-polysaccharide systems under controlled conditions. These hydrogel particles may be useful for encapsulation of functional food components. PMID:17567036

Hong, Youn-Ho; McClements, David Julian



Comparison of the function of the beta(C) and beta(E) subunits of activin in AML12 hepatocytes.  


To investigate the function of the beta(C) and beta(E) subunits of activin, we overexpressed these subunits in AML12 cells, a normal hepatocyte cell line, using adenovirus vector. Overexpression of the beta(C) subunit increased [3H]thymidine incorporation and the cell number. In contrast, both [3H]thymidine incorporation and the cell number were reduced in the beta(E) overexpressing cells. When AML cells overexpressing the beta(E) subunit were cultured in medium containing 1% serum for 48 h, many of the cells died by apoptosis, whereas cells overexpressing the beta(C) subunit or beta-galactosidase survived in the same condition. To examine dimer formation, the beta(C) and beta(E) subunits were expressed in AML12 cells. In these cells, the beta(C) homodimer, the beta(E) homodimer and the beta(C)-beta(E) heterodimer were detected. When the expression level of the beta(E) subunit was increased, formation of the beta(E) homodimer was increased, while formation of the beta(C)-beta(E) heterodimer was slightly reduced. Overexpression of the beta(E) subunit did not significantly affect the formation of the beta(C) homodimer. These results indicate that the beta(C) and beta(E) subunits form homo- and heterodimers, and that the functions of the two subunits are quite different. PMID:15863943

Wada, Wataru; Medina, Johan J; Kuwano, Hiroyuki; Kojima, Itaru



Assessment sheets  

NSDL National Science Digital Library

This website offers assessment sheets on humans, plants, habitats, materials, light, earth and beyond, sound, forces, electricity, and science. The sheets tell you what the student should know from each objective.



Drosophila Transforming Growth Factor beta Superfamily Proteins Induce Endochondral Bone Formation in Mammals  

Microsoft Academic Search

Both decapentaplegic (dpp) protein and 60A protein have been implicated in pattern formation during Drosophila melanogaster embryogenesis. Within the C-terminal domain, dpp and 60A are similar to human bone morphogenetic protein 2 (75% identity) and human osteogenic protein 1 (70% identity), respectively. Both recombinant human bone morphogenetic protein 2 and recombinant human osteogenic protein 1 have been shown to induce

T. K. Sampath; K. E. Rashka; J. S; R. F. Tucker; F. M. Hoffmann



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

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

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



Wetlands Fact Sheets  

NSDL National Science Digital Library

The U.S. Environmental Protection Agency has provided an extensive list of over 40 fact sheets relating to various aspects of wetlands. Most are provided in a low resoluion format for viewing or a high resolution format for printing. A great deal of basic information regarding the definition, values, and functions of wetlands is provided.



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

PubMed Central

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

Marzec, C J; Day, L A



Ice Sheets  

NSDL National Science Digital Library

This educational brief describes the nature and properties of the Greenland and Antarctica ice sheets. Topics include the thickness and aereal extent of the ice sheets, volume of water contained in them, mass balance, and the mechanisms by which ice is lost from or accumulated by the ice sheets.


Suppressors of transforming growth factor-beta pathway mutants in the Caenorhabditis elegans dauer formation pathway.  


The dauer is a developmentally arrested alternative third larval stage of Caenorhabditis elegans. Entry into this state is regulated by environmental cues, including temperature, food, and the concentration of constitutively secreted dauer pheromone. Genetically, three parallel pathways have been found that regulate this process. Of these, the group 2 pathway, which includes the genes daf-1, daf-3, daf-4, daf-5, daf-7, daf-8, and daf-14, mediates the transduction of environmental signals through the ASI chemosensory neuron and encodes a TGF-beta-related signaling pathway. To identify additional genes that function in this pathway, we carried out a screen for suppressors of mutations in daf-1, daf-8, and daf-14. From the total of 36 mutations, seven complementation groups were identified. Three complementation groups correspond to the previously described genes daf-3, daf-5, and daf-12. Three correspond to novel genes scd-1, scd-2, and scd-3. Genetic analysis of these scd genes is presented here. A fourth complementation group was represented by a single mutation sa315, which affects the daf-2/age-1 insulin-related signaling pathway. PMID:11063683

Inoue, T; Thomas, J H



A novel mechanism for cyclic adenosine monophosphate-mediated memory formation: Role of amyloid beta.  


Cyclic adenosine monophosphate (cAMP) regulates long-term potentiation (LTP) and ameliorates memory in healthy and diseased brain. Increasing evidence shows that, under physiological conditions, low concentrations of amyloid ? (A?) are necessary for LTP expression and memory formation. Here, we report that cAMP controls amyloid precursor protein (APP) translation and A? levels, and that the modulatory effects of cAMP on LTP occur through the stimulation of APP synthesis and A? production. PMID:24591104

Ricciarelli, Roberta; Puzzo, Daniela; Bruno, Olga; Canepa, Elisa; Gardella, Elena; Rivera, Daniela; Privitera, Lucia; Domenicotti, Cinzia; Marengo, Barbara; Marinari, Umberto Maria; Palmeri, Agostino; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto



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


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

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



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


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

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



Release of cAMP gating by the alpha6beta4 integrin stimulates lamellae formation and the chemotactic migration of invasive carcinoma cells.  


The alpha6beta4 integrin promotes carcinoma in-vasion by its activation of a phosphoinositide 3-OH (PI3-K) signaling pathway (Shaw, L.M., I. Rabinovitz, H.H.-F. Wang, A. Toker, and A.M. Mercurio. Cell. 91: 949-960). We demonstrate here using MDA-MB-435 breast carcinoma cells that alpha6beta4 stimulates chemotactic migration, a key component of invasion, but that it has no influence on haptotaxis. Stimulation of chemotaxis by alpha6beta4 expression was observed in response to either lysophosphatidic acid (LPA) or fibroblast conditioned medium. Moreover, the LPA-dependent formation of lamellae in these cells is dependent upon alpha6beta4 expression. Both lamellae formation and chemotactic migration are inhibited or "gated" by cAMP and our results reveal that a critical function of alpha6beta4 is to suppress the intracellular cAMP concentration by increasing the activity of a rolipram-sensitive, cAMP-specific phosphodiesterase (PDE). This PDE activity is essential for lamellae formation, chemotactic migration and invasion based on data obtained with PDE inhibitors. Although PI3-K and cAMP-specific PDE activities are both required to promote lamellae formation and chemotactic migration, our data indicate that they are components of distinct signaling pathways. The essence of our findings is that alpha6beta4 stimulates the chemotactic migration of carcinoma cells through its ability to influence key signaling events that underlie this critical component of carcinoma invasion. PMID:9852165

O'Connor, K L; Shaw, L M; Mercurio, A M



Application of a robust [beta]pdf treatment to analysis of thermal NO formation in nonpremixed hydrogen-air flame  

Microsoft Academic Search

The assumed [beta]-pdf is widely used in turbulent flame simulation with the moment closure method. However, implementation of the [beta]-pdf in turbulent flame simulation may sometimes encounter singularity difficulties in numerical calculation. The study proposes a robust [beta]-pdf treatment to overcome these numerical difficulties. The proposed [beta]-pdf treatment associated with the partial equilibrium chemistry model and the k-[epsilon] turbulence model

C. S. Chen; K. C. Chang; J. Y. Chen



A hydrocarbon exploration model for the Beta Member of the Permian Kaibab Formation, with emphasis on the potential for hydrodynamically displaced oil, in east-central Utah  

Microsoft Academic Search

In Utah, the Beta Member of the Permian Kaibab Formation produces oil at the Ferron field in the western part of the study area, and the Upper Valley field, 30 mi southwest of the study area. Production at Upper Valley is hydrodynamically controlled; it is unknown if production at Ferron field is hydrodynamically controlled due to the lack of well



Genetic analysis of microtubule structure: a beta-tubulin mutation causes the formation of aberrant microtubules in vivo and in vitro  

Microsoft Academic Search

A recessive male sterile mutation (B2t s) that encodes a stable variant of the testis-specific 132-tubulin of Drosophila causes the assembly of aber- rant microtubules both in vivo and in vitro. The B2t s mutation appears to cause defects in the formation of in- terprotofilament bonds. In testes from homozygous mutant males, the most commonly observed aberrant structures were sheets

Margaret T. Fuller; Joan H. Caulton; Jeffrey A. Hutchens; Thomas C. Kaufman; Elizabeth C. Raft



Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils.  


The discovery of methods suitable for the conversion in vitro of native proteins into amyloid fibrils has shed light on the molecular basis of amyloidosis and has provided fundamental tools for drug discovery. We have studied the capacity of a small library of tetracycline analogues to modulate the formation or destructuration of ?2-microglobulin fibrils. The inhibition of fibrillogenesis of the wild type protein was first established in the presence of 20% trifluoroethanol and confirmed under a more physiologic environment including heparin and collagen. The latter conditions were also used to study the highly amyloidogenic variant, P32G. The NMR analysis showed that doxycycline inhibits ?2-microglobulin self-association and stabilizes the native-like species through fast exchange interactions involving specific regions of the protein. Cell viability assays demonstrated that the drug abolishes the natural cytotoxic activity of soluble ?2-microglobulin, further strengthening a possible in vivo therapeutic exploitation of this drug. Doxycycline can disassemble preformed fibrils, but the IC(50) is 5-fold higher than that necessary for the inhibition of fibrillogenesis. Fibril destructuration is a dynamic and time-dependent process characterized by the early formation of cytotoxic protein aggregates that, in a few hours, convert into non-toxic insoluble material. The efficacy of doxycycline as a drug against dialysis-related amyloidosis would benefit from the ability of the drug to accumulate just in the skeletal system where amyloid is formed. In these tissues, the doxycycline concentration reaches values several folds higher than those resulting in inhibition of amyloidogenesis and amyloid destructuration in vitro. PMID:21068391

Giorgetti, Sofia; Raimondi, Sara; Pagano, Katiuscia; Relini, Annalisa; Bucciantini, Monica; Corazza, Alessandra; Fogolari, Federico; Codutti, Luca; Salmona, Mario; Mangione, Palma; Colombo, Lino; De Luigi, Ada; Porcari, Riccardo; Gliozzi, Alessandra; Stefani, Massimo; Esposito, Gennaro; Bellotti, Vittorio; Stoppini, Monica



Quasi-adiabatic particle acceleration in magnetic field reversals and the formation of the plasma sheet boundary layer in the earth's magnetotail  

NASA Astrophysics Data System (ADS)

The acceleration of magnetic field reversal (MFR) particles in the stationary and homogeneous electric field induced by the motion of MFR through the ambient plasma (i.e., solar wind) is considered. Assuming that the time scale of acceleration is slow in comparison with the period of orbital motion, the longitudinal invariant is introduced to describe the process of acceleration in a closed form and to obtain the laws governing the quasiadiabatic ion acceleration in the Earth's magnetotail. The similarities and differences in adiabatic and quasiadiabatic acceleration mechanisms are discussed. The results give insights to the problem of particle heating in the Earth's magnetotail and to the formation of accelerated plasma streams along the edges of the plasma sheet.

Zelenyi, L. M.; Zogin, D. V.; Buechner, J. M.



EGF-induced MAPK signaling inhibits hemidesmosome formation through phosphorylation of the integrin {beta}4.  


Migration of keratinocytes requires a regulated and dynamic turnover of hemidesmosomes (HDs). We and others have previously identified three serine residues on the integrin ?4 cytoplasmic domain that play a critical role in the regulation of HD disassembly. In this study we show that only two of these residues (Ser-1356 and Ser-1364) are phosphorylated in keratinocytes after stimulation with either PMA or EGF. Furthermore, in direct contrast to previous studies performed in vitro, we found that the PMA- and EGF-stimulated phosphorylation of ?4 is not mediated by PKC, but by ERK1/2 and its downstream effector kinase p90RSK1/2. EGF-stimulated phosphorylation of ?4 increased keratinocyte migration, and reduced the number of stable HDs. Furthermore, mutation of the two serines in ?4 to phospho-mimicking aspartic acid decreased its interaction with the cytoskeletal linker protein plectin, as well as the strength of ?6?4-mediated adhesion to laminin-332. During mitotic cell rounding, when the overall cell-substrate area is decreased and the number of HDs is reduced, ?4 was only phosphorylated on Ser-1356 by a distinct, yet unidentified, kinase. Collectively, these data demonstrate an important role of ?4 phosphorylation on residues Ser-1356 and Ser-1364 in the formation and/or stability of HDs. PMID:20870721

Frijns, Evelyne; Sachs, Norman; Kreft, Maaike; Wilhelmsen, Kevin; Sonnenberg, Arnoud



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

PubMed Central

Tannerella forsythia is an important pathogen in periodontal disease. Previously, we showed that sialidase activity is key to its utilisation 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 since biofilm growth and initial cell adhesion is inhibited by PugNAc. In contrast, adhesion to siallo-protein 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.

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



The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer  

PubMed Central

Breast cancer is a major cause of cancer-related deaths in American women; therefore, the identification of novel breast-cancer related molecules for the discovery of new markers and drug targets remains essential. The human DEK gene, which encodes a chromatin-binding protein and DNA topology regulator, is up-regulated in many types of cancer. DEK has been implicated as an oncogene in breast cancer based on mRNA expression studies, but its functional significance in breast cancer growth and progression has not yet been tested directly. We demonstrate that DEK is highly expressed in breast cancer cells compared to normal tissue, and functionally important for cellular growth, invasion and mammosphere formation. DEK over-expression in non-tumorigenic MCF10A cells resulted in increased growth and motility with a concomitant down-regulation of E-cadherin. Conversely, DEK knockdown in MCF7 and MDA-MB-468 breast cancer cells resulted in decreased growth and motility with up-regulation of E-cadherin. The use of DEK-proficient and -deficient breast cancer cells in orthotopic xenografts provided further in vivo evidence that DEK contributes to tumor growth. Activation of the ?-catenin signaling pathway is important for normal and cancer stem cell character, growth and metastasis. We show that DEK expression stimulated and DEK knockdown repressed ?-catenin nuclear translocation and activity. Importantly, the expression of constitutively active ?-catenin rescued breast cancer invasion defects of DEK knockdown cells. Together, our data indicate that DEK expression stimulates the growth, stem cell character, and motility of breast cancer cells, and that DEK-dependent cellular invasion occurs at least in part via ?-catenin activation.

Privette Vinnedge, Lisa M.; McClaine, Rebecca; Wagh, Purnima K.; Wikenheiser-Brokamp, Kathryn A.; Waltz, Susan E.; Wells, Susanne I.



Single and combined effects of alphavbeta3- and alpha5beta1-integrins on capillary tube formation in a human fibrinous matrix.  


The fibrinous exudate of a wound or tumor stroma facilitates angiogenesis. We studied the involvement of RGD-binding integrins during tube formation in human plasma-derived fibrin clots and human purified fibrin matrices. Capillary-like tube formation by human microvascular endothelial cells in a 3D plasma-derived fibrinous matrix was induced by FGF-2 and TNF-alpha and depended largely on cell-bound u-PA and plasmin activities. While tube formation was minimally affected by the addition of either the alphavbeta3-integrin inhibiting mAb LM609 or the alpha5-integrin inhibiting mAb IIA1, the general RGD-antagonist echistatin completely inhibited this process. Remarkably, when alphavbeta3- and alpha5beta1-integrins were inhibited simultaneously, tube formation was reduced by 78%. It was accompanied by a 44% reduction of u-PA antigen accumulation and 41% less production of fibrin degradation products. alphavbeta5-integrin-blocking antibodies further enhanced the inhibition by mAb LM609 and mAb IIA1 to 94%, but had no effect by themselves. alphav-specific cRGD only inhibited angiogenesis when alpha5beta1-integrin was simultaneously blocked. Endostatin mimicked the effect of alpha5beta1-integrin and inhibited tube formation only in the presence of LM609 or cRGD (73 and 80%, respectively). Comparable results were obtained when purified fibrin matrices were used instead of the plasma-derived fibrinous matrices. These data show that blocking of tube formation in a fibrinous exudate requires the simultaneous inhibition of alphavbeta3- and alpha5beta1-integrins. This may bear impact on attempts to influence angiogenesis in a fibrinous environment. PMID:19449108

Laurens, Nancy; Engelse, Marten A; Jungerius, Clarissa; Löwik, Clemens W; van Hinsbergh, Victor W M; Koolwijk, Pieter



Chitinase, beta-1,3-glucanase, osmotin, and extensin are expressed in tobacco explants during flower formation.  

PubMed Central

Sequence analysis of five gene families that were isolated from tobacco thin cell layer explants initiating floral development [Meeks-Wagner et al. (1989). Plant Cell 1, 25-35] showed that two encode the pathogenesis-related proteins basic chitinase and basic beta-1,3-glucanase, while a third encodes the cell wall protein extensin, which also accumulates during pathogen attack. Another sequence family encodes the water stress-induced protein osmotin [Singh et al. (1989). Plant Physiol. 90, 1096-1101]. We found that osmotin was also induced by viral infection and wounding and, hence, could be considered a pathogenesis-related protein. These genes, which were highly expressed in explants during de novo flower formation but not in explants forming vegetative shoots [Meeks-Wagner et al. (1989). Plant Cell 1, 25-35], were also regulated developmentally in day-neutral and photoresponsive tobacco plants with high expression levels in the roots and moderate- to low-level expression in other plant organs including flowers. An unidentified gene family, FB7-4, had its highest level of expression in the basal internodes. Our findings indicate that these genes, some of which are conventionally considered to encode pathogen-related proteins, also have a complex association with normal developmental processes, including the floral response, in healthy plants.

Neale, A D; Wahleithner, J A; Lund, M; Bonnett, H T; Kelly, A; Meeks-Wagner, D R; Peacock, W J; Dennis, E S



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

SciTech Connect

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.

Vitagliano, Luigi; Esposito, Luciana; Pedone, Carlo [Istituto di Biostrutture e Bioimmagini, CNR via Mezzocannone 16, I-80134 Napoli (Italy); De Simone, Alfonso [Department of Chemistry, University of Cambridge, Lensfield Road CB2 1EW, Cambridge (United Kingdom)], E-mail:



Formation, characterization, and thermal degradation behavior of a novel tricomponent aggregate of beta-cyclodextrin, ferrocene, and polypropylene glycol.  


A tricomponent aggregate PPG-Fc-beta-CD formed by polypropylene glycol (PPG), ferrocene (Fc), and beta-cyclodextrin (beta-CD) was obtained and characterized by a series of physical methods, such as (1)H nuclear magnetic resonance, flame atomic absorption spectrometry, high performance liquid chromatography, UV-vis absorption spectroscopy, thermogravimetry, and gas chromatography coupled to time-of-flight mass spectrometry. First, the tricomponent aggregate exhibited a component ratio of 1:28:32 (PPG/Fc/beta-CD) in the solid state, and showed a completely different order in thermal stability when compared with beta-CD: under a nitrogen atmosphere, beta-CD > PPG-Fc-beta-CD, and in a vacuum, PPG-Fc-beta-CD > beta-CD. Second, the appearance of two peculiar points p and q at the end of TG curve of the aggregate gave a strong impression that the degradation rate further increased after the sharp decomposition of the aggregate reached point p and the amount present in the residual fraction at point q about 780.0 K was lower than 1%, both of which were rather different from those reported previously. This finding implied that the molecular assembly resulting from the binding interaction among Fc, PPG, and beta-CD induced more efficiently the degradation of each of them. Third, an interesting phenomenon was found that the order of thermal release of the three assembled components in PPG-Fc-beta-CD was Fc > beta-CD > PPG. Results of this study provide some insight into an initial attempt to construct a supramolecule among a polymer, a coordination compound, and an organic compound. PMID:20055361

Song, Le Xin; Du, Fang Yun; Guo, Xue Qing; Pan, Shu Zhen



Removal of the N-terminal hexapeptide from human beta2-microglobulin facilitates protein aggregation and fibril formation.  

PubMed Central

The solution structure and stability of N-terminally truncated beta2-microglobulin (deltaN6beta2-m), the major modification in ex vivo fibrils, have been investigated by a variety of biophysical techniques. The results show that deltaN6beta2-m has a free energy of stabilization that is reduced by 2.5 kcal/mol compared to the intact protein. Hydrogen exchange of a mixture of the truncated and full-length proteins at microM concentrations at pH 6.5 monitored by electrospray mass spectrometry reveals that deltaN6beta2-m is significantly less protected than its wild-type counterpart. Analysis of deltaN6beta2-m by NMR shows that this loss of protection occurs in beta strands I, III, and part of II. At mM concentration gel filtration analysis shows that deltaN6beta2-m forms a series of oligomers, including trimers and tetramers, and NMR analysis indicates that strand V is involved in intermolecular interactions that stabilize this association. The truncated species of beta2-microglobulin was found to have a higher tendency to self-associate than the intact molecule, and unlike wild-type protein, is able to form amyloid fibrils at physiological pH. Limited proteolysis experiments and analysis by mass spectrometry support the conformational modifications identified by NMR and suggest that deltaN6beta2-m could be a key intermediate of a proteolytic pathway of beta2-microglobulin. Overall, the data suggest that removal of the six residues from the N-terminus of beta2-microglobulin has a major effect on the stability of the overall fold. Part of the tertiary structure is preserved substantially by the disulfide bridge between Cys25 and Cys80, but the pairing between beta-strands far removed from this constrain is greatly perturbed.

Esposito, G.; Michelutti, R.; Verdone, G.; Viglino, P.; Hernandez, H.; Robinson, C. V.; Amoresano, A.; Dal Piaz, F.; Monti, M.; Pucci, P.; Mangione, P.; Stoppini, M.; Merlini, G.; Ferri, G.; Bellotti, V.



Disintegration of liquid sheets  

NASA Technical Reports Server (NTRS)

The development, stability, and disintegration of liquid sheets issuing from a two-dimensional air-assisted nozzle is studied. Detailed measurements of mean drop size and velocity are made using a phase Doppler particle analyzer. Without air flow the liquid sheet converges toward the axis as a result of surface tension forces. With airflow a quasi-two-dimensional expanding spray is formed. The air flow causes small variations in sheet thickness to develop into major disturbances with the result that disruption starts before the formation of the main break-up region. In the two-dimensional variable geometry air-blast atomizer, it is shown that the air flow is responsible for the formation of large, ordered, and small chaotic 'cell' structures.

Mansour, Adel; Chigier, Norman



Multiprotein complex formation at the beta myosin heavy chain distal muscle CAT element correlates with slow muscle expression but not mechanical overload responsiveness.  


To examine the role of the beta-myosin heavy chain (betaMyHC) distal muscle CAT (MCAT) element in muscle fiber type-specific expression and mechanical overload (MOV) responsiveness, we conducted transgenic and in vitro experiments. In adult transgenic mice, mutation of the distal MCAT element led to significant reductions in chloramphenicol acetyltransferase (CAT) specific activity measured in control soleus and plantaris muscles when compared with wild type transgene beta293WT but did not abolish MOV-induced CAT specific activity. Electrophoretic mobility shift assay revealed the formation of a specific low migrating nuclear protein complex (LMC) at the betaMyHC MCAT element that was highly enriched only when using either MOV plantaris or control soleus nuclear extract. Scanning mutagenesis of the betaMyHC distal MCAT element revealed that only the nucleotides comprising the core MCAT element were essential for LMC formation. The proteins within the LMC when using either MOV plantaris or control soleus nuclear extracts were antigenically related to nominal transcription enhancer factor 1 (NTEF-1), poly(ADP-ribose) polymerase (PARP), and Max. Only in vitro translated TEF-1 protein bound to the distal MCAT element, suggesting that this multiprotein complex is tethered to the DNA via TEF-1. Protein-protein interaction assays revealed interactions between nominal TEF-1, PARP, and Max. Our studies show that for transgene beta293 the distal MCAT element is not required for MOV responsiveness but suggest that a multiprotein complex likely comprised of nominal TEF-1, PARP, and Max forms at this element to contribute to basal slow fiber expression. PMID:11010974

Vyas, D R; McCarthy, J J; Tsika, G L; Tsika, R W



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

PubMed Central

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 blood–brain 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.



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

NASA Astrophysics Data System (ADS)

Ning Ding,Zuoxun Zeng,China University of Geosciences,Wuhan,430074,China 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] Fig.1 Fig.2 Fig.3a,3b

Ding, N.



?-Sheet Pore-Forming Peptides Selected from a Rational Combinatorial Library: Mechanism of Pore Formation in Lipid Vesicles and Activity in Biological Membranes†  

PubMed Central

In a previous report we described the selection of potent, ?-sheet pore-forming peptides from a combinatorial library designed to mimic membrane-spanning ?-hairpins (Rausch JM, Marks JR and Wimley WC, (2005) PNAS, 102:10511-5). Here, we characterize their mechanism of action and compare the structure-function relationships in lipid vesicles to their activity in biological membranes. The pore-forming peptides bind to membrane interfaces and self-assemble into ?-sheets that cause a transient burst of graded leakage across the bilayers. Despite the continued presence of the structured peptides in the bilayer, at most peptide concentrations leakage is incomplete and ceases quickly after peptide addition with a deactivation half-time of several minutes. Molecules up to 3,000 Da escape from the transient pores, but much larger molecules do not. Fluorescence spectroscopy and quenching showed that the peptides reside mainly on the bilayer surface and are partially exposed to water, rather than in a membrane-spanning state. The “carpet” or “sinking raft” model of peptide pore formation offers a viable explanation for our observations and suggests that the selected pore formers function with a mechanism that is similar to the natural pore-forming antimicrobial peptides. We therefore also characterized the antimicrobial and cytotoxic activity of these peptides. All peptides studied, including non pore-formers, had sterilizing antimicrobial activity against at least some microbes, and most have low activity against mammalian cell membranes. Thus, the structure-function relationships that were apparent in the vesicle systems are similar to, but do not correlate completely with the activity of the same peptides in biological membranes. However, of the peptides tested, only the pore-formers selected in the high throughput screen have potent, broad-spectrum sterilizing activity against Gram-positive and Gram-negative bacteria as well as against fungi, while having only small lytic effects on human cells.

Rausch, Joshua M.; Marks, Jessica R.; Rathinakumar, Ramesh; Wimley, William C.



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

ERIC Educational Resources Information Center

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…

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



Cloning, baculovirus expression, and characterization of a second mouse prolyl 4-hydroxylase alpha-subunit isoform: formation of an alpha 2 beta 2 tetramer with the protein disulfide-isomerase/beta subunit.  

PubMed Central

Prolyl 4-hydroxylase (EC catalyzes the posttranslational formation of 4-hydroxyproline in collagens. The vertebrate enzyme is an alpha 2 beta 2 tetramer, the beta subunit of which is a highly unusual multifunctional polypeptide, being identical to protein disulfide-isomerase (EC We report here the cloning of a second mouse alpha subunit isoform, termed the alpha (II) subunit. This polypeptide consists of 518 aa and a signal peptide of 19 aa. The processed polypeptide is one residue longer than the mouse alpha (I) subunit (the previously known type), the cloning of which is also reported here. The overall amino acid sequence identity between the mouse alpha (II) and alpha (I) subunits is 63%. The mRNA for the alpha (II) subunit was found to be expressed in a variety of mouse tissues. When the alpha (II) subunit was expressed together with the human protein disulfide-isomerase/beta subunit in insect cells by baculovirus vectors, an active prolyl 4-hydroxylase was formed, and this protein appeared to be an alpha (II) 2 beta 2 tetramer. The activity of this enzyme was very similar to that of the human alpha (I) 2 beta 2 tetramer, and most of its catalytic properties were also highly similar, but it differed distinctly from the latter in that it was inhibited by poly(L-proline) only at very high concentrations. This property may explain why the type II enzyme was not recognized earlier, as an early step in the standard purification procedure for prolyl 4-hydroxylase is affinity chromatography on a poly(L-proline) column. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5

Helaakoski, T; Annunen, P; Vuori, K; MacNeil, I A; Pihlajaniemi, T; Kivirikko, K I



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

SciTech Connect

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 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.

Colford, J.; Parker, R.S.



A hydrocarbon exploration model for the Beta Member of the Permian Kaibab Formation, with emphasis on the potential for hydrodynamically displaced oil, in east-central Utah  

SciTech Connect

In Utah, the Beta Member of the Permian Kaibab Formation produces oil at the Ferron field in the western part of the study area, and the Upper Valley field, 30 mi southwest of the study area. Production at Upper Valley is hydrodynamically controlled; it is unknown if production at Ferron field is hydrodynamically controlled due to the lack of well control. With the exception of the Ferron and Upper Valley fields, Kaibab oil production has remained an elusive goal. Numerous oil shows have been encountered in dozens of tests of the Beta Member of the Permian Kaibab Formation within the study area. Many of these wells have targeted the crests of small anticlinal structures associated with the San Rafael swell. The history of Upper Valley field, and the lack of Kaibab oil production on the crests of anticlinal structures within the region, creates the potential for hydrodynamically displaced oil to be present within this area. Results from stratigraphic cross sections and subsurface structural, isopach, and porosity mapping were combined with hydrodynamic mapping methods to define four areas with oil entrapment potential in the Beta Member of the Permian Kaibab Formation.

Tripp, C.N.



A Simple Lattice Model That Captures Protein Folding, Aggregation and Amyloid Formation  

PubMed Central

The ability of many proteins to convert from their functional soluble state to amyloid fibrils can be attributed to inter-molecular beta strand formation. Such amyloid formation is associated with neurodegenerative disorders like Alzheimer's and Parkinson's. Molecular modelling can play a key role in providing insight into the factors that make proteins prone to fibril formation. However, fully atomistic models are computationally too expensive to capture the length and time scales associated with fibril formation. As the ability to form fibrils is the rule rather than the exception, much insight can be gained from the study of coarse-grained models that capture the key generic features associated with amyloid formation. Here we present a simple lattice model that can capture both protein folding and beta strand formation. Unlike standard lattice models, this model explicitly incorporates the formation of hydrogen bonds and the directionality of side chains. The simplicity of our model makes it computationally feasible to investigate the interplay between folding, amorphous aggregation and fibril formation, and maintains the capability of classic lattice models to simulate protein folding with high specificity. In our model, the folded proteins contain structures that resemble naturally occurring beta-sheets, with alternating polar and hydrophobic amino acids. Moreover, fibrils with intermolecular cross-beta strand conformations can be formed spontaneously out of multiple short hydrophobic peptide sequences. Both the formation of hydrogen bonds in folded structures and in fibrils is strongly dependent on the amino acid sequence, indicating that hydrogen-bonding interactions alone are not strong enough to initiate the formation of beta sheets. This result agrees with experimental observations that beta sheet and amyloid formation is strongly sequence dependent, with hydrophobic sequences being more prone to form such structures. Our model should open the way to a systematic study of the interplay between the factors that lead to amyloid formation.

Abeln, Sanne; Vendruscolo, Michele; Dobson, Christopher M.; Frenkel, Daan



Electron beam cutting in amorphous alumina sheets  

SciTech Connect

We have found that nanometer diameter holes and slots can be cut in thin sheets of amorphous alumina using an intense electron beam. The holes, formed by a nonthermal process, are uniform in diameter, are surrounded by metallic aluminum, and can penetrate a 100-nm sheet in a few seconds. The amorphous alumina sheets are formed by anodization of electropolished high purity aluminum. The electron beam cutting seems very similar to the process reported in the metal ..beta..-aluminas. Since uniform, stable, and easily handled sheets of amorphous alumina can be fabricated and electron beam cut, this process is now practical for nanolithography as well as many other applications.

Mochel, M.E.; Eades, J.A.; Metzger, M.; Meyer, J.I.; Mochel, J.M.



Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.  


Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These transgenic mice may provide new insights into the processes of ectopic endochondrial bone formation associated with mixed tumor formation and serve as a useful model for human heterotopic bone disease. PMID:10498897

Maroulakou, I G; Shibata, M A; Anver, M; Jorcyk, C L; Liu, M l; Roche, N; Roberts, A B; Tsarfaty, I; Reseau, J; Ward, J; Green, J E



Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42.  


The amyloid beta peptide (Abeta), composed of 40 or 42 amino acids, is a critical component in the etiology of the neurodegenerative Alzheimer disease. Abeta is prone to aggregate and forms amyloid fibrils progressively both in vitro and in vivo. To understand the process of amyloidogenesis, it is pivotal to examine the initial stages of the folding process. We examined the equilibrium folding properties, assembly states, and stabilities of the early folding stages of Abeta40 and Abeta42 prior to fibril formation. We found that Abeta40 and Abeta42 have different conformations and assembly states upon refolding from their unfolded ensembles. Abeta40 is predominantly an unstable and collapsed monomeric species, whereas Abeta42 populates a stable structured trimeric or tetrameric species at concentrations above approximately 12.5 microm. Thermodynamic analysis showed that the free energies of Abeta40 monomer and Abeta42 trimer/tetramer are approximately 1.1 and approximately 15/ approximately 22 kcal/mol, respectively. The early aggregation stages of Abeta40 and Abeta42 contain different solvent-exposed hydrophobic surfaces that are located at the sequences flanking its protease-resistant segment. The amyloidogenic folded structure of Abeta is important for the formation of spherical beta oligomeric species. However, beta oligomers are not an obligatory intermediate in the process of fibril formation because oligomerization is inhibited at concentrations of urea that have no effect on fibril formation. The distinct initial folding properties of Abeta40 and Abeta42 may play an important role in the higher aggregation potential and pathological significance of Abeta42. PMID:16809342

Chen, Yun-Ru; Glabe, Charles G



Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide. III. Formation of a novel cycloimidazole nucleoside and its cleavage reactions.  

PubMed Central

A new cycloimidazole nucleoside, 5-(1 inch -benzamido-1 inch-hydroxymethylene) amino-2', 1 inch-anhydro-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (III) was synthesized by reaction of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with benzoyl isothiocyanate followed by methylation with methyl iodide. The structure of III was elucidated on the basis of its nmr spectra and chemical reactions. Of special interest are reactions of III with various nucleophiles. For example, guanosine (IX) was obtained by amination of III wtih ammonia in 72% yield. Analogous reactions of III with methylamine and dimethylamine gave N2-methylguanosine (X) and N2-dimethylguanosine (XI), respectively. Refluxing of III in alkaline solution afforded xanthosine (VII). The probable mechanism of formation and facile ring-opening of III is also discussed.

Okutsu, M; Yamazaki, A



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

NASA Astrophysics Data System (ADS)

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 intr

Phelps, Erin Melissa


Self-Assembled Hydrogels from Poly[N-(2-hydroxypropyl)methacrylamide] Grafted with ?-Sheet Peptides  

PubMed Central

A new hybrid hydrogel based on poly[N-(2-hydroxypropyl)methacrylamide] grafted with a ?-sheet peptide, Beta11, was designed. Circular dichroism spectroscopy indicated that the folding ability of ?-sheet peptide was retained in the hybrid system, whereas the sensitivity of the peptide towards temperature and pH variations was hindered. The polymer backbone also prevented the twisting of the fibrils that resulted from the antiparallel arrangement of the ?-strands, as proved by Fourier transform infrared spectroscopy. Thioflavin T binding experiments and transmission electron microscopy showed fibril formation with minimal lateral aggregation. As a consequence, the graft copolymer self-assembled into a hydrogel in aqueous environment. This process was mediated by association of ?-sheet domains. Scanning electron microscopy revealed a particular morphology of the network, characterized by long-range order and uniformly aligned lamellae. Microrheology results confirmed that concentration-dependent gelation occurred.

Radu-Wu, Larisa C.; Yang, Jiyuan; Wu, Kuangshi; Kopecek, Jindrich



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


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

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



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

SciTech Connect

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.

Hu Xiaotang [School of Natural and Health Science, Barry University, 11300 Northeast Second Avenue, Miami Shores, FL 33161 (United States)], E-mail:



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

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

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



The Ketel(D) dominant-negative mutations identify maternal function of the Drosophila importin-beta gene required for cleavage nuclei formation.  

PubMed Central

The Ketel(D) dominant female-sterile mutations and their ketel(r) revertant alleles identify the Ketel gene, which encodes the importin-beta (karyopherin-beta) homologue of Drosophila melanogaster. Embryogenesis does not commence in the Ketel(D) eggs deposited by the Ketel(D)/+ females due to failure of cleavage nuclei formation. When injected into wild-type cleavage embryos, cytoplasm of the Ketel(D) eggs does not inhibit nuclear protein import but prevents cleavage nuclei formation following mitosis. The Ketel(+) transgenes slightly reduce effects of the Ketel(D) mutations. The paternally derived Ketel(D) alleles act as recessive zygotic lethal mutations: the Ketel(D)/- hemizygotes, like the ketel(r)/ketel(r) and the ketel(r)/- zygotes, perish during second larval instar. The Ketel maternal dowry supports their short life. The Ketel(D)-related defects originate most likely following association of the Ketel(D)-encoded mutant molecules with a maternally provided partner. As in the Ketel(D) eggs, embryogenesis does not commence in eggs of germline chimeras with ketel(r)/- germline cells and normal soma, underlining the dominant-negative nature of the Ketel(D) mutations. The ketel(r) homozygous clones are fully viable in the follicle epithelium in wings and tergites. The Ketel gene is not expressed in most larval tissues, as revealed by the expression pattern of a Ketel promoter-lacZ reporter gene.

Tirian, L; Puro, J; Erdelyi, M; Boros, I; Papp, B; Lippai, M; Szabad, J



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)

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.

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



Effect of ?-sheet propensity on peptide aggregation  

NASA Astrophysics Data System (ADS)

The effect of ?-sheet propensity on the structural features of peptide aggregates was investigated using an off-lattice coarse-grained peptide model. A phase diagram as a function of temperature and ?-sheet propensity reveals a diverse family of supramolecular assemblies. Highly rigid peptides (peptides with high ?-sheet propensity) are seen to assemble predominantly into fibrillar structures. Increasing the flexibility of the peptide (reducing ?-sheet propensity) leads to a variety of structures, including fibrils, ?-barrel structures, and amorphous aggregates. Nonfibrillar entities have been suggested as primary causative agents in amyloid diseases and our simulations indicate that mutations that decrease ?-sheet propensity will decrease fibril formation and favor the formation of such toxic oligomers. Parallels between ?-sheet aggregates and nematic liquid crystals are discussed.

Bellesia, Giovanni; Shea, Joan-Emma



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)

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.

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



Fluorescence determination of sulphobutylether-beta-cyclodextrin in human plasma by size exclusion chromatography with inclusion complex formation.  


A selective method for the determination of sulphobutylether-beta-cyclodextrin (SBECD) in human plasma has been developed and validated over the range 4-200 microg ml(-1). SBECD is extracted from plasma using end-capped cyclohexyl solid phase extraction cartridges. This is followed by high performance size exclusion chromatography with a mobile phase consisting of 1-naphthol (0.1 mM) in methanol-potassium nitrate (0.2 M) (1:9 v/v), 1 ml min(-1). The high aqueous content of the mobile phase quenches the fluorescence of 1-naphthol. However, the naphthol forms an inclusion complex with SBECD. The non-polar 'bucket' environment of the inclusion region restores the fluorescence, which is measured at excitation and emission wavelengths of 290 and 360 nm, respectively, when SBECD elutes from the column. PMID:10815720

Gage, R; Venn, R F; Bayliss, M A; Edgington, A M; Roffey, S J; Sorrell, B



Loss of Ca2+/calmodulin kinase kinase beta affects the formation of some, but not all, types of hippocampus-dependent long-term memory.  


Long-term memory (LTM) requires activation of the transcription factor cAMP-responsive element binding protein (CREB). Signaling by the Ca2+/calmodulin (CaM) kinase cascade has been implicated in CREB activation and memory consolidation processes in the hippocampus. The CaM kinase kinase beta isoforms belong to the CaM kinase cascade, and we have generated null mutant mice to investigate the role of these kinases in several forms of learning and memory. The null mutants were impaired in spatial training-induced CREB activation and spatial memory formation. Furthermore, the mutants lacked late, but not early, long-term potentiation at the hippocampal CA1 synapse, and they were impaired in LTM, but not short-term memory, for the social transmission of food preferences. We suggest that the CaM kinase kinasebeta isoforms are required for the formation of hippocampal LTM. Surprisingly, however, these kinases were not needed for contextual, trace fear, and passive avoidance LTM. Our results demonstrate that different signaling processes underlie the formation of these types of hippocampal LTM. PMID:14586002

Peters, Marco; Mizuno, Keiko; Ris, Laurence; Angelo, Marco; Godaux, Emile; Giese, K Peter



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

SciTech Connect

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.

Pai, Jinkeon; Pachter, J.A.; Bishop, W.R. (Schering-Plough Research, Bloomfield, NJ (United States)); Weinstein, I.B. (Columbia Univ., New York, NY (United States))



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

SciTech Connect

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.

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.



Pinch sheets and reconnection in astrophysics  

Microsoft Academic Search

Magnetic reconnection processes involving the formation and destruction of pinch current sheets in plasma are a universal phenomenon typical of both laboratory and space plasmas. In current sheets a rapid dissipation of the magnetic field is possible in conditions of high conductivity and large scales of the plasma. This effect results from specific features of the flow near the null

S. I. Syrovatskii



Application of a magnetized coaxial plasma gun for formation of a high-beta field-reversed configuration  

Microsoft Academic Search

We have tested a field-reversed configuration (FRC) formation with a spheromak injection for the first time. In this method, initial pre-ionized plasma is injected as a magnetized spheromak-like plasmoid into the discharge chamber prior to main field reversal. The FRC plasma with an electron density of 1.3×1021m?3, a separatrix radius of 0.04m and a plasma length of 0.8m was produced

T. Nishida; T. Kiguchi; T. Asai; T. Takahashi; Y. Matsuzawa; T. Okano; Y. Nogi



Texture in Inhomogeneously Rolled Aluminium Sheet.  

National Technical Information Service (NTIS)

The change of stress state in cold rolled aluminum sheet with large pass reduction, the combining activation process of slip systems as well as the formation mechanism of corresponding shear textures were investigated. It is shown that the rolling deforma...

W. M. Mao



Structural model of the amyloid fibril formed by beta(2)-microglobulin #21-31 fragment based on vibrational spectroscopy.  


A structural model of amyloid fibril formed by the #21-31 fragment of beta2-microglobulin is proposed from microscope IR measurements on specifically 13C-labeled peptide fibrils and Raman spectra of the dispersed fibril solution. The 13C-shifted amide frequency indicated the secondary structure of the labeled residues. The IR spectra have demonstrated that the region between F22 and V27 forms the core part with the extended beta-sheet structure. Raman spectra indicated the formation of a dimer with a disulfide bridge between C25 residues. PMID:15926803

Hiramatsu, Hirotsugu; Goto, Yuji; Naiki, Hironobu; Kitagawa, Teizo



Oncoprotein E7 from Beta Human Papillomavirus 38 Induces Formation of an Inhibitory Complex for a Subset of p53-Regulated Promoters  

PubMed Central

Our previous studies on cutaneous beta human papillomavirus 38 (HPV38) E6 and E7 oncoproteins highlighted a novel activity of I?B kinase beta (IKK?) in the nucleus of human keratinocytes, where it phosphorylates and stabilizes ?Np73?, an antagonist of p53/p73 functions. Here, we further characterize the role of the IKK? nuclear form. We show that IKK? nuclear translocation and ?Np73? accumulation are mediated mainly by HPV38 E7 oncoprotein. Chromatin immunoprecipitation (ChIP)/Re-ChIP experiments showed that ?Np73? and IKK? are part, together with two epigenetic enzymes DNA methyltransferase 1 (DNMT1) and the enhancer of zeste homolog 2 (EZH2), of a transcriptional regulatory complex that inhibits the expression of some p53-regulated genes, such as PIG3. Recruitment to the PIG3 promoter of EZH2 and DNMT1 resulted in trimethylation of histone 3 on lysine 27 and in DNA methylation, respectively, both events associated with gene expression silencing. Decreases in the intracellular levels of HPV38 E7 or ?Np73? strongly affected the recruitment of the inhibitory transcriptional complex to the PIG3 promoter, with consequent restoration of p53-regulated gene expression. Finally, the ?Np73?/IKK?/DNMT1/EZH2 complex appears to bind a subset of p53-regulated promoters. In fact, the complex is efficiently recruited to several promoters of genes encoding proteins involved in DNA repair and apoptosis, whereas it does not influence the expression of the prosurvival factor Survivin. In summary, our data show that HPV38 via E7 protein promotes the formation of a multiprotein complex that negatively regulates the expression of several p53-regulated genes.

Saidj, Djamel; Cros, Marie-Pierre; Hernandez-Vargas, Hector; Guarino, Francesca; Sylla, Bakary S.; Tommasino, Massimo



IL-1beta, BK, and TGF-beta1 attenuate PGI2-mediated cAMP formation in human pulmonary artery smooth muscle cells by multiple mechanisms involving p38 MAP kinase and PKA.  


We have previously shown that interleukin (IL)-1beta, transforming growth factor (TGF)-beta1, or bradykinin (BK) impair cAMP generation in response to prostacyclin analogs in human pulmonary artery smooth muscle (PASM), suggesting that inflammation can impair the effects of prostacyclin analogs on PASM in pulmonary hypertension. Here we explored the biochemical mechanisms involved. We found that IL-1beta, BK, and TGF-beta1 reduced adenylyl cyclase isoform 1, 2, and 4 mRNA, increased Galphai protein levels, and reduced prostacyclin receptor (IP receptor) mRNA expression. In contrast, Galphas protein levels were unchanged. Protein kinase A (PKA) (H-89, KT-2750, PKIm) and p38 mitogen-activated protein (MAP) kinase (SB-202190) inhibitors attenuated these effects, but protein kinase C (bisindolylmaleide) or phosphoinositol 3-kinase (LY-294002) inhibitors did not. Fluorescent kemptide assay and Western blotting confirmed that PKA and p38 MAP kinase were activated by IL-1beta, BK, and TGF-beta1. These studies suggest that IL-1beta, BK, and TGF-beta1 impair IP receptor-mediated cAMP accumulation by multiple effects on different components of the signaling pathway and that these effects are PKA and p38 MAP kinase dependent. PMID:18156442

El-Haroun, H; Clarke, D L; Deacon, K; Bradbury, D; Clayton, A; Sutcliffe, A; Knox, Alan J



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

SciTech Connect

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.

Sorin Zaharia; C.Z. Cheng



Molecular basis for amyloid-[beta] polymorphism  

SciTech Connect

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.

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



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)

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.

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.



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

SciTech Connect

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.

Doi, Takashi [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)] [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Masuda, Yuichi, E-mail: [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan) [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 (Japan); Irie, Kazuhiro [Graduate School of Agriculture, Kyoto University, Kyoto 606-8502 (Japan)] [Graduate School of Agriculture, Kyoto University, Kyoto 606-8502 (Japan); Akagi, Ken-ichi; Monobe, Youko; Imazawa, Takayoshi [Section of Laboratory Equipment, Division of Biomedical Research, National Institute of Biomedical Innovation, Osaka 567-0085 (Japan)] [Section of Laboratory Equipment, Division of Biomedical Research, National Institute of Biomedical Innovation, Osaka 567-0085 (Japan); Takegoshi, K. [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)] [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)



Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation.  


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

Cui, Xiaofeng; Breitenkamp, Kurt; Lotz, Martin; D'Lima, Darryl



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

PubMed Central

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.

Cui, Xiaofeng; Breitenkamp, Kurt; Lotz, Martin; D'Lima, Darryl



Genetically engineered myoblast sheet for therapeutic angiogenesis.  


Peripheral arterial disease is a common manifestation of systemic atherosclerosis, which results in more serious consequences of ischemic events in peripheral tissues such as the lower extremities. Cell therapy has been tested as a treatment for peripheral ischemia that functions by inducing angiogenesis in the ischemic region. However, the poor survival and engraftment of transplanted cells limit the efficacy of cell therapy. In order to overcome such challenges, we applied genetically engineered cell sheets using a cell-interactive and thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were then transfected with vascular endothelial growth factor (VEGF) plasmids using poly(?-amino ester) nanoparticles to increase the angiogenic potential of the sheets. The transfection increased the VEGF expression and secretion from the C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets was confirmed using an in vitro capillary formation assay. More importantly, the transplantation of the VEGF-transfected C2C12 sheets promoted the formation of capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss. In conclusion, the combination of cell sheet engineering and genetic modification can provide more effective treatment for therapeutic angiogenesis. PMID:24304175

Lee, Joan; Jun, Indong; Park, Hyun-Ji; Kang, Taek Jin; Shin, Heungsoo; Cho, Seung-Woo



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

PubMed Central

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.

Richard, Julie-Andree; Kelly, Isabelle; Marion, Didier; Pezolet, Michel; Auger, Michele



Beta-escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21(waf1/cip1) in colon cancer cells.  


Extracts of Aesculus hippocastanum (horse chestnut) seed have been used in the treatment of chronic venous insufficiency, edema, and hemorrhoids. Most of the beneficial effects of horse chestnut are attributed to its principal component beta-escin or aescin. Recent studies suggest that beta-escin may possess anti-inflammatory, anti-hyaluronidase, and anti-histamine properties. We have evaluated the chemopreventive efficacy of dietary beta-escin on azoxymethane-induced colonic aberrant crypt foci (ACF). In addition, we analyzed the cell growth inhibitory effects and the induction of apoptosis in HT-29 human colon cancer cell line. To evaluate the inhibitory properties of beta-escin on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0%, 0.025%, or 0.05% beta-escin. After 1 week, the rats received s.c. injections of azoxymethane (15 mg/kg body weight, once weekly for 2 weeks) or an equal volume of normal saline (vehicle). Rats were continued on respective experimental diets and sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated histopathologically for ACF. Administration of dietary 0.025% and 0.05% beta-escin significantly suppressed total colonic ACF formation up to approximately 40% (P < 0.001) and approximately 50% (P < 0.0001), respectively, when compared with control diet group. Importantly, rats fed beta-escin showed dose-dependent inhibition (approximately 49% to 65%, P < 0.0001) of foci containing four or more aberrant crypts. To understand the growth inhibitory effects, HT-29 human colon carcinoma cell lines were treated with various concentrations of beta-escin and analyzed by flow cytometry for apoptosis and cell cycle progression. Beta-escin treatment in HT-29 cells induced growth arrest at the G1-S phase, which was associated with the induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), and this correlated with reduced phosphorylation of retinoblastoma protein. Results also indicate that beta-escin inhibited growth of colon cancer cells with either wild-type or mutant p53. This novel feature of beta-escin, a triterpene saponin, may be a useful candidate agent for colon cancer chemoprevention and treatment. PMID:16818504

Patlolla, Jagan M R; Raju, Jayadev; Swamy, Malisetty V; Rao, Chinthalapally V



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.  


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

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



Sequence-specific binding and photocrosslinking of. cap alpha. and. beta. oligodeoxynucleotides to the major groove of DNA via triple-helix formation  

SciTech Connect

A photocrosslinking reagent (p-azidophenacyl) was covalently linked to an octothymidylate synthesized with either the natural (..beta..) anomer of thymidine or the synthetic (..cap alpha..) anomer. The oligothymidylate was further substituted by an acridine derivative to stabilize the hybrid formed with a complementary octadeoxyadenylate sequence via intercalation. A single-stranded 27-mer containing a (dA)/sub 8/ sequence and a 27-mer duplex containing a (dA x dT)/sub 8/ sequence were used as targets. Upon UV irradiation, photocrosslinking of the octathymidylate to its target sequence was observed, generating bands that migrated more slowly in denaturing gels. In the 27-mer duplex, both strands were photocrosslinked to the octathymidylate. Upon alkaline treatment of the irradiated samples, cleavage of the 27-mers was observed at specific sites. These reactions were analyzed at different salt concentrations. These results show that it is possible to recognize an oligopurine-oligopyrimidine sequence in a DNA double helix via local triple-helix formation and to target photochemical reactions to specific sequences in both double-stranded and single-stranded nuclei acids.

Praseuth, D.; Perrouault, L.; Le Doan, T.; Chassignol, M.; Thuong, N.; Helene, C.



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

SciTech Connect

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.

T.A. Carter, M. Yamada, H. Ji, R.M. Kulsrud, and F. Trintchouk



Beta-H transfer from the metallacyclobutane: a key step in the deactivation and byproduct formation for the well-defined silica-supported rhenium alkylidene alkene metathesis catalyst.  


The surface complex [([triple bond]SiO)Re([triple bond]CtBu)(=CHtBu)(CH2tBu)] (1) is a highly efficient propene metathesis catalyst with high initial activities and a good productivity. However, it undergoes a fast deactivation process with time on stream, which is first order in active sites and ethene. Noteworthy, 1-butene and pentenes, unexpected products in the metathesis of propene, are formed as primary products, in large amount relative to Re (>1 equiv/Re), showing that their formation is not associated with the formation of inactive species. DFT calculations on molecular model systems show that byproduct formation and deactivation start by a beta-H transfer trans to the weak sigma-donor ligand (siloxy) at the metallacyclobutane intermediate having a square-based pyramid geometry. This key step has an energy barrier slightly higher than that calculated for olefin metathesis. After beta-H transfer, the most accessible pathway is the insertion of ethene in the Re-H bond. The resulting pentacoordinated trisperhydrocarbyl complex rearranges via either (1) alpha-H abstraction yielding the unexpected 1-butene byproduct and the regeneration of the catalyst or (2) beta-H abstraction leading to degrafting. These deactivation and byproduct formation pathways are in full agreement with the experimental data. PMID:18402448

Leduc, Anne-Marie; Salameh, Alain; Soulivong, Daravong; Chabanas, Mathieu; Basset, Jean-Marie; Copéret, Christophe; Solans-Monfort, Xavier; Clot, Eric; Eisenstein, Odile; Böhm, Volker P W; Röper, Michael



Two-dimensional structure of {beta}-Amyloid(10-35) fibrils.  

SciTech Connect

{beta}-Amyloid (A{beta}) peptides are the main protein component of the pathognomonic plaques found in the brains of patients with Alzheimer's disease. These heterogeneous peptides adopt a highly organized fibril structure both in vivo and in vitro. Here we use solid-state NMR on stable, homogeneous fibrils of A{beta}{sub (10-35)}. Specific interpeptide distance constraints are determined with dipolar recoupling NMR on fibrils prepared from a series of singly labeled peptides containing {sup 13}C-carbonyl-enriched amino acids, and skipping no more than three residues in the sequence. From these studies, we demonstrate that the peptide adopts the structure of an extended parallel {beta}-sheet in-register at pH 7.4. Analysis of DRAWS data indicates interstrand distances of 5.3 {+-} 0.3 {angstrom} (mean {+-} standard deviation) throughout the entire length of the peptide, which is compatible only with a parallel {beta}-strand in-register. Intrastrand NMR constraints, obtained from peptides containing labels at two adjacent amino acids, confirm the secondary structural findings obtained using DRAWS. Using peptides with {sup 13}C incorporated at the carbonyl position of adjacent amino acids, structural transitions from {alpha}-helix to {beta}-sheet were observed at residues 19 and 20, but using similar techniques, no evidence for a turn could be found in the putative turn region comprising residues 25-29. Implications of this extended parallel organization for A{beta}{sub (10-35)} for overall fibril formation, stability, and morphology based upon specific amino acid contacts are discussed.

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



Magic angle spinning NMR analysis of beta2-microglobulin amyloid fibrils in two distinct morphologies.  


Beta(2)-microglobulin (beta(2)m) is the major structural component of amyloid fibrils deposited in a condition known as dialysis-related amyloidosis. Despite numerous studies that have elucidated important aspects of the fibril formation process in vitro, and a magic angle spinning (MAS) NMR study of the fibrils formed by a small peptide fragment, structural details of beta(2)m fibrils formed by the full-length 99-residue protein are largely unknown. Here, we present a site-specific MAS NMR analysis of fibrils formed by the full-length beta(2)m protein and compare spectra of fibrils prepared under two different conditions. Specifically, long straight (LS) fibrils are formed at pH 2.5, while a very different morphology denoted as worm-like (WL) fibrils is observed in preparations at pH 3.6. High-resolution MAS NMR spectra have allowed us to obtain (13)C and (15)N resonance assignments for 64 residues of beta(2)m in LS fibrils, including part of the highly mobile N-terminus. Approximately 25 residues did not yield observable signals. Chemical shift analysis of the sequentially assigned residues indicates that these fibrils contain an extensive beta-sheet core organized in a non-native manner, with a trans-P32 conformation. In contrast, WL fibrils exhibit more extensive dynamics and appear to have a smaller beta-sheet core than LS fibrils, although both cores seem to share some common elements. Our results suggest that the distinct macroscopic morphological features observed for the two types of fibrils result from variations in structure and dynamics at the molecular level. PMID:20662519

Debelouchina, Galia T; Platt, Geoffrey W; Bayro, Marvin J; Radford, Sheena E; Griffin, Robert G



Network structure of polyfluorene sheets as a function of alkyl side chain length.  


The formation of self-organized structures in poly(9,9-di-n-alkylfluorene)s ?1 vol % methylcyclohexane (MCH) and deuterated MCH (MCH-d(14)) solutions was studied at room temperature using neutron and x-ray scattering (with the overall q range of 0.00058-4.29 Å(-1)) and optical spectroscopy. The number of side chain carbons (N) ranged from 6 to 10. The phase behavior was rationalized in terms of polymer overlap, cross-link density, and blending rules. For N=6-9, the system contains isotropic areas and lyotropic areas where sheetlike assemblies (lateral size of >400 Å) and free polymer chains form ribbonlike agglomerates (characteristic dimension of >1500 Å) leading to a gel-like appearance of the solutions. The ribbons are largely packed together with surface fractal characteristics for N=6-7 but become open networklike structures with mass fractal characteristics for N=8-9, until the system goes through a transition to an isotropic phase of overlapping rodlike polymers for N=10. The polymer order within sheets varies allowing classification for loose membranes and ordered sheets, including the so-called ? phase. The polymers within the ordered sheets have restricted motion for N=6-7 but more freedom to vibrate for N=8-9. The nodes in the ribbon network are suggested to contain ordered sheets cross-linking the ribbons together, while the nodes in the isotropic phase appear as weak density fluctuations cross-linking individual chains together. The tendencies for macrophase separation and the formation of non beta sheets decrease while the proportion of free chains increases with increasing N. The fraction of ? phase varies nonlinearly, reaching its maximum at N = 8. PMID:21728563

Knaapila, M; Bright, D W; Stepanyan, R; Torkkeli, M; Almásy, L; Schweins, R; Vainio, U; Preis, E; Galbrecht, F; Scherf, U; Monkman, A P



Superfund fact sheet: Arsenic. Fact sheet  

SciTech Connect

The fact sheet describes arsenic (chemical symbol As), how and where it occurs both naturally and artificially, and how it can get into the body and affect human health. The fact sheet is one in a series providing reference information about Superfund issues and is intended for readers with no formal scientific training.

Not Available



Directed Fluid Sheets.  

National Technical Information Service (NTIS)

This paper is concerned mainly with incompressible inviscid fluid sheets but the incompressible linearly viscous fluid sheet is also considered. The development is based on a direct formulation using the two-dimensional theory of directed media called Cos...

A. E. Green P. M. Naghdi



Coculture of peripheral blood CD34+ cell and mesenchymal stem cell sheets increase the formation of bone in calvarial critical-size defects in rabbits.  


The reconstruction of large bony defects remains a clinical challenge, and angiogenesis and neovascularisation are being given more attention in bone tissue engineering. In this study we cocultured peripheral blood CD34+ cells (PB-CD34+ cells), an endothelial progenitor cell/haematopoietic stem cell-enriched population, with bone marrow-derived mesenchymal stem cells (MSC) to investigate their potential for bony regeneration. Cocultured cells showed better osteogenic differentiation than MSC alone in vitro. The cocultured cells and MSC sheets were also composited with hydroxyapatite and implanted in calvarial critical-size defects in rabbits. The rabbits were killed before microcomputed tomographic (MicroCT) and histological analysis. The results showed that cocultured cell composites had promoted bony regeneration more efficiently by 8 weeks after implantation. Our results indicate that the coculture of PB-CD34+ cells and MSC increases bony regeneration in calvarial critical-size defects in rabbits, and provide a new promising therapeutic strategy to aid skeletal healing. PMID:24210781

Li, Guanghui; Wang, Xi; Cao, Jian; Ju, Zhaoyu; Ma, Dongyang; Liu, Yanpu; Zhang, Junrui



Reactivity of Zirconocene Azametallacyclobutenes: Insertion of Aldehydes, Carbon Monoxide, and Formation of alpha,beta-Unsaturated Imines. Formation and Trapping of [Cp(2)Zr=O] in a [4 + 2] Retrocycloaddition(1).  


Azametallacyclobutene Cp(2)ZrN-t-BuCEt=CEt (1) underwent an insertion reaction with CO to form the acyl complex 2 (Cp(2)Zr(N-t-BuCEtCEtCO), 67% yield). The addition of acetone to azametallacyclobutene 3 (Cp(2)Zr(NArCMeCPh), Ar = 2,6-dimethylphenyl) yielded the N-bonded enamine and O-bonded enolate complex of zirconocene 4 (Cp(2)Zr(NArCMeCPhH)(OCMeCH(2)), 76% yield). The addition of aldehydes RCOH to metallacycle 3 resulted in the insertion of the aldehyde into the Zr-C bond to form complexes Cp(2)Zr(NArCMeCPhCRHO) (8a) and Cp(2)Zr(NArCMeCPhC(i-Pr)HO (9) in 85% (R = Ph) and 73% yields, respectively. Similarly, treatment of metallacycle 10 (Cp(2)Zr(NArCEtCEt)) with benzaldehyde yielded the insertion product 11 (Cp(2)Zr(NArCEtCEtCPhHO)) in 56% isolated yield. The structure of complex 11 was confirmed by an X-ray crystallographic study. Heating the insertion products 8a and 9 led to elimination of the alpha,beta-unsaturated imines 13 and 14a (ArN=CMeCPh=CRH) in 53% and 72% yields, respectively, and the formation of oxozirconocene oligomer (Cp(2)ZrO)(n)(). The oxozirconocene monomer was trapped by dimethylzirconocene, preventing the formation of oligomer and resulting in the isolation of product 15. A kinetic study of this retrocycloaddition produced the following activation parameters: DeltaH() = 26.5 kcal/mol, DeltaS() = 3.48 eu. A Hammett sigma/rho study showed that electron-donating groups alpha to the metallacycle oxygen accelerate the retrocycloaddition (rho = -0.8). PMID:11667377

Hanna, Tracy A.; Baranger, Anne M.; Bergman, Robert G.



Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation  

PubMed Central

Background Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods One gram each of either a porous beta-tricalcium phosphate (?-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.



Secondary structure formation in peptide amphiphile micelles  

NASA Astrophysics Data System (ADS)

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.

Tirrell, Matthew



Beta experiment  

NASA Technical Reports Server (NTRS)

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.



Statistical mechanical model for helix-sheet-coil transitions in homopolypeptides.  


In this paper, we propose a simple statistical mechanical model to study the conformation transition between the alpha helix, beta sheet, and random coil in homopolypeptides. In our model, five parameters are introduced to obtain the partition function. There are two factors for helical propagation and initiation, which are the same as those used in the Zimm-Bragg model, and three newly introduced parameters for beta structures: the strand propagation factor for residues in beta strands and two correction factors for the initiation effect of the beta strand and beta sheet. Our model shows that the variation of these parameters may induce conformation transition from alpha helix or random coil to beta sheet. The sharpness of the transition depends on the initiation factors. PMID:19113152

Hong, Liu; Lei, Jinzhi



MHD Ballooning Instability in the Plasma Sheet  

SciTech Connect

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.

C.Z. Cheng; S. Zaharia



Structural Studies of Copper(I) Complexes of Amyloid-Beta Peptide Fragments: Formation of Two-Coordinate Bis(Histidine) Complexes  

SciTech Connect

The beta bind: Copper(I) binds to amyloid {beta}-peptide fragments (see structure) as a stable bis(histidine), two-coordinate, near-linear complex, even in the presence of potential additional ligands. As has been proposed or assumed in other studies, the copper(I)-peptide complexes react with dioxygen to form the reactive oxygen species H{sub 2}O{sub 2}, without the need for a third histidine ligand to promote the chemistry.

Himes, R.A.; Park, G.Young.; Siluvai, G.Sutha.; Blackburn, N.J.; Karlin, K.D.



Superfund fact sheet: Public involvement. Fact sheet  

SciTech Connect

The fact sheet describes how citizens can participate in the decision-making process regarding Superfund activities in their communities. Explanations of how citizens can report potential Superfund sites, address public health hazards from both the site itself and cleanup activities, and provide input to limit the effects of the cleanup on their communities 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.

Not Available



Nkx6.1 and nkx6.2 regulate alpha- and beta-cell formation in zebrafish by acting on pancreatic endocrine progenitor cells.  


In mice, the Nkx6 genes are crucial to alpha- and beta-cell differentiation, but the molecular mechanisms by which they regulate pancreatic subtype specification remain elusive. Here it is shown that in zebrafish, nkx6.1 and nkx6.2 are co-expressed at early stages in the first pancreatic endocrine progenitors, but that their expression domains gradually segregate into different layers, nkx6.1 being expressed ventrally with respect to the forming islet while nkx6.2 is expressed mainly in beta-cells. Knockdown of nkx6.2 or nkx6.1 expression leads to nearly complete loss of alpha-cells but has no effect on beta-, delta-, or epsilon-cells. In contrast, nkx6.1/nkx6.2 double knockdown leads additionally to a drastic reduction of beta-cells. Synergy between the effects of nkx6.1 and nkx6.2 knockdown on both beta- and alpha-cell differentiation suggests that nkx6.1 and nkx6.2 have the same biological activity, the required total nkx6 threshold being higher for alpha-cell than for beta-cell differentiation. Finally, we demonstrate that the nkx6 act on the establishment of the pancreatic endocrine progenitor pool whose size is correlated with the total nkx6 expression level. On the basis of our data, we propose a model in which nkx6.1 and nkx6.2, by allowing the establishment of the endocrine progenitor pool, control alpha- and beta-cell differentiation. PMID:20122912

Binot, A-C; Manfroid, I; Flasse, L; Winandy, M; Motte, P; Martial, J A; Peers, B; Voz, M L



Turbulence driven by singularities in vortex sheet dynamics.  


High-precision numerical simulations of vortex sheets in two-dimensional flows show a cascade of Kelvin-Helmholtz instabilities and the appearance of a large spectrum of spatial scales. We found a physical mechanism, combining advection and self-interaction of the sheet vorticity, that leads to the formation of a flow singularity. An unexpected consequence of these singularities and of the complex vorticity distribution along the sheet is the emergence of an energy spectrum following a power law. PMID:21929101

Abid, Malek; Verga, Alberto



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)

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.

Reynaud, F.



Flexible magnetic disk sheet  

US Patent & Trademark Office Database

A flexible magnetic disk sheet having a central circular hole is described, through which an apparatus for reading and writing is engaged, and enclosed in an jacket having a larger central circular hole exposing the hole of the disk sheet within the hole of the jacket, wherein a reinforcing plastic ring containing a solid lubricating agent is provided on the region of the flexible magnetic disk sheet immediately surrounding the central circular hole thereof.



Comparative study of the effect of beta-blockers with different pharmacological properties on cholesteryl ester formation in mouse peritoneal macrophages.  


The effect of three beta-blockers: non-selective (propranolol), beta 1-selective (metoprolol), and with intrinsic sympathomimetic activity (pindolol), was investigated on 14C-oleic acid incorporation into cholesteryl esters in mouse peritoneal macrophages. Incorporation of 14C-oleic acid into cholesteryl esters was reduced about 10-fold by propranolol at 10(-4) M while incorporation into triacylglycerols was only 30% decreased at the same concentration. Metoprolol and pindolol had no significant effect on 14C-oleic incorporation into cholesteryl esters or triacylglycerols. Finally, propranolol inhibited the acyl-coenzyme A: cholesterol-O-acyltransferase activity, measured in vitro on macrophages homogenates, while the other studied beta-blockers were ineffective. These results suggest that propranolol could antagonize cholesteryl ester accumulation by macrophages, one of the main processes involved in atherogenesis. PMID:2882755

Islam, S; Houtia, N E; Mazière, J C; Mazière, C; Polonovski, J



Identification, classification, and analysis of beta-bulges in proteins.  

PubMed Central

A beta-bulge is a region of irregularity in a beta-sheet involving two beta-strands. It usually involves two or more residues in the bulged strand opposite to a single residue on the adjacent strand. These irregularities in beta-sheets were identified and classified automatically, extending the definition of beta-bulges given by Richardson et al. (Richardson, J.S., Getzoff, E.D., & Richardson, D.C., 1978, Proc. Natl. Acad. Sci. USA 75, 2574-2578). A set of 182 protein chains (170 proteins) was used, and a total of 362 bulges were extracted. Five types of beta-bulges were found: classic, G1, wide, bent, and special. Their characteristic amino acid preferences were found for most classes of bulges. Basically, bulges occur frequently in proteins; on average there are more than two bulges per protein. In general, beta-bulges produce two main changes in the structure of a beta-sheet: (1) disrupt the normal alternation of side-chain direction; (2) accentuate the twist of the sheet, altering the direction of the surrounding strands.

Chan, A. W.; Hutchinson, E. G.; Harris, D.; Thornton, J. M.



Beta Thalassemia  


... 1 Beta thalassemia is found in people of Mediterranean, Middle Eastern, African, South Asian (Indian, Pakistani, etc.), ... is commonly found in people of African or Mediterranean ancestry, such as Africans, Italians, Greeks, Turks, and ...


Beta-peptidic peptidomimetics.  


For more than a decade now, a search for answers to the following two questions has taken us on a new and exciting journey into the world of beta- and gamma-peptides: What happens if the oxygen atoms in a 3i-helix of a polymeric chain composed of (R)-3-hydroxybutanoic acid are replaced by NH units? What happens if one or two CH2 groups are introduced into each amino acid building block in the chain of a peptide or protein, thereby providing homologues of the proteinogenic alpha-amino acids? Our journey has repeatedly thrown up surprises, continually expanding the potential of these classes of compound and deepening our understanding of the structures, properties, and multifaceted functions of the natural "models" to which they are related. Beta-peptides differ from their natural counterparts, the alpha-peptides, by having CH2 groups inserted into every amino acid residue, either between the C=O groups and the alpha-carbon atoms (beta(3)) or between the alpha-carbon and nitrogen atoms (beta(2)). The synthesis of these homologated proteinogenic amino acids and their assembly into beta-peptides can be performed using known methods. Despite the increased number of possible conformers, the beta-peptides form secondary structures (helices, turns, sheets) even when the chain lengths are as short as four residues. Furthermore, they are stable toward degrading and metabolizing enzymes in living organisms. Linear, helical, and hairpin-type structures of beta-peptides can now be designed in such a way that they resemble the characteristic and activity-related structural features ("epitopes") of corresponding natural peptides or protein sections. This Account presents examples of beta-peptidic compounds binding, as agonists or antagonists (inhibitors), to (i) major histocompatibility complex (MHC) proteins (immune response), (ii) the lipid-transport protein SR-B1 (cholesterol uptake from the small intestine), (iii) the core (1-60) of interleukin-8 (inflammation), (iv) the oncoprotein RDM2, (v) the HIVgp41 fusion protein, (vi) G-protein-coupled somatostatin hsst receptors, (vii) the TNF immune response receptor CD40 (apoptosis), and (viii) DNA. Short-chain beta-peptides may be orally bioavailable and excreted from the body of mammals; long-chain beta-peptides may require intravenous administration but will have longer half-lives of clearance. It has been said that an interesting field of research distinguishes itself in that the results always throw up new questions; in this sense, the structural and biological investigation of beta-peptides has been a gold mine. We expect that these peptidic peptidomimetics will play an increasing role in biomedical research and drug development in the near future. PMID:18578513

Seebach, Dieter; Gardiner, James



The thermographic nondestructive evaluation of iron aluminide green sheet  

Microsoft Academic Search

The recent development of manufacturing techniques for the fabrication of thin iron aluminide 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

Michael Lee Watkins



3D simulation of Wiggler field focusing sheet electron beam  

Microsoft Academic Search

Under the condition of the solenoid focusing magnetic fields, Diocotron instability easily forms in the sheet electron beam, which could lead to collapse in beam propagation. This formation of Diocotron instability is presented in detail in this paper by using a three dimensional (3D) particle-in-cell (PIC) simulation. Then the Wiggler field is used to focus sheet electron beam, and the

Zhaoyun Duan; Tongbo Wang; Yubin Gong; Zhanliang Wang; Xiankui Guo; Yanyu Wei; Wenxiang Wang



Magnetic reconnection via current sheets  

SciTech Connect

A general picture of magnetic reconnection in the framework of 2-D incompressible resistive magnetohydrodynamic theory is presented. Numerical studies of (quasi-) steady-state driven reconnection reveal current sheet formation for Mach numbers M = u/v/sub A/ exceeding the Sweet--Parker reconnection rate M/sub SP/ = (eta/Lv/sub A/)/sup 1//sup ///sup 2/. Since the thickness delta of the current sheet is found to be invariant to a change of the resistivity eta, its length increases rapidly with decreasing eta or increasing M, which can be written in the form SP/)/sup 4/, so that reaches the global system size L within a short range of the parameter M/M/sub SP/. The results are rather insensitive to the particular choice of boundary conditions. Because of the presence of a current sheet, the overall reconnection process is quite slow. This picture essentially agrees with Syrovatsky's (Sov. Phys. JETP 33, 933 (1971)) theory and disproves Petschek's (AAS/NASA Symposium on the Physics of Solar Flares, (NASA, Washington, DC, 1964) p. 425) mechanism of fast magnetic reconnection. A theory of the solution in the external and in the diffusion region is developed and analytical expressions in agreement with the simulation results are obtained by means of a variational principle.

Biskamp, D.



Curved Cap Corrugated Sheet.  

National Technical Information Service (NTIS)

The invention is 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...

R. C. Davis T. T. Bales D. M. K. Royster L. R. Jackson



Superfund Fact Sheet: PCBs.  

National Technical Information Service (NTIS)

The fact sheet describes polychlorinated biphenyls (PCBs), where PCBs can be found and how they can enter the body and affect human health. The fact sheet is one in a series providing reference information about Superfund issues and is intended for reader...



Superfund Fact Sheet: Arsenic.  

National Technical Information Service (NTIS)

The fact sheet describes arsenic (chemical symbol As), how and where it occurs both naturally and artificially, and how it can get into the body and affect human health. The fact sheet is one in a series providing reference information about Superfund iss...



Quahog Fact Sheet  

NSDL National Science Digital Library

This Rhode Island Sea Grant Fact Sheet describes quahogs, a type of shellfish, and their role in commercial fishery. It includes information about quahog physical description, habitat preference, and the rise of quahog harvests in Rhode Island. The Fact Sheet concludes with a section describing how to dig up your own quahogs, shuck (open) them, and eat them.

Ely, Eleanor; Grant, Rhode I.



Safety Data Sheet-Plasmid DNA 4a-CRT-E7 (detox) (JHU) coated gold (2) Page 1 of 3 SAFETY DATA SHEET HUMAN PAPILLOMA VIRUS/CALRETICULIN PLASMID DNA (4a-CRT/E7 (DETOX)) COATED GOLD Reference: PowderMed DNA vaccine – Plasmid DNA/gold/TA201.5


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

SciTech Connect

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.

Biancalana, Matthew; Makabe, Koki; Koide, Shohei (UC)



Emittance Measurements for a Thin Liquid Sheet Flow  

NASA Technical Reports Server (NTRS)

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.

Englehart, Amy N.; McConley, Marc W.; Chubb, Donald L.



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

SciTech Connect

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.

Browning, James Frederick (Oak Ridge National Laboratory, Oak Ridge, TN); Llobet, Anna (Los Alamos National Laboratory, Los Alamos, NM); Snow, Clark Sheldon; Rodriguez, Mark Andrew; Wixom, Ryan R.



Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum.  


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

Weber, Michael E; Clark, Peter U; Ricken, Werner; Mitrovica, Jerry X; Hostetler, Steven W; Kuhn, Gerhard



Interhemispheric Ice-Sheet Synchronicity During the Last Glacial Maximum  

NASA Astrophysics Data System (ADS)

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.

Weber, Michael E.; Clark, Peter U.; Ricken, Werner; Mitrovica, Jerry X.; Hostetler, Steven W.; Kuhn, Gerhard



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

NASA Technical Reports Server (NTRS)

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.

Copland, Evan



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

NASA Technical Reports Server (NTRS)

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.

Copeland, Evan



Forced crumpling of self-avoiding elastic sheets.  


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. PMID:16462740

Vliegenthart, G A; Gompper, G



Forced crumpling of self-avoiding elastic sheets  

NASA Astrophysics Data System (ADS)

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.

Vliegenthart, G. A.; Gompper, G.



Liquid sheet radiator  

NASA Technical Reports Server (NTRS)

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.

Chubb, Donald L.; White, K. Alan, III



Microcomponent sheet architecture  


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.

Wegeng, Robert S. (Richland, WA); Drost, M. Kevin (Richland, WA); McDonald, Carolyn E. (Richland, WA)



Microcomponent sheet architecture  


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.

Wegeng, R.S.; Drost, M.K..; McDonald, C.E.




Microsoft Academic Search

A process for formation of the stretched spiral vortex was investigated using the DNS data of homogeneous turbulence. It was shown that vortex tube was generated not by a rolling up of single vortex sheet but through an interaction of dual sheets. Depending on the alignment of vorticity vectors on vortex tube and vortex sheets which emanate from vortex tube,

Kiyosi Horiuti; Yohei Takagi; Syouji Abe


Fiber formation of a synthetic spider peptide derived from Nephila clavata.  


Dragline silk is a high-performance biopolymer with exceptional mechanical properties. Artificial spider dragline silk is currently prepared by a recombinant technique or chemical synthesis. However, the recombinant process is costly and large-sized synthetic peptides are needed for fiber formation. In addition, the silk fibers that are produced are much weaker than a fiber derived from a native spider. In this study, a small peptide was chemically synthesized and examined for its ability to participate in fiber formation. A short synthetic peptide derived from Nephila clavata was prepared by a solid-phase peptide method, based on a prediction using the hydrophobic parameter of each individual amino acid residue. After purification of the spider peptide, fiber formation was examined under several conditions. Fiber formation proceeded in the acidic pH range, and larger fibers were produced when organic solvents such as trifluoroethanol and acetonitrile were used at an acidic pH. Circular dichroism measurements of the spider peptide indicate that the peptide has a beta-sheet structure and that the formation of a beta-sheet structure is required for the spider peptide to undergo fiber formation. PMID:20564008

Hidaka, Yuji; Kontani, Ko-Ichi; Taniguchi, Rina; Saiki, Masatoshi; Yokoi, Sayoko; Yukuhiro, Kenji; Yamaguchi, Hiroshi; Miyazawa, Mitsuhiro



Beta Section Beta: Biogeographical Patterns of Variation and Taxonomy.  

National Technical Information Service (NTIS)

Contents: Classification and taxonomy; Morphometric analysis of variation in Beta section Beta; Patterns of allozyme differentiation in Beta section Beta; Generative development and life cycles in Beta section Beta; Germination ecology of some Beta specie...

J. P. W. Letschert



Material Safety Data Sheet

Erbitux ™ ImClone Systems Incorporated Page 1 of 7 Material Safety Data Sheet Section 1. CHEMICAL PRODUCT AND COMPANY IDENTIFICATION 1.1 Product Information / Product Identification Product Name: Erbitux


Pesticide Fact Sheet: Spinosad.  

National Technical Information Service (NTIS)

This document contains up-to-date chemical information, including a summary of the Agency's regulatory position and rationale, on a specific pesticide or group of pesticides. A Fact Sheet is issued after Registration of a new chemical.



Global ice sheet modeling  

SciTech Connect

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.

Hughes, T.J.; Fastook, J.L. [Univ. of Maine, Orono, ME (United States). Institute for Quaternary Studies



Pesticide Fact Sheet: Imazapyr.  

National Technical Information Service (NTIS)

This document contains up-to-date chemical information, including a summary of the Agency's regulatory position and rationale, on a specific pesticide or group of pesticides. A Fact Sheet is issued after registration of a significantly changed use pattern...



Pesticide Fact Sheet: Flumetsulam.  

National Technical Information Service (NTIS)

This document contains up-to-date chemical information, including a summary of the Agency's regulatory position and rationale, on a specific pesticides or group of pesticides. A Fact Sheet is issued after, registration of a new chemical.



Gallium Arsenide Data Sheets.  

National Technical Information Service (NTIS)

These data sheets present a compilation of a wide range of electrical, optical and energy values for pure and variously-doped gallium arsenide in bulk and film form. Electrical properties include conductivity, resistivity, dielectric constant, Hall coeffi...

M. Neuberger



Pesticide Fact Sheet: Fluroxypyr.  

National Technical Information Service (NTIS)

This document contains up-to-date chemical information, including a summary of the Agency's regulatory position and rationale, on a specific pesticide or group of pesticides. A Fact Sheet is issued after registration of a new chemical.



Domoic Acid Fact Sheet  

NSDL National Science Digital Library

This online fact sheet illustrates the transfer of domoic acid through the food web. Domoic acid is a nerve toxin produced by a naturally occurring Harmful Algal Bloom (HAB) usually (but not always) of the genus Pseudonitzchia. The sheet explains what to do if you find a sick or dead animal and includes contact information for injured/sick/entangled animal rescue networks in California.

Sanctuary, Channel I.


Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1).  

PubMed Central

beta 2-GP1 is a serum protein which influences binding of anticardiolipin antibodies to cardiolipin, may influence induction of these antibodies in animals and may play a role in anticardiolipin-mediated thrombosis. Various investigators have proposed that when beta 2-GP1 binds cardiolipin, structural alterations occur in one or both molecules, resulting in exposure of new epitopes for anticardiolipin binding, but there has been no proof that such alterations occur. Utilizing Fourier transform infrared spectroscopy, this study analysed the structure of cardiolipin and beta 2-GP1 alone, then mixed with each other. For pure cardiolipin, analysis of the CH2 stretching, scissoring and carbonyl bands suggested this molecule assumes a hexagonal crystal lattice packing structure in both anhydrous and aqueous samples. Based on the second derivative analysis of the amide 1 band from the beta 2-GP1 protein backbone, as well as Fourier self-deconvolution and curve fit algorithms, beta 2-GP1 was calculated to contain 18% turns, 37% alpha-helix, and 45% beta-sheet structure. beta 2-GP1 binding with cardiolipin results in a significant change in the conformation as well as geometry of the lipid and protein components. This is indicated by a broadening of the CH stretching band and a marked shift in intensity of the carbonyl band of cardiolipin, indicating less hydrogen bonding. There was a decrease in beta-sheet structure of beta 2-GP1 from 46% to 23% and appearance of 26% to 28% random structure. These findings indicate that mixing beta 2-GP1 with cardiolipin results in profound changes in both molecules which might explain the effect of beta 2-GP1 on anticardiolipin binding activity.

Borchman, D; Harris, E N; Pierangeli, S S; Lamba, O P



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

SciTech Connect

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.

Vitiello, Giuseppe [Department of Chemistry, University of Naples 'Federico II', Naples (Italy) [Department of Chemistry, University of Naples 'Federico II', Naples (Italy); CSGI (Consorzio per lo Sviluppo dei Sistemi a Grande Interfase), Florence (Italy)] [Consorzio per lo Sviluppo dei Sistemi a Grande Interfase; Italy; Grimaldi, Manuela; D'Ursi, Anna Maria [Department of Pharmaceutical Science, University of Salerno, Fisciano (Italy)] [Department of Pharmaceutical Science, University of Salerno, Fisciano (Italy); D'Errico, Gerardino, E-mail: [Department of Chemistry, University of Naples 'Federico II', Naples (Italy) [Department of Chemistry, University of Naples 'Federico II', Naples (Italy); CSGI (Consorzio per lo Sviluppo dei Sistemi a Grande Interfase), Florence (Italy)] [Consorzio per lo Sviluppo dei Sistemi a Grande Interfase; Italy



Testing Stochastic Structural Stability Theory predictions for turbulent jet formation and equilibration in barotropic beta-plane turbulence using nonlinear and quasi-linear simulations  

NASA Astrophysics Data System (ADS)

Coherent large scale jets that are not forced directly at the jet scale are a prominent feature of planetary turbulence. These jets arise through systematic organization of the turbulent Reynolds stresses. Understanding the mechanism producing the required systematic eddy momentum flux convergence, and how the jets and associated eddy field mutually adjust to maintain statistically steady finite amplitude jets constitute fundamental theoretical problems. Stochastic Structural Stability Theory (SSST) provides a dynamics for the evolution of the statistical mean state of a turbulent system that is quasi-linear in that it retains the perturbation-mean flow interaction while parameterizing stochastically the perturbation-perturbation interactions and external forcing. The result is a dynamics for the turbulent state which is closed at second order. This system allows formulation of a stability theory that predicts the emergence of jets from homogeneous turbulence as well as the equilibration of these jets at finite amplitude. Comparison of the predictions of SSST with quasi-linear and nonlinear simulations of barotropic turbulence on a beta-plane will be presented. These examples show that SSST accurately predicts both the initial emergence and the finite amplitude equilibration of jets in beta-plane turbulence provided that the stochastic parameterization of turbulence used in the perturbation dynamics approximates the spectrum of the background turbulence in which the jets form

Farrell, B.; Constantinou, N.; Ioannou, P.



Bioactivation of Nephrotoxic Haloalkenes by Glutathione Conjugation: Formation of Toxic and Mutagenic Intermediates by Cysteine Conjugate Beta-Lyase. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

The concept that glutathione S-conjugate biosynthesis, which leads to mercapturic acid formation and excretion, is an important mechanism of drug and chemical detoxification is well established. Glutathione S-conjugates are synthesized by the hepatic cyto...

W. Dekant S. Vamvakas M. W. Anders



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

NASA Astrophysics Data System (ADS)

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.

Hule, Rohan; Pochan, Darrin; Nagarkar, Radhika; Schneider, Joel



The thermographic nondestructive evaluation of iron aluminide green sheet  

NASA Astrophysics Data System (ADS)

The recent development of manufacturing techniques for the fabrication of thin iron aluminide 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 by cold rolling FeAl powder mixed with organic binding agents. The green sheet composite has a bulk density, which is typically less than about 3.6 g/cc. The finished sheet, with a density of about 6.1 g/cc, 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. The production environment and physical characteristics of the composite provide for unique challenges in developing a rapid nondestructive inspection capability. The method must be non-contact due to the fragile nature of the composite. Limited access to the material also demands a one-sided inspection technique. An active thermographic method providing for 100% on-line inspection within an industrial, process has been developed. 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 mechanism of flaw formation and the transformation of green sheet flaws into defects that appear in intermediate and finished sheet products are described. A mathematical model which describes the green sheet heat transfer propagation, in the context of the inspection technique and the compact heterogeneity, is also presented. The potential for feedback within the production process is also discussed.

Watkins, Michael Lee


Monolithic graphene oxide sheets with controllable composition  

NASA Astrophysics Data System (ADS)

Graphene oxide potentially has multiple applications and is typically prepared by solution-based chemical means. To date, the synthesis of a monolithic form of graphene oxide that is crucial to the precision assembly of graphene-based devices has not been achieved. Here we report the physical approach to produce monolithic graphene oxide sheets on copper foil using solid carbon, with tunable oxygen-to-carbon composition. Experimental and theoretical studies show that the copper foil provides an effective pathway for carbon diffusion, trapping the oxygen species dissolved in copper and enabling the formation of monolithic graphene oxide sheets. Unlike chemically derived graphene oxide, the as-synthesized graphene oxide sheets are electrically active, and the oxygen-to-carbon composition can be tuned during the synthesis process. As a result, the resulting graphene oxide sheets exhibit tunable bandgap energy and electronic properties. Our solution-free, physical approach may provide a path to a new class of monolithic, two-dimensional chemically modified carbon sheets.

Chu, Jae Hwan; Kwak, Jinsung; Kim, Sung-Dae; Lee, Mi Jin; Kim, Jong Jin; Park, Soon-Dong; Choi, Jae-Kyung; Ryu, Gyeong Hee; Park, Kibog; Kim, Sung Youb; Kim, Ji Hyun; Lee, Zonghoon; Kim, Young-Woon; Kwon, Soon-Yong



Towards Understanding the Early Events in the Conformational Transition of Amyloid Beta Peptides  

Microsoft Academic Search

It is experimentally known that oligomerization of amyloid beta peptides is accompanied by a conformational transition from mainly alpha or random coil to beta sheets. The aim of this study is to analyze and compare the spatial orientation of hydration water near the peptide surface during this conformational transition of amyloid-beta 42 (Ab42) and amyloid-beta 40 (Ab40) peptides. Therefore, molecular

Sikander Hayat; Volkhard Helms


Relevance of organic farming and effect of climatological conditions on the formation of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol in hop (Humulus lupulus L.).  


The concentrations of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol were monitored in the hop varieties Admiral (A), Wye Challenger (WC), and First Gold (FG) during the harvest seasons of 2003 through 2005. Hops grown under an organic regimen were compared to plants grown conventionally in hop fields in close vicinity. The concentrations of the key compounds depended very much on climatological conditions showing, in general, highest levels in poorest weather conditions (2004). Of the three varieties studied, FG was the only one showing a clear trend for higher concentrations of secondary metabolites under organic growing conditions than under conventional farming conditions. Cultivation of A and WC seems to be very sensitive to climatic conditions and environmental stresses caused by pests and diseases, thereby leading to various results. WC proved to be a rich source of bioactive chalcones, particularly desmethylxanthohumol. PMID:17199314

Keukeleire, Jelle De; Janssens, Ina; Heyerick, Arne; Ghekiere, Greet; Cambie, Joris; Roldan-Ruiz, Isabel; Bockstaele, Erik Van; Keukeleire, Denis De



Impacts on thin elastic sheets  

NASA Astrophysics Data System (ADS)

The radial cracks developing from the impact point of a projectile on a windshield are of common experience. We investigate the origin of this phenomenon using thin elastic sheets as an experimental model. A projectile launched at controlled speed impacts a free membrane at rest. A tensile front sets out from the point of impact and propagates radially at the speed of sound. Flexural waves can propagate in the extended area. Specifically, the interaction between the rigid body and the elastic sheet gives birth to a conical flexural shape whose base expands radially at a well defined velocity. During the propagation of both the tensile and flexural fronts, the radial tensile stress field results in a compressive stress in the azimuthal direction, which triggers a buckling instability. That instability is responsible for the formation of radial folds, with a well defined azimuthal wave number. Based on detailed experimental observations and measurements, we propose a model to understand the wave motion and stress field consecutive to the impact; in addition, we provide a prediction for the number of folds selected during the buckling instability as a function of the relevant parameters, including impact velocity.

Vermorel, Romain; Vandenberghe, Nicolas; Villermaux, Emmanuel



California Sheet Music Project  

NSDL National Science Digital Library

With oversight provided by Professor Mary Kay Duggan of the University of California at Berkeley, the California Sheet Music Project provides online access to some 2000 pieces of sheet music published in California between 1852 and 1900. The project was funded by the U.S. Institute of Museum and Library Services, and also contains interesting ephemera ranging from a music publisher's catalog from 1872, advertisements, and photographs. The entire database may be searched or browsed by image subject (from the frontispiece of each composition) or by the subject addressed by each piece of music. Some of the songs included in the archive deal with beggars ("Just One Penny to Buy Bread," babies ("Baby's Asleep"), and politicians ("Horace Greeley's Grand March"). Finally the site also has several musical performances of pieces from the collection for the listening pleasure of those compelled to visit this interesting tribute to the sheet music of the Golden State.

Duggan, Mary K.


Monoatomically thin polarizable sheets  

NASA Astrophysics Data System (ADS)

We consider a flat lattice of dipoles modeled by harmonic oscillators interacting with the electromagnetic field in the dipole approximation. Eliminating the variables from the coupled equations of motion, we come to effective Maxwell equations. These allow for taking the lattice spacing a to zero. As a result, we obtain reflection coefficients for the scattering of electromagnetic waves off the sheet. These are a generalization of that known from the hydrodynamic model. For instance, we get a nontrivial scattering for polarizability perpendicular to the sheet. Also, we show that the case of polarizability parallel to the sheet can be obtained in a natural way from a plasma layer of finite thickness. As an alternative approach, we discuss the elimination of the electromagnetic fields resulting in effective equations for the oscillators. These are shown, for a?0, divergent behavior, resulting from the electrostatic interaction of the dipoles.

Bordag, M.



Historic American Sheet Music  

NSDL National Science Digital Library

Duke University's Historic American Sheet Music Project (HASM) presents digital images of 3,042 pieces of sheet music from Duke's collections, published between 1850 and 1920. Highlights of the collection include "antebellum Southern music, Confederate imprints, and Civil war songs." The search capabilities at the site are sophisticated, allowing users to look for music by publisher name, composer, title, performer, and many other terms. There is online help for searching and a glossary of subject headings. Much of the sheet music is illustrated, and it is possible to search for pictures by "illustration type" (theme), allowing access to the subjects of the illustrations as well as the music itself. It is also possible to browse all the cover illustrations. HASM was originally funded by Ameritech as part of the ongoing Library of Congress/Ameritech Digital Library Competition; it will soon be part of the American Memory Collections at the Library of Congress (described in the November 6, 1998 Scout Report).



Historic Sheet Music  

NSDL National Science Digital Library

If you're looking for compelling sheet music from decades gone by, this website from the University of Oregon Libraries is just the ticket. Initially created to showcase sheet music from the Oregon Music Collection, their digitization work continues apace, and there are already over 650 pieces of sheet music available here. Visitors to the site can browse the collection by title, composer, or topic. Perhaps the most unique items here are those pieces composed by Oregonian women, such as Amy Beach, Marion Bauer, and Liza Lehmann. Not surprisingly, the collection is also strong in the area of Western Americana, as attested to by songs like "Broncho Buster", "Oh you round up, let 'er buck", and "The Gray Haired Pioneer".


Simulating Thin Sheets: Buckling, Wrinkling, Folding and Growth  

NASA Astrophysics Data System (ADS)

Numerical simulations of thin sheets undergoing large deformations are computationally challenging. Depending on the scenario, they may spontaneously buckle, wrinkle, fold, or crumple. Nature's thin tissues often experience significant anisotropic growth, which can act as the driving force for such instabilities. We use a recently developed finite element model to simulate the rich variety of nonlinear responses of Kirchhoff-Love sheets. The model uses subdivision surface shape functions in order to guarantee convergence of the method, and to allow a finite element description of anisotropically growing sheets in the classical Rayleigh-Ritz formalism. We illustrate the great potential in this approach by simulating the inflation of airbags, the buckling of a stretched cylinder, as well as the formation and scaling of wrinkles at free boundaries of growing sheets. Finally, we compare the folding of spatially confined sheets subject to growth and shrinking confinement to find that the two processes are equivalent.

Vetter, Roman; Stoop, Norbert; Wittel, Falk K.; Herrmann, Hans J.




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


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


Beta Blockers  

PubMed Central

Infantile hemangiomas are benign vascular tumors seen in 4.5 percent of neonates and infants. While most infantile hemangiomas can be managed with active nonintervention, a subset of patients will require more aggressive management. Here the authors review the use of beta-blockers in the treatment of infantile hemangiomas, including oral, topical, and multimodal treatment options. They discuss the latest data on propranolol, including criteria for patient selection, dosing recommendations, and appropriate monitoring for side effects and efficacy. Lastly, they review indications for topical timolol treatment and the potential benefits of concomitant laser therapy.

Admani, Shehla; Feldstein, Stephanie; Gonzalez, Ernesto M.



Analysis of Residual Stresses in High-Pressure Sheet Metal Forming  

Microsoft Academic Search

The further development of innovative forming processes like sheet metal hydroforming is only possible with the help of detailed knowledge about the workpiece properties and their formation depending on the particular process strategy. Up to now, the detailed understanding regarding the formation of residual stresses in hydroforming processes like the high-pressure sheet metal forming (HBU) is insufficient. Therefore, numerical (FEM)

M. Kleiner; R. Krux; W. Homberg



Anisotropy in thin Canning sheet metals  

Microsoft Academic Search

The in-plane anisotropy of ductile sheet metal may be characterised by r-values within a uniform tensile strain range. In iow ductiiity material, tensile failure occurs by the formation of an inciined groove within which the plasticity is localised. Under these conditions, where lateral and axial displacements cannot determine an r-value reliably, the inclination of the local groove is used. Anisotropy

D. W. A. Rees



Playground Injuries: Fact Sheet  


... Research Update: Smoke Alarm Installation and Fire Safety Education Fire Prevention Week Fire Safety and Prevention Tools Playground Injuries Playground Injuries: Fact Sheet Protect the Ones You Love: Falls Bicycle-Related Injuries Dog Bites Injury Center Topics Saving Lives & Protecting People ...


Youth Demographics. Fact Sheet  

ERIC Educational Resources Information Center

This fact sheet compares the numbers of 18-25 year-old residents and citizens by gender, race, ethnicity, geographic distribution, marital status, military status, unemployment, educational attainment, and assesses population trends from 1968-2006. It explores such demographic characteristics of young people using data from the March Annual…

Lopez, Mark Hugo; Marcelo, Karlo Barrios



Superfund Fact Sheet: Trichloroethylene.  

National Technical Information Service (NTIS)

The fact sheet describes trichloroethylene (TCE), a chemical that can be found in a variety of products, including some glues, paints and paint removers, and spot removers and cleaners. Explanations of how TCE can get into the body and how it can affect h...



Mineral Properties Sheets  

NSDL National Science Digital Library

These sheets are designed to give students a framework for making observations of minerals in hand specimen and (for selected minerals) in thin section. I place most of the emphasis on the distinguishing properties, rather than requiring an exhaustive list. Students use hand specimen observation, thin section observation (for selected minerals) and references to complete the forms.

Hirsch, Dave


GED Testing Fact Sheet  

ERIC Educational Resources Information Center

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;…

GED Testing Service, 2009



Cascading Style Sheets  

NSDL National Science Digital Library

Cascading style sheets allow for greater control over how a web document is presented, and this site can help interested users learn about them. W3C's CSS page offers even more information regarding CSS, it's history, and what's new. It also provides a listing of other related guides and tools.



Radiation Therapy Side Effects Sheets

Radiation therapy fact sheets that help patients understand their treatment and manage side effects. The fact sheets (also available in audio) have tips from patients and healthcare providers, and questions to ask providers.


Rubella - Fact Sheet for Parents  


... Vaccines Home Vaccines & Preventable Diseases Rubella Vaccination Rubella - Fact Sheet for Parents Diseases and the Vaccines that ... Measles) Infant Immunizations FAQs Vaccines website for parents Fact Sheets for Parents Diseases and the Vaccines that ...


Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity  

SciTech Connect

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.

Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China) [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)] [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China)] [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)] [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)



Electron-microscopic investigation of the formation of colloidal beta FeOOH during slow hydrolysis of an aqueous ferric chloride solution at room temperature  

Microsoft Academic Search

Summary  The occurrence and the morphology of spindle-shaped particles of colloidal?-FeOOH, formed by slow hydrolysis of the aqueous solution of FeCl3 at the room temperature, have been examined by electron microscope.\\u000a \\u000a The region of the formation of spindle-shaped particles is limited by the concentration of FeCl3 solution and the age of the system (figs. 1 and 2). The increase of the

R. H. H. Wolf; M. Wrischer; J. Šipalo-Žuljevi?



Synthesis of ductile titanium-titanium boride (Ti-TiB) composites with a beta-titanium matrix: The nature of TiB formation and composite properties  

Microsoft Academic Search

The study focused on the in-situ synthesis of titanium (Ti)-titanium boride (TiB) composites with ? phase in the matrix by reaction sintering of TiB2 with Ti and alloying element powders. The goal was to examine the nature of TiB whisker formation in three different kinds\\u000a of powder mixtures: (1) ?-Ti alloy powders and TiB2; (2) ?-Ti powder, a master alloy

K. B. Panda; K. S. Ravi Chandran



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.  


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

Hernández-Rodríguez, Maricarmen; Correa-Basurto, José; Benitez-Cardoza, Claudia G; Resendiz-Albor, Aldo Arturo; Rosales-Hernández, Martha C



Fast Light-Sheet Scanner  

NASA Technical Reports Server (NTRS)

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.

Hunter, William W., Jr.; Humphreys, William M., Jr.; Bartram, Scott M.



Raman and AFM study of gamma irradiated plastic bottle sheets  

SciTech Connect

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.

Ali, Yasir; Kumar, Vijay; Dhaliwal, A. S. [Department of Physics, Sant Longowal Institute of Engineering and Technology Longowal, Punjab-148106 (India); Sonkawade, R. G. [School of Physical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow-226025 (India)



US Geological Survey Fact Sheets  

NSDL National Science Digital Library

The US Geological Survey (USGS) Fact Sheets Web site summarizes research and investigations done by the agency and provides details about particular activities. The sheets are organized by theme, including resources, hazards, environment, information management, by individual state, and by scientific discipline. The fact sheets give basic summations of the research and provide links to more detailed pages for those seeking further information.



Device for Tensioning Sheet Members.  

National Technical Information Service (NTIS)

The device for tensioning sheet material applies a tensioning force around the outer edge of a sheet material to prevent the sheet material from wrinkling. These devices are attached to a supporting member forming the outer frame of a structure upon which...

M. A. Brown B. Whalen



Casimir forces and graphene sheets  

Microsoft Academic Search

The Casimir force between two infinitely thin parallel sheets in a setting of N such sheets is found. The finite two-dimensional conductivities, which describe the dispersive and absorptive properties of each sheet, are taken into account, whereupon the theory is applied to interacting graphenes. By exploring similarities with in-plane optical spectra for graphite, the conductivity of graphene is modeled as

D. Drosdoff; Lilia M. Woods



Skill Sheets for Agricultural Mechanics.  

ERIC Educational Resources Information Center

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…

Iowa State Univ. of Science and Technology, Ames. Dept. of Agricultural Education.


Beta structures of alternating polypeptides and their possible prebiotic significance  

NASA Technical Reports Server (NTRS)

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.

Brack, A.; Orgel, L. E.



beta structures of alternating polypeptides and their possible prebiotic significance  

Microsoft Academic Search

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 hydro-phobic and hydrophilic residues alternate, tends to form beta structures. We show that bilayers with a hydrophobic interior and a hydrophilic exterior

André Brack; Leslie E. Orgel



Functional polymer sheet patterning using microfluidics.  


Poly(dimethylsiloxane) (PDMS)-based microfluidics provide a novel approach to advanced material synthesis. While PDMS has been successfully used in a wide range of industrial applications, due to the weak mechanical property channels generally possess low aspect ratios (AR) and thus produce microparticles with similarly low ARs. By increasing the channel width to nearly 1 cm, AR to 267, and implementing flow lithography, we were able to establish the slit-channel lithography. Not only does this allow us to synthesize sheet materials bearing multiscale features and tunable chemical anisotropy but it also allows us to fabricate functional layered sheet structures in a one-step, high-throughput fashion. We showcased the technique's potential role in various applications, such as the synthesis of planar material with micro- and nanoscale features, surface morphologies, construction of tubular and 3D layered hydrogel tissue scaffolds, and one-step formation of radio frequency identification (RFID) tags. The method introduced offers a novel route to functional sheet material synthesis and sheet system fabrication. PMID:24967616

Li, Minggan; Humayun, Mouhita; Kozinski, Janusz A; Hwang, Dae Kun



Sheet Music from Canada's Past  

NSDL National Science Digital Library

The National Library of Canada has recently updated their collection of historical Canadian sheet music. Sheet Music from Canada's Past (see the November 17, 2000 Scout Report for an earlier mention) has updated their collection of sheet music from the World War I era with sheet music published before the Confederation in 1867. One can search the entire collection or search the World War I and pre-Confederation collections separately. The site also features articles devoted to describing each collection, and the posted music may be printed out from the site. Future plans include digitizing sheet music published between 1867 and 1913.



Oligomerization of beta-amyloid of the Alzheimer's and the Dutch-cerebral-haemorrhage types.  

PubMed Central

A novel ELISA has been developed which detects oligomerization of beta-amyloid (A beta). Oligomerization, fibrillization and neurotoxicity of native A beta associated with Alzheimer's disease (AD) type has been compared with E22Q A beta (amyloid beta-protein containing residues 1--40 with the native Glu at residue 22 changed to Gln) implicated in Dutch cerebral haemorrhage disease. Solutions of A beta rapidly yield soluble oligomers in a concentration-dependent manner, which are detected by the ELISA, and by size-exclusion gel chromatography. Conformational changes from disordered to beta-sheet occur more slowly than oligomerization, and fibrils are produced after prolonged incubation. The E22Q A beta oligomerizes, changes conformation and fibrillizes more rapidly than the native form and produces shorter stubbier fibrils. Aged fibrillar preparations of E22Q A beta are more potent than aged fibrils of native A beta in inducing apoptotic changes and toxic responses in human neuroblastoma cell lines, whereas low-molecular-mass oligomers in briefly incubated solutions are much less potent. The differences in the rates of oligomerization of the two A beta forms, their conformational behaviour over a range of pH values, and NMR data reported elsewhere, are consistent with a molecular model of oligomerization in which strands of A beta monomers initially overcome charge repulsion to form dimers in parallel beta-sheet arrangement, stabilized by intramolecular hydrophobic interactions, with amino acids of adjacent chains in register.

Sian, A K; Frears, E R; El-Agnaf, O M; Patel, B P; Manca, M F; Siligardi, G; Hussain, R; Austen, B M



Irish Sheet Music Archives  

NSDL National Science Digital Library

Based out of Milwaukee, the Ward Irish Music Archives were established in 1992 and is dedicated to the preservation of Irish and Irish-American music in all of its forms. Visitors to this remarkable site can browse over 5,000 pieces of Irish and Irish-American sheet music. While some of these ditties are not in the public domain, the collection can be narrowed down by filtering for only publicly available items. The History section contains a topical history of sheet music from the days of the broadside to the more challenging days of the early 21st century when digital versions became dominant. The Galleries are another great feature, containing additional information about cover artists, composers, and themes. It's an amazing collection and one that will inspire a few sing-a-longs from Dublin to Boston.