The Structure of Coronal Loops

NASA Technical Reports Server (NTRS)

Antiochos, Spiro K.

2009-01-01

It is widely believed that the simple coronal loops observed by XUV imagers, such as EIT, TRACE, or XRT, actually have a complex internal structure consisting of many (perhaps hundreds) of unresolved, interwoven "strands". According to the nanoflare model, photospheric motions tangle the strands, causing them to reconnect and release the energy required to produce the observed loop plasma. Although the strands, themselves, are unresolved by present-generation imagers, there is compelling evidence for their existence and for the nanoflare model from analysis of loop intensities and temporal evolution. A problem with this scenario is that, although reconnection can eliminate some of the strand tangles, it cannot destroy helicity, which should eventually build up to observable scales. we consider, therefore, the injection and evolution of helicity by the nanoflare process and its implications for the observed structure of loops and the large-scale corona. we argue that helicity does survive and build up to observable levels, but on spatial and temporal scales larger than those of coronal loops. we discuss the implications of these results for coronal loops and the corona, in general .

On the Mysterious Propulsion of Synechococcus

PubMed Central

Ehlers, Kurt; Oster, George

2012-01-01

We propose a model for the self-propulsion of the marine bacterium Synechococcus utilizing a continuous looped helical track analogous to that found in Myxobacteria [1]. In our model cargo-carrying protein motors, driven by proton-motive force, move along a continuous looped helical track. The movement of the cargo creates surface distortions in the form of small amplitude traveling ridges along the S-layer above the helical track. The resulting fluid motion adjacent to the helical ribbon provides the propulsive thrust. A variation on the helical rotor model of [1] allows the motors to be anchored to the peptidoglycan layer, where they drive rotation of the track creating traveling helical waves along the S-layer. We derive expressions relating the swimming speed to the amplitude, wavelength, and velocity of the surface waves induced by the helical rotor, and show that they fall in reasonable ranges to explain the velocity and rotation rate of swimming Synechococcus. PMID:22567124

The Role of Magnetic Helicity in Structuring the Solar Corona

NASA Technical Reports Server (NTRS)

Knizhnik, K. J.; Antiochos, S. K.; DeVore, C. R.

2017-01-01

Two of the most widely observed and striking features of the Suns magnetic field are coronal loops, which are smooth and laminar, and prominences or filaments, which are strongly sheared. Loops are puzzling because they show little evidence of tangling or braiding, at least on the quiet Sun, despite the chaotic nature of the solar surface convection. Prominences are mysterious because the origin of their underlying magnetic structure filament channels is poorly understood at best. These two types of features would seem to be quite unrelated and wholly distinct. We argue that, on the contrary, they are inextricably linked and result from a single process: the injection of magnetic helicity into the corona by photospheric motions and the subsequent evolution of this helicity by coronal reconnection. In this paper, we present numerical simulations of the response of a Parker (1972) corona to photospheric driving motions that have varying degrees of helicity preference. We obtain four main conclusions: (1) in agreement with the helicity condensation model of Antiochos (2013), the inverse cascade of helicity by magnetic reconnection in the corona results in the formation of filament channels localized about polarity inversion lines; (2) this same process removes most complex fine structure from the rest of the corona, resulting in smooth and laminar coronal loops; (3) the amount of remnant tangling in coronal loops is inversely dependent on the net helicity injected by the driving motions; and (4) the structure of the solar corona depends only on the helicity preference of the driving motions and not on their detailed time dependence. We discuss the implications of our results for high-resolution observations of the corona.

THE ROLE OF MAGNETIC HELICITY IN STRUCTURING THE SOLAR CORONA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knizhnik, K. J.; Antiochos, S. K.; DeVore, C. R.

Two of the most widely observed and striking features of the Sun's magnetic field are coronal loops, which are smooth and laminar, and prominences or filaments, which are strongly sheared. Loops are puzzling because they show little evidence of tangling or braiding, at least on the quiet Sun, despite the chaotic nature of the solar surface convection. Prominences are mysterious because the origin of their underlying magnetic structure—filament channels—is poorly understood at best. These two types of features would seem to be quite unrelated and wholly distinct. We argue that, on the contrary, they are inextricably linked and result frommore » a single process: the injection of magnetic helicity into the corona by photospheric motions and the subsequent evolution of this helicity by coronal reconnection. In this paper, we present numerical simulations of the response of a Parker (1972) corona to photospheric driving motions that have varying degrees of helicity preference. We obtain four main conclusions: (1) in agreement with the helicity condensation model of Antiochos (2013), the inverse cascade of helicity by magnetic reconnection in the corona results in the formation of filament channels localized about polarity inversion lines; (2) this same process removes most complex fine structure from the rest of the corona, resulting in smooth and laminar coronal loops; (3) the amount of remnant tangling in coronal loops is inversely dependent on the net helicity injected by the driving motions; and (4) the structure of the solar corona depends only on the helicity preference of the driving motions and not on their detailed time dependence. We discuss the implications of our results for high-resolution observations of the corona.« less

Cardiac looping may be driven by compressive loads resulting from unequal growth of the heart and pericardial cavity. Observations on a physical simulation model

PubMed Central

Bayraktar, Meriç; Männer, Jörg

2014-01-01

The transformation of the straight embryonic heart tube into a helically wound loop is named cardiac looping. Such looping is regarded as an essential process in cardiac morphogenesis since it brings the building blocks of the developing heart into an approximation of their definitive topographical relationships. During the past two decades, a large number of genes have been identified which play important roles in cardiac looping. However, how genetic information is physically translated into the dynamic form changes of the looping heart is still poorly understood. The oldest hypothesis of cardiac looping mechanics attributes the form changes of the heart loop (ventral bending → simple helical coiling → complex helical coiling) to compressive loads resulting from growth differences between the heart and the pericardial cavity. In the present study, we have tested the physical plausibility of this hypothesis, which we call the growth-induced buckling hypothesis, for the first time. Using a physical simulation model, we show that growth-induced buckling of a straight elastic rod within the confined space of a hemispherical cavity can generate the same sequence of form changes as observed in the looping embryonic heart. Our simulation experiments have furthermore shown that, under bilaterally symmetric conditions, growth-induced buckling generates left- and right-handed helices (D-/L-loops) in a 1:1 ratio, while even subtle left- or rightward displacements of the caudal end of the elastic rod at the pre-buckling state are sufficient to direct the buckling process toward the generation of only D- or L-loops, respectively. Our data are discussed with respect to observations made in biological “models.” We conclude that compressive loads resulting from unequal growth of the heart and pericardial cavity play important roles in cardiac looping. Asymmetric positioning of the venous heart pole may direct these forces toward a biased generation of D- or L-loops. PMID:24772086

One-loop corrections to light cone wave functions: The dipole picture DIS cross section

NASA Astrophysics Data System (ADS)

Hänninen, H.; Lappi, T.; Paatelainen, R.

2018-06-01

We develop methods to perform loop calculations in light cone perturbation theory using a helicity basis, refining the method introduced in our earlier work. In particular this includes implementing a consistent way to contract the four-dimensional tensor structures from the helicity vectors with d-dimensional tensors arising from loop integrals, in a way that can be fully automatized. We demonstrate this explicitly by calculating the one-loop correction to the virtual photon to quark-antiquark dipole light cone wave function. This allows us to calculate the deep inelastic scattering cross section in the dipole formalism to next-to-leading order accuracy. Our results, obtained using the four dimensional helicity scheme, agree with the recent calculation by Beuf using conventional dimensional regularization, confirming the regularization scheme independence of this cross section.

Numerical Simulations of Helicity Condensation in the Solar Corona

NASA Technical Reports Server (NTRS)

Zhao, L.; DeVore, C. R.; Antiochos, S. K.; Zurbuchen, T. H.

2015-01-01

The helicity condensation model has been proposed by Antiochos (2013) to explain the observed smoothness of coronal loops and the observed buildup of magnetic shear at filament channels. The basic hypothesis of the model is that magnetic reconnection in the corona causes the magnetic stress injected by photospheric motions to collect only at those special locations where prominences form. In this work we present the first detailed quantitative MHD simulations of the reconnection evolution proposed by the helicity condensation model. We use the well-known ansatz of modeling the closed corona as an initially uniform field between two horizontal photospheric plates. The system is driven by applying photospheric rotational flows that inject magnetic helicity into the system. The flows are confined to a finite region on the photosphere so as to mimic the finite flux system of, for example, a bipolar active region. The calculations demonstrate that, contrary to common belief, coronal loops having opposite helicity do not reconnect, whereas loops having the same sense of helicity do reconnect. Furthermore, we find that for a given amount of helicity injected into the corona, the evolution of the magnetic shear is insensitive to whether the pattern of driving photospheric motions is fixed or quasi-random. In all cases, the shear propagates via reconnection to the boundary of the flow region while the total magnetic helicity is conserved, as predicted by the model. We discuss the implications of our results for solar observations and for future, more realistic simulations of the helicity condensation process.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wemmer, D.E.; Kumar, N.V.; Metrione, R.M.

Toxin II from Radianthus paumotensis (Rp/sub II/) has been investigated by high-resolution NMR and chemical sequencing methods. Resonance assignments have been obtained for this protein by the sequential approach. NMR assignments could not be made consistent with the previously reported primary sequence for this protein, and chemical methods have been used to determine a sequence with which the NMR data are consistent. Analysis of the 2D NOE spectra shows that the protein secondary structure is comprised of two sequences of ..beta..-sheet, probably joined into a distorted continuous sheet, connected by turns and extended loops, without any regular ..cap alpha..-helical segments.more » The residues previously implicated in activity in this class of proteins, D8 and R13, occur in a loop region.« less

Scattering of glue by glue on the light-cone worldsheet: Helicity nonconserving amplitudes

NASA Astrophysics Data System (ADS)

Chakrabarti, D.; Qiu, J.; Thorn, C. B.

2005-09-01

We give the light-cone gauge calculation of the one-loop on-shell scattering amplitudes for gluon-gluon scattering which violate helicity conservation. We regulate infrared divergences by discretizing the p+ integrations, omitting the terms with p+=0. Collinear divergences are absent diagram by diagram for the helicity nonconserving amplitudes. We also employ a novel ultraviolet regulator that is natural for the light-cone worldsheet description of planar Feynman diagrams. We show that these regulators give the known answers for the helicity nonconserving one-loop amplitudes, which do not suffer from the usual infrared vagaries of massless particle scattering. For the maximal helicity violating process we elucidate the physics of the remarkable fact that the loop momentum integrand for the on-shell Green function associated with this process, with a suitable momentum routing of the different contributing topologies, is identically zero. We enumerate the counterterms that must be included to give Lorentz covariant results to this order, and we show that they can be described locally in the light-cone worldsheet formulation of the sum of planar diagrams.

Studying the Transfer of Magnetic Helicity in Solar Active Regions with the Connectivity-based Helicity Flux Density Method

NASA Astrophysics Data System (ADS)

Dalmasse, K.; Pariat, É.; Valori, G.; Jing, J.; Démoulin, P.

2018-01-01

In the solar corona, magnetic helicity slowly and continuously accumulates in response to plasma flows tangential to the photosphere and magnetic flux emergence through it. Analyzing this transfer of magnetic helicity is key for identifying its role in the dynamics of active regions (ARs). The connectivity-based helicity flux density method was recently developed for studying the 2D and 3D transfer of magnetic helicity in ARs. The method takes into account the 3D nature of magnetic helicity by explicitly using knowledge of the magnetic field connectivity, which allows it to faithfully track the photospheric flux of magnetic helicity. Because the magnetic field is not measured in the solar corona, modeled 3D solutions obtained from force-free magnetic field extrapolations must be used to derive the magnetic connectivity. Different extrapolation methods can lead to markedly different 3D magnetic field connectivities, thus questioning the reliability of the connectivity-based approach in observational applications. We address these concerns by applying this method to the isolated and internally complex AR 11158 with different magnetic field extrapolation models. We show that the connectivity-based calculations are robust to different extrapolation methods, in particular with regard to identifying regions of opposite magnetic helicity flux. We conclude that the connectivity-based approach can be reliably used in observational analyses and is a promising tool for studying the transfer of magnetic helicity in ARs and relating it to their flaring activity.

Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.

PubMed

Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun

2015-01-02

G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Helix formation in arrestin accompanies recognition of photoactivated rhodopsin.

PubMed

Feuerstein, Sophie E; Pulvermüller, Alexander; Hartmann, Rudolf; Granzin, Joachim; Stoldt, Matthias; Henklein, Peter; Ernst, Oliver P; Heck, Martin; Willbold, Dieter; Koenig, Bernd W

2009-11-17

Binding of arrestin to photoactivated phosphorylated rhodopsin terminates the amplification of visual signals in photoreceptor cells. Currently, there is no crystal structure of a rhodopsin-arrestin complex available, although structures of unbound rhodopsin and arrestin have been determined. High-affinity receptor binding is dependent on distinct arrestin sites responsible for recognition of rhodopsin activation and phosphorylation. The loop connecting beta-strands V and VI in rod arrestin has been implicated in the recognition of active rhodopsin. We report the structure of receptor-bound arrestin peptide Arr(67-77) mimicking this loop based on solution NMR data. The peptide binds photoactivated rhodopsin in the unphosphorylated and phosphorylated form with similar affinities and stabilizes the metarhodopsin II photointermediate. A largely alpha-helical conformation of the receptor-bound peptide is observed.

Tempest in a sugar-coated lab vial.

PubMed

Dragun, Duska; Philippe, Aurélie

2018-06-23

Angiotensin II type 1 receptor (AT 1 R) is a classical G-protein-coupled-receptor (GPCR) displaying complex structure consisting of 7-transmembrane helices connected by intracellular and extracellular loops. Beside Angiotensin II binding within transmembrane sites and mechanically induced ligand free activation, AT 1 R can be also activated by agonistic autoantibodies (AT 1 R-Ab) recognizing conformational epitopes contained in the second extracellular loop. Direct pathophysiologic involvement of AT 1 R-Abs is well established in several autoimmune contexts and organ transplantation (1). A commercially available sandwich ELISA appreciating native receptor conformation relies on cell membrane AT 1 R extracts from human AT 1 R overexpressing Chinese hamster ovary (CHO) cells as a solid phase. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Superposition and detection of two helical beams for optical orbital angular momentum communication

NASA Astrophysics Data System (ADS)

Liu, Yi-Dong; Gao, Chunqing; Gao, Mingwei; Qi, Xiaoqing; Weber, Horst

2008-07-01

A loop-like system with a Dove prism is used to generate a collinear superposition of two helical beams with different azimuthal quantum numbers in this manuscript. After the generation of the helical beams distributed on the circle centered at the optical axis by using a binary amplitude grating, the diffractive field is separated into two polarized ones with the same distribution. Rotated by the Dove prism in the loop-like system in counter directions and combined together, the two fields will generate the collinear superposition of two helical beams in certain direction. The experiment shows consistency with the theoretical analysis. This method has potential applications in optical communication by using orbital angular momentum of laser beams (optical vortices).

Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel.

PubMed

Yamada, Toshiki; Krzeminski, Mickael; Bozoky, Zoltan; Forman-Kay, Julie D; Strange, Kevin

2016-11-01

Eukaryotic CLC anion channels and transporters are homodimeric proteins composed of multiple α-helical membrane domains and large cytoplasmic C-termini containing two cystathionine-β-synthase domains (CBS1 and CBS2) that dimerize to form a Bateman domain. The Bateman domains of adjacent CLC subunits interact to form a Bateman domain dimer. The functions of CLC CBS and Bateman domains are poorly understood. We utilized the Caenorhabditis elegans CLC-1/2/Ka/Kb anion channel homolog CLH-3b to characterize the regulatory roles of CLC cytoplasmic domains. CLH-3b activity is reduced by phosphorylation or deletion of a 14-amino-acid activation domain (AD) located on the linker connecting CBS1 and CBS2. We demonstrate here that phosphorylation-dependent reductions in channel activity require an intact Bateman domain dimer and concomitant phosphorylation or deletion of both ADs. Regulation of a CLH-3b AD deletion mutant is reconstituted by intracellular perfusion with recombinant 14-amino-acid AD peptides. The sulfhydryl reactive reagent 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET) alters in a phosphorylation-dependent manner the activity of channels containing single cysteine residues that are engineered into the short intracellular loop connecting membrane α-helices H and I (H-I loop), the AD, CBS1, and CBS2. In contrast, MTSET has no effect on channels in which cysteine residues are engineered into intracellular regions that are dispensable for regulation. These studies together with our previous work suggest that binding and unbinding of the AD to the Bateman domain dimer induces conformational changes that are transduced to channel membrane domains via the H-I loop. Our findings provide new, to our knowledge, insights into the roles of CLC Bateman domains and the structure-function relationships that govern the regulation of CLC protein activity by diverse ligands and signaling pathways. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler.

PubMed

Bindewald, Eckart; Grunewald, Calvin; Boyle, Brett; O'Connor, Mary; Shapiro, Bruce A

2008-10-01

One approach to designing RNA nanoscale structures is to use known RNA structural motifs such as junctions, kissing loops or bulges and to construct a molecular model by connecting these building blocks with helical struts. We previously developed an algorithm for detecting internal loops, junctions and kissing loops in RNA structures. Here we present algorithms for automating or assisting many of the steps that are involved in creating RNA structures from building blocks: (1) assembling building blocks into nanostructures using either a combinatorial search or constraint satisfaction; (2) optimizing RNA 3D ring structures to improve ring closure; (3) sequence optimisation; (4) creating a unique non-degenerate RNA topology descriptor. This effectively creates a computational pipeline for generating molecular models of RNA nanostructures and more specifically RNA ring structures with optimized sequences from RNA building blocks. We show several examples of how the algorithms can be utilized to generate RNA tecto-shapes.

Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler☆

PubMed Central

Bindewald, Eckart; Grunewald, Calvin; Boyle, Brett; O’Connor, Mary; Shapiro, Bruce A.

2013-01-01

One approach to designing RNA nanoscale structures is to use known RNA structural motifs such as junctions, kissing loops or bulges and to construct a molecular model by connecting these building blocks with helical struts. We previously developed an algorithm for detecting internal loops, junctions and kissing loops in RNA structures. Here we present algorithms for automating or assisting many of the steps that are involved in creating RNA structures from building blocks: (1) assembling building blocks into nanostructures using either a combinatorial search or constraint satisfaction; (2) optimizing RNA 3D ring structures to improve ring closure; (3) sequence optimisation; (4) creating a unique non-degenerate RNA topology descriptor. This effectively creates a computational pipeline for generating molecular models of RNA nanostructures and more specifically RNA ring structures with optimized sequences from RNA building blocks. We show several examples of how the algorithms can be utilized to generate RNA tecto-shapes. PMID:18838281

DIRECT OBSERVATIONS OF TETHER-CUTTING RECONNECTION DURING A MAJOR SOLAR EVENT FROM 2014 FEBRUARY 24 TO 25

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Huadong; Zhang, Jun; Yang, Shuhong

2014-12-20

Using multi-wavelength data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we investigated two successive solar flares, a C5.1 confined flare and an X4.9 ejective flare with a halo coronal mass ejection, in NOAA active region 11990 from 2014 February 24 to 25. Before the confined flare onset, EUV brightening beneath the filament was detected. As the flare began, a twisted helical flux rope (FR) wrapping around the filament moved upward and then stopped, and in the meantime an obvious X-ray source below it was observed. Prior to the ejective X4.9 flare, some pre-existing loop structures inmore » the active region interacted with each other, which produced a brightening region beneath the filament. Meanwhile, a small flaring loop appeared below the interaction region and some new helical lines connecting the far ends of the loop structures were gradually formed and continually added into the former twisted FR. Then, due to the resulting imbalance between the magnetic pressure and tension, the new FR, together with the filament, erupted outward. Our observations coincide well with a tether-cutting model, suggesting that the two flares probably have the same triggering mechanism, i.e., tether-cutting reconnection. To our knowledge, this is the first direct observation of tether-cutting reconnection occurring between pre-existing loops in an active region. In the ejective flare case, the erupting filament exhibited an Ω-like kinked structure and underwent an exponential rise after a slow-rise phase, indicating that the kink instability might be also responsible for the eruption initiation.« less

Enzymatic properties of a GH19 chitinase isolated from rice lacking a major loop structure involved in chitin binding.

PubMed

Tanaka, Jun; Fukamizo, Tamo; Ohnuma, Takayuki

2017-05-01

The catalytic domains of family GH19 chitinases have been found to consist of a conserved, α-helical core-region and different numbers (1-6) of loop structures, located at both ends of the substrate-binding groove and which extend over the glycon- and aglycon-binding sites. We expressed, purified and enzymatically characterized a GH19 chitinase from rice, Oryza sativa L. cv. Nipponbare (OsChia2a), lacking a major loop structure (loop III) connected to the functionally important β-stranded region. The new enzyme thus contained the five remaining loop structures (loops I, II, IV, V and C-term). The OsChia2a recombinant protein catalyzed hydrolysis of chitin oligosaccharides, (GlcNAc)n (n = 3-6), with inversion of anomeric configuration, indicating that OsChia2a correctly folded without loop III. From thermal unfolding experiments and calorimetric titrations using the inactive OsChia2a mutant (OsChia2a-E68Q), in which the catalytic residue Glu68 was mutated to glutamine, we found that the binding affinities towards (GlcNAc)n (n = 2-6) were almost proportional to the degree of polymerization of (GlcNAc)n, but were much lower than those obtained for a moss GH19 chitinase having only loop III [Ohnuma T, Sørlie M, Fukuda T, Kawamoto N, Taira T, Fukamizo T. 2011. Chitin oligosaccharide binding to a family GH19 chitinase from the moss, Bryum coronatum. FEBS J. 278:3991-4001]. Nevertheless, OsChia2a exhibited significant antifungal activity. It appears that loop III connected to the β-stranded region is important for (GlcNAc)n binding, but is not essential for antifungal activity. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Key issues in the computational simulation of GPCR function: representation of loop domains

NASA Astrophysics Data System (ADS)

Mehler, E. L.; Periole, X.; Hassan, S. A.; Weinstein, H.

2002-11-01

Some key concerns raised by molecular modeling and computational simulation of functional mechanisms for membrane proteins are discussed and illustrated for members of the family of G protein coupled receptors (GPCRs). Of particular importance are issues related to the modeling and computational treatment of loop regions. These are demonstrated here with results from different levels of computational simulations applied to the structures of rhodopsin and a model of the 5-HT2A serotonin receptor, 5-HT2AR. First, comparative Molecular Dynamics (MD) simulations are reported for rhodopsin in vacuum and embedded in an explicit representation of the membrane and water environment. It is shown that in spite of a partial accounting of solvent screening effects by neutralization of charged side chains, vacuum MD simulations can lead to severe distortions of the loop structures. The primary source of the distortion appears to be formation of artifactual H-bonds, as has been repeatedly observed in vacuum simulations. To address such shortcomings, a recently proposed approach that has been developed for calculating the structure of segments that connect elements of secondary structure with known coordinates, is applied to 5-HT2AR to obtain an initial representation of the loops connecting the transmembrane (TM) helices. The approach consists of a simulated annealing combined with biased scaled collective variables Monte Carlo technique, and is applied to loops connecting the TM segments on both the extra-cellular and the cytoplasmic sides of the receptor. Although this initial calculation treats the loops as independent structural entities, the final structure exhibits a number of interloop interactions that may have functional significance. Finally, it is shown here that in the case where a given loop from two different GPCRs (here rhodopsin and 5-HT2AR) has approximately the same length and some degree of sequence identity, the fold adopted by the loops can be similar. Thus, in such special cases homology modeling might be used to obtain initial structures of these loops. Notably, however, all other loops in these two receptors appear to be very different in sequence and structure, so that their conformations can be found reliably only by ab initio, energy based methods and not by homology modeling.

Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops

PubMed Central

Paslawski, Wojciech; Lillelund, Ove K.; Kristensen, Julie Veje; Schafer, Nicholas P.; Baker, Rosanna P.; Urban, Sinisa; Otzen, Daniel E.

2015-01-01

Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2–3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3–6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state–level structure in the transition state. We propose that loops 1–3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated. PMID:26056273

A Structural Biology and Protein Engineering Approach to the Development of Antidotes Against the Inhibition of Human Acetylcholinesterase by OP-based Nerve Agents

DTIC Science & Technology

2015-05-01

structures that we reported earlier (Kryger et al [2000] Acta Crystallogr D Biol Crystallogr 56:1385-1394) were of complexes with the snake venom...interactions between conserved residues in the loop connecting α13 to α14 and residues from helices α18’-α19’, and, conversely, between residues in the...residues in the 4-helix bundle, including Glu376, Thr383, Asp384, Trp385, Gln508, Gln527, Phe535 and Lys538 (hAChE numbering), are strictly conserved in

HIT-SI Injector Voltage Measurements Using Injector Langmuir Probes

NASA Astrophysics Data System (ADS)

Aboul Hosn, Rabih; Smith, Roger; Jarboe, Thomas

2006-10-01

A pair of Langmuir probe arrays have been designed and built to measure floating potentials of the plasma at the injector mouth of the HIT-SI device. The Helicity Injected Torus using Steady Inductive Helicity Injection (HIT-SI) [1,2] is a ``bow tie'' spheromak using an electrodeless formation and sustainment concept. HIT-SI is powered by two inductive helicity injectors operated in quadrature to maintain a constant helicity injection rate. The electric probes consist of an array of four floating potential Langmuir probes measuring the voltage distribution in each injector from the shell to midpoint of the injector mouth. The probe measurements combine to determine the part of the injector loop voltage driving the n = 0 spheromak equilibrium region. Preliminary data suggest the spheromak voltage is the loop voltage minus the nearly constant injector voltage of 150-180 volts. These probe data will be used to calculate the helicity decay time of the spheromak. [1] T. R. Jarboe. Steady inductive helicity injection and its application to a high-beta spheromak. Fusion Technology, 36(1):85--91, July 1999. [2] P.E.Sieck et al., ``Demonstration of Steady Inductive Helicity Injection'', Nuc. Fusion, in press (2006).

Optical fiber loops and helices: tools for integrated photonic device characterization and microfluidic trapping

NASA Astrophysics Data System (ADS)

Ren, Yundong; Zhang, Rui; Ti, Chaoyang; Liu, Yuxiang

2016-09-01

Tapered optical fibers can deliver guided light into and carry light out of micro/nanoscale systems with low loss and high spatial resolution, which makes them ideal tools in integrated photonics and microfluidics. Special geometries of tapered fibers are desired for probing monolithic devices in plane as well as optical manipulation of micro particles in fluids. However, for many specially shaped tapered fibers, it remains a challenge to fabricate them in a straightforward, controllable, and repeatable way. In this work, we fabricated and characterized two special geometries of tapered optical fibers, namely fiber loops and helices, that could be switched between one and the other. The fiber loops in this work are distinct from previous ones in terms of their superior mechanical stability and high optical quality factors in air, thanks to a post-annealing process. We experimentally measured an intrinsic optical quality factor of 32,500 and a finesse of 137 from a fiber loop. A fiber helix was used to characterize a monolithic cavity optomechanical device. Moreover, a microfluidic "roller coaster" was demonstrated, where microscale particles in water were optically trapped and transported by a fiber helix. Tapered fiber loops and helices can find various applications ranging from on-the-fly characterization of integrated photonic devices to particle manipulation and sorting in microfluidics.

A dihydropyridine receptor alpha1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor.

PubMed

Cui, Yanfang; Tae, Han-Shen; Norris, Nicole C; Karunasekara, Yamuna; Pouliquin, Pierre; Board, Philip G; Dulhunty, Angela F; Casarotto, Marco G

2009-03-01

The II-III loop of the dihydropyridine receptor (DHPR) alpha(1s) subunit is a modulator of the ryanodine receptor (RyR1) Ca(2+) release channel in vitro and is essential for skeletal muscle contraction in vivo. Despite its importance, the structure of this loop has not been reported. We have investigated its structure using a suite of NMR techniques which revealed that the DHPR II-III loop is an intrinsically unstructured protein (IUP) and as such belongs to a burgeoning structural class of functionally important proteins. The loop does not possess a stable tertiary fold: it is highly flexible, with a strong N-terminal helix followed by nascent helical/turn elements and unstructured segments. Its residual structure is loosely globular with the N and C termini in close proximity. The unstructured nature of the II-III loop may allow it to easily modify its interaction with RyR1 following a surface action potential and thus initiate rapid Ca(2+) release and contraction. The in vitro binding partner for the II-III was investigated. The II-III loop interacts with the second of three structurally distinct SPRY domains in RyR1, whose function is unknown. This interaction occurs through two preformed N-terminal alpha-helical regions and a C-terminal hydrophobic element. The A peptide corresponding to the helical N-terminal region is a common probe of RyR function and binds to the same SPRY domain as the full II-III loop. Thus the second SPRY domain is an in vitro binding site for the II-III loop. The possible in vivo role of this region is discussed.

Model for the loop voltage of reversed field pinches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarboe, T.R.; Alper, B.

1987-04-01

A simple model is presented that uses the concept of helicity balance to predict the toroidal loop voltage of reversed field pinches (RFP's). Data from the RFP's at Culham (Plasma Phys. Controlled Fusion 27, 1307 (1985)) are used to calibrate and verify the model. The model indicates that most of the helicity dissipation occurs in edge regions that are outside the limiters or in regions where field lines contact the walls. The value of this new interpretation to future RFP and spheromak experiments is discussed.

The 1.25 Å resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Javid-Majd, Farah; Yang, Dong; Ioerger, Thomas R.

2008-06-01

The crystal structure of M. tuberculosis phosphoribosyl-ATP pyrophosphohydrolase, the second enzyme in the histidine-biosynthetic pathway, is presented. The structural and inferred functional relationships between M. tuberculosis phosphoribosyl-ATP pyrophosphohydrolase and other members of the nucleoside-triphosphate pyrophosphatase-fold family are described. Phosphoribosyl-ATP pyrophosphohydrolase is the second enzyme in the histidine-biosynthetic pathway, irreversibly hydrolyzing phosphoribosyl-ATP to phosphoribosyl-AMP and pyrophosphate. It is encoded by the hisE gene, which is present as a separate gene in many bacteria and archaea but is fused to hisI in other bacteria, fungi and plants. Because of its essentiality for growth in vitro, HisE is a potential drug target formore » tuberculosis. The crystal structures of two native (uncomplexed) forms of HisE from Mycobacterium tuberculosis have been determined to resolutions of 1.25 and 1.79 Å. The structure of the apoenzyme reveals that the protein is composed of five α-helices with connecting loops and is a member of the α-helical nucleoside-triphosphate pyrophosphatase superfamily. The biological unit of the protein is a homodimer, with an active site on each subunit composed of residues exclusively from that subunit. A comparison with the Campylobacter jejuni dUTPase active site allowed the identification of putative metal- and substrate-binding sites in HisE, including four conserved glutamate and glutamine residues in the sequence that are consistent with a motif for pyrophosphohydrolase activity. However, significant differences between family members are observed in the loop region between α-helices H1 and H3. The crystal structure of M. tuberculosis HisE provides insights into possible mechanisms of substrate binding and the diversity of the nucleoside-triphosphate pyrophosphatase superfamily.« less

The UNC-45 Myosin Chaperone: From Worms to Flies to Vertebrates

PubMed Central

Lee, Chi F.; Melkani, Girish C.; Bernstein, Sanford I.

2014-01-01

UNC-45 is a UCS domain protein that is critical for myosin stability and function. It likely aides in folding myosin during cellular differentiation and maintenance and protects myosin from denaturation during stress. Invertebrates have a single unc-45 gene that is expressed in both muscle and non-muscle tissues. Vertebrates possess one gene expressed in striated muscle (unc-45b) and one that is more generally expressed (unc-45a). Structurally, UNC-45 is composed of a series of alpha-helices connected by loops. It has an N-terminal TPR domain that binds to Hsp90 and a central domain composed of armadillo repeats. Its C-terminal UCS domain, which is also comprised of helical armadillo repeats, interacts with myosin. In this review, we present biochemical, structural and genetic analyses of UNC-45 in Caenorhabditis elegans, Drosophila melanogaster and various vertebrates. Further, we provide insights into UNC-45 functions, its potential mechanism of action and its roles in human disease. PMID:25376491

An auto-inhibitory helix in CTP:phosphocholine cytidylyltransferase hijacks the catalytic residue and constrains a pliable, domain-bridging helix pair

PubMed Central

Ramezanpour, Mohsen; Lee, Jaeyong; Taneva, Svetla G.; Tieleman, D. Peter; Cornell, Rosemary B.

2018-01-01

The activity of CTP:phosphocholine cytidylyltransferase (CCT), a key enzyme in phosphatidylcholine synthesis, is regulated by reversible interactions of a lipid-inducible amphipathic helix (domain M) with membrane phospholipids. When dissociated from membranes, a portion of the M domain functions as an auto-inhibitory (AI) element to suppress catalysis. The AI helix from each subunit binds to a pair of α helices (αE) that extend from the base of the catalytic dimer to create a four-helix bundle. The bound AI helices make intimate contact with loop L2, housing a key catalytic residue, Lys122. The impacts of the AI helix on active-site dynamics and positioning of Lys122 are unknown. Extensive MD simulations with and without the AI helix revealed that backbone carbonyl oxygens at the point of contact between the AI helix and loop L2 can entrap the Lys122 side chain, effectively competing with the substrate, CTP. In silico, removal of the AI helices dramatically increased αE dynamics at a predicted break in the middle of these helices, enabling them to splay apart and forge new contacts with loop L2. In vitro cross-linking confirmed the reorganization of the αE element upon membrane binding of the AI helix. Moreover, when αE bending was prevented by disulfide engineering, CCT activation by membrane binding was thwarted. These findings suggest a novel two-part auto-inhibitory mechanism for CCT involving capture of Lys122 and restraint of the pliable αE helices. We propose that membrane binding enables bending of the αE helices, bringing the active site closer to the membrane surface. PMID:29519816

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter

NASA Astrophysics Data System (ADS)

Wang, Li-Ying; Ravi, Vidhya M.; Leblanc, Gérard; Padrós, Esteve; Cladera, Josep; Perálvarez-Marín, Alex

2016-09-01

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.

Eukaryotic RNA polymerase subunit RPB8 is a new relative of the OB family.

PubMed

Krapp, S; Kelly, G; Reischl, J; Weinzierl, R O; Matthews, S

1998-02-01

RNA polymerase II subunit RPB8 is an essential subunit that is highly conserved throughout eukaryotic evolution and is present in all three types of nuclear RNA polymerases. We report the first high resolution structural insight into eukaryotic RNA polymerase architecture with the solution structure of RPB8 from Saccharomyces cerevisiae. It consists of an eight stranded, antiparallel beta-barrel, four short helical regions and a large, unstructured omega-loop. The strands are connected in classic Greek-key fashion. The overall topology is unusual and contains a striking C2 rotational symmetry. Furthermore, it is most likely a novel associate of the oligonucleotide/oligosaccharide (OB) binding protein class.

Interacting cytoplasmic loops of subunits a and c of Escherichia coli F1F0 ATP synthase gate H+ transport to the cytoplasm.

PubMed

Steed, P Ryan; Kraft, Kaitlin A; Fillingame, Robert H

2014-11-25

H(+)-transporting F1F0 ATP synthase catalyzes the synthesis of ATP via coupled rotary motors within F0 and F1. H(+) transport at the subunit a-c interface in transmembranous F0 drives rotation of a cylindrical c10 oligomer within the membrane, which is coupled to rotation of subunit γ within the α3β3 sector of F1 to mechanically drive ATP synthesis. F1F0 functions in a reversible manner, with ATP hydrolysis driving H(+) transport. ATP-driven H(+) transport in a select group of cysteine mutants in subunits a and c is inhibited after chelation of Ag(+) and/or Cd(+2) with the substituted sulfhydryl groups. The H(+) transport pathway mapped via these Ag(+)(Cd(+2))-sensitive Cys extends from the transmembrane helices (TMHs) of subunits a and c into cytoplasmic loops connecting the TMHs, suggesting these loop regions could be involved in gating H(+) release to the cytoplasm. Here, using select loop-region Cys from the single cytoplasmic loop of subunit c and multiple cytoplasmic loops of subunit a, we show that Cd(+2) directly inhibits passive H(+) transport mediated by F0 reconstituted in liposomes. Further, in extensions of previous studies, we show that the regions mediating passive H(+) transport can be cross-linked to each other. We conclude that the loop-regions in subunits a and c that are implicated in H(+) transport likely interact in a single structural domain, which then functions in gating H(+) release to the cytoplasm.

Connecting dark matter annihilation to the vertex functions of Standard Model fermions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Jason; Light, Christopher, E-mail: jkumar@hawaii.edu, E-mail: lightc@hawaii.edu

We consider scenarios in which dark matter is a Majorana fermion which couples to Standard Model fermions through the exchange of charged mediating particles. The matrix elements for various dark matter annihilation processes are then related to one-loop corrections to the fermion-photon vertex, where dark matter and the charged mediators run in the loop. In particular, in the limit where Standard Model fermion helicity mixing is suppressed, the cross section for dark matter annihilation to various final states is related to corrections to the Standard Model fermion charge form factor. These corrections can be extracted in a gauge-invariant manner frommore » collider cross sections. Although current measurements from colliders are not precise enough to provide useful constraints on dark matter annihilation, improved measurements at future experiments, such as the International Linear Collider, could improve these constraints by several orders of magnitude, allowing them to surpass the limits obtainable by direct observation.« less

The 1.25 Å resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Javid-Majd, Farah; Yang, Dong; Ioerger, Thomas R.

2008-06-23

Phosphoribosyl-ATP pyrophosphohydrolase is the second enzyme in the histidine-biosynthetic pathway, irreversibly hydrolyzing phosphoribosyl-ATP to phosphoribosyl-AMP and pyrophosphate. It is encoded by the hisE gene, which is present as a separate gene in many bacteria and archaea but is fused to hisI in other bacteria, fungi and plants. Because of its essentiality for growth in vitro, HisE is a potential drug target for tuberculosis. The crystal structures of two native (uncomplexed) forms of HisE from Mycobacterium tuberculosis have been determined to resolutions of 1.25 and 1.79 {angstrom}. The structure of the apoenzyme reveals that the protein is composed of five -helicesmore » with connecting loops and is a member of the {alpha}-helical nucleoside-triphosphate pyrophosphatase superfamily. The biological unit of the protein is a homodimer, with an active site on each subunit composed of residues exclusively from that subunit. A comparison with the Campylobacter jejuni dUTPase active site allowed the identification of putative metal- and substrate-binding sites in HisE, including four conserved glutamate and glutamine residues in the sequence that are consistent with a motif for pyrophosphohydrolase activity. However, significant differences between family members are observed in the loop region between {alpha}-helices H1 and H3. The crystal structure of M. tuberculosis HisE provides insights into possible mechanisms of substrate binding and the diversity of the nucleoside-triphosphate pyrophosphatase superfamily.« less

Conformational landscape of the HIV-V3 hairpin loop from all-atom free-energy simulations

NASA Astrophysics Data System (ADS)

Verma, Abhinav; Wenzel, Wolfgang

2008-03-01

Small beta hairpins have many distinct biological functions, including their involvement in chemokine and viral receptor recognition. The relevance of structural similarities between different hairpin loops with near homologous sequences is not yet understood, calling for the development of methods for de novo hairpin structure prediction and simulation. De novo folding of beta strands is more difficult than that of helical proteins because of nonlocal hydrogen bonding patterns that connect amino acids that are distant in the amino acid sequence and there is a large variety of possible hydrogen bond patterns. Here we use a greedy version of the basin hopping technique with our free-energy forcefield PFF02 to reproducibly and predictively fold the hairpin structure of a HIV-V3 loop. We performed 20 independent basin hopping runs for 500cycles corresponding to 7.4×107 energy evaluations each. The lowest energy structure found in the simulation has a backbone root mean square deviation (bRMSD) of only 2.04Å to the native conformation. The lowest 9 out of the 20 simulations converged to conformations deviating less than 2.5Å bRMSD from native.

Conformational landscape of the HIV-V3 hairpin loop from all-atom free-energy simulations.

PubMed

Verma, Abhinav; Wenzel, Wolfgang

2008-03-14

Small beta hairpins have many distinct biological functions, including their involvement in chemokine and viral receptor recognition. The relevance of structural similarities between different hairpin loops with near homologous sequences is not yet understood, calling for the development of methods for de novo hairpin structure prediction and simulation. De novo folding of beta strands is more difficult than that of helical proteins because of nonlocal hydrogen bonding patterns that connect amino acids that are distant in the amino acid sequence and there is a large variety of possible hydrogen bond patterns. Here we use a greedy version of the basin hopping technique with our free-energy forcefield PFF02 to reproducibly and predictively fold the hairpin structure of a HIV-V3 loop. We performed 20 independent basin hopping runs for 500 cycles corresponding to 7.4 x 10(7) energy evaluations each. The lowest energy structure found in the simulation has a backbone root mean square deviation (bRMSD) of only 2.04 A to the native conformation. The lowest 9 out of the 20 simulations converged to conformations deviating less than 2.5 A bRMSD from native.

Crystal Structure of FadA Adhesin from Fusobacterium nucleatum Reveals a Novel Oligomerization Motif, the Leucine Chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nithianantham, Stanley; Xu, Minghua; Yamada, Mitsunori

2009-04-07

Many bacterial appendages have filamentous structures, often composed of repeating monomers assembled in a head-to-tail manner. The mechanisms of such linkages vary. We report here a novel protein oligomerization motif identified in the FadA adhesin from the Gram-negative bacterium Fusobacterium nucleatum. The 2.0 {angstrom} crystal structure of the secreted form of FadA (mFadA) reveals two antiparallel {alpha}-helices connected by an intervening 8-residue hairpin loop. Leucine-leucine contacts play a prominent dual intra- and intermolecular role in the structure and function of FadA. First, they comprise the main association between the two helical arms of the monomer; second, they mediate the head-to-tailmore » association of monomers to form the elongated polymers. This leucine-mediated filamentous assembly of FadA molecules constitutes a novel structural motif termed the 'leucine chain.' The essential role of these residues in FadA is corroborated by mutagenesis of selected leucine residues, which leads to the abrogation of oligomerization, filament formation, and binding to host cells.« less

Structure of a Double Transmembrane Fragment of a G-Protein-Coupled Receptor in Micelles

PubMed Central

Neumoin, Alexey; Cohen, Leah S.; Arshava, Boris; Tantry, Subramanyam; Becker, Jeffrey M.; Zerbe, Oliver; Naider, Fred

2009-01-01

Abstract The structure and dynamic properties of an 80-residue fragment of Ste2p, the G-protein-coupled receptor for α-factor of Saccharomyces cerevisiae, was studied in LPPG micelles with the use of solution NMR spectroscopy. The fragment Ste2p(G31-T110) (TM1-TM2) consisted of 19 residues from the N-terminal domain, the first TM helix (TM1), the first cytoplasmic loop, the second TM helix (TM2), and seven residues from the first extracellular loop. Multidimensional NMR experiments on [15N], [15N, 13C], [15N, 13C, 2H]-labeled TM1-TM2 and on protein fragments selectively labeled at specific amino acid residues or protonated at selected methyl groups resulted in >95% assignment of backbone and side-chain nuclei. The NMR investigation revealed the secondary structure of specific residues of TM1-TM2. TALOS constraints and NOE connectivities were used to calculate a structure for TM1-TM2 that was highlighted by the presence of three α-helices encompassing residues 39–47, 49–72, and 80–103, with higher flexibility around the internal Arg58 site of TM1. RMSD values of individually superimposed helical segments 39–47, 49–72, and 80–103 were 0.25 ± 0.10 Å, 0.40 ± 0.13 Å, and 0.57 ± 0.19 Å, respectively. Several long-range interhelical connectivities supported the folding of TM1-TM2 into a tertiary structure typified by a crossed helix that splays apart toward the extracellular regions and contains considerable flexibility in the G56VRSG60 region. 15N-relaxation and hydrogen-deuterium exchange data support a stable fold for the TM parts of TM1-TM2, whereas the solvent-exposed segments are more flexible. The NMR structure is consistent with the results of biochemical experiments that identified the ligand-binding site within this region of the receptor. PMID:19383463

Probing the Self-Assembly and the Accompanying Structural Changes of Hydrophobin SC3 on a Hydrophobic Surface by Mass Spectrometry

PubMed Central

Wang, X.; Permentier, H. P.; Rink, R.; Kruijtzer, J. A. W.; Liskamp, R. M. J.; Wösten, H. A. B.; Poolman, B.; Robillard, G. T.

2004-01-01

The fungal class I hydrophobin SC3 self-assembles into an amphipathic membrane at hydrophilic-hydrophobic interfaces such as the water-air and water-Teflon interface. During self-assembly, the water-soluble state of SC3 proceeds via the intermediate α-helical state to the stable end form called the β-sheet state. Self-assembly of the hydrophobin at the Teflon surface is arrested in the α-helical state. The β-sheet state can be induced at elevated temperature in the presence of detergent. The structural changes of SC3 were monitored by various mass spectrometry techniques. We show that the so-called second loop of SC3 (C39–S72) has a high affinity for Teflon. Binding of this part of SC3 to Teflon was accompanied by the formation of α-helical structure and resulted in low solvent accessibility. The solvent-protected region of the second loop extended upon conversion to the β-sheet state. In contrast, the C-terminal part of SC3 became more exposed to the solvent. The results indicate that the second loop of class I hydrophobins plays a pivotal role in self-assembly at the hydrophilic-hydrophobic interface. Of interest, this loop is much smaller in case of class II hydrophobins, which may explain the differences in their assembly. PMID:15345568

γ5 in the four-dimensional helicity scheme

NASA Astrophysics Data System (ADS)

Gnendiger, C.; Signer, A.

2018-05-01

We investigate the regularization-scheme dependent treatment of γ5 in the framework of dimensional regularization, mainly focusing on the four-dimensional helicity scheme (fdh). Evaluating distinctive examples, we find that for one-loop calculations, the recently proposed four-dimensional formulation (fdf) of the fdh scheme constitutes a viable and efficient alternative compared to more traditional approaches. In addition, we extend the considerations to the two-loop level and compute the pseudoscalar form factors of quarks and gluons in fdh. We provide the necessary operator renormalization and discuss at a practical level how the complexity of intermediate calculational steps can be reduced in an efficient way.

Analysis of inter-residue contacts reveals folding stabilizers in P-loops of potassium, sodium, and TRPV channels.

PubMed

Korkosh, V S; Zhorov, B S; Tikhonov, D B

2016-05-01

The family of P-loop channels includes potassium, sodium, calcium, cyclic nucleotide-gated and TRPV channels, as well as ionotropic glutamate receptors. Despite vastly different physiological and pharmacological properties, the channels have structurally conserved folding of the pore domain. Furthermore, crystallographic data demonstrate surprisingly similar mutual disposition of transmembrane and membrane-diving helices. To understand determinants of this conservation, here we have compared available high-resolution structures of sodium, potassium, and TRPV1 channels. We found that some residues, which are in matching positions of the sequence alignment, occur in different positions in the 3D alignment. Surprisingly, we found 3D mismatches in well-packed P-helices. Analysis of energetics of individual residues in Monte Carlo minimized structures revealed cyclic patterns of energetically favorable inter- and intra-subunit contacts of P-helices with S6 helices. The inter-subunit contacts are rather conserved in all the channels, whereas the intra-subunit contacts are specific for particular types of the channels. Our results suggest that these residue-residue contacts contribute to the folding stabilization. Analysis of such contacts is important for structural and phylogenetic studies of homologous proteins.

CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

PubMed

Mercurio, Flavia A; Scognamiglio, Pasqualina L; Di Natale, Concetta; Marasco, Daniela; Pellecchia, Maurizio; Leone, Marilisa

2014-11-01

The lipid phosphatase Ship2 is a protein that intervenes in several diseases such as diabetes, cancer, neurodegeneration, and atherosclerosis. It is made up of a catalytic domain and several protein docking modules such as a C-terminal Sam (Sterile alpha motif) domain. The Sam domain of Ship2 (Ship2-Sam) binds to the Sam domains of the EphA2 receptor (EphA2-Sam) and the PI3K effector protein Arap3 (Arap3-Sam). These heterotypic Sam-Sam interactions occur through formation of dimers presenting the canonical "Mid Loop/End Helix" binding mode. The central region of Ship2-Sam, spanning the C-terminal end of α2, the α3 and α4 helices together with the α2α3 and α3α4 interhelical loops, forms the Mid Loop surface that is needed to bind partners Sam domains. A peptide encompassing most of the Ship2-Sam Mid Loop interface (Shiptide) capable of binding to both EphA2-Sam and Arap3-Sam, was previously identified. Here we investigated the conformational features of this peptide, through solution CD and NMR studies in different conditions. These studies reveal that the peptide is highly flexible in aqueous buffer, while it adopts a helical conformation in presence of 2,2,2-trifluoroethanol. The discovered structural insights and in particular the identification of a helical motif, may lead to the design of more constrained and possibly cell permeable Shiptide analogs that could work as efficient antagonists of Ship2-Sam heterotypic interactions and embrace therapeutic applications. © 2014 Wiley Periodicals, Inc.

A SOLAR TORNADO OBSERVED BY AIA/SDO: ROTATIONAL FLOW AND EVOLUTION OF MAGNETIC HELICITY IN A PROMINENCE AND CAVITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xing; Morgan, Huw; Leonard, Drew

During 2011 September 24, as observed by the Atmospheric Imaging Assembly instrument of the Solar Dynamic Observatory and ground-based H{alpha} telescopes, a prominence and associated cavity appeared above the southwest limb. On 2011 September 25 8:00 UT, material flows upward from the prominence core along a narrow loop-like structure, accompanied by a rise ({>=}50,000 km) of the prominence core and the loop. As the loop fades by 10:00, small blobs and streaks of varying brightness rotate around the top part of the prominence and cavity, mimicking a cyclone. The most intense and coherent rotation lasts for over three hours, withmore » emission in both hot ({approx}1 MK) and cold (hydrogen and helium) lines. We suggest that the cyclonic appearance and overall evolution of the structure can be interpreted in terms of the expansion of helical structures into the cavity, and the movement of plasma along helical structures which appears as a rotation when viewed along the helix axis. The coordinated movement of material between prominence and cavity suggests that they are structurally linked. Complexity is great due to the combined effect of these actions and the line-of-sight integration through the structure which contains tangled fields.« less

Structural plasticity of 4-α-helical bundles exemplified by the puzzle-like molecular assembly of the Rop protein

PubMed Central

Amprazi, Maria; Kotsifaki, Dina; Providaki, Mary; Kapetaniou, Evangelia G.; Fellas, Georgios; Kyriazidis, Ioannis; Pérez, Javier; Kokkinidis, Michael

2014-01-01

The dimeric Repressor of Primer (Rop) protein, a widely used model system for the study of coiled-coil 4-α-helical bundles, is characterized by a remarkable structural plasticity. Loop region mutations lead to a wide range of topologies, folding states, and altered physicochemical properties. A protein-folding study of Rop and several loop variants has identified specific residues and sequences that are linked to the observed structural plasticity. Apart from the native state, native-like and molten-globule states have been identified; these states are sensitive to reducing agents due to the formation of nonnative disulfide bridges. Pro residues in the loop are critical for the establishment of new topologies and molten globule states; their effects, however, can be in part compensated by Gly residues. The extreme plasticity in the assembly of 4-α-helical bundles reflects the capacity of the Rop sequence to combine a specific set of hydrophobic residues into strikingly different hydrophobic cores. These cores include highly hydrated ones that are consistent with the formation of interchain, nonnative disulfide bridges and the establishment of molten globules. Potential applications of this structural plasticity are among others in the engineering of bio-inspired materials. PMID:25024213

Molecular dynamics simulations of electrostatics and hydration distributions around RNA and DNA motifs

NASA Astrophysics Data System (ADS)

Marlowe, Ashley E.; Singh, Abhishek; Semichaevsky, Andrey V.; Yingling, Yaroslava G.

2009-03-01

Nucleic acid nanoparticles can self-assembly through the formation of complementary loop-loop interactions or stem-stem interactions. Presence and concentration of ions can significantly affect the self-assembly process and the stability of the nanostructure. In this presentation we use explicit molecular dynamics simulations to examine the variations in cationic distributions and hydration environment around DNA and RNA helices and loop-loop interactions. Our simulations show that the potassium and sodium ionic distributions are different around RNA and DNA motifs which could be indicative of ion mediated relative stability of loop-loop complexes. Moreover in RNA loop-loop motifs ions are consistently present and exchanged through a distinct electronegative channel. We will also show how we used the specific RNA loop-loop motif to design a RNA hexagonal nanoparticle.

Consequences of non-uniformity in the stoichiometry of component fractions within one and two loops models of alpha-helical peptides

USDA-ARS?s Scientific Manuscript database

Atoms in biomolecular structures like alpha helices contain an array of distances and angles which include abundant multiple patterns of redundancies. Thus all peptides backbones contain the three atom sequence N-C*C, whereas the repeating set of a four atom sequences (N-C*C-N, C*-C-N-C*, and C-N-C...

HIGH TEMPERATURE REACTOR

DOEpatents

Kulsrud, R.M.; Spitzer, L. Jr.

1961-12-12

An apparatus of the stellarator type for heating a plasma to high temperatures is designed. Circularizers at the end of then helical windings produce a circular magnetic surface and provide improved confining and heating of the plasma. Reverse curvature sections formed in the end loops of the reaction tube provide increased plasma pressure for a given magnetic field pressure and thereby minimize the current flow in the helical windings. (AEC)

The helical MreB cytoskeleton in Escherichia coli MC1000/pLE7 is an artifact of the N-Terminal yellow fluorescent protein tag.

PubMed

Swulius, Matthew T; Jensen, Grant J

2012-12-01

Based on fluorescence microscopy, the actin homolog MreB has been thought to form extended helices surrounding the cytoplasm of rod-shaped bacterial cells. The presence of these and other putative helices has come to dominate models of bacterial cell shape regulation, chromosome segregation, polarity, and motility. Here we use electron cryotomography to show that MreB does in fact form extended helices and filaments in Escherichia coli when yellow fluorescent protein (YFP) is fused to its N terminus but native (untagged) MreB expressed to the same levels does not. In contrast, mCherry fused to an internal loop (MreB-RFP(SW)) does not induce helices. The helices are therefore an artifact of the placement of the fluorescent protein tag. YFP-MreB helices were also clearly distinguishable from the punctate, "patchy" localization patterns of MreB-RFP(SW), even by standard light microscopy. The many interpretations in the literature of such punctate patterns as helices should therefore be reconsidered.

Elucidating Molecular Motion through Structural and Dynamic Filters of Energy-Minimized Conformer Ensembles

PubMed Central

2015-01-01

Complex RNA structures are constructed from helical segments connected by flexible loops that move spontaneously and in response to binding of small molecule ligands and proteins. Understanding the conformational variability of RNA requires the characterization of the coupled time evolution of interconnected flexible domains. To elucidate the collective molecular motions and explore the conformational landscape of the HIV-1 TAR RNA, we describe a new methodology that utilizes energy-minimized structures generated by the program “Fragment Assembly of RNA with Full-Atom Refinement (FARFAR)”. We apply structural filters in the form of experimental residual dipolar couplings (RDCs) to select a subset of discrete energy-minimized conformers and carry out principal component analyses (PCA) to corroborate the choice of the filtered subset. We use this subset of structures to calculate solution T1 and T1ρ relaxation times for 13C spins in multiple residues in different domains of the molecule using two simulation protocols that we previously published. We match the experimental T1 times to within 2% and the T1ρ times to within less than 10% for helical residues. These results introduce a protocol to construct viable dynamic trajectories for RNA molecules that accord well with experimental NMR data and support the notion that the motions of the helical portions of this small RNA can be described by a relatively small number of discrete conformations exchanging over time scales longer than 1 μs. PMID:24479561

Analytic Result for the Two-loop Six-point NMHV Amplitude in N = 4 Super Yang-Mills Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dixon, Lance J.; /SLAC; Drummond, James M.

2012-02-15

We provide a simple analytic formula for the two-loop six-point ratio function of planar N = 4 super Yang-Mills theory. This result extends the analytic knowledge of multi-loop six-point amplitudes beyond those with maximal helicity violation. We make a natural ansatz for the symbols of the relevant functions appearing in the two-loop amplitude, and impose various consistency conditions, including symmetry, the absence of spurious poles, the correct collinear behavior, and agreement with the operator product expansion for light-like (super) Wilson loops. This information reduces the ansatz to a small number of relatively simple functions. In order to fix these parametersmore » uniquely, we utilize an explicit representation of the amplitude in terms of loop integrals that can be evaluated analytically in various kinematic limits. The final compact analytic result is expressed in terms of classical polylogarithms, whose arguments are rational functions of the dual conformal cross-ratios, plus precisely two functions that are not of this type. One of the functions, the loop integral {Omega}{sup (2)}, also plays a key role in a new representation of the remainder function R{sub 6}{sup (2)} in the maximally helicity violating sector. Another interesting feature at two loops is the appearance of a new (parity odd) x (parity odd) sector of the amplitude, which is absent at one loop, and which is uniquely determined in a natural way in terms of the more familiar (parity even) x (parity even) part. The second non-polylogarithmic function, the loop integral {tilde {Omega}}{sup (2)}, characterizes this sector. Both {Omega}{sup (2)} and {tilde {Omega}}{sup (2)} can be expressed as one-dimensional integrals over classical polylogarithms with rational arguments.« less

Purification and characterization of Escherichia coli MreB protein.

PubMed

Nurse, Pearl; Marians, Kenneth J

2013-02-01

The actin homolog MreB is required in rod-shaped bacteria for maintenance of cell shape and is intimately connected to the holoenzyme that synthesizes the peptidoglycan layer. The protein has been reported variously to exist in helical loops under the cell surface, to rotate, and to move in patches in both directions around the cell surface. Studies of the Escherichia coli protein in vitro have been hampered by its tendency to aggregate. Here we report the purification and characterization of native E. coli MreB. The protein requires ATP hydrolysis for polymerization, forms bundles with a left-hand twist that can be as long as 4 μm, forms sheets in the presence of calcium, and has a critical concentration for polymerization of 1.5 μM.

Purification and Characterization of Escherichia coli MreB Protein*

PubMed Central

Nurse, Pearl; Marians, Kenneth J.

2013-01-01

The actin homolog MreB is required in rod-shaped bacteria for maintenance of cell shape and is intimately connected to the holoenzyme that synthesizes the peptidoglycan layer. The protein has been reported variously to exist in helical loops under the cell surface, to rotate, and to move in patches in both directions around the cell surface. Studies of the Escherichia coli protein in vitro have been hampered by its tendency to aggregate. Here we report the purification and characterization of native E. coli MreB. The protein requires ATP hydrolysis for polymerization, forms bundles with a left-hand twist that can be as long as 4 μm, forms sheets in the presence of calcium, and has a critical concentration for polymerization of 1.5 μm. PMID:23235161

A novel representation of the conformational structure of transfer RNAs. Correlation of the folding patterns of the polynucleotide chain with the base sequence and the nucleotide backbone torsions.

PubMed Central

Srinivasan, A R; Yathindra, N

1977-01-01

A novel description of the conformational characteristics of all the individual nucleotides and the phosphodiesters in tRNAs is presented in the form of a circular plot. This representation furnishes information of the base sequence with the folding patterns of the polynucleotide chain as one traverses along the circumference and with the individual nucleotide and phosphodiester linkage torsions along the radii. The circular plot obtained for yeast tRNAPhe strikingly distinguishes the helical and the loop regions. The variation of the different nucleotide torsions along the entire chain length and their effect on the secondary helical and tertiary loop regions become readily apparent. PMID:339206

Prokaryotic and eukaryotic features observed on the secondary structures of Giardia SSU rRNAs and its phylogenetic implications.

PubMed

Hwang, Ui Wook

2007-04-01

Phylogenetic position of a diplomonad protist Giardia, a principle cause of diarrhea, among eukaryotes has been vigorously debated so far. Through the comparisons of primary and secondary structures of SSU rRNAs of G. intestinalis, G. microti, G. ardeae, and G. muris, I found two major indel regions (a 6-nt indel and a 22-26-nt indel), which correspond to the helix 10 of the V2 region and helices E23-8 to E23-9 of the V4 region, respectively. As generally shown in eukaryotes, G. intestinalis and G. microti have commonly a relatively longer helix 10 (a 7-bp stem and a 4-nt loop), and also the eukaryote-specific helices E23-6 to E23-9. On the other hand, G. muris and G. ardeae have a shorter helix 10: a 2-bp stem and a 6-nt loop in G. ardeae and a 3-bp stem and a 6-nt loop in G. muris. In the V4, they have a single long helix (like the P23-1 helix in prokaryotes) instead of the helices E23-6 to E23-9. Among the four Giardia species, co-appearance of prokaryote- and eukaryote-typical features might be significant evidence to suggest that Giardia (Archezoa) is a living fossil showing an "intermediate stage" during the evolution from prokaryotes to eukaryotes.

Energy and helicity of magnetic torus knots and braids

NASA Astrophysics Data System (ADS)

Oberti, Chiara; Ricca, Renzo L.

2018-02-01

By considering steady magnetic fields in the shape of torus knots and unknots in ideal magnetohydrodynamics, we compute some fundamental geometric and physical properties to provide estimates for magnetic energy and helicity. By making use of an appropriate parametrization, we show that knots with dominant toroidal coils that are a good model for solar coronal loops have negligible total torsion contribution to magnetic helicity while writhing number provides a good proxy. Hence, by the algebraic definition of writhe based on crossing numbers, we show that the estimated values of writhe based on image analysis provide reliable information for the exact values of helicity. We also show that magnetic energy is linearly related to helicity, and the effect of the confinement of magnetic field can be expressed in terms of geometric information. These results can find useful application in solar and plasma physics, where braided structures are often present.

A consensus-guided approach yields a heat-stable alkane-producing enzyme and identifies residues promoting thermostability.

PubMed

Shakeel, Tabinda; Gupta, Mayank; Fatma, Zia; Kumar, Rakesh; Kumar, Raubins; Singh, Rahul; Sharma, Medha; Jade, Dhananjay; Gupta, Dinesh; Fatma, Tasneem; Yazdani, Syed Shams

2018-06-15

Aldehyde-deformylating oxygenase (ADO) is an essential enzyme for production of long-chain alkanes as drop-in biofuels, which are compatible with existing fuel systems. The most active ADOs are present in mesophilic cyanobacteria, especially Nostoc punctiforme Given the potential applications of thermostable enzymes in biorefineries, here we generated a thermostable (Cts)-ADO based on a consensus of ADO sequences from several thermophilic cyanobacterial strains. Using an in silico design pipeline and a metagenome library containing 41 hot-spring microbial communities, we created Cts-ADO. Cts-ADO displayed a 3.8-fold increase in pentadecane production on raising the temperature from 30 to 42 °C, whereas ADO from N. punctiforme (Np-ADO) exhibited a 1.7-fold decline. 3D structure modeling and molecular dynamics simulations of Cts- and Np-ADO at different temperatures revealed differences between the two enzymes in residues clustered on exposed loops of these variants, which affected the conformation of helices involved in forming the ADO catalytic core. In Cts-ADO, this conformational change promoted ligand binding to its preferred iron, Fe2, in the di-iron cluster at higher temperature, but the reverse was observed in Np-ADO. Detailed mapping of residues conferring Cts-ADO thermostability identified four amino acids, which we substituted individually and together in Np-ADO. Among these substitution variants, A161E was remarkably similar to Cts-ADO in terms of activity optima, kinetic parameters, and structure at higher temperature. A161E was located in loop L6, which connects helices H5 and H6, and supported ligand binding to Fe2 at higher temperatures, thereby promoting optimal activity at these temperatures and explaining the increased thermostability of Cts-ADO. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Inter-species chimeras of leukaemia inhibitory factor define a major human receptor-binding determinant.

PubMed Central

Owczarek, C M; Layton, M J; Metcalf, D; Lock, P; Willson, T A; Gough, N M; Nicola, N A

1993-01-01

Human leukaemia inhibitory factor (hLIF) binds to both human and mouse LIF receptors (LIF-R), while mouse LIF (mLIF) binds only to mouse LIF-R. Moreover, hLIF binds with higher affinity to the mLIF-R than does mLIF. In order to define the regions of the hLIF molecule responsible for species-specific interaction with the hLIF-R and for the unusual high-affinity binding to the mLIF-R, a series of 15 mouse/human LIF hybrids has been generated. Perhaps surprisingly, both of these properties mapped to the same region of the hLIF molecule. The predominant contribution was from residues in the loop linking the third and fourth helices, with lesser contributions from residues in the third helix and the loop connecting the second and third helices in the predicted three-dimensional structure. Since all chimeras retained full biological activity and receptor-binding activity on mouse cells, and there was little variation in the specific biological activity of the purified proteins, it can be concluded that the overall secondary and tertiary structures of each chimera were intact. This observation also implied that the primary binding sites on mLIF and hLIF for the mLIF-R were unaltered by inter-species domain swapping. Consequently, the site on the hLIF molecule that confers species-specific binding to the hLIF-R and higher affinity binding to the mLIF-R, must constitute an additional interaction site to that used by both mLIF and hLIF to bind to the mLIF-R. These studies define a maximum of 15 amino acid differences between hLIF and mLIF that are responsible for the different properties of these proteins. Images PMID:8253075

Behavior of Solvent-Exposed Hydrophobic Groove in the Anti-Apoptotic Bcl-XL Protein: Clues for Its Ability to Bind Diverse BH3 Ligands from MD Simulations

PubMed Central

Sankararamakrishnan, Ramasubbu

2013-01-01

Bcl-XL is a member of Bcl-2 family of proteins involved in the regulation of intrinsic pathway of apoptosis. Its overexpression in many human cancers makes it an important target for anti-cancer drugs. Bcl-XL interacts with the BH3 domain of several pro-apoptotic Bcl-2 partners. This helical bundle protein has a pronounced hydrophobic groove which acts as a binding region for the BH3 domains. Eight independent molecular dynamics simulations of the apo/holo forms of Bcl-XL were carried out to investigate the behavior of solvent-exposed hydrophobic groove. The simulations used either a twin-range cut-off or particle mesh Ewald (PME) scheme to treat long-range interactions. Destabilization of the BH3 domain-containing helix H2 was observed in all four twin-range cut-off simulations. Most of the other major helices remained stable. The unwinding of H2 can be related to the ability of Bcl-XL to bind diverse BH3 ligands. The loss of helical character can also be linked to the formation of homo- or hetero-dimers in Bcl-2 proteins. Several experimental studies have suggested that exposure of BH3 domain is a crucial event before they form dimers. Thus unwinding of H2 seems to be functionally very important. The four PME simulations, however, revealed a stable helix H2. It is possible that the H2 unfolding might occur in PME simulations at longer time scales. Hydrophobic residues in the hydrophobic groove are involved in stable interactions among themselves. The solvent accessible surface areas of bulky hydrophobic residues in the groove are significantly buried by the loop LB connecting the helix H2 and subsequent helix. These observations help to understand how the hydrophobic patch in Bcl-XL remains stable in the solvent-exposed state. We suggest that both the destabilization of helix H2 and the conformational heterogeneity of loop LB are important factors for binding of diverse ligands in the hydrophobic groove of Bcl-XL. PMID:23468841

First Plasma Results from the HIT-SI Spheromak

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Smith, R. J.

2003-10-01

HIT-SI is the newest device in the Helicity Injected Torus (HIT) program. HIT-SI is a ``bow tie'' spheromak formed and sustained by Steady Inductive Helicity Injection (SIHI) current drive. SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary. (T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT-SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria. (U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Diagnostics currently include surface magnetic probes and flux loops, visible light imaging, H-alpha line radiation monitors, voltage measurements across insulating breaks, injector current Rogowski coils, and injector flux loops. HIT-SI is currently operating in parallel with experiments on HIT-II. At the conclusion of HIT-II operations, HIT-SI will inherit a multi-point Thomson Scattering system, a scanning two-chord FIR interferometer, and other advanced diagnostics, as well as more power supplies to extend the discharge duration. Results are presented which characterize injector operation and possible evidence for spheromak formation.

Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder.

PubMed

Posner, Jonathan; Marsh, Rachel; Maia, Tiago V; Peterson, Bradley S; Gruber, Allison; Simpson, H Blair

2014-06-01

Cortico-striato-thalamo-cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive-Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional-connectivity MRI (rs-fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs-fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs-fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity. Copyright © 2013 Wiley Periodicals, Inc.

All two-loop maximally helicity-violating amplitudes in multi-Regge kinematics from applied symbology

NASA Astrophysics Data System (ADS)

Prygarin, Alexander; Spradlin, Marcus; Vergu, Cristian; Volovich, Anastasia

2012-04-01

Recent progress on scattering amplitudes has benefited from the mathematical technology of symbols for efficiently handling the types of polylogarithm functions which frequently appear in multiloop computations. The symbol for all two-loop maximally helicity violating amplitudes in planar supersymmetric Yang-Mills theory is known, but explicit analytic formulas for the amplitudes are hard to come by except in special limits where things simplify, such as multi-Regge kinematics. By applying symbology we obtain a formula for the leading behavior of the imaginary part (the Mandelstam cut contribution) of this amplitude in multi-Regge kinematics for any number of gluons. Our result predicts a simple recursive structure which agrees with a direct Balitsky-Fadin-Kuraev-Lipatov computation carried out in a parallel publication.

Viscous-enstrophy scaling law for Navier-Stokes reconnection

NASA Astrophysics Data System (ADS)

Kerr, Robert M.

2017-11-01

Simulations of perturbed, helical trefoil vortex knots and anti-parallel vortices find ν-independent collapse of temporally scaled (√{ ν} Z) - 1 / 2, Z enstrophy, between when the loops first touch at tΓ, and when reconnection ends at tx for the viscosity ν varying by 256. Due to mathematical bounds upon higher-order norms, this collapse requires that the domain increase as ν decreases, possibly to allow large-scale negative helicity to grow as compensation for small-scale positive helicity and enstrophy growth. This mechanism could be a step towards explaining how smooth solutions of the Navier-Stokes can generate finite-energy dissipation in a finite time as ν -> 0 .

Cascade unlooping of a low-pitch helical spring under tension

NASA Astrophysics Data System (ADS)

Starostin, E. L.; van der Heijden, G. H. M.

2009-06-01

We study the force vs. extension behaviour of a helical spring made of a thin torsionally stiff anisotropic elastic rod. Our focus is on springs of very low helical pitch. For certain parameters of the problem such a spring is found not to unwind when pulled but rather to form hockles that pop out one by one and lead to a highly non-monotonic force-extension curve. Between abrupt loop pop-outs this curve is well described by the planar elastica whose relevant solutions are classified. Our results may be relevant for tightly coiled nanosprings in future micro- and nano(electro)mechanical devices.

Site-directed mutagenesis of the hinge peptide from the hemagglutinin protein: enhancement of the pH-responsive conformational change.

PubMed

Casali, Monica; Banta, Scott; Zambonelli, Carlo; Megeed, Zaki; Yarmush, Martin L

2008-06-01

Environmentally responsive proteins and peptides are increasingly finding utility in various engineered systems due to their ability to respond to the presentation of external stimuli. A classic example of this behavior is the influenza hemagglutinin (HA) fusion protein. At neutral pH, HA exists in a non-fusogenic state, but upon exposure to low pH, the conformation of the structure changes to expose a fusogenic peptide. During this structural change, massive rearrangements occur in a subunit of HA (HA2). Crystallography data has shown that a loop of 28 amino acids (residues 54-81) undergoes a dramatic transition from a random coil to an alpha-helix. This segment connects to two flanking helical regions (short and long) to form a long, continuous helix. Here, we report the results of site-directed mutagenesis study on LOOP-36 to further understand the mechanism of this important stimulus-responsive peptide. The conformational transition of a bacterially expressed LOOP-36 was found to be less dramatic than has been previously reported. The systematic mutation of glutamate and histidine residues in the peptide to glutamines (glutamine scanning) did not impact the conformational behavior of the peptide, but the substitution of the glycine residue at position 22 with alanine resulted in significant pH-responsive behavior. Therefore this mutant stimulus-responsive peptide may be more valuable for future protein engineering and bionanotechnology efforts.

Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution

PubMed Central

Wu, Jianping; Li, Zhangqiang; Xie, Tian; Peng, Wei; Yin, Changcheng; Li, Xueming; Scheres, Sjors H.W.; Shi, Yigong; Yan, Nieng

2014-01-01

The ryanodine receptors (RyRs) are high-conductance intracellular Ca2+ channels that play a pivotal role in the excitation-contraction coupling of skeletal and cardiac muscles. RyRs are the largest known ion channels, with a homotetrameric organization and approximately 5000 residues in each protomer. Here we report the structure of the rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 Å, determined by single-particle electron cryo-microscopy. Three previously uncharacterized domains, named Central, Handle, and Helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity filter vestibule. The four elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the Central domains and the channel domain. These structural features explain high ion conductance by RyRs and the long-range allosteric regulation of channel activities. PMID:25517095

Structural and sequencing analysis of local target DNA recognition by MLV integrase.

PubMed

Aiyer, Sriram; Rossi, Paolo; Malani, Nirav; Schneider, William M; Chandar, Ashwin; Bushman, Frederic D; Montelione, Gaetano T; Roth, Monica J

2015-06-23

Target-site selection by retroviral integrase (IN) proteins profoundly affects viral pathogenesis. We describe the solution nuclear magnetic resonance structure of the Moloney murine leukemia virus IN (M-MLV) C-terminal domain (CTD) and a structural homology model of the catalytic core domain (CCD). In solution, the isolated MLV IN CTD adopts an SH3 domain fold flanked by a C-terminal unstructured tail. We generated a concordant MLV IN CCD structural model using SWISS-MODEL, MMM-tree and I-TASSER. Using the X-ray crystal structure of the prototype foamy virus IN target capture complex together with our MLV domain structures, residues within the CCD α2 helical region and the CTD β1-β2 loop were predicted to bind target DNA. The role of these residues was analyzed in vivo through point mutants and motif interchanges. Viable viruses with substitutions at the IN CCD α2 helical region and the CTD β1-β2 loop were tested for effects on integration target site selection. Next-generation sequencing and analysis of integration target sequences indicate that the CCD α2 helical region, in particular P187, interacts with the sequences distal to the scissile bonds whereas the CTD β1-β2 loop binds to residues proximal to it. These findings validate our structural model and disclose IN-DNA interactions relevant to target site selection. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Multi-Regge kinematics and the moduli space of Riemann spheres with marked points

DOE PAGES

Del Duca, Vittorio; Druc, Stefan; Drummond, James; ...

2016-08-25

We show that scattering amplitudes in planar N = 4 Super Yang-Mills in multi-Regge kinematics can naturally be expressed in terms of single-valued iterated integrals on the moduli space of Riemann spheres with marked points. As a consequence, scattering amplitudes in this limit can be expressed as convolutions that can easily be computed using Stokes’ theorem. We apply this framework to MHV amplitudes to leading-logarithmic accuracy (LLA), and we prove that at L loops all MHV amplitudes are determined by amplitudes with up to L + 4 external legs. We also investigate non-MHV amplitudes, and we show that they canmore » be obtained by convoluting the MHV results with a certain helicity flip kernel. We classify all leading singularities that appear at LLA in the Regge limit for arbitrary helicity configurations and any number of external legs. In conclusion, we use our new framework to obtain explicit analytic results at LLA for all MHV amplitudes up to five loops and all non-MHV amplitudes with up to eight external legs and four loops.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Qiaozhen; Krug, Robert M.; Tao, Yizhi Jane

Influenza A viruses pose a serious threat to world public health, particularly the currently circulating avian H5N1 viruses. The influenza viral nucleoprotein forms the protein scaffold of the helical genomic ribonucleoprotein complexes, and has a critical role in viral RNA replication. Here we report a 3.2 Angstrom crystal structure of this nucleoprotein, the overall shape of which resembles a crescent with a head and a body domain, with a protein fold different compared with that of the rhabdovirus nucleoprotein. Oligomerization of the influenza virus nucleoprotein is mediated by a flexible tail loop that is inserted inside a neighboring molecule. Thismore » flexibility in the tail loop enables the nucleoprotein to form loose polymers as well as rigid helices, both of which are important for nucleoprotein functions. Single residue mutations in the tail loop result in the complete loss of nucleoprotein oligomerization. An RNA-binding groove, which is found between the head and body domains at the exterior of the nucleoprotein oligomer, is lined with highly conserved basic residues widely distributed in the primary sequence. The nucleoprotein structure shows that only one of two proposed nuclear localization signals are accessible, and suggests that the body domain of nucleoprotein contains the binding site for the viral polymerase. Our results identify the tail loop binding pocket as a potential target for antiviral development.« less

An RNA internal loop acts as a hinge to facilitate ribozyme folding and catalysis.

PubMed Central

Szewczak, A A; Cech, T R

1997-01-01

RNA molecules commonly consist of helical regions separated by internal loops, and in many cases these internal loops have been found to assume stable structures. We have examined the function and dynamics of an internal loop, J5/5a, that joins the two halves of the P4-P6 domain of the Tetrahymena self-splicing group I intron. P4-P6 RNAs with mutations in the J5/5a region showed nondenaturing gel electrophoretic mobilities and levels of Fe(II)-EDTA cleavage protection intermediate between those of wild-type RNA and a mutant incapable of folding into the native P4-P6 tertiary structure. Mutants with the least structured J5/5a loops behaved the most like wild-type P4-P6, and required smaller amounts of Mg2+ to rescue folding. The activity of reconstituted introns containing mutant P4-P6 RNAs correlated similarly with the nature of the J5/5a mutation. Our results suggest that, in solution, the P4-P6 RNA is in a two-state equilibrium between folded and unfolded states. We conclude that this internal loop mainly acts as a flexible hinge, allowing the coaxially stacked helical regions on either side of it to interact via specific tertiary contacts. To a lesser extent, the specific bases within the loop contribute to folding. Furthermore, it is crucial that the junction remain unstructured in the unfolded state. These conclusions cannot be derived from a simple examination of the P4-P6 crystal structure (Cate JH et al., 1996, Science 273:1678-1685), showing once again that structure determination must be supplemented with mutational and thermodynamic analysis to provide a complete picture of a folded macromolecule. PMID:9257643

Helical screw viscometer

DOEpatents

Aubert, J.H.; Chapman, R.N.; Kraynik, A.M.

1983-06-30

A helical screw viscometer for the measurement of the viscosity of Newtonian and non-Newtonian fluids comprising an elongated cylindrical container closed by end caps defining a circular cylindrical cavity within the container, a cylindrical rotor member having a helical screw or ribbon flight carried by the outer periphery thereof rotatably carried within the cavity whereby the fluid to be measured is confined in the cavity filling the space between the rotor and the container wall. The rotor member is supported by axle members journaled in the end caps, one axle extending through one end cap and connectable to a drive source. A pair of longitudinally spaced ports are provided through the wall of the container in communication with the cavity and a differential pressure meter is connected between the ports for measuring the pressure drop caused by the rotation of the helical screw rotor acting on the confined fluid for computing viscosity.

Solvent-induced assembly of two helical Eu(III) metal-organic frameworks and fluorescence sensing activities towards nitrobenzene and Cu2+ ions

NASA Astrophysics Data System (ADS)

Ma, Ranran; Chen, Zhiwei; Wang, Suna; Yao, Qingxia; Li, Yunwu; Lu, Jing; Li, Dacheng; Dou, Jianmin

2017-08-01

Two helical Eu(III) metal-organic frameworks, namely, {[Eu(L)(DMF)(H2O)]·0.5DMF}n (1) and [Eu(L)(DEF)(H2O)]n (2) (H3L=3,5-bis(2-carboxylphenoxy)benzoic acid, DMF=N,N-dimethylformamide, DEF=N,N-diethylformamide), have been solvothermally synthesized in different solvents, respectively. Both complexes possess helical structures through the connectivity of Eu atoms and phenolic-oxygen containing branches of the flexible multicarboxylate ligand. Based on different helices, these two complexes exhibited hexagonal and tetragonal channels, respectively. Both complexes possess (3,6)-connected (4.62)2(42.610.83) topology but with different long Schlafli symbol. The solvent plays an important role in the formation of the final frameworks. Both complexes can sensitively and selectively detect nitrobenzene and Cu2+ ions.

Synthesis, structure, and magnetic properties of two 1-D helical coordination polymeric Cu(II) complexes

NASA Astrophysics Data System (ADS)

Bian, He-Dong; Yang, Xiao-E.; Yu, Qing; Chen, Zi-Lu; Liang, Hong; Yan, Shi-Ping; Liao, Dai-Zheng

2008-01-01

Two helical coordination polymeric copper(II) complexes bearing amino acid Schiff bases HL or HL', which are condensed from 2-hydroxy-1-naphthaldehyde with 2-aminobenzoic acid or L-valine, respectively, have been prepared and characterised by X-ray crystallography. In [CuL] n ( 1) the copper(II) atoms are bridged by syn- anti carboxylate groups giving infinite 1-D right-handed helical chains which are further connected by weak C-H⋯Cu interactions to build a 2-D network. While in [CuL'] n ( 2) the carboxylate group acts as a rare monatomic bridge to connect the adjacent copper(II) atoms leading to the formation of a left-handed helical chain. Magnetic susceptibility measurements indicate that 1 exhibits weak ferromagnetic interactions whereas an antiferromagnetic coupling is established for 2. The magnetic behavior can be satisfactorily explained on the basis of the structural data.

Structural effects of extracellular loop mutations in CFTR helical hairpins.

PubMed

Chang, Yuan-Heng; Stone, Tracy A; Chin, Stephanie; Glibowicka, Mira; Bear, Christine E; Deber, Charles M

2018-05-01

Missense mutations constitute 40% of 2000 cystic fibrosis-phenotypic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) database, yet the precise mechanism as to how a point mutation can render the entire 1480-residue CFTR protein dysfunctional is not well-understood. Here we investigate the structural effects of two CF-phenotypic mutations - glutamic acid to glycine at position 217 (E217G) and glutamine to arginine at position 220 (Q220R) - in the extracellular (ECL2) loop region of human CFTR using helical hairpin constructs derived from transmembrane (TM) helices 3 and 4 of the first membrane domain. We systematically replaced the wild type (WT) residues E217 and Q220 with the subset of missense mutations that could arise through a single nucleotide change in their respective codons. Circular dichroism spectra of E217G revealed that a significant increase in helicity vs. WT arises in the membrane-mimetic environment of sodium dodecylsulfate (SDS) micelles, while this mutant showed a similar gel shift to WT on SDS-PAGE gels. In contrast, the CF-mutant Q220R showed similar helicity but an increased gel shift vs. WT. These structural variations are compared with the maturation levels of the corresponding mutant full-length CFTRs, which we found are reduced to approx. 50% for E217G and 30% for Q220R vs. WT. The overall results with CFTR hairpins illustrate the range of impacts that single mutations can evoke in intramolecular protein-protein and/or protein-lipid interactions - and the levels to which corresponding mutations in full-length CFTR may be flagged by quality control mechanisms during biosynthesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Structural variations of single and tandem mismatches in RNA duplexes: a joint MD simulation and crystal structure database analysis.

PubMed

Halder, Sukanya; Bhattacharyya, Dhananjay

2012-10-04

Internal loops within RNA duplex regions are formed by single or tandem basepairing mismatches with flanking canonical Watson-Crick basepairs on both sides. They are the most common motif observed in RNA secondary structures and play integral functional and structural roles. In this report, we have studied the structural features of 1 × 1, 2 × 2, and 3 × 3 internal loops using all-atom molecular dynamics (MD) simulation technique with explicit solvent model. As MD simulation is intricately dependent on the choice of force-field and these are often rather approximate, we have used both the most popular force-fields for nucleic acids-CHARMM27 and AMBER94-for a comparative analysis. We find that tandem noncanonical basepairs forming 2 × 2 and 3 × 3 internal loops are considerably more stable than the single mismatches forming 1 × 1 internal loops, irrespective of the force field. We have also analyzed crystal structure database to study the conservation of these helical fragments in the corresponding sets of RNA structures. We observe that the nature of stability in MD simulations mimic their fluctuating natures in crystal data sets also, probably indicating reliable natures of both the force fields to reproduce experimental results. We also notice significant structural changes in the wobble G:U basepairs present in these double helical stretches, leading to a biphasic stability for these wobble pairs to release the deformational strains introduced by internal loops within duplex regions.

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling.

PubMed

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-05-30

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50-55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome.

Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket.

PubMed

Keiper, Sonja; Bebenroth, Dirk; Seelig, Burckhard; Westhof, Eric; Jäschke, Andres

2004-09-01

Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5' terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5'-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices.

Comparison of confinement in resistive-shell reversed-field pinch devices with two different magnetic shell penetration times

NASA Astrophysics Data System (ADS)

Gravestijn, R. M.; Drake, J. R.; Hedqvist, A.; Rachlew, E.

2004-01-01

A loop voltage is required to sustain the reversed-field pinch (RFP) equilibrium. The configuration is characterized by redistribution of magnetic helicity but with the condition that the total helicity is maintained constant. The magnetic field shell penetration time, tgrs, has a critical role in the stability and performance of the RFP. Confinement in the EXTRAP device has been studied with two values of tgrs, first (EXTRAP-T2) with tgrs of the order of the typical relaxation cycle timescale and then (EXTRAP-T2R) with tgrs much longer than the relaxation cycle timescale, but still much shorter than the pulse length. Plasma parameters show significant improvements in confinement in EXTRAP-T2R. The typical loop voltage required to sustain comparable electron poloidal beta values is a factor of 3 lower in the EXTRAP-T2R device. The improvement is attributed to reduced magnetic turbulence.

Three-dimensional prominence-hosting magnetic configurations: Creating a helical magnetic flux rope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, C.; Keppens, R.; Guo, Y.

2014-01-10

The magnetic configuration hosting prominences and their surrounding coronal structure is a key research topic in solar physics. Recent theoretical and observational studies strongly suggest that a helical magnetic flux rope is an essential ingredient to fulfill most of the theoretical and observational requirements for hosting prominences. To understand flux rope formation details and obtain magnetic configurations suitable for future prominence formation studies, we here report on three-dimensional isothermal magnetohydrodynamic simulations including finite gas pressure and gravity. Starting from a magnetohydrostatic corona with a linear force-free bipolar magnetic field, we follow its evolution when introducing vortex flows around the mainmore » polarities and converging flows toward the polarity inversion line near the bottom of the corona. The converging flows bring the feet of different loops together at the polarity inversion line, where magnetic reconnection and flux cancellation happen. Inflow and outflow signatures of the magnetic reconnection process are identified, and thereby the newly formed helical loops wind around preexisting ones so that a complete flux rope grows and ascends. When a macroscopic flux rope is formed, we switch off the driving flows and find that the system relaxes to a stable state containing a helical magnetic flux rope embedded in an overlying arcade structure. A major part of the formed flux rope is threaded by dipped field lines that can stably support prominence matter, while the total mass of the flux rope is in the order of 4-5× 10{sup 14} g.« less

Scattering of glue by glue on the light-cone worldsheet. II. Helicity conserving amplitudes

NASA Astrophysics Data System (ADS)

Chakrabarti, D.; Qiu, J.; Thorn, C. B.

2006-08-01

This is the second of a pair of articles on scattering of glue by glue, in which we give the light-cone gauge calculation of the one-loop on-shell helicity conserving scattering amplitudes for gluon-gluon scattering (neglecting quark loops). The 1/p+ factors in the gluon propagator are regulated by replacing p+ integrals with discretized sums omitting the p+=0 terms in each sum. We also employ a novel ultraviolet regulator that is convenient for the light-cone worldsheet description of planar Feynman diagrams. The helicity conserving scattering amplitudes are divergent in the infrared. The infrared divergences in the elastic one-loop amplitude are shown to cancel, in their contribution to cross sections, against ones in the cross section for unseen bremsstrahlung gluons. We include here the explicit calculation of the latter, because it assumes an unfamiliar form due to the peculiar way discretization of p+ regulates infrared divergences. In resolving the infrared divergences we employ a covariant definition of jets, which allows a transparent demonstration of the Lorentz invariance of our final results. Because we use an explicit cutoff of the ultraviolet divergences in exactly four spacetime dimensions, we must introduce explicit counterterms to achieve this final covariant result. These counterterms are polynomials in the external momenta of the precise order dictated by power counting. We discuss the modifications they entail for the light-cone worldsheet action that reproduces the bare planar diagrams of the gluonic sector of QCD. The simplest way to do this is to interpret the QCD string as moving in six spacetime dimensions.

Internal loop/bulge and hairpin loop of the iron-responsive element of ferritin mRNA contribute to maximal iron regulatory protein 2 binding and translational regulation in the iso-iron-responsive element/iso-iron regulatory protein family.

PubMed

Ke, Y; Sierzputowska-Gracz, H; Gdaniec, Z; Theil, E C

2000-05-23

Iron-responsive elements (IREs), a natural group of mRNA-specific sequences, bind iron regulatory proteins (IRPs) differentially and fold into hairpins [with a hexaloop (HL) CAGUGX] with helical distortions: an internal loop/bulge (IL/B) (UGC/C) or C-bulge. C-bulge iso-IREs bind IRP2 more poorly, as oligomers (n = 28-30), and have a weaker signal response in vivo. Two trans-loop GC base pairs occur in the ferritin IRE (IL/B and HL) but only one in C-bulge iso-IREs (HL); metal ions and protons perturb the IL/B [Gdaniec et al. (1998) Biochemistry 37, 1505-1512]. IRE function (translation) and physical properties (T(m) and accessibility to nucleases) are now compared for IL/B and C-bulge IREs and for HL mutants. Conversion of the IL/B into a C-bulge by a single deletion in the IL/B or by substituting the HL CG base pair with UA both derepressed ferritin synthesis 4-fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding observed for the oligomers. Since the engineered C-bulge IRE was more helical near the IL/B [Cu(phen)(2) resistant] and more stable (T(m) increased) and the HL mutant was less helical near the IL/B (ribonuclease T1 sensitive) and less stable (T(m) decreased), both CG trans-loop base pairs contribute to maximum IRP2 binding and translational regulation. The (1)H NMR spectrum of the Mg-IRE complex revealed, in contrast to the localized IL/B effects of Co(III) hexaammine observed previously, perturbation of the IL/B plus HL and interloop helix. The lower stability and greater helix distortion in the ferritin IL/B-IRE compared to the C-bulge iso-IREs create a combinatorial set of RNA/protein interactions that control protein synthesis rates with a range of signal sensitivities.

The solution structure of the prototype foamy virus RNase H domain indicates an important role of the basic loop in substrate binding.

PubMed

Leo, Berit; Schweimer, Kristian; Rösch, Paul; Hartl, Maximilian J; Wöhrl, Birgitta M

2012-09-10

The ribonuclease H (RNase H) domains of retroviral reverse transcriptases play an essential role in the replication cycle of retroviruses. During reverse transcription of the viral genomic RNA, an RNA/DNA hybrid is created whose RNA strand needs to be hydrolyzed by the RNase H to enable synthesis of the second DNA strand by the DNA polymerase function of the reverse transcriptase. Here, we report the solution structure of the separately purified RNase H domain from prototype foamy virus (PFV) revealing the so-called C-helix and the adjacent basic loop, which both were suggested to be important in substrate binding and activity. The solution structure of PFV RNase H shows that it contains a mixed five-stranded β-sheet, which is sandwiched by four α-helices (A-D), including the C-helix, on one side and one α-helix (helix E) on the opposite side. NMR titration experiments demonstrate that upon substrate addition signal changes can be detected predominantly in the basic loop as well as in the C-helix. All these regions are oriented towards the bound substrate. In addition, signal intensities corresponding to residues in the B-helix and the active site decrease, while only minor or no changes of the overall structure of the RNase H are detectable upon substrate binding. Dynamic studies confirm the monomeric state of the RNase H domain. Structure comparisons with HIV-1 RNase H, which lacks the basic protrusion, indicate that the basic loop is relevant for substrate interaction, while the C-helix appears to fulfill mainly structural functions, i.e. positioning the basic loop in the correct orientation for substrate binding. The structural data of PFV RNase H demonstrate the importance of the basic loop, which contains four positively charged lysines, in substrate binding and the function of the C-helix in positioning of the loop. In the dimeric full length HIV-1 RT, the function of the basic loop is carried out by a different loop, which also harbors basic residues, derived from the connection domain of the p66 subunit. Our results suggest that RNases H which are also active as separate domains might need a functional basic loop for proper substrate binding.

Fine flow structures in the transition region small-scale loops

NASA Astrophysics Data System (ADS)

Yan, L.; Peter, H.; He, J.; Wei, Y.

2016-12-01

The observation and model have suggested that the transition region EUV emission from the quiet sun region is contributed by very small scale loops which have not been resolved. Recently, the observation from IRIS has revealed that this kind of small scale loops. Based on the high resolution spectral and imaging observation from IRIS, much more detail work needs to be done to reveal the fine flow features in this kind of loop to help us understand the loop heating. Here, we present a detail statistical study of the spatial and temporal evolution of Si IV line profiles of small scale loops and report the spectral features: there is a transition from blue (red) wing enhancement dominant to red (blue) wing enhancement dominant along the cross-section of the loop, which is independent of time. This feature appears as the loop appear and disappear as the loop un-visible. This is probably the signature of helical flow along the loop. The result suggests that the brightening of this kind of loop is probably due to the current dissipation heating in the twisted magnetic field flux tube.

Constrained dynamics of the sole tryptophan in the third intracellular loop of the serotonin1A receptor.

PubMed

Pal, Sreetama; Aute, Ramdas; Sarkar, Parijat; Bose, Shroddha; Deshmukh, Mandar V; Chattopadhyay, Amitabha

2018-06-01

G protein-coupled receptors (GPCRs) are major signaling proteins in eukaryotic cells and are important drug targets. In spite of their role in GPCR function, the extramembranous regions of GPCRs are relatively less appreciated. The third intracellular loop (ICL3), which connects transmembrane helices V and VI, is important in this context since its crucial role in signaling has been documented for a number of GPCRs. Unfortunately, the structure of this loop is generally not visualized in x-ray crystallographic studies since this flexible loop is either stabilized using a monoclonal antibody or replaced with lysozyme. In this work, we expressed and purified the ICL3 region of the serotonin 1A receptor and monitored its motional restriction and organization utilizing red edge excitation shift (REES) of its sole tryptophan and circular dichroism (CD) spectroscopy. Our results show that the tryptophan in ICL3 exhibits REES of 4 nm, implying that it is localized in a restricted microenvironment. These results are further supported by wavelength-selective changes in fluorescence anisotropy and lifetime. This constrained dynamics was relaxed upon denaturation of the peptide, thereby suggesting the involvement of the peptide secondary structure in the observed motional restriction, as evident from CD spectroscopy and apparent rotational correlation time. To the best of our knowledge, these results constitute one of the first measurements of motional constraint in the ICL3 region of GPCRs. Our results are relevant in the context of the reported intrinsically disordered nature of ICL3 and its role in providing functional diversity to GPCRs due to conformational plasticity. Copyright © 2018 Elsevier B.V. All rights reserved.

Novel Structural Components Contribute to the High Thermal Stability of Acyl Carrier Protein from Enterococcus faecalis*

PubMed Central

Park, Young-Guen; Jung, Min-Cheol; Song, Heesang; Jeong, Ki-Woong; Bang, Eunjung; Hwang, Geum-Sook; Kim, Yangmee

2016-01-01

Enterococcus faecalis is a Gram-positive, commensal bacterium that lives in the gastrointestinal tracts of humans and other mammals. It causes severe infections because of high antibiotic resistance. E. faecalis can endure extremes of temperature and pH. Acyl carrier protein (ACP) is a key element in the biosynthesis of fatty acids responsible for acyl group shuttling and delivery. In this study, to understand the origin of high thermal stabilities of E. faecalis ACP (Ef-ACP), its solution structure was investigated for the first time. CD experiments showed that the melting temperature of Ef-ACP is 78.8 °C, which is much higher than that of Escherichia coli ACP (67.2 °C). The overall structure of Ef-ACP shows the common ACP folding pattern consisting of four α-helices (helix I (residues 3–17), helix II (residues 39–53), helix III (residues 60–64), and helix IV (residues 68–78)) connected by three loops. Unique Ef-ACP structural features include a hydrophobic interaction between Phe45 in helix II and Phe18 in the α1α2 loop and a hydrogen bonding between Ser15 in helix I and Ile20 in the α1α2 loop, resulting in its high thermal stability. Phe45-mediated hydrophobic packing may block acyl chain binding subpocket II entry. Furthermore, Ser58 in the α2α3 loop in Ef-ACP, which usually constitutes a proline in other ACPs, exhibited slow conformational exchanges, resulting in the movement of the helix III outside the structure to accommodate a longer acyl chain in the acyl binding cavity. These results might provide insights into the development of antibiotics against pathogenic drug-resistant E. faecalis strains. PMID:26631734

Evanescent effects can alter ultraviolet divergences in quantum gravity without physical consequences

DOE PAGES

Bern, Zvi; Cheung, Clifford; Chi, Huan -Hang; ...

2015-11-17

Evanescent operators such as the Gauss-Bonnet term have vanishing perturbative matrix elements in exactly D = 4 dimensions. Similarly, evanescent fields do not propagate in D = 4; a three-form field is in this class, since it is dual to a cosmological-constant contribution. In this Letter, we show that evanescent operators and fields modify the leading ultraviolet divergence in pure gravity. To analyze the divergence, we compute the two-loop identical-helicity four-graviton amplitude and determine the coefficient of the associated (nonevanescent) R 3 counterterm studied long ago by Goroff and Sagnotti. We compare two pairs of theories that are dual inmore » D = 4: gravity coupled to nothing or to three-form matter, and gravity coupled to zero-form or to two-form matter. Duff and van Nieuwenhuizen showed that, curiously, the one-loop trace anomaly—the coefficient of the Gauss-Bonnet operator—changes under p-form duality transformations. In addition, we concur and also find that the leading R 3 divergence changes under duality transformations. Nevertheless, in both cases, the physical renormalized two-loop identical-helicity four-graviton amplitude can be chosen to respect duality. In particular, its renormalization-scale dependence is unaltered.« less

Evanescent Effects can Alter Ultraviolet Divergences in Quantum Gravity without Physical Consequences.

PubMed

Bern, Zvi; Cheung, Clifford; Chi, Huan-Hang; Davies, Scott; Dixon, Lance; Nohle, Josh

2015-11-20

Evanescent operators such as the Gauss-Bonnet term have vanishing perturbative matrix elements in exactly D=4 dimensions. Similarly, evanescent fields do not propagate in D=4; a three-form field is in this class, since it is dual to a cosmological-constant contribution. In this Letter, we show that evanescent operators and fields modify the leading ultraviolet divergence in pure gravity. To analyze the divergence, we compute the two-loop identical-helicity four-graviton amplitude and determine the coefficient of the associated (nonevanescent) R^{3} counterterm studied long ago by Goroff and Sagnotti. We compare two pairs of theories that are dual in D=4: gravity coupled to nothing or to three-form matter, and gravity coupled to zero-form or to two-form matter. Duff and van Nieuwenhuizen showed that, curiously, the one-loop trace anomaly-the coefficient of the Gauss-Bonnet operator-changes under p-form duality transformations. We concur and also find that the leading R^{3} divergence changes under duality transformations. Nevertheless, in both cases, the physical renormalized two-loop identical-helicity four-graviton amplitude can be chosen to respect duality. In particular, its renormalization-scale dependence is unaltered.

π Spin Berry Phase in a Quantum-Spin-Hall-Insulator-Based Interferometer: Evidence for the Helical Spin Texture of the Edge States

NASA Astrophysics Data System (ADS)

Chen, Wei; Deng, Wei-Yin; Hou, Jing-Min; Shi, D. N.; Sheng, L.; Xing, D. Y.

2016-08-01

The quantum spin Hall insulator is characterized by helical edge states, with the spin polarization of the electron being locked to its direction of motion. Although the edge-state conduction has been observed, unambiguous evidence of the helical spin texture is still lacking. Here, we investigate the coherent edge-state transport in an interference loop pinched by two point contacts. Because of the helical character, the forward interedge scattering enforces a π spin rotation. Two successive processes can only produce a nontrivial 2 π or trivial 0 spin rotation, which can be controlled by the Rashba spin-orbit coupling. The nontrivial spin rotation results in a geometric π Berry phase, which can be detected by a π phase shift of the conductance oscillation relative to the trivial case. Our results provide smoking gun evidence for the helical spin texture of the edge states. Moreover, it also provides the opportunity to all electrically explore the trajectory-dependent spin Berry phase in condensed matter.

EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles

DOE PAGES

Fan, Yao; Tan, Kemin; Chhor, Gekleng; ...

2015-07-03

The EsxB protein from Bacillus anthracis belongs to the WXG100 family, a group of proteins secreted by a specialized secretion system. We have determined the crystal structures of recombinant EsxB and discovered that the small protein (~10 kDa), comprised of a helix-loop-helix (HLH) hairpin, is capable of associating into two different helical bundles. The two basic quaternary assemblies of EsxB are an antiparallel (AP) dimer and a rarely observed bisecting U (BU) dimer. This structural duality of EsxB is believed to originate from the heptad repeat sequence diversity of the first helix of its HLH hairpin, which allows for twomore » alternative helix packing. The flexibility of EsxB and the ability to form alternative helical bundles underscore the possibility that this protein can serve as an adaptor in secretion and can form hetero-oligomeric helix bundle(s) with other secreted members of the WXG100 family, such as EsxW. The highly conserved WXG motif is located within the loop of the HLH hairpin and is mostly buried within the helix bundle suggesting that its role is mainly structural. The exact functions of the motif, including a proposed role as a secretion signal, remain unknown.« less

Long-wave instabilities of two interlaced helical vortices

NASA Astrophysics Data System (ADS)

Quaranta, H. U.; Brynjell-Rahkola, M.; Leweke, T.; Henningson, D. S.

2016-09-01

We present a comparison between experimental observations and theoretical predictions concerning long-wave displacement instabilities of the helical vortices in the wake of a two-bladed rotor. Experiments are performed with a small-scale rotor in a water channel, using a set-up that allows the individual triggering of various instability modes at different azimuthal wave numbers, leading to local or global pairing of successive vortex loops. The initial development of the instability and the measured growth rates are in good agreement with the predictions from linear stability theory, based on an approach where the helical vortex system is represented by filaments. At later times, local pairing develops into large-scale distortions of the vortices, whereas for global pairing the non-linear evolution returns the system almost to its initial geometry.

NEUTRONIC REACTOR MANIPULATING DEVICE

DOEpatents

Ohlinger, L.A.

1962-08-01

A cable connecting a control rod in a reactor with a motor outside the reactor for moving the rod, and a helical conduit in the reactor wall, through which the cable passes are described. The helical shape of the conduit prevents the escape of certain harmful radiations from the reactor. (AEC)

Biot-Savart helicity versus physical helicity: A topological description of ideal flows

NASA Astrophysics Data System (ADS)

Sahihi, Taliya; Eshraghi, Homayoon

2014-08-01

For an isentropic (thus compressible) flow, fluid trajectories are considered as orbits of a family of one parameter, smooth, orientation-preserving, and nonsingular diffeomorphisms on a compact and smooth-boundary domain in the Euclidian 3-space which necessarily preserve a finite measure, later interpreted as the fluid mass. Under such diffeomorphisms the Biot-Savart helicity of the pushforward of a divergence-free and tangent to the boundary vector field is proved to be conserved and since these circumstances present an isentropic flow, the conservation of the "Biot-Savart helicity" is established for such flows. On the other hand, the well known helicity conservation in ideal flows which here we call it "physical helicity" is found to be an independent constant with respect to the Biot-Savart helicity. The difference between these two helicities reflects some topological features of the domain as well as the velocity and vorticity fields which is discussed and is shown for simply connected domains the two helicities coincide. The energy variation of the vorticity field is shown to be formally the same as for the incompressible flow obtained before. For fluid domains consisting of several disjoint solid tori, at each time, the harmonic knot subspace of smooth vector fields on the fluid domain is found to have two independent base sets with a special type of orthogonality between these two bases by which a topological description of the vortex and velocity fields depending on the helicity difference is achieved since this difference is shown to depend only on the harmonic knot parts of velocity, vorticity, and its Biot-Savart vector field. For an ideal magnetohydrodynamics (MHD) flow three independent constant helicities are reviewed while the helicity of magnetic potential is generalized for non-simply connected domains by inserting a special harmonic knot field in the dynamics of the magnetic potential. It is proved that the harmonic knot part of the vorticity in hydrodynamics and the magnetic field in MHD is presented by constant coefficients (fluxes) when expanded in terms of one of the time dependent base functions.

On the Construction and Dynamics of Knotted Fields

NASA Astrophysics Data System (ADS)

Kedia, Hridesh

Representing a physical field in terms of its field lines has often enabled a deeper understanding of complex physical phenomena, from Faraday's law of magnetic induction, to the Helmholtz laws of vortex motion, to the free energy density of liquid crystals in terms of the distortions of the lines of the director field. At the same time, the application of ideas from topology--the study of properties that are invariant under continuous deformations--has led to robust insights into the nature of complex physical systems from defects in crystal structures, to the earth's magnetic field, to topological conservation laws. The study of knotted fields, physical fields in which the field lines encode knots, emerges naturally from the application of topological ideas to the investigation of the physical phenomena best understood in terms of the lines of a field. A knot--a closed loop tangled with itself which can not be untangled without cutting the loop--is the simplest topologically non-trivial object constructed from a line. Remarkably, knots in the vortex (magnetic field) lines of a dissipationless fluid (plasma), persist forever as they are transported by the flow, stretching and rotating as they evolve. Moreover, deeply entwined with the topology-preserving dynamics of dissipationless fluids and plasmas, is an additional conserved quantity--helicity, a measure of the average linking of the vortex (magnetic field) lines in a fluid (plasma)--which has had far-reaching consequences for fluids and plasmas. Inspired by the persistence of knots in dissipationless flows, and their far-reaching physical consequences, we seek to understand the interplay between the dynamics of a field and the topology of its field lines in a variety of systems. While it is easy to tie a knot in a shoelace, tying a knot in the the lines of a space-filling field requires contorting the lines everywhere to match the knotted region. The challenge of analytically constructing knotted field configurations has impeded a deeper understanding of the interplay between topology and dynamics in fluids and plasmas. We begin by analytically constructing knotted field configurations which encode a desired knot in the lines of the field, and show that their helicity can be tuned independently of the encoded knot. The nonlinear nature of the physical systems in which these knotted field configurations arise, makes their analytical study challenging. We ask if a linear theory such as electromagnetism can allow knotted field configurations to persist with time. We find analytical expressions for an infinite family of knotted solutions to Maxwell's equations in vacuum and elucidate their connections to dissipationless flows. We present a design rule for constructing such persistently knotted electromagnetic fields, which could possibly be used to transfer knottedness to matter such as quantum fluids and plasmas. An important consequence of the persistence of knots in classical dissipationless flows is the existence of an additional conserved quantity, helicity, which has had far-reaching implications. To understand the existence of analogous conserved quantities, we ask if superfluids, which flow without dissipation just like classical dissipationless flows, have an additional conserved quantity akin to helicity. We address this question using an analytical approach based on defining the particle relabeling symmetry--the symmetry underlying helicity conservation--in superfluids, and find that an analogous conserved quantity exists but vanishes identically owing to the intrinsic geometry of complex scalar fields. Furthermore, to address the question of a ``classical limit'' of superfluid vortices which recovers classical helicity conservation, we perform numerical simulations of \\emph{bundles} of superfluid vortices, and find behavior akin to classical viscous flows.

NUMERICAL SIMULATIONS OF HELICITY CONDENSATION IN THE SOLAR CORONA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, L.; Zurbuchen, T. H.; DeVore, C. R.

The helicity condensation model has been proposed by Antiochos to explain the observed smoothness of coronal loops and the observed buildup of magnetic shear at filament channels. The basic hypothesis of the model is that magnetic reconnection in the corona causes the magnetic stress injected by photospheric motions to collect only at those special locations where prominences are observed to form. In this work we present the first detailed quantitative MHD simulations of the reconnection evolution proposed by the helicity condensation model. We use the well-known ansatz of modeling the closed corona as an initially uniform field between two horizontalmore » photospheric plates. The system is driven by applying photospheric rotational flows that inject magnetic helicity into the corona. The flows are confined to a finite region on the photosphere so as to mimic the finite flux system of a bipolar active region, for example. The calculations demonstrate that, contrary to common belief, opposite helicity twists do not lead to significant reconnection in such a coronal system, whereas twists with the same sense of helicity do produce substantial reconnection. Furthermore, we find that for a given amount of helicity injected into the corona, the evolution of the magnetic shear is insensitive to whether the pattern of driving photospheric motions is fixed or quasi-random. In all cases, the shear propagates via reconnection to the boundary of the flow region while the total magnetic helicity is conserved, as predicted by the model. We discuss the implications of our results for solar observations and for future, more realistic simulations of the helicity condensation process.« less

Cutting Edge: Molecular Structure of the IL-1R-Associated Kinase-4 Death Domain and Its Implications for TLR Signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lasker, Michael V.; Gajjar, Mark M.; Nair, Satish K.

2010-07-19

IL-1R-associated kinase (IRAK) 4 is an essential component of innate immunity. IRAK-4 deficiency in mice and humans results in severe impairment of IL-1 and TLR signaling. We have solved the crystal structure for the death domain of Mus musculus IRAK-4 to 1.7 {angstrom} resolution. This is the first glimpse of the structural details of a mammalian IRAK family member. The crystal structure reveals a six-helical bundle with a prominent loop, which among IRAKs and Pelle, a Drosophila homologue, is unique to IRAK-4. This highly structured loop contained between helices two and three, comprises an 11-aa stretch. Although innate immune domainmore » recognition is thought to be very similar between Drosophila and mammals, this structural component points to a drastic difference. This structure can be used as a framework for future mutation and deletion studies and potential drug design.« less

Topics in Nonsupersymmetric Scattering Amplitudes in Gauge and Gravity Theories

NASA Astrophysics Data System (ADS)

Nohle, Joshua David

In Chapters 1 and 2, we introduce and review the duality between color and kinematics in Yang-Mills theory uncovered by Bern, Carrasco and Johansson (BCJ). In Chapter 3, we provide evidence in favor of the conjectured duality between color and kinematics for the case of nonsupersymmetric pure Yang-Mills amplitudes by constructing a form of the one-loop four-point amplitude of this theory that makes the duality manifest. Our construction is valid in any dimension. We also describe a duality-satisfying representation for the two-loop four-point amplitude with identical four-dimensional external helicities. We use these results to obtain corresponding gravity integrands for a theory containing a graviton, dilaton, and antisymmetric tensor, simply by replacing color factors with specified diagram numerators. Using this, we give explicit forms of ultraviolet divergences at one loop in four, six, and eight dimensions, and at two loops in four dimensions. In Chapter 4, we extend the four-point one-loop nonsupersymmetric pure Yang-Mills discussion of Chapter 3 to include fermions and scalars circulating in the loop with all external gluons. This gives another nontrivial loop-level example showing that the duality between color and kinematics holds in nonsupersymmetric gauge theory. The construction is valid in any spacetime dimension and written in terms of formal polarization vectors. We also convert these expressions into a four-dimensional form with explicit external helicity states. Using this, we compare our results to one-loop duality-satisfying amplitudes that are already present in literature. In Chapter 5, we switch from the topic of color-kinematics duality to discuss the recently renewed interest in the soft behavior of gravitons and gluons. Specifically, we discuss the subleading low-energy behavior. Cachazo and Strominger recently proposed an extension of the soft-graviton theorem found by Weinberg. In addition, they proved the validity of their extension at tree level. This was motivated by a Virasoro symmetry of the gravity S-matrix related to BMS symmetry. As shown long ago by Weinberg, the leading soft behavior is not corrected by loops. In contrast, we show in Chapter 6 that with the standard definition of soft limits in dimensional regularization, the subleading behavior is anomalous and modified by loop effects. We argue that there are no new types of corrections to the first subleading behavior beyond one loop and to the second subleading behavior beyond two loops. To facilitate our investigation, we introduce a new momentum-conservation prescription for defining the subleading terms of the soft limit. We discuss the loop-level subleading soft behavior of gauge-theory amplitudes before turning to gravity amplitudes. In Chapter 7, we show that at tree level, on-shell gauge invariance can be used to fully determine the first subleading soft-gluon behavior and the first two subleading soft-graviton behaviors. Our proofs of the behaviors for n-gluon and n-graviton tree amplitudes are valid in D dimensions and are similar to Low's proof of universality of the first subleading behavior of photons. In contrast to photons coupling to massive particles, in four dimensions the soft behaviors of gluons and gravitons are corrected by loop effects. We comment on how such corrections arise from this perspective. We also show that loop corrections in graviton amplitudes arising from scalar loops appear only at the second soft subleading order. This case is particularly transparent because it is not entangled with graviton infrared singularities. Our result suggests that if we set aside the issue of infrared singularities, soft-graviton Ward identities of extended BMS symmetry are not anomalous through the first subleading order. Finally, in Chapter 8, we conclude this dissertation with a discussion of the evanescent effects on nonsupersymmetric gravity at two loops. Evanescent operators such as the Gauss- Bonnet term have vanishing perturbative matrix elements in exactly D = 4 dimensions. Similarly, evanescent fields do not propagate in D = 4; a three-form field is in this class, since it is dual to a cosmological-constant contribution. In this chapter, we show that evanescent operators and fields modify the leading ultraviolet divergence in pure gravity. To analyze the divergence, we compute the two-loop identical-helicity four-graviton amplitude and determine the coefficient of the associated (non-evanescent) R3 counterterm studied long ago by Goroff and Sagnotti. We compare two pairs of theories that are dual in D = 4: gravity coupled to nothing or to three-form matter, and gravity coupled to zero-form or to two-form matter. Duff and van Nieuwenhuizen showed that, curiously, the one-loop conformal anomaly---the coefficient of the Gauss-Bonnet operator---changes under p-form duality transformations. We concur, and also find that the leading R3 divergence changes under duality transformations. Nevertheless, in both cases the physical renormalized two-loop identical-helicity four-graviton amplitude can be chosen to respect duality. Its renormalization-scale dependence is unaltered. (Abstract shortened by UMI.).

Folding of the natural hammerhead ribozyme is enhanced by interaction of auxiliary elements

PubMed Central

PENEDO, J. CARLOS; WILSON, TIMOTHY J.; JAYASENA, SUMEDHA D.; KHVOROVA, ANASTASIA; LILLEY, DAVID M.J.

2004-01-01

It has been shown that the activity of the hammerhead ribozyme at μM magnesium ion concentrations is markedly increased by the inclusion of loops in helices I and II. We have studied the effect of such loops on the magnesium ion-induced folding of the ribozyme, using fluorescence resonance energy transfer. We find that with the loops in place, folding into the active conformation occurs in a single step, in the μM range of magnesium ion concentration. Disruption of the loop–loop interaction leads to a reversion to two-step folding, with the second stage requiring mM concentrations of magnesium ion. Sodium ions also promote the folding of the natural form of the ribozyme at high concentrations, but the folding occurs as a two-stage process. The loops clearly act as important auxiliary elements in the function of the ribozyme, permitting folding to occur efficiently under physiological conditions. PMID:15100442

Theory of polymorphism in bacterial flagella

NASA Astrophysics Data System (ADS)

Powers, Thomas

2004-03-01

Escherichia coli and Salmonella swim using several flagella, each of which consists of a rotary motor, a universal joint known as the hook, and a helical filament which acts a propeller. The filament is normally left-handed in the absence of external stress, but undergoes mechanical phase transitions to other helical states ("polymorphs") in response to external torque. The filament is made of identical flagellin protein subunits which are organized into eleven protofilaments which wind around the filament. We develop an effective theory in which the flagellin subunits and their connections along the protofilaments are modelled with a double-well potential. A helical spring represents the other connections of the subunits, and introduces a twist-stretch coupling and an element of frustration in our model. We solve for the ground states and the phase diagram for filament shapes.

Predicting RNA folding thermodynamics with a reduced chain representation model

PubMed Central

CAO, SONG; CHEN, SHI-JIE

2005-01-01

Based on the virtual bond representation for the nucleotide backbone, we develop a reduced conformational model for RNA. We use the experimentally measured atomic coordinates to model the helices and use the self-avoiding walks in a diamond lattice to model the loop conformations. The atomic coordinates of the helices and the lattice representation for the loops are matched at the loop–helix junction, where steric viability is accounted for. Unlike the previous simplified lattice-based models, the present virtual bond model can account for the atomic details of realistic three-dimensional RNA structures. Based on the model, we develop a statistical mechanical theory for RNA folding energy landscapes and folding thermodynamics. Tests against experiments show that the theory can give much more improved predictions for the native structures, the thermal denaturation curves, and the equilibrium folding/unfolding pathways than the previous models. The application of the model to the P5abc region of Tetrahymena group I ribozyme reveals the misfolded intermediates as well as the native-like intermediates in the equilibrium folding process. Moreover, based on the free energy landscape analysis for each and every loop mutation, the model predicts five lethal mutations that can completely alter the free energy landscape and the folding stability of the molecule. PMID:16251382

Multifunctional Dumbbell-Shaped DNA-Templated Selective Formation of Fluorescent Silver Nanoclusters or Copper Nanoparticles for Sensitive Detection of Biomolecules.

PubMed

Chen, Jinyang; Ji, Xinghu; Tinnefeld, Philip; He, Zhike

2016-01-27

In this work, a multifunctional template for selective formation of fluorescent silver nanoclusters (AgNCs) or copper nanoparticles (CuNPs) is put forward. This dumbbell-shaped (DS) DNA template is made up of two cytosine hairpin loops and an adenine-thymine-rich double-helical stem which is closed by the loops. The cytosine loops act as specific regions for the growth of AgNCs, and the double-helical stem serves as template for the CuNPs formation. By carefully investigating the sequence and length of DS DNA, we present the optimal design of the template. Benefiting from the smart design and facile synthesis, a simple, label-free, and ultrasensitive fluorescence strategy for adenosine triphosphate (ATP) detection is proposed. Through the systematic comparison, it is found that the strategy based on CuNPs formation is more sensitive for ATP assay than that based on AgNCs synthesis, and the detection limitation was found to be 81 pM. What's more, the CuNPs formation-based method is successfully applied in the detection of ATP in human serum as well as the determination of cellular ATP. In addition to small target molecule, the sensing strategy was also extended to the detection of biomacromolecule (DNA), which illustrates the generality of this biosensor.

Screech tones from free and ducted supersonic jets

NASA Technical Reports Server (NTRS)

Tam, C. K. W.; Ahuja, K. K.; Jones, R. R., III

1994-01-01

It is well known that screech tones from supersonic jets are generated by a feedback loop. The loop consists of three main components. They are the downstream propagating instability wave, the shock cell structure in the jet plume, and the feedback acoustic waves immediately outside the jet. Evidence will be presented to show that the screech frequency is largely controlled by the characteristics of the feedback acoustic waves. The feedback loop is driven by the instability wave of the jet. Thus the tone intensity and its occurrence are dictated by the characteristics of the instability wave. In this paper the dependence of the instability wave spectrum on the azimuthal mode number (axisymmetric or helical/flapping mode, etc.), the jet-to-ambient gas temperature ratio, and the jet Mach number are studied. The results of this study provide an explanation for the observed screech tone mode switch phenomenon (changing from axisymmetric to helical mode as Mach number increases) and the often-cited experimental observation that tone intensity reduces with increase in jet temperature. For ducted supersonic jets screech tones can also be generated by feedback loops formed by the coupling of normal duct modes to instability waves of the jet. The screech frequencies are dictated by the frequencies of the duct modes. Super resonance, resonance involving very large pressure oscillations, can occur when the feedback loop is powered by the most amplified instability wave. It is proposed that the observed large amplitude pressure fluctuations and tone in the test cells of Arnold Engineering Development Center were generated by super resonance. Estimated super-resonance frequency for a Mach 1.3 axisymmetric jet tested in the facility agrees well with measurement.

Automated main-chain model building by template matching and iterative fragment extension.

PubMed

Terwilliger, Thomas C

2003-01-01

An algorithm for the automated macromolecular model building of polypeptide backbones is described. The procedure is hierarchical. In the initial stages, many overlapping polypeptide fragments are built. In subsequent stages, the fragments are extended and then connected. Identification of the locations of helical and beta-strand regions is carried out by FFT-based template matching. Fragment libraries of helices and beta-strands from refined protein structures are then positioned at the potential locations of helices and strands and the longest segments that fit the electron-density map are chosen. The helices and strands are then extended using fragment libraries consisting of sequences three amino acids long derived from refined protein structures. The resulting segments of polypeptide chain are then connected by choosing those which overlap at two or more C(alpha) positions. The fully automated procedure has been implemented in RESOLVE and is capable of model building at resolutions as low as 3.5 A. The algorithm is useful for building a preliminary main-chain model that can serve as a basis for refinement and side-chain addition.

Method and apparatus for converting hydrocarbon fuel into hydrogen gas and carbon dioxide

DOEpatents

Clawson, Lawrence G.; Mitchell, William L.; Bentley, Jeffrey M.; Thijssen, Johannes H.J.

2000-01-01

An apparatus and a method are disclosed for converting hydrocarbon fuel or an alcohol into hydrogen gas and carbon dioxide. The apparatus includes a first vessel having a partial oxidation reaction zone and a separate steam reforming reaction zone that is distinct from the partial oxidation reaction zone. The first vessel has a first vessel inlet at the partial oxidation reaction zone and a first vessel outlet at the steam reforming zone. The reformer also includes a helical tube extending about the first vessel. The helical tube has a first end connected to an oxygen-containing source and a second end connected to the first vessel at the partial oxidation reaction zone. Oxygen gas from an oxygen-containing source can be directed through the helical tube to the first vessel. A second vessel having a second vessel inlet and second vessel outlet is annularly disposed about the first vessel. The helical tube is disposed between the first vessel and the second vessel and gases from the first vessel can be directed through second vessel.

Nuclear reactor safety device

DOEpatents

Hutter, Ernest

1986-01-01

A safety device is disclosed for use in a nuclear reactor for axially repositioning a control rod with respect to the reactor core in the event of an upward thermal excursion. Such safety device comprises a laminated helical ribbon configured as a tube-like helical coil having contiguous helical turns with slidably abutting edges. The helical coil is disclosed as a portion of a drive member connected axially to the control rod. The laminated ribbon is formed of outer and inner laminae. The material of the outer lamina has a greater thermal coefficient of expansion than the material of the inner lamina. In the event of an upward thermal excursion, the laminated helical coil curls inwardly to a smaller diameter. Such inward curling causes the total length of the helical coil to increase by a substantial increment, so that the control rod is axially repositioned by a corresponding amount to reduce the power output of the reactor.

Comparative NMR Analysis of an 80-Residue G Protein-Coupled Receptor Fragment in Two Membrane Mimetic Environments

PubMed Central

LS, Cohen; B, Arshava; A, Neumoin; JM, Becker; P, Güntert; O, Zerbe; Naider, F

2011-01-01

Fragments of integral membrane proteins have been used to study the physical chemical properties of regions of transporters and receptors. Ste2p(G31-T110) is an 80-residue polypeptide which contains a portion of the N-terminal domain, transmembrane domain 1 (TM1), intracellular loop 1, TM2 and part of extracellular loop 2 of the α-factor receptor (Ste2p) from Saccharomyces cerevisiae. The structure of this peptide was previously determined to form a helical hairpin in lyso-palmitoylphosphatidyl-glycerol micelles (LPPG)[1]. Herein, we perform a systematic comparison of the structure of this protein fragment in micelles and trifluoroethanol(TFE):water in order to understand whether spectra recorded in organic:aqueous medium can facilitate the structure determination in a micellar environment. Using uniformly labeled peptide and peptide selectively protonated on Ile, Val and Leu methyl groups in a perdeuterated background and a broad set of 3D NMR experiments we assigned 89% of the observable atoms. NOEs and chemical shift analysis were used to define the helical regions of the fragment. Together with constraints from paramagnetic spin labeling, NOEs were used to calculate a transiently folded helical hairpin structure for this peptide in TFE:water. Correlation of chemical shifts was insufficient to transfer assignments from TFE:water to LPPG spectra in the absence of further information. PMID:21791199

Advancing High Current Startup via Localized Helicity Injection in the PEGASUS Toroidal Experiment

NASA Astrophysics Data System (ADS)

Hinson, E. T.; Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

2013-10-01

Non-solenoidal startup via local helicity injection (LHI) and poloidal field induction is used to produce Ip = 0 . 17 MA tokamak discharges. Impurity contamination has been reduced to negligible levels by use of conical frustum cathode geometry and local scraper limiters. Attainable currents are governed by global limits of helicity and energy balance, and Taylor relaxation. A simple lumped parameter model based on these limits is used to project discharge evolution, and indicates that attaining 1 MA in NSTX-U will require LHI-driven effective loop voltages to dominate contributions from dLp / dt . This regime contrasts with results to date and will be tested at 0.3 MA in PEGASUS with a new integrated multi-injector array. Injector impedance characteristics are consistent with magnetically-limited regimes observed in higher-power foilless diodes. Bursts of MHD are measured on time scales of order ~ 100 μ s, and correlate with rapid equilibrium changes, discrete rises in Ip, redistribution of the toroidal current, ion heating (Ti ~ 1 keV), transient drops in injector voltage, and apparent n = 1 line-tied kink activity at the injector. NIMROD simulations of high-field-side HI discharges in PEGASUS are in qualitative agreement, suggesting Ip buildup results from inward propagating toroidal current loops created by intermittent reconnection of injected current streams. Work supported by US DOE Grant DE-FG02-96ER54375.

Insights into the Photoprotective Switch of the Major Light-harvesting Complex II (LHCII)

PubMed Central

Sunku, Kiran; de Groot, Huub. J. M.; Pandit, Anjali

2013-01-01

Light-harvesting antennae of the LHC family form transmembrane three-helix bundles of which two helices are interlocked by conserved arginine-glutamate (Arg-Glu) ion pairs that form ligation sites for chlorophylls. The antenna proteins of photosystem II have an intriguing dual function. In excess light, they can switch their conformation from a light-harvesting into a photoprotective state, in which the excess and harmful excitation energies are safely dissipated as heat. Here we applied magic angle spinning NMR and selective Arg isotope enrichment as a noninvasive method to analyze the Arg structures of the major light-harvesting complex II (LHCII). The conformations of the Arg residues that interlock helix A and B appear to be preserved in the light-harvesting and photoprotective state. Several Arg residues have very downfield-shifted proton NMR responses, indicating that they stabilize the complex by strong hydrogen bonds. For the Arg Cα chemical shifts, differences are observed between LHCII in the active, light-harvesting and in the photoprotective, quenched state. These differences are attributed to a conformational change of the Arg residue in the stromal loop region. We conclude that the interlocked helices of LHCII form a rigid core. Consequently, the LHCII conformational switch does not involve changes in A/B helix tilting but likely involves rearrangements of the loops and helical segments close to the stromal and lumenal ends. PMID:23629658

New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation

PubMed Central

Mustoe, Anthony M.; Bailor, Maximillian H.; Teixeira, Robert M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

2012-01-01

Recent studies have shown that topological constraints encoded at the RNA secondary structure level involving basic steric and stereochemical forces can significantly restrict the orientations sampled by helices across two-way RNA junctions. Here, we formulate these topological constraints in greater quantitative detail and use this topological framework to rationalize long-standing but poorly understood observations regarding the basic behavior of RNA two-way junctions. Notably, we show that the asymmetric nature of the A-form helix and the finite length of a bulge provide a physical basis for the experimentally observed directionality and bulge-length amplitude dependence of bulge induced inter-helical bends. We also find that the topologically allowed space can be modulated by variations in sequence, particularly with the addition of non-canonical GU base pairs at the junction, and, surprisingly, by the length of the 5′ and 3′ helices. A survey of two-way RNA junctions in the protein data bank confirms that junction residues have a strong preference to adopt looped-in, non-canonically base-paired conformations, providing a route for extending our bulge-directed framework to internal loop motifs and implying a simplified link between secondary and tertiary structure. Finally, our results uncover a new simple mechanism for coupling junction-induced topological constraints with tertiary interactions. PMID:21937512

NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion.

PubMed

Mahajan, Mukesh; Chatterjee, Deepak; Bhuvaneswari, Kannaian; Pillay, Shubhadra; Bhattacharjya, Surajit

2018-02-01

The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. 15 N{ 1 H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV. Copyright © 2017 Elsevier B.V. All rights reserved.

Proof of principle in a de novo designed protein maquette: an allosterically regulated, charge-activated conformational switch in a tetra-alpha-helix bundle.

PubMed

Grosset, A M; Gibney, B R; Rabanal, F; Moser, C C; Dutton, P L

2001-05-08

New understanding of the engineering and allosteric regulation of natural protein conformational switches (such as those that couple chemical and ionic signals, mechanical force, and electro/chemical free energy for biochemical activation, catalysis, and motion) can be derived from simple de novo designed synthetic protein models (maquettes). We demonstrate proof of principle of both reversible switch action and allosteric regulation in a tetra-alpha-helical bundle protein composed of two identical di-helical subunits containing heme coordinated at a specific position close to the disulfide loop region. Individual bundles assume one of two switch states related by large-scale mechanical changes: a syn-topology (helices of the different subunits parallel) or anti-topology (helices antiparallel). Both the spectral properties of a coproporphyrin probe appended to the loop region and the distance-dependent redox interaction between the hemes identify the topologies. Beginning from a syn-topology, introduction of ferric heme in each subunit (either binding or redox change) shifts the topological balance by 25-50-fold (1.9-2.3 kcal/mol) to an anti-dominance. Charge repulsion between the two internal cationic ferric hemes drives the syn- to anti-switch, as demonstrated in two ways. When fixed in the syn-topology, the second ferric heme binding is 25-80-fold (1.9-2.6 kcal/mol) weaker than the first, and adjacent heme redox potentials are split by 80 mV (1.85 kcal/mol), values that energetically match the shift in topological balance. Allosteric and cooperative regulation of the switch by ionic strength exploits the shielded charge interactions between the two hemes and the exposed, cooperative interactions between the coproporphyrin carboxylates.

The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

PubMed Central

Varela Chavez, Carolina; Haustant, Georges Michel; Baron, Bruno; England, Patrick; Chenal, Alexandre; Pauillac, Serge; Blondel, Arnaud; Popoff, Michel-Robert

2016-01-01

Clostridium sordellii lethal toxin (TcsL) is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT) family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP)-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat) into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain) recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases. PMID:27023605

Quadrifilar Helical Antenna Array for Line-of-Sight Communications Above the Ocean Surface

DTIC Science & Technology

2007-06-25

placing the copper-covered sheet into a mechanical plotter and using a diamond scribe to cut the edges. 5 27 (a) i (bI 900 PUTTR 180 SPTTER ANTENN 11Z...soldering of the cable to the hole and to avoid any possible radio frequency (RF) ground loops that may form. However, because it was determined that...prevent any RF ground loops that may be produced that could induce undesirable currents along the brass tube. Figure 4-9 is a closeup view of an

Ribosome protection by antibiotic resistance ATP-binding cassette protein.

PubMed

Su, Weixin; Kumar, Veerendra; Ding, Yichen; Ero, Rya; Serra, Aida; Lee, Benjamin Sian Teck; Wong, Andrew See Weng; Shi, Jian; Sze, Siu Kwan; Yang, Liang; Gao, Yong-Gui

2018-05-15

The ribosome is one of the richest targets for antibiotics. Unfortunately, antibiotic resistance is an urgent issue in clinical practice. Several ATP-binding cassette family proteins confer resistance to ribosome-targeting antibiotics through a yet unknown mechanism. Among them, MsrE has been implicated in macrolide resistance. Here, we report the cryo-EM structure of ATP form MsrE bound to the ribosome. Unlike previously characterized ribosomal protection proteins, MsrE is shown to bind to ribosomal exit site. Our structure reveals that the domain linker forms a unique needle-like arrangement with two crossed helices connected by an extended loop projecting into the peptidyl-transferase center and the nascent peptide exit tunnel, where numerous antibiotics bind. In combination with biochemical assays, our structure provides insight into how MsrE binding leads to conformational changes, which results in the release of the drug. This mechanism appears to be universal for the ABC-F type ribosome protection proteins. Copyright © 2018 the Author(s). Published by PNAS.

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

PubMed Central

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-01-01

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50–55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome. DOI: http://dx.doi.org/10.7554/eLife.25642.001 PMID:28556777

Transmembrane helix prediction: a comparative evaluation and analysis.

PubMed

Cuthbertson, Jonathan M; Doyle, Declan A; Sansom, Mark S P

2005-06-01

The prediction of transmembrane (TM) helices plays an important role in the study of membrane proteins, given the relatively small number (approximately 0.5% of the PDB) of high-resolution structures for such proteins. We used two datasets (one redundant and one non-redundant) of high-resolution structures of membrane proteins to evaluate and analyse TM helix prediction. The redundant (non-redundant) dataset contains structure of 434 (268) TM helices, from 112 (73) polypeptide chains. Of the 434 helices in the dataset, 20 may be classified as 'half-TM' as they are too short to span a lipid bilayer. We compared 13 TM helix prediction methods, evaluating each method using per segment, per residue and termini scores. Four methods consistently performed well: SPLIT4, TMHMM2, HMMTOP2 and TMAP. However, even the best methods were in error by, on average, about two turns of helix at the TM helix termini. The best and worst case predictions for individual proteins were analysed. In particular, the performance of the various methods and of a consensus prediction method, were compared for a number of proteins (e.g. SecY, ClC, KvAP) containing half-TM helices. The difficulties of predicting half-TM helices suggests that current prediction methods successfully embody the two-state model of membrane protein folding, but do not accommodate a third stage in which, e.g., short helices and re-entrant loops fold within a bundle of stable TM helices.

Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures

PubMed Central

Sloma, Michael F.; Mathews, David H.

2016-01-01

RNA secondary structure prediction is widely used to analyze RNA sequences. In an RNA partition function calculation, free energy nearest neighbor parameters are used in a dynamic programming algorithm to estimate statistical properties of the secondary structure ensemble. Previously, partition functions have largely been used to estimate the probability that a given pair of nucleotides form a base pair, the conditional stacking probability, the accessibility to binding of a continuous stretch of nucleotides, or a representative sample of RNA structures. Here it is demonstrated that an RNA partition function can also be used to calculate the exact probability of formation of hairpin loops, internal loops, bulge loops, or multibranch loops at a given position. This calculation can also be used to estimate the probability of formation of specific helices. Benchmarking on a set of RNA sequences with known secondary structures indicated that loops that were calculated to be more probable were more likely to be present in the known structure than less probable loops. Furthermore, highly probable loops are more likely to be in the known structure than the set of loops predicted in the lowest free energy structures. PMID:27852924

Ultrastructural organization of connective tissue microfibrils in the posterior chamber of the eye in vivo and in vitro.

PubMed

Inoue, S

1995-02-01

The ultrastructural organization of connective tissue microfibrils was studied in the mouse eye and also by means of in vitro experiments for reconstituting microfibrils. In the posterior chamber of the eye of the C57BL/6J mouse, 3 nm-wide ribbon-like double-tracked structures were present and were periodically associated on either side with 3.5 nm-wide particulate structures identified as pentosomes, the subunits of amyloid P component (AP). At certain sites, such composite structures were observed in various stages of helical winding, and in these helices, pentosomes were preferentially localized internally. In helices in the final stages of winding, the resulting rods appeared increasingly similar to those of microfibrils. In experiments in vitro, incubation of chondroitin sulfate proteoglycan (CSPG) in TRIS buffer, pH 7.4, at 35 degrees C for 1 h produced random aggregates of 3 nm-wide double-tracked structures similar to those observed in the eye. Co-incubation of CSPG and AP resulted in the formation of rod-like structures arranged parallel to one another in approximately 50 nm-thick sheet-like layers. These rods were ultrastructurally similar to microfibrils and were made up of helically wound, 3 nm-wide double-tracked structures containing pentosomes within their core. The results of in vivo as well as in vitro experiments suggest the possibility that the connective tissue microfibril is composed of helically wound, CSPG-containing, 3 nm-wide double-tracked structures periodically associated with pentosomes which, as the helix becomes progressively tighter, fit with one another at the core of the helix to form successive 8.5 nm-wide disks of AP segments.

Molecular contacts in the transmembrane c-subunit oligomer of F-ATPases identified by tryptophan substitution mutagenesis.

PubMed

Schnick, C; Forrest, L R; Sansom, M S; Groth, G

2000-07-20

When isolated in its monomeric form, subunit c of the proton transporting ATP synthase of Escherichia coli was shown to fold in a hairpin-like structure consisting of two hydrophobic membrane spanning helices and a short connecting hydrophilic loop. In the plasma membrane of Escherichia coli, however, about 9-12 c-subunit monomers form an oligomeric complex that functions in transmembrane proton conduction and in energy transduction to the catalytic F1 domain. The arrangement of the monomers and the molecular architecture of the complex were studied by tryptophan scanning mutagenesis and restrained MD simulations. Residues 12-24 of the N-terminal transmembrane segment of subunit c were individually substituted by the large and moderately hydrophobic tryptophan side chain. Effects on the activity of the mutant proteins were studied in selective growth experiments and various ATP synthase specific activity assays. The results identify potential intersubunit contacts and structurally non-distorted, accessible residues in the c-oligomer and add constraints to the arrangement of monomers in the oligomeric complex. Results from our mutagenesis experiments were interpreted in structural models of the c-oligomer that have been obtained by restrained MD simulations. Different stoichiometries and monomer orientations were applied in these calculations. A cylindrical complex consisting of 10 monomers that are arranged in two concentric rings with the N-terminal helices of the monomers located at the periphery shows the best match with the experimental data.

Local Helicity Injection Systems for Non-solenoidal Startup in the PEGASUS Toroidal Experiment

NASA Astrophysics Data System (ADS)

Perry, J. M.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Hinson, E. T.; Lewicki, B. T.; Redd, A. J.

2013-10-01

Local helicity injection is being developed in the PEGASUS Toroidal Experiment for non-solenoidal startup in spherical tokamaks. The effective loop voltage due to helicity injection scales with the area of the injectors, requiring the development of electron current injectors with areas much larger than the 2 cm2 plasma arc injectors used to date. Solid and gas-effused metallic electrodes were found to be unusable due to reduced injector area utilization from localized cathode spots and narrow operational regimes. An integrated array of 8 compact plasma arc sources is thus being developed for high current startup. It employs two monolithic power systems, for the plasma arc sources and the bias current extraction system. The array effectively eliminates impurity fueling from plasma-material interaction by incorporating a local scraper-limiter and conical-frustum bias electrodes to mitigate the effects of cathode spots. An energy balance model of helicity injection indicates that the resulting 20 cm2 of total injection area should provide sufficient current drive to reach 0.3 MA. At that level, helicity injection drive exceeds that from poloidal induction, which is the relevant operational regime for large-scale spherical tokamaks. Future placement of the injector array near an expanded boundary divertor region will test simultaneous optimization of helicity drive and the Taylor relaxation current limit. Work supported by US DOE Grant DE-FG02-96ER54375.

STAND, a class of P-loop NTPases including animal and plant regulators of programmed cell death: multiple, complex domain architectures, unusual phyletic patterns, and evolution by horizontal gene transfer.

PubMed

Leipe, Detlef D; Koonin, Eugene V; Aravind, L

2004-10-08

Using sequence profile analysis and sequence-based structure predictions, we define a previously unrecognized, widespread class of P-loop NTPases. The signal transduction ATPases with numerous domains (STAND) class includes the AP-ATPases (animal apoptosis regulators CED4/Apaf-1, plant disease resistance proteins, and bacterial AfsR-like transcription regulators) and NACHT NTPases (e.g. NAIP, TLP1, Het-E-1) that have been studied extensively in the context of apoptosis, pathogen response in animals and plants, and transcriptional regulation in bacteria. We show that, in addition to these well-characterized protein families, the STAND class includes several other groups of (predicted) NTPase domains from diverse signaling and transcription regulatory proteins from bacteria and eukaryotes, and three Archaea-specific families. We identified the STAND domain in several biologically well-characterized proteins that have not been suspected to have NTPase activity, including soluble adenylyl cyclases, nephrocystin 3 (implicated in polycystic kidney disease), and Rolling pebble (a regulator of muscle development); these findings are expected to facilitate elucidation of the functions of these proteins. The STAND class belongs to the additional strand, catalytic E division of P-loop NTPases together with the AAA+ ATPases, RecA/helicase-related ATPases, ABC-ATPases, and VirD4/PilT-like ATPases. The STAND proteins are distinguished from other P-loop NTPases by the presence of unique sequence motifs associated with the N-terminal helix and the core strand-4, as well as a C-terminal helical bundle that is fused to the NTPase domain. This helical module contains a signature GxP motif in the loop between the two distal helices. With the exception of the archaeal families, almost all STAND NTPases are multidomain proteins containing three or more domains. In addition to the NTPase domain, these proteins typically contain DNA-binding or protein-binding domains, superstructure-forming repeats, such as WD40 and TPR, and enzymatic domains involved in signal transduction, including adenylate cyclases and kinases. By analogy to the AAA+ ATPases, it can be predicted that STAND NTPases use the C-terminal helical bundle as a "lever" to transmit the conformational changes brought about by NTP hydrolysis to effector domains. STAND NTPases represent a novel paradigm in signal transduction, whereby adaptor, regulatory switch, scaffolding, and, in some cases, signal-generating moieties are combined into a single polypeptide. The STAND class consists of 14 distinct families, and the evolutionary history of most of these families is riddled with dramatic instances of lineage-specific expansion and apparent horizontal gene transfer. The STAND NTPases are most abundant in developmentally and organizationally complex prokaryotes and eukaryotes. Transfer of genes for STAND NTPases from bacteria to eukaryotes on several occasions might have played a significant role in the evolution of eukaryotic signaling systems.

Secondary structural analyses of ITS1 in Paramecium.

PubMed

Hoshina, Ryo

2010-01-01

The nuclear ribosomal RNA gene operon is interrupted by internal transcribed spacer (ITS) 1 and ITS2. Although the secondary structure of ITS2 has been widely investigated, less is known about ITS1 and its structure. In this study, the secondary structure of ITS1 sequences for Paramecium and other ciliates was predicted. Each Paramecium ITS1 forms an open loop with three helices, A through C. Helix B was highly conserved among Paramecium, and similar helices were found in other ciliates. A phylogenetic analysis using the ITS1 sequences showed high-resolution, implying that ITS1 is a good tool for species-level analyses.

Towards quantitative classification of folded proteins in terms of elementary functions.

PubMed

Hu, Shuangwei; Krokhotin, Andrei; Niemi, Antti J; Peng, Xubiao

2011-04-01

A comparative classification scheme provides a good basis for several approaches to understand proteins, including prediction of relations between their structure and biological function. But it remains a challenge to combine a classification scheme that describes a protein starting from its well-organized secondary structures and often involves direct human involvement, with an atomary-level physics-based approach where a protein is fundamentally nothing more than an ensemble of mutually interacting carbon, hydrogen, oxygen, and nitrogen atoms. In order to bridge these two complementary approaches to proteins, conceptually novel tools need to be introduced. Here we explain how an approach toward geometric characterization of entire folded proteins can be based on a single explicit elementary function that is familiar from nonlinear physical systems where it is known as the kink soliton. Our approach enables the conversion of hierarchical structural information into a quantitative form that allows for a folded protein to be characterized in terms of a small number of global parameters that are in principle computable from atomary-level considerations. As an example we describe in detail how the native fold of the myoglobin 1M6C emerges from a combination of kink solitons with a very high atomary-level accuracy. We also verify that our approach describes longer loops and loops connecting α helices with β strands, with the same overall accuracy. ©2011 American Physical Society

The interaction between the yeast telomerase RNA and the Est1 protein requires three structural elements.

PubMed

Lubin, Johnathan W; Tucey, Timothy M; Lundblad, Victoria

2012-09-01

In the budding yeast Saccharomyces cerevisiae, the telomerase enzyme is composed of a 1.3-kb TLC1 RNA that forms a complex with Est2 (the catalytic subunit) and two regulatory proteins, Est1 and Est3. Previous work has identified a conserved 5-nt bulge, present in a long helical arm of TLC1, which mediates binding of Est1 to TLC1. However, increased expression of Est1 can bypass the consequences of removal of this RNA bulge, indicating that there are additional binding site(s) for Est1 on TLC1. We report here that a conserved single-stranded internal loop immediately adjacent to the bulge is also required for the Est1-RNA interaction; furthermore, a TLC1 variant that lacks this internal loop but retains the bulge cannot be suppressed by Est1 overexpression, arguing that the internal loop may be a more critical element for Est1 binding. An additional structural feature consisting of a single-stranded region at the base of the helix containing the bulge and internal loop also contributes to recognition of TLC1 by Est1, potentially by providing flexibility to this helical arm. Association of Est1 with each of these TLC1 motifs was assessed using a highly sensitive biochemical assay that simultaneously monitors the relative levels of the Est1 and Est2 proteins in the telomerase complex. The identification of three elements of TLC1 that are required for Est1 association provides a detailed view of this particular protein-RNA interaction.

On-the-fly reduction of open loops

NASA Astrophysics Data System (ADS)

Buccioni, Federico; Pozzorini, Stefano; Zoller, Max

2018-01-01

Building on the open-loop algorithm we introduce a new method for the automated construction of one-loop amplitudes and their reduction to scalar integrals. The key idea is that the factorisation of one-loop integrands in a product of loop segments makes it possible to perform various operations on-the-fly while constructing the integrand. Reducing the integrand on-the-fly, after each segment multiplication, the construction of loop diagrams and their reduction are unified in a single numerical recursion. In this way we entirely avoid objects with high tensor rank, thereby reducing the complexity of the calculations in a drastic way. Thanks to the on-the-fly approach, which is applied also to helicity summation and for the merging of different diagrams, the speed of the original open-loop algorithm can be further augmented in a very significant way. Moreover, addressing spurious singularities of the employed reduction identities by means of simple expansions in rank-two Gram determinants, we achieve a remarkably high level of numerical stability. These features of the new algorithm, which will be made publicly available in a forthcoming release of the OpenLoops program, are particularly attractive for NLO multi-leg and NNLO real-virtual calculations.

Mitigating Communication Delays in Remotely Connected Hardware-in-the-loop Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cale, James; Johnson, Brian; Dall'Anese, Emiliano

Here, this paper introduces a potential approach for mitigating the effects of communication delays between multiple, closed-loop hardware-in-the-loop experiments which are virtually connected, yet physically separated. The method consists of an analytical method for the compensation of communication delays, along with the supporting computational and communication infrastructure. The control design leverages tools for the design of observers for the compensation of measurement errors in systems with time-varying delays. The proposed methodology is validated through computer simulation and hardware experimentation connecting hardware-in-the-loop experiments conducted between laboratories separated by a distance of over 100 km.

Mitigating Communication Delays in Remotely Connected Hardware-in-the-loop Experiments

DOE PAGES

Cale, James; Johnson, Brian; Dall'Anese, Emiliano; ...

2018-03-30

Here, this paper introduces a potential approach for mitigating the effects of communication delays between multiple, closed-loop hardware-in-the-loop experiments which are virtually connected, yet physically separated. The method consists of an analytical method for the compensation of communication delays, along with the supporting computational and communication infrastructure. The control design leverages tools for the design of observers for the compensation of measurement errors in systems with time-varying delays. The proposed methodology is validated through computer simulation and hardware experimentation connecting hardware-in-the-loop experiments conducted between laboratories separated by a distance of over 100 km.

Probing the Interaction of Brain Fatty Acid Binding Protein (B-FABP) with Model Membranes

PubMed Central

Dyszy, Fábio; Pinto, Andressa P. A.; Araújo, Ana P. U.; Costa-Filho, Antonio J.

2013-01-01

Brain fatty acid-binding protein (B-FABP) interacts with biological membranes and delivers polyunsaturated fatty acids (FAs) via a collisional mechanism. The binding of FAs in the protein and the interaction with membranes involve a motif called “portal region”, formed by two small α-helices, A1 and A2, connected by a loop. We used a combination of site-directed mutagenesis and electron spin resonance to probe the changes in the protein and in the membrane model induced by their interaction. Spin labeled B-FABP mutants and lipidic spin probes incorporated into a membrane model confirmed that B-FABP interacts with micelles through the portal region and led to structural changes in the protein as well in the micelles. These changes were greater in the presence of LPG when compared to the LPC models. ESR spectra of B-FABP labeled mutants showed the presence of two groups of residues that responded to the presence of micelles in opposite ways. In the presence of lysophospholipids, group I of residues, whose side chains point outwards from the contact region between the helices, had their mobility decreased in an environment of lower polarity when compared to the same residues in solution. The second group, composed by residues with side chains situated at the interface between the α-helices, experienced an increase in mobility in the presence of the model membranes. These modifications in the ESR spectra of B-FABP mutants are compatible with a less ordered structure of the portal region inner residues (group II) that is likely to facilitate the delivery of FAs to target membranes. On the other hand, residues in group I and micelle components have their mobilities decreased probably as a result of the formation of a collisional complex. Our results bring new insights for the understanding of the gating and delivery mechanisms of FABPs. PMID:23555925

Using Magnetic Helicity Diagnostics to Determine the Nature of Solar Active-Region Formation

NASA Astrophysics Data System (ADS)

Georgoulis, Manolis K.

Employing a novel nonlinear force-free (NLFF) method that self-consistently infers instantaneous free magnetic-energy and relative magnetic-helicity budgets from single photospheric vector magnetograms, we recently constructed the magnetic energy-helicity (EH) diagram of solar active regions. The EH diagram implies dominant relative helicities of left-handed or right-handed chiralities for the great majority of active regions. The amplitude (budget) of these helicities scales monotonically with the free magnetic energy. This constructive, strongly preferential accumulation of a certain sense of magnetic helicity seems to disqualify recently proposed mechanisms relying on a largely random near-surface convection for the formation of the great majority of active regions. The existing qualitative formation mechanism for these regions remains the conventional Omega-loop emergence following a buoyant ascension from the bottom of the convection zone. However, exceptions to this rule include even eruptive active regions: NOAA AR 11283 is an obvious outlier to the EH diagram, involving significant free magnetic energy with a small relative magnetic helicity. Relying on a timeseries of vector magnetograms of this region, our methodology shows nearly canceling amounts of both senses of helicity and an overall course from a weakly left-handed to a weakly right-handed structure, in the course of which a major eruption occurs. For this and similarly behaving active regions the latest near-surface formation scenario might conceivably be employed successfully. Research partially supported by the EU Seventh Framework Programme under grant agreement No. PIRG07-GA-2010-268245 and by the European Union Social Fund (ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program: Thales. Investing in knowledge society through the European Social Fund.

Magnetic Helicities and Dynamo Action in Magneto-rotational Turbulence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bodo, G.; Rossi, P.; Cattaneo, F.

We examine the relationship between magnetic flux generation, taken as an indicator of large-scale dynamo action, and magnetic helicity, computed as an integral over the dynamo volume, in a simple dynamo. We consider dynamo action driven by magneto-rotational turbulence (MRT) within the shearing-box approximation. We consider magnetically open boundary conditions that allow a flux of helicity in or out of the computational domain. We circumvent the problem of the lack of gauge invariance in open domains by choosing a particular gauge—the winding gauge—that provides a natural interpretation in terms of the average winding number of pairwise field lines. We usemore » this gauge precisely to define and measure the helicity and the helicity flux for several realizations of dynamo action. We find in these cases that the system as a whole does not break reflectional symmetry and that the total helicity remains small even in cases when substantial magnetic flux is generated. We find no particular connection between the generation of magnetic flux and the helicity or the helicity flux through the boundaries. We suggest that this result may be due to the essentially nonlinear nature of the dynamo processes in MRT.« less

A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

PubMed Central

Le Garrec, Jean-François; Ivanovitch, Kenzo D; Raphaël, Etienne; Bangham, J Andrew; Torres, Miguel; Coen, Enrico; Mohun, Timothy J

2017-01-01

How left-right patterning drives asymmetric morphogenesis is unclear. Here, we have quantified shape changes during mouse heart looping, from 3D reconstructions by HREM. In combination with cell labelling and computer simulations, we propose a novel model of heart looping. Buckling, when the cardiac tube grows between fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium. We have identified sequential left-right asymmetries at the poles, which bias the buckling in opposite directions, thus leading to a helical shape. Our predictive model is useful to explore the parameter space generating shape variations. The role of the dorsal mesocardium was validated in Shh-/- mutants, which recapitulate heart shape changes expected from a persistent dorsal mesocardium. Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects. PMID:29179813

The structural coupling between ATPase activation and recovery stroke in the myosin II motor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koppole, Sampath; Smith, Jeremy C; Fischer, S.

2007-07-01

Before the myosin motor head can perform the next power stroke, it undergoes a large conformational transition in which the converter domain, bearing the lever arm, rotates {approx} 65{sup o}. Simultaneous with this 'recovery stroke', myosin activates its ATPase function by closing the Switch-2 loop over the bound ATP. This coupling between the motions of the converter domain and of the 40 {angstrom}-distant Switch-2 loop is essential to avoid unproductive ATP hydrolysis. The coupling mechanism is determined here by finding a series of optimized intermediates between crystallographic end structures of the recovery stroke (Dictyostelium discoideum), yielding movies of the transitionmore » at atomic detail. The successive formation of two hydrogen bonds by the Switch-2 loop is correlated with the successive see-saw motions of the relay and SH1 helices that hold the converter domain. SH1 helix and Switch-2 loop communicate via a highly conserved loop that wedges against the SH1-helix upon Switch-2 closing.« less

A curved RNA helix incorporating an internal loop with G·A and A·A non-Watson–Crick base pairing

PubMed Central

Baeyens, Katrien J.; De Bondt, Hendrik L.; Pardi, Arthur; Holbrook, Stephen R.

1996-01-01

The crystal structure of the RNA dodecamer 5′-GGCC(GAAA)GGCC-3′ has been determined from x-ray diffraction data to 2.3-Å resolution. In the crystal, these oligomers form double helices around twofold symmetry axes. Four consecutive non-Watson–Crick base pairs make up an internal loop in the middle of the duplex, including sheared G·A pairs and novel asymmetric A·A pairs. This internal loop sequence produces a significant curvature and narrowing of the double helix. The helix is curved by 34° from end to end and the diameter is narrowed by 24% in the internal loop. A Mn2+ ion is bound directly to the N7 of the first guanine in the Watson–Crick region following the internal loop and the phosphate of the preceding residue. This Mn2+ location corresponds to a metal binding site observed in the hammerhead catalytic RNA. PMID:8917508

The structural coupling between ATPase activation and recovery stroke in the myosin II motor.

PubMed

Koppole, Sampath; Smith, Jeremy C; Fischer, Stefan

2007-07-01

Before the myosin motor head can perform the next power stroke, it undergoes a large conformational transition in which the converter domain, bearing the lever arm, rotates approximately 65 degrees . Simultaneous with this "recovery stroke," myosin activates its ATPase function by closing the Switch-2 loop over the bound ATP. This coupling between the motions of the converter domain and of the 40 A-distant Switch-2 loop is essential to avoid unproductive ATP hydrolysis. The coupling mechanism is determined here by finding a series of optimized intermediates between crystallographic end structures of the recovery stroke (Dictyostelium discoideum), yielding movies of the transition at atomic detail. The successive formation of two hydrogen bonds by the Switch-2 loop is correlated with the successive see-saw motions of the relay and SH1 helices that hold the converter domain. SH1 helix and Switch-2 loop communicate via a highly conserved loop that wedges against the SH1-helix upon Switch-2 closing.

Modulating RNA Alignment Using Directional Dynamic Kinks: Application in Determining an Atomic-Resolution Ensemble for a Hairpin using NMR Residual Dipolar Couplings.

PubMed

Salmon, Loïc; Giambaşu, George M; Nikolova, Evgenia N; Petzold, Katja; Bhattacharya, Akash; Case, David A; Al-Hashimi, Hashim M

2015-10-14

Approaches that combine experimental data and computational molecular dynamics (MD) to determine atomic resolution ensembles of biomolecules require the measurement of abundant experimental data. NMR residual dipolar couplings (RDCs) carry rich dynamics information, however, difficulties in modulating overall alignment of nucleic acids have limited the ability to fully extract this information. We present a strategy for modulating RNA alignment that is based on introducing variable dynamic kinks in terminal helices. With this strategy, we measured seven sets of RDCs in a cUUCGg apical loop and used this rich data set to test the accuracy of an 0.8 μs MD simulation computed using the Amber ff10 force field as well as to determine an atomic resolution ensemble. The MD-generated ensemble quantitatively reproduces the measured RDCs, but selection of a sub-ensemble was required to satisfy the RDCs within error. The largest discrepancies between the RDC-selected and MD-generated ensembles are observed for the most flexible loop residues and backbone angles connecting the loop to the helix, with the RDC-selected ensemble resulting in more uniform dynamics. Comparison of the RDC-selected ensemble with NMR spin relaxation data suggests that the dynamics occurs on the ps-ns time scales as verified by measurements of R(1ρ) relaxation-dispersion data. The RDC-satisfying ensemble samples many conformations adopted by the hairpin in crystal structures indicating that intrinsic plasticity may play important roles in conformational adaptation. The approach presented here can be applied to test nucleic acid force fields and to characterize dynamics in diverse RNA motifs at atomic resolution.

Pressure response of protein backbone structure. Pressure-induced amide 15N chemical shifts in BPTI.

PubMed Central

Akasaka, K.; Li, H.; Yamada, H.; Li, R.; Thoresen, T.; Woodward, C. K.

1999-01-01

The effect of pressure on amide 15N chemical shifts was studied in uniformly 15N-labeled basic pancreatic trypsin inhibitor (BPTI) in 90%1H2O/10%2H2O, pH 4.6, by 1H-15N heteronuclear correlation spectroscopy between 1 and 2,000 bar. Most 15N signals were low field shifted linearly and reversibly with pressure (0.468 +/- 0.285 ppm/2 kbar), indicating that the entire polypeptide backbone structure is sensitive to pressure. A significant variation of shifts among different amide groups (0-1.5 ppm/2 kbar) indicates a heterogeneous response throughout within the three-dimensional structure of the protein. A tendency toward low field shifts is correlated with a decrease in hydrogen bond distance on the order of 0.03 A/2 kbar for the bond between the amide nitrogen atom and the oxygen atom of either carbonyl or water. The variation of 15N shifts is considered to reflect site-specific changes in phi, psi angles. For beta-sheet residues, a decrease in psi angles by 1-2 degrees/2 kbar is estimated. On average, shifts are larger for helical and loop regions (0.553 +/- 0.343 and 0.519 +/- 0.261 ppm/2 kbar, respectively) than for beta-sheet (0.295 +/- 0.195 ppm/2 kbar), suggesting that the pressure-induced structural changes (local compressibilities) are larger in helical and loop regions than in beta-sheet. Because compressibility is correlated with volume fluctuation, the result is taken to indicate that the volume fluctuation is larger in helical and loop regions than in beta-sheet. An important aspect of the volume fluctuation inferred from pressure shifts is that they include motions in slower time ranges (less than milliseconds) in which many biological processes may take place. PMID:10548039

Standard model light-by-light scattering in SANC: Analytic and numeric evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bardin, D. Yu., E-mail: bardin@nu.jinr.ru; Kalinovskaya, L. V., E-mail: kalinov@nu.jinr.ru; Uglov, E. D., E-mail: corner@nu.jinr.r

2010-11-15

The implementation of the Standard Model process {gamma}{gamma} {yields} {gamma}{gamma} through a fermion and boson loop into the framework of SANC system and additional precomputation modules used for calculation of massive box diagrams are described. The computation of this process takes into account nonzero mass of loop particles. The covariant and helicity amplitudes for this process, some particular cases of D{sub 0} and C{sub 0} Passarino-Veltman functions, and also numerical results of corresponding SANC module evaluation are presented. Whenever possible, the results are compared with those existing in the literature.

Dislocation dynamics simulations of interactions between gliding dislocations and radiation induced prismatic loops in zirconium

NASA Astrophysics Data System (ADS)

Drouet, Julie; Dupuy, Laurent; Onimus, Fabien; Mompiou, Frédéric; Perusin, Simon; Ambard, Antoine

2014-06-01

The mechanical behavior of Pressurized Water Reactor fuel cladding tubes made of zirconium alloys is strongly affected by neutron irradiation due to the high density of radiation induced dislocation loops. In order to investigate the interaction mechanisms between gliding dislocations and loops in zirconium, a new nodal dislocation dynamics code, adapted to Hexagonal Close Packed metals, has been used. Various configurations have been systematically computed considering different glide planes, basal or prismatic, and different characters, edge or screw, for gliding dislocations with -type Burgers vectors. Simulations show various interaction mechanisms such as (i) absorption of a loop on an edge dislocation leading to the formation of a double super-jog, (ii) creation of a helical turn, on a screw dislocation, that acts as a strong pinning point or (iii) sweeping of a loop by a gliding dislocation. It is shown that the clearing of loops is more favorable when the dislocation glides in the basal plane than in the prismatic plane explaining the easy dislocation channeling in the basal plane observed after neutron irradiation by transmission electron microscopy.

Plant tendrils: Nature's hygroscopic springs

NASA Astrophysics Data System (ADS)

Gerbode, Sharon; Puzey, Joshua; McCormick, Andrew; Mahadevan, L.

2012-02-01

Plant tendrils are specialized climbing organs that have fascinated biologists and physicists alike for centuries. Initially straight tendrils attach at the tip to an elevated rigid support and then winch the plant upward by coiling into a helical morphology characterized by two helices of opposite handedness connected by a helical perversion. In his renowned treatise on twining and tendril-bearing plants, Charles Darwin surmised that coiled tendrils serve as soft, springy attachments for the climbing plant. Yet, the true effect of the perverted helical shape of a coiled plant tendril has not been fully revealed. Using a combination of experiments on Cucurbitaceae tendrils, physical models constructed from strained rubber sheets, and numerical models of helical perversions, we have uncovered that tendril coiling occurs via anisotropic shrinkage of a strip of specialized cells in the interior of the tendril. Furthermore, variations in the mechanical behavior of tendrils as they become drier and ``woodier'' adds a new twist to the story of tendril coiling.

Circulating heat exchangers for oscillating wave engines and refrigerators

DOEpatents

Swift, Gregory W.; Backhaus, Scott N.

2003-10-28

An oscillating-wave engine or refrigerator having a regenerator or a stack in which oscillating flow of a working gas occurs in a direction defined by an axis of a trunk of the engine or refrigerator, incorporates an improved heat exchanger. First and second connections branch from the trunk at locations along the axis in selected proximity to one end of the regenerator or stack, where the trunk extends in two directions from the locations of the connections. A circulating heat exchanger loop is connected to the first and second connections. At least one fluidic diode within the circulating heat exchanger loop produces a superimposed steady flow component and oscillating flow component of the working gas within the circulating heat exchanger loop. A local process fluid is in thermal contact with an outside portion of the circulating heat exchanger loop.

Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures.

PubMed

Sloma, Michael F; Mathews, David H

2016-12-01

RNA secondary structure prediction is widely used to analyze RNA sequences. In an RNA partition function calculation, free energy nearest neighbor parameters are used in a dynamic programming algorithm to estimate statistical properties of the secondary structure ensemble. Previously, partition functions have largely been used to estimate the probability that a given pair of nucleotides form a base pair, the conditional stacking probability, the accessibility to binding of a continuous stretch of nucleotides, or a representative sample of RNA structures. Here it is demonstrated that an RNA partition function can also be used to calculate the exact probability of formation of hairpin loops, internal loops, bulge loops, or multibranch loops at a given position. This calculation can also be used to estimate the probability of formation of specific helices. Benchmarking on a set of RNA sequences with known secondary structures indicated that loops that were calculated to be more probable were more likely to be present in the known structure than less probable loops. Furthermore, highly probable loops are more likely to be in the known structure than the set of loops predicted in the lowest free energy structures. © 2016 Sloma and Mathews; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

The growth pattern of the human intestine and its mesentery.

PubMed

Soffers, Jelly H M; Hikspoors, Jill P J M; Mekonen, Hayelom K; Koehler, S Eleonore; Lamers, Wouter H

2015-08-22

It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. We distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1st secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2nd secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3rd and 4th secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4th secondary loop (distal ileum, cecum) rapidly "slid" into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin. The interpretation of "intestinal rotation" as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of "en-bloc rotation" of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.

NON-POTENTIAL FIELDS IN THE QUIET SUN NETWORK: EXTREME-ULTRAVIOLET AND MAGNETIC FOOTPOINT OBSERVATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chesny, D. L.; Oluseyi, H. M.; Orange, N. B.

The quiet Sun (QS) magnetic network is known to contain dynamics which are indicative of non-potential fields. Non-potential magnetic fields forming ''S-shaped'' loop arcades can lead to the breakdown of static activity and have only been observed in high temperature X-ray coronal structures—some of which show eruptive behavior. Thus, analysis of this type of atmospheric structuring has been restricted to large-scale coronal fields. Here we provide the first identification of non-potential loop arcades exclusive to the QS supergranulation network. High-resolution Atmospheric Imaging Assembly data from the Solar Dynamics Observatory have allowed for the first observations of fine-scale ''S-shaped'' loop arcadesmore » spanning the network. We have investigated the magnetic footpoint flux evolution of these arcades from Heliospheric and Magnetic Imager data and find evidence of evolving footpoint flux imbalances accompanying the formation of these non-potential fields. The existence of such non-potentiality confirms that magnetic field dynamics leading to the build up of helicity exist at small scales. QS non-potentiality also suggests a self-similar formation process between the QS network and high temperature corona and the existence of self-organized criticality (SOC) in the form of loop-pair reconnection and helicity dissipation. We argue that this type of behavior could lead to eruptive forms of SOC as seen in active region (AR) and X-ray sigmoids if sufficient free magnetic energy is available. QS magnetic network dynamics may be considered as a coronal proxy at supergranular scales, and events confined to the network can even mimic those in coronal ARs.« less

Effects of magnesium ions on the stabilization of RNA oligomers of defined structures.

PubMed Central

Serra, Martin J; Baird, John D; Dale, Taraka; Fey, Bridget L; Retatagos, Kimberly; Westhof, Eric

2002-01-01

Optical melting was used to determine the stabilities of 11 small RNA oligomers of defined secondary structure as a function of magnesium ion concentration. The oligomers included helices composed of Watson-Crick base pairs, GA tandem base pairs, GU tandem base pairs, and loop E motifs (both eubacterial and eukaryotic). The effect of magnesium ion concentration on stability was interpreted in terms of two simple models. The first assumes an uptake of metal ion upon duplex formation. The second assumes nonspecific electrostatic attraction of metal ions to the RNA oligomer. For all oligomers, except the eubacterial loop E, the data could best be interpreted as nonspecific binding of metal ions to the RNAs. The effect of magnesium ions on the stability of the eubacterial loop E was distinct from that seen with the other oligomers in two ways. First, the extent of stabilization by magnesium ions (as measured by either change in melting temperature or free energy) was three times greater than that observed for the other helical oligomers. Second, the presence of magnesium ions produces a doubling of the enthalpy for the melting transition. These results indicate that magnesium ion stabilizes the eubacterial loop E sequence by chelating the RNA specifically. Further, these results on a rather small system shed light on the large enthalpy changes observed upon thermal unfolding of large RNAs like group I introns. It is suggested that parts of those large enthalpy changes observed in the folding of RNAs may be assigned to variations in the hydration states and types of coordinating atoms in some specifically bound magnesium ions and to an increase in the observed cooperativity of the folding transition due to the binding of those magnesium ions coupling the two stems together. Brownian dynamic simulations, carried out to visualize the metal ion binding sites, reveal rather delocalized ionic densities in all oligomers, except for the eubacterial loop E, in which precisely located ion densities were previously calculated. PMID:12003491

Structural features of the DNA hairpin d(ATCCTA-GTTA-TAGGAT): formation of a G-A base pair in the loop.

PubMed Central

van Dongen, M J; Mooren, M M; Willems, E F; van der Marel, G A; van Boom, J H; Wijmenga, S S; Hilbers, C W

1997-01-01

The three-dimensional structure of the hairpin formed by d(ATCCTA-GTTA-TAGGAT) has been determined by means of two-dimensional NMR studies, distance geometry and molecular dynamics calculations. The first and the last residues of the tetraloop of this hairpin form a sheared G-A base pair on top of the six Watson-Crick base pairs in the stem. The glycosidic torsion angles of the guanine and adenine residues in the G-A base pair reside in the anti and high- anti domain ( approximately -60 degrees ) respectively. Several dihedral angles in the loop adopt non-standard values to accommodate this base pair. The first and second residue in the loop are stacked in a more or less normal helical fashion; the fourth loop residue also stacks upon the stem, while the third residue is directed away from the loop region. The loop structure can be classified as a so-called type-I loop, in which the bases at the 5'-end of the loop stack in a continuous fashion. In this situation, loop stability is unlikely to depend heavily on the nature of the unpaired bases in the loop. Moreover, the present study indicates that the influence of the polarity of a closing A.T pair is much less significant than that of a closing C.G base pair. PMID:9092659

Tubular Crystals and Helical Arrays: Structural Determination of HIV-1 Capsid Assemblies Using Iterative Helical Real-Space Reconstruction

PubMed Central

Zhang, Peijun; Meng, Xin; Zhao, Gongpu

2013-01-01

Helical structures are important in many different life forms and are well-suited for structural studies by cryo-EM. A unique feature of helical objects is that a single projection image contains all the views needed to perform a three-dimensional (3D) crystallographic reconstruction. Here, we use HIV-1 capsid assemblies to illustrate the detailed approaches to obtain 3D density maps from helical objects. Mature HIV-1 particles contain a conical- or tubular-shaped capsid that encloses the viral RNA genome and performs essential functions in the virus life cycle. The capsid is composed of capsid protein (CA) oligomers which are helically arranged on the surface. The N-terminal domain (NTD) of CA is connected to its C-terminal domain (CTD) through a flexible hinge. Structural analysis of two- and three-dimensional crystals provided molecular models of the capsid protein (CA) and its oligomer forms. We determined the 3D density map of helically assembled HIV-1 CA hexamers at 16 Å resolution using an iterative helical real-space reconstruction method. Docking of atomic models of CA-NTD and CA-CTD dimer into the electron density map indicated that the CTD dimer interface is retained in the assembled CA. Furthermore, molecular docking revealed an additional, novel CTD trimer interface. PMID:23132072

Free-fall dynamics of a pair of rigidly linked disks

NASA Astrophysics Data System (ADS)

Kim, Taehyun; Chang, Jaehyeock; Kim, Daegyoum

2018-03-01

We investigate experimentally the free-fall motion of a pair of identical disks rigidly connected to each other. The three-dimensional coordinates of the pair of falling disks were constructed to quantitatively describe its trajectory, and the flow structure formed by the disk pair was identified by using dye visualization. The rigidly linked disk pair exhibits a novel falling pattern that creates a helical path with a conical configuration in which the lower disk rotates in a wider radius than the upper disk with respect to a vertical axis. The helical motion occurs consistently for the range of disk separation examined in this study. The dye visualization reveals that a strong, noticeable helical vortex core is generated from the outer tip of the lower disk during the helical motion. With an increasing length ratio, which is the ratio of the disk separation to the diameter of the disks, the nutation angle and the rate of change in the precession angle that characterize the combined helical and conical kinematics decrease linearly, whereas the pitch of the helical path increases linearly. Although all disk pairs undergo this helical motion, the horizontal-drift patterns of the disk pair depend on the length ratio.

Dipole Alignment in Rotating MHD Turbulence

NASA Technical Reports Server (NTRS)

Shebalin, John V.; Fu, Terry; Morin, Lee

2012-01-01

We present numerical results from long-term CPU and GPU simulations of rotating, homogeneous, magnetohydrodynamic (MHD) turbulence, and discuss their connection to the spherically bounded case. We compare our numerical results with a statistical theory of geodynamo action that has evolved from the absolute equilibrium ensemble theory of ideal MHD turbulence, which is based on the ideal MHD invariants are energy, cross helicity and magnetic helicity. However, for rotating MHD turbulence, the cross helicity is no longer an exact invariant, although rms cross helicity becomes quasistationary during an ideal MHD simulation. This and the anisotropy imposed by rotation suggests an ansatz in which an effective, nonzero value of cross helicity is assigned to axisymmetric modes and zero cross helicity to non-axisymmetric modes. This hybrid statistics predicts a large-scale quasistationary magnetic field due to broken ergodicity , as well as dipole vector alignment with the rotation axis, both of which are observed numerically. We find that only a relatively small value of effective cross helicity leads to the prediction of a dipole moment vector that is closely aligned (less than 10 degrees) with the rotation axis. We also discuss the effect of initial conditions, dissipation and grid size on the numerical simulations and statistical theory.

Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore*

PubMed Central

El Hiani, Yassine; Linsdell, Paul

2015-01-01

As an ion channel, the cystic fibrosis transmembrane conductance regulator must form a continuous pathway for the movement of Cl− and other anions between the cytoplasm and the extracellular solution. Both the structure and the function of the membrane-spanning part of this pathway are well defined. In contrast, the structure of the pathway that connects the cytoplasm to the membrane-spanning regions is unknown, and functional roles for different parts of the protein forming this pathway have not been described. We used patch clamp recording and substituted cysteine accessibility mutagenesis to identify positively charged amino acid side chains that attract cytoplasmic Cl− ions to the inner mouth of the pore. Our results indicate that the side chains of Lys-190, Arg-248, Arg-303, Lys-370, Lys-1041, and Arg-1048, located in different intracellular loops of the protein, play important roles in the electrostatic attraction of Cl− ions. Mutation and covalent modification of these residues have charge-dependent effects on the rate of Cl− permeation, demonstrating their functional role in maximization of Cl− flux. Other nearby positively charged side chains were not involved in electrostatic interactions with Cl−. The location of these Cl−-attractive residues suggests that cytoplasmic Cl− ions enter the pore via a lateral portal located between the cytoplasmic extensions to the fourth and sixth transmembrane helices; a secondary, functionally less relevant portal might exist between the extensions to the 10th and 12th transmembrane helices. These results define the cytoplasmic mouth of the pore and show how it attracts Cl− ions from the cytoplasm. PMID:25944907

Power in the loop real time simulation platform for renewable energy generation

NASA Astrophysics Data System (ADS)

Li, Yang; Shi, Wenhui; Zhang, Xing; He, Guoqing

2018-02-01

Nowadays, a large scale of renewable energy sources has been connecting to power system and the real time simulation platform is widely used to carry out research on integration control algorithm, power system stability etc. Compared to traditional pure digital simulation and hardware in the loop simulation, power in the loop simulation has higher accuracy and degree of reliability. In this paper, a power in the loop analog digital hybrid simulation platform has been built and it can be used not only for the single generation unit connecting to grid, but also for multiple new energy generation units connecting to grid. A wind generator inertia control experiment was carried out on the platform. The structure of the inertia control platform was researched and the results verify that the platform is up to need for renewable power in the loop real time simulation.

Role of a continuous MHD dynamo in the formation of 3D equilibria in fusion plasmas

NASA Astrophysics Data System (ADS)

Piovesan, P.; Bonfiglio, D.; Cianciosa, M.; Luce, T. C.; Taylor, N. Z.; Terranova, D.; Turco, F.; Wilcox, R. S.; Wingen, A.; Cappello, S.; Chrystal, C.; Escande, D. F.; Holcomb, C. T.; Marrelli, L.; Paz-Soldan, C.; Piron, L.; Predebon, I.; Zaniol, B.; DIII-D, The; RFX-Mod Teams

2017-07-01

Stationary 3D equilibria can form in fusion plasmas via saturation of magnetohydrodynamic (MHD) instabilities or stimulated by external 3D fields. In these cases the current profile is anomalously broad due to magnetic flux pumping produced by the MHD modes. Flux pumping plays an important role in hybrid tokamak plasmas, maintaining the minimum safety factor above unity and thus removing sawteeth. It also enables steady-state hybrid operation, by redistributing non-inductive current driven near the center by electron cyclotron waves. A validated flux pumping model is not yet available, but it would be necessary to extrapolate hybrid operation to future devices. In this work flux pumping physics is investigated for helical core equilibria stimulated by external 3D fields in DIII-D hybrid plasmas. We show that flux pumping can be produced in a continuous way by an MHD dynamo emf. The same effect maintains helical equilibria in reversed-field pinch (RFP) plasmas. The effective MHD dynamo loop voltage is calculated for experimental 3D equilibrium reconstructions, by balancing Ohm’s law over helical flux surfaces, and is consistent with the expected current redistribution. Similar results are also obtained with more sophisticated nonlinear MHD simulations. The same modelling approach is applied to helical RFP states forming spontaneously in RFX-mod as the plasma current is raised above 0.8-1 MA. This comparison allows to identify the underlying physics common to tokamak and RFP: a helical core displacement modulates parallel current density along flux tubes, which requires a helical electrostatic potential to build up, giving rise to a helical MHD dynamo flow.

Common and divergent structural features of a series of corticotropin releasing factor-related peptides.

PubMed

Grace, Christy Rani R; Perrin, Marilyn H; Cantle, Jeffrey P; Vale, Wylie W; Rivier, Jean E; Riek, Roland

2007-12-26

Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

Role of a continuous MHD dynamo in the formation of 3D equilibria in fusion plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piovesan, P.; Bonfiglio, D.; Cianciosa, M.

Stationary 3D equilibria can form in fusion plasmas via saturation of magnetohydrodynamic (MHD) instabilities or stimulated by external 3D fields. In these cases the current profile is anomalously broad due to magnetic flux pumping produced by the MHD modes. Flux pumping plays an important role in hybrid tokamak plasmas, maintaining the minimum safety factor above unity and thus removing sawteeth. It also enables steady-state hybrid operation, by redistributing non-inductive current driven near the center by electron cyclotron waves. A validated flux pumping model is not yet available, but it would be necessary to extrapolate hybrid operation to future devices. Inmore » this work flux pumping physics is investigated for helical core equilibria stimulated by external 3D fields in DIII-D hybrid plasmas. We show that flux pumping can be produced in a continuous way by an MHD dynamo emf. The same effect maintains helical equilibria in reversed-field pinch (RFP) plasmas. The effective MHD dynamo loop voltage is calculated for experimental 3D equilibrium reconstructions, by balancing Ohm’s law over helical flux surfaces, and is consistent with the expected current redistribution. Similar results are also obtained with more sophisticated nonlinear MHD simulations. The same modelling approach is applied to helical RFP states forming spontaneously in RFX-mod as the plasma current is raised above 0.8–1 MA. This comparison allows to identify the underlying physics common to tokamak and RFP: a helical core displacement modulates parallel current density along flux tubes, which requires a helical electrostatic potential to build up, giving rise to a helical MHD dynamo flow.« less

Role of a continuous MHD dynamo in the formation of 3D equilibria in fusion plasmas

DOE PAGES

Piovesan, P.; Bonfiglio, D.; Cianciosa, M.; ...

2017-04-28

Stationary 3D equilibria can form in fusion plasmas via saturation of magnetohydrodynamic (MHD) instabilities or stimulated by external 3D fields. In these cases the current profile is anomalously broad due to magnetic flux pumping produced by the MHD modes. Flux pumping plays an important role in hybrid tokamak plasmas, maintaining the minimum safety factor above unity and thus removing sawteeth. It also enables steady-state hybrid operation, by redistributing non-inductive current driven near the center by electron cyclotron waves. A validated flux pumping model is not yet available, but it would be necessary to extrapolate hybrid operation to future devices. Inmore » this work flux pumping physics is investigated for helical core equilibria stimulated by external 3D fields in DIII-D hybrid plasmas. We show that flux pumping can be produced in a continuous way by an MHD dynamo emf. The same effect maintains helical equilibria in reversed-field pinch (RFP) plasmas. The effective MHD dynamo loop voltage is calculated for experimental 3D equilibrium reconstructions, by balancing Ohm’s law over helical flux surfaces, and is consistent with the expected current redistribution. Similar results are also obtained with more sophisticated nonlinear MHD simulations. The same modelling approach is applied to helical RFP states forming spontaneously in RFX-mod as the plasma current is raised above 0.8–1 MA. This comparison allows to identify the underlying physics common to tokamak and RFP: a helical core displacement modulates parallel current density along flux tubes, which requires a helical electrostatic potential to build up, giving rise to a helical MHD dynamo flow.« less

A generalized analysis of hydrophobic and loop clusters within globular protein sequences

PubMed Central

Eudes, Richard; Le Tuan, Khanh; Delettré, Jean; Mornon, Jean-Paul; Callebaut, Isabelle

2007-01-01

Background Hydrophobic Cluster Analysis (HCA) is an efficient way to compare highly divergent sequences through the implicit secondary structure information directly derived from hydrophobic clusters. However, its efficiency and application are currently limited by the need of user expertise. In order to help the analysis of HCA plots, we report here the structural preferences of hydrophobic cluster species, which are frequently encountered in globular domains of proteins. These species are characterized only by their hydrophobic/non-hydrophobic dichotomy. This analysis has been extended to loop-forming clusters, using an appropriate loop alphabet. Results The structural behavior of hydrophobic cluster species, which are typical of protein globular domains, was investigated within banks of experimental structures, considered at different levels of sequence redundancy. The 294 more frequent hydrophobic cluster species were analyzed with regard to their association with the different secondary structures (frequencies of association with secondary structures and secondary structure propensities). Hydrophobic cluster species are predominantly associated with regular secondary structures, and a large part (60 %) reveals preferences for α-helices or β-strands. Moreover, the analysis of the hydrophobic cluster amino acid composition generally allows for finer prediction of the regular secondary structure associated with the considered cluster within a cluster species. We also investigated the behavior of loop forming clusters, using a "PGDNS" alphabet. These loop clusters do not overlap with hydrophobic clusters and are highly associated with coils. Finally, the structural information contained in the hydrophobic structural words, as deduced from experimental structures, was compared to the PSI-PRED predictions, revealing that β-strands and especially α-helices are generally over-predicted within the limits of typical β and α hydrophobic clusters. Conclusion The dictionary of hydrophobic clusters described here can help the HCA user to interpret and compare the HCA plots of globular protein sequences, as well as provides an original fundamental insight into the structural bricks of protein folds. Moreover, the novel loop cluster analysis brings additional information for secondary structure prediction on the whole sequence through a generalized cluster analysis (GCA), and not only on regular secondary structures. Such information lays the foundations for developing a new and original tool for secondary structure prediction. PMID:17210072

Deformation of a soft helical filament in an axial flow at low Reynolds number.

PubMed

Jawed, Mohammad K; Reis, Pedro M

2016-02-14

We perform a numerical investigation of the deformation of a rotating helical filament subjected to an axial flow, under low Reynolds number conditions, motivated by the propulsion of bacteria using helical flagella. Given its slenderness, the helical rod is intrinsically soft and deforms due to the interplay between elastic forces and hydrodynamic loading. We make use of a previously developed and experimentally validated computational tool framework that models the elasticity of the filament using the discrete elastic rod method and the fluid forces are treated using Lighthill's slender body theory. Under axial flow, and in the absence of rotation, the initially helical rod is extended. Above a critical flow speed its configuration comprises a straight portion connected to a localized helix near the free end. When the rod is also rotated about its helical axis, propulsion is only possible in a finite range of angular velocity, with an upper bound that is limited by buckling of the soft helix arising due to viscous stresses. A systematic exploration of the parameter space allows us to quantify regimes for successful propulsion for a number of specific bacteria.

Controllable rotational inversion in nanostructures with dual chirality.

PubMed

Dai, Lu; Zhu, Ka-Di; Shen, Wenzhong; Huang, Xiaojiang; Zhang, Li; Goriely, Alain

2018-04-05

Chiral structures play an important role in natural sciences due to their great variety and potential applications. A perversion connecting two helices with opposite chirality creates a dual-chirality helical structure. In this paper, we develop a novel model to explore quantitatively the mechanical behavior of normal, binormal and transversely isotropic helical structures with dual chirality and apply these ideas to known nanostructures. It is found that both direction and amplitude of rotation can be finely controlled by designing the cross-sectional shape. A peculiar rotational inversion of overwinding followed by unwinding, observed in some gourd and cucumber tendril perversions, not only exists in transversely isotropic dual-chirality helical nanobelts, but also in the binormal/normal ones when the cross-sectional aspect ratio is close to 1. Beyond this rotational inversion region, the binormal and normal dual-chirality helical nanobelts exhibit a fixed directional rotation of unwinding and overwinding, respectively. Moreover, in the binormal case, the rotation of these helical nanobelts is nearly linear, which is promising as a possible design for linear-to-rotary motion converters. The present work suggests new designs for nanoscale devices.

Two new frameworks of potassium saccharate obtained from acidic and alkaline solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lv, Yao-Kang; Feng, Yun-Long, E-mail: sky37@zjnu.edu.c; Liu, Ji-Wei

2011-05-15

Two chiral K(I) complexes based on D-saccharic acid (H{sub 2}sac), [K(Hsac)]{sub n} (1) and [K{sub 2}(sac)]{sub n} (2) were obtained from acidic and alkaline solution. The 3D framework of 1 includes K(I) polyhedral rods and typical pairwise coaxial right- and left-handed helical chains, and displays binodal 6-connected pcu topology. 2 contains 2D polyhedral sheets consisting of left-handed helical chains, and generates 3D network with an unprecedented (7,11)-connected net. Cyclic voltammetry tests and charge-discharge tests indicate that the addition of complex 2 to the electrolyte could improve the electrochemical properties of the nickel hydroxide electrode. -- Graphical abstract: Two K(I) complexesmore » based on D-saccharic acid (H{sub 2}sac), [K(Hsac)]{sub n} (1) and [K{sub 2}(sac)]{sub n} (2) were obtained and characterized. Electrochemical studies indicate the potential use of 2 in Ni-MH battery. Display Omitted highlights: > Two novel chiral K(I) frameworks based on D-saccharic acid were obtained. > The structure of 1 includes K(I) polyhedral rods and typical helical chains. > 2 contains 2D polyhedral sheets and generates an unprecedented (7,11)-connected net. > Addition of 2 to electrolyte could improve the nickel hydroxide electrode's property.« less

A double chain reversal loop and two diagonal loops define the architecture of a unimolecular DNA quadruplex containing a pair of stacked G(syn)-G(syn)-G(anti)-G(anti) tetrads flanked by a G-(T-T) Triad and a T-T-T triple.

PubMed

Kuryavyi, V; Majumdar, A; Shallop, A; Chernichenko, N; Skripkin, E; Jones, R; Patel, D J

2001-06-29

The architecture of G-G-G-G tetrad-aligned DNA quadruplexes in monovalent cation solution is dependent on the directionality of the four strands, which in turn are defined by loop connectivities and the guanine syn/anti distribution along individual strands and within individual G-G-G-G tetrads. The smallest unimolecular G-quadruplex belongs to the d(G2NnG2NnG2NnG2) family, which has the potential to form two stacked G-tetrads linked by Nn loop connectivities. Previous studies have focused on the thrombin-binding DNA aptamer d(G2T2G2TGTG2T2G2), where Nn was T2 for the first and third connecting loops and TGT for the middle connecting loop. This DNA aptamer in K(+) cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)-G(anti)-G(syn)-G(anti) tetrads, adjacent strands which are antiparallel to each other and edge-wise connecting T2, TGT and T2 loops. We now report on the NMR-based solution structure of the d(G2T4G2CAG2GT4G2T) sequence, which differs from the thrombin-binding DNA aptamer sequence in having longer first (T4) and third (GT4) loops and a shorter (CA) middle loop. This d(G2T4G2CAG2GT4G2T) sequence in Na(+) cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)-G(syn)-G(anti)-G(anti) tetrads, adjacent strands which have one parallel and one antiparallel neighbors and distinct non-edge-wise loop connectivities. Specifically, the longer first (T4) and third (GT4) loops are of the diagonal type while the shorter middle loop is of the double chain reversal type. In addition, the pair of stacked G-G-G-G tetrads are flanked on one side by a G-(T-T) triad and on the other side by a T-T-T triple. The distinct differences in strand directionalities, loop connectivities and syn/anti distribution within G-G-G-G tetrads between the thrombin-binding DNA aptamer d(G2T2G2TGTG2T2G2) quadruplex reported previously, and the d(G2T4G2CAG2GT4G2T) quadruplex reported here, reinforces the polymorphic nature of higher-order DNA architectures. Further, these two small unimolecular G-quadruplexes, which are distinct from each other and from parallel-stranded G-quadruplexes, provide novel targets for ligand recognition. Our results demonstrate that the double chain reversal loop connectivity identified previously by our laboratory within the Tetrahymena telomere d(T2G4)4 quadruplex, is a robust folding topology, since it has now also been observed within the d(G2T4G2CAG2GT4G2T) quadruplex. The identification of a G-(T-T) triad and a T-T-T triple, expands on the available recognition alignments for base triads and triples. Copyright 2001 Academic Press.

Vortex multiplication in applied flow: A precursor to superfluid turbulence.

PubMed

Finne, A P; Eltsov, V B; Eska, G; Hänninen, R; Kopu, J; Krusius, M; Thuneberg, E V; Tsubota, M

2006-03-03

A surface-mediated process is identified in 3He-B which generates vortices at a roughly constant rate. It precedes a faster form of turbulence where intervortex interactions dominate. This precursor becomes observable when vortex loops are introduced in low-velocity rotating flow at sufficiently low mutual friction dissipation at temperatures below 0.5Tc. Our measurements indicate that the formation of new loops is associated with a single vortex interacting in the applied flow with the sample boundary. Numerical calculations show that the single-vortex instability arises when a helical Kelvin wave expands from a reconnection kink at the wall and then intersects again with the wall.

Coronal loops and active region structure

NASA Technical Reports Server (NTRS)

Webb, D. F.; Zirin, H.

1981-01-01

Synoptic H-alpha Ca K, magnetograph and Skylab soft X-ray and EUV data were compared for the purpose of identifying the basic coronal magnetic structure of loops in a 'typical' active region and studying its evolution. A complex of activity in July 1973, especially McMath 12417, was emphasized. The principal results are: (1) most of the brightest loops connected the bright f plage to either the sunspot penumbra or to p satellite spots; no non-flaring X-ray loops end in umbrae; (2) short, bright loops had one or both ends in regions of emergent flux, strong field or high field gradients; (3) stable, strongly sheared loop arcades formed over filaments; (4) EFRs were always associated with compact X-ray arcades; and (5) loops connecting to other active regions had their bases in outlying plage of weak field strength in McM 417 where H-alpha fibrils marked the direction of the loops

The RNase P RNA from cyanobacteria: short tandemly repeated repetitive (STRR) sequences are present within the RNase P RNA gene in heterocyst-forming cyanobacteria.

PubMed Central

Vioque, A

1997-01-01

The RNase P RNA gene (rnpB) from 10 cyanobacteria has been characterized. These new RNAs, together with the previously available ones, provide a comprehensive data set of RNase P RNA from diverse cyanobacterial lineages. All heterocystous cyanobacteria, but none of the non-heterocystous strains analyzed, contain short tandemly repeated repetitive (STRR) sequences that increase the length of helix P12. Site-directed mutagenesis experiments indicate that the STRR sequences are not required for catalytic activity in vitro. STRR sequences seem to have recently and independently invaded the RNase P RNA genes in heterocyst-forming cyanobacteria because closely related strains contain unrelated STRR sequences. Most cyanobacteria RNase P RNAs lack the sequence GGU in the loop connecting helices P15 and P16 that has been established to interact with the 3'-end CCA in precursor tRNA substrates in other bacteria. This character is shared with plastid RNase P RNA. Helix P6 is longer than usual in most cyanobacteria as well as in plastid RNase P RNA. PMID:9254706

Tornado-Like Evolution of A Kink-Unstable Solar Prominence

NASA Astrophysics Data System (ADS)

Wang, W.; Liu, R.; Wang, Y.

2016-12-01

We report on the tornado-like evolution of a quiescent prominence on 2014 November 1. The evolution started with a slow rise of the eastern section of the prominence into an arch-shaped structure as high as 150 Mm above the limb, and then the arch experienced a moderate, left-handed writhing. Following the writhing, the originally dark prominence material became in emission in the Fe IX 171 °A passband, and a braiding structure appeared at the eastern edge of the writhing prominence body, whose unraveling process was associated with a transient brightening in EUV and apparently contributed to the formation of a curtain-like structure (CLS), which consisted of myriads of thread-like loops rotating counterclockwise about the vertical if viewed from above. Material sliding along these loops landed outside of the prominence channel. The tornado was eventually disintegrated and the remaining material flew along a lefthanded helical path of approximately a full turn, as confirmed through stereoscopic reconstruction, into the cavity of the stable, western section of the prominence. We suggest that the tornado-like evolution of the prominence was regulated by the helical kink instability, and that the CLS forms through magnetic reconnections between the flux-rope flux and the overlying flux.

NMR structural study of the intracellular loop 3 of the serotonin 5-HT(1A) receptor and its interaction with calmodulin.

PubMed

Chen, Angela Shuyi; Kim, Young Mee; Gayen, Shovanlal; Huang, Qiwei; Raida, Manfred; Kang, Congbao

2011-09-01

The serotonin (5-HT(1A)) receptor, a G-protein-coupled receptor (GPCR), plays important roles in serotonergic signaling in the central nervous system. The third intracellular loop (ICL3) of the 5-HT(1A) receptor has been shown to be important for the regulation of this receptor through interactions with proteins such as G-proteins and calmodulin. In this study, the ICL3 of 5-HT(1A) receptor was expressed in E. coli and purified. Gel filtration and mass spectrometry were used to confirm the molecular weight of the purified ICL3. Secondary structure analysis using circular dichroism (CD) demonstrated the presence of α-helical structures. Backbone assignment of ICL3 was achieved using three-dimensional experiments. A chemical shift index and Talos+ analysis showed that residues E326 to R339 form α-helical structure. Residues G256 to S269 of ICL3 were shown to be a novel region that has a molecular interaction with calmodulin in titration assays. Peptide derived from the ICL3 containing residues from G256 to S269 also showed molecular interaction with calmodulin. Copyright © 2011 Elsevier B.V. All rights reserved.

Tornado-like Evolution of a Kink-unstable Solar Prominence

NASA Astrophysics Data System (ADS)

Wang, Wensi; Liu, Rui; Wang, Yuming

2017-01-01

We report on the tornado-like evolution of a quiescent prominence on 2014 November 1. The eastern section of the prominence first rose slowly, transforming into an arch-shaped structure as high as ˜150 Mm above the limb; the arch then writhed moderately in a left-handed sense, while the original dark prominence material emitted in the Fe ix 171 Å passband, and a braided structure appeared at the eastern edge of the warped arch. The unraveling of the braided structure was associated with a transient brightening in the EUV and apparently contributed to the formation of a curtain-like structure (CLS). The CLS consisted of myriad thread-like loops rotating counterclockwise about the vertical if viewed from above. Heated prominence material was observed to slide along these loops and land outside the filament channel. The tornado eventually disintegrated and the remaining material flew along a left-handed helical path constituting approximately a full turn, as corroborated through stereoscopic reconstruction, into the cavity of the stable, western section of the prominence. We suggest that the tornado-like evolution of the prominence was governed by the helical kink instability, and that the CLS formed through magnetic reconnections between the prominence field and the overlying coronal field.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Yao; Tan, Kemin; Chhor, Gekleng

The EsxB protein from Bacillus anthracis belongs to the WXG100 family, a group of proteins secreted by a specialized secretion system. We have determined the crystal structures of recombinant EsxB and discovered that the small protein (~10 kDa), comprised of a helix-loop-helix (HLH) hairpin, is capable of associating into two different helical bundles. The two basic quaternary assemblies of EsxB are an antiparallel (AP) dimer and a rarely observed bisecting U (BU) dimer. This structural duality of EsxB is believed to originate from the heptad repeat sequence diversity of the first helix of its HLH hairpin, which allows for twomore » alternative helix packing. The flexibility of EsxB and the ability to form alternative helical bundles underscore the possibility that this protein can serve as an adaptor in secretion and can form hetero-oligomeric helix bundle(s) with other secreted members of the WXG100 family, such as EsxW. The highly conserved WXG motif is located within the loop of the HLH hairpin and is mostly buried within the helix bundle suggesting that its role is mainly structural. The exact functions of the motif, including a proposed role as a secretion signal, remain unknown.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, M.; Lombardo, V.; Turrioni, D.

Helical solenoids that provide solenoid, helical dipole and helical gradient field components are designed for a helical cooling channel (HCC) proposed for cooling of muon beams in a muon collider. The high temperature superconductor (HTS), 12 mm wide and 0.1 mm thick YBCO tape, is used as the conductor for the highest-field section of HCC due to certain advantages, such as its electrical and mechanical properties. To study and address the design, and technological and performance issues related to magnets based on YBCO tapes, a short helical solenoid model based on double-pancake coils was designed, fabricated and tested at Fermilab.more » Splicing joints were made with Sn-Pb solder as the power leads and the connection between coils, which is the most critical element in the magnet that can limit the performance significantly. This paper summarizes the test results of YBCO tape and double-pancake coils in liquid nitrogen and liquid helium, and then focuses on the study of YBCO splices, including the soldering temperatures and pressures, and splice bending test.« less

Crenactin from Pyrobaculum calidifontis is closely related to actin in structure and forms steep helical filaments

PubMed Central

Izoré, Thierry; Duman, Ramona; Kureisaite-Ciziene, Danguole; Löwe, Jan

2014-01-01

Polymerising proteins of the actin family are nearly ubiquitous. Crenactins, restricted to Crenarchaea, are more closely related to actin than bacterial MreB. Crenactins occur in gene clusters hinting at an unknown, but conserved function. We solved the crystal structure of crenactin at 3.2 Å resolution. The protein crystallises as a continuous right-handed helix with 8 subunits per complete turn, spanning 419 Å. The structure of crenactin shows several loops that are longer than in actin, but overall, crenactin is closely related to eukaryotic actin, with an RMSD of 1.6 Å. Crenactin filaments imaged by electron microscopy showed polymers with very similar helical parameters. PMID:24486010

Series Connected Converter for Control of Multi-Bus Spacecraft Power Utility

NASA Technical Reports Server (NTRS)

Beach, Raymond F. (Inventor); Brush, Andy (Inventor)

1997-01-01

The invention provides a power system using series connected regulators. Power from a source, such as a solar array, is processed through the regulators and provided to corresponding buses used to charge a battery and supply loads. The regulators employ a bypass loop around a DC-DC converter. The bypass loop connects a hot input of the converter to a return output, preferably though an inductor. Part of the current from the source passes through the bypass loop to the power bus. The converter bucks or boosts the voltage from the source to maintain the desired voltage at the bus. Thus, only part of the power is processed through the converter. The converter can also be used without the bypass loop to provide isolation. All of the converters can be substantially identical.

Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model.

PubMed

Zoratto, F; Palombelli, G M; Ruocco, L A; Carboni, E; Laviola, G; Sadile, A G; Adriani, W; Canese, R

2017-08-30

Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo, we investigated the connectivity of neuronal networks belonging to limbic vs. cortical loops in NHE and NRB rats (n=10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Chiral direction and interconnection of helical three-connected networks in metal-organic frameworks.

PubMed

Prior, T J; Rosseinsky, M J

2003-03-10

The control of the interpenetration and chirality of a family of metal-organic frameworks is discussed. These systems contain two- (A) and four-fold (B) interpenetration of helical three-connected networks generated by binding the 1,3,5-benzenetricarboxylate (btc) ligand to a metal center. These frameworks have the general formula Ni(3)(btc)(2)X(m)Y(n).solvent (where X = pyridine or 4-picoline, Y = ethylene glycol, 1,2-propanediol, 1,4-butanediol, meso-2,3-butanediol, 1,2,6-hexanetriol, glycerol). The structural and chemical effects of modifying the alcohol and aromatic amine ligands bound to the metal center include controlling the thermal stability and the degree of interpenetration. Covalent linking of the four interpenetrating networks in the A family and the switching of diol binding from mono- to bidentate are demonstrated. Recognition of chiral diols by the hand of the network helices is investigated by binding an alcohol ligand with two chiral centers of opposite sense to the same helix. This reveals the subtle nature of the helix-ligand interaction.

Granular Material Scoop and Near-Vertical Lifting Feeder/Conveyor

NASA Technical Reports Server (NTRS)

Walton, Otis (Inventor); Vollmer, Hubert J. (Inventor)

2017-01-01

An integrated granular-material scoop and near-vertical lifting feeder/conveyor includes special connections and skirts between a bullnose rotating scoop and an open-helical screw that provides the rotations and material lift and evacuation. A conical working-face of the bullnose rotating scoop has symmetrically distributed graters and vents to break loose and force-in granular material from natural deposits and cargo holds. The bullnose rotating scoop and the open-helical screw its attached to move the material into a continuous layer on the inside surface of an outer stationary sheathing. A motor drive attached to the open-helical screw above at the delivery end provides the lifting force necessary.

Extension of loop quantum gravity to f(R) theories.

PubMed

Zhang, Xiangdong; Ma, Yongge

2011-04-29

The four-dimensional metric f(R) theories of gravity are cast into connection-dynamical formalism with real su(2) connections as configuration variables. Through this formalism, the classical metric f(R) theories are quantized by extending the loop quantization scheme of general relativity. Our results imply that the nonperturbative quantization procedure of loop quantum gravity is valid not only for general relativity but also for a rather general class of four-dimensional metric theories of gravity.

Open and Lys–His Hexacoordinated Closed Structures of a Globin with Swapped Proximal and Distal Sites

PubMed Central

Teh, Aik-Hong; Saito, Jennifer A.; Najimudin, Nazalan; Alam, Maqsudul

2015-01-01

Globins are haem-binding proteins with a conserved fold made up of α-helices and can possess diverse properties. A putative globin-coupled sensor from Methylacidiphilum infernorum, HGbRL, contains an N-terminal globin domain whose open and closed structures reveal an untypical dimeric architecture. Helices E and F fuse into an elongated helix, resulting in a novel site-swapped globin fold made up of helices A–E, hence the distal site, from one subunit and helices F–H, the proximal site, from another. The open structure possesses a large cavity binding an imidazole molecule, while the closed structure forms a unique Lys–His hexacoordinated species, with the first turn of helix E unravelling to allow Lys52(E10) to bind to the haem. Ligand binding induces reorganization of loop CE, which is stabilized in the closed form, and helix E, triggering a large conformational movement in the open form. These provide a mechanical insight into how a signal may be relayed between the globin domain and the C-terminal domain of HGbRL, a Roadblock/LC7 domain. Comparison with HGbI, a closely related globin, further underlines the high degree of structural versatility that the globin fold is capable of, enabling it to perform a diversity of functions. PMID:26094577

Split radiator design for heat rejection optimization for a waste heat recovery system

DOEpatents

Ernst, Timothy C.; Nelson, Christopher R.

2016-10-18

A cooling system provides improved heat recovery by providing a split core radiator for both engine cooling and condenser cooling for a Rankine cycle (RC). The cooling system includes a radiator having a first cooling core portion and a second cooling core portion. An engine cooling loop is fluidly connected the second cooling core portion. A condenser of an RC has a cooling loop fluidly connected to the first cooling core portion. A valve is provided between the engine cooling loop and the condenser cooling loop adjustably control the flow of coolant in the condenser cooling loop into the engine cooling loop. The cooling system includes a controller communicatively coupled to the valve and adapted to determine a load requirement for the internal combustion engine and adjust the valve in accordance with the engine load requirement.

SANC: the process γγ → ΖΖ

NASA Astrophysics Data System (ADS)

Bardin, D.; Bondarenko, S.; Christova, P.; Kalinovskaya, L.; von Schlippe, W.; Uglov, E.

2017-11-01

The implementation of the process γγ → ΖΖ at the one-loop level within SANC system multichannel approach is considered. The derived one-loop scalar form factors can be used for any cross channel after an appropriate permutation of their arguments-Mandelstam variables s, t, u. To check of the correctness of the results we observe the independence of the scalar form factors on the gauge parameters and the validity of Ward identity (external photon transversality). We present the complete analytical results for the covariant and tensor structures and helicity amplitudes for this process. We make an extensive comparison of our analytical and numerical results with those existing in the literature.

NMR and Bioinformatics Discovery of Exosites That Tune Metalloelastase Specificity for Solubilized Elastin and Collagen Triple Helices*

PubMed Central

Palmier, Mark O.; Fulcher, Yan G.; Bhaskaran, Rajagopalan; Duong, Vinh Q.; Fields, Gregg B.; Van Doren, Steven R.

2010-01-01

The catalytic domain of metalloelastase (matrix metalloproteinase-12 or MMP-12) is unique among MMPs in exerting high proteolytic activity upon fibrils that resist hydrolysis, especially elastin from lungs afflicted with chronic obstructive pulmonary disease or arteries with aneurysms. How does the MMP-12 catalytic domain achieve this specificity? NMR interface mapping suggests that α-elastin species cover the primed subsites, a strip across the β-sheet from β-strand IV to the II–III loop, and a broad bowl from helix A to helix C. The many contacts may account for the comparatively high affinity, as well as embedding of MMP-12 in damaged elastin fibrils in vivo. We developed a strategy called BINDSIght, for bioinformatics and NMR discovery of specificity of interactions, to evaluate MMP-12 specificity without a structure of a complex. BINDSIght integration of the interface mapping with other ambiguous information from sequences guided choice mutations in binding regions nearer the active site. Single substitutions at each of ten locations impair specific activity toward solubilized elastin. Five of them impair release of peptides from intact elastin fibrils. Eight lesions also impair specific activity toward triple helices from collagen IV or V. Eight sites map to the “primed” side in the III–IV, V–B, and S1′ specificity loops. Two map to the “unprimed” side in the IV–V and B–C loops. The ten key residues circumscribe the catalytic cleft, form an exosite, and are distinctive features available for targeting by new diagnostics or therapeutics. PMID:20663866

The structure of the ends of α-helices in globular proteins: effect of additional hydrogen bonds and implications for helix formation.

PubMed

Leader, David P; Milner-White, E James

2011-03-01

We prepared a set of about 2000 α-helices from a relational database of high-resolution three-dimensional structures of globular proteins, and identified additional main chain i ← i+3 hydrogen bonds at the ends of the helices (i.e., where the hydrogen bonding potential is not fulfilled by canonical i ← i+4 hydrogen bonds). About one-third of α-helices have such additional hydrogen bonds at the N-terminus, and more than half do so at the C-terminus. Although many of these additional hydrogen bonds at the C-terminus are associated with Schellman loops, the majority are not. We compared the dihedral angles at the termini of α-helices having or lacking the additional hydrogen bonds. Significant differences were found, especially at the C-terminus, where the dihedral angles at positions C2 and C1 in the absence of additional hydrogen bonds deviate substantially from those occurring within the α-helix. Using a novel approach we show how the structure of the C-terminus of the α-helix can emerge from that of constituent overlapping α-turns and β-turns, which individually show a variation in dihedral angles at different positions. We have also considered the direction of propagation of the α-helix using this approach. If one assumes that helices start as a single α-turn and grow by successive addition of further α-turns, the paths for growth in the N → C and C → N directions differ in a way that suggests that extension in the C → N direction is favored. Copyright © 2010 Wiley-Liss, Inc.

Sequence and conformational preferences at termini of α-helices in membrane proteins: role of the helix environment.

PubMed

Shelar, Ashish; Bansal, Manju

2014-12-01

α-Helices are amongst the most common secondary structural elements seen in membrane proteins and are packed in the form of helix bundles. These α-helices encounter varying external environments (hydrophobic, hydrophilic) that may influence the sequence preferences at their N and C-termini. The role of the external environment in stabilization of the helix termini in membrane proteins is still unknown. Here we analyze α-helices in a high-resolution dataset of integral α-helical membrane proteins and establish that their sequence and conformational preferences differ from those in globular proteins. We specifically examine these preferences at the N and C-termini in helices initiating/terminating inside the membrane core as well as in linkers connecting these transmembrane helices. We find that the sequence preferences and structural motifs at capping (Ncap and Ccap) and near-helical (N' and C') positions are influenced by a combination of features including the membrane environment and the innate helix initiation and termination property of residues forming structural motifs. We also find that a large number of helix termini which do not form any particular capping motif are stabilized by formation of hydrogen bonds and hydrophobic interactions contributed from the neighboring helices in the membrane protein. We further validate the sequence preferences obtained from our analysis with data from an ultradeep sequencing study that identifies evolutionarily conserved amino acids in the rat neurotensin receptor. The results from our analysis provide insights for the secondary structure prediction, modeling and design of membrane proteins. © 2014 Wiley Periodicals, Inc.

Monitoring transients in low inductance circuits

DOEpatents

Guilford, Richard P.; Rosborough, John R.

1987-01-01

A pair of flat cable transmission lines are monitored for transient current spikes by using a probe connected to a current transformer by a pickup loop and monitoring the output of the current transformer. The approach utilizes a U-shaped pickup probe wherein the pair of flat cable transmission lines are received between the legs of the U-shaped probe. The U-shaped probe is preferably formed of a flat coil conductor adhered to one side of a flexible substrate. On the other side of the flexible substrate there is a copper foil shield. The copper foil shield is connected to one end of the flat conductor coil and connected to one leg of the pickup loop which passes through the current transformer. The other end of the flat conductor coil is connected to the other leg of the pickup loop.

Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore.

PubMed

El Hiani, Yassine; Linsdell, Paul

2015-06-19

As an ion channel, the cystic fibrosis transmembrane conductance regulator must form a continuous pathway for the movement of Cl(-) and other anions between the cytoplasm and the extracellular solution. Both the structure and the function of the membrane-spanning part of this pathway are well defined. In contrast, the structure of the pathway that connects the cytoplasm to the membrane-spanning regions is unknown, and functional roles for different parts of the protein forming this pathway have not been described. We used patch clamp recording and substituted cysteine accessibility mutagenesis to identify positively charged amino acid side chains that attract cytoplasmic Cl(-) ions to the inner mouth of the pore. Our results indicate that the side chains of Lys-190, Arg-248, Arg-303, Lys-370, Lys-1041, and Arg-1048, located in different intracellular loops of the protein, play important roles in the electrostatic attraction of Cl(-) ions. Mutation and covalent modification of these residues have charge-dependent effects on the rate of Cl(-) permeation, demonstrating their functional role in maximization of Cl(-) flux. Other nearby positively charged side chains were not involved in electrostatic interactions with Cl(-). The location of these Cl(-)-attractive residues suggests that cytoplasmic Cl(-) ions enter the pore via a lateral portal located between the cytoplasmic extensions to the fourth and sixth transmembrane helices; a secondary, functionally less relevant portal might exist between the extensions to the 10th and 12th transmembrane helices. These results define the cytoplasmic mouth of the pore and show how it attracts Cl(-) ions from the cytoplasm. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus

PubMed Central

Bhaskar, Baki Vijaya; Babu, Tirumalasetty Muni Chandra; Reddy, Netala Vasudeva; Rajendra, Wudayagiri

2016-01-01

Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds. PMID:27757014

Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus.

PubMed

Bhaskar, Baki Vijaya; Babu, Tirumalasetty Muni Chandra; Reddy, Netala Vasudeva; Rajendra, Wudayagiri

2016-01-01

Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds.

Experimental demonstration of plasma startup by coaxial helicity injection

NASA Astrophysics Data System (ADS)

Raman, R.; Jarboe, T. R.; Nelson, B. A.; Hamp, W. T.; Izzo, V. A.; O'Neill, R. G.; Redd, A. J.; Sieck, P. E.; Smith, R. J.

2004-05-01

Experimental results on the transfer of a coaxial-helicity-injection (CHI) produced discharge to inductive operation are reported. CHI assisted plasma startup is more robust than inductive only operation and reduces volt-seconds consumption. After handoff to inductive operation, the initial 100 kA of CHI produced current drops to 50 kA, then ramps up to 180 kA, using only 30 mVs, about 40% higher than that produced by induction alone. Results show that initiation of CHI discharges at lower densities produce higher levels of coupling current. Coupling a CHI produced discharge to induction from a precharged central solenoid has produced record currents of 290 kA using only 52 mWb of central solenoid flux. CHI discharges can also be generated while the central transformer is in the process of being precharged, during which period it induces a negative loop voltage on the CHI discharge. These significant results were obtained on the Helicity Injected Torus-II (HIT-II) [T.R. Jarboe, Fusion Technol. 15, 7 (1989)] spherical torus experiment (major/minor radius of 0.3/0.2 m and elongation of 1.5).

Local conformational dynamics in alpha-helices measured by fast triplet transfer.

PubMed

Fierz, Beat; Reiner, Andreas; Kiefhaber, Thomas

2009-01-27

Coupling fast triplet-triplet energy transfer (TTET) between xanthone and naphthylalanine to the helix-coil equilibrium in alanine-based peptides allowed the observation of local equilibrium fluctuations in alpha-helices on the nanoseconds to microseconds time scale. The experiments revealed faster helix unfolding in the terminal regions compared with the central parts of the helix with time constants varying from 250 ns to 1.4 micros at 5 degrees C. Local helix formation occurs with a time constant of approximately 400 ns, independent of the position in the helix. Comparing the experimental data with simulations using a kinetic Ising model showed that the experimentally observed dynamics can be explained by a 1-dimensional boundary diffusion with position-independent elementary time constants of approximately 50 ns for the addition and of approximately 65 ns for the removal of an alpha-helical segment. The elementary time constant for helix growth agrees well with previously measured time constants for formation of short loops in unfolded polypeptide chains, suggesting that helix elongation is mainly limited by a conformational search.

Bak Conformational Changes Induced by Ligand Binding: Insight into BH3 Domain Binding and Bak Homo-Oligomerization

PubMed Central

Pang, Yuan-Ping; Dai, Haiming; Smith, Alyson; Meng, X. Wei; Schneider, Paula A.; Kaufmann, Scott H.

2012-01-01

Recently we reported that the BH3-only proteins Bim and Noxa bind tightly but transiently to the BH3-binding groove of Bak to initiate Bak homo-oligomerization. However, it is unclear how such tight binding can induce Bak homo-oligomerization. Here we report the ligand-induced Bak conformational changes observed in 3D models of Noxa·Bak and Bim·Bak refined by molecular dynamics simulations. In particular, upon binding to the BH3-binding groove, Bim and Noxa induce a large conformational change of the loop between helices 1 and 2 and in turn partially expose a remote groove between helices 1 and 6 in Bak. These observations, coupled with the reported experimental data, suggest formation of a pore-forming Bak octamer, in which the BH3-binding groove is at the interface on one side of each monomer and the groove between helices 1 and 6 is at the interface on the opposite side, initiated by ligand binding to the BH3-binding groove. PMID:22355769

Multiphase soft switched DC/DC converter and active control technique for fuel cell ripple current elimination

DOEpatents

Lai, Jih-Sheng; Liu, Changrong; Ridenour, Amy

2009-04-14

DC/DC converter has a transformer having primary coils connected to an input side and secondary coils connected to an output side. Each primary coil connects a full-bridge circuit comprising two switches on two legs, the primary coil being connected between the switches on each leg, each full-bridge circuit being connected in parallel wherein each leg is disposed parallel to one another, and the secondary coils connected to a rectifying circuit. An outer loop control circuit that reduces ripple in a voltage reference has a first resistor connected in series with a second resistor connected in series with a first capacitor which are connected in parallel with a second capacitor. An inner loop control circuit that reduces ripple in a current reference has a third resistor connected in series with a fourth resistor connected in series with a third capacitor which are connected in parallel with a fourth capacitor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lello, Louis; Boyanovsky, Daniel; Pisarski, Robert D.

Here, in the standard model extended with a seesaw mass matrix, we study the production of sterile neutrinos from the decay of vector bosons at temperatures near the masses of the electroweak bosons. We derive a general quantum kinetic equation for the production of sterile neutrinos and their effective mixing angles, which is applicable over a wide range of temperature, to all orders in interactions of the standard model and to leading order in a small mixing angle for the neutrinos. We emphasize the relation between the production rate and Landau damping at one-loop order and show that production rates and effective mixing angles depend sensitively upon the neutrino’s helicity. Sterile neutrinos with positive helicity interact more weakly with the medium than those with negative helicity, and their effective mixing angle is not modified significantly. Negative helicity states couple more strongly to the vector bosons, but their mixing angle is strongly suppressed by the medium. Consequently, if the mass of the sterile neutrino is ≲ 8.35 MeV , there are fewer states with negative helicity produced than those with positive helicity. There is an Mikheyev-Smirnov-Wolfenstein-type resonance in the absence of lepton asymmetry, but due to screening by the damping rate, the production rate is not enhanced. Sterile neutrinos with negative helicity freeze out at Tmore » $$-\\atop{f}$$ ≃ 5 GeV , whereas positive helicity neutrinos freeze out at T$$+\\atop{f}$$≃ 8 GeV , with both distributions far from thermal. As the temperature decreases, due to competition between a decreasing production rate and an increasing mixing angle, the distribution function for states with negative helicity is broader in momentum and hotter than that for those with positive helicity. Sterile neutrinos produced via vector boson decay do not satisfy the abundance, lifetime, and cosmological constraints to be the sole dark matter component in the Universe. Massive sterile neutrinos produced via vector boson decay might solve the 7Li problem, albeit at the very edge of the possible parameter space. A heavy sterile neutrino with a mass of a few MeV could decay into light sterile neutrinos, of a few keV in mass, that contribute to warm dark matter. In conclusion, we argue that heavy sterile neutrinos with lifetime ≤1/H 0 reach local thermodynamic equilibrium.« less

Production of heavy sterile neutrinos from vector boson decay at electroweak temperatures

NASA Astrophysics Data System (ADS)

Lello, Louis; Boyanovsky, Daniel; Pisarski, Robert D.

2017-02-01

In the standard model extended with a seesaw mass matrix, we study the production of sterile neutrinos from the decay of vector bosons at temperatures near the masses of the electroweak bosons. We derive a general quantum kinetic equation for the production of sterile neutrinos and their effective mixing angles, which is applicable over a wide range of temperature, to all orders in interactions of the standard model and to leading order in a small mixing angle for the neutrinos. We emphasize the relation between the production rate and Landau damping at one-loop order and show that production rates and effective mixing angles depend sensitively upon the neutrino's helicity. Sterile neutrinos with positive helicity interact more weakly with the medium than those with negative helicity, and their effective mixing angle is not modified significantly. Negative helicity states couple more strongly to the vector bosons, but their mixing angle is strongly suppressed by the medium. Consequently, if the mass of the sterile neutrino is ≲8.35 MeV , there are fewer states with negative helicity produced than those with positive helicity. There is an Mikheyev-Smirnov-Wolfenstein-type resonance in the absence of lepton asymmetry, but due to screening by the damping rate, the production rate is not enhanced. Sterile neutrinos with negative helicity freeze out at Tf-≃5 GeV , whereas positive helicity neutrinos freeze out at Tf+≃8 GeV , with both distributions far from thermal. As the temperature decreases, due to competition between a decreasing production rate and an increasing mixing angle, the distribution function for states with negative helicity is broader in momentum and hotter than that for those with positive helicity. Sterile neutrinos produced via vector boson decay do not satisfy the abundance, lifetime, and cosmological constraints to be the sole dark matter component in the Universe. Massive sterile neutrinos produced via vector boson decay might solve the 7Li problem, albeit at the very edge of the possible parameter space. A heavy sterile neutrino with a mass of a few MeV could decay into light sterile neutrinos, of a few keV in mass, that contribute to warm dark matter. We argue that heavy sterile neutrinos with lifetime ≤1 /H0 reach local thermodynamic equilibrium.

Production of heavy sterile neutrinos from vector boson decay at electroweak temperatures

DOE PAGES

Lello, Louis; Boyanovsky, Daniel; Pisarski, Robert D.

2017-02-22

Here, in the standard model extended with a seesaw mass matrix, we study the production of sterile neutrinos from the decay of vector bosons at temperatures near the masses of the electroweak bosons. We derive a general quantum kinetic equation for the production of sterile neutrinos and their effective mixing angles, which is applicable over a wide range of temperature, to all orders in interactions of the standard model and to leading order in a small mixing angle for the neutrinos. We emphasize the relation between the production rate and Landau damping at one-loop order and show that production rates and effective mixing angles depend sensitively upon the neutrino’s helicity. Sterile neutrinos with positive helicity interact more weakly with the medium than those with negative helicity, and their effective mixing angle is not modified significantly. Negative helicity states couple more strongly to the vector bosons, but their mixing angle is strongly suppressed by the medium. Consequently, if the mass of the sterile neutrino is ≲ 8.35 MeV , there are fewer states with negative helicity produced than those with positive helicity. There is an Mikheyev-Smirnov-Wolfenstein-type resonance in the absence of lepton asymmetry, but due to screening by the damping rate, the production rate is not enhanced. Sterile neutrinos with negative helicity freeze out at Tmore » $$-\\atop{f}$$ ≃ 5 GeV , whereas positive helicity neutrinos freeze out at T$$+\\atop{f}$$≃ 8 GeV , with both distributions far from thermal. As the temperature decreases, due to competition between a decreasing production rate and an increasing mixing angle, the distribution function for states with negative helicity is broader in momentum and hotter than that for those with positive helicity. Sterile neutrinos produced via vector boson decay do not satisfy the abundance, lifetime, and cosmological constraints to be the sole dark matter component in the Universe. Massive sterile neutrinos produced via vector boson decay might solve the 7Li problem, albeit at the very edge of the possible parameter space. A heavy sterile neutrino with a mass of a few MeV could decay into light sterile neutrinos, of a few keV in mass, that contribute to warm dark matter. In conclusion, we argue that heavy sterile neutrinos with lifetime ≤1/H 0 reach local thermodynamic equilibrium.« less

Simultaneous Determination of Two Subdomain Folding Rates Using the "Transfer-Quench" Method.

PubMed

Rahamim, Gil; Amir, Dan; Haas, Elisha

2017-05-09

The investigation of the mechanism of protein folding is complicated by the context dependence of the rates of intramolecular contact formation. Methods based on site-specific labeling and ultrafast spectroscopic detection of fluorescence signals were developed for monitoring the rates of individual subdomain folding transitions in situ, in the context of the whole molecule. However, each site-specific labeling modification might affect rates of folding of near-neighbor structural elements, and thus limit the ability to resolve fine differences in rates of folding of these elements. Therefore, it is highly desirable to be able to study the rates of folding of two or more neighboring subdomain structures using a single mutant to facilitate resolution of the order and interdependence of such steps. Here, we report the development of the "Transfer-Quench" method for measuring the rate of formation of two structural elements using a single triple-labeled mutant. This method is based on Förster resonance energy transfer combined with fluorescence quenching. We placed the donor and acceptor at the loop ends, and a quencher at an α-helical element involved in the node forming the loop. The folding of the triple-labeled mutant is monitored by the acceptor emission. The formation of nonlocal contact (loop closure) increases the time-dependent acceptor emission, while the closure of the labeled helix turn reduces this emission. The method was applied in a study of the folding mechanism of the common model protein, the B domain of staphylococcal protein A. Only natural amino acids were used as probes, and thus possible structural perturbations were minimized. Tyr and Trp residues served as donor and acceptor at the ends of a long loop between helices I and II, and a Cys residue as a quencher for the acceptor. We found that the closure of the loop (segment 14-33) occurs with the same rate constant as the nucleation of helix HII (segment 33-29), in line with the nucleation-condensation model. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Microstructure evolution of recrystallized Zircaloy-4 under charged particles irradiation

NASA Astrophysics Data System (ADS)

Gaumé, M.; Onimus, F.; Dupuy, L.; Tissot, O.; Bachelet, C.; Mompiou, F.

2017-11-01

Recrystallized zirconium alloys are used as nuclear fuel cladding tubes of Pressurized Water Reactors. During operation, these alloys are submitted to fast neutron irradiation which leads to their in-reactor deformation and to a change of their mechanical properties. These phenomena are directly related to the microstructure evolution under irradiation and especially to the formation of -type dislocation loops. In the present work, the radiation damage evolution in recrystallized Zircaloy-4 has been studied using charged particles irradiation. The loop nucleation and growth kinetics, and also the helical climb of linear dislocations, were observed in-situ using a High Voltage Electron Microscope (HVEM) under 1 MeV electron irradiation at 673 and 723 K. In addition, 600 keV Zr+ ion irradiations were conducted at the same temperature. Transmission Electron Microscopy (TEM) characterizations have been performed after both types of irradiations, and show dislocation loops with a Burgers vector belonging to planes close to { 10 1 bar 0 } first order prismatic planes. The nature of the loops has been characterized. Only interstitial dislocation loops have been observed after ion irradiation at 723 K. However, after electron irradiation conducted at 673 and 723 K, both interstitial and vacancy loops were observed, the proportion of interstitial loops increasing as the temperature is increased. The loop growth kinetics analysis shows that as the temperature increases, the loop number density decreases and the loop growth rate tends to increase. An increase of the flux leads to an increase of the loop number density and a decrease of the loop growth rate. The results are compared to previous works and discussed in the light of point defects diffusion.

Thermodynamic characterization of a triple-helical three-way junction containing a Hoogsteen branch point.

PubMed

Hüsler, P L; Klump, H H

1995-09-10

We have designed a Hoogsteen (HG) triple-helical three-way junction (ternary complex) constructed from three 33-mer oligonucleotides based on the same subset of sequences used for the Watson-Crick (WC) triple-helical three-way junction, characterized previously (P. L. Hüsler and H. H. Klump (1994) Arch. Biochem. Biophys., 313, 29-38). The junction differs primarily in the assembly of the branch point and the ends of the arms. The three oligonucleotides can each fold into a WC hairpin, linked by a four-member cytosine loop, each containing a homo-pyrimidine 10-mer single-strand extension. On lowering the pH (between 6 and 4), the extensions mutually associate to one of the other hairpins via Hoogsteen (HG) hydrogen bonding. Collectively, this process results in the formation of the branch point and the triple-helical arms. The HG triple-helical three-way junction is characterized by gel electrophoresis, circular dichroism, uv melting, and differential scanning calorimetry. The junction undergoes thermal unfolding in two distinct temperature regions. In the temperature range 15 to 50 degrees C loss of HG base pairing results in the dissociation of the three-way junction. Between 55 and 95 degrees C the resulting hairpins undergo further successive unfolding. The overall calorimetric unfolding enthalpy and entropy changes associated with the loss of HG base pairing are approximately equal to the sum of the enthalpy and entropy changes associated with the dissociation of the HG base pairing in the isolated arms (170.6 kcal.mol-1; 540.1 cal.mol-1.K-1). It is apparent from these results that in the proximity of the branch point the structure is not perturb or strain. This result is contrary to the results obtained for the WC triple-helical three-way and for three-way junctions constructed from canonical double-helical DNA. Complete folding of the junction requires either high Na+ (600 mM) ion concentrations or 40-60 mM Mg2+.

Skylab observations of X-ray loops connecting separate active regions. [solar activity

NASA Technical Reports Server (NTRS)

Chase, R. C.; Krieger, A. S.; Svestka, Z.; Vaiana, G. S.

1976-01-01

One hundred loops interconnecting 94 separate active solar regions detectable in soft X-rays were identified during the Skylab mission. While close active regions are commonly interconnected with loops, the number of such interconnections decreases steeply for longer distances; the longest interconnecting loop observed in the Skylab data connected regions separated by 37 deg. Several arguments are presented which support the point of view that this is the actual limit of the size of magnetic interconnections between active regions. No sympathetic flares could be found in the interconnected regions. These results cast doubt on the hypothesis that accelerated particles can be guided in interconnecting loops from one active region to another over distances of 100 deg or more and eventually produce sympathetic flares in them.

TORNADO-LIKE EVOLUTION OF A KINK-UNSTABLE SOLAR PROMINENCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wensi; Liu, Rui; Wang, Yuming, E-mail: rliu@ustc.edu.cn

We report on the tornado-like evolution of a quiescent prominence on 2014 November 1. The eastern section of the prominence first rose slowly, transforming into an arch-shaped structure as high as ∼150 Mm above the limb; the arch then writhed moderately in a left-handed sense, while the original dark prominence material emitted in the Fe ix 171 Å passband, and a braided structure appeared at the eastern edge of the warped arch. The unraveling of the braided structure was associated with a transient brightening in the EUV and apparently contributed to the formation of a curtain-like structure (CLS). The CLSmore » consisted of myriad thread-like loops rotating counterclockwise about the vertical if viewed from above. Heated prominence material was observed to slide along these loops and land outside the filament channel. The tornado eventually disintegrated and the remaining material flew along a left-handed helical path constituting approximately a full turn, as corroborated through stereoscopic reconstruction, into the cavity of the stable, western section of the prominence. We suggest that the tornado-like evolution of the prominence was governed by the helical kink instability, and that the CLS formed through magnetic reconnections between the prominence field and the overlying coronal field.« less

Structural basis for nuclear import complex dissociation by RanGTP.

PubMed

Lee, Soo Jae; Matsuura, Yoshiyuki; Liu, Sai Man; Stewart, Murray

2005-06-02

Nuclear protein import is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then transports it through nuclear pore complexes. This active transport is driven by disassembly of the import complex by nuclear RanGTP. The switch I and II loops of Ran change conformation with nucleotide state, and regulate its interactions with nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that are based on a pair of antiparallel alpha-helices (referred to as the A- and B-helices). The HEAT repeats stack to yield two C-shaped arches, linked together to form a helicoidal molecule that has considerable conformational flexibility. Here we present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed with RanGTP, which provides a basis for understanding the crucial cargo-release step of nuclear import. We identify a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p. This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Two conceptual designs of helical fusion reactor FFHR-d1A based on ITER technologies and challenging ideas

NASA Astrophysics Data System (ADS)

Sagara, A.; Miyazawa, J.; Tamura, H.; Tanaka, T.; Goto, T.; Yanagi, N.; Sakamoto, R.; Masuzaki, S.; Ohtani, H.; The FFHR Design Group

2017-08-01

The Fusion Engineering Research Project (FERP) at the National Institute for Fusion Science (NIFS) is conducting conceptual design activities for the LHD-type helical fusion reactor FFHR-d1A. This paper newly defines two design options, ‘basic’ and ‘challenging.’ Conservative technologies, including those that will be demonstrated in ITER, are chosen in the basic option in which two helical coils are made of continuously wound cable-in-conduit superconductors of Nb3Sn strands, the divertor is composed of water-cooled tungsten monoblocks, and the blanket is composed of water-cooled ceramic breeders. In contrast, new ideas that would possibly be beneficial for making the reactor design more attractive are boldly included in the challenging option in which the helical coils are wound by connecting high-temperature REBCO superconductors using mechanical joints, the divertor is composed of a shower of molten tin jets, and the blanket is composed of molten salt FLiNaBe including Ti powers to increase hydrogen solubility. The main targets of the challenging option are early construction and easy maintenance of a large and three-dimensionally complicated helical structure, high thermal efficiency, and, in particular, realistic feasibility of the helical reactor.

Morphology of blazar-induced gamma ray halos due to a helical intergalactic magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, Andrew J.; Vachaspati, Tanmay, E-mail: andrewjlong@asu.edu, E-mail: tvachasp@asu.edu

We study the characteristic size and shape of idealized blazar-induced cascade halos in the 1–100,GeV energy range assuming various non-helical and helical configurations for the intergalactic magnetic field (IGMF). While the magnetic field creates an extended halo, the helicity provides the halo with a twist. Under simplifying assumptions, we assess the parameter regimes for which it is possible to measure the size and shape of the halo from a single source and then to deduce properties of the IGMF. We find that blazar halo measurements with an experiment similar to Fermi-LAT are best suited to probe a helical magnetic fieldmore » with strength and coherence length today in the ranges 10{sup −17} ∼< B{sub 0} / Gauss ∼< 10{sup −13} and 10 Mpc ∼< λ ∼< 10 Gpc where H ∼ B{sub 0}{sup 2} / λ is the magnetic helicity density. Stronger magnetic fields or smaller coherence scales can still potentially be investigated, but the connection between the halo morphology and the magnetic field properties is more involved. Weaker magnetic fields or longer coherence scales require high photon statistics or superior angular resolution.« less

Absorber arc mitigation during CHI on NSTX

NASA Astrophysics Data System (ADS)

Mueller, D.; Bell, M. G.; Roquemore, A. L.; Raman, R.; Nelson, B. A.; Jarboe, T. R.

2009-11-01

A method of non-inductive startup, referred to as transient coaxial helicity injection (CHI), was successfully developed on the Helicity Injected Torus (HIT-II) experiment and employed on the National Spherical Torus Experiment (NSTX). This technique has produced 160 kA of plasma current on closed flux surfaces. Over 100 kA of the CHI current has been coupled to inductively driven current ramp-up. In transient CHI, a voltage is applied across the insulating gap separating the inner and outer vacuum vessel and gas is introduced at the lower gap (the injector). The resulting current in the injector follows the helical magnetic field connecting the electrodes, forms a toroidal current and expands into the vacuum vessel. At higher CHI current, the poloidal field due to the plasma can connect the inner and outer vessels at the insulating gap at the top (called the absorber) of NSTX and lower the impedance there. This results in arcs in the absorber which are a source of impurities and which reduce the desired current in the injector. Two coils installed in the absorber will be used to reduce the magnetic field across the absorber gap and mitigate the absorber arcs.

Why double-stranded RNA resists condensation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolokh, Igor S.; Pabit, Suzette; Katz, Andrea M.

2014-09-15

The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to attraction between the negatively charged helices and eventually to condensation. Surprisingly, this effect is suppressed in double-stranded RNA, which carries the same charge as the DNA, but assumes a different double helical form. However, additional characterization of short (25 base-pairs) nucleic acid (NA) duplex structures by circular dichroism shows that measured differences in condensation are not solely determined by duplex helical geometry. Here we combine experiment, theory, and atomistic simulations to propose a mechanism that connects the observed variations in condensation of short NA duplexesmore » with the spatial variation of cobalt hexammine (CoHex) binding at the NA duplex surface. The atomistic picture that emerged showed that CoHex distributions around the NA reveals two major NA-CoHex binding modes -- internal and external -- distinguished by the proximity of bound CoHex to the helical axis. Decreasing trends in experimentally observed condensation propensity of the four studied NA duplexes (from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA) are explained by the progressive decrease of a single quantity: the fraction of CoHex ions in the external binding mode. Thus, while NA condensation depends on a complex interplay between various structural and sequence features, our coupled experimental and theoretical results suggest a new model in which a single parameter connects the NA condensation propensity with geometry and sequence dependence of CoHex binding.« less

Connected, disconnected and strange quark contributions to HVP

NASA Astrophysics Data System (ADS)

Bijnens, Johan; Relefors, Johan

2016-11-01

We calculate all neutral vector two-point functions in Chiral Perturbation Theory (ChPT) to two-loop order and use these to estimate the ratio of disconnected to connected contributions as well as contributions involving the strange quark. We extend the ratio of -1/10 derived earlier in two flavour ChPT at one-loop order to a large part of the higher order contributions and discuss corrections to it. Our final estimate of the ratio disconnected to connected is negative and a few % in magnitude.

ON THE STRENGTH OF THE HEMISPHERIC RULE AND THE ORIGIN OF ACTIVE-REGION HELICITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Y.-M., E-mail: yi.wang@nrl.navy.mil

Vector magnetograph and morphological observations have shown that the solar magnetic field tends to have negative (positive) helicity in the northern (southern) hemisphere, although only ∼60%-70% of active regions appear to obey this 'hemispheric rule'. In contrast, at least ∼80% of quiescent filaments and filament channels that form during the decay of active regions follow the rule. We attribute this discrepancy to the difficulty in determining the helicity sign of newly emerged active regions, which are dominated by their current-free component; as the transverse field is canceled at the polarity inversion lines, however, the axial component becomes dominant there, allowingmore » a more reliable determination of the original active-region chirality. We thus deduce that the hemispheric rule is far stronger than generally assumed, and cannot be explained by stochastic processes. Earlier studies have shown that the twist associated with the axial tilt of active regions is too small to account for the observed helicity; here, both tilt and twist are induced by the Coriolis force acting on the diverging flow in the emerging flux tube. However, in addition to this east-west expansion about the apex of the loop, each of its legs must expand continually in cross section during its rise through the convection zone, thereby acquiring a further twist through the Coriolis force. Since this transverse pressure effect is not limited by drag or tension forces, the final twist depends mainly on the rise time, and may be large enough to explain the observed active-region helicity.« less

Down hole transmission system

DOEpatents

Hall, David R [Provo, UT; Hall, Jr., H. Tracy

2007-07-24

A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. The electrically conducting coil comprises at least two generally fractional loops. In the preferred embodiment, the transmission elements are connected by an electrical conductor. Preferably, the electrical conductor is a coaxial cable. Preferably, the MCEI trough comprises ferrite. In the preferred embodiment, the fractional loops are connected by a connecting cable. In one aspect of the present invention, the connecting cable is a pair of twisted wires. In one embodiment the connecting cable is a shielded pair of twisted wires. In another aspect of the present invention, the connecting cable is a coaxial cable. The connecting cable may be disposed outside of the MCEI circular trough.

Secondary Structural Changes of Intact and Disulfide Bridges-Cleaved Human Serum Albumins in Thermal Denaturation up to 130°C - Additive Effects of Sodium Dodecyl Sulfate on the Changes.

PubMed

Moriyama, Yoshiko; Takeda, Kunio

2017-05-01

The secondary structural changes of human serum albumin with the intact 17 disulfide bridges (HSA) and the disulfide bridges-cleaved human serum albumin (RCM-HSA) in thermal denaturation were examined. Most of the helical structures of HSA, whose original helicity was 66%, were sharply disrupted between 50 and 100°C. However, 14% helicity remained even at 130°C. The temperature dependence of the degree of disrupted helical structures of HSA was discussed in connection with questions about a general protein denaturation model. When HSA lost the disulfide bridges, about two-thirds of the original helices were disrupted. Although the helices of RCM-HSA remaining after the cleavage of the disulfide bridges were relatively resistant against the heat treatment, the helicity changed from 22% at 25°C to 14% at 130℃. The helicity of RCM-HSA at 130°C agreed with the helicity of HSA at the same temperature, indicating that the same helical moieties of the polypeptides remained unaffected at this high temperature. The additive effects of sodium dodecyl sulfate (SDS) on the structural changes of HSA and RCM-HSA in thermal denaturation were also examined. A slight amount of SDS protected the helical structures of HSA from thermal denaturation below 80°C. Upon cooling to 25°C after heat treatment at temperatures below 70°C with the coexistence of SDS of low concentrations, the helical structures of HSA were reformed to the original level at 25°C before heating. A similar tendency was also observed after heat treatment at 80°C. In contrast, the helical structures of the RCM-HSA complexes with SDS are completely recovered upon cooling to 25°C even after heat treatment up to 100°C. Similar investigations were also carried out on bovine serum albumins which had the intact 17 disulfide bridges and lost all of the bridges.

Plasma response to sustainment with imposed-dynamo current drive in HIT-SI and HIT-SI3

NASA Astrophysics Data System (ADS)

Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Penna, J. M.; Everson, C. J.; Nelson, B. A.

2017-07-01

The helicity injected torus—steady inductive (HIT-SI) program studies efficient, steady-state current drive for magnetic confinement plasmas using a novel experimental method. Stable, high-beta spheromaks have been sustained using steady, inductive current drive. Externally induced loop voltage and magnetic flux are oscillated together so that helicity and power injection are always positive, sustaining the edge plasma current indefinitely. Imposed-dynamo current drive (IDCD) theory further shows that the entire plasma current is sustained. The method is ideal for low aspect ratio, toroidal geometries with closed flux surfaces. Experimental studies of spheromak plasmas sustained with IDCD have shown stable magnetic profiles with evidence of pressure confinement. New measurements show coherent motion of a stable spheromak in response to the imposed perturbations. On the original device two helicity injectors were mounted on either side of the spheromak and the injected mode spectrum was predominantly n  =  1. Coherent, rigid motion indicates that the spheromak is stable and a lack of plasma-generated n  =  1 energy indicates that the maximum q is maintained below 1 during sustainment. Results from the HIT-SI3 device are also presented. Three inductive helicity injectors are mounted on one side of the spheromak flux conserver. Varying the relative injector phasing changes the injected mode spectrum which includes n  =  2, 3, and higher modes.

Enhanced Control for Local Helicity Injection on the Pegasus ST

NASA Astrophysics Data System (ADS)

Pierren, C.; Bongard, M. W.; Fonck, R. J.; Lewicki, B. T.; Perry, J. M.

2017-10-01

Local helicity injection (LHI) experiments on Pegasus rely upon programmable control of a 250 MVA modular power supply system that drives the electromagnets and helicity injection systems. Precise control of the central solenoid is critical to experimental campaigns that test the LHI Taylor relaxation limit and the coupling efficiency of LHI-produced plasmas to Ohmic current drive. Enhancement and expansion of the present control system is underway using field programmable gate array (FPGA) technology for digital logic and control, coupled to new 10 MHz optical-to-digital transceivers for semiconductor level device communication. The system accepts optical command signals from existing analog feedback controllers, transmits them to multiple devices in parallel H-bridges, and aggregates their status signals for fault detection. Present device-level multiplexing/de-multiplexing and protection logic is extended to include bridge-level protections with the FPGA. An input command filter protects against erroneous and/or spurious noise generated commands that could otherwise cause device failures. Fault registration and response times with the FPGA system are 25 ns. Initial system testing indicates an increased immunity to power supply induced noise, enabling plasma operations at higher working capacitor bank voltage. This can increase the applied helicity injection drive voltage, enable longer pulse lengths and improve Ohmic loop voltage control. Work supported by US DOE Grant DE-FG02-96ER54375.

Equilibrium Reconstruction on the Large Helical Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samuel A. Lazerson, D. Gates, D. Monticello, H. Neilson, N. Pomphrey, A. Reiman S. Sakakibara, and Y. Suzuki

Equilibrium reconstruction is commonly applied to axisymmetric toroidal devices. Recent advances in computational power and equilibrium codes have allowed for reconstructions of three-dimensional fields in stellarators and heliotrons. We present the first reconstructions of finite beta discharges in the Large Helical Device (LHD). The plasma boundary and magnetic axis are constrained by the pressure profile from Thomson scattering. This results in a calculation of plasma beta without a-priori assumptions of the equipartition of energy between species. Saddle loop arrays place additional constraints on the equilibrium. These reconstruction utilize STELLOPT, which calls VMEC. The VMEC equilibrium code assumes good nested fluxmore » surfaces. Reconstructed magnetic fields are fed into the PIES code which relaxes this constraint allowing for the examination of the effect of islands and stochastic regions on the magnetic measurements.« less

Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity

NASA Astrophysics Data System (ADS)

Howson, Suzanne E.; Bolhuis, Albert; Brabec, Viktor; Clarkson, Guy J.; Malina, Jaroslav; Rodger, Alison; Scott, Peter

2012-01-01

The helicates—chiral assemblies of two or more metal atoms linked by short or relatively rigid multidentate organic ligands—may be regarded as non-peptide mimetics of α-helices because they are of comparable size and have shown some relevant biological activity. Unfortunately, these beautiful helical compounds have remained difficult to use in the medicinal arena because they contain mixtures of isomers, cannot be optimized for specific purposes, are insoluble, or are too difficult to synthesize. Instead, we have now prepared thermodynamically stable single enantiomers of monometallic units connected by organic linkers. Our highly adaptable self-assembly approach enables the rapid preparation of ranges of water-stable, helicate-like compounds with high stereochemical purity. One such iron(II) ‘flexicate’ system exhibits specific interactions with DNA, promising antimicrobial activity against a Gram-positive bacterium (methicillin-resistant Staphylococcus aureus, MRSA252), but also, unusually, a Gram-negative bacterium (Escherichia coli, MC4100), as well as low toxicity towards a non-mammalian model organism (Caenorhabditis elegans).

Specific arrangement of alpha-helical coiled coils in the core domain of the bacterial flagellar hook for the universal joint function.

PubMed

Fujii, Takashi; Kato, Takayuki; Namba, Keiichi

2009-11-11

The bacterial flagellar hook is a short, highly curved tubular structure connecting the rotary motor to the filament acting as a helical propeller. The bending flexibility of the hook allows it to work as a universal joint. A partial atomic model of the hook revealed a sliding intersubunit domain interaction along the protofilament to produce bending flexibility. However, it remained unclear how the tightly packed inner core domains can still permit axial extension and compression. We report advances in cryoEM image analysis for high-resolution, high-throughput structural analysis and a density map of the hook that reveals most of the secondary structures, including the terminal alpha helices forming a coiled coil. The orientations and axial packing interactions of these two alpha helices are distinctly different from those of the filament, allowing them to have a room for axial compression and extension for bending flexibility without impairing the mechanical stability of the hook.

α-Helix Unwinding as Force Buffer in Spectrins.

PubMed

Takahashi, Hirohide; Rico, Felix; Chipot, Christophe; Scheuring, Simon

2018-03-27

Spectrins are cytoskeletal proteins located at the inner face of the plasma membrane, making connections between membrane anchors and the actin cortex, and between actin filaments. Spectrins share a common structure forming a bundle of 3 α-helices and play a major role during cell deformation. Here, we used high-speed force spectroscopy and steered molecular dynamics simulations to understand the mechanical stability of spectrin, revealing a molecular force buffering function. We find that spectrin acts as a soft spring at short extensions (70-100 Å). Under continuous external stretching, its α-helices unwind, leading to a viscous mechanical response over larger extensions (100-300 Å), represented by a constant-force plateau in force/extension curves. This viscous force buffering emerges from a quasi-equilibrium competition between disruption and re-formation of α-helical hydrogen bonds. Our results suggest that, in contrast to β-sheet proteins, which unfold in a catastrophic event, α-helical spectrins dominantly unwind, providing a viscous force buffer over extensions about 5 times their folded length.

Emergent perversions in the buckling of heterogeneous elastic strips

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shuangping; Yao, Zhenwei; Chiou, Kevin

A perversion in an otherwise uniform helical structure, such as a climbing plant tendril, refers to a kink that connects two helices with opposite chiralities. Such singularity structures are widely seen in natural and artificial mechanical systems, and they provide the fundamental mechanism of helical symmetry breaking. However, it is still not clear how perversions arise in various helical structures and which universal principles govern them. As such, a heterogeneous elastic bistrip system provides an excellent model to address these questions. In this paper, we investigate intrinsic perversion properties which are independent of strip shapes. This study reveals the richmore » physics of perversions in the 3D elastic system, including the condensation of strain energy over perversions during their formation, the repulsive nature of the perversion–perversion interaction, and the coalescence of perversions that finally leads to a linear defect structure. Finally, this study may have implications for understanding relevant biological motifs and for use of perversions as energy storers in the design of micromuscles and soft robotics.« less

Magneto-orbital helices: a novel coupling mechanism between magnetism and ferroelectricity in multiferroic CaMn7O12

NASA Astrophysics Data System (ADS)

Radaelli, Paolo G.; Perks, Natasha; Johnson, Roger D.; Martin, Christine; Chapon, Laurent

2013-03-01

The trigonal quadruple perovskite CaMn7O12 displays one of the largest magnetically induced ferroelectric polarisations measured to date (2870 μC m-2). Ferroelectricity appears below 90 K, together with an incommensurate helical magnetic modulation, and cannot be explained within the framework developed for cycloidal magnets. We report an unprecedented magneto-orbital texture in multiferroic CaMn7O12, which is directly connected to ferroelectricity. X-ray and neutron diffraction characterisation of the structural and magnetic modulations in these ``magneto-orbital helices'', and analysis of magnetic exchange shows that orbital order is crucial in stabilising a chiral magnetic structure. Additionally, the presence of a global structural rotation enables the magnetic helicity to couple with the lattice, giving rise to electric polarisation. These novel principles open up the possibility of discovering new multiferroics with even larger polarization and higher transition temperatures. Work at Oxford was funded by EPSRC grant EP/J003557/1.

Emergent perversions in the buckling of heterogeneous elastic strips

DOE PAGES

Liu, Shuangping; Yao, Zhenwei; Chiou, Kevin; ...

2016-06-14

A perversion in an otherwise uniform helical structure, such as a climbing plant tendril, refers to a kink that connects two helices with opposite chiralities. Such singularity structures are widely seen in natural and artificial mechanical systems, and they provide the fundamental mechanism of helical symmetry breaking. However, it is still not clear how perversions arise in various helical structures and which universal principles govern them. As such, a heterogeneous elastic bistrip system provides an excellent model to address these questions. In this paper, we investigate intrinsic perversion properties which are independent of strip shapes. This study reveals the richmore » physics of perversions in the 3D elastic system, including the condensation of strain energy over perversions during their formation, the repulsive nature of the perversion–perversion interaction, and the coalescence of perversions that finally leads to a linear defect structure. Finally, this study may have implications for understanding relevant biological motifs and for use of perversions as energy storers in the design of micromuscles and soft robotics.« less

Modelling DNA origami self-assembly at the domain level.

PubMed

Dannenberg, Frits; Dunn, Katherine E; Bath, Jonathan; Kwiatkowska, Marta; Turberfield, Andrew J; Ouldridge, Thomas E

2015-10-28

We present a modelling framework, and basic model parameterization, for the study of DNA origami folding at the level of DNA domains. Our approach is explicitly kinetic and does not assume a specific folding pathway. The binding of each staple is associated with a free-energy change that depends on staple sequence, the possibility of coaxial stacking with neighbouring domains, and the entropic cost of constraining the scaffold by inserting staple crossovers. A rigorous thermodynamic model is difficult to implement as a result of the complex, multiply connected geometry of the scaffold: we present a solution to this problem for planar origami. Coaxial stacking of helices and entropic terms, particularly when loop closure exponents are taken to be larger than those for ideal chains, introduce interactions between staples. These cooperative interactions lead to the prediction of sharp assembly transitions with notable hysteresis that are consistent with experimental observations. We show that the model reproduces the experimentally observed consequences of reducing staple concentration, accelerated cooling, and absent staples. We also present a simpler methodology that gives consistent results and can be used to study a wider range of systems including non-planar origami.

Modelling DNA origami self-assembly at the domain level

NASA Astrophysics Data System (ADS)

Dannenberg, Frits; Dunn, Katherine E.; Bath, Jonathan; Kwiatkowska, Marta; Turberfield, Andrew J.; Ouldridge, Thomas E.

2015-10-01

We present a modelling framework, and basic model parameterization, for the study of DNA origami folding at the level of DNA domains. Our approach is explicitly kinetic and does not assume a specific folding pathway. The binding of each staple is associated with a free-energy change that depends on staple sequence, the possibility of coaxial stacking with neighbouring domains, and the entropic cost of constraining the scaffold by inserting staple crossovers. A rigorous thermodynamic model is difficult to implement as a result of the complex, multiply connected geometry of the scaffold: we present a solution to this problem for planar origami. Coaxial stacking of helices and entropic terms, particularly when loop closure exponents are taken to be larger than those for ideal chains, introduce interactions between staples. These cooperative interactions lead to the prediction of sharp assembly transitions with notable hysteresis that are consistent with experimental observations. We show that the model reproduces the experimentally observed consequences of reducing staple concentration, accelerated cooling, and absent staples. We also present a simpler methodology that gives consistent results and can be used to study a wider range of systems including non-planar origami.

Detailed noise measurements on the SR-7A propeller: Tone behavior with helical tip Mach number

NASA Technical Reports Server (NTRS)

Dittmar, James H.; Hall, David G.

1991-01-01

Detailed noise measurements were taken on the SR-7A propeller to investigate the behavior of the noise with helical tip Mach number and then to level off as Mach number was increased further. This behavior was further investigated by obtaining detailed pressure-time histories of data. The pressure-time histories indicate that a portion of the primary pressure pulse is progressively cancelled by a secondary pulse which results in the noise leveling off as the helical tip Mach number is increased. This second pulse appears to originate on the same blade as the primary pulse and is in some way connected to the blade itself. This leaves open the possibility of redesigning the blade to improve the cancellation; thereby, the propeller noise is reduced.

Detailed noise measurements on the SR-7A propeller: Tone behavior with helical tip Mach number

NASA Astrophysics Data System (ADS)

Dittmar, James H.; Hall, David G.

1991-12-01

Detailed noise measurements were taken on the SR-7A propeller to investigate the behavior of the noise with helical tip Mach number and then to level off as Mach number was increased further. This behavior was further investigated by obtaining detailed pressure-time histories of data. The pressure-time histories indicate that a portion of the primary pressure pulse is progressively cancelled by a secondary pulse which results in the noise leveling off as the helical tip Mach number is increased. This second pulse appears to originate on the same blade as the primary pulse and is in some way connected to the blade itself. This leaves open the possibility of redesigning the blade to improve the cancellation; thereby, the propeller noise is reduced.

Anderson transition in a multiply-twisted helix.

PubMed

Ugajin, R

2001-06-01

We investigated the Anderson transition in a multiply-twisted helix in which a helical chain of components, i.e., atoms or nanoclusters, is twisted to produce a doubly-twisted helix, which itself can be twisted to produce a triply-twisted helix, and so on, in which there are couplings between adjacent rounds of helices. As the strength of the on-site random potentials increases, an Anderson transition occurs, suggesting that the number of dimensions is 3 for electrons running along the multiply-twisted helix when the couplings between adjacent rounds are strong enough. If the couplings are weakened, the dimensionality becomes less, resulting in localization of electrons. The effect of random connections between adjacent rounds of helices and random magnetic fields that thread the structure is analyzed using the spectral statistics of a quantum particle.

Current systems of coronal loops in 3D MHD simulations

NASA Astrophysics Data System (ADS)

Warnecke, J.; Chen, F.; Bingert, S.; Peter, H.

2017-11-01

Aims: We study the magnetic field and current structure associated with a coronal loop. Through this we investigate to what extent the assumptions of a force-free magnetic field break down and where they might be justified. Methods: We analyze a three-dimensional (3D) magnetohydrodynamic (MHD) model of the solar corona in an emerging active region with the focus on the structure of the forming coronal loops. The lower boundary of this simulation is taken from a model of an emerging active region. As a consequence of the emerging magnetic flux and the horizontal motions at the surface a coronal loop forms self-consistently. We investigate the current density along magnetic field lines inside (and outside) this loop and study the magnetic and plasma properties in and around this loop. The loop is defined as the bundle of field lines that coincides with enhanced emission in extreme UV. Results: We find that the total current along the emerging loop changes its sign from being antiparallel to parallel to the magnetic field. This is caused by the inclination of the loop together with the footpoint motion. Around the loop, the currents form a complex non-force-free helical structure. This is directly related to a bipolar current structure at the loop footpoints at the base of the corona and a local reduction of the background magnetic field (I.e., outside the loop) caused by the plasma flow into and along the loop. Furthermore, the locally reduced magnetic pressure in the loop allows the loop to sustain a higher density, which is crucial for the emission in extreme UV. The action of the flow on the magnetic field hosting the loop turns out to also be responsible for the observed squashing of the loop. Conclusions: The complex magnetic field and current system surrounding it can only be modeled in 3D MHD models where the magnetic field has to balance the plasma pressure. A one-dimensional coronal loop model or a force-free extrapolation cannot capture the current system and the complex interaction of the plasma and the magnetic field in the coronal loop, despite the fact that the loop is under low-β conditions.

Structural and mechanistic insights into Mps1 kinase activation.

PubMed

Wang, Wei; Yang, Yuting; Gao, Yuefeng; Xu, Quanbin; Wang, Feng; Zhu, Songcheng; Old, William; Resing, Katheryn; Ahn, Natalie; Lei, Ming; Liu, Xuedong

2009-08-01

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-A-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation. Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the loop between helices EF and F that are essential for substrate recruitment and maintaining high levels of kinase activity. Our studies reveal critical biochemical mechanisms for Mps1 kinase regulation.

Space confinement and rotation stress induced self-organization of double-helix nanostructure: a nanotube twist with a moving catalyst head.

PubMed

Zhao, Meng-Qiang; Zhang, Qiang; Tian, Gui-Li; Huang, Jia-Qi; Wei, Fei

2012-05-22

Inorganic materials with double-helix structure have attracted intensive attention due to not only their elegant morphology but also their amazing morphology-related potential applications. The investigation on the formation mechanism of the inorganic double-helix nanostructure is the first step for the fundamental studies of their materials or physical properties. Herein, we demonstrated the space confinement and rotation stress induced self-organization mechanism of the carbon nanotube (CNT)-array double helices under scanning electron microscopy by directly observing their formation process from individual layered double hydroxide flakes, which is a kind of hydrotalcite-like material composed of positively charged layers and charge-balancing interlayer anions. Space confinement is considered to be the most important extrinsic factor for the formation of CNT-array double helices. Synchronous growth of the CNT arrays oppositely from LDH flakes with space confinement on both sides at the same time is essential for the growth of CNT-array double helices. Coiling of the as-grown CNT arrays into double helices will proceed by self-organization, tending to the most stable morphology in order to release their internal rotation stress. Based on the demonstrated mechanism, effective routes were carried out to improve the selectivity for CNT-array double helices. The work provides a promising method for the fabrication of double-helix nanostructures with their two helices connected at the end by self-assembly.

Random single amino acid deletion sampling unveils structural tolerance and the benefits of helical registry shift on GFP folding and structure.

PubMed

Arpino, James A J; Reddington, Samuel C; Halliwell, Lisa M; Rizkallah, Pierre J; Jones, D Dafydd

2014-06-10

Altering a protein's backbone through amino acid deletion is a common evolutionary mutational mechanism, but is generally ignored during protein engineering primarily because its effect on the folding-structure-function relationship is difficult to predict. Using directed evolution, enhanced green fluorescent protein (EGFP) was observed to tolerate residue deletion across the breadth of the protein, particularly within short and long loops, helical elements, and at the termini of strands. A variant with G4 removed from a helix (EGFP(G4Δ)) conferred significantly higher cellular fluorescence. Folding analysis revealed that EGFP(G4Δ) retained more structure upon unfolding and refolded with almost 100% efficiency but at the expense of thermodynamic stability. The EGFP(G4Δ) structure revealed that G4 deletion caused a beneficial helical registry shift resulting in a new polar interaction network, which potentially stabilizes a cis proline peptide bond and links secondary structure elements. Thus, deletion mutations and registry shifts can enhance proteins through structural rearrangements not possible by substitution mutations alone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

On the Origin of Tremor in Parkinson’s Disease

PubMed Central

Dovzhenok, Andrey; Rubchinsky, Leonid L.

2012-01-01

The exact origin of tremor in Parkinson’s disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson’s disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop. PMID:22848541

MHD Simulation of the HIT-SI Experiment

NASA Astrophysics Data System (ADS)

Marklin, George

2003-10-01

The Helicity Injected Torus (HIT) experiment at the University of Washington has been reconfigured into a high beta spheromak with steady state AC current drive [1]. Helicity is injected by two half torus Reversed Field Pinches (RFP's) connected to the ends of the cylindrically symmetric flux conserver, rotated by 90 degrees from each other. The RFP's are driven with sinusoidally varying voltage and flux. Each side has its voltage and flux in phase, but is 90 degrees out of phase from the other side. The helicity injection rate, which is proportional to the voltage times the flux, goes like sin(wt)^2 on one side and cos(wt)^2 on the other, making the total injection rate constant in time. The complex multiply connected 3-dimensional geometry of this device make it difficult to simulate with existing codes that typically use a structured mesh. This poster will describe a new 3D MHD simulation code and a new 3D Taylor state code which both use an unstructured finite element mesh. The mesh is generated from a CAD-like description of an arbitrary arrangement of 3D geometrical objects. Taylor states in the HIT-SI geometry will be shown for different combinations of fluxes in the two injectors. MHD simulation results will be shown starting from a Taylor state with uniform density and temperature and continuing through several cycles of time dependent helicity injection. Field line tracing plots will show the quality of the flux surfaces at various stages in the injection cycle. [1] T. R. Jarboe, Fusion Technology, vol. 36, p. 85, 1999

A Sun-to-Earth Analysis of Magnetic Helicity of the 2013 March 17–18 Interplanetary Coronal Mass Ejection

NASA Astrophysics Data System (ADS)

Pal, Sanchita; Gopalswamy, Nat; Nandy, Dibyendu; Akiyama, Sachiko; Yashiro, Seiji; Makela, Pertti; Xie, Hong

2017-12-01

We compare the magnetic helicity in the 2013 March 17–18 interplanetary coronal mass ejection (ICME) flux rope at 1 au and in its solar counterpart. The progenitor coronal mass ejection (CME) erupted on 2013 March 15 from NOAA active region 11692 and is associated with an M1.1 flare. We derive the source region reconnection flux using the post-eruption arcade (PEA) method that uses the photospheric magnetogram and the area under the PEA. The geometrical properties of the near-Sun flux rope is obtained by forward-modeling of white-light CME observations. Combining the geometrical properties and the reconnection flux, we extract the magnetic properties of the CME flux rope. We derive the magnetic helicity of the flux rope using its magnetic and geometric properties obtained near the Sun and at 1 au. We use a constant-α force-free cylindrical flux rope model fit to the in situ observations in order to derive the magnetic and geometric information of the 1 au ICME. We find a good correspondence in both amplitude and sign of the helicity between the ICME and the CME, assuming a semi-circular (half torus) ICME flux rope with a length of π au. We find that about 83% of the total flux rope helicity at 1 au is injected by the magnetic reconnection in the low corona. We discuss the effect of assuming flux rope length in the derived value of the magnetic helicity. This study connecting the helicity of magnetic flux ropes through the Sun–Earth system has important implications for the origin of helicity in the interplanetary medium and the topology of ICME flux ropes at 1 au and hence their space weather consequences.

Self-Organized Stationary States of Tokamaks

DOE PAGES

Jardin, S. C.; Ferraro, N.; Krebs, I.

2015-11-17

We demonstrate that in a 3D resistive magnetohydrodynamic (MHD) simulation, for some parameters it is possible to form a stationary state in a tokamak where a saturated interchange mode in the center of the discharge drives a near helical flow pattern that acts to non-linearly sustain the configuration by adjusting the central loop voltage through a dynamo action. This could explain the physical mechanism for maintaining stationary non-sawtoothing “hybrid” discharges, often referred to as “flux-pumping”.

Loop-to-helix transition in the structure of multidrug regulator AcrR at the entrance of the drug-binding cavity.

PubMed

Manjasetty, Babu A; Halavaty, Andrei S; Luan, Chi-Hao; Osipiuk, Jerzy; Mulligan, Rory; Kwon, Keehwan; Anderson, Wayne F; Joachimiak, Andrzej

2016-04-01

Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices α4 and α7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helix α4 is stabilized by the hydrogen bond between Glu67 (helix α4) and Gln130 (helix α7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix α4. This local conformational switch of helix α4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution small-molecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol. Copyright © 2016. Published by Elsevier Inc.

Persistence of evolutionary memory: primordial six-transmembrane helical domain mu opiate receptors selectively linked to endogenous morphine signaling.

PubMed

Kream, Richard M; Sheehan, Melinda; Cadet, Patrick; Mantione, Kirk J; Zhu, Wei; Casares, Federico; Stefano, George B

2007-12-01

Biochemical, molecular and pharmacological evidence for two unique six-transmembrane helical (TMH) domain opiate receptors expressed from the micro opioid receptor (MOR) gene have been shown. Designated micro3 and micro4 receptors, both protein species are Class A rhodopsin-like members of the superfamily of G-protein coupled receptors but are selectively tailored to mediate the cellular regulatory effects of endogenous morphine and related morphinan alkaloids via stimulation of nitric oxide (NO) production and release. Both micro3 and micro4 receptors lack an amino acid sequence of approximately 90 amino acids that constitute the extracellular N-terminal and TMH1 domains and part of the first intracellular loop of the micro1 receptor, but retain the empirically defined ligand binding pocket distributed across conserved TMH2, TMH3, and TMH7 domains of the micro1 sequence. Additionally, the receptor proteins are terminated by unique intracellular C-terminal amino acid sequences that serve as putative coupling or docking domains required for constitutive NO synthase activation. Because the recognition profile of micro3 and micro4 receptors is restricted to rigid benzylisoquinoline alkaloids typified by morphine and its extended family of chemical congeners, it is hypothesized that conformational stabilization provided by interaction of extended extracellular N-terminal protein domains and the extracellular loops is required for binding of endogenous opioid peptides as well as synthetic flexible opiate alkaloids.

A four-way junction with triple-helical arms: design, characterization, and stability.

PubMed

Makube, N; Klump, H H

2000-05-01

The formation of the four-way junction containing four triple-helical arms has been demonstrated using chemical methods (polyacrylamide gel electrophoresis and chemical footprinting using OsO(4) as a probe) and physical methods (UV absorbance melting and DSC). The junction J(T1T3) was assembled from two 20-mer purine strands and two 44-mer pyrimidine strands. To determine the contribution of the different arms to the stability of the complete structure of J(T1T3), the junction was compared to two simplified substructures, J(T1) and J(T3), respectively. Common to these complexes is the underlying double-helical four-way junction Js. Addition of Na(+) had a profound effect on stabilizing and subsequently folding the junctions into the stacked X-structures. The following results support the structure present: (i) The native polyacrylamide electrophoresis exhibits only a single band(s) corresponding to one species present when all four single strands are mixed in equal amounts. (ii) OsO(4) modifications were investigated at pH 5.0 and in the presence of 10 mM Mg(2+) and 100 mM Na(+). There is no cleavage of thymine residues at the branch point and throughout the structure. (iii) The thermal unfolding of J(T1) and J(T3) illustrates that the triple-helical arms are more stable than the double-helical arms which are contained in these junctions and that J(T1T3) with four triple-helical arms is slightly more stable than J(T1) and J(T3). (iv) The calorimetric transition enthalpies determined for the arms of J(T1T3) are comparable to those associated with the unfolding of its corresponding arms in J(T1) and J(T3). The results also illustrate that the formation of the junctions is not restricted by the pH, [Na(+)], sequence composition of the arms, and/or the loop position. Copyright 2000 Academic Press.

A small modified hammerhead ribozyme and its conformational characteristics determined by mutagenesis and lattice calculation.

PubMed Central

Lustig, B; Lin, N H; Smith, S M; Jernigan, R L; Jeang, K T

1995-01-01

A prototypic hammerhead ribozyme has three helices that surround an asymmetrical central core loop. We have mutagenized a hammerhead type ribozyme. In agreement with previous studies, progressive removal of stem-loop II from a three stemmed ribozyme showed that this region is not absolutely critical for catalysis. However, complete elimination of stem II and its loop did reduce, but did not eliminate, function. In a stem-loop II-deleted ribozyme, activity was best preserved when a purine, preferably a G, was present at position 10.1. This G contributed to catalysis irregardless of its role as either one part of a canonical pair with a C residue at 11.1 or a lone nucleotide with C (11.1) deleted. Computational methods using lattices generated 87 million three-dimensional chain forms for a stem-loop II-deleted RNA complex that preserved one potential G.C base pair at positions 10.1 and 11.1. This exhaustive set of chain forms included one major class of structures with G(10.1) being spatially proximal to the GUCX cleavage site of the substrate strand. Strong correlations were observed between colinear arrangement of stems I and III, constraints of base-pairing in the central core loop, and one particular placement of G(10.1) relative to the cleavage site. Our calculations of a stem-loop II-deleted ribozyme indicate that without needing to invoke any other constraints, the inherent asymmetry in the lengths of the two loop strands (3 nt in one and 7 nt in the other) that compose the core and flank G10.1-C11.1 stipulated strongly this particular G placement. This suggests that the hammerhead ribozyme maintains an asymmetry in its internal loop for a necessary structure/function reason. Images PMID:7567466

Predicting stability of alpha-helical, orthogonal-bundle proteins on surfaces

NASA Astrophysics Data System (ADS)

Wei, Shuai; Knotts, Thomas A.

2010-09-01

The interaction of proteins with surfaces is a key phenomenon in many applications, but current understanding of the biophysics involved is lacking. At present, rational design of such emerging technologies is difficult as no methods or theories exist that correctly predict how surfaces influence protein behavior. Using molecular simulation and a coarse-grain model, this study illustrates for the first time that stability of proteins on surfaces can be correlated with tertiary structural elements for alpha-helical, orthogonal-bundle proteins. Results show that several factors contribute to stability on surfaces including the nature of the loop region where the tether is placed and the ability of the protein to freely rotate on the surface. A thermodynamic analysis demonstrates that surfaces stabilize proteins entropically and that any destabilization is an enthalpic effect. Moreover, the entropic effects are concentrated on the unfolded state of the protein while the ethalpic effects are focused on the folded state.

Histidine residues in the Na+-coupled ascorbic acid transporter-2 (SVCT2) are central regulators of SVCT2 function, modulating pH sensitivity, transporter kinetics, Na+ cooperativity, conformational stability, and subcellular localization.

PubMed

Ormazabal, Valeska; Zuñiga, Felipe A; Escobar, Elizabeth; Aylwin, Carlos; Salas-Burgos, Alexis; Godoy, Alejandro; Reyes, Alejandro M; Vera, Juan Carlos; Rivas, Coralia I

2010-11-19

Na(+)-coupled ascorbic acid transporter-2 (SVCT2) activity is impaired at acid pH, but little is known about the molecular determinants that define the transporter pH sensitivity. SVCT2 contains six histidine residues in its primary sequence, three of which are exofacial in the transporter secondary structure model. We used site-directed mutagenesis and treatment with diethylpyrocarbonate to identify histidine residues responsible for SVCT2 pH sensitivity. We conclude that five histidine residues, His(109), His(203), His(206), His(269), and His(413), are central regulators of SVCT2 function, participating to different degrees in modulating pH sensitivity, transporter kinetics, Na(+) cooperativity, conformational stability, and subcellular localization. Our results are compatible with a model in which (i) a single exofacial histidine residue, His(413), localized in the exofacial loop IV that connects transmembrane helices VII-VIII defines the pH sensitivity of SVCT2 through a mechanism involving a marked attenuation of the activation by Na(+) and loss of Na(+) cooperativity, which leads to a decreased V(max) without altering the transport K(m); (ii) exofacial histidine residues His(203), His(206), and His(413) may be involved in maintaining a functional interaction between exofacial loops II and IV and influence the general folding of the transporter; (iii) histidines 203, 206, 269, and 413 affect the transporter kinetics by modulating the apparent transport K(m); and (iv) histidine 109, localized at the center of transmembrane helix I, might be fundamental for the interaction of SVCT2 with the transported substrate ascorbic acid. Thus, histidine residues are central regulators of SVCT2 function.

A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations.

PubMed

Schweikardt, Thorsten; Olivares, Concepción; Solano, Francisco; Jaenicke, Elmar; García-Borrón, José Carlos; Decker, Heinz

2007-10-01

Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase.

Solution structure of the C-terminal X domain of the measles virus phosphoprotein and interaction with the intrinsically disordered C-terminal domain of the nucleoprotein.

PubMed

Gely, Stéphane; Lowry, David F; Bernard, Cédric; Jensen, Malene R; Blackledge, Martin; Costanzo, Stéphanie; Bourhis, Jean-Marie; Darbon, Hervé; Daughdrill, Gary; Longhi, Sonia

2010-01-01

In this report, the solution structure of the nucleocapsid-binding domain of the measles virus phosphoprotein (XD, aa 459-507) is described. A dynamic description of the interaction between XD and the disordered C-terminal domain of the nucleocapsid protein, (N(TAIL), aa 401-525), is also presented. XD is an all alpha protein consisting of a three-helix bundle with an up-down-up arrangement of the helices. The solution structure of XD is very similar to the crystal structures of both the free and bound form of XD. One exception is the presence of a highly dynamic loop encompassing XD residues 489-491, which is involved in the embedding of the alpha-helical XD-binding region of N(TAIL). Secondary chemical shift values for full-length N(TAIL) were used to define the precise boundaries of a transient helical segment that coincides with the XD-binding domain, thus shedding light on the pre-recognition state of N(TAIL). Titration experiments with unlabeled XD showed that the transient alpha-helical conformation of N(TAIL) is stabilized upon binding. Lineshape analysis of NMR resonances revealed that residues 483-506 of N(TAIL) are in intermediate exchange with XD, while the 475-482 and 507-525 regions are in fast exchange. The N(TAIL) resonance behavior in the titration experiments is consistent with a complex binding model with more than two states.

Entropic benefit of a cross-link in protein association.

PubMed

Zaman, Muhammad H; Berry, R Stephen; Sosnick, Tobin R

2002-08-01

We introduce a method to estimate the loss of configurational entropy upon insertion of a cross-link to a dimeric system. First, a clear distinction is established between the loss of entropy upon tethering and binding, two quantities that are often considered to be equivalent. By comparing the probability distribution of the center-to-center distances for untethered and cross-linked versions, we are able to calculate the loss of translational entropy upon cross-linking. The distribution function for the untethered helices is calculated from the probability that a given helix is closer to its partner than to all other helices, the "Nearest Neighbor" method. This method requires no assumptions about the nature of the solvent, and hence resolves difficulties normally associated with calculations for systems in liquids. Analysis of the restriction of angular freedom upon tethering indicates that the loss of rotational entropy is negligible. The method is applied in the context of the folding of a ten turn helical coiled coil with the tether modeled as a Gaussian chain or a flexible amino acid chain. After correcting for loop closure entropy in the docked state, we estimate the introduction of a six-residue tether in the coiled coil results in an effective concentration of the chain to be about 4 or 100 mM, depending upon whether the helices are denatured or pre-folded prior to their association. Thus, tethering results in significant stabilization for systems with millimolar or stronger dissociation constants. Copyright 2002 Wiley-Liss, Inc.

The roles of the conserved tyrosine in the β2-α2 loop of the prion protein.

PubMed

Huang, Danzhi; Caflisch, Amedeo

2015-01-01

Prions cause neurodegenerative diseases for which no cure exists. Despite decades of research activities the function of the prion protein (PrP) in mammalians is not known. Moreover, little is known on the molecular mechanisms of the self-assembly of the PrP from its monomeric state (cellular PrP, PrP(C)) to the multimeric state. The latter state includes the toxic species (scrapie PrP, PrP(Sc)) knowledge of which would facilitate the development of drugs against prion diseases. Here we analyze the role of a tyrosine residue (Y169) which is strictly conserved in mammalian PrPs. Nuclear magnetic resonance (NMR) spectroscopy studies of many mammalian PrP(C) proteins have provided evidence of a conformational equilibrium between a 3(10)-helical turn and a type I β turn conformation in the β2-α2 loop (residues 165-175). In vitro cell-free experiments of the seeded conversion of PrP(C) indicate that non-aromatic residues at position 169 reduce the formation of proteinase K-resistant PrP. Recent molecular dynamics (MD) simulations of monomeric PrP and several single-point mutants show that Y169 stabilizes the 3(10)-helical turn conformation more than single-point mutants at position 169 or residues in contact with it. In the 3(10)-helical turn conformation the hydrophobic and aggregation-prone segment 169-YSNQNNF-175 is buried and thus not-available for self-assembly. From the combined analysis of simulation and experimental results it emerges that Y169 is an aggregation gatekeeper with a twofold role. Mutations related to 3 human prion diseases are interpreted on the basis of the gatekeeper role in the monomeric state. Another potential role of the Y169 side chain is the stabilization of the ordered aggregates, i.e., reduction of frangibility of filamentous protofibrils and fibrils, which is likely to reduce the generation of toxic species.

Energy Systems Integration News | Energy Systems Integration Facility |

Science.gov Websites

-the-loop" (HIL) to connect physical devices to software models, EdgePower is drawing on NREL's are putting their controller into a synthetic environment that is called 'controller in-the-loop controller-in-the-loop platform allows us to observe the dynamics of these buildings as they implement the

Mutational Analyses of HAMP Helices Suggest a Dynamic Bundle Model of Input-Output Signaling in Chemoreceptors

PubMed Central

Zhou, Qin; Ames, Peter; Parkinson, John S.

2009-01-01

SUMMARY To test the gearbox model of HAMP signaling in the E. coli serine receptor, Tsr, we generated a series of amino acid replacements at each residue of the AS1 and AS2 helices. The residues most critical for Tsr function defined hydrophobic packing faces consistent with a 4-helix bundle. Suppression patterns of helix lesions conformed to the the predicted packing layers in the bundle. Although the properties and patterns of most AS1 and AS2 lesions were consistent with both proposed gearbox structures, some mutational features specifically indicate the functional importance of an x-da bundle over an alternative a-d bundle. These genetic data suggest that HAMP signaling could simply involve changes in the stability of its x-da bundle. We propose that Tsr HAMP controls output signals by modulating destabilizing phase clashes between the AS2 helices and the adjoining kinase control helices. Our model further proposes that chemoeffectors regulate HAMP bundle stability through a control cable connection between the transmembrane segments and AS1 helices. Attractant stimuli, which cause inward piston displacements in chemoreceptors, should reduce cable tension, thereby stabilizing the HAMP bundle. This study shows how transmembrane signaling and HAMP input-output control could occur without the helix rotations central to the gearbox model. PMID:19656294

The NMR solution structure of a mutant of the Max b/HLH/LZ free of DNA: insights into the specific and reversible DNA binding mechanism of dimeric transcription factors.

PubMed

Sauvé, Simon; Tremblay, Luc; Lavigne, Pierre

2004-09-17

Basic region-helix1-loop-helix2-leucine zipper (b/H(1)LH(2)/LZ) transcription factors bind specific DNA sequence in their target gene promoters as dimers. Max, a b/H(1)LH(2)/LZ transcription factor, is the obligate heterodimeric partner of the related b/H(1)LH(2)/LZ proteins of the Myc and Mad families. These heterodimers specifically bind E-box DNA sequence (CACGTG) to activate (e.g. c-Myc/Max) and repress (e.g. Mad1/Max) transcription. Max can also homodimerize and bind E-box sequences in c-Myc target gene promoters. While the X-ray structure of the Max b/H(1)LH(2)/LZ/DNA complex and that of others have been reported, the precise sequence of events leading to the reversible and specific binding of these important transcription factors is still largely unknown. In order to provide insights into the DNA binding mechanism, we have solved the NMR solution structure of a covalently homodimerized version of a Max b/H(1)LH(2)/LZ protein with two stabilizing mutations in the LZ, and characterized its backbone dynamics from (15)N spin-relaxation measurements in the absence of DNA. Apart from minor differences in the pitch of the LZ, possibly resulting from the mutations in the construct, we observe that the packing of the helices in the H(1)LH(2) domain is almost identical to that of the two crystal structures, indicating that no important conformational change in these helices occurs upon DNA binding. Conversely to the crystal structures of the DNA complexes, the first 14 residues of the basic region are found to be mostly unfolded while the loop is observed to be flexible. This indicates that these domains undergo conformational changes upon DNA binding. On the other hand, we find the last four residues of the basic region form a persistent helical turn contiguous to H(1). In addition, we provide evidence of the existence of internal motions in the backbone of H(1) that are of larger amplitude and longer time-scale (nanoseconds) than the ones in the H(2) and LZ domain. Most interestingly, we note that conformers in the ensemble of calculated structures have highly conserved basic residues (located in the persistent helical turn of the basic region and in the loop) known to be important for specific binding in a conformation that matches that of the DNA-bound state. These partially prefolded conformers can directly fit into the major groove of DNA and as such are proposed to lie on the pathway leading to the reversible and specific DNA binding. In these conformers, the conserved basic side-chains form a cluster that elevates the local electrostatic potential and could provide the necessary driving force for the generation of the internal motions localized in the H(1) and therefore link structural determinants with the DNA binding function. Overall, our results suggests that the Max homodimeric b/H(1)LH(2)/LZ can rapidly and preferentially bind DNA sequence through transient and partially prefolded states and subsequently, adopt the fully helical bound state in a DNA-assisted mechanism or induced-fit.

Mediator and Cohesin Connect Gene Expression and Chromatin Architecture

PubMed Central

Kagey, Michael H.; Newman, Jamie J.; Bilodeau, Steve; Zhan, Ye; Orlando, David A.; van Berkum, Nynke L.; Ebmeier, Christopher C.; Goossens, Jesse; Rahl, Peter B.; Levine, Stuart S.; Taatjes, Dylan J.; Dekker, Job; Young, Richard A.

2010-01-01

Summary Transcription factors control cell specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. We report here that Mediator and Cohesin physically and functionally connect the enhancers and core promoters of active genes in embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with Cohesin, which can form rings that connect two DNA segments. The Cohesin loading factor Nipbl is associated with Mediator/Cohesin complexes, providing a means to load Cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and Cohesin. Mediator and Cohesin occupy different promoters in different cells, thus generating cell-type specific DNA loops linked to the gene expression program of each cell. PMID:20720539

Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.

PubMed

Massiah, M A; Starich, M R; Paschall, C; Summers, M F; Christensen, A M; Sundquist, W I

1994-11-25

The HIV-1 matrix protein forms an icosahedral shell associated with the inner membrane of the mature virus. Genetic analyses have indicated that the protein performs important functions throughout the viral life-cycle, including anchoring the transmembrane envelope protein on the surface of the virus, assisting in viral penetration, transporting the proviral integration complex across the nuclear envelope, and localizing the assembling virion to the cell membrane. We now report the three-dimensional structure of recombinant HIV-1 matrix protein, determined at high resolution by nuclear magnetic resonance (NMR) methods. The HIV-1 matrix protein is the first retroviral matrix protein to be characterized structurally and only the fourth HIV-1 protein of known structure. NMR signal assignments required recently developed triple-resonance (1H, 13C, 15N) NMR methodologies because signals for 91% of 132 assigned H alpha protons and 74% of the 129 assignable backbone amide protons resonate within chemical shift ranges of 0.8 p.p.m. and 1 p.p.m., respectively. A total of 636 nuclear Overhauser effect-derived distance restraints were employed for distance geometry-based structure calculations, affording an average of 13.0 NMR-derived distance restraints per residue for the experimentally constrained amino acids. An ensemble of 25 refined distance geometry structures with penalties (sum of the squares of the distance violations) of 0.32 A2 or less and individual distance violations under 0.06 A was generated; best-fit superposition of ordered backbone heavy atoms relative to mean atom positions afforded root-mean-square deviations of 0.50 (+/- 0.08) A. The folded HIV-1 matrix protein structure is composed of five alpha-helices, a short 3(10) helical stretch, and a three-strand mixed beta-sheet. Helices I to III and the 3(10) helix pack about a central helix (IV) to form a compact globular domain that is capped by the beta-sheet. The C-terminal helix (helix V) projects away from the beta-sheet to expose carboxyl-terminal residues essential for early steps in the HIV-1 infectious cycle. Basic residues implicated in membrane binding and nuclear localization functions cluster about an extruded cationic loop that connects beta-strands 1 and 2. The structure suggests that both membrane binding and nuclear localization may be mediated by complex tertiary structures rather than simple linear determinants.

The Role of ABC Proteins in Drug Resistant Breast Cancer Cells

DTIC Science & Technology

2008-04-01

are indicated. (B) Cartoon of the predicted PfMDR1 secondary structure indicating helices ( gray ), loops (lines), and Walker A (vertical stripes...GTC 6 22 2 18 11 GTG 11 20 5 2 13 GTT 41 41 31 13 5 6064 Biochemistry, Vol. 46, No. 20, 2007 Amoah et al. to vanadate (Figure 4E) but high sensitivity... gray vs black bars) as were inhibitory effects seen at high dose CQ (Figure 9C, solid bars). DISCUSSION Reproducible high level overexpression of

Peptoid architectures: elaboration, actuation, and application.

PubMed

Yoo, Barney; Kirshenbaum, Kent

2008-12-01

Peptoids are peptidomimetic oligomers composed of N-substituted glycine units. Their convenient synthesis enables strict control over the sequence of highly diverse monomers and is capable of generating extensive compound libraries. Recent studies are beginning to explore the relationship between peptoid sequence, structure and function. We describe new approaches to direct the conformation of the peptoid backbone, leading to secondary structures such as helices, loops, and turns. These advances are enabling the discovery of bioactive peptoids and will establish modules for the design and assembly of protein mimetics.

Complete Michel parameter analysis of the inclusive semileptonic b{yields}c transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dassinger, Benjamin; Feger, Robert; Mannel, Thomas

2009-04-01

We perform a complete 'Michel parameter' analysis of all possible helicity structures which can appear in the process B{yields}X{sub c}l{nu}{sub l}. We take into account the full set of operators parametrizing the effective Hamiltonian and include the complete one-loop QCD corrections as well as the nonperturbative contributions. The moments of the leptonic energy as well as the combined moments of the hadronic energy and hadronic invariant mass are calculated including the nonstandard contributions.

In and out of the loop: external and internal modulation of the olivo-cerebellar loop

PubMed Central

Libster, Avraham M.; Yarom, Yosef

2013-01-01

Cerebellar anatomy is known for its crystal like structure, where neurons and connections are precisely and repeatedly organized with minor variations across the Cerebellar Cortex. The olivo-cerebellar loop, denoting the connections between the Cerebellar cortex, Inferior Olive and Cerebellar Nuclei (CN), is also modularly organized to form what is known as the cerebellar module. In contrast to the relatively organized and static anatomy, the cerebellum is innervated by a wide variety of neuromodulator carrying axons that are heterogeneously distributed along the olivo-cerebellar loop, providing heterogeneity to the static structure. In this manuscript we review modulatory processes in the olivo-cerebellar loop. We start by discussing the relationship between neuromodulators and the animal behavioral states. This is followed with an overview of the cerebellar neuromodulatory signals and a short discussion of why and when the cerebellar activity should be modulated. We then devote a section for three types of neurons where we briefly review its properties and propose possible neuromodulation scenarios. PMID:23626524

Helicity and potential vorticity in the surface boundary layer turbulence

NASA Astrophysics Data System (ADS)

Chkhetiani, Otto; Kurgansky, Michael; Koprov, Boris; Koprov, Victor

2016-04-01

An experimental measurement of all three components of the velocity and vorticity vectors, as well as the temperature and its gradient, and potential vorticity, has been developed using four acoustic anemometers. Anemometers were placed at vertices of a tetrahedron, the horizontal base of which was a rectangular triangle with equal legs, and the upper point was exactly above the top of the right angle. The distance from the surface to the tetrahedron its base was 5.5 m, and the lengths of legs and a vertical edge were 5 m. The measurements were carried out of total duration near 100 hours both in stable and unstable stratification conditions (at the Tsimlyansk Scientific Station in a uniform area of virgin steppe 700 x 650 m, August 2012). A covariance-correlation matrix for turbulent variations in all measured values has been calculated. In the daytime horizontal and vertical components of the helicity are of the order of -0.03 and +0.01 m s-2, respectively. The nighttime signs remain unchanged, but the absolute values are several times smaller. It is confirmed also by statistics of a relative helicity. The cospectra and spectral correlation coefficients have been calculated for all helicity components. The time variations in the components of "instantaneous" relative helicity and potential vorticity are considered. Connections of helicity with Monin-Obukhov length and the wind vertical profile structure are discussed. This work was supported by the Russian Science Foundation (Project No 14-27-00134).

The Minimum M3-M4 Loop Length of Neurotransmitter-activated Pentameric Receptors Is Critical for the Structural Integrity of Cytoplasmic Portals*

PubMed Central

Baptista-Hon, Daniel T.; Deeb, Tarek Z.; Lambert, Jeremy J.; Peters, John A.; Hales, Tim G.

2013-01-01

The 5-HT3A receptor homology model, based on the partial structure of the nicotinic acetylcholine receptor from Torpedo marmorata, reveals an asymmetric ion channel with five portals framed by adjacent helical amphipathic (HA) stretches within the 114-residue loop between the M3 and M4 membrane-spanning domains. The positive charge of Arg-436, located within the HA stretch, is a rate-limiting determinant of single channel conductance (γ). Further analysis reveals that positive charge and volume of residue 436 are determinants of 5-HT3A receptor inward rectification, exposing an additional role for portals. A structurally unresolved stretch of 85 residues constitutes the bulk of the M3-M4 loop, leaving a >45-Å gap in the model between M3 and the HA stretch. There are no additional structural data for this loop, which is vestigial in bacterial pentameric ligand-gated ion channels and was largely removed for crystallization of the Caenorhabditis elegans glutamate-activated pentameric ligand-gated ion channels. We created 5-HT3A subunit loop truncation mutants, in which sequences framing the putative portals were retained, to determine the minimum number of residues required to maintain their functional integrity. Truncation to between 90 and 75 amino acids produced 5-HT3A receptors with unaltered rectification. Truncation to 70 residues abolished rectification and increased γ. These findings reveal a critical M3-M4 loop length required for functions attributable to cytoplasmic portals. Examination of all 44 subunits of the human neurotransmitter-activated Cys-loop receptors reveals that, despite considerable variability in their sequences and lengths, all M3-M4 loops exceed 70 residues, suggesting a fundamental requirement for portal integrity. PMID:23740249

Axial flow positive displacement worm compressor

NASA Technical Reports Server (NTRS)

Murrow, Kurt David (Inventor); Giffin, Rollin George (Inventor); Fakunle, Oladapo (Inventor)

2010-01-01

An axial flow positive displacement compressor has an inlet axially spaced apart and upstream from an outlet. Inner and outer bodies have offset inner and outer axes extend from the inlet to the outlet through first and second sections of a compressor assembly in serial downstream flow relationship. At least one of the bodies is rotatable about its axis. The inner and outer bodies have intermeshed inner and outer helical blades wound about the inner and outer axes respectively. The inner and outer helical blades extend radially outwardly and inwardly respectively. The helical blades have first and second twist slopes in the first and second sections respectively. The first twist slopes are less than the second twist slopes. An engine including the compressor has in downstream serial flow relationship from the compressor a combustor and a high pressure turbine drivingly connected to the compressor by a high pressure shaft.

A helical scintillating fiber hodoscope

NASA Astrophysics Data System (ADS)

Altmeier, M.; Bauer, F.; Bisplinghoff, J.; Bissel, T.; Bollmann, R.; Busch, M.; Büßer, K.; Colberg, T.; Demirörs, L.; Diehl, O.; Dohrmann, F.; Engelhardt, H. P.; Eversheim, P. D.; Felden, O.; Gebel, R.; Glende, M.; Greiff, J.; Groß, A.; Groß-Hardt, R.; Hinterberger, F.; Jahn, R.; Jeske, M.; Jonas, E.; Krause, H.; Lahr, U.; Langkau, R.; Lindemann, T.; Lindlein, J.; Maier, R.; Maschuw, R.; Mayer-Kuckuck, T.; Meinerzhagen, A.; Nähle, O.; Pfuff, M.; Prasuhn, D.; Rohdjeß, H.; Rosendaal, D.; von Rossen, P.; Sanz, B.; Schirm, N.; Schulz-Rojahn, M.; Schwarz, V.; Scobel, W.; Thomas, S.; Trelle, H. J.; Weise, E.; Wellinghausen, A.; Wiedmann, W.; Woller, K.; Ziegler, R.; EDDA Collaboration

1999-07-01

A novel scintillating fiber hodoscope in helically cylindric geometry has been developed for detection of low multiplicity events of fast protons and other light charged particles in the internal target experiment EDDA at the Cooler Synchrotron COSY. The hodoscope consists of 640 scintillating fibers (2.5 mm diameter), arranged in four layers surrounding the COSY beam pipe. The fibers are helically wound in opposing directions and read out individually using 16-channel photomultipliers connected to a modified commercial encoding system. The detector covers an angular range of 9°⩽ Θ⩽72° and 0°⩽ ϕ⩽360° in the lab frame. The detector length is 590 mm, the inner diameter 161 mm. Geometry and granularity of the hodoscope afford a position resolution of about 1.3 mm. The detector design took into consideration a maximum of reliability and a minimum of maintenance. An LED array may be used for monitoring purposes.

Symmetric modular torsatron

DOEpatents

Rome, J.A.; Harris, J.H.

1984-01-01

A fusion reactor device is provided in which the magnetic fields for plasma confinement in a toroidal configuration is produced by a plurality of symmetrical modular coils arranged to form a symmetric modular torsatron referred to as a symmotron. Each of the identical modular coils is helically deformed and comprise one field period of the torsatron. Helical segments of each coil are connected by means of toroidally directed windbacks which may also provide part of the vertical field required for positioning the plasma. The stray fields of the windback segments may be compensated by toroidal coils. A variety of magnetic confinement flux surface configurations may be produced by proper modulation of the winding pitch of the helical segments of the coils, as in a conventional torsatron, winding the helix on a noncircular cross section and varying the poloidal and radial location of the windbacks and the compensating toroidal ring coils.

Single-molecule magnet behavior in an octanuclear dysprosium(iii) aggregate inherited from helical triangular Dy3 SMM-building blocks.

PubMed

Zhang, Li; Zhang, Peng; Zhao, Lang; Wu, Jianfeng; Guo, Mei; Tang, Jinkui

2016-06-28

An unprecedented octanuclear dysprosium(iii) cluster with the formula [Dy8L6(μ3-OH)4(μ2-CH3O)2(CH3OH)6(H2O)2]·6H2O·10CH3OH·2CH3CN () based on a nonlinearly tritopic aroylhydrazone ligand H3L has been isolated, realizing the successful linking of pairwise interesting triangular Dy3 SMMs. It is noteworthy that two enantiomers (Λ and Δ configurations) individually behaving as a coordination-induced chirality presented in the Dy3 helicate are connected in the meso Dy8 cluster. Remarkably, alternating-current magnetic susceptibility measurements revealed that the Dy8 cluster shows typical SMM behavior inherited from its Dy3 helical precursor. It is one of the rare polynuclear Lnn SMMs (n > 7) under zero dc field.

40 CFR 264.1055 - Standards: Sampling connection systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Standards: Sampling connection systems... FACILITIES Air Emission Standards for Equipment Leaks § 264.1055 Standards: Sampling connection systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed-vent...

40 CFR 265.1055 - Standards: Sampling connection systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Standards: Sampling connection systems..., STORAGE, AND DISPOSAL FACILITIES Air Emission Standards for Equipment Leaks § 265.1055 Standards: Sampling connection systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop...

40 CFR 63.1013 - Sampling connection systems standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Sampling connection systems standards... (CONTINUED) National Emission Standards for Equipment Leaks-Control Level 1 § 63.1013 Sampling connection... sampling connection system shall be equipped with a closed purge, closed loop, or closed vent system...

40 CFR 264.1055 - Standards: Sampling connection systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Standards: Sampling connection systems... FACILITIES Air Emission Standards for Equipment Leaks § 264.1055 Standards: Sampling connection systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed-vent...

40 CFR 265.1055 - Standards: Sampling connection systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Standards: Sampling connection systems..., STORAGE, AND DISPOSAL FACILITIES Air Emission Standards for Equipment Leaks § 265.1055 Standards: Sampling connection systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop...

Structural and mechanistic insights into Mps1 kinase activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei; Yang, Yuting; Gao, Yuefeng

2010-11-05

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-{angstrom}-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the {alpha}C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation.more » Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the loop between helices {alpha}EF and {alpha}F that are essential for substrate recruitment and maintaining high levels of kinase activity. Our studies reveal critical biochemical mechanisms for Mps1 kinase regulation.« less

Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface.

PubMed

Jiang, Jianwen; Taylor, Alexander B; Prasad, Kondury; Ishikawa-Brush, Yumiko; Hart, P John; Lafer, Eileen M; Sousa, Rui

2003-05-20

J-domains are widespread protein interaction modules involved in recruiting and stimulating the activity of Hsp70 family chaperones. We have determined the crystal structure of the J-domain of auxilin, a protein which is involved in uncoating clathrin-coated vesicles. Comparison to the known structures of J-domains from four other proteins reveals that the auxilin J-domain is the most divergent of all J-domain structures described to date. In addition to the canonical J-domain features described previously, the auxilin J-domain contains an extra N-terminal helix and a long loop inserted between helices I and II. The latter loop extends the positively charged surface which forms the Hsc70 binding site, and is shown by directed mutagenesis and surface plasmon resonance to contain side chains important for binding to Hsc70.

Hydrothermal synthesis, crystal structure and properties of 2-D and 3-D lanthanide sulfates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Yan; Ding Shaohua; Zheng Xuefang

2007-07-15

Two new lanthanum sulfates DySO{sub 4}(OH) 1 and Eu{sub 2}(SO{sub 4}){sub 3}(H{sub 2}O){sub 8} 2 have been hydrothermally synthesized. The colorless crystals were characterized by IR, TGA, ICP and XRD. The structure was determined by single-crystal X-ray diffraction. 1 crystallizes with monoclinic symmetry, space group P2(1)/n [a=7.995(4) A, b=10.945(5) A, c=8.164(4) A, {alpha}=90{sup o}, {beta}=93.619(6){sup o}, {gamma}=90{sup o}, V=713.0(5) A{sup 3}, Z=8]. It displays a three-dimensional framework, based on the novel Dy-O chains connected by the sulfate groups through helical chains. 2 crystallizes with monoclinic symmetry, space group C2/c, [a=13.5605(17) A, b=6.7676(8) A, c=18.318(2) A, {alpha}=90{sup o}, {beta}=102.265(2){sup o}, {gamma}=90{supmore » o}, V=1642.7 (4) A{sup 3}, Z=4]. Its layered framework is attained by the europium atoms connected by the sulfate groups arranged in a helical manner. - Graphical abstract: Two new lanthanum sulfates DySO{sub 4}(OH) 1 and Eu{sub 2} (SO{sub 4}){sub 3} (H{sub 2}O){sub 8} 2 have been hydrothermally synthesized. The colorless crystals were characterized by IR, TGA, ICP and XRD. The structure was determined by single-crystal X-ray diffraction. It displays a three dimensional framework, based on the novel Dy-O chains connected by the sulfate groups through helical chains.« less

40 CFR 60.482-5a - Standards: Sampling connection systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Standards: Sampling connection systems..., Reconstruction, or Modification Commenced After November 7, 2006 § 60.482-5a Standards: Sampling connection systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed...

40 CFR 61.242-5 - Standards: Sampling connecting systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Standards: Sampling connecting systems... for Equipment Leaks (Fugitive Emission Sources) § 61.242-5 Standards: Sampling connecting systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed vent...

40 CFR 60.482-5a - Standards: Sampling connection systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standards: Sampling connection systems..., Reconstruction, or Modification Commenced After November 7, 2006 § 60.482-5a Standards: Sampling connection systems. (a) Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed...

Crystal structure of Escherichia coli-expressed Haloarcula marismortui bacteriorhodopsin I in the trimeric form.

PubMed

Shevchenko, Vitaly; Gushchin, Ivan; Polovinkin, Vitaly; Round, Ekaterina; Borshchevskiy, Valentin; Utrobin, Petr; Popov, Alexander; Balandin, Taras; Büldt, Georg; Gordeliy, Valentin

2014-01-01

Bacteriorhodopsins are a large family of seven-helical transmembrane proteins that function as light-driven proton pumps. Here, we present the crystal structure of a new member of the family, Haloarcula marismortui bacteriorhodopsin I (HmBRI) D94N mutant, at the resolution of 2.5 Å. While the HmBRI retinal-binding pocket and proton donor site are similar to those of other archaeal proton pumps, its proton release region is extended and contains additional water molecules. The protein's fold is reinforced by three novel inter-helical hydrogen bonds, two of which result from double substitutions relative to Halobacterium salinarum bacteriorhodopsin and other similar proteins. Despite the expression in Escherichia coli and consequent absence of native lipids, the protein assembles as a trimer in crystals. The unique extended loop between the helices D and E of HmBRI makes contacts with the adjacent protomer and appears to stabilize the interface. Many lipidic hydrophobic tail groups are discernible in the membrane region, and their positions are similar to those of archaeal isoprenoid lipids in the crystals of other proton pumps, isolated from native or native-like sources. All these features might explain the HmBRI properties and establish the protein as a novel model for the microbial rhodopsin proton pumping studies.

Camps 2.0: exploring the sequence and structure space of prokaryotic, eukaryotic, and viral membrane proteins.

PubMed

Neumann, Sindy; Hartmann, Holger; Martin-Galiano, Antonio J; Fuchs, Angelika; Frishman, Dmitrij

2012-03-01

Structural bioinformatics of membrane proteins is still in its infancy, and the picture of their fold space is only beginning to emerge. Because only a handful of three-dimensional structures are available, sequence comparison and structure prediction remain the main tools for investigating sequence-structure relationships in membrane protein families. Here we present a comprehensive analysis of the structural families corresponding to α-helical membrane proteins with at least three transmembrane helices. The new version of our CAMPS database (CAMPS 2.0) covers nearly 1300 eukaryotic, prokaryotic, and viral genomes. Using an advanced classification procedure, which is based on high-order hidden Markov models and considers both sequence similarity as well as the number of transmembrane helices and loop lengths, we identified 1353 structurally homogeneous clusters roughly corresponding to membrane protein folds. Only 53 clusters are associated with experimentally determined three-dimensional structures, and for these clusters CAMPS is in reasonable agreement with structure-based classification approaches such as SCOP and CATH. We therefore estimate that ∼1300 structures would need to be determined to provide a sufficient structural coverage of polytopic membrane proteins. CAMPS 2.0 is available at http://webclu.bio.wzw.tum.de/CAMPS2.0/. Copyright © 2011 Wiley Periodicals, Inc.

Response of SCP-2L domain of human MFE-2 to ligand removal: binding site closure and burial of peroxisomal targeting signal.

PubMed

Lensink, M F; Haapalainen, A M; Hiltunen, J K; Glumoff, T; Juffer, A H

2002-10-11

In the study of the structure and function relationship of human MFE-2, we have investigated the dynamics of human MFE-2SCP-2L (hSCP-2L) and its response to ligand removal. A comparison was made with homologous rabbit SCP-2. Breathing and a closing motion are found, identifiable with an adjustment in size and a closing off of the binding pocket. Crucial residues for structural integrity have been identified. Particularly mobile areas of the protein are loop 1 that is connecting helices A and C in space, and helix D, next to the entrance of the pocket. In hSCP-2L, the binding pocket gets occupied by Phe93, which is making a tight hydrophobic contact with Trp36. In addition, it is found that the C-terminal peroxisomal targeting signal (PTS1) that is solvent exposed in the complexed structure becomes buried when no ligand is present. Moreover, an anti-correlation exists between burial of PTS1 and the size of the binding pocket. The results are in accordance with plant nsLTPs, where a similar accommodation of binding pocket size was found after ligand binding/removal. Furthermore, the calculations support the suggestion of a ligand-assisted targeting mechanism.

O2 sensing-associated glycosylation exposes the F-box-combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases.

PubMed

Sheikh, M Osman; Thieker, David; Chalmers, Gordon; Schafer, Christopher M; Ishihara, Mayumi; Azadi, Parastoo; Woods, Robert J; Glushka, John N; Bendiak, Brad; Prestegard, James H; West, Christopher M

2017-11-17

Skp1 is a conserved protein linking cullin-1 to F-box proteins in SCF ( S kp1/ C ullin-1/ F -box protein) E3 ubiquitin ligases, which modify protein substrates with polyubiquitin chains that typically target them for 26S proteasome-mediated degradation. In Dictyostelium (a social amoeba), Toxoplasma gondii (the agent for human toxoplasmosis), and other protists, Skp1 is regulated by a unique pentasaccharide attached to hydroxylated Pro-143 within its C-terminal F-box-binding domain. Prolyl hydroxylation of Skp1 contributes to O 2 -dependent Dictyostelium development, but full glycosylation at that position is required for optimal O 2 sensing. Previous studies have shown that the glycan promotes organization of the F-box-binding region in Skp1 and aids in Skp1's association with F-box proteins. Here, NMR and MS approaches were used to determine the glycan structure, and then a combination of NMR and molecular dynamics simulations were employed to characterize the impact of the glycan on the conformation and motions of the intrinsically flexible F-box-binding domain of Skp1. Molecular dynamics trajectories of glycosylated Skp1 whose calculated monosaccharide relaxation kinetics and rotational correlation times agreed with the NMR data indicated that the glycan interacts with the loop connecting two α-helices of the F-box-combining site. In these trajectories, the helices separated from one another to create a more accessible and dynamic F-box interface. These results offer an unprecedented view of how a glycan modification influences a disordered region of a full-length protein. The increased sampling of an open Skp1 conformation can explain how glycosylation enhances interactions with F-box proteins in cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Crystal structure of archaeal ribonuclease P protein Ph1771p from Pyrococcus horikoshii OT3: An archaeal homolog of eukaryotic ribonuclease P protein Rpp29

PubMed Central

NUMATA, TOMOYUKI; ISHIMATSU, IKUKO; KAKUTA, YOSHIMITSU; TANAKA, ISAO; KIMURA, MAKOTO

2004-01-01

Ribonuclease P (RNase P) is the endonuclease responsible for the removal of 5′ leader sequences from tRNA precursors. The crystal structure of an archaeal RNase P protein, Ph1771p (residues 36–127) from hyperthermophilic archaeon Pyrococcus horikoshii OT3 was determined at 2.0 Å resolution by X-ray crystallography. The structure is composed of four helices (α1–α4) and a six-stranded antiparallel β-sheet (β1–β6) with a protruding β-strand (β7) at the C-terminal region. The strand β7 forms an antiparallel β-sheet by interacting with strand β4 in a symmetry-related molecule, suggesting that strands β4 and β7 could be involved in protein-protein interactions with other RNase P proteins. Structural comparison showed that the β-barrel structure of Ph1771p has a topological resemblance to those of Staphylococcus aureus translational regulator Hfq and Haloarcula marismortui ribosomal protein L21E, suggesting that these RNA binding proteins have a common ancestor and then diverged to specifically bind to their cognate RNAs. The structure analysis as well as structural comparison suggested two possible RNA binding sites in Ph1771p, one being a concave surface formed by terminal α-helices (α1–α4) and β-strand β6, where positively charged residues are clustered. A second possible RNA binding site is at a loop region connecting strands β2 and β3, where conserved hydrophilic residues are exposed to the solvent and interact specifically with sulfate ion. These two potential sites for RNA binding are located in close proximity. The crystal structure of Ph1771p provides insight into the structure and function relationships of archaeal and eukaryotic RNase P. PMID:15317976

Polyoxometalates-based chiral frameworks involving helical motifs generated by spontaneous resolution

NASA Astrophysics Data System (ADS)

Li, Ning; Jiang, Dingding; Pan, Qiliang; Zhao, Jianguo; Zhang, Sufang; Xing, Baoyan; Du, Yaqin; Zhang, Zhong; Liu, Shuxia

2018-05-01

Two enantiomerically 3D chiral polyoxometalate frameworks L,D-[K(H2O)]6[H2GeMo2W10O40]3ṡ40H2O (1a and 1b), were conventionally synthesized and characterized by X-ray single-crystal diffraction, IR spectrum, elemental analysis, powder X-ray diffraction, thermogravimetric analysis, UV-Vis spectroscopy, circular dichroism spectra. Structural analysis indicates that 1a and 1b are enantiomers. The terminal O and μ2-O atoms of Keggin-type polyanion [GeMo2W10O40]4- and {K(H2O)}n segments are connected one another to form 1D chiral helical chains, which are further extended by the achiral Keggin-type [GeMo2W10O40]4- anion to construct 3D 4,8-connected chiral frameworks. The enantiomers were isolated by spontaneous resolution during crystallization without any chiral auxiliary. They represent rare examples of enantiomerically pure chiral polyoxometalate-based inorganic porous frameworks.

Behavior of MHD Instabilities of the Large Helical Device near the Effective Plasma Boundary in the Magnetic Stochastic Region

NASA Astrophysics Data System (ADS)

Ohdachi, S.; Suzuki, Y.; Sakakibara, S.; Watanabe, K. Y.; Ida, K.; Goto, M.; Du, X. D.; Narushima, Y.; Takemura, Y.; Yamada, H.

In the high beta experiments of the Large Helical Device (LHD), the plasma tends to expand from the last closed flux surface (LCFS) determined by the vacuum magnetic field. The pressure/temperature gradient in the external region is finite. The scale length of the pressure profile does not change so much even when the mean free path of electrons exceeds the connection length of the magnetic field line to the wall. There appear MHD instabilities with amplitude of 10-4 of the toroidal magnetic field. From the mode number of the activities (m/n = 2/3, 1/2, 2/4), the location of the corresponding rational surface is outside the vacuum LCFS. The location of the mode is consistent with the fluctuation measurement, e.g., soft X-ray detector arrays. The MHD mode localized in the magnetic stochastic region is affected by the magnetic field structure estimated by the connection length to the wall using 3D equilibrium calculation.

Anomalous basal ganglia connectivity and obsessive–compulsive behaviour in patients with Prader Willi syndrome

PubMed Central

Pujol, Jesus; Blanco-Hinojo, Laura; Esteba-Castillo, Susanna; Caixàs, Assumpta; Harrison, Ben J.; Bueno, Marta; Deus, Joan; Rigla, Mercedes; Macià, Dídac; Llorente-Onaindia, Jone; Novell-Alsina, Ramón

2016-01-01

Background Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive–compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive–compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive–compulsive behaviour in patients with Prader Willi syndrome. Methods We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive–compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour. Results We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive–compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex–putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala. Limitations Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging. Conclusion Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the primary sensorimotor loop that correlated with the most impulsive aspects of the behaviour and 2) reduced coupling of the ventral striatum with limbic structures for basic internal homeostasis that correlated with the obsession to eat. PMID:26645739

A constraint logic programming approach to associate 1D and 3D structural components for large protein complexes.

PubMed

Dal Palù, Alessandro; Pontelli, Enrico; He, Jing; Lu, Yonggang

2007-01-01

The paper describes a novel framework, constructed using Constraint Logic Programming (CLP) and parallelism, to determine the association between parts of the primary sequence of a protein and alpha-helices extracted from 3D low-resolution descriptions of large protein complexes. The association is determined by extracting constraints from the 3D information, regarding length, relative position and connectivity of helices, and solving these constraints with the guidance of a secondary structure prediction algorithm. Parallelism is employed to enhance performance on large proteins. The framework provides a fast, inexpensive alternative to determine the exact tertiary structure of unknown proteins.

GAS METERING PUMP

DOEpatents

George, C.M.

1957-12-31

A liquid piston gas pump is described, capable of pumping minute amounts of gas in accurately measurable quantities. The pump consists of a flanged cylindrical regulating chamber and a mercury filled bellows. Sealed to the ABSTRACTS regulating chamber is a value and having a gas inlet and outlet, the inlet being connected by a helical channel to the bellows. A gravity check valve is in the gas outlet, so the gas passes through the inlet and the helical channel to the bellows where the pumping action as well as the metering is accomplished by the actuation of the mercury filled bellows. The gas then flows through the check valve and outlet to any associated apparatus.

Computer-aided active-site-directed modeling of the Herpes Simplex Virus 1 and human thymidine kinase

NASA Astrophysics Data System (ADS)

Folkers, Gerd; Trumpp-Kallmeyer, Susanne; Gutbrod, Oliver; Krickl, Sabine; Fetzer, Jürgen; Keil, Günther M.

1991-10-01

Thymidine kinase (TK), which is induced by Herpes Simplex Virus 1 (HSV1), plays a key role in the antiviral activity of guanine derivatives such as aciclovir (ACV). In contrast, ACV shows only low affinity to the corresponding host cell enzyme. In order to define the differences in substrate binding of the two enzymes on molecular level, models for the three-dimensional (3-D) structures of the active sites of HSV1-TK and human TK were developed. The reconstruction of the active sites started from primary and secondary structure analysis of various kinases. The results were validated to homologous enzymes with known 3-D structures. The models predict that both enzymes consist of a central core β-sheet structure, connected by loops and α-helices very similar to the overall structure of other nucleotide binding enzymes. The phosphate binding is made up of a highly conserved glycine-rich loop at the N-terminus of the proteins and a conserved region at the C-terminus. The thymidine recognition site was found about 100 amino acids downstream from the phosphate binding loop. The differing substrate specificity of human and HSV1-TK can be explained by amino-acid substitutions in the homologous regions. To achieve a better understanding of the structure of the active site and how the thymidine kinase proteins interact with their substrates, the corresponding complexes of thymidine and dihydroxypropoxyguanine (DHPG) with HSV1 and human TK were built. For the docking of the guanine derivative, the X-ray structure of Elongation Factor Tu (EF-Tu), co-crystallized with guanosine diphosphate, was taken as reference. Fitting of thymidine into the active sites was done with respect to similar interactions found in thymidylate kinase. To complement the analysis of the 3-D structures of the two kinases and the substrate enzyme interactions, site-directed mutagenesis of the thymidine recognition site of HSV1-TK has been undertaken, changing Asp162 in the thymidine recognition site into Asn. First investigations reveal that the enzymatic activity of the mutant protein is destroyed.

Fluorescence spectroscopic characterization of Humicola lanuginosa lipase dissolved in its substrate.

PubMed

Jutila, Arimatti; Zhu, Keng; Tuominen, Esa K J; Kinnunen, Paavo K J

2004-11-01

The conformational dynamics of Humicola lanuginosa lipases (HLL) and its three mutants were investigated by steady state and time-resolved fluorescence spectroscopy in two different media, aqueous buffer and the substrate triacetin. The fluorescence of the four Trps of the wild-type HLL (wt) reports on the global changes of the whole lipase molecule. In order to monitor conformational changes specifically in the alpha-helical surface loop, the so-called 'lid' of HLL comprised of residues 86-93, the single Trp mutant W89m (W117F, W221H, W260H) was employed. Mutants W89L and W89mN33Q (W117F, W221H, W260H, N33Q) were used to survey the impact of Trp89 and mannose residues, respectively. Based on the data obtained, the following conclusions can be drawn. (i) HLL adapts the 'open' conformation in triacetin, with the alpha-helical surface loop moving so as to expose the active site. (ii) Trp89 contained in the lid plays an unprecedently important role in the structural stability of HLL. (iii) In triacetin, but not in the buffer, the motion of the Trp89 side chain becomes distinguishable from the motion of the lid. (iv) The carbohydrate moiety at Asn33 has only minor effects on the dynamics of Trp89 in the lid as judged from the fluorescence characteristics of the latter residue.

Structure/cleavage-based insights into helical perturbations at bulge sites within T. thermophilus Argonaute silencing complexes

PubMed Central

Sheng, Gang; Gogakos, Tasos; Wang, Jiuyu; Zhao, Hongtu; Serganov, Artem; Juranek, Stefan

2017-01-01

Abstract We have undertaken a systematic structural study of Thermus thermophilus Argonaute (TtAgo) ternary complexes containing single-base bulges positioned either within the seed segment of the guide or target strands and at the cleavage site. Our studies establish that single-base bulges 7T8, 5A6 and 4A5 on the guide strand are stacked-into the duplex, with conformational changes localized to the bulge site, thereby having minimal impact on the cleavage site. By contrast, single-base bulges 6’U7’ and 6’A7’ on the target strand are looped-out of the duplex, with the resulting conformational transitions shifting the cleavable phosphate by one step. We observe a stable alignment for the looped-out 6’N7’ bulge base, which stacks on the unpaired first base of the guide strand, with the looped-out alignment facilitated by weakened Watson–Crick and reversed non-canonical flanking pairs. These structural studies are complemented by cleavage assays that independently monitor the impact of bulges on TtAgo-mediated cleavage reaction. PMID:28911094

3D Studies of the Solar Corona and its Evolution with SOHO/EIT

NASA Astrophysics Data System (ADS)

Portier-Fozzani, F.

This thesis deals with 3D evolution of coronal structures based upon the ultraviolet telescope of SOHO : EIT. Anaglyphs and incertainties on a complete stereovision reconstruction are described. Stereoscopic methods for loop reconstruction were successfully made to find 3D parameters. With dynamical stereoscopy, physical conditions were derived for 30 loops of temperature around 1MK. A method which is able to derive twist variation were also built. Emerging loops were found highly twisted and they detwist as they grow. According to helicity conservation, this correspond to a transfert of twist into expansion. Long time twist evolution of magnetic flux tubes are followed in relation with flares as relaxation. Interaction between magnetic field lines were analysed. An example of reconnection between open and closed field line were observed. Other interactions were found with multi-wavelength observations : coronal holes borders (and thus CH) are better defined when an active region nearby is growing. Other imaging techniques were used to better take profit as possible of SOHO/EIT. A multiscale vision model (MVM) was applied with success to show small coronal structures evolutions hidden by the noise level.

The Caltech experimental investigation of fast 3D non-equilbrium dynamics: an overview

NASA Astrophysics Data System (ADS)

Bellan, Paul; Shikama, Taiichi; Chai, Kilbyoung; Ha, Bao; Chaplin, Vernon; Kendall, Mark; Moser, Auna; Stenson, Eve; Tobin, Zachary; Zhai, Xiang

2012-10-01

The formation and dynamics of writhing, plasma-filled, twisted open magnetic flux tubes is being investigated using pulsed-power laboratory experiments. This work is relevant to solar corona loops, astrophysical jets, spheromak formation, and open field lines in tokamaks and RFP's. MHD forces have been observed to drive fast axial plasma flows into the flux tube from the boundary it intercepts. These flows fill the flux tube with plasma while simultaneously injecting linked frozen-in azimuthal flux; helicity injection is thus associated with mass injection. Recent results include observation of a secondary instability (Rayleigh-Taylor driven by the effective gravity of an exponentially growing kink mode), color-coded plasmas manifesting bidirectional axial flows in a geometry similar to a solar corona loop, and spectroscopic measurements of the internal vector magnetic field. Experiments underway include investigating how an external magnetic field straps down a solar loop, investigation of the details of the Rayleigh-Taylor instability, development of a fast EUV movie camera, increasing the jet velocity, excitation of Alfven waves, and investigating 3D magnetic reconnection.

A loop-based neural architecture for structured behavior encoding and decoding.

PubMed

Gisiger, Thomas; Boukadoum, Mounir

2018-02-01

We present a new type of artificial neural network that generalizes on anatomical and dynamical aspects of the mammal brain. Its main novelty lies in its topological structure which is built as an array of interacting elementary motifs shaped like loops. These loops come in various types and can implement functions such as gating, inhibitory or executive control, or encoding of task elements to name a few. Each loop features two sets of neurons and a control region, linked together by non-recurrent projections. The two neural sets do the bulk of the loop's computations while the control unit specifies the timing and the conditions under which the computations implemented by the loop are to be performed. By functionally linking many such loops together, a neural network is obtained that may perform complex cognitive computations. To demonstrate the potential offered by such a system, we present two neural network simulations. The first illustrates the structure and dynamics of a single loop implementing a simple gating mechanism. The second simulation shows how connecting four loops in series can produce neural activity patterns that are sufficient to pass a simplified delayed-response task. We also show that this network reproduces electrophysiological measurements gathered in various regions of the brain of monkeys performing similar tasks. We also demonstrate connections between this type of neural network and recurrent or long short-term memory network models, and suggest ways to generalize them for future artificial intelligence research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suppression of Heating of Coronal Loops Rooted in Opposite Polarity Sunspot Umbrae

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Moore, Ronald L.; Panesar, Navdeep K.; Winebarger, Amy R.

2016-01-01

EUV observations of active region (AR) coronae reveal the presence of loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 Å images we identify many clearly discernible coronal loops that connect plage or a sunspot of one polarity to an opposite-­polarity plage region. The AIA 94 Å images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the Heliosesmic Magnetic Imager (HMI) onboard SDO. The NLFFF model, validated by comparison of calculated model field lines with observed loops in AIA 193 and 94 Å, specifies the photospheric roots of the model field lines. Some model coronal magnetic field lines arch from the dim umbral area of the positive-polarity sunspot to the dim umbral area of a negative-polarity sunspot. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.

Structural Analysis of a β-Helical Protein Motif Stabilized by Targeted Replacements with Conformationally Constrained Amino Acids

PubMed Central

Ballano, Gema; Zanuy, David; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

2009-01-01

Here we study conformational stabilization induced in a β-helical nanostructure by position-specific mutations. The nanostructure is constructed through the self-assembly of the β-helical building block excised from E. coli galactoside acetyltransferase (PDB code 1krr, chain A; residues 131-165). The mutations involve substitutions by cyclic, conformationally constrained amino acids. Specifically, a complete structural analysis of the Pro-Xaa-Val sequence [with Xaa being Gly, Ac3c (1-aminocyclopropane-1-carboxylic acid) and Ac5c (1-aminocyclopentane-1-carboxylic acid)], corresponding to the 148-150 loop region in the wild-type (Gly) and mutated (Ac3c and Ac5c) 1krr, has been performed using Molecular Dynamics simulations and X-ray crystallography. Simulations have been performed for the wild-type and mutants of three different systems, namely the building block, the nanoconstruct and the isolated Pro-Xaa-Val tripeptide. Furthermore, the crystalline structures of five peptides of Pro-Xaa-Val or Xaa-Val sequences have been solved by X-ray diffraction analysis and compared with theoretical predictions. Both the theoretical and crystallographic studies indicate that the Pro-Acnc-Val sequences exhibit a high propensity to adopt turn-like conformations, and this propensity is little affected by the chemical environment. Overall, the results indicate that replacement of Gly149 by Ac3c or Ac5c significantly reduce the conformational flexibility of the target site enhancing the structural specificity of the building block and the nanoconstruct derived from the 1krr β-helical motif. PMID:18811190

Analysis of Glucose Transporter Topology and Structural Dynamics*

PubMed Central

Blodgett, David M.; Graybill, Christopher; Carruthers, Anthony

2008-01-01

Homology modeling and scanning cysteine mutagenesis studies suggest that the human glucose transport protein GLUT1 and its distant bacterial homologs LacY and GlpT share similar structures. We tested this hypothesis by mapping the accessibility of purified, reconstituted human erythrocyte GLUT1 to aqueous probes. GLUT1 contains 35 potential tryptic cleavage sites. Fourteen of 16 lysine residues and 18 of 19 arginine residues were accessible to trypsin. GLUT1 lysine residues were modified by isothiocyanates and N-hydroxysuccinimide (NHS) esters in a substrate-dependent manner. Twelve lysine residues were accessible to sulfo-NHS-LC-biotin. GLUT1 trypsinization released full-length transmembrane helix 1, cytoplasmic loop 6–7, and the long cytoplasmic C terminus from membranes. Trypsin-digested GLUT1 retained cytochalasin B and d-glucose binding capacity and released full-length transmembrane helix 8 upon cytochalasin B (but not d-glucose) binding. Transmembrane helix 8 release did not abrogate cytochalasin B binding. GLUT1 was extensively proteolyzed by α-chymotrypsin, which cuts putative pore-forming amphipathic α-helices 1, 2, 4, 7, 8, 10, and 11 at multiple sites to release transmembrane peptide fragments into the aqueous solvent. Putative scaffolding membrane helices 3, 6, 9, and 12 are strongly hydrophobic, resistant to α-chymotrypsin, and retained by the membrane bilayer. These observations provide experimental support for the proposed GLUT1 architecture; indicate that the proposed topology of membrane helices 5, 6, and 12 requires adjustment; and suggest that the metastable conformations of transmembrane helices 1 and 8 within the GLUT1 scaffold destabilize a sugar translocation intermediate. PMID:18981181

Magnetic Helicity Injection and Thermal Transport

NASA Astrophysics Data System (ADS)

Moses, Ronald; Gerwin, Richard; Schoenberg, Kurt

1999-11-01

In magnetic helicity injection, a current is driven between electrodes, parallel to the magnetic field in the edge plasma of a machine.^1 Plasma instabilities distribute current throughout the plasma. To model the injection of magnetic helicity, K, into an arbitrary closed surface, K is defined as the volume integral of A^.B. To make K unique, a gauge is chosen where the tangential surface components of A are purely solenoidal. If magnetic fields within a plasma are time varying, yet undergo no macroscopic changes over an extended period, and if the plasma is subject to an Ohm’s law with Hall terms, then it is shown that no closed magnetic surfaces with sustained internal currents can exist continuously within the plasma.^2 It is also shown that parallel thermal transport connects all parts of the plasma to the helicity injection electrodes and requires the electrode voltage difference to be at least 2.5 to 3 times the peak plasma temperature. This ratio is almost independent of the length of the electron mean-free path. If magnetic helicity injection is to be used for fusion-grade plasmas, then high-voltage, high-impedance injection techniques must be developed. ^1T. R. Jarboe, Plasma Physics and Controlled Fusion, V36, 945-990 (June 1994). ^2R. W. Moses, 1991 Sherwood International Fusion Theory Conference, Seattle, WA (April 22-24, 1991).

Molecular dynamics studies on the buffalo prion protein.

PubMed

Zhang, Jiapu; Wang, Feng; Chatterjee, Subhojyoti

2016-01-01

It was reported that buffalo is a low susceptibility species resisting to transmissible spongiform encephalopathies (TSEs) (same as rabbits, horses, and dogs). TSEs, also called prion diseases, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species (except for rabbits, dogs, horses, and buffalo), manifesting as scrapie in sheep and goats; bovine spongiform encephalopathy (BSE or "mad-cow" disease) in cattle; chronic wasting disease in deer and elk; and Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and Kulu in humans etc. In molecular structures, these neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrP(C)), predominantly with α-helices, into insoluble abnormally folded infectious prions (PrP(Sc)), rich in β-sheets. In this article, we studied the molecular structure and structural dynamics of buffalo PrP(C) (BufPrP(C)), in order to understand the reason why buffalo is resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the NMR structure of bovine and cattle PrP(124-227); immediately we found that for BufPrP(C)(124-227), there are five hydrogen bonds (HBs) at Asn143, but at this position, bovine/cattle do not have such HBs. Same as that of rabbits, dogs, or horses, our molecular dynamics studies also revealed there is a strong salt bridge (SB) ASP178-ARG164 (O-N) keeping the β2-α2 loop linked in buffalo. We also found there is a very strong HB SER170-TYR218 linking this loop with the C-terminal end of α-helix H3. Other information, such as (i) there is a very strong SB HIS187-ARG156 (N-O) linking α-helices H2 and H1 (if mutation H187R is made at position 187, then the hydrophobic core of PrP(C) will be exposed (L.H. Zhong (2010). Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. Journal of Biomolecular Structure and Dynamics 28(3), 355-361)), (ii) at D178, there is a HB Y169-D178 and a polar contact R164-D178 for BufPrP(C) instead of a polar contact Q168-D178 for bovine PrP(C) (C.J. Cheng, & V. Daggett. (2014). Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4(1), 181-201), (iii) BufPrP(C) owns three 310 helices at 125-127, 152-156, and in the β2-α2 loop, respectively, and (iv) in the β2-α2 loop, there is a strong π-π stacking and a strong π-cation F175-Y169-R164.(N)NH2, has been discovered.

Introduction of a proline residue into position 31 of the loop of the dimeric 4-alpha-helical protein ROP causes a drastic destabilization.

PubMed

Peters, K; Hinz, H J; Cesareni, G

1997-10-01

The exchange of an alanine with a proline residue in position 31 of the loop region of the dimeric 4-alpha-helical-bundle protein ROP causes a reduction in the alpha-helix content of 7% and a reduction in stability of about 40% compared to the wild type parameters. The Gibbs energy of unfolding by denaturants extrapolated linearly to zero denaturant concentration, delta G0D (buffer, 25 degrees C), has been determined to be 43 kJ (mol dimer)-1. The corresponding ROPwt value is 72 kJ (mol dimer)-1 (Steif et al., 1993). The extrapolated delta G0D values obtained from urea and GdmHCI un- and refolding studies are identical within error limits. Deconvolution of the stability values into enthalpy and entropy terms resulted in the following parameters. At T1/2 = 43 degrees C (Cprotein = 0.05 mg.ml-1) the ROP A31P mutant is characterized by delta Hv.H.0 = 272 kJ (mol dimer)-1, delta Cp = 7.2 kJ (mol dimer)-1 K-1, delta S0 = 762 J (mol dimer)-1 K-1. These parameters are only approximately 50% as large as the corresponding values of ROPwt. We assume that the significant reduction in stability reflects the absence of at least one hydrogen bond as well as deformation of the protein structure. This interpretation is supported by the reduction in the change in heat capacity observed for the A31P mutant relative to ROPwt, by the increased aggregation tendency of the mutant and by the reduced specific CD absorption at 222 nm. All results support the view that in the case of ROP protein the loop region plays a significant role in the maintenance of native structure and conformational stability.

NIMROD simulations and physics assessment of possible designs for a next generation Steady Inductive Helicity Injection HIT device

NASA Astrophysics Data System (ADS)

Penna, James; Morgan, Kyle; Grubb, Isaac; Jarboe, Thomas

2017-10-01

The Helicity Injected Torus - Steady Inductive 3 (HIT-SI3) experiment forms and maintains spheromaks via Steady Inductive Helicity Injection (SIHI) using discrete injectors that inject magnetic helicity via a non-axisymmetric perturbation and drive toroidally symmetric current. Newer designs for larger SIHI-driven spheromaks incorporate a set of injectors connected to a single external manifold to allow more freedom for the toroidal structure of the applied perturbation. Simulations have been carried out using the NIMROD code to assess the effectiveness of various imposed mode structures and injector schema in driving current via Imposed Dynamo Current Drive (IDCD). The results are presented here for varying flux conserver shapes on a device approximately 1.5 times larger than the current HIT-SI3 experiment. The imposed mode structures and spectra of simulated spheromaks are analyzed in order to examine magnetic structure and stability and determine an optimal regime for IDCD sustainment in a large device. The development of scaling laws for manifold operation is also presented, and simulation results are analyzed and assessed as part of the development path for the large scale device.

A minimal approach to the scattering of physical massless bosons

NASA Astrophysics Data System (ADS)

Boels, Rutger H.; Luo, Hui

2018-05-01

Tree and loop level scattering amplitudes which involve physical massless bosons are derived directly from physical constraints such as locality, symmetry and unitarity, bypassing path integral constructions. Amplitudes can be projected onto a minimal basis of kinematic factors through linear algebra, by employing four dimensional spinor helicity methods or at its most general using projection techniques. The linear algebra analysis is closely related to amplitude relations, especially the Bern-Carrasco-Johansson relations for gluon amplitudes and the Kawai-Lewellen-Tye relations between gluons and graviton amplitudes. Projection techniques are known to reduce the computation of loop amplitudes with spinning particles to scalar integrals. Unitarity, locality and integration-by-parts identities can then be used to fix complete tree and loop amplitudes efficiently. The loop amplitudes follow algorithmically from the trees. A number of proof-of-concept examples are presented. These include the planar four point two-loop amplitude in pure Yang-Mills theory as well as a range of one loop amplitudes with internal and external scalars, gluons and gravitons. Several interesting features of the results are highlighted, such as the vanishing of certain basis coefficients for gluon and graviton amplitudes. Effective field theories are naturally and efficiently included into the framework. Dimensional regularisation is employed throughout; different regularisation schemes are worked out explicitly. The presented methods appear most powerful in non-supersymmetric theories in cases with relatively few legs, but with potentially many loops. For instance, in the introduced approach iterated unitarity cuts of four point amplitudes for non-supersymmetric gauge and gravity theories can be computed by matrix multiplication, generalising the so-called rung-rule of maximally supersymmetric theories. The philosophy of the approach to kinematics also leads to a technique to control colour quantum numbers of scattering amplitudes with matter, especially efficient in the adjoint and fundamental representations.

Enzymatically cross-linked tilapia gelatin hydrogels: physical, chemical, and hybrid networks.

PubMed

Bode, Franziska; da Silva, Marcelo Alves; Drake, Alex F; Ross-Murphy, Simon B; Dreiss, Cécile A

2011-10-10

This Article investigates different types of networks formed from tilapia fish gelatin (10% w/w) in the presence and absence of the enzymatic cross-linker microbial transglutaminase. The influence of the temperature protocol and cross-linker concentration (0-55 U mTGase/g gelatin) was examined in physical, chemical, and hybrid gels, where physical gels arise from the formation of triple helices that act as junction points when the gels are cooled below the gelation point. A combination of rheology and optical rotation was used to study the evolution of the storage modulus (G') over time and the number of triple helices formed for each type of gel. We attempted to separate the final storage modulus of the gels into its chemical and physical contributions to examine the existence or otherwise of synergism between the two types of networks. Our experiments show that the gel characteristics vary widely with the thermal protocol. The final storage modulus in chemical gels increased with enzyme concentration, possibly due to the preferential formation of closed loops at low cross-linker amount. In chemical-physical gels, where the physical network (helices) was formed consecutively to the covalent one, we found that below a critical enzyme concentration the more extensive the chemical network is (as measured by G'), the weaker the final gel is. The storage modulus attributed to the physical network decreased exponentially as a function of G' from the chemical network, but both networks were found to be purely additive. Helices were not thermally stabilized. The simultaneous formation of physical and chemical networks (physical-co-chemical) resulted in G' values higher than the individual networks formed under the same conditions. Two regimes were distinguished: at low enzyme concentration (10-20 U mTGase/g gelatin), the networks were formed in series, but the storage modulus from the chemical network was higher in the presence of helices (compared to pure chemical gels); at higher enzyme concentration (30-40 U mTGase/g gelatin), strong synergistic effects were found as a large part of the covalent network became ineffective upon melting of the helices.

Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

PubMed Central

Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

2014-01-01

G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599

X-ray structures and mechanism of the human serotonin transporter.

PubMed

Coleman, Jonathan A; Green, Evan M; Gouaux, Eric

2016-04-21

The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 Å resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.

Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix

PubMed Central

Brown, Jessica A.; Bulkley, David; Wang, Jimin; Valenstein, Max L.; Yario, Therese A.; Steitz, Thomas A.; Steitz, Joan A.

2014-01-01

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly-abundant nuclear long noncoding RNA that promotes malignancy. A 3′-stem-loop structure is predicted to confer stability by engaging a downstream A-rich tract in a triple helix, similar to the expression and nuclear retention element (ENE) from the KSHV polyadenylated nuclear RNA. The 3.1-Å resolution crystal structure of the human MALAT1 ENE and A-rich tract reveals a bipartite triple helix containing stacks of five and four U•A-U triples separated by a C+•G-C triplet and C-G doublet, extended by two A-minor interactions. In vivo decay assays indicate that this blunt-ended triple helix, with the 3′ nucleotide in a U•A-U triple, inhibits rapid nuclear RNA decay. Interruption of the triple helix by the C-G doublet induces a “helical reset” that explains why triple-helical stacks longer than six do not occur in nature. PMID:24952594

Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability.

PubMed

Deng, Xian; Fink, Gero; Bharat, Tanmay A M; He, Shaoda; Kureisaite-Ciziene, Danguole; Löwe, Jan

2017-07-18

Microtubules, the dynamic, yet stiff hollow tubes built from αβ-tubulin protein heterodimers, are thought to be present only in eukaryotic cells. Here, we report a 3.6-Å helical reconstruction electron cryomicroscopy structure of four-stranded mini microtubules formed by bacterial tubulin-like Prosthecobacter dejongeii BtubAB proteins. Despite their much smaller diameter, mini microtubules share many key structural features with eukaryotic microtubules, such as an M-loop, alternating subunits, and a seam that breaks overall helical symmetry. Using in vitro total internal reflection fluorescence microscopy, we show that bacterial mini microtubules treadmill and display dynamic instability, another hallmark of eukaryotic microtubules. The third protein in the btub gene cluster, BtubC, previously known as "bacterial kinesin light chain," binds along protofilaments every 8 nm, inhibits BtubAB mini microtubule catastrophe, and increases rescue. Our work reveals that some bacteria contain regulated and dynamic cytomotive microtubule systems that were once thought to be only useful in much larger and sophisticated eukaryotic cells.

Low Power, High Voltage Power Supply with Fast Rise/Fall Time

NASA Technical Reports Server (NTRS)

Bearden, Douglas B. (Inventor)

2007-01-01

A low power, high voltage power supply system includes a high voltage power supply stage and a preregulator for programming the power supply stage so as to produce an output voltage which is a predetermined fraction of a desired voltage level. The power supply stage includes a high voltage, voltage doubler stage connected to receive the output voltage from the preregulator and for, when activated, providing amplification of the output voltage to the desired voltage level. A first feedback loop is connected between the output of the preregulator and an input of the preregulator while a second feedback loop is connected between the output of the power supply stage and the input of the preregulator.

Low power, high voltage power supply with fast rise/fall time

NASA Technical Reports Server (NTRS)

Bearden, Douglas B. (Inventor)

2007-01-01

A low power, high voltage power supply system includes a high voltage power supply stage and a preregulator for programming the power supply stage so as to produce an output voltage which is a predetermined fraction of a desired voltage level. The power supply stage includes a high voltage, voltage doubler stage connected to receive the output voltage from the preregulator and for, when activated, providing amplification of the output voltage to the desired voltage level. A first feedback loop is connected between the output of the preregulator and an input of the preregulator while a second feedback loop is connected between the output of the power supply stage and the input of the preregulator.

Preliminary design of a Primary Loop Pump Assembly (PLPA), using electromagnetic pumps

NASA Technical Reports Server (NTRS)

Moss, T. A.; Matlin, G.; Donelan, L.; Johnson, J. L.; Rowe, I.

1972-01-01

A preliminary design study of flight-type dc conduction-permanent magnetic, ac helical induction, and ac linear induction pumps for circulating 883 K (1130 F) NaK at 9.1 kg/sec (20 lb/sec) is described. Various electromagnetic pump geometrics are evaluated against hydraulic performance, and the effects of multiple windings and numbers of pumps per assembly on overall reliability were determined. The methods used in the electrical-hydraulic, stress, and thermal analysis are discussed, and the high temperature electrical materials selected for the application are listed.

Screech tones from free and ducted supersonic jets

NASA Technical Reports Server (NTRS)

Tam, C. K. W.; Ahuja, K. K.; Jones, R. R., III

1993-01-01

The dependence of the instability wave spectrum on azimuthal mode number, the jet to ambient gas temperature ratio, and the jet Mach number is studied. It is shown that the switch of the dominant screech mode (axisymmetric to helical/flapping) as Mach number increases is due to the switch in dominance of the corresponding mode of instability waves. Super-resonance can occur when the feedback loop is powered by the most amplified instability wave. It is suggested that the large amplitude pressure fluctuations and tone in the test cells are generated by super-resonance.

Predicting RNA pseudoknot folding thermodynamics

PubMed Central

Cao, Song; Chen, Shi-Jie

2006-01-01

Based on the experimentally determined atomic coordinates for RNA helices and the self-avoiding walks of the P (phosphate) and C4 (carbon) atoms in the diamond lattice for the polynucleotide loop conformations, we derive a set of conformational entropy parameters for RNA pseudoknots. Based on the entropy parameters, we develop a folding thermodynamics model that enables us to compute the sequence-specific RNA pseudoknot folding free energy landscape and thermodynamics. The model is validated through extensive experimental tests both for the native structures and for the folding thermodynamics. The model predicts strong sequence-dependent helix-loop competitions in the pseudoknot stability and the resultant conformational switches between different hairpin and pseudoknot structures. For instance, for the pseudoknot domain of human telomerase RNA, a native-like and a misfolded hairpin intermediates are found to coexist on the (equilibrium) folding pathways, and the interplay between the stabilities of these intermediates causes the conformational switch that may underlie a human telomerase disease. PMID:16709732

Structure of the human smoothened receptor 7TM bound to an antitumor agent

PubMed Central

Wang, Chong; Wu, Huixian; Katritch, Vsevolod; Han, Gye Won; Huang, Xi-Ping; Liu, Wei; Siu, Fai Yiu; Roth, Bryan L.; Cherezov, Vadim; Stevens, Raymond C.

2013-01-01

The smoothened (SMO) receptor, a key signal transducer in the Hedgehog (Hh) signaling pathway is both responsible for the maintenance of normal embryonic development and implicated in carcinogenesis. The SMO receptor is classified as a class Frizzled (class F) G protein-coupled receptor (GPCR), although the canonical Hh signaling pathway involves the transcription factor Gli and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure at 2.5 Å resolution of the transmembrane domain of the human SMO receptor bound to the small molecule antagonist LY2940680. Although the SMO receptor shares the seven transmembrane helical (7TM) fold, most conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulfide bonds. The ligand binds at the extracellular end of the 7TM bundle and forms extensive contacts with the loops. PMID:23636324

40 CFR 63.1032 - Sampling connection systems standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Sampling connection systems standards... (CONTINUED) National Emission Standards for Equipment Leaks-Control Level 2 Standards § 63.1032 Sampling.... Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed vent...

Torque-balanced vibrationless rotary coupling

DOEpatents

Miller, Donald M.

1980-01-01

This disclosure describes a torque-balanced vibrationless rotary coupling for transmitting rotary motion without unwanted vibration into the spindle of a machine tool. A drive member drives a driven member using flexible connecting loops which are connected tangentially and at diametrically opposite connecting points through a free floating ring.

LOOP marine and estuarine monitoring program, 1978-95 : volume 4 : zooplankton and ichthyoplankton.

DOT National Transportation Integrated Search

1998-01-01

The Louisiana Offshore Oil Port (LOOP) facilities in coastal Louisiana provide the United States with the country's only Superport for off-loading deep draft tankers. The three single-point mooring (SPM) structures connected by pipelines to a platfor...

Two-loop controller for maximizing performance of a grid-connected photovoltaic - fuel cell hybrid power plant

NASA Astrophysics Data System (ADS)

Ro, Kyoungsoo

The study started with the requirement that a photovoltaic (PV) power source should be integrated with other supplementary power sources whether it operates in a stand-alone or grid-connected mode. First, fuel cells for a backup of varying PV power were compared in detail with batteries and were found to have more operational benefits. Next, maximizing performance of a grid-connected PV-fuel cell hybrid system by use of a two-loop controller was discussed. One loop is a neural network controller for maximum power point tracking, which extracts maximum available solar power from PV arrays under varying conditions of insolation, temperature, and system load. A real/reactive power controller (RRPC) is the other loop. The RRPC meets the system's requirement for real and reactive powers by controlling incoming fuel to fuel cell stacks as well as switching control signals to a power conditioning subsystem. The RRPC is able to achieve more versatile control of real/reactive powers than the conventional power sources since the hybrid power plant does not contain any rotating mass. Results of time-domain simulations prove not only effectiveness of the proposed computer models of the two-loop controller, but also their applicability for use in transient stability analysis of the hybrid power plant. Finally, environmental evaluation of the proposed hybrid plant was made in terms of plant's land requirement and lifetime COsb2 emissions, and then compared with that of the conventional fossil-fuel power generating forms.

Assessing catchment connectivity using hysteretic loops

NASA Astrophysics Data System (ADS)

Davis, Jason; Masselink, Rens; Goni, Mikel; Gimenez, Rafael; Casali, Javier; Seeger, Manuel; Keesstra, Saskia

2017-04-01

Storm events mobilize large proportions of sediments in catchment systems. Therefore understanding catchment sediment dynamics throughout the continuity of storms and how initial catchment states act as controls on the transport of sediment to catchment outlets is important for effective catchment management. Sediment connectivity is a concept which can explain the origin, pathways and sinks of sediments within catchments (Baartman et al., 2013; Parsons et al., 2015; Masselink et al., 2016a,b; Mekonnen et al., 2016). However, sediment connectivity alone does not provide a practicable mechanism by which the catchment's initial state - and thus the location of entrained sediment in the sediment transport cascade - can be characterized. Studying the dynamic relationship between water discharge (Q) and suspended sediment (SS) at the catchment outlet can provide a valuable research tool to infer the likely source areas and flow pathways contributing to sediment transport because the relationship can be characterized by predictable hysteresis patterns. Hysteresis is observed when the sediment concentration associated with a certain flow rate is different depending on the direction in which the analysis is performed - towards the increase or towards the diminution of the flow. However, the complexity of the phenomena and factors which determine the hysteresis make its interpretation ambiguous. Previous work has described various types of hysteretic loops as well as the cause for the shape of the loop, mainly pointing to the origin of the sediments. The data set for this study comes from four experimental watersheds in Navarre (Spain), owned and maintained by the Government of Navarre. These experimental watersheds have been monitored and studied since 1996 (La Tejería and Latxaga) and 2001 (Oskotz principal and Oskotz woodland). La Tejería and Latxaga watersheds are similar to each other regarding size (approximately 200 ha), geology (marls and sandstones), soils (fine texture topsoil), climate (humid sub Mediterranean) and land use (80-90% cultivated with winter grain crops). Ozkotz principal (ca.1,700 ha) is covered with forest and pasture (cattle-breeding); while Oskotz woodland (ca. 500 ha), a sub-watershed of the Oskotz principal, is almost completely covered with forest. The predominant climate in the Oskotz catchments sub-Atlantic. Furthermore, antecedent conditions and event characteristics were analysed. The loops were compared quantitatively and qualitatively between catchments for similar events and within the catchments for events with different characteristics. In this study, several measures to objectively classify hysteresis loops in an automated way were developed. These were consecutively used to classify several hundreds of loops from several agricultural catchments in Northern Spain. These loop characteristics were compared to event specific characteristics such as antecedent precipitation, time of year, and precipitation intensity, duration and total. The combination of hysteresis loops and variables influencing connectivity can then tell something about the sources of sediments for different events and catchments. References Baartman, J.E.M., Masselink, R.H., Keesstra, S.D., Temme, A.J.A.M., 2013. Linking landscape morphological complexity and sediment connectivity. Earth Surface Processes and Landforms 38: 1457-1471. Masselink RJH, Heckmann T, Temme AJAM, Anders NS, Gooren HPA, Keesstra SD. 2016. A network theory approach for a better understanding of overland flow connectivity. Hydrological Processes. DOI: 10.1002/hyp.10993 Masselink, R.J.H., Keesstra, S.D., Temme, A.J.A.M., Seeger, M., Giménez, R., Casalí, J., 2016. Modelling Discharge and Sediment Yield at Catchment Scale Using Connectivity Components. Land Degradation and Development 27: 933-945, DOI: 10.1002/ldr.2512 Mekonnen, M., Keesstra, S.D., Baartman, J.E.M., Stroosnijder, L., Maroulis, J., Reducing sediment connectivity through man-made and natural sediment sinks in the Minizr catchment, north-west Ethiopia. Accepted to Land Degradation and Development. Parsons A.J., Bracken L., Peoppl , R., Wainwright J., Keesstra, S.D., 2015. Editorial: Introduction to special issue on connectivity in water and sediment dynamics. In press in Earth Surface Processes and Landforms. DOI: 10.1002/esp.3714

Characterization of a native hammerhead ribozyme derived from schistosomes

PubMed Central

OSBORNE, EDITH M.; SCHAAK, JANELL E.; DEROSE, VICTORIA J.

2005-01-01

A recent re-examination of the role of the helices surrounding the conserved core of the hammerhead ribozyme has identified putative loop–loop interactions between stems I and II in native hammerhead sequences. These extended hammerhead sequences are more active at low concentrations of divalent cations than are minimal hammerheads. The loop–loop interactions are proposed to stabilize a more active conformation of the conserved core. Here, a kinetic and thermodynamic characterization of an extended hammerhead sequence derived from Schistosoma mansoni is performed. Biphasic kinetics are observed, suggesting the presence of at least two conformers, one cleaving with a fast rate and the other with a slow rate. Replacing loop II with a poly(U) sequence designed to eliminate the interaction between the two loops results in greatly diminished activity, suggesting that the loop–loop interactions do aid in forming a more active conformation. Previous studies with minimal hammerheads have shown deleterious effects of Rp-phosphorothioate substitutions at the cleavage site and 5′ to A9, both of which could be rescued with Cd2+. Here, phosphorothioate modifications at the cleavage site and 5′ to A9 were made in the schistosome-derived sequence. In Mg2+, both phosphorothioate substitutions decreased the overall fraction cleaved without significantly affecting the observed rate of cleavage. The addition of Cd2+ rescued cleavage in both cases, suggesting that these are still putative metal binding sites in this native sequence. PMID:15659358

pH-regulated metal-ligand switching in the HM loop of ATP7A: a new paradigm for metal transfer chemistry.

PubMed

Kline, Chelsey D; Gambill, Benjamin F; Mayfield, Mary; Lutsenko, Svetlana; Blackburn, Ninian J

2016-08-01

Cuproproteins such as PHM and DBM mature in late endosomal vesicles of the mammalian secretory pathway where changes in vesicle pH are employed for sorting and post-translational processing. Colocation with the P1B-type ATPase ATP7A suggests that the latter is the source of copper and supports a mechanism where selectivity in metal transfer is achieved by spatial colocation of partner proteins in their specific organelles or vesicles. In previous work we have suggested that a lumenal loop sequence located between trans-membrane helices TM1 and TM2 of the ATPase, and containing five histidines and four methionines, acts as an organelle-specific chaperone for metallation of the cuproproteins. The hypothesis posits that the pH of the vesicle regulates copper ligation and loop conformation via a mechanism which involves His to Met ligand switching induced by histidine protonation. Here we report the effect of pH on the HM loop copper coordination using X-ray absorption spectroscopy (XAS), and show via selenium substitution of the Met residues that the HM loop undergoes similar conformational switching to that found earlier for its partner PHM. We hypothesize that in the absence of specific chaperones, HM motifs provide a template for building a flexible, pH-sensitive transfer site whose structure and function can be regulated to accommodate the different active site structural elements and pH environments of its partner proteins.

Equilibrium models of coronal loops that involve curvature and buoyancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindman, Bradley W.; Jain, Rekha, E-mail: hindman@solarz.colorado.edu

2013-12-01

We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to amore » detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of the curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.« less

Using THz Spectroscopy, Evolutionary Network Analysis Methods, and MD Simulation to Map the Evolution of Allosteric Communication Pathways in c-Type Lysozymes.

PubMed

Woods, Kristina N; Pfeffer, Juergen

2016-01-01

It is now widely accepted that protein function is intimately tied with the navigation of energy landscapes. In this framework, a protein sequence is not described by a distinct structure but rather by an ensemble of conformations. And it is through this ensemble that evolution is able to modify a protein's function by altering its landscape. Hence, the evolution of protein functions involves selective pressures that adjust the sampling of the conformational states. In this work, we focus on elucidating the evolutionary pathway that shaped the function of individual proteins that make-up the mammalian c-type lysozyme subfamily. Using both experimental and computational methods, we map out specific intermolecular interactions that direct the sampling of conformational states and accordingly, also underlie shifts in the landscape that are directly connected with the formation of novel protein functions. By contrasting three representative proteins in the family we identify molecular mechanisms that are associated with the selectivity of enhanced antimicrobial properties and consequently, divergent protein function. Namely, we link the extent of localized fluctuations involving the loop separating helices A and B with shifts in the equilibrium of the ensemble of conformational states that mediate interdomain coupling and concurrently moderate substrate binding affinity. This work reveals unique insights into the molecular level mechanisms that promote the progression of interactions that connect the immune response to infection with the nutritional properties of lactation, while also providing a deeper understanding about how evolving energy landscapes may define present-day protein function. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Structure of the bacterial flagellar hook and implication for the molecular universal joint mechanism.

PubMed

Samatey, Fadel A; Matsunami, Hideyuki; Imada, Katsumi; Nagashima, Shigehiro; Shaikh, Tanvir R; Thomas, Dennis R; Chen, James Z; Derosier, David J; Kitao, Akio; Namba, Keiichi

2004-10-28

The bacterial flagellum is a motile organelle, and the flagellar hook is a short, highly curved tubular structure that connects the flagellar motor to the long filament acting as a helical propeller. The hook is made of about 120 copies of a single protein, FlgE, and its function as a nano-sized universal joint is essential for dynamic and efficient bacterial motility and taxis. It transmits the motor torque to the helical propeller over a wide range of its orientation for swimming and tumbling. Here we report a partial atomic model of the hook obtained by X-ray crystallography of FlgE31, a major proteolytic fragment of FlgE lacking unfolded terminal regions, and by electron cryomicroscopy and three-dimensional helical image reconstruction of the hook. The model reveals the intricate molecular interactions and a plausible switching mechanism for the hook to be flexible in bending but rigid against twisting for its universal joint function.

Capillary pumped loop body heat exchanger

NASA Technical Reports Server (NTRS)

Swanson, Theodore D. (Inventor); Wren, deceased, Paul (Inventor)

1998-01-01

A capillary pumped loop for transferring heat from one body part to another body part, the capillary pumped loop comprising a capillary evaporator for vaporizing a liquid refrigerant by absorbing heat from a warm body part, a condenser for turning a vaporized refrigerant into a liquid by transferring heat from the vaporized liquid to a cool body part, a first tube section connecting an output port of the capillary evaporator to an input of the condenser, and a second tube section connecting an output of the condenser to an input port of the capillary evaporator. A wick may be provided within the condenser. A pump may be provided between the second tube section and the input port of the capillary evaporator. Additionally, an esternal heat source or heat sink may be utilized.

Discretization of 3d gravity in different polarizations

NASA Astrophysics Data System (ADS)

Dupuis, Maïté; Freidel, Laurent; Girelli, Florian

2017-10-01

We study the discretization of three-dimensional gravity with Λ =0 following the loop quantum gravity framework. In the process, we realize that different choices of polarization are possible. This allows us to introduce a new discretization based on the triad as opposed to the connection as in the standard loop quantum gravity framework. We also identify the classical nontrivial symmetries of discrete gravity, namely the Drinfeld double, given in terms of momentum maps. Another choice of polarization is given by the Chern-Simons formulation of gravity. Our framework also provides a new discretization scheme of Chern-Simons, which keeps track of the link between the continuum variables and the discrete ones. We show how the Poisson bracket we recover between the Chern-Simons holonomies allows us to recover the Goldman bracket. There is also a transparent link between the discrete Chern-Simons formulation and the discretization of gravity based on the connection (loop gravity) or triad variables (dual loop gravity).

OT2_wlanger_7: Dynamics of Giant Magnetic Gas Loops and Their Connection to the CMZ in the Galactic Center

NASA Astrophysics Data System (ADS)

Langer, W.

2011-09-01

Understanding the mass transfer and dynamics among the Galactic Center, the disk, and the halo of the Milky Way is fundamental to the study of the evolution of galaxies and star formation. Recently several giant loops of molecular gas (GML) have been found in the Galactic Center from CO maps, which are likely the result of the magnetic Parker instability. There is new evidence of a possible connection between these loops and the Central Molecular Zone as shown in a sparse [CII] sampling made by the Herschel Key Project GOT C+. Here we propose to map various features of the GMLs and the interface region in [CII] with HIFI. We will also map the foot points of the loop, which are thought to be highly shocked regions, in the ortho 110-101 line of water, which is a known shock tracer. With this data we will characterize different ISM components and their flow among these Galactic Center features.

Quantization ambiguities and bounds on geometric scalars in anisotropic loop quantum cosmology

NASA Astrophysics Data System (ADS)

Singh, Parampreet; Wilson-Ewing, Edward

2014-02-01

We study quantization ambiguities in loop quantum cosmology that arise for space-times with non-zero spatial curvature and anisotropies. Motivated by lessons from different possible loop quantizations of the closed Friedmann-Lemaître-Robertson-Walker cosmology, we find that using open holonomies of the extrinsic curvature, which due to gauge-fixing can be treated as a connection, leads to the same quantum geometry effects that are found in spatially flat cosmologies. More specifically, in contrast to the quantization based on open holonomies of the Ashtekar-Barbero connection, the expansion and shear scalars in the effective theories of the Bianchi type II and Bianchi type IX models have upper bounds, and these are in exact agreement with the bounds found in the effective theories of the Friedmann-Lemaître-Robertson-Walker and Bianchi type I models in loop quantum cosmology. We also comment on some ambiguities present in the definition of inverse triad operators and their role.

Cosmological perturbation theory using the FFTLog: formalism and connection to QFT loop integrals

NASA Astrophysics Data System (ADS)

Simonović, Marko; Baldauf, Tobias; Zaldarriaga, Matias; Carrasco, John Joseph; Kollmeier, Juna A.

2018-04-01

We present a new method for calculating loops in cosmological perturbation theory. This method is based on approximating a ΛCDM-like cosmology as a finite sum of complex power-law universes. The decomposition is naturally achieved using an FFTLog algorithm. For power-law cosmologies, all loop integrals are formally equivalent to loop integrals of massless quantum field theory. These integrals have analytic solutions in terms of generalized hypergeometric functions. We provide explicit formulae for the one-loop and the two-loop power spectrum and the one-loop bispectrum. A chief advantage of our approach is that the difficult part of the calculation is cosmology independent, need be done only once, and can be recycled for any relevant predictions. Evaluation of standard loop diagrams then boils down to a simple matrix multiplication. We demonstrate the promise of this method for applications to higher multiplicity/loop correlation functions.

Control and optimization system

DOEpatents

Xinsheng, Lou

2013-02-12

A system for optimizing a power plant includes a chemical loop having an input for receiving an input parameter (270) and an output for outputting an output parameter (280), a control system operably connected to the chemical loop and having a multiple controller part (230) comprising a model-free controller. The control system receives the output parameter (280), optimizes the input parameter (270) based on the received output parameter (280), and outputs an optimized input parameter (270) to the input of the chemical loop to control a process of the chemical loop in an optimized manner.

Current collector for AMTEC

NASA Technical Reports Server (NTRS)

Williams, Roger M. (Inventor)

1989-01-01

An electrode having higher power output is formed of an open mesh current collector such as expanded nickel covering an electrode film applied to a tube of beta-alumina solid electrolyte (BASE). A plurality of cross-members such as spaced, parallel loops of molybdenum metal wire surround the BASE tube. The loops are electrically connected by a bus wire. As the AMTEC cell is heated, the grid of expanded nickel expands more than the BASE tube and the surrounding loop of wire and become diffusion welded to the electrode film and to the wire loops.

Suppression of heating of coronal loops rooted in opposite polarity sunspot umbrae

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Moore, Ronald L.; Panesar, Navdeep; Winebarger, Amy R.

2016-05-01

EUV observations of active region (AR) coronae reveal the presence of loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 A images we identify many clearly discernible coronal loops that connect plage or a sunspot of one polarity to an opposite-polarity plage region. The AIA 94 A images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the HMI onboard SDO. After validation of the NLFFF model by comparison of calculated model field lines and observed loops in AIA 193 and 94, we specify the photospheric roots of the model field lines. The model field then shows the coronal magnetic loops that arch from the dim umbral areas of the opposite polarity sunspots. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.We hypothesize that the convective freedom at the feet of a coronal loop, together with the strength of the field in the body of the loop, determines the strength of the heating. In particular, we expect the hottest coronal loops to have one foot in an umbra and the other foot in opposite-polarity penumbra or plage (coronal moss), the areas of strong field in which convection is not as strongly suppressed as in umbra. Many transient, outstandingly bright, loops in the AIA 94 movie of the AR do have this expected rooting pattern. We will also present another example of AR in which we find a similar rooting pattern of coronal loops.

Twisting and Writhing with George Ellery Hale

NASA Astrophysics Data System (ADS)

Canfield, Richard C.

2013-06-01

Early in his productive career in astronomy, George Ellery Hale developed innovative solar instrumentation that allowed him to make narrow-band images. Among the solar phenomena he discovered were sunspot vortices, which he attributed to storms akin to cyclones in our own atmosphere. Using the concept of magnetic helicity, physicists and mathematicians describe the topology of magnetic fields, including twisting and writhing. Our contemporary understanding of Hale's vortices as a consequence of large-scale twist in sunspot magnetic fields hinges on a key property of helicity: conservation. I will describe the critical role that this property plays, when applied to twist and writhe, in a fundamental aspect of global solar magnetism: the hemispheric and solar cycle dependences of active region electric currents with respect to magnetic fields. With the advent of unbroken sequences of high-resolution magnetic images, such as those presently available from the Helioseismic and Magnetic Imager on Solar Dynamics Observatory, the flux of magnetic helicity through the photosphere can be observed quantitatively. As magnetic flux tubes buoy up through the convection zone, buffeted and shredded by turbulence, they break up into fragments by repeated random bifurcation. We track these rising flux fragments in the photosphere, and calculate the flux of energy and magnetic helicity there. Using a quantitative model of coronal currents, we also track connections between these fragments to calculate the energy and magnetic helicity stored at topological interfaces that are in some ways analogous to the storage of stress at faults in the Earth's crust. Comparison of these values to solar flares and interplanetary coronal mass ejections implies that this is the primary storage mechanism for energy and magnetic helicity released in those phenomena, and suggests a useful tool for quantitative prediction of geomagnetic storms.

Helical patterns of magnetization and magnetic charge density in iron whiskers

NASA Astrophysics Data System (ADS)

Templeton, Terry L.; Hanham, Scott D.; Arrott, Anthony S.

2018-05-01

Studies with the (1 1 1) axis along the long axis of an iron whisker, 40 years ago, showed two phenomena that have remained unexplained: 1) In low fields, there are six peaks in the ac susceptibility, separated by 0.2 mT; 2) Bitter patterns showed striped domain patterns. Multipole columns of magnetic charge density distort to form helical patterns of the magnetization, accounting for the peaks in the susceptibility from the propagation of edge solitons along the intersections of the six sides of a (1 1 1) whisker. The stripes follow the helices. We report micromagnetic simulations in cylinders with various geometries for the cross-sections from rectangular, to hexagonal, to circular, with wide ranges of sizes and lengths, and different anisotropies, including (0 0 1) whiskers and the hypothetical case of no anisotropy. The helical patterns have been there in previous studies, but overlooked. The surface swirls and body helices are connected, but have their own individual behaviors. The magnetization patterns are more easily understood when viewed observing the scalar divergences of the magnetization as isosurfaces of magnetic charge density. The plus and minus charge densities form columns that interact with unlike charges attracting, but not annihilating as they are paid for by a decrease in exchange energy. Just as they start to form the helix, the columns are multipoles. If one could stretch the columns, the self-energy of the charges in a column would be diminished while making the attractive interactions of the unlike charges larger. The columns elongate by becoming helical. The visualization of 3-D magnetic charge distributions aids in the understanding of magnetization in soft magnetic materials.

New formulae for magnetic relative helicity and field line helicity

NASA Astrophysics Data System (ADS)

Aly, Jean-Jacques

2018-01-01

We consider a magnetic field {B} occupying the simply connected domain D and having all its field lines tied to the boundary S of D. We assume here that {B} has a simple topology, i.e., the mapping {M} from positive to negative polarity areas of S associating to each other the two footpoints of any magnetic line, is continuous. We first present new formulae for the helicity H of {B} relative to a reference field {{B}}r having the same normal component {B}n on S, and for its field line helicity h relative to a reference vector potential {{C}}r of {{B}}r. These formulae make immediately apparent the well known invariance of these quantities under all the ideal MHD deformations that preserve the positions of the footpoints on S. They express indeed h and H either in terms of {M} and {B}n, or in terms of the values on S of a pair of Euler potentials of {B}. We next show that, for a specific choice of {{C}}r, the field line helicity h of {B} fully characterizes the magnetic mapping {M} and then the topology of the lines. Finally, we give a formula that describes the rate of change of h in a situation where the plasma moves on the perfectly conducting boundary S without changing {B}n and/or non-ideal processes, described by an unspecified term {N} in Ohm’s law, are at work in some parts of D.

Stabilization and Anomalous Hydration of Collagen Fibril under Heating

PubMed Central

Gevorkian, Sasun G.; Allahverdyan, Armen E.; Gevorgyan, David S.; Simonian, Aleksandr L.; Hu, Chin-Kun

2013-01-01

Background Type I collagen is the most common protein among higher vertebrates. It forms the basis of fibrous connective tissues (tendon, chord, skin, bones) and ensures mechanical stability and strength of these tissues. It is known, however, that separate triple-helical collagen macromolecules are unstable at physiological temperatures. We want to understand the mechanism of collagen stability at the intermolecular level. To this end, we study the collagen fibril, an intermediate level in the collagen hierarchy between triple-helical macromolecule and tendon. Methodology/Principal Finding When heating a native fibril sample, its Young’s modulus decreases in temperature range 20–58°C due to partial denaturation of triple-helices, but it is approximately constant at 58–75°C, because of stabilization by inter-molecular interactions. The stabilization temperature range 58–75°C has two further important features: here the fibril absorbs water under heating and the internal friction displays a peak. We relate these experimental findings to restructuring of collagen triple-helices in fibril. A theoretical description of the experimental results is provided via a generalization of the standard Zimm-Bragg model for the helix-coil transition. It takes into account intermolecular interactions of collagen triple-helices in fibril and describes water adsorption via the Langmuir mechanism. Conclusion/Significance We uncovered an inter-molecular mechanism that stabilizes the fibril made of unstable collagen macromolecules. This mechanism can be relevant for explaining stability of collagen. PMID:24244320

Amino acid sequence analysis of the annexin super-gene family of proteins.

PubMed

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.

Flux rope breaking and formation of a rotating blowout jet

NASA Astrophysics Data System (ADS)

Joshi, Navin Chandra; Nishizuka, Naoto; Filippov, Boris; Magara, Tetsuya; Tlatov, Andrey G.

2018-05-01

We analysed a small flux rope eruption converted into a helical blowout jet in a fan-spine configuration using multiwavelength observations taken by Solar Dynamics Observatory, which occurred near the limb on 2016 January 9. In our study, first, we estimated the fan-spine magnetic configuration with the potential-field calculation and found a sinistral small filament inside it. The filament along with the flux rope erupted upwards and interacted with the surrounding fan-spine magnetic configuration, where the flux rope breaks in the middle section. We observed compact brightening, flare ribbons, and post-flare loops underneath the erupting filament. The northern section of the flux rope reconnected with the surrounding positive polarity, while the southern section straightened. Next, we observed the untwisting motion of the southern leg, which was transformed into a rotating helical blowout jet. The sign of the helicity of the mini-filament matches the one of the rotating jets. This is consistent with recent jet models presented by Adams et al. and Sterling et al. We focused on the fine thread structure of the rotating jet and traced three blobs with the speed of 60-120 km s- 1, while the radial speed of the jet is ˜400 km s- 1. The untwisting motion of the jet accelerated plasma upwards along the collimated outer spine field lines, and it finally evolved into a narrow coronal mass ejection at the height of ˜9Rsun. On the basis of detailed analysis, we discussed clear evidence of the scenario of the breaking of the flux rope and the formation of the helical blowout jet in the fan-spine magnetic configuration.

Expanded turn conformations: characterization and sequence-structure correspondence in alpha-turns with implications in helix folding.

PubMed

Dasgupta, Bhaskar; Pal, Lipika; Basu, Gautam; Chakrabarti, Pinak

2004-05-01

Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding. Copyright 2004 Wiley-Liss, Inc.

Helix formation and stability in membranes.

PubMed

McKay, Matthew J; Afrose, Fahmida; Koeppe, Roger E; Greathouse, Denise V

2018-02-13

In this article we review current understanding of basic principles for the folding of membrane proteins, focusing on the more abundant alpha-helical class. Membrane proteins, vital to many biological functions and implicated in numerous diseases, fold into their active conformations in the complex environment of the cell bilayer membrane. While many membrane proteins rely on the translocon and chaperone proteins to fold correctly, others can achieve their functional form in the absence of any translation apparatus or other aides. Nevertheless, the spontaneous folding process is not well understood at the molecular level. Recent findings suggest that helix fraying and loop formation may be important for overall structure, dynamics and regulation of function. Several types of membrane helices with ionizable amino acids change their topology with pH. Additionally we note that some peptides, including many that are rich in arginine, and a particular analogue of gramicidin, are able passively to translocate across cell membranes. The findings indicate that a final protein structure in a lipid-bilayer membrane is sequence-based, with lipids contributing to stability and regulation. While much progress has been made toward understanding the folding process for alpha-helical membrane proteins, it remains a work in progress. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo. Copyright © 2018 Elsevier B.V. All rights reserved.

Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines.

PubMed

Panayotatos, N; Radziejewska, E; Acheson, A; Somogyi, R; Thadani, A; Hendrickson, W A; McDonald, N Q

1995-06-09

By rational mutagenesis, receptor-specific functional analysis, and visualization of complex formation in solution, we identified individual amino acid side chains involved specifically in the interaction of ciliary neurotrophic factor (CNTF) with CNTFR alpha and not with the beta-components, gp130 and LIFR. In the crystal structure, the side chains of these residues, which are located in helix A, the AB loop, helix B, and helix D, are surface accessible and are clustered in space, thus constituting an epitope for CNTFR alpha. By the same analysis, a partial epitope for gp130 was also identified on the surface of helix A that faces away from the alpha-epitope. Superposition of the CNTF and growth hormone structures showed that the location of these epitopes on CNTF is analogous to the location of the first and second receptor epitopes on the surface of growth hormone. Further comparison with proposed binding sites for alpha- and beta-receptors on interleukin-6 and leukemia inhibitory factor indicated that this epitope topology is conserved among helical cytokines. In each case, epitope I is utilized by the specificity-conferring component, whereas epitopes II and III are used by accessory components. Thus, in addition to a common fold, helical cytokines share a conserved order of receptor epitopes that is function related.

Assignment of the sup 1 H and sup 15 N NMR spectra of Rhodobacter capsulatus ferrocytochrome c sub 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gooley, P.R.; Caffrey, M.S.; Cusanovich, M.A.

1990-03-06

The peptide resonances of the {sup 1}H and {sup 15}N nuclear magnetic resonance spectra of ferrocytochrome c{sub 2} from Rhodobacter capsulatus are sequentially assigned by a combination of 2D {sup 1}H-{sup 1}H and {sup 1}H-{sup 15}N spectroscopy, the latter performed on {sup 15}N-enriched protein. Short-range nuclear Overhauser effect (NOE) data show {alpha}-helices from residues 3-17, 55-65, 69-88, and 103-115. Within the latter two {alpha}-helices, there are three single 3{sub 10} turns, 70-72, 76-78, and 107-109. In addition {alpha}H-NH{sub i+1} and {alpha}H-NH{sub i+2} NOEs indicate that the N-terminal helix (3-17) is distorted. Compared to horse or tuna cytochrome c and cytochromemore » c{sub 2} of Rhodospirillium rubrum, there is a 6-residue insertion at residues 23-29 in R. capsulatus cytochrome c{sub 2}. The NOE data show that this insertion forms a loop, probably an {Omega} loop. {sup 1}H-{sup 15}N heteronuclear multiple quantum correlation experiments are used to follow NH exchange over a period of 40 h. As the 2D spectra are acquired in short time periods (30 min), rates for intermediate exchanging protons can be measured. Comparison of the NH exchange data for the N-terminal helix of cytochrome c{sub 2} of R. capsulatus with the highly homologous horse heart cytochrome c shows that this helix is less stable in cytochrome c{sub 2}.« less

Amylose-dicarboxylic acid inclusion complexes: Characterization and comparison to monocarboxylic acid complexes

USDA-ARS?s Scientific Manuscript database

One of the main components in starch, amylose is an essentially linear polymer composed of glucose connected through alpha-1,4-bonds. Amylose is well known to form helical inclusion complexes with various types of ligands such as iodine, medium and long chain fatty acids, alcohols, lactones, and fl...

A diffusion tensor imaging tractography algorithm based on Navier-Stokes fluid mechanics.

PubMed

Hageman, Nathan S; Toga, Arthur W; Narr, Katherine L; Shattuck, David W

2009-03-01

We introduce a fluid mechanics based tractography method for estimating the most likely connection paths between points in diffusion tensor imaging (DTI) volumes. We customize the Navier-Stokes equations to include information from the diffusion tensor and simulate an artificial fluid flow through the DTI image volume. We then estimate the most likely connection paths between points in the DTI volume using a metric derived from the fluid velocity vector field. We validate our algorithm using digital DTI phantoms based on a helical shape. Our method segmented the structure of the phantom with less distortion than was produced using implementations of heat-based partial differential equation (PDE) and streamline based methods. In addition, our method was able to successfully segment divergent and crossing fiber geometries, closely following the ideal path through a digital helical phantom in the presence of multiple crossing tracts. To assess the performance of our algorithm on anatomical data, we applied our method to DTI volumes from normal human subjects. Our method produced paths that were consistent with both known anatomy and directionally encoded color images of the DTI dataset.

A Diffusion Tensor Imaging Tractography Algorithm Based on Navier-Stokes Fluid Mechanics

PubMed Central

Hageman, Nathan S.; Toga, Arthur W.; Narr, Katherine; Shattuck, David W.

2009-01-01

We introduce a fluid mechanics based tractography method for estimating the most likely connection paths between points in diffusion tensor imaging (DTI) volumes. We customize the Navier-Stokes equations to include information from the diffusion tensor and simulate an artificial fluid flow through the DTI image volume. We then estimate the most likely connection paths between points in the DTI volume using a metric derived from the fluid velocity vector field. We validate our algorithm using digital DTI phantoms based on a helical shape. Our method segmented the structure of the phantom with less distortion than was produced using implementations of heat-based partial differential equation (PDE) and streamline based methods. In addition, our method was able to successfully segment divergent and crossing fiber geometries, closely following the ideal path through a digital helical phantom in the presence of multiple crossing tracts. To assess the performance of our algorithm on anatomical data, we applied our method to DTI volumes from normal human subjects. Our method produced paths that were consistent with both known anatomy and directionally encoded color (DEC) images of the DTI dataset. PMID:19244007

An Efficient Solution Method for Multibody Systems with Loops Using Multiple Processors

NASA Technical Reports Server (NTRS)

Ghosh, Tushar K.; Nguyen, Luong A.; Quiocho, Leslie J.

2015-01-01

This paper describes a multibody dynamics algorithm formulated for parallel implementation on multiprocessor computing platforms using the divide-and-conquer approach. The system of interest is a general topology of rigid and elastic articulated bodies with or without loops. The algorithm divides the multibody system into a number of smaller sets of bodies in chain or tree structures, called "branches" at convenient joints called "connection points", and uses an Order-N (O (N)) approach to formulate the dynamics of each branch in terms of the unknown spatial connection forces. The equations of motion for the branches, leaving the connection forces as unknowns, are implemented in separate processors in parallel for computational efficiency, and the equations for all the unknown connection forces are synthesized and solved in one or several processors. The performances of two implementations of this divide-and-conquer algorithm in multiple processors are compared with an existing method implemented on a single processor.

Evidence of suppressed heating of coronal loops rooted in opposite polarity sunspot umbrae

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Winebarger, Amy R.; Panesar, Navdeep K.; Moore, Ronald

2015-04-01

Observations of active region (AR) coronae in different EUV wavelengths reveal the presence of various loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 A images we identify many clearly discernible coronal loops that connect opposite-polarity plage or a sunspot to a opposite-polarity plage region. The AIA 94 A images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the Heliosesmic Magnetic Imager (HMI) onboard SDO. After validation of the NLFFF model by comparison of calculated model field lines and observed loops in AIA 193 and 94 A, we specify the photospheric roots of the model field lines. The model field then shows the coronal magnetic loops that arch from the dim umbral area of the positive-polarity sunspot to the dim umbral area of a negative-polarity sunspot. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.From this result, we further hypothesize that the convective freedom at the feet of a coronal loop, together with the strength of the field in the body of the loop, determines the strength of the heating. In particular, we expect the hottest coronal loops to have one foot in an umbra and the other foot in opposite-polarity penumbra or plage (coronal moss), the areas of strong field in which convection is not as strongly suppressed as in umbrae. Many transient, outstandingly bright, loops in the AIA 94 A movie of the AR do have this expected rooting pattern.

Actin Hydrophobic Loop (262-274) and Filament Nucleation and Elongation

PubMed Central

Shvetsov, Alexander; Galkin, Vitold E.; Orlova, Albina; Phillips, Martin; Bergeron, Sarah E.; Rubenstein, Peter A.; Egelman, Edward H.; Reisler, Emil

2014-01-01

Summary The importance of actin hydrophobic loop 262-274 dynamics to actin polymerization and filament stability has been shown recently using a yeast actin mutant, L180C/L269C/C374A, in which the hydrophobic loop could be locked in a “parked” conformation by a disulfide bond between C180 and C269. Such a cross-linked G-actin does not form filaments, suggesting nucleation and/or elongation inhibition. To determine the role of loop dynamics in filament nucleation and/or elongation, we studied the polymerization of the cross-linked actin in the presence of cofilin - to assist with actin nucleation - and with phalloidin, to stabilize the elongating filament segments. We demonstrate here that together, but not alone, phalloidin and cofilin co-rescue the polymerization of cross-linked actin. The polymerization was also rescued by filament seeds added together with phalloidin but not with cofilin. Thus, loop immobilization via cross-linking inhibits both filament nucleation and elongation. Nevertheless, the conformational changes needed to catalyze ATP hydrolysis by actin occur in the cross-linked actin. When actin filaments are fully decorated by cofilin the helical twist of F-actin changes by ~ 5° per subunit. Electron microscopic analysis of filaments rescued by cofilin and phalloidin revealed a dense contact between opposite strands in F-actin, and a change of twist by ~ 1° per subunit, indicating either partial or disordered attachment of cofilin to F-actin and/or a competition between cofilin and phalloidin to alter F-actin symmetry. Our findings show an importance of the hydrophobic loop conformational dynamics to both actin nucleation and elongation and reveal that the inhibition of these two steps in the cross-linked actin can be relieved by appropriate factors. PMID:18037437

Investigation of RNA Hairpin Loop Folding with Time-Resolved Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Stancik, Aaron Lee

Ribonucleic acids (RNAs) are a group of functional biopolymers central to the molecular underpinnings of life. To complete the many processes they mediate, RNAs must fold into precise three-dimensional structures. Hairpin loops are the most ubiquitous and basic structural elements present in all folded RNAs, and are the foundation upon which all complex tertiary structures are built. A hairpin loop forms when a single stranded RNA molecule folds back on itself creating a helical stem of paired bases capped by a loop. This work investigates the formation of UNCG hairpin loops with the sequence 5'-GC(UNCG)GC-3' (N = A, U, G, or C) using both equilibrium infrared (IR) and time-resolved IR spectroscopy. Equilibrium IR melting data were used to determine thermodynamic parameters. Melting temperatures ranged from 50 to 60°C, and enthalpies of unfolding were on the order of 100 kJ/mol. In the time-resolved work, temperature jumps of up to 20°C at 2.5°C increments were obtained with transient relaxation kinetics spanning nanoseconds to hundreds of microseconds. The relaxation kinetics for all of the oligomers studied were fit to first or second order exponentials. Multiple vibrational transitions were probed on each oligomer for fully folded and partially denatured structures. In the time-resolved limit, in contrast to equilibrium melting, RNA does not fold according to two-state behavior. These results are some of the first to show that RNA hairpins fold according to a rugged energy landscape, which contradicts their relatively simple nature. In addition, this work has proven that time-resolved IR spectroscopy is a powerful and novel tool for investigating the earliest events of RNA folding, the formation of the hairpin loop.

DNA sequence-dependent mechanics and protein-assisted bending in repressor-mediated loop formation

PubMed Central

Boedicker, James Q.; Garcia, Hernan G.; Johnson, Stephanie; Phillips, Rob

2014-01-01

As the chief informational molecule of life, DNA is subject to extensive physical manipulations. The energy required to deform double-helical DNA depends on sequence, and this mechanical code of DNA influences gene regulation, such as through nucleosome positioning. Here we examine the sequence-dependent flexibility of DNA in bacterial transcription factor-mediated looping, a context for which the role of sequence remains poorly understood. Using a suite of synthetic constructs repressed by the Lac repressor and two well-known sequences that show large flexibility differences in vitro, we make precise statistical mechanical predictions as to how DNA sequence influences loop formation and test these predictions using in vivo transcription and in vitro single-molecule assays. Surprisingly, sequence-dependent flexibility does not affect in vivo gene regulation. By theoretically and experimentally quantifying the relative contributions of sequence and the DNA-bending protein HU to DNA mechanical properties, we reveal that bending by HU dominates DNA mechanics and masks intrinsic sequence-dependent flexibility. Such a quantitative understanding of how mechanical regulatory information is encoded in the genome will be a key step towards a predictive understanding of gene regulation at single-base pair resolution. PMID:24231252

Chimeric microbial rhodopsins for optical activation of Gs-proteins

PubMed Central

Yoshida, Kazuho; Yamashita, Takahiro; Sasaki, Kengo; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

2017-01-01

We previously showed that the chimeric proteins of microbial rhodopsins, such as light-driven proton pump bacteriorhodopsin (BR) and Gloeobacter rhodopsin (GR) that contain cytoplasmic loops of bovine rhodopsin, are able to activate Gt protein upon light absorption. These facts suggest similar protein structural changes in both the light-driven proton pump and animal rhodopsin. Here we report two trials to engineer chimeric rhodopsins, one for the inserted loop, and another for the microbial rhodopsin template. For the former, we successfully activated Gs protein by light through the incorporation of the cytoplasmic loop of β2-adrenergic receptor (β2AR). For the latter, we did not observe any G-protein activation for the light-driven sodium pump from Indibacter alkaliphilus (IndiR2) or a light-driven chloride pump halorhodopsin from Natronomonas pharaonis (NpHR), whereas the light-driven proton pump GR showed light-dependent G-protein activation. This fact suggests that a helix opening motion is common to G protein coupled receptor (GPCR) and GR, but not to IndiR2 and NpHR. Light-induced difference FTIR spectroscopy revealed similar structural changes between WT and the third loop chimera for each light-driven pump. A helical structural perturbation, which was largest for GR, was further enhanced in the chimera. We conclude that similar structural dynamics that occur on the cytoplasmic side of GPCR are needed to design chimeric microbial rhodopsins. PMID:29362703

Quantum properties of affine-metric gravity with the cosmological term

NASA Astrophysics Data System (ADS)

Baurov, A. Yu; Pronin, P. I.; Stepanyantz, K. V.

2018-04-01

The paper contains analysis of the one-loop effective action for affine-metric gravity of the Hilbert–Einstein type with the cosmological term. We discuss different approaches to the calculation of the effective action, which depends on two independent variables, namely, the metric tensor and the affine connection. In the one-loop approximation we explain how the effective action can be obtained, if, at the first step of the calculation, the metric tensor is integrated out. It is demonstrated that the result is the same as in the case when one starts by integrating out the connection.

SPECTRO-POLARIMETRIC IMAGING REVEALS HELICAL MAGNETIC FIELDS IN SOLAR PROMINENCE FEET

DOE Office of Scientific and Technical Information (OSTI.GOV)

González, M. J. Martínez; Sainz, R. Manso; Ramos, A. Asensio

2015-03-20

Solar prominences are clouds of cool plasma levitating above the solar surface and insulated from the million-degree corona by magnetic fields. They form in regions of complex magnetic topology, characterized by non-potential fields, which can evolve abruptly, disintegrating the prominence and ejecting magnetized material into the heliosphere. However, their physics is not yet fully understood because mapping such complex magnetic configurations and their evolution is extremely challenging, and must often be guessed by proxy from photometric observations. Using state-of-the-art spectro-polarimetric data, we reconstruct the structure of the magnetic field in a prominence. We find that prominence feet harbor helical magneticmore » fields connecting the prominence to the solar surface below.« less

A Simpler Nucleic Acid

NASA Technical Reports Server (NTRS)

Orgel, Leslie

2000-01-01

It has been supposed that for a nucleic acid analog to pair with RNA it must, like RNA, have a backbone with at least a sixatom repeat; a shorter backbone presumably would not stretch far enough to bind RNA properly. The Eschenmoser group has shown, however, that this first impression is incorrect.As they report in their new paper, Eschenmoser and co-workers ( I ) have now synthesized a substantial number of these polymers, which are called (L)-a-threofuranosyl oligonucleotides or TNAs. They are composed of bases linked to a threose sugar-phosphate backbone, with phosphodiester bonds connecting the nucleotides. The investigators discovered that pairs of complementary TNAs do indeed form stable Watson-Crick double helices and, perhaps more importantly, that TNAs form stable double helices with complementary RNAs and DNAs.

Tone based command system for reception of very weak signals

NASA Technical Reports Server (NTRS)

Bokulic, Robert Steven (Inventor); Jensen, James Robert (Inventor)

2006-01-01

This disclosure presents a communication receiver system for spacecraft that includes an open loop receiver adapted to receive a communication signal. An ultrastable oscillator (USO) and a tone detector are connected to the open loop receiver. The open loop receiver translates the communication signal to an intermediate frequency signal using a highly stable reference frequency from the USO. The tone detector extracts commands from the communication signal by evaluating the difference between tones of the communication signal.

When proteome meets genome: the alpha helix and the beta strand of proteins are eschewed by mRNA splice junctions and may define the minimal indivisible modules of protein architecture.

PubMed

Barik, Sailen

2004-09-01

The significance of the intron-exon structure of genes is a mystery. As eukaryotic proteins are made up of modular functional domains, each exon was suspected to encode some form of module; however, the definition of a module remained vague. Comparison of pre-mRNA splice junctions with the three-dimensional architecture of its protein product from different eukaryotes revealed that the junctions were far less likely to occur inside the alpha-helices and beta-strands of proteins than within the more flexible linker regions ('turns' and 'loops') connecting them. The splice junctions were equally distributed in the different types of linkers and throughout the linker sequence, although a slight preference for the central region of the linker was observed. The avoidance of the alpha-helix and the beta-strand by splice junctions suggests the existence of a selection pressure against their disruption, perhaps underscoring the investment made by nature in building these intricate secondary structures. A corollary is that the helix and the strand are the smallest integral architectural units of a protein and represent the minimal modules in the evolution of protein structure. These results should find use in comparative genomics, designing of cloning strategies, and in the mutual verification of genome sequences with protein structures.

Molecular cloning and functional analysis of a H(+)-dependent phosphate transporter gene from the ectomycorrhizal fungus Boletus edulis in southwest China.

PubMed

Wang, Junling; Li, Tao; Wu, Xiaogang; Zhao, Zhiwei

2014-01-01

Phosphate transporters (PTs), as entry points for phosphorus (P) in organisms, are involved in a number of P nutrition processes such as phosphate uptake, transport, and transfer. In the study, a PT gene 1632 bp long (named BePT) was cloned, identified, and functionally characterized from Boletus edulis. BePT was expected to encode a polypeptide with 543 amino acid residues. The BePT polypeptide belonged to the major facilitator superfamily and showed a high degree of sequence identity to the Pht1 family. A topology model revealed that BePT exhibited 12 transmembrane helices, divided into two halves, and connected by a large hydrophilic loop in the middle. A yeast mutant complementation analysis suggested that BePT was a functional PT which mediated orthophosphate uptake of yeast at micromolar concentrations. Green fluorescent protein-BePT fusion proteins expressed were extensively restricted to the plasma membrane in BePT transformed yeast, and its activity was dependent on electrochemical membrane potential. In vitro, quantitative PCR confirmed that the expression of BePT was significantly upregulated at lower phosphorus availability, which may enhance phosphate uptake and transport under phosphate starvation. Our results suggest that BePT plays a key role in phosphate acquisition in the ectomycorrhizal fungus B. edulis. Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Transmembrane topology of the arsenite permease Acr3 from Saccharomyces cerevisiae.

PubMed

Wawrzycka, Donata; Markowska, Katarzyna; Maciaszczyk-Dziubinska, Ewa; Migocka, Magdalena; Wysocki, Robert

2017-01-01

Acr3 is a plasma membrane transporter, a member of the bile/arsenite/riboflavin transporter (BART) superfamily, which confers high-level resistance to arsenicals in the yeast Saccharomyces cerevisiae. We have previously shown that the yeast Acr3 acts as a low affinity As(III)/H + and Sb(III)/H + antiporter. We have also identified several amino acid residues that are localized in putative transmembrane helices (TM) and appeared to be critical for the Acr3 activity. In the present study, the topology of Acr3 was investigated by insertion of glycosylation and factor Xa protease cleavage sites at predicted hydrophilic regions. The analysis of the glycosylation pattern and factor Xa cleavage products of resulting Acr3 fusion constructs provide evidence supporting a topological model of Acr3 with 10 TM segments and cytoplasmically oriented N- and C-terminal domains. Next, we investigated the role of the hydrophilic loop connecting TM8 and TM9, the large size of which is unique to members of the yeast Acr3 family of metalloid transporters. We found that a 28 amino acid deletion in this region does not affect Acr3 folding, trafficking substrate binding, or transport activity. Finally, we constructed a homology-based structural model of Acr3 using the crystal structure of the Yersinia frederiksenii homologue of the human bile acid sodium symporter ASBT. Copyright © 2016 Elsevier B.V. All rights reserved.

Circumnutation as an autonomous root movement in plants.

PubMed

Migliaccio, Fernando; Tassone, Paola; Fortunati, Alessio

2013-01-01

Although publications on circumnutation of the aerial parts of flowering plants are numerous and primarily from the time between Darwin (1880) and the 1950s, reports on circumnutation of roots are scarce. With the introduction of modern molecular biology techniques, many topics in the plant sciences have been revitalized; among these is root circumnutation. The most important research in this area has been done on Arabidopsis thaliana, which has roots that behave differently from those of many other plants; roots grown on inclined agar dishes produce a pattern of half waves slanted to one side. When grown instead on horizontally set dishes, the roots grow in loops or in tight right-handed coils that are characterized by a tight torsion to the left-hand. The roots of the few plants that differ from Arabidopsis and have been similarly tested do not present such patterns, because even if they circumnutate generally in a helical pattern, they subsequently straighten. Research on plants in space or on a clinostat has allowed the testing of these roots in a habitat lacking gravity or simulating the lack. Recently, molecular geneticists have started to connect various root behaviors to specific groups of genes. For example, anomalies in auxin responses caused by some genes can be overcome by complementation with wild-type genes. Such important studies contribute to understanding the mechanisms of growth and elongation, processes that are only superficially understood.

Solution structure of the C-terminal domain of Ole e 9, a major allergen of olive pollen

PubMed Central

Treviño, Miguel Á.; Palomares, Oscar; Castrillo, Inés; Villalba, Mayte; Rodríguez, Rosalía; Rico, Manuel; Santoro, Jorge; Bruix, Marta

2008-01-01

Ole e 9 is an olive pollen allergen belonging to group 2 of pathogenesis-related proteins. The protein is composed of two immunological independent domains: an N-terminal domain (NtD) with 1,3-β-glucanase activity, and a C-terminal domain (CtD) that binds 1,3-β-glucans. We have determined the three-dimensional structure of CtD-Ole e 9 (101 amino acids), which consists of two parallel α-helices forming an angle of ∼55°, a small antiparallel β-sheet with two short strands, and a 3–10 helix turn, all connected by long coil segments, resembling a novel type of folding among allergens. Two regions surrounded by aromatic residues (F49, Y60, F96, Y91 and Y31, H68, Y65, F78) have been localized on the protein surface, and a role for sugar binding is suggested. The epitope mapping of CtD-Ole e 9 shows that B-cell epitopes are mainly located on loops, although some of them are contained in secondary structural elements. Interestingly, the IgG and IgE epitopes are contiguous or overlapped, rather than coincident. The three-dimensional structure of CtD-Ole e 9 might help to understand the underlying mechanism of its biochemical function and to determine possible structure–allergenicity relationships. PMID:18096638

Identification of the ubiquinone-binding domain in the disulfide catalyst disulfide bond protein B.

PubMed

Xie, Tong; Yu, Linda; Bader, Martin W; Bardwell, James C A; Yu, Chang-An

2002-01-18

Disulfide bond (Dsb) formation is catalyzed in the periplasm of prokaryotes by the Dsb proteins. DsbB, a key enzyme in this process, generates disulfides de novo by using the oxidizing power of quinones. To explore the mechanism of this newly described enzymatic activity, we decided to study the ubiquinone-protein interaction and identify the ubiquinone-binding domain in DsbB by cross-linking to photoactivatable quinone analogues. When purified Escherichia coli DsbB was incubated with an azidoubiquinone derivative, 3-azido-2-methyl-5-[(3)H]methoxy-6-decyl-1,4-benzoquinone ([(3)H]azido-Q), and illuminated with long wavelength UV light, the decrease in enzymatic activity correlated with the amount of 3-azido-2-methyl-5-methoxy-6-decyl-1,4-benzoquinone (azido-Q) incorporated into the protein. One azido-Q-linked peptide with a retention time of 33.5 min was obtained by high performance liquid chromatography of the V8 digest of [(3)H]azido-Q-labeled DsbB. This peptide has a partial NH(2)-terminal amino acid sequence of NH(2)-HTMLQLY corresponding to residues 91-97. This sequence occurs in the second periplasmic domain of the inner membrane protein DsbB in a loop connecting transmembrane helices 3 and 4. We propose that the quinone-binding site is within or very near to this sequence.

Structure and Interactions of a Dimeric Variant of sHIP, a Novel Virulence Determinant of Streptococcus pyogenes.

PubMed

Diehl, Carl; Wisniewska, Magdalena; Frick, Inga-Maria; Streicher, Werner; Björck, Lars; Malmström, Johan; Wikström, Mats

2016-01-01

Streptococcus pyogenes is one of the most significant bacterial pathogens in the human population mostly causing superficial and uncomplicated infections (pharyngitis and impetigo) but also invasive and life-threatening disease. We have previously identified a virulence determinant, protein sHIP, which is secreted at higher levels by an invasive compared to a non-invasive strain of S. pyogenes. The present work presents a further characterization of the structural and functional properties of this bacterial protein. Biophysical and structural studies have shown that protein sHIP forms stable tetramers both in the crystal and in solution. The tetramers are composed of four helix-loop-helix motifs with the loop regions connecting the helices displaying a high degree of flexibility. Owing to interactions at the tetramer interface, the observed tetramer can be described as a dimer of dimers. We identified three residues at the tetramer interface (Leu84, Leu88, Tyr95), which due to largely non-polar side-chains, could be important determinants for protein oligomerization. Based on these observations, we produced a sHIP variant in which these residues were mutated to alanines. Biophysical experiments clearly indicated that the sHIP mutant appear only as dimers in solution confirming the importance of the interfacial residues for protein oligomerisation. Furthermore, we could show that the sHIP mutant interacts with intact histidine-rich glycoprotein (HRG) and the histidine-rich repeats in HRG, and inhibits their antibacterial activity to the same or even higher extent as compared to the wild type protein sHIP. We determined the crystal structure of the sHIP mutant, which, as a result of the high quality of the data, allowed us to improve the existing structural model of the protein. Finally, by employing NMR spectroscopy in solution, we generated a model for the complex between the sHIP mutant and an HRG-derived heparin-binding peptide, providing further molecular details into the interactions involving protein sHIP.

Osmotic mechanism of the loop extrusion process

NASA Astrophysics Data System (ADS)

Yamamoto, Tetsuya; Schiessel, Helmut

2017-09-01

The loop extrusion theory assumes that protein factors, such as cohesin rings, act as molecular motors that extrude chromatin loops. However, recent single molecule experiments have shown that cohesin does not show motor activity. To predict the physical mechanism involved in loop extrusion, we here theoretically analyze the dynamics of cohesin rings on a loop, where a cohesin loader is in the middle and unloaders at the ends. Cohesin monomers bind to the loader rather frequently and cohesin dimers bind to this site only occasionally. Our theory predicts that a cohesin dimer extrudes loops by the osmotic pressure of cohesin monomers on the chromatin fiber between the two connected rings. With this mechanism, the frequency of the interactions between chromatin segments depends on the loading and unloading rates of dimers at the corresponding sites.

40 CFR 63.166 - Standards: Sampling connection systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... defined in 40 CFR part 261. (c) In-situ sampling systems and sampling systems without purges are exempt..., closed-loop, or closed-vent system, except as provided in § 63.162(b) of this subpart. Gases displaced...-purge, closed-loop, or closed-vent system as required in paragraph (a) of this section shall: (1) Return...

Asynchronous Movements Prior to Pore Opening in NMDA Receptors

PubMed Central

Kazi, Rashek; Gan, Quan; Talukder, Iehab; Markowitz, Michael; Salussolia, Catherine L.

2013-01-01

Glutamate-gated ion channels embedded within the neuronal membrane are the primary mediators of fast excitatory synaptic transmission in the CNS. The ion channel of these glutamate receptors contains a pore-lining transmembrane M3 helix surrounded by peripheral M1 and M4 helices. In the NMDA receptor subtype, opening of the ion channel pore, mediated by displacement of the M3 helices away from the central pore axis, occurs in a highly concerted fashion, but the associated temporal movements of the peripheral helices are unknown. To address the gating dynamics of the peripheral helices, we constrained the relative movements of the linkers that connect these helices to the ligand-binding domain using engineered cross-links, either within (intra-GluN1 or GluN2A) or between subunits. Constraining the peripheral linkers in any manner dramatically curtailed channel opening, highlighting the requirement for rearrangements of these peripheral structural elements for efficient gating to occur. However, the magnitude of this gating effect depended on the specific subunit being constrained, with the most dramatic effects occurring when the constraint was between subunits. Based on kinetic and thermodynamic analysis, our results suggest an asynchrony in the displacement of the peripheral linkers during the conformational and energetic changes leading to pore opening. Initially there are large-scale rearrangements occurring between the four subunits. Subsequently, rearrangements occur within individual subunits, mainly GluN2A, leading up to or in concert with pore opening. Thus, the conformational changes induced by agonist binding in NMDA receptors converge asynchronously to permit pore opening. PMID:23864691

High salt solution structure of a left-handed RNA double helix

PubMed Central

Popenda, Mariusz; Milecki, Jan; Adamiak, Ryszard W.

2004-01-01

Right-handed RNA duplexes of (CG)n sequence undergo salt-induced helicity reversal, forming left-handed RNA double helices (Z-RNA). In contrast to the thoroughly studied Z-DNA, no Z-RNA structure of natural origin is known. Here we report the NMR structure of a half-turn, left-handed RNA helix (CGCGCG)2 determined in 6 M NaClO4. This is the first nucleic acid motif determined at such high salt. Sequential assignments of non-exchangeable proton resonances of the Z-form were based on the hitherto unreported NOE connectivity path [H6(n)-H5′/H5″(n)-H8(n+1)-H1′(n+1)-H6(n+2)] found for left-handed helices. Z-RNA structure shows several conformational features significantly different from Z-DNA. Intra-strand but no inter-strand base stacking was observed for both CpG and GpC steps. Helical twist angles for CpG steps have small positive values (4–7°), whereas GpC steps have large negative values (−61°). In the full-turn model of Z-RNA (12.4 bp per turn), base pairs are much closer to the helix axis than in Z-DNA, thus both the very deep, narrow minor groove with buried cytidine 2′-OH groups, and the major groove are well defined. The 2′-OH group of cytidines plays a crucial role in the Z-RNA structure and its formation; 2′-O-methylation of cytidine, but not of guanosine residues prohibits A to Z helicity reversal. PMID:15292450

Crystal structure of a looped-chain CoII coordination polymer: catena-poly[[bis-(nitrato-κO)cobalt(II)]bis-[μ-bis-(pyridin-3-ylmeth-yl)sulfane-κ2N:N'

PubMed

Moon, Suk-Hee; Seo, Joobeom; Park, Ki-Min

2017-11-01

The asymmetric unit of the title compound, [Co(NO 3 ) 2 (C 12 H 12 N 2 S) 2 ] n , contains a bis-(pyridin-3-ylmeth-yl)sulfane ( L ) ligand, an NO 3 - anion and half a Co II cation, which lies on an inversion centre. The Co II cation is six-coordinated, being bound to four pyridine N atoms from four symmetry-related L ligands. The remaining coordination sites are occupied by two O atoms from two symmetry-related nitrate anions in a monodentate manner. Thus, the Co II centre adopts a distorted octa-hedral geometry. Two symmetry-related L ligands are connected by two symmetry-related Co II cations, forming a 20-membered cyclic dimer, in which the Co II atoms are separated by 10.2922 (7) Å. The cyclic dimers are connected to each other by sharing Co II atoms, giving rise to the formation of an infinite looped chain propagating along the [101] direction. Inter-molecular C-H⋯π (H⋯ring centroid = 2.89 Å) inter-actions between one pair of corresponding L ligands and C-H⋯O hydrogen bonds between the L ligands and the nitrate anions occur in the looped chain. In the crystal, adjacent looped chains are connected by inter-molecular π-π stacking inter-actions [centroid-to-centroid distance = 3.8859 (14) Å] and C-H⋯π hydrogen bonds (H⋯ring centroid = 2.65 Å), leading to the formation of layers parallel to (101). These layers are further connected through C-H⋯O hydrogen bonds between the layers, resulting in the formation of a three-dimensional supra-molecular architecture.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Jun; Byrne, Noel; Wang, John

Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle. Comparison with an additional 2.2-Å structure of the hGPR40–MK-8666 binary complex reveals an induced-fit conformational couplingmore » between the partial agonist and AgoPAM binding sites, involving rearrangements of the transmembrane helices 4 and 5 (TM4 and TM5) and transition of the intracellular loop 2 (ICL2) into a short helix. These conformational changes likely prime GPR40 to a more active-like state and explain the binding cooperativity between these ligands.« less

The 2.6 Angstrom Crystal Structure of a Human A[subscript 2A] Adenosine Receptor Bound to an Antagonist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaakola, Veli-Pekka; Griffith, Mark T.; Hanson, Michael A.

2009-01-15

The adenosine class of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined the crystal structure of the human A{sub 2A} adenosine receptor, in complex with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom resolution. Four disulfide bridges in the extracellular domain, combined with a subtle repacking of the transmembrane helices relative to the adrenergic and rhodopsin receptor structures, define a pocket distinct from that of other structurally determined GPCRs. The arrangement allows for the binding of the antagonist in an extendedmore » conformation, perpendicular to the membrane plane. The binding site highlights an integral role for the extracellular loops, together with the helical core, in ligand recognition by this class of GPCRs and suggests a role for ZM241385 in restricting the movement of a tryptophan residue important in the activation mechanism of the class A receptors.« less

A Structural Model for the Single-Stranded DNA Genome of Filamentous Bacteriophage Pf1†

PubMed Central

Tsuboi, Masamichi; Tsunoda, Masaru; Overman, Stacy A.; Benevides, James M.; Thomas, George J.

2010-01-01

The filamentous bacteriophage Pf1, which infects strain PAK of Pseudomonas aeruginosa, is a flexible filament (~2000 × 6.5 nm) consisting of a covalently closed DNA loop of 7349 nucleotides sheathed by 7350 copies of a 46-residue α-helical subunit. The subunit α-helices, which are inclined at a small average angle (~16°) from the virion axis, are arranged compactly around the DNA core. Orientations of the Pf1 DNA nucleotides with respect to the filament axis are not known. In this work we report and interpret the polarized Raman spectra of oriented Pf1 filaments. We demonstrate that the polarizations of DNA Raman band intensities establish that the nucleotide bases of packaged Pf1 DNA are well ordered within the virion and that the base planes are positioned close to parallel to the filament axis. The present results are combined with a previously proposed projection of the intraviral path of Pf1 DNA (1) to develop a novel molecular model for the Pf1 assembly. PMID:20078135

Glue Spin and Helicity in the Proton from Lattice QCD.

PubMed

Yang, Yi-Bo; Sufian, Raza Sabbir; Alexandru, Andrei; Draper, Terrence; Glatzmaier, Michael J; Liu, Keh-Fei; Zhao, Yong

2017-03-10

We report the first lattice QCD calculation of the glue spin in the nucleon. The lattice calculation is carried out with valence overlap fermions on 2+1 flavor domain-wall fermion gauge configurations on four lattice spacings and four volumes including an ensemble with physical values for the quark masses. The glue spin S_{G} in the Coulomb gauge in the modified minimal subtraction (MS[over ¯]) scheme is obtained with one-loop perturbative matching. We find the results fairly insensitive to lattice spacing and quark masses. We also find that the proton momentum dependence of S_{G} in the range 0≤|p[over →]|<1.5  GeV is very mild, and we determine it in the large-momentum limit to be S_{G}=0.251(47)(16) at the physical pion mass in the MS[over ¯] scheme at μ^{2}=10  GeV^{2}. If the matching procedure in large-momentum effective theory is neglected, S_{G} is equal to the glue helicity measured in high-energy scattering experiments.

Improving RNA nearest neighbor parameters for helices by going beyond the two-state model.

PubMed

Spasic, Aleksandar; Berger, Kyle D; Chen, Jonathan L; Seetin, Matthew G; Turner, Douglas H; Mathews, David H

2018-06-01

RNA folding free energy change nearest neighbor parameters are widely used to predict folding stabilities of secondary structures. They were determined by linear regression to datasets of optical melting experiments on small model systems. Traditionally, the optical melting experiments are analyzed assuming a two-state model, i.e. a structure is either complete or denatured. Experimental evidence, however, shows that structures exist in an ensemble of conformations. Partition functions calculated with existing nearest neighbor parameters predict that secondary structures can be partially denatured, which also directly conflicts with the two-state model. Here, a new approach for determining RNA nearest neighbor parameters is presented. Available optical melting data for 34 Watson-Crick helices were fit directly to a partition function model that allows an ensemble of conformations. Fitting parameters were the enthalpy and entropy changes for helix initiation, terminal AU pairs, stacks of Watson-Crick pairs and disordered internal loops. The resulting set of nearest neighbor parameters shows a 38.5% improvement in the sum of residuals in fitting the experimental melting curves compared to the current literature set.

Three dimensional equilibrium solutions for a current-carrying reversed-field pinch plasma with a close-fitting conducting shell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koliner, J. J.; Boguski, J., E-mail: boguski@wisc.edu; Anderson, J. K.

2016-03-15

In order to characterize the Madison Symmetric Torus (MST) reversed-field pinch (RFP) plasmas that bifurcate to a helical equilibrium, the V3FIT equilibrium reconstruction code was modified to include a conducting boundary. RFP plasmas become helical at a high plasma current, which induces large eddy currents in MST's thick aluminum shell. The V3FIT conducting boundary accounts for the contribution from these eddy currents to external magnetic diagnostic coil signals. This implementation of V3FIT was benchmarked against MSTFit, a 2D Grad-Shafranov solver, for axisymmetric plasmas. The two codes both fit B{sub θ} measurement loops around the plasma minor diameter with qualitative agreementmore » between each other and the measured field. Fits in the 3D case converge well, with q-profile and plasma shape agreement between two distinct toroidal locking phases. Greater than 60% of the measured n = 5 component of B{sub θ} at r = a is due to eddy currents in the shell, as calculated by the conducting boundary model.« less

Three dimensional equilibrium solutions for a current-carrying reversed-field pinch plasma with a close-fitting conducting shell

DOE PAGES

Koliner, J. J.; Boguski, J.; Anderson, J. K.; ...

2016-03-25

In order to characterize the Madison Symmetric Torus (MST) reversed-field pinch(RFP)plasmas that bifurcate to a helical equilibrium, the V3FIT equilibrium reconstruction code was modified to include a conducting boundary. RFPplasmas become helical at a high plasma current, which induces large eddy currents in MST's thick aluminum shell. The V3FIT conducting boundary accounts for the contribution from these eddy currents to external magnetic diagnostic coil signals. This implementation of V3FIT was benchmarked against MSTFit, a 2D Grad-Shafranov solver, for axisymmetric plasmas. The two codes both fit B measurement loops around the plasma minor diameter with qualitative agreement between each other andmore » the measured field. Fits in the 3D case converge well, with q-profile and plasma shape agreement between two distinct toroidal locking phases. Greater than 60% of the measured n = 5 component of B at r = a is due to eddy currents in the shell, as calculated by the conducting boundary model.« less

Conformational Preference of ‘CαNN’ Short Peptide Motif towards Recognition of Anions

PubMed Central

Banerjee, Raja

2013-01-01

Among several ‘anion binding motifs’, the recently described ‘CαNN’ motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring ‘CαNN’ motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the ‘CαNN’ segment has an intrinsic affinity for anions. Molecular Dynamics (MD) simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the ‘CαNN’ segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the ‘CαNN’ sequence for anion recognition through “local” interaction. PMID:23516403

Structure of Arabidopsis thaliana Rubisco activase.

PubMed

Hasse, Dirk; Larsson, Anna M; Andersson, Inger

2015-04-01

The CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is inactivated by the formation of dead-end complexes with inhibitory sugar phosphates. In plants and green algae, the ATP-dependent motor protein Rubisco activase restores catalytic competence by facilitating conformational changes in Rubisco that promote the release of the inhibitory compounds from the active site. Here, the crystal structure of Rubisco activase from Arabidopsis thaliana is presented at 2.9 Å resolution. The structure reveals an AAA+ two-domain structure. More than 100 residues in the protein were not visible in the electron-density map owing to conformational disorder, but were verified to be present in the crystal by mass spectrometry. Two sulfate ions were found in the structure. One was bound in the loop formed by the Walker A motif at the interface of the domains. A second sulfate ion was bound at the N-terminal end of the first helix of the C-terminal domain. The protein packs in a helical fashion in the crystal, as observed previously for Rubisco activase, but differences in the helical pitch indicate flexibility in the packing of the protein.

Assessing Command and Control System Vulnerabilities in Underdeveloped, Degraded and Denied Operational Environments

DTIC Science & Technology

2013-06-01

simulation of complex systems (Sterman 2000, Meadows 2008): a) Causal Loop Diagrams. A Causal Loop Diagram ( CLD ) is used to represent the feedback...structure of the dynamic system. CLDs consist of variables in the system being connected by arrows to show their causal influences and relationships. It is...distribution of orders will be included in the model. 6.4.2 Causal Loop Diagrams The CLD , as seen in Figure 5, is derived from the WDA constructs for the

On the predictability of the orientation of protein domains joined by a spanning alpha-helical linker.

PubMed

Lai, Yen-Ting; Jiang, Lin; Chen, Wuyang; Yeates, Todd O

2015-11-01

Connecting proteins together in prescribed geometric arrangements is an important element in new areas of biomolecular design. In this study, we characterize the degree of three-dimensional orientational control that can be achieved when two protein domains that have alpha-helical termini are joined using an alpha-helical linker. A fusion between naturally oligomeric protein domains was designed in this fashion with the intent of creating a self-assembling 12-subunit tetrahedral protein cage. While the designed fusion protein failed to assemble into a tetrahedral cage in high yield, a series of crystal structures showed that the two fused components were indeed bridged by an intact alpha helix, although the fusion protein was distorted from the intended ideal configuration by bending of the helix, ranging from 7 to 35°. That range of deviation in orientation creates challenges for designing large, perfectly symmetric protein assemblies, although it should offer useful outcomes for other less geometrically demanding applications in synthetic biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Self-assembly of Janus particles into helices with tunable pitch

NASA Astrophysics Data System (ADS)

Fernández, M. Sobrino; Misko, V. R.; Peeters, F. M.

2015-10-01

Janus particles present an important class of building blocks for directional assembly. These are compartmentalized colloids with two different hemispheres. In this work we consider a three-dimensional model of Janus spheres that contain one hydrophobic and one charged hemisphere. Using molecular dynamics simulations, we study the morphology of these particles when confined in a channel-like environment. The interplay between the attractive and repulsive forces on each particle gives rise to a rich phase space where the relative orientation of each particle plays a dominant role in the formation of large-scale clusters. The interest in this system is primarily due to the fact that it could give a better understanding of the mechanisms of the formation of polar membranes. A variety of ordered membranelike morphologies is found consisting of single and multiple connected chain configurations. The helicity of these chains can be chosen by simply changing the salt concentration of the solution. Special attention is given to the formation of Bernal spirals. These helices are composed of regular tetrahedra and are known to exhibit nontrivial translational and rotational symmetry.

[Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

PubMed

Arens, C; Glanz, H; Voigt-Zimmermann, S

2015-11-01

The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

Feasibility of outpatient fully integrated closed-loop control: first studies of wearable artificial pancreas.

PubMed

Kovatchev, Boris P; Renard, Eric; Cobelli, Claudio; Zisser, Howard C; Keith-Hynes, Patrick; Anderson, Stacey M; Brown, Sue A; Chernavvsky, Daniel R; Breton, Marc D; Farret, Anne; Pelletier, Marie-Josée; Place, Jérôme; Bruttomesso, Daniela; Del Favero, Simone; Visentin, Roberto; Filippi, Alessio; Scotton, Rachele; Avogaro, Angelo; Doyle, Francis J

2013-07-01

To evaluate the feasibility of a wearable artificial pancreas system, the Diabetes Assistant (DiAs), which uses a smart phone as a closed-loop control platform. Twenty patients with type 1 diabetes were enrolled at the Universities of Padova, Montpellier, and Virginia and at Sansum Diabetes Research Institute. Each trial continued for 42 h. The United States studies were conducted entirely in outpatient setting (e.g., hotel or guest house); studies in Italy and France were hybrid hospital-hotel admissions. A continuous glucose monitoring/pump system (Dexcom Seven Plus/Omnipod) was placed on the subject and was connected to DiAs. The patient operated the system via the DiAs user interface in open-loop mode (first 14 h of study), switching to closed-loop for the remaining 28 h. Study personnel monitored remotely via 3G or WiFi connection to DiAs and were available on site for assistance. The total duration of proper system communication functioning was 807.5 h (274 h in open-loop and 533.5 h in closed-loop), which represented 97.7% of the total possible time from admission to discharge. This exceeded the predetermined primary end point of 80% system functionality. This study demonstrated that a contemporary smart phone is capable of running outpatient closed-loop control and introduced a prototype system (DiAs) for further investigation. Following this proof of concept, future steps should include equipping insulin pumps and sensors with wireless capabilities, as well as studies focusing on control efficacy and patient-oriented clinical outcomes.

Circulating current battery heater

DOEpatents

Ashtiani, Cyrus N.; Stuart, Thomas A.

2001-01-01

A circuit for heating energy storage devices such as batteries is provided. The circuit includes a pair of switches connected in a half-bridge configuration. Unidirectional current conduction devices are connected in parallel with each switch. A series resonant element for storing energy is connected from the energy storage device to the pair of switches. An energy storage device for intermediate storage of energy is connected in a loop with the series resonant element and one of the switches. The energy storage device which is being heated is connected in a loop with the series resonant element and the other switch. Energy from the heated energy storage device is transferred to the switched network and then recirculated back to the battery. The flow of energy through the battery causes internal power dissipation due to electrical to chemical conversion inefficiencies. The dissipated power causes the internal temperature of the battery to increase. Higher internal temperatures expand the cold temperature operating range and energy capacity utilization of the battery. As disclosed, either fixed frequency or variable frequency modulation schemes may be used to control the network.

Structure of the β-form of human MK2 in complex with the non-selective kinase inhibitor TEI-L03090

PubMed Central

Fujino, Aiko; Fukushima, Kei; Kubota, Takaharu; Matsumoto, Yoshiyuki; Takimoto-Kamimura, Midori

2013-01-01

Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2), a serine/threonine kinase from the p38 mitogen-activated protein kinase signalling pathway, plays an important role in the production of TNF-α and other cytokines. In a previous report, it was shown that MK2 in complex with the selective inhibitor TEI-I01800 adopts an α-helical glycine-rich loop that is induced by the stable nonplanar conformer of TEI-I01800. To understand the mechanism of the structural change, the structure of MK2 bound to TEI-L03090, which lacks the key substituent found in TEI-I01800, was determined. MK2–TEI-L03090 has a β-sheet glycine-rich loop in common with other kinases, as predicted. This result suggests that a small compound can induce a drastic conformational change in the target protein structure and can be used to design potent and selective inhibitors. PMID:24316826

T -odd correlations in polarized top quark decays in the sequential decay t (↑)→Xb+W+(→ℓ++νℓ) and in the quasi-three-body decay t (↑)→ Xb+ℓ++νℓ

NASA Astrophysics Data System (ADS)

Fischer, M.; Groote, S.; Körner, J. G.

2018-05-01

We identify the T -odd structure functions that appear in the description of polarized top quark decays in the sequential decay t (↑)→Xb+W+(→ℓ++νℓ) (two structure functions) and the quasi-three-body decay t (↑)→X b+ℓ++νℓ (one structure function). A convenient measure of the magnitude of the T -odd structure functions is the contribution of the imaginary part Im gR of the right-chiral tensor coupling gR to the T -odd structure functions which we work out. Contrary to the case of QCD, the NLO electroweak corrections to polarized top quark decays admit absorptive one-loop vertex contributions. We analytically calculate the imaginary parts of the relevant four electroweak one-loop triangle vertex diagrams and determine their contributions to the T -odd helicity structure functions that appear in the description of polarized top quark decays.

Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands.

PubMed Central

Richardson, J; Thomas, K A; Rubin, B H; Richardson, D C

1975-01-01

An electron density map at 3 angstrom resolution has been calculated for Cu2+, Zn2+ superoxide dismutase from bovine erythrocytes, and the course of the main chain has been traced. The dominant structural feature is an 8-stranded barrel of antiparallel beta-pleated sheet. There is one very short helical section and two long loops of non-repetitive structure. The Cu and Zn are bound between the loops and one side of the beta barrel and are about 6 Angstrom apart, with a common histidine ligand. The Cu has four histidine ligands in a somewhat distorted square plane, and the Zn has three histidines and an aspartate in approximately tetrahedral arrangement. The two coppers of a dimer are about 34 Angstrom apart. The two subunits have essentially the same conformation and have an extensive contact area that mainly involves hydrophobic side chain interactions. The overall folding pattern of the polypeptide chain is very similar to that of an immunoglobulin domain. Images PMID:1055410

Using synthetic bacterial enhancers to reveal a looping-based mechanism for quenching-like repression

PubMed Central

Brunwasser-Meirom, Michal; Pollak, Yaroslav; Goldberg, Sarah; Levy, Lior; Atar, Orna; Amit, Roee

2016-01-01

We explore a model for ‘quenching-like' repression by studying synthetic bacterial enhancers, each characterized by a different binding site architecture. To do so, we take a three-pronged approach: first, we compute the probability that a protein-bound dsDNA molecule will loop. Second, we use hundreds of synthetic enhancers to test the model's predictions in bacteria. Finally, we verify the mechanism bioinformatically in native genomes. Here we show that excluded volume effects generated by DNA-bound proteins can generate substantial quenching. Moreover, the type and extent of the regulatory effect depend strongly on the relative arrangement of the binding sites. The implications of these results are that enhancers should be insensitive to 10–11 bp insertions or deletions (INDELs) and sensitive to 5–6 bp INDELs. We test this prediction on 61 σ54-regulated qrr genes from the Vibrio genus and confirm the tolerance of these enhancers' sequences to the DNA's helical repeat. PMID:26832446

Using synthetic bacterial enhancers to reveal a looping-based mechanism for quenching-like repression.

PubMed

Brunwasser-Meirom, Michal; Pollak, Yaroslav; Goldberg, Sarah; Levy, Lior; Atar, Orna; Amit, Roee

2016-02-02

We explore a model for 'quenching-like' repression by studying synthetic bacterial enhancers, each characterized by a different binding site architecture. To do so, we take a three-pronged approach: first, we compute the probability that a protein-bound dsDNA molecule will loop. Second, we use hundreds of synthetic enhancers to test the model's predictions in bacteria. Finally, we verify the mechanism bioinformatically in native genomes. Here we show that excluded volume effects generated by DNA-bound proteins can generate substantial quenching. Moreover, the type and extent of the regulatory effect depend strongly on the relative arrangement of the binding sites. The implications of these results are that enhancers should be insensitive to 10-11 bp insertions or deletions (INDELs) and sensitive to 5-6 bp INDELs. We test this prediction on 61 σ(54)-regulated qrr genes from the Vibrio genus and confirm the tolerance of these enhancers' sequences to the DNA's helical repeat.

Trigger loop dynamics can explain stimulation of intrinsic termination by bacterial RNA polymerase without terminator hairpin contact.

PubMed

Ray-Soni, Ananya; Mooney, Rachel A; Landick, Robert

2017-10-31

In bacteria, intrinsic termination signals cause disassembly of the highly stable elongating transcription complex (EC) over windows of two to three nucleotides after kilobases of RNA synthesis. Intrinsic termination is caused by the formation of a nascent RNA hairpin adjacent to a weak RNA-DNA hybrid within RNA polymerase (RNAP). Although the contributions of RNA and DNA sequences to termination are largely understood, the roles of conformational changes in RNAP are less well described. The polymorphous trigger loop (TL), which folds into the trigger helices to promote nucleotide addition, also is proposed to drive termination by folding into the trigger helices and contacting the terminator hairpin after invasion of the hairpin in the RNAP main cleft [Epshtein V, Cardinale CJ, Ruckenstein AE, Borukhov S, Nudler E (2007) Mol Cell 28:991-1001]. To investigate the contribution of the TL to intrinsic termination, we developed a kinetic assay that distinguishes effects of TL alterations on the rate at which ECs terminate from effects of the TL on the nucleotide addition rate that indirectly affect termination efficiency by altering the time window in which termination can occur. We confirmed that the TL stimulates termination rate, but found that stabilizing either the folded or unfolded TL conformation decreased termination rate. We propose that conformational fluctuations of the TL (TL dynamics), not TL-hairpin contact, aid termination by increasing EC conformational diversity and thus access to favorable termination pathways. We also report that the TL and the TL sequence insertion (SI3) increase overall termination efficiency by stimulating pausing, which increases the flux of ECs into the termination pathway. Published under the PNAS license.

Twelve Transmembrane Helices Form the Functional Core of Mammalian MATE1 (Multidrug and Toxin Extruder 1) Protein*

PubMed Central

Zhang, Xiaohong; He, Xiao; Baker, Joseph; Tama, Florence; Chang, Geoffrey; Wright, Stephen H.

2012-01-01

The x-ray structure of the prototypic MATE family member, NorM from Vibrio cholerae, reveals a protein fold composed of 12 transmembrane helices (TMHs), confirming hydropathy analyses of the majority of (prokaryotic and plant) MATE transporters. However, the mammalian MATEs are generally predicted to have a 13th TMH and an extracellular C terminus. Here we affirm this prediction, showing that the C termini of epitope-tagged, full-length human, rabbit, and mouse MATE1 were accessible to antibodies from the extracellular face of the membrane. Truncation of these proteins at or near the predicted junction between the 13th TMH and the long cytoplasmic loop that precedes it resulted in proteins that (i) trafficked to the membrane and (ii) interacted with antibodies only after permeabilization of the plasma membrane. CHO cells expressing rbMate1 truncated at residue Gly-545 supported levels of pH-sensitive transport similar to that of cells expressing the full-length protein. Although the high transport rate of the Gly-545 truncation mutant was associated with higher levels of membrane expression (than full-length MATE1), suggesting the 13th TMH may influence substrate translocation, the selectivity profile of the mutant indicated that TMH13 has little impact on ligand binding. We conclude that the functional core of MATE1 consists of 12 (not 13) TMHs. Therefore, we used the x-ray structure of NorM to develop a homology model of the first 12 TMHs of MATE1. The model proved to be stable in molecular dynamic simulations and agreed with topology evident from preliminary cysteine scanning of intracellular versus extracellular loops. PMID:22722930

Helicon modes in uniform plasmas. I. Low m modes

NASA Astrophysics Data System (ADS)

Urrutia, J. M.; Stenzel, R. L.

2015-09-01

Helicons are whistler modes with azimuthal wave numbers. They arise in bounded gaseous and solid state plasmas, but the present work shows that very similar modes also exist in unbounded uniform plasmas. The antenna properties determine the mode structure. A simple antenna is a magnetic loop with dipole moment aligned either along or across the ambient background magnetic field B0. For such configurations, the wave magnetic field has been measured in space and time in a large and uniform laboratory plasma. The observed wave topology for a dipole along B0 is similar to that of an m = 0 helicon mode. It consists of a sequence of alternating whistler vortices. For a dipole across B0, an m = 1 mode is excited which can be considered as a transverse vortex which rotates around B0. In m = 0 modes, the field lines are confined to each half-wavelength vortex while for m = 1 modes they pass through the entire wave train. A subset of m = 1 field lines forms two nested helices which rotate in space and time like corkscrews. Depending on the type of the antenna, both m = + 1 and m = -1 modes can be excited. Helicons in unbounded plasmas also propagate transverse to B0. The transverse and parallel wave numbers are about equal and form oblique phase fronts as in whistler Gendrin modes. By superimposing small amplitude fields of several loop antennas, various antenna combinations have been created. These include rotating field antennas, helical antennas, and directional antennas. The radiation efficiency is quantified by the radiation resistance. Since helicons exist in unbounded laboratory plasmas, they can also arise in space plasmas.

NMR structure of the bovine prion protein

PubMed Central

López García, Francisco; Zahn, Ralph; Riek, Roland; Wüthrich, Kurt

2000-01-01

The NMR structures of the recombinant 217-residue polypeptide chain of the mature bovine prion protein, bPrP(23–230), and a C-terminal fragment, bPrP(121–230), include a globular domain extending from residue 125 to residue 227, a short flexible chain end of residues 228–230, and an N-terminal flexibly disordered “tail” comprising 108 residues for the intact protein and 4 residues for bPrP(121–230), respectively. The globular domain contains three α-helices comprising the residues 144–154, 173–194, and 200–226, and a short antiparallel β-sheet comprising the residues 128–131 and 161–164. The best-defined parts of the globular domain are the central portions of the helices 2 and 3, which are linked by the only disulfide bond in bPrP. Significantly increased disorder and mobility is observed for helix 1, the loop 166–172 leading from the β-strand 2 to helix 2, the end of helix 2 and the following loop, and the last turn of helix 3. Although there are characteristic local differences relative to the conformations of the murine and Syrian hamster prion proteins, the bPrP structure is essentially identical to that of the human prion protein. On the other hand, there are differences between bovine and human PrP in the surface distribution of electrostatic charges, which then appears to be the principal structural feature of the “healthy” PrP form that might affect the stringency of the species barrier for transmission of prion diseases between humans and cattle. PMID:10899999

Trigger loop dynamics can explain stimulation of intrinsic termination by bacterial RNA polymerase without terminator hairpin contact

PubMed Central

Ray-Soni, Ananya; Mooney, Rachel A.; Landick, Robert

2017-01-01

In bacteria, intrinsic termination signals cause disassembly of the highly stable elongating transcription complex (EC) over windows of two to three nucleotides after kilobases of RNA synthesis. Intrinsic termination is caused by the formation of a nascent RNA hairpin adjacent to a weak RNA−DNA hybrid within RNA polymerase (RNAP). Although the contributions of RNA and DNA sequences to termination are largely understood, the roles of conformational changes in RNAP are less well described. The polymorphous trigger loop (TL), which folds into the trigger helices to promote nucleotide addition, also is proposed to drive termination by folding into the trigger helices and contacting the terminator hairpin after invasion of the hairpin in the RNAP main cleft [Epshtein V, Cardinale CJ, Ruckenstein AE, Borukhov S, Nudler E (2007) Mol Cell 28:991–1001]. To investigate the contribution of the TL to intrinsic termination, we developed a kinetic assay that distinguishes effects of TL alterations on the rate at which ECs terminate from effects of the TL on the nucleotide addition rate that indirectly affect termination efficiency by altering the time window in which termination can occur. We confirmed that the TL stimulates termination rate, but found that stabilizing either the folded or unfolded TL conformation decreased termination rate. We propose that conformational fluctuations of the TL (TL dynamics), not TL-hairpin contact, aid termination by increasing EC conformational diversity and thus access to favorable termination pathways. We also report that the TL and the TL sequence insertion (SI3) increase overall termination efficiency by stimulating pausing, which increases the flux of ECs into the termination pathway. PMID:29078293

Crystal and Molecular Structure of a Collagen-Like Peptide at 1.9 overset{circ}{A} Resolution

NASA Astrophysics Data System (ADS)

Bella, Jordi; Eaton, Mark; Brodsky, Barbara; Berman, Helen M.

1994-10-01

The structure of a protein triple helix has been determined at 1.9 angstrom resolution by x-ray crystallographic studies of a collagen-like peptide containing a single substitution of the consensus sequence. This peptide adopts a triple-helical structure that confirms the basic features determined from fiber diffraction studies on collagen: supercoiling of polyproline II helices and interchain hydrogen bonding that follows the model II of Rich and Crick. In addition, the structure provides new information concerning the nature of this protein fold. Each triple helix is surrounded by a cylinder of hydration, with an extensive hydrogen bonding network between water molecules and peptide acceptor groups. Hydroxyproline residues have a critical role in this water network. The interaxial spacing of triple helices in the crystal is similar to that in collagen fibrils, and the water networks linking adjacent triple helices in the crystal structure are likely to be present in connective tissues. The breaking of the repeating (X-Y-Gly)_n pattern by a Gly-->Ala substitution results in a subtle alteration of the conformation, with a local untwisting of the triple helix. At the substitution site, direct interchain hydrogen bonds are replaced with interstitial water bridges between the peptide groups. Similar conformational changes may occur in Gly-->X mutated collagens responsible for the diseases osteogenesis imperfecta, chondrodysplasias, and Ehlers-Danlos syndrome IV.

Chemotaxis without Conventional Two-Component System, Based on Cell Polarity and Aerobic Conditions in Helicity-Switching Swimming of Spiroplasma eriocheiris

PubMed Central

Liu, Peng; Zheng, Huajun; Meng, Qingguo; Terahara, Natsuho; Gu, Wei; Wang, Shengyue; Zhao, Guoping; Nakane, Daisuke; Wang, Wen; Miyata, Makoto

2017-01-01

Spiroplasma eriocheiris is a pathogen that causes mass mortality in Chinese mitten crab, Eriocheir sinensis. S. eriocheiris causes tremor disease and infects almost all of the artificial breeding crustaceans, resulting in disastrous effects on the aquaculture economy in China. S. eriocheiris is a wall-less helical bacterium, measuring 2.0 to 10.0 μm long, and can swim up to 5 μm per second in a viscous medium without flagella by switching the cell helicity at a kink traveling from the front to the tail. In this study, we showed that S. eriocheiris performs chemotaxis without the conventional two-component system, a system commonly found in bacterial chemotaxis. The chemotaxis of S. eriocheiris was observed more clearly when the cells were cultivated under anaerobic conditions. The cells were polarized as evidenced by a tip structure, swimming in the direction of the tip, and were shown to reverse their swimming direction in response to attractants. Triton X-100 treatment revealed the internal structure, a dumbbell-shaped core in the tip that is connected by a flat ribbon, which traces the shortest line in the helical cell shape from the tip to the other pole. Sixteen proteins were identified as the components of the internal structure by mass spectrometry, including Fibril protein and four types of MreB proteins. PMID:28217108

Imaging diagnosis--Complex intrahepatic portosystemic shunt in a dog.

PubMed

D'Anjou, Marc-André; Huneault, Louis

2008-01-01

An unusual form of congenital intrahepatic portosystemic shunt was identified in a 3 1/2-month-old female Labrador Retriever with neurologic signs. Ultrasonography and contrast-enhanced computed tomography were used to characterize the shunt morphology. An unusual, looping right-divisional shunt connected back to the portal vein that formed an ampula in the right-central portion of the liver. An irregularly shaped window-like opening connected the combined right-divisional loop and aneurysmal portal vein, and the caudal vena cava, while this vascular pool gradually fused more cranially. Imaging features of this complex vascular anomaly, which has not been previously reported, are presented.

Fuzzy logic control and optimization system

DOEpatents

Lou, Xinsheng [West Hartford, CT

2012-04-17

A control system (300) for optimizing a power plant includes a chemical loop having an input for receiving an input signal (369) and an output for outputting an output signal (367), and a hierarchical fuzzy control system (400) operably connected to the chemical loop. The hierarchical fuzzy control system (400) includes a plurality of fuzzy controllers (330). The hierarchical fuzzy control system (400) receives the output signal (367), optimizes the input signal (369) based on the received output signal (367), and outputs an optimized input signal (369) to the input of the chemical loop to control a process of the chemical loop in an optimized manner.

Mining protein loops using a structural alphabet and statistical exceptionality

PubMed Central

2010-01-01

Background Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied. Results We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 Å). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of amino-acid conservation with at least four significant positions and 87% of long loops contain at least one such word. We complement our analysis with the detection of statistically over-represented patterns of structural letters as in conventional DNA sequence analysis. About 30% (930) of structural words are over-represented, and cover about 40% of loop lengths. Interestingly, these words exhibit lower structural variability and higher sequential specificity, suggesting structural or functional constraints. Conclusions We developed a method to systematically decompose and study protein loops using recurrent structural motifs. This method is based on the structural alphabet HMM-SA and not on structural alignment and geometrical parameters. We extracted meaningful structural motifs that are found in both short and long loops. To our knowledge, it is the first time that pattern mining helps to increase the signal-to-noise ratio in protein loops. This finding helps to better describe protein loops and might permit to decrease the complexity of long-loop analysis. Detailed results are available at http://www.mti.univ-paris-diderot.fr/publication/supplementary/2009/ACCLoop/. PMID:20132552

Mining protein loops using a structural alphabet and statistical exceptionality.

PubMed

Regad, Leslie; Martin, Juliette; Nuel, Gregory; Camproux, Anne-Claude

2010-02-04

Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied. We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 A). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of amino-acid conservation with at least four significant positions and 87% of long loops contain at least one such word. We complement our analysis with the detection of statistically over-represented patterns of structural letters as in conventional DNA sequence analysis. About 30% (930) of structural words are over-represented, and cover about 40% of loop lengths. Interestingly, these words exhibit lower structural variability and higher sequential specificity, suggesting structural or functional constraints. We developed a method to systematically decompose and study protein loops using recurrent structural motifs. This method is based on the structural alphabet HMM-SA and not on structural alignment and geometrical parameters. We extracted meaningful structural motifs that are found in both short and long loops. To our knowledge, it is the first time that pattern mining helps to increase the signal-to-noise ratio in protein loops. This finding helps to better describe protein loops and might permit to decrease the complexity of long-loop analysis. Detailed results are available at http://www.mti.univ-paris-diderot.fr/publication/supplementary/2009/ACCLoop/.

Signal connection for a downhole tool string

DOEpatents

Hall, David R.; Hall, Jr., H. Tracy; Pixton, David S.; Bradford, Kline; Fox, Joe; Briscoe, Michael

2006-08-29

A signal transmission connection for a tool string used in exploration and production of natural resources, namely: oil, gas, and geothermal energy resources. The connection comprises first and second annular elements deployed in cooperative association with each other. The respective elements comprise inductive transducers that are capable of two-way signal transmission between each other, with downhole components of the tool string, and with ground-level equipment. The respective inductive transducers comprise one or more conductive loops housed within ferrite troughs, or within ferrite trough segments. When energized, the conductive loops produce a magnetic field suitable for transmitting the signal. The second element may be rotational in drilling applications. The respective elements may be fitted with electronic equipment to aid and manipulate the transmission of the signal. The first element may also be in communication with the World Wide Web.

Frequency multiplexed flux locked loop architecture providing an array of DC SQUIDS having both shared and unshared components

DOEpatents

Ganther, Jr., Kenneth R.; Snapp, Lowell D.

2002-01-01

Architecture for frequency multiplexing multiple flux locked loops in a system comprising an array of DC SQUID sensors. The architecture involves dividing the traditional flux locked loop into multiple unshared components and a single shared component which, in operation, form a complete flux locked loop relative to each DC SQUID sensor. Each unshared flux locked loop component operates on a different flux modulation frequency. The architecture of the present invention allows a reduction from 2N to N+1 in the number of connections between the cryogenic DC SQUID sensors and their associated room temperature flux locked loops. Furthermore, the 1.times.N architecture of the present invention can be paralleled to form an M.times.N array architecture without increasing the required number of flux modulation frequencies.

Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.

PubMed

Hamperl, Stephan; Bocek, Michael J; Saldivar, Joshua C; Swigut, Tomek; Cimprich, Karlene A

2017-08-10

Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

Connecting apparatus for limited rotary of rectilinear motion (II)

DOEpatents

Hardin, Jr., Roy T.; Kurinko, Carl D.

1981-01-01

Apparatus for providing connection between two members having relative movement in a horizontal plane in a rotary or linear fashion. The apparatus includes a set of vertical surfaces affixed to each of the members, laterally aligned across a selected vertical gap. A number of cables or hoses, for electrical, hydraulic, or pneumatic connection are arranged between consecutive surfaces in a C-shaped traveling loop, connected through their end portions to the two respective members, so that through a sliding motion portions of the cable are transferred from between one set of surfaces to the other aligned set, across the gap, upon relative motion of the members. A number of flexible devices are affixed to the upper set of surfaces for supporting the upper portion of each looped cable. The apparatus is particularly adaptable to an area having limited lateral clearances and requiring signal level separation between electrical cables, such as found in the rotating plugs and associated equipment of the reactor vessel head of a nuclear reactor.

Finite element generation of arbitrary 3-D fracture networks for flow analysis in complicated discrete fracture networks

NASA Astrophysics Data System (ADS)

Zhang, Qi-Hua

2015-10-01

Finite element generation of complicated fracture networks is the core issue and source of technical difficulty in three-dimensional (3-D) discrete fracture network (DFN) flow models. Due to the randomness and uncertainty in the configuration of a DFN, the intersection lines (traces) are arbitrarily distributed in each face (fracture and other surfaces). Hence, subdivision of the fractures is an issue relating to subdivision of two-dimensional (2-D) domains with arbitrarily-distributed constraints. When the DFN configuration is very complicated, the well-known approaches (e.g. Voronoi Delaunay-based methods and advancing-front techniques) cannot operate properly. This paper proposes an algorithm to implement end-to-end connection between traces to subdivide 2-D domains into closed loops. The compositions of the vertices in the common edges between adjacent loops (which may belong to a single fracture or two connected fractures) are thus ensured to be topologically identical. The paper then proposes an approach for triangulating arbitrary loops which does not add any nodes to ensure consistency of the meshes at the common edges. In addition, several techniques relating to tolerance control and improving code robustness are discussed. Finally, the equivalent permeability of the rock mass is calculated for some very complicated DFNs (the DFN may contain 1272 fractures, 633 connected fractures, and 16,270 closed loops). The results are compared with other approaches to demonstrate the veracity and efficiency of the approach proposed in this paper.

Structure of the Bacillus subtilis phage SPO1-encoded type II DNA-binding protein TF1 in solution.

PubMed

Jia, X; Grove, A; Ivancic, M; Hsu, V L; Geiduscheck, E P; Kearns, D R

1996-10-25

The solution structure of a type II DNA-binding protein, the bacteriophage SPO1-encoded transcription factor 1 (TF1), was determined using NMR spectroscopy. Selective 2H-labeling, 13C-labeling and isotopic heterodimers were used to distinguish contacts between and within monomers of the dimeric protein. A total of 1914 distance and dihedral angle constraints derived from NMR experiments were used in structure calculations using restrained molecular dynamics and simulated annealing protocols. The ensemble of 30 calculated structures has a root-mean-square deviation (r.m.s.d.) of 0.9 A, about the average structure for the backbone atoms, and 1.2 A for all heavy-atoms of the dimeric core (helices 1 and 2) and the beta-sheets. A severe helix distortion at residues 92-93 in the middle of helix 3 is associated with r.m.s.d. of approximately 1.5 A for the helix 3 backbone. Deviations of approximately 5 A or larger are noted for the very flexible beta-ribbon arms that constitute part of a proposed DNA-binding region. A structural model of TF1 has been calculated based on the previously reported crystal structure of the homologous HU protein and this model was used as the starting structure for calculations. A comparison between the calculated average solution structure of TF1 and a solution structure of HU indicates a similarity in the dimeric core (excluding the nine amino acid residue tail) with pairwise deviations of 2 to 3 A. The largest deviations between the average structure and the HU solution structure were found in the beta-ribbon arms, as expected. A 4 A deviation is found at residue 15 of TF1 which is in a loop connecting two helical segments; it has been reported that substitution of Glu15 by Gly increases the thermostability of TF1. The homology between TF1 and other proteins of this family leads us to anticipate similar tertiary structures.

The Global Solar Dynamo

NASA Astrophysics Data System (ADS)

Cameron, R. H.; Dikpati, M.; Brandenburg, A.

2017-09-01

A brief summary of the various observations and constraints that underlie solar dynamo research are presented. The arguments that indicate that the solar dynamo is an alpha-omega dynamo of the Babcock-Leighton type are then shortly reviewed. The main open questions that remain are concerned with the subsurface dynamics, including why sunspots emerge at preferred latitudes as seen in the familiar butterfly wings, why the cycle is about 11 years long, and why the sunspot groups emerge tilted with respect to the equator (Joy's law). Next, we turn to magnetic helicity, whose conservation property has been identified with the decline of large-scale magnetic fields found in direct numerical simulations at large magnetic Reynolds numbers. However, magnetic helicity fluxes through the solar surface can alleviate this problem and connect theory with observations, as will be discussed.

Enigmatic insight into collagen

PubMed Central

Deshmukh, Shrutal Narendra; Dive, Alka M; Moharil, Rohit; Munde, Prashant

2016-01-01

Collagen is a unique, triple helical molecule which forms the major part of extracellular matrix. It is the most abundant protein in the human body, representing 30% of its dry weight. It is the fibrous structural protein that makes up the white fibers (collagen fibers) of skin, tendons, bones, cartilage and all other connective tissues. Collagens are not only essential for the mechanical resistance and resilience of multicellular organisms, but are also signaling molecules defining cellular shape and behavior. The human body has at least 16 types of collagen, but the most prominent types are I, II and III. Collagens are produced by several cell types and are distinguishable by their molecular compositions, morphologic characteristics, distribution, functions and pathogenesis. This is the major fibrous glycoprotein present in the extracellular matrix and in connective tissue and helps in maintaining the structural integrity of these tissues. It has a triple helical structure. Various studies have proved that mutations that modify folding of the triple helix result in identifiable genetic disorders. Collagen diseases share certain similarities with autoimmune diseases, because autoantibodies specific to each collagen disease are produced. Therefore, this review highlights the role of collagen in normal health and also the disorders associated with structural and functional defects in collagen. PMID:27601823

Free Energy and Structure of Helix-forming Peptides: A Theoretical Investigation

NASA Astrophysics Data System (ADS)

Karpusenka, Vadzim

This thesis focuses on the structure and free energy of helical secondary structures of short peptides in a variety of experimental settings. Specifically, the formation of alpha-, pi- and 310-helices was investigated using large-scale classical molecular dynamics simulations with state-of-the-art force fields. In addition, the recently developed Adaptively Biased Molecular Dynamics (ABMD) and Steered Molecular Dynamics (SMD) methods were used to calculate the corresponding free energies. The most important results are as follows. For the examined peptide homopolymers, the observed minima on the free energy landscapes (based on suitable collective variables such as the radius of gyration, number of hydrogen bonds, and handedness) were associated with alpha-helices and "globular" or "knot-like" configurations only. No evidence was found to indicate that 310- or pi-helices represent equilibrium structures for these systems. In addition, the free energy landscape of short peptide chains formed by mixing two different amino acids were also examined. These results too indicate that the alpha-helix is only equilibrium helical secondary structure, and that the mixing of different amino acids does not result in the introduction of any significant new minima into the free energy landscapes. These results are in agreement with experimental observations insofar as these indicate that helical structural motifs are primary based on alpha-helices, with 310- and pi-helices being observed only rarely. Although pi- and 310-helices represent nonequilibrium structures, we were still able to estimate their free energies by means of SMD simulations. The helical secondary structure of the examined polypeptide chains is due to the formation of hydrogen bonds. However, there are other mechanisms that may allow for the additional stabilization of these structures. Specifically, in the so-called AK-(4,7) protein, the possible presence of disulfide bonds connecting cysteine residues may significantly alter the free energy landscapes and therefore the stability of different helical structures. We therefore examined this issue with ABMD simulations. However, our results show that while the free energy landscapes are indeed significantly altered only the formation of alpha-helices is favored as a secondary structural motif. Since all the results indicate that alpha-helix formation dominates, it is natural to think in terms of an alpha-helix forming propensity for different amino acids. To address this question, we carried out an extensive residue-by-residue population analysis of different amino acid guests in an alanine-based host setting. Such an analysis allows us to rank the different amino acid guests based on whether they increased or decreased the population in the alpha-helix region of the corresponding Ramachandran plots. Our ranking of the different guest amino acids is in reasonable correspondence with the experimental results, although some differences are observed. Finally, using a four-beads coarse-grained model were have investigated the stability of GA88 and GB88 proteins, which are quite similar in terms of their amino acid sequence, by means of 10mus simulations. The results indicate that while the three alpha-helix bundle of the GA88 protein remains stable, the 2beta--alpha--2beta configuration of the GB88 protein does not: the latter rapidly converts to a structure consisting mostly of helices similar to the GA88 protein design. These results indicate that this particular four-bead coarse-grained model is not able to properly grasp the dynamics of the beta-sheet secondary structure and overstabilizes the corresponding helical content.

Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase

PubMed Central

2012-01-01

Background During elongation, multi-subunit RNA polymerases (RNAPs) cycle between phosphodiester bond formation and nucleic acid translocation. In the conformation associated with catalysis, the mobile “trigger loop” of the catalytic subunit closes on the nucleoside triphosphate (NTP) substrate. Closing of the trigger loop is expected to exclude water from the active site, and dehydration may contribute to catalysis and fidelity. In the absence of a NTP substrate in the active site, the trigger loop opens, which may enable translocation. Another notable structural element of the RNAP catalytic center is the “bridge helix” that separates the active site from downstream DNA. The bridge helix may participate in translocation by bending against the RNA/DNA hybrid to induce RNAP forward movement and to vacate the active site for the next NTP loading. The transition between catalytic and translocation conformations of RNAP is not evident from static crystallographic snapshots in which macromolecular motions may be restrained by crystal packing. Results All atom molecular dynamics simulations of Thermus thermophilus (Tt) RNAP reveal flexible hinges, located within the two helices at the base of the trigger loop, and two glycine hinges clustered near the N-terminal end of the bridge helix. As simulation progresses, these hinges adopt distinct conformations in the closed and open trigger loop structures. A number of residues (described as “switch” residues) trade atomic contacts (ion pairs or hydrogen bonds) in response to changes in hinge orientation. In vivo phenotypes and in vitro activities rendered by mutations in the hinge and switch residues in Saccharomyces cerevisiae (Sc) RNAP II support the importance of conformational changes predicted from simulations in catalysis and translocation. During simulation, the elongation complex with an open trigger loop spontaneously translocates forward relative to the elongation complex with a closed trigger loop. Conclusions Switching between catalytic and translocating RNAP forms involves closing and opening of the trigger loop and long-range conformational changes in the atomic contacts of amino acid side chains, some located at a considerable distance from the trigger loop and active site. Trigger loop closing appears to support chemistry and the fidelity of RNA synthesis. Trigger loop opening and limited bridge helix bending appears to promote forward nucleic acid translocation. PMID:22676913

Crystal structure of human dual specificity phosphatase, JNK stimulatory phosphatase-1, at 1.5 A resolution.

PubMed

Yokota, Takehiro; Nara, Yukinori; Kashima, Akiko; Matsubara, Keiko; Misawa, Satoru; Kato, Ryohei; Sugio, Shigetoshi

2007-02-01

Human JNK stimulatory phosphatase-1 (JSP-1) is a novel member of dual specificity phosphatases. A C-terminus truncated JSP-1 was expressed in Escherichia coli and was crystallized using the sitting-drop vapor diffusion method. Thin-plate crystals obtained at 278 K belong to a monoclinic space group, C2, with unit-cell parameters a = 84.0 A, b = 49.3 A, c = 47.3 A, and beta = 119.5 degrees , and diffract up to 1.5 A resolution at 100 K. The structure of JSP-1 has a single compact (alpha/beta) domain, which consists of six alpha-helices and five beta-strands, and shows a conserved structural scaffold in regard to both DSPs and PTPs. A cleft formed by a PTP-loop at the active site is very shallow, and is occupied by one sulfonate compound, MES, at the bottom. In the binary complex structure of JSP-1 with MES, the conformations of three important segments in regard to the catalytic mechanism are not similar to those in PTP1B. JSP-1 has no loop corresponding to the Lys120-loop of PTP1B, and tryptophan residue corresponding to the substrate-stacking in PTP1B is substituted by alanine residue in JSP-1. Copyright 2006 Wiley-Liss, Inc.

The four-loop six-gluon NMHV ratio function

DOE PAGES

Dixon, Lance J.; von Hippel, Matt; McLeod, Andrew J.

2016-01-11

We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar N=4 super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a Q¯ differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We test the result againstmore » multi-Regge predictions at NNLL and N 3LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We study the analytical and numerical behavior of the parity-even and parity-odd parts on various lines and surfaces traversing the three-dimensional space of cross ratios. As part of this program, we characterize all irreducible hexagon functions through weight eight in terms of their coproduct. As a result, we also provide representations of the ratio function in particular kinematic regions in terms of multiple polylogarithms.« less

The four-loop six-gluon NMHV ratio function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dixon, Lance J.; von Hippel, Matt; McLeod, Andrew J.

2016-01-11

We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar N = 4 super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a Q - differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We testmore » the result against multi- Regge predictions at NNLL and N 3LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We also study the analytical and numerical behavior of the parity-even and parity-odd parts on various lines and surfaces traversing the three-dimensional space of cross ratios. As part of this program, we characterize all irreducible hexagon functions through weight eight in terms of their coproduct. Furthermore, we provide representations of the ratio function in particular kinematic regions in terms of multiple polylogarithms.« less

Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity

NASA Astrophysics Data System (ADS)

Li, Chunmei; Teng, Xin; Qi, Yifei; Tang, Bo; Shi, Hailing; Ma, Xiaomin; Lai, Luhua

2016-02-01

The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 310-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 310-helix and helps to stabilize the active conformation. The coil-310-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations.

The pH-dependent tertiary structure of a designed helix-loop-helix dimer.

PubMed

Dolphin, G T; Baltzer, L

1997-01-01

De novo designed helix-loop-helix motifs can fold into well-defined tertiary structures if residues or groups of residues are incorporated at the helix-helix boundary to form helix-recognition sites that restrict the conformational degrees of freedom of the helical segments. Understanding the relationship between structure and function of conformational constraints therefore forms the basis for the engineering of non-natural proteins. This paper describes the design of an interhelical HisH+-Asp- hydrogen-bonded ion pair and the conformational stability of the folded helix-loop-helix motif. GTD-C, a polypeptide with 43 amino acid residues, has been designed to fold into a hairpin helix-loop-helix motif that can dimerise to form a four-helix bundle. The folded motif is in slow conformational exchange on the NMR timescale and has a well-dispersed 1H NMR spectrum, a narrow temperature interval for thermal denaturation and a near-UV CD spectrum with some fine structure. The conformational stability is pH dependent with an optimum that corresponds to the pH for maximum formation of a hydrogen-bonded ion pair between HisH17+ in helix I and Asp27- in helix II. The formation of an interhelical salt bridge is strongly suggested by the pH dependence of a number of spectroscopic probes to generate a well-defined tertiary structure in a designed helix-loop-helix motif. The thermodynamic stability of the folded motif is not increased by the formation of the salt bridge, but neighbouring conformations are destabilised. The use of this novel design principle in combination with hydrophobic interactions that provide sufficient binding energy in the folded structure should be of general use in de novo design of native-like proteins.

Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

PubMed

Nakashima, T; Yao, M; Kawamura, S; Iwasaki, K; Kimura, M; Tanaka, I

2001-05-01

Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic representation suggest that the concave surface and loop regions are involved in 5S rRNA binding. To identify amino acid residues responsible for 5S rRNA binding, we made use of Ala-scanning mutagenesis of evolutionarily conserved amino acids occurring in the beta-strands and loop regions. The mutations of Asn37 at the beta1-strand and Gln63 at the loop between helix 2 and beta3-strand as well as that of Phe77 at the tip of the loop structure between the beta2- and beta3-strands caused a significant reduction in 5S rRNA binding. In addition, the mutations of Thr90 on the beta3-strand and Ile141 and Asp144 at the loop between beta4- and beta5-strands moderately reduced the 5S rRNA-binding affinity. Comparison of these results with the more recently analyzed structure of the 50S subunit from Haloarcula marismortui suggests that there are significant differences in the structure at N- and C-terminal regions and probably in the 5S rRNA binding.

Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

PubMed Central

Nakashima, T; Yao, M; Kawamura, S; Iwasaki, K; Kimura, M; Tanaka, I

2001-01-01

Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic representation suggest that the concave surface and loop regions are involved in 5S rRNA binding. To identify amino acid residues responsible for 5S rRNA binding, we made use of Ala-scanning mutagenesis of evolutionarily conserved amino acids occurring in the beta-strands and loop regions. The mutations of Asn37 at the beta1-strand and Gln63 at the loop between helix 2 and beta3-strand as well as that of Phe77 at the tip of the loop structure between the beta2- and beta3-strands caused a significant reduction in 5S rRNA binding. In addition, the mutations of Thr90 on the beta3-strand and Ile141 and Asp144 at the loop between beta4- and beta5-strands moderately reduced the 5S rRNA-binding affinity. Comparison of these results with the more recently analyzed structure of the 50S subunit from Haloarcula marismortui suggests that there are significant differences in the structure at N- and C-terminal regions and probably in the 5S rRNA binding. PMID:11350033

Properties of the electrostatically driven helical plasma state

NASA Astrophysics Data System (ADS)

Akçay, Cihan; Finn, John M.; Nebel, Richard A.; Barnes, Daniel C.; Martin, Neal

2018-02-01

A novel plasma state has been found [Akçay et al., Phys. Plasmas 24, 052503 (2017)] in the presence of a uniform applied axial magnetic field in periodic cylindrical geometry. This state is driven by external electrostatic fields provided by helical electrodes with a (m =1 ,n =1 ) (helical) symmetry where m and n represent the poloidal and axial harmonics. The resulting plasma is a function of the cylinder radius r

Zn(II) coordination polymers with flexible V-shaped dicarboxylate ligand: Syntheses, helical structures and properties

NASA Astrophysics Data System (ADS)

Li, Lin; Liu, Chong-Bo; Yang, Gao-Shan; Xiong, Zhi-Qiang; Liu, Hong; Wen, Hui-Liang

2015-11-01

Hydrothermal reactions of 2,2‧-[hexafluoroisopropylidenebis(p-phenyleneoxy)]diacetic acid (H2L) and zinc ions in the presence of N-donor ancillary ligands afford four novel coordination polymers, namely, [Zn2(μ2-OH)(μ4-O)0.5(L)]·0.5H2O (1), [Zn(L)(2,2‧-bipy)(H2O)] (2), [Zn3(L)3(phen)2]·H2O (3) and [Zn2(L)2(4,4‧-bipy)] (4) (2,2‧-bipy=2,2‧-bipyridine; 4,4‧-bipy=4,4‧-bipyridine; phen=1,10-phenanthroline). Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, powder X-ray diffraction (PXRD), and thermogravimetric (TG) analyses. Complex 1 shows a 3-D clover framework consisting of [Zn4(μ4-O)(μ2-OH)2]4+ clusters, and exhibits a novel (3,8)-connected topological net with the Schläfli symbol of {3·4·5}2{34·44·52·66·710·82}, and contains double-stranded and two kinds of meso-helices. 2 displays a helical chain structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with meso-helix chains. 3 displays a 2-D {44·62} parallelogram structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with single-stranded helical chains. 4 shows a 2-D {44·62} square structure with left- and right-handed helical chains. Moreover, the luminescent properties of 1-4 have been investigated.

Phase-lock-loop application for fiber optic receiver

NASA Astrophysics Data System (ADS)

Ruggles, Stephen L.; Wills, Robert W.

1991-02-01

Phase-locked loop circuits are frequently employed in communication systems. In recent years, digital phase-locked loop circuits were utilized in optical communications systems. In an optical transceiver system, the digital phase-locked loop circuit is connected to the output of the receiver to extract a clock signal from the received coded data (NRZ, Bi-Phase, or Manchester). The clock signal is then used to reconstruct or recover the original data from the coded data. A theoretical approach to the design of a digital phase-locked loop circuit operation at 1 and 50 MHz is described. Hardware implementation of a breadboard design to function at 1 MHz and a printed-circuit board designed to function at 50 MHz were assembled using emitter coupled logic (ECL) to verify experimentally the theoretical design.

Phase-lock-loop application for fiber optic receiver

NASA Technical Reports Server (NTRS)

Ruggles, Stephen L.; Wills, Robert W.

1991-01-01

Phase-locked loop circuits are frequently employed in communication systems. In recent years, digital phase-locked loop circuits were utilized in optical communications systems. In an optical transceiver system, the digital phase-locked loop circuit is connected to the output of the receiver to extract a clock signal from the received coded data (NRZ, Bi-Phase, or Manchester). The clock signal is then used to reconstruct or recover the original data from the coded data. A theoretical approach to the design of a digital phase-locked loop circuit operation at 1 and 50 MHz is described. Hardware implementation of a breadboard design to function at 1 MHz and a printed-circuit board designed to function at 50 MHz were assembled using emitter coupled logic (ECL) to verify experimentally the theoretical design.

Vehicle to wireless power transfer coupling coil alignment sensor

DOEpatents

Miller, John M.; Chambon, Paul H.; Jones, Perry T.; White, Clifford P.

2016-02-16

A non-contacting position sensing apparatus includes at least one vehicle-mounted receiver coil that is configured to detect a net flux null when the vehicle is optimally aligned relative to the primary coil in the charging device. Each of the at least one vehicle-mounted receiver coil includes a clockwise winding loop and a counterclockwise winding loop that are substantially symmetrically configured and serially connected to each other. When the non-contacting position sensing apparatus is located directly above the primary coil of the charging device, the electromotive forces from the clockwise winding loop and the counterclockwise region cancel out to provide a zero electromotive force, i.e., a zero voltage reading across the coil that includes the clockwise winding loop and the counterclockwise winding loop.

An improved external recycle reactor for determining gas-solid reaction kinetics

NASA Technical Reports Server (NTRS)

Miller, Irvin M.; Hoyt, Ronald F.

1987-01-01

These improvements in the recycle system effectively eliminate initial concentration variation by two modifications: (1) a vacuum line connection to the recycle loop which permits this loop to be evacuated and then filled with the test gas mixture to slightly above atmospheric pressure; and (2) a bypass line across the reactor which permits the reactor to be held under vacuum while the rest of the recycle loop is filled with test gas. A three-step procedure for bringing the feed gas mixture into contact with the catalyst at time zero is described.

Differential Resonant Ring YIG Tuned Oscillator

NASA Technical Reports Server (NTRS)

Parrott, Ronald A.

2010-01-01

A differential SiGe oscillator circuit uses a resonant ring-oscillator topology in order to electronically tune the oscillator over multi-octave bandwidths. The oscillator s tuning is extremely linear, because the oscillator s frequency depends on the magnetic tuning of a YIG sphere, whose resonant frequency is equal to a fundamental constant times the DC magnetic field. This extremely simple circuit topology uses two coupling loops connecting a differential pair of SiGe bipolar transistors into a feedback configuration using a YIG tuned filter creating a closed-loop ring oscillator. SiGe device technology is used for this oscillator in order to keep the transistor s 1/f noise to an absolute minimum in order to achieve minimum RF phase noise. The single-end resonant ring oscillator currently has an advantage in fewer parts, but when the oscillation frequency is greater than 16 GHz, the package s parasitic behavior couples energy to the sphere and causes holes and poor phase noise performance. This is because the coupling to the YIG is extremely low, so that the oscillator operates at near the unloaded Q. With the differential resonant ring oscillator, the oscillation currents are just in the YIG coupling mechanisms. The phase noise is even better, and the physical size can be reduced to permit monolithic microwave integrated circuit oscillators. This invention is a YIG tuned oscillator circuit making use of a differential topology to simultaneously achieve an extremely broadband electronic tuning range and ultra-low phase noise. As a natural result of its differential circuit topology, all reactive elements, such as tuning stubs, which limit tuning bandwidth by contributing excessive open loop phase shift, have been eliminated. The differential oscillator s open-loop phase shift is associated with completely non-dispersive circuit elements such as the physical angle of the coupling loops, a differential loop crossover, and the high-frequency phase shift of the n-p-n transistors. At the input of the oscillator s feedback loop is a pair of differentially connected n-p-n SiGe transistors that provides extremely high gain, and because they are bulk-effect devices, extremely low 1/f noise (leading to ultralow RF phase noise). The 1/f corner frequency for n-p-n SiGe transistors is approximately 500 Hz. The RF energy from the transistor s collector output is connected directly to the top-coupling loop (the excitation loop) of a single-sphere YIG tuned filter. A uniform magnetic field to bias the YIG must be at a right angle to any vector associated with an RF current in a coupling loop in order for the precession to interact with the RF currents.

Crystal structure of four-stranded Oxytricha telomeric DNA

NASA Technical Reports Server (NTRS)

Kang, C.; Zhang, X.; Ratliff, R.; Moyzis, R.; Rich, A.

1992-01-01

The sequence d(GGGGTTTTGGGG) from the 3' overhang of the Oxytricha telomere has been crystallized and its three-dimensional structure solved to 2.5 A resolution. The oligonucleotide forms hairpins, two of which join to make a four-stranded helical structure with the loops containing four thymine residues at either end. The guanine residues are held together by cyclic hydrogen bonding and an ion is located in the centre. The four guanine residues in each segment have a glycosyl conformation that alternates between anti and syn. There are two four-stranded molecules in the asymmetric unit showing that the structure has some intrinsic flexibility.

Dynamic simulation of perturbation responses in a closed-loop virtual arm model.

PubMed

Du, Yu-Fan; He, Xin; Lan, Ning

2010-01-01

A closed-loop virtual arm (VA) model has been developed in SIMULINK environment by adding spinal reflex circuits and propriospinal neural networks to the open-loop VA model developed in early study [1]. An improved virtual muscle model (VM4.0) is used to speed up simulation and to generate more precise recruitment of muscle force at low levels of muscle activation. Time delays in the reflex loops are determined by their synaptic connections and afferent transmission back to the spinal cord. Reflex gains are properly selected so that closed-loop responses are stable. With the closed-loop VA model, we are developing an approach to evaluate system behaviors by dynamic simulation of perturbation responses. Joint stiffness is calculated based on simulated perturbation responses by a least-squares algorithm in MATLAB. This method of dynamic simulation will be essential for further evaluation of feedforward and reflex control of arm movement and position.

40 CFR 65.113 - Standards: Sampling connection systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (d) In-situ sampling systems. In-situ sampling systems and sampling systems without purges are exempt... implementation date specified in § 65.1(f). (b) Equipment requirement. Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed vent system except as provided in paragraph (d) of...

40 CFR 65.113 - Standards: Sampling connection systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (d) In-situ sampling systems. In-situ sampling systems and sampling systems without purges are exempt... implementation date specified in § 65.1(f). (b) Equipment requirement. Each sampling connection system shall be equipped with a closed-purge, closed-loop, or closed vent system except as provided in paragraph (d) of...

Functional and Structural Characterization of Novel Type of Linker Connecting Capsid and Nucleocapsid Protein Domains in Murine Leukemia Virus.

PubMed

Doležal, Michal; Hadravová, Romana; Kožíšek, Milan; Bednárová, Lucie; Langerová, Hana; Ruml, Tomáš; Rumlová, Michaela

2016-09-23

The assembly of immature retroviral particles is initiated in the cytoplasm by the binding of the structural polyprotein precursor Gag with viral genomic RNA. The protein interactions necessary for assembly are mediated predominantly by the capsid (CA) and nucleocapsid (NC) domains, which have conserved structures. In contrast, the structural arrangement of the CA-NC connecting region differs between retroviral species. In HIV-1 and Rous sarcoma virus, this region forms a rod-like structure that separates the CA and NC domains, whereas in Mason-Pfizer monkey virus, this region is densely packed, thus holding the CA and NC domains in close proximity. Interestingly, the sequence connecting the CA and NC domains in gammaretroviruses, such as murine leukemia virus (MLV), is unique. The sequence is called a charged assembly helix (CAH) due to a high number of positively and negatively charged residues. Although both computational and deletion analyses suggested that the MLV CAH forms a helical conformation, no structural or biochemical data supporting this hypothesis have been published. Using an in vitro assembly assay, alanine scanning mutagenesis, and biophysical techniques (circular dichroism, NMR, microcalorimetry, and electrophoretic mobility shift assay), we have characterized the structure and function of the MLV CAH. We provide experimental evidence that the MLV CAH belongs to a group of charged, E(R/K)-rich, single α-helices. This is the first single α-helix motif identified in viral proteins. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Loop quantum cosmology with self-dual variables

NASA Astrophysics Data System (ADS)

Wilson-Ewing, Edward

2015-12-01

Using the complex-valued self-dual connection variables, the loop quantum cosmology of a closed Friedmann space-time coupled to a massless scalar field is studied. It is shown how the reality conditions can be imposed in the quantum theory by choosing a particular inner product for the kinematical Hilbert space. While holonomies of the self-dual Ashtekar connection are not well defined in the kinematical Hilbert space, it is possible to introduce a family of generalized holonomylike operators of which some are well defined; these operators in turn are used in the definition of the Hamiltonian constraint operator where the scalar field can be used as a relational clock. The resulting quantum theory is closely related, although not identical, to standard loop quantum cosmology constructed from the Ashtekar-Barbero variables with a real Immirzi parameter. Effective Friedmann equations are derived which provide a good approximation to the full quantum dynamics for sharply peaked states whose volume remains much larger than the Planck volume, and they show that for these states quantum gravity effects resolve the big-bang and big-crunch singularities and replace them by a nonsingular bounce. Finally, the loop quantization in self-dual variables of a flat Friedmann space-time is recovered in the limit of zero spatial curvature and is identical to the standard loop quantization in terms of the real-valued Ashtekar-Barbero variables.

Bifurcation of Limit Cycles in a Near-Hamiltonian System with a Cusp of Order Two and a Saddle

NASA Astrophysics Data System (ADS)

Bakhshalizadeh, Ali; Zangeneh, Hamid R. Z.; Kazemi, Rasool

In this paper, the asymptotic expansion of first-order Melnikov function of a heteroclinic loop connecting a cusp of order two and a hyperbolic saddle for a planar near-Hamiltonian system is given. Next, we consider the limit cycle bifurcations of a hyper-elliptic Liénard system with this kind of heteroclinic loop and study the least upper bound of limit cycles bifurcated from the period annulus inside the heteroclinic loop, from the heteroclinic loop itself and the center. We find that at most three limit cycles can be bifurcated from the period annulus, also we present different distributions of bifurcated limit cycles.

Experiments Using Local Helicity Injectors in the Lower Divertor Region as the Majority Current Drive in a Tokamak Plasma

NASA Astrophysics Data System (ADS)

Perry, Justin M.

Local helicity injection (LHI) is a non-solenoidal current drive capable of achieving high-Ip tokamak startup with a relatively compact and non-invasive array of current injectors in the plasma scrape-off layer. The choice of injector location within the edge region is flexible, but has a profound influence on the nature of the current drive in LHI discharges. Past experiments on the Pegasus ST with injection on the low-field-side near the outboard midplane produced plasmas dominated by inductive drive resulting primarily from plasma geometry evolution over the discharge. Recent experiments with injection on the high-field- side in the lower divertor region produce plasmas dominated by helicity injection current drive, with relatively static plasma geometry, and thus negligible inductive drive. Plasma current up to 200 kA is driven with helicity injection as the dominant current drive using a pair of 4 cm2 area injectors sourcing 8 kA of total injected current. Steady sustainment with LHI current drive alone is demonstrated, with 100 kA sustained for 18 ms. Maximum achievable plasma current is found to scale approximately linearly with a plasma-geometry- normalized form of the effective loop voltage from LHI, Vnorm = AinjVinj/Rinj, where A inj is the total injector area, Vinj is the injector bias voltage, and Rinj is the major radius of the injectors. A newly-discovered MHD regime for LHI-driven plasmas is described, in which the large-amplitude n = 1 fluctuations at 20-50 kHz which are generally dominant during LHI are abruptly reduced by an order of magnitude on the outboard side. High frequency fluctuations ( f > 400 kHz) increase inside the plasma edge at the same time. This regime results in improved plasma current and pervasive changes to plasma behavior, and may suggest short wavelength turbulence as a current drive mechanism during LHI.

Direct Ubiquitin Independent Recognition and Degradation of a Folded Protein by the Eukaryotic Proteasomes-Origin of Intrinsic Degradation Signals

PubMed Central

Singh Gautam, Amit Kumar; Balakrishnan, Satish; Venkatraman, Prasanna

2012-01-01

Eukaryotic 26S proteasomes are structurally organized to recognize, unfold and degrade globular proteins. However, all existing model substrates of the 26S proteasome in addition to ubiquitin or adaptor proteins require unstructured regions in the form of fusion tags for efficient degradation. We report for the first time that purified 26S proteasome can directly recognize and degrade apomyoglobin, a globular protein, in the absence of ubiquitin, extrinsic degradation tags or adaptor proteins. Despite a high affinity interaction, absence of a ligand and presence of only helices/loops that follow the degradation signal, apomyoglobin is degraded slowly by the proteasome. A short floppy F-helix exposed upon ligand removal and in conformational equilibrium with a disordered structure is mandatory for recognition and initiation of degradation. Holomyoglobin, in which the helix is buried, is neither recognized nor degraded. Exposure of the floppy F-helix seems to sensitize the proteasome and primes the substrate for degradation. Using peptide panning and competition experiments we speculate that initial encounters through the floppy helix and additional strong interactions with N-terminal helices anchors apomyoglobin to the proteasome. Stabilizing helical structure in the floppy F-helix slows down degradation. Destabilization of adjacent helices accelerates degradation. Unfolding seems to follow the mechanism of helix unraveling rather than global unfolding. Our findings while confirming the requirement for unstructured regions in degradation offers the following new insights: a) origin and identification of an intrinsic degradation signal in the substrate, b) identification of sequences in the native substrate that are likely to be responsible for direct interactions with the proteasome, and c) identification of critical rate limiting steps like exposure of the intrinsic degron and destabilization of an unfolding intermediate that are presumably catalyzed by the ATPases. Apomyoglobin emerges as a new model substrate to further explore the role of ATPases and protein structure in proteasomal degradation PMID:22506054

Normalization for sparse encoding of odors by a wide-field interneuron.

PubMed

Papadopoulou, Maria; Cassenaer, Stijn; Nowotny, Thomas; Laurent, Gilles

2011-05-06

Sparse coding presents practical advantages for sensory representations and memory storage. In the insect olfactory system, the representation of general odors is dense in the antennal lobes but sparse in the mushroom bodies, only one synapse downstream. In locusts, this transformation relies on the oscillatory structure of antennal lobe output, feed-forward inhibitory circuits, intrinsic properties of mushroom body neurons, and connectivity between antennal lobe and mushroom bodies. Here we show the existence of a normalizing negative-feedback loop within the mushroom body to maintain sparse output over a wide range of input conditions. This loop consists of an identifiable "giant" nonspiking inhibitory interneuron with ubiquitous connectivity and graded release properties.

One-loop topological expansion for spin glasses in the large connectivity limit

NASA Astrophysics Data System (ADS)

Chiara Angelini, Maria; Parisi, Giorgio; Ricci-Tersenghi, Federico

2018-01-01

We apply for the first time a new one-loop topological expansion around the Bethe solution to the spin-glass model with a field in the high connectivity limit, following the methodological scheme proposed in a recent work. The results are completely equivalent to the well-known ones, found by standard field-theoretical expansion around the fully connected model (Bray and Roberts 1980, and following works). However this method has the advantage that the starting point is the original Hamiltonian of the model, with no need to define an associated field theory, nor to know the initial values of the couplings, and the computations have a clear and simple physical meaning. Moreover this new method can also be applied in the case of zero temperature, when the Bethe model has a transition in field, contrary to the fully connected model that is always in the spin-glass phase. Sharing with finite-dimensional model the finite connectivity properties, the Bethe lattice is clearly a better starting point for an expansion with respect to the fully connected model. The present work is a first step towards the generalization of this new expansion to more difficult and interesting cases as the zero-temperature limit, where the expansion could lead to different results with respect to the standard one.

Alteration of the mode of antibacterial action of a defensin by the amino-terminal loop substitution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Bin; Zhu, Shunyi, E-mail: Zhusy@ioz.ac.cn

Highlights: Black-Right-Pointing-Pointer Al-M is an engineered fungal defensin with the n-loop of an insect defensin. Black-Right-Pointing-Pointer Al-M adopts a native defensin-like structure with high antibacterial potency. Black-Right-Pointing-Pointer Al-M kills bacteria through a membrane disruptive mechanism. Black-Right-Pointing-Pointer This work sheds light on the functional evolution of CS{alpha}{beta}-type defensins. -- Abstract: Ancient invertebrate-type and classical insect-type defensins (AITDs and CITDs) are two groups of evolutionarily related antimicrobial peptides (AMPs) that adopt a conserved cysteine-stabilized {alpha}-helical and {beta}-sheet (CS{alpha}{beta}) fold with a different amino-terminal loop (n-loop) size and diverse modes of antibacterial action. Although they both are identified as inhibitors of cell wallmore » biosynthesis, only CITDs evolved membrane disruptive ability by peptide oligomerization to form pores. To understand how this occurred, we modified micasin, a fungus-derived AITDs with a non-membrane disruptive mechanism, by substituting its n-loop with that of an insect-derived CITDs. After air oxidization, the synthetic hybrid defensin (termed Al-M) was structurally identified by circular dichroism (CD) and functionally evaluated by antibacterial and membrane permeability assays and electronic microscopic observation. Results showed that Al-M folded into a native-like defensin structure, as determined by its CD spectrum that is similar to that of micasin. Al-M was highly efficacious against the Gram-positive bacterium Bacillus megaterium with a lethal concentration of 1.76 {mu}M. As expected, in contrast to micasin, Al-M killed the bacteria through a membrane disruptive mechanism of action. The alteration in modes of action supports a key role of the n-loop extension in assembling functional surface of CITDs for membrane disruption. Our work provides mechanical evidence for evolutionary relationship between AITDs and CITDs.« less

Dynamin's helical geometry does not destabilize membranes during fission.

PubMed

McDargh, Zachary A; Deserno, Markus

2018-05-01

It is now widely accepted that dynamin-mediated fission is a fundamentally mechanical process: dynamin undergoes a GTP-dependent conformational change, constricting the neck between two compartments, somehow inducing their fission. However, the exact connection between dynamin's conformational change and the scission of the neck is still unclear. In this paper, we re-evaluate the suggestion that a change in the pitch or radius of dynamin's helical geometry drives the lipid bilayer through a mechanical instability, similar to a well-known phenomenon occurring in soap films. We find that, contrary to previous claims, there is no such instability. This lends credence to an alternative model, in which dynamin drives the membrane up an energy barrier, allowing thermal fluctuations to take it into the hemifission state. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

On the Helicity in 3D-Periodic Navier-Stokes Equations II: The Statistical Case

NASA Astrophysics Data System (ADS)

Foias, Ciprian; Hoang, Luan; Nicolaenko, Basil

2009-09-01

We study the asymptotic behavior of the statistical solutions to the Navier-Stokes equations using the normalization map [9]. It is then applied to the study of mean energy, mean dissipation rate of energy, and mean helicity of the spatial periodic flows driven by potential body forces. The statistical distribution of the asymptotic Beltrami flows are also investigated. We connect our mathematical analysis with the empirical theory of decaying turbulence. With appropriate mathematically defined ensemble averages, the Kolmogorov universal features are shown to be transient in time. We provide an estimate for the time interval in which those features may still be present. Our collaborator and friend Basil Nicolaenko passed away in September of 2007, after this work was completed. Honoring his contribution and friendship, we dedicate this article to him.

Perversions with a twist

NASA Astrophysics Data System (ADS)

Silva, Pedro E. S.; Trigueiros, Joao L.; Trindade, Ana C.; Simoes, Ricardo; Dias, Ricardo G.; Godinho, Maria Helena; de Abreu, Fernao Vistulo

2016-03-01

Perversions connecting two helices with symmetric handedness are a common occurrence in nature, for example in tendrils. These defects can be found in our day life decorating ribbon gifts or when plants use tendrils to attach to a support. Perversions arise when clamped elastic filaments coil into a helical shape but have to conserve zero overall twist. We investigate whether other types of perversions exist and if they display different properties. Here we show mathematically and experimentally that a continuous range of different perversions can exist and present different geometries. Experimentally, different perversions were generated using micro electrospun fibres. Our experimental results also confirm that these perversions behave differently upon release and adopt different final configurations. These results also demonstrate that it is possible to control on demand the formation and shape of microfilaments, in particular, of electrospun fibres by using ultraviolet light.

The Nature of Bonding in Bulk Tellurium Composed of One-Dimensional Helical Chains.

PubMed

Yi, Seho; Zhu, Zhili; Cai, Xiaolin; Jia, Yu; Cho, Jun-Hyung

2018-05-07

Bulk tellurium (Te) is composed of one-dimensional (1D) helical chains which have been considered to be coupled by van der Waals (vdW) interactions. However, on the basis of first-principles density functional theory calculations, we here propose a different bonding nature between neighboring chains: i.e., helical chains made of normal covalent bonds are connected together by coordinate covalent bonds. It is revealed that the lone pairs of electrons of Te atoms participate in forming coordinate covalent bonds between neighboring chains, where each Te atom behaves as both an electron donor to neighboring chains and an electron acceptor from neighboring chains. This ligand-metal-like bonding nature in bulk Te results in the same order of bulk moduli along the directions parallel and perpendicular to the chains, contrasting with the large anisotropy of bulk moduli in vdW crystals. We further find that the electron effective masses parallel and perpendicular to the chains are almost the same as each other, consistent with the observed nearly isotropic electrical resistivity. It is thus demonstrated that the normal/coordinate covalent bonds parallel/perpendicular to the chains in bulk Te lead to a minor anisotropy in structural and transport properties.

Three-dimensional scrape off layer transport in the helically symmetric experiment HSX

NASA Astrophysics Data System (ADS)

Akerson, A. R.; Bader, A.; Hegna, C. C.; Schmitz, O.; Stephey, L. A.; Anderson, D. T.; Anderson, F. S. B.; Likin, K. M.

2016-08-01

The edge topology of helically symmetric experiment (HSX) in the quasi-helically symmetric configuration is characterized by an 8/7 magnetic island remnant embedded in a short connection length scrape-off layer (SOL) domain. A 2D mapping of edge plasma profiles within this heterogeneous SOL has been constructed using a movable, multi-pin Langmuir probe. Comparisons of these measurements to edge simulations using the EMC3-EIRENE 3D plasma fluid and kinetic neutral gas transport model have been performed. The measurements provide strong evidence that particle transport is diffusive within the island region and dominantly convective in the SOL region. Measurements indicate that phenomenological cross-field diffusion coefficients are low in the SOL region between the last closed flux surface and edge island (i.e. {{D}\\bot}≈ 0.03 m2 s-1). This level of transport was found to increase by a factor of two when a limiter is inserted almost completely into the magnetic island. A reduction in gradients of the edge electrostatic plasma potential was also measured in this configuration, suggesting that the reduced electric field may be linked to the increased cross-field transport observed.

Helical Poly(5-alkyl-2,3-thiophene)s: Controlled Synthesis and Structure Characterization

DOE PAGES

Zhang, Hong-Hai; Ma, Chuanxu; Bonnesen, Peter V.; ...

2016-07-12

Whereas Poly(3-alkyl-2,5-thiophene)s (P3AT), with many potential applications, have been extensively investigated, their ortho-connected isomers, poly(5-alkyl-2,3-thiophene)s (P5AT), have never been reported because of the difficulty in their syntheses. We herein present the first synthesis of regioregular P5AT via controlled Suzuki cross-coupling polymerization with PEPPSI-IPr as catalyst, affording the polymers with tunable molecular weight, narrow polydispersity (PDI) and well-defined functional end groups at the gram scale. The helical geometry of P5AT was studied by a combination of NMR, small angle x-ray scattering (SAXS) and scanning tunneling microscopy (STM). Particularly, the single polymer chain of poly(5- 2 butyl-2,3-thiophene) (P5BT) on highly oriented pyrolyticmore » graphite (HOPG) substrates with either M or P helical conformation was directly observed by STM. The comparison of UV-vis absorption between poly(5-hexyl-2,3-thiophene) (P5HT) (λ = 345 nm) and poly(3-hexyl-2,5- thiophene) (P3HT) (λ = 450 nm) indicated that the degree of conjugation of the backbone in P5HT is less than in P3HT, which may be a consequence of the helical geometry of the former compared to the more planar geometry of the latter. Moreover, we found that P5HT can emit green fluorescence under UV (λ = 360 nm) irradiation« less

OSCILLATION OF NEWLY FORMED LOOPS AFTER MAGNETIC RECONNECTION IN THE SOLAR CHROMOSPHERE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shuhong; Xiang, Yongyuan, E-mail: shuhongyang@nao.cas.cn

With the high spatial and temporal resolution Hα images from the New Vacuum Solar Telescope, we focus on two groups of loops with an X-shaped configuration in the dynamic chromosphere. We find that the anti-directed loops approach each other and reconnect continually. The connectivity of the loops is changed and new loops are formed and stack together. The stacked loops are sharply bent, implying that they are greatly impacted by the magnetic tension force. When another reconnection process takes place, one new loop is formed and stacks with the previously formed ones. Meanwhile, the stacked loops retract suddenly and movemore » toward the balance position, performing an overshoot movement, which led to an oscillation with an average period of about 45 s. The oscillation of newly formed loops after magnetic reconnection in the chromosphere is observed for the first time. We suggest that the stability of the stacked loops is destroyed due to the attachment of the last new loop and then suddenly retract under the effect of magnetic tension. Because of the retraction, another lower loop is pushed outward and performs an oscillation with a period of about 25 s. The different oscillation periods may be due to their difference in three parameters, i.e., loop length, plasma density, and magnetic field strength.« less

Automated Detection of Solar Loops by the Oriented Connectivity Method

NASA Technical Reports Server (NTRS)

Lee, Jong Kwan; Newman, Timothy S.; Gary, G. Allen

2004-01-01

An automated technique to segment solar coronal loops from intensity images of the Sun s corona is introduced. It exploits physical characteristics of the solar magnetic field to enable robust extraction from noisy images. The technique is a constructive curve detection approach, constrained by collections of estimates of the magnetic fields orientation. Its effectiveness is evaluated through experiments on synthetic and real coronal images.

Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

NASA Astrophysics Data System (ADS)

Pichierri, Fabio

2014-08-01

Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

Mutations in STRA6 Cause a Broad Spectrum of Malformations Including Anophthalmia, Congenital Heart Defects, Diaphragmatic Hernia, Alveolar Capillary Dysplasia, Lung Hypoplasia, and Mental Retardation

PubMed Central

Pasutto, Francesca; Sticht, Heinrich; Hammersen, Gerhard; Gillessen-Kaesbach, Gabriele; FitzPatrick, David R.; Nürnberg, Gudrun; Brasch, Frank; Schirmer-Zimmermann, Heidemarie; Tolmie, John L.; Chitayat, David; Houge, Gunnar; Fernández-Martínez, Lorena; Keating, Sarah; Mortier, Geert; Hennekam, Raoul C. M.; von der Wense, Axel; Slavotinek, Anne; Meinecke, Peter; Bitoun, Pierre; Becker, Christian; Nürnberg, Peter; Reis, André; Rauch, Anita

2007-01-01

We observed two unrelated consanguineous families with malformation syndromes sharing anophthalmia and distinct eyebrows as common signs, but differing for alveolar capillary dysplasia or complex congenital heart defect in one and diaphragmatic hernia in the other family. Homozygosity mapping revealed linkage to a common locus on chromosome 15, and pathogenic homozygous mutations were identified in STRA6, a member of a large group of “stimulated by retinoic acid” genes encoding novel transmembrane proteins, transcription factors, and secreted signaling molecules or proteins of largely unknown function. Subsequently, homozygous STRA6 mutations were also demonstrated in 3 of 13 patients chosen on the basis of significant phenotypic overlap to the original cases. While a homozygous deletion generating a premature stop codon (p.G50AfsX22) led to absence of the immunoreactive protein in patient’s fibroblast culture, structural analysis of three missense mutations (P90L, P293L, and T321P) suggested significant effects on the geometry of the loops connecting the transmembrane helices of STRA6. Two further variations in the C-terminus (T644M and R655C) alter specific functional sites, an SH2-binding motif and a phosphorylation site, respectively. STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the “STRA” group. PMID:17273977

MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding.

PubMed

Asamitsu, Kaori; Hirokawa, Takatsugu; Okamoto, Takashi

2017-01-01

In this study, we applied molecular dynamics (MD) simulation to analyze the dynamic behavior of the Tat/CycT1/CDK9 tri-molecular complex and revealed the structural changes of P-TEFb upon Tat binding. We found that Tat could deliberately change the local flexibility of CycT1. Although the structural coordinates of the H1 and H2 helices did not substantially change, H1', H2', and H3' exhibited significant changes en masse. Consequently, the CycT1 residues involved in Tat binding, namely Tat-recognition residues (TRRs), lost their flexibility with the addition of Tat to P-TEFb. In addition, we clarified the structural variation of CDK9 in complex with CycT1 in the presence or absence of Tat. Interestingly, Tat addition significantly reduced the structural variability of the T-loop, thus consolidating the structural integrity of P-TEFb. Finally, we deciphered the formation of the hidden catalytic cavity of CDK9 upon Tat binding. MD simulation revealed that the PITALRE signature sequence of CDK9 flips the inactive kinase cavity of CDK9 into the active form by connecting with Thr186, which is crucial for its activity, thus presumably recruiting the substrate peptide such as the C-terminal domain of RNA pol II. These findings provide vital information for the development of effective novel anti-HIV drugs with CDK9 catalytic activity as the target.

Cooperative control between AtRGS1 and AtHXK1 in a WD40-repeat protein pathway in Arabidopsis thaliana

DOE PAGES

Huang, Jian -Ping; Tunc-Ozdemir, Meral; Chang, Ying; ...

2015-10-13

HEXOKINASE 1 (AtHXK1) and Regulator of G-protein Signaling 1 (AtRGS1) pathways, mediate D-glucose signaling in Arabidopsis. However, it is not known the degree, if any, that these pathways overlap and how. We show modest signaling crosstalk between these pathways, albeit complex with both epistatic interactions and additive effects that may be indirect. The action of HXK1 on AtRGS1 signaling lies downstream of the primary step in G protein-mediated sugar signaling in which the WD-repeat protein, AGB1, is the propelling signaling element. RHIP1, a previously unknown protein predicted here to have a 3-stranded helical structure, interacts with both AtRGS1 and AtHXK1more » in planta and is required for some glucose-regulated gene expression, providing a physical connection between these two proteins in sugar signaling. The rhip1 null mutant displays similar seedling growth phenotypes as rgs1-2 in response to glucose, further suggesting a role for RHIP1 in glucose signaling. Lastly, glucose signaling is a complex hierarchical relationship which is specific to the target gene and sugar phenotype and suggests that there are two glycolysis-independent glucose signaling sensors: AtRGS1 and AtHXK1 that weakly communicate with each other via feed-back and feed-forward loops to fine tune the response to glucose.« less

Concerted Interconversion between Ionic Lock Substates of the β2 Adrenergic Receptor Revealed by Microsecond Timescale Molecular Dynamics

PubMed Central

Romo, Tod D.; Grossfield, Alan; Pitman, Michael C.

2010-01-01

Abstract The recently solved crystallographic structures for the A2A adenosine receptor and the β1 and β2 adrenergic receptors have shown important differences between members of the class-A G-protein-coupled receptors and their archetypal model, rhodopsin, such as the apparent breaking of the ionic lock that stabilizes the inactive structure. Here, we characterize a 1.02 μs all-atom simulation of an apo-β2 adrenergic receptor that is missing the third intracellular loop to better understand the inactive structure. Although we find that the structure is remarkably rigid, there is a rapid influx of water into the core of the protein, as well as a slight expansion of the molecule relative to the crystal structure. In contrast to the x-ray crystal structures, the ionic lock rapidly reforms, although we see an activation-precursor-like event wherein the ionic lock opens for ∼200 ns, accompanied by movements in the transmembrane helices associated with activation. When the lock reforms, we see the structure return to its inactive conformation. We also find that the ionic lock exists in three states: closed (or locked), semi-open with a bridging water molecule, and open. The interconversion of these states involves the concerted motion of the entire protein. We characterize these states and the concerted motion underlying their interconversion. These findings may help elucidate the connection between key local events and the associated global structural changes during activation. PMID:20074514

Integrin Engagement by the Helical RGD Motif of the Helicobacter pylori CagL Protein Is Regulated by pH-induced Displacement of a Neighboring Helix*

PubMed Central

Bonsor, Daniel A.; Pham, Kieu T.; Beadenkopf, Robert; Diederichs, Kay; Haas, Rainer; Beckett, Dorothy; Fischer, Wolfgang; Sundberg, Eric J.

2015-01-01

Arginine-aspartate-glycine (RGD) motifs are recognized by integrins to bridge cells to one another and the extracellular matrix. RGD motifs typically reside in exposed loop conformations. X-ray crystal structures of the Helicobacter pylori protein CagL revealed that RGD motifs can also exist in helical regions of proteins. Interactions between CagL and host gastric epithelial cell via integrins are required for the translocation of the bacterial oncoprotein CagA. Here, we have investigated the molecular basis of the CagL-host cell interactions using structural, biophysical, and functional analyses. We solved an x-ray crystal structure of CagL that revealed conformational changes induced by low pH not present in previous structures. Using analytical ultracentrifugation, we found that pH-induced conformational changes in CagL occur in solution and not just in the crystalline environment. By designing numerous CagL mutants based on all available crystal structures, we probed the functional roles of CagL conformational changes on cell surface integrin engagement. Together, our data indicate that the helical RGD motif in CagL is buried by a neighboring helix at low pH to inhibit CagL binding to integrin, whereas at neutral pH the neighboring helix is displaced to allow integrin access to the CagL RGD motif. This novel molecular mechanism of regulating integrin-RGD motif interactions by changes in the chemical environment provides new insight to H. pylori-mediated oncogenesis. PMID:25837254

Biosynthesis and NMR-studies of a double transmembrane domain from the Y4 receptor, a human GPCR.

PubMed

Zou, Chao; Naider, Fred; Zerbe, Oliver

2008-12-01

The human Y4 receptor, a class A G-protein coupled receptor (GPCR) primarily targeted by the pancreatic polypeptide (PP), is involved in a large number of physiologically important functions. This paper investigates a Y4 receptor fragment (N-TM1-TM2) comprising the N-terminal domain, the first two transmembrane (TM) helices and the first extracellular loop followed by a (His)(6) tag, and addresses synthetic problems encountered when recombinantly producing such fragments from GPCRs in Escherichia coli. Rigorous purification and usage of the optimized detergent mixture 28 mM dodecylphosphocholine (DPC)/118 mM% 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG) resulted in high quality TROSY spectra indicating protein conformational homogeneity. Almost complete assignment of the backbone, including all TM residue resonances was obtained. Data on internal backbone dynamics revealed a high secondary structure content for N-TM1-TM2. Secondary chemical shifts and sequential amide proton nuclear Overhauser effects defined the TM helices. Interestingly, the properties of the N-terminal domain of this large fragment are highly similar to those determined on the isolated N-terminal domain in the presence of DPC micelles.

Posttranscriptional modifications in the A-loop of 23S rRNAs from selected archaea and eubacteria.

PubMed

Hansen, M A; Kirpekar, F; Ritterbusch, W; Vester, B

2002-02-01

Posttranscriptional modifications were mapped in helices 90-92 of 23S rRNA from the following phylogenetically diverse organisms: Haloarcula marismortui, Sulfolobus acidocaldarius, Bacillus subtilis, and Bacillus stearothermophilus. Helix 92 is a component of the ribosomal A-site, which contacts the aminoacyl-tRNA during protein synthesis, implying that posttranscriptional modifications in helices 90-92 may be important for ribosome function. RNA fragments were isolated from 23S rRNA by site-directed RNase H digestion. A novel method of mapping modifications by analysis of short, nucleotide-specific, RNase digestion fragments with Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) was utilized. The MALDI-MS data were complemented by two primer extension techniques using reverse transcriptase. One technique utilizes decreasing concentrations of deoxynucleotide triphosphates to map 2'-O-ribose methylations. In the other, the rRNA is chemically modified, followed by mild alkaline hydrolysis to map pseudouridines (psis). A total of 10 posttranscriptionally methylated nucleotides and 6 psis were detected in the five organisms. Eight of the methylated nucleotides and one psi have not been reported previously. The distribution of modified nucleotides and their locations on the surface of the ribosomal peptidyl transferase cleft suggests functional importance.

Inhibitor-induced structural change in the HCV IRES domain IIa RNA

PubMed Central

Paulsen, Ryan B.; Seth, Punit P.; Swayze, Eric E.; Griffey, Richard H.; Skalicky, Jack J.; Cheatham, Thomas E.; Davis, Darrell R.

2010-01-01

Translation of the hepatitis C virus (HCV) RNA is initiated from a highly structured internal ribosomal entry site (IRES) in the 5′ untranslated region (5′ UTR) of the RNA genome. An important structural feature of the native RNA is an approximately 90° helical bend localized to domain IIa that positions the apical loop of domain IIb of the IRES near the 40S ribosomal E-site to promote eIF2-GDP release, facilitating 80S ribosome assembly. We report here the NMR structure of a domain IIa construct in complex with a potent small-molecule inhibitor of HCV replication. Molecular dynamics refinement in explicit solvent and subsequent energetic analysis indicated that each inhibitor stereoisomer bound with comparable affinity and in an equivalent binding mode. The in silico analysis was substantiated by fluorescence-based assays showing that the relative binding free energies differed by only 0.7 kcal/mol. Binding of the inhibitor displaces key nucleotide residues within the bulge region, effecting a major conformational change that eliminates the bent RNA helical trajectory, providing a mechanism for the antiviral activity of this inhibitor class. PMID:20360559

A kMC-MD method with generalized move-sets for the simulation of folding of α-helical and β-stranded peptides.

PubMed

Peter, Emanuel K; Pivkin, Igor V; Shea, Joan-Emma

2015-04-14

In Monte-Carlo simulations of protein folding, pathways and folding times depend on the appropriate choice of the Monte-Carlo move or process path. We developed a generalized set of process paths for a hybrid kinetic Monte Carlo-Molecular dynamics algorithm, which makes use of a novel constant time-update and allows formation of α-helical and β-stranded secondary structures. We apply our new algorithm to the folding of 3 different proteins: TrpCage, GB1, and TrpZip4. All three systems are seen to fold within the range of the experimental folding times. For the β-hairpins, we observe that loop formation is the rate-determining process followed by collapse and formation of the native core. Cluster analysis of both peptides reveals that GB1 folds with equal likelihood along a zipper or a hydrophobic collapse mechanism, while TrpZip4 follows primarily a zipper pathway. The difference observed in the folding behavior of the two proteins can be attributed to the different arrangements of their hydrophobic core, strongly packed, and dry in case of TrpZip4, and partially hydrated in the case of GB1.

Institute for High Heat Flux Removal (IHHFR). Phases I, II, and III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyd, Ronald D.

2014-08-31

The IHHFR focused on interdisciplinary applications as it relates to high heat flux engineering issues and problems which arise due to engineering systems being miniaturized, optimized, or requiring increased high heat flux performance. The work in the IHHFR focused on water as a coolant and includes: (1) the development, design, and construction of the high heat flux flow loop and facility; (2) test section development, design, and fabrication; and, (3) single-side heat flux experiments to produce 2-D boiling curves and 3-D conjugate heat transfer measurements for single-side heated test sections. This work provides data for comparisons with previously developed andmore » new single-side heated correlations and approaches that address the single-side heated effect on heat transfer. In addition, this work includes the addition of single-side heated circular TS and a monoblock test section with a helical wire insert. Finally, the present work includes: (1) data base expansion for the monoblock with a helical wire insert (only for the latter geometry), (2) prediction and verification using finite element, (3) monoblock model and methodology development analyses, and (4) an alternate model development for a hypervapotron and related conjugate heat transfer controlling parameters.« less

NMR investigations of molecular dynamics

NASA Astrophysics Data System (ADS)

Palmer, Arthur

2011-03-01

NMR spectroscopy is a powerful experimental approach for characterizing protein conformational dynamics on multiple time scales. The insights obtained from NMR studies are complemented and by molecular dynamics (MD) simulations, which provide full atomistic details of protein dynamics. Homologous mesophilic (E. coli) and thermophilic (T. thermophilus) ribonuclease H (RNase H) enzymes serve to illustrate how changes in protein sequence and structure that affect conformational dynamic processes can be monitored and characterized by joint analysis of NMR spectroscopy and MD simulations. A Gly residue inserted within a putative hinge between helices B and C is conserved among thermophilic RNases H, but absent in mesophilic RNases H. Experimental spin relaxation measurements show that the dynamic properties of T. thermophilus RNase H are recapitulated in E. coli RNase H by insertion of a Gly residue between helices B and C. Additional specific intramolecular interactions that modulate backbone and sidechain dynamical properties of the Gly-rich loop and of the conserved Trp residue flanking the Gly insertion site have been identified using MD simulations and subsequently confirmed by NMR spin relaxation measurements. These results emphasize the importance of hydrogen bonds and local steric interactions in restricting conformational fluctuations, and the absence of such interactions in allowing conformational adaptation to substrate binding.

Unsteady numerical analysis of solid-liquid two-phase flow in stirred tank with double helical ribbon impeller

NASA Astrophysics Data System (ADS)

Bai, He; Chen, Xiangshan; Zhao, Guangyu; Xiao, Chenglei; Li, Chen; Zhong, Cheng; Chen, Yu

2017-08-01

In order to enhance the mixing process of soil contaminated by oil and water, one kind of double helical ribbon (DHR) impeller was developed. In this study, the unsteady simulation analysis of solid-liquid two-phase flow in stirring tank with DHR impeller was conducted by the the computational fluid dynamics and the multi-reference frame (MRF) method. It was found that at 0-3.0 s stage, the rate of liquid was greater than the rate of solid particles, while the power consumption was 5-6 times more than the smooth operation. The rates of the liquid and the solid particles were almost the same, and the required power was 32 KW at t > 3.0 s. The flow of the solid particles in the tank was a typical axial circle flow, and the dispersed sequence of the solid that was accumulated at the bottom of the tank was: the bottom loop region, the annular region near the wall of the groove and finally the area near axial center. The results show that the DHR impeller was suitable for the mixing of liquid-solid two-phase.

Detection of endoscopic looping during colonoscopy procedure by using embedded bending sensors

PubMed Central

Bruce, Michael; Choi, JungHun

2018-01-01

Background Looping of the colonoscope shaft during procedure is one of the most common obstacles encountered by colonoscopists. It occurs in 91% of cases with the N-sigmoid loop being the most common, occurring in 79% of cases. Purpose Herein, a novel system is developed that will give a complete three-dimensional (3D) vector image of the shaft as it passes through the colon, to aid the colonoscopist in detecting loops before they form. Patients and methods A series of connected links spans the middle 50% of the shaft, where loops are likely to form. Two potentiometers are attached at each joint to measure angular deflection in two directions to allow for 3D positioning. This 3D positioning is converted into a 3D vector image using computer software. MATLAB software has been used to display the image on a computer monitor. For the different configuration of the colon model, the system determined the looping status. Results Different configurations (N loop, reverse gamma loop, and reverse splenic flexure) of the loops were well defined using 3D vector image. Conclusion The novel sensory system can accurately define the various configuration of the colon during the colonoscopy procedure. PMID:29849469

Camera Based Closed Loop Control for Partial Penetration Welding of Overlap Joints

NASA Astrophysics Data System (ADS)

Abt, F.; Heider, A.; Weber, R.; Graf, T.; Blug, A.; Carl, D.; Höfler, H.; Nicolosi, L.; Tetzlaff, R.

Welding of overlap joints with partial penetration in automotive applications is a challenging process, since the laser power must be set very precisely to achieve a proper connection between the two joining partners without damaging the backside of the sheet stack. Even minor changes in welding conditions can lead to bad results. To overcome this problem a camera based closed loop control for partial penetration welding of overlap joints was developed. With this closed loop control it is possible to weld such configurations with a stable process result even under changing welding conditions.

Automated fluid analysis apparatus and techniques

DOEpatents

Szecsody, James E.

2004-03-16

An automated device that couples a pair of differently sized sample loops with a syringe pump and a source of degassed water. A fluid sample is mounted at an inlet port and delivered to the sample loops. A selected sample from the sample loops is diluted in the syringe pump with the degassed water and fed to a flow through detector for analysis. The sample inlet is also directly connected to the syringe pump to selectively perform analysis without dilution. The device is airtight and used to detect oxygen-sensitive species, such as dithionite in groundwater following a remedial injection to treat soil contamination.

Loop electrostatics modulates the intersubunit interactions in ferritin.

PubMed

Bernacchioni, Caterina; Ghini, Veronica; Pozzi, Cecilia; Di Pisa, Flavio; Theil, Elizabeth C; Turano, Paola

2014-11-21

Functional ferritins are 24-mer nanocages that self-assemble with extended contacts between pairs of 4-helix bundle subunits coupled in an antiparallel fashion along the C2 axes. The largest intersubunit interaction surface in the ferritin nanocage involves helices, but contacts also occur between groups of three residues midway in the long, solvent-exposed L-loops of facing subunits. The anchor points between intersubunit L-loop pairs are the salt bridges between the symmetry-related, conserved residues Asp80 and Lys82. The resulting quaternary structure of the cage is highly soluble and thermostable. Substitution of negatively charged Asp80 with a positively charged Lys in homopolymeric M ferritin introduces electrostatic repulsions that inhibit the oligomerization of the ferritin subunits. D80K ferritin was present in inclusion bodies under standard overexpressing conditions in E. coli, contrasting with the wild type protein. Small amounts of fully functional D80K nanocages formed when expression was slowed. The more positively charged surface results in a different solubility profile and D80K crystallized in a crystal form with a low density packing. The 3D structure of D80K variant is the same as wild type except for the side chain orientations of Lys80 and facing Lys82. When three contiguous Lys groups are introduced in D80KI81K ferritin variant the nanocage assembly is further inhibited leading to lower solubility and reduced thermal stability. Here, we demonstrate that the electrostatic pairing at the center of the L-loops has a specific kinetic role in the self-assembly of ferritin nanocages.

Anthropomorphic cardiac ultrasound phantom.

PubMed

Smith, S W; Rinaldi, J E

1989-10-01

A new phantom is described which simulates the human cardiac anatomy for applications in ultrasound imaging, ultrasound Doppler, and color-flow Doppler imaging. The phantom consists of a polymer left ventricle which includes a prosthetic mitral and aortic valve and is connected to a mock circulatory loop. Aerated tap water serves as a blood simulating fluid and ultrasound contrast medium within the circulatory loop. The left ventricle is housed in a Lexan ultrasound visualization chamber which includes ultrasound viewing ports and acoustic absorbers. A piston pump connected to the visualization chamber by a single port pumps degassed water within the chamber which in turn pumps the left ventricle. Real-time ultrasound images and Doppler studies measure flow patterns through the valves and within the left ventricle.

Method for reworkable packaging of high speed, low electrical parasitic power electronics modules through gate drive integration

DOEpatents

Passmore, Brandon; Cole, Zach; Whitaker, Bret; Barkley, Adam; McNutt, Ty; Lostetter, Alexander

2016-08-02

A multichip power module directly connecting the busboard to a printed-circuit board that is attached to the power substrate enabling extremely low loop inductance for extreme environments such as high temperature operation. Wire bond interconnections are taught from the power die directly to the busboard further enabling enable low parasitic interconnections. Integration of on-board high frequency bus capacitors provide extremely low loop inductance. An extreme environment gate driver board allows close physical proximity of gate driver and power stage to reduce overall volume and reduce impedance in the control circuit. Parallel spring-loaded pin gate driver PCB connections allows a reliable and reworkable power module to gate driver interconnections.

Zn(II) coordination polymers with flexible V-shaped dicarboxylate ligand: Syntheses, helical structures and properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Lin; Liu, Chong-Bo, E-mail: cbliu@nchu.edu.cn; Yang, Gao-Shan

2015-11-15

Hydrothermal reactions of 2,2′-[hexafluoroisopropylidenebis(p-phenyleneoxy)]diacetic acid (H{sub 2}L) and zinc ions in the presence of N-donor ancillary ligands afford four novel coordination polymers, namely, [Zn{sub 2}(μ{sub 2}-OH)(μ{sub 4}-O){sub 0.5}(L)]·0.5H{sub 2}O (1), [Zn(L)(2,2′-bipy)(H{sub 2}O)] (2), [Zn{sub 3}(L){sub 3}(phen){sub 2}]·H{sub 2}O (3) and [Zn{sub 2}(L){sub 2}(4,4′-bipy)] (4) (2,2′-bipy=2,2′-bipyridine; 4,4′-bipy=4,4′-bipyridine; phen=1,10-phenanthroline). Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, powder X-ray diffraction (PXRD), and thermogravimetric (TG) analyses. Complex 1 shows a 3-D clover framework consisting of [Zn{sub 4}(µ{sub 4}-O)(µ{sub 2}-OH){sub 2}]{sup 4+} clusters, and exhibits a novel (3,8)-connected topological net with the Schläfli symbol of {3·4·5}{sub 2}{3"4·4"4·5"2·6"6·7"1"0·8"2}, andmore » contains double-stranded and two kinds of meso-helices. 2 displays a helical chain structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with meso-helix chains. 3 displays a 2-D {4"4·6"2} parallelogram structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with single-stranded helical chains. 4 shows a 2-D {4"4·6"2} square structure with left- and right-handed helical chains. Moreover, the luminescent properties of 1–4 have been investigated. - Graphical abstract: Four new Zn(II) coordination polymers with helical structures based on flexible V-shaped dicarboxylate ligand have been synthesized and structurally characterized. Photoluminescent properties have been investigated. - Highlights: • Four novel Zn(II) coordination polymers with V-shaped ligand were characterized. • Complexes 1–4 show diverse intriguing helical characters. • Fluorescence properties of complexes 1–4 were investigated.« less

On inducing finite dimensional physical field representations for massless particles in even dimensions

NASA Technical Reports Server (NTRS)

Bhansali, Vineer

1993-01-01

Assuming trivial action of Euclidean translations, the method of induced representations is used to derive a correspondence between massless field representations transforming under the full generalized even dimensional Lorentz group, and highest weight states of the relevant little group. This gives a connection between 'helicity' and 'chirality' in all dimensions. Restrictions on 'gauge independent' representations for physical particles that this induction imposes are also stated.

Helix coupling

DOEpatents

Ginell, W.S.

1982-03-17

A coupling for connecting helix members in series, which consists of a pair of U-shaped elements, one of which is attached to each helix end with the U sections of the elements interlocked. The coupling is particularly beneficial for interconnecting helical Nitinol elements utilized in thermal actuators or engines. Each coupling half is attached to the associated helix at two points, thereby providing axial load while being easily removed from the helix, and reusable.

Helix coupling

DOEpatents

Ginell, William S.

1989-04-25

A coupling for connecting helix members in series, which consists of a pair of U-shaped elements, one of which is attached to each helix end with the "U" sections of the elements interlocked. The coupling is particularly beneficial for interconnecting helical Nitinol elements utilized in thermal actuators or engines. Each coupling half is attached to the associated helix at two points, thereby providing axial load while being easily removed from the helix, and reusable.

Towards loop quantum gravity without the time gauge.

PubMed

Cianfrani, Francesco; Montani, Giovanni

2009-03-06

The Hamiltonian formulation of the Holst action is reviewed and it provides a solution of second-class constraints corresponding to a generic local Lorentz frame. Within this scheme the form of rotation constraints can be reduced to a Gauss-like one by a proper generalization of Ashtekar-Barbero-Immirzi connections. This result emphasizes that the loop quantum gravity quantization procedure can be applied when the time-gauge condition does not stand.

Quick connect coupling

NASA Technical Reports Server (NTRS)

Lomax, Curtis (Inventor); Webbon, Bruce (Inventor)

1995-01-01

A cooling apparatus includes a container filled with a quantity of coolant fluid initially cooled to a solid phase, a cooling loop disposed between a heat load and the container, a pump for circulating a quantity of the same type of coolant fluid in a liquid phase through the cooling loop, and a pair of couplings for communicating the liquid phase coolant fluid into the container in a direct interface with the solid phase coolant fluid.

PRESSURE SYSTEM CONTROL

DOEpatents

Esselman, W.H.; Kaplan, G.M.

1961-06-20

The control of pressure in pressurized liquid systems, especially a pressurized liquid reactor system, may be achieved by providing a bias circuit or loop across a closed loop having a flow restriction means in the form of an orifice, a storage tank, and a pump connected in series. The subject invention is advantageously utilized where control of a reactor can be achieved by response to the temperature and pressure of the primary cooling system.

Pumped two-phase heat transfer loop

NASA Technical Reports Server (NTRS)

Edelstein, Fred

1988-01-01

A pumped loop two-phase heat transfer system, operating at a nearly constant temperature throughout, includes several independently operating grooved capillary heat exchanger plates supplied with working fluid through independent flow modulation valves connected to a liquid supply line, a vapor line for collecting vapor from the heat exchangers, a condenser between the vapor and the liquid lines, and a fluid circulating pump between the condenser and the heat exchangers.

Pumped two-phase heat transfer loop

NASA Technical Reports Server (NTRS)

Edelstein, Fred (Inventor)

1987-01-01

A pumped loop two-phase heat transfer system, operating at a nearly constant temperature throughout, includes a plurality of independently operating grooved capillary heat exchanger plates supplied with working fluid through independent flow modulation valves connected to a liquid supply line, a vapor line for collecting vapor from the heat exchangers, a condenser between the vapor and the liquid lines, and a fluid circulating pump between the condenser and the heat exchangers.

Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors

NASA Astrophysics Data System (ADS)

Jakubík, Jan; Randáková, Alena; Zimčík, Pavel; El-Fakahany, Esam E.; Doležal, Vladimír

2017-01-01

Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding. The affinity of NMS at the allosteric site is in the micromolar range for all receptor subtypes. Using molecular modelling of the M2 receptor we found that E172 and E175 in the second extracellular loop and N419 in the third extracellular loop are involved in allosteric binding of NMS. Mutation of these amino acids to alanine decreased affinity of NMS for the allosteric binding site confirming results of molecular modelling. The allosteric binding site of NMS overlaps with the binding site of some allosteric, ectopic and bitopic ligands. Understanding of interactions of NMS at the allosteric binding site is essential for correct analysis of binding and action of these ligands.

Structural basis of arrestin-3 activation and signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Qiuyan; Perry, Nicole A.; Vishnivetskiy, Sergey A.

A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP6) is a non-receptor activator of arrestin-3 and report the structure of IP6-activated arrestin-3 at 2.4-Å resolution. IP6-activated arrestin-3 exhibits an inter-domain twist and a displaced C-tail, hallmarks of active arrestin. IP6 binds to the arrestin phosphate sensor, and is stabilized by trimerization. Analysis of the trimerization surface, which is also the receptor-binding surface, suggests a feature called the finger loop as a key region of the activation sensor. We show that finger loop helicity and flexibility may underliemore » coupling to hundreds of diverse receptors and also promote arrestin-3 activation by IP6. Importantly, we show that effector-binding sites on arrestins have distinct conformations in the basal and activated states, acting as switch regions. These switch regions may work with the inter-domain twist to initiate and direct arrestin-mediated signaling.« less

Top-forms of leading singularities in nonplanar multi-loop amplitudes

NASA Astrophysics Data System (ADS)

Chen, Baoyi; Chen, Gang; Cheung, Yeuk-Kwan E.; Xie, Ruofei; Xin, Yuan

2018-02-01

The on-shell diagram is a very important tool in studying scattering amplitudes. In this paper we discuss the on-shell diagrams without external BCFW bridges. We introduce an extra step of adding an auxiliary external momentum line. Then we can decompose the on-shell diagrams by removing external BCFW bridges to a planar diagram whose top-form is well known now. The top-form of the on-shell diagram with the auxiliary line can be obtained by adding the BCFW bridges in an inverse order as discussed in our former paper (Chen et al. in Eur Phys J C 77(2):80 2017). To get the top-form of the original diagram, the soft limit of the auxiliary line is needed. We obtain the evolution rule for the Grassmannian integral and the geometry constraint in the soft limit. This completes the top-form description of leading singularities in nonplanar scattering amplitudes of N=4 Super Yang-Mills (SYM), which is valid for arbitrary higher-loops and beyond the Maximally-Helicity-Violation (MHV) amplitudes.

3′ Cap-Independent Translation Enhancers of Plant Viruses

PubMed Central

Simon, Anne E.; Miller, W. Allen

2014-01-01

In the absence of a 5′ cap, plant positive-strand RNA viruses have evolved a number of different elements in their 3′ untranslated region (UTR) to attract initiation factors and/or ribosomes to their templates. These 3′ cap-independent translational enhancers (3′ CITEs) take different forms, such as I-shaped, Y-shaped, T-shaped, or pseudoknotted structures, or radiate multiple helices from a central hub. Common features of most 3′ CITEs include the ability to bind a component of the translation initiation factor eIF4F complex and to engage in an RNA-RNA kissing-loop interaction with a hairpin loop located at the 5′ end of the RNA. The two T-shaped structures can bind to ribosomes and ribosomal subunits, with one structure also able to engage in a simultaneous long-distance RNA-RNA interaction. Several of these 3′ CITEs are interchangeable and there is evidence that natural recombination allows exchange of modular CITE units, which may overcome genetic resistance or extend the virus’s host range. PMID:23682606

Wzi is an outer membrane lectin that underpins group 1 capsule assembly in Escherichia coli.

PubMed

Bushell, Simon R; Mainprize, Iain L; Wear, Martin A; Lou, Hubing; Whitfield, Chris; Naismith, James H

2013-05-07

Many pathogenic bacteria encase themselves in a polysaccharide capsule that provides a barrier to the physical and immunological challenges of the host. The mechanism by which the capsule assembles around the bacterial cell is unknown. Wzi, an integral outer-membrane protein from Escherichia coli, has been implicated in the formation of group 1 capsules. The 2.6 Å resolution structure of Wzi reveals an 18-stranded β-barrel fold with a novel arrangement of long extracellular loops that blocks the extracellular entrance and a helical bundle that plugs the periplasmic end. Mutagenesis shows that specific extracellular loops are required for in vivo capsule assembly. The data show that Wzi binds the K30 carbohydrate polymer and, crucially, that mutants functionally deficient in vivo show no binding to K30 polymer in vitro. We conclude that Wzi is a novel outer-membrane lectin that assists in the formation of the bacterial capsule via direct interaction with capsular polysaccharides. Copyright © 2013 Elsevier Ltd. All rights reserved.

The basic helix-loop-helix region of the transcriptional repressor hairy and enhancer of split 1 is preorganized to bind DNA.

PubMed

Popovic, Matija; Wienk, Hans; Coglievina, Maristella; Boelens, Rolf; Pongor, Sándor; Pintar, Alessandro

2014-04-01

Hairy and enhancer of split 1, one of the main downstream effectors in Notch signaling, is a transcriptional repressor of the basic helix-loop-helix (bHLH) family. Using nuclear magnetic resonance methods, we have determined the structure and dynamics of a recombinant protein, H1H, which includes an N-terminal segment, b1, containing functionally important phosphorylation sites, the basic region b2, required for binding to DNA, and the HLH domain. We show that a proline residue in the sequence divides the protein in two parts, a flexible and disordered N-terminal region including b1 and a structured, mainly helical region comprising b2 and the HLH domain. Binding of H1H to a double strand DNA oligonucleotide was monitored through the chemical shift perturbation of backbone amide resonances, and showed that the interaction surface involves not only the b2 segment but also several residues in the b1 and HLH regions. Copyright © 2014 Wiley Periodicals, Inc.

Structural Basis for Ligand Regulation of the Fatty Acid-binding Protein 5, Peroxisome Proliferator-activated Receptor β/δ (FABP5-PPARβ/δ) Signaling Pathway*

PubMed Central

Armstrong, Eric H.; Goswami, Devrishi; Griffin, Patrick R.; Noy, Noa; Ortlund, Eric A.

2014-01-01

Fatty acid-binding proteins (FABPs) are a widely expressed group of calycins that play a well established role in solubilizing cellular fatty acids. Recent studies, however, have recast FABPs as active participants in vital lipid-signaling pathways. FABP5, like its family members, displays a promiscuous ligand binding profile, capable of interacting with numerous long chain fatty acids of varying degrees of saturation. Certain “activating” fatty acids induce the protein's cytoplasmic to nuclear translocation, stimulating PPARβ/δ transactivation; however, the rules that govern this process remain unknown. Using a range of structural and biochemical techniques, we show that both linoleic and arachidonic acid elicit FABP5's translocation by permitting allosteric communication between the ligand-sensing β2 loop and a tertiary nuclear localization signal within the α-helical cap of the protein. Furthermore, we show that more saturated, nonactivating fatty acids inhibit nuclear localization signal formation by destabilizing this activation loop, thus implicating FABP5 specifically in cis-bonded, polyunsaturated fatty acid signaling. PMID:24692551

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks.

PubMed

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-02-02

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user's burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency.

Switch loop flexibility affects substrate transport of the AcrB efflux pump

DOE PAGES

Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea; ...

2017-10-05

The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutionsmore » on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.« less

Switch loop flexibility affects substrate transport of the AcrB efflux pump

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea

The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutionsmore » on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.« less

Mini-filament Eruption as the Initiation of a Jet along Coronal Loops

NASA Astrophysics Data System (ADS)

Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Yang, Bo; Xu, Zhe; Xiang, Yongyuan

2016-10-01

Minifilament eruptions (MFEs) and coronal jets are different types of solar small-scale explosive events. We report an MFE observed at the New Vacuum Solar Telescope (NVST). As seen in the NVST Hα images, during the rising phase, the minifilament erupts outward orthogonally to its length, accompanied with a flare-like brightening at the bottom. Afterward, dark materials are found to possibly extend along the axis of the expanded filament body. The MFE is analogous to large filament eruptions. However, a simultaneous observation of the Solar Dynamics Observatory shows that a jet is initiated and flows out along nearby coronal loops during the rising phase of the MFE. Meanwhile, small hot loops, which connect the original eruptive site of the minifilament to the footpoints of the coronal loops, are formed successively. A differential emission measure analysis demonstrates that, on the top of the new small loops, a hot cusp structure exists. We conjecture that the magnetic fields of the MFE interact with magnetic fields of the coronal loops. This interaction is interpreted as magnetic reconnection that produces the jet and the small hot loops.

Bus-Programmable Slave Card

NASA Technical Reports Server (NTRS)

Hall, William A.

1990-01-01

Slave microprocessors in multimicroprocessor computing system contains modified circuit cards programmed via bus connecting master processor with slave microprocessors. Enables interactive, microprocessor-based, single-loop control. Confers ability to load and run program from master/slave bus, without need for microprocessor development station. Tristate buffers latch all data and information on status. Slave central processing unit never connected directly to bus.

Hippocampal closed-loop modeling and implications for seizure stimulation design

NASA Astrophysics Data System (ADS)

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2015-10-01

Objective. Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main results. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Hippocampal closed-loop modeling and implications for seizure stimulation design.

PubMed

Sandler, Roman A; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W; Marmarelis, Vasilis Z

2015-10-01

Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Hippocampal Closed-Loop Modeling and Implications for Seizure Stimulation Design

PubMed Central

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2016-01-01

Objective Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the Entorhinal Cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3→CA1, via the Schaffer-Collateral synapse, and CA1→CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (Principal Dynamic Modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main Results Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance DBS is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy. PMID:26355815

Positions of the cytoplasmic end of BK α S0 helix relative to S1–S6 and of β1 TM1 and TM2 relative to S0–S6

PubMed Central

Liu, Guoxia; Zakharov, Sergey I.; Yao, Yongneng

2015-01-01

The large-conductance, voltage- and Ca2+-gated K+ (BK) channel consists of four α subunits, which form a voltage- and Ca2+-gated channel, and up to four modulatory β subunits. The β1 subunit is expressed in smooth muscle, where it slows BK channel kinetics and shifts the conductance–voltage (G-V) curve to the left at [Ca2+] > 2 µM. In addition to the six transmembrane (TM) helices, S1–S6, conserved in all voltage-dependent K+ channels, BK α has a unique seventh TM helix, S0, which may contribute to the unusual rightward shift in the G-V curve of BK α in the absence of β1 and to a leftward shift in its presence. Such a role is supported by the close proximity of S0 to S3 and S4 in the voltage-sensing domain. Furthermore, on the extracellular side of the membrane, one of the two TM helices of β1, TM2, is adjacent to S0. We have now analyzed induced disulfide bond formation between substituted Cys residues on the cytoplasmic side of the membrane. There, in contrast, S0 is closest to the S2–S3 loop, from which position it is displaced on the addition of β1. The cytoplasmic ends of β1 TM1 and TM2 are adjacent and are located between the S2–S3 loop of one α subunit and S1 of a neighboring α subunit and are not adjacent to S0; i.e., S0 and TM2 have different trajectories through the membrane. In the absence of β1, 70% of disulfide bonding of W43C (S0) and L175C (S2–S3) has no effect on V50 for activation, implying that the cytoplasmic end of S0 and the S2–S3 loop move in concert, if at all, during activation. Otherwise, linking them together in one state would obstruct the transition to the other state, which would certainly change V50. PMID:25667410

Crystal structure of an antigenic outer-membrane protein from Salmonella Typhi suggests a potential antigenic loop and an efflux mechanism.

PubMed

Guan, Hong-Hsiang; Yoshimura, Masato; Chuankhayan, Phimonphan; Lin, Chien-Chih; Chen, Nai-Chi; Yang, Ming-Chi; Ismail, Asma; Fun, Hoong-Kun; Chen, Chun-Jung

2015-11-13

ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOT(TM)). The crystal structure of ST50 at a resolution of 2.98 Å reveals a trimer that forms an α-helical tunnel and a β-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-β-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen.

Crystallographic and Computational Analyses of AUUCU Repeating RNA That Causes Spinocerebellar Ataxia Type 10 (SCA10).

PubMed

Park, HaJeung; González, Àlex L; Yildirim, Ilyas; Tran, Tuan; Lohman, Jeremy R; Fang, Pengfei; Guo, Min; Disney, Matthew D

2015-06-23

Spinocerebellar ataxia type 10 (SCA10) is caused by a pentanucleotide repeat expansion of r(AUUCU) within intron 9 of the ATXN10 pre-mRNA. The RNA causes disease by a gain-of-function mechanism in which it inactivates proteins involved in RNA biogenesis. Spectroscopic studies showed that r(AUUCU) repeats form a hairpin structure; however, there were no high-resolution structural models prior to this work. Herein, we report the first crystal structure of model r(AUUCU) repeats refined to 2.8 Å and analysis of the structure via molecular dynamics simulations. The r(AUUCU) tracts adopt an overall A-form geometry in which 3 × 3 nucleotide (5')UCU(3')/(3')UCU(5') internal loops are closed by AU pairs. Helical parameters of the refined structure as well as the corresponding electron density map on the crystallographic model reflect dynamic features of the internal loop. The computational analyses captured dynamic motion of the loop closing pairs, which can form single-stranded conformations with relatively low energies. Overall, the results presented here suggest the possibility for r(AUUCU) repeats to form metastable A-from structures, which can rearrange into single-stranded conformations and attract proteins such as heterogeneous nuclear ribonucleoprotein K (hnRNP K). The information presented here may aid in the rational design of therapeutics targeting this RNA.

Crystallographic and Computational Analyses of AUUCU Repeating RNA That Causes Spinocerebellar Ataxia Type 10 (SCA10)

PubMed Central

Park, HaJeung; González, Àlex L.; Yildirim, Ilyas; Tran, Tuan; Lohman, Jeremy R.; Fang, Pengfei; Guo, Min; Disney, Matthew D.

2016-01-01

Spinocerebellar ataxia type 10 (SCA10) is caused by a pentanucleotide repeat expansion of r(AUUCU) within intron 9 of the ATXN10 pre-mRNA. The RNA causes disease by a gain-of-function mechanism in which it inactivates proteins involved in RNA biogenesis. Spectroscopic studies showed that r(AUUCU) repeats form a hairpin structure; however, there were no high-resolution structural models prior to this work. Herein, we report the first crystal structure of model r(AUUCU) repeats refined to 2.8 Å and analysis of the structure via molecular dynamics simulations. The r(AUUCU) tracts adopt an overall A-form geometry in which 3 × 3 nucleotide 5′UCU3′/3′UCU5′ internal loops are closed by AU pairs. Helical parameters of the refined structure as well as the corresponding electron density map on the crystallographic model reflect dynamic features of the internal loop. The computational analyses captured dynamic motion of the loop closing pairs, which can form single-stranded conformations with relatively low energies. Overall, the results presented here suggest the possibility for r(AUUCU) repeats to form metastable A-from structures, which can rearrange into single-stranded conformations and attract proteins such as heterogeneous nuclear ribonucleoprotein K (hnRNP K). The information presented here may aid in the rational design of therapeutics targeting this RNA. PMID:26039897

Biopolymer Chain Elasticity: a novel concept and a least deformation energy principle predicts backbone and overall folding of DNA TTT hairpins in agreement with NMR distances

PubMed Central

Pakleza, Christophe; Cognet, Jean A. H.

2003-01-01

A new molecular modelling methodology is presented and shown to apply to all published solution structures of DNA hairpins with TTT in the loop. It is based on the theory of elasticity of thin rods and on the assumption that single-stranded B-DNA behaves as a continuous, unshearable, unstretchable and flexible thin rod. It requires four construction steps: (i) computation of the tri-dimensional trajectory of the elastic line, (ii) global deformation of single-stranded helical DNA onto the elastic line, (iii) optimisation of the nucleoside rotations about the elastic line, (iv) energy minimisation to restore backbone bond lengths and bond angles. This theoretical approach called ‘Biopolymer Chain Elasticity’ (BCE) is capable of reproducing the tri-dimensional course of the sugar–phosphate chain and, using NMR-derived distances, of reproducing models close to published solution structures. This is shown by computing three different types of distance criteria. The natural description provided by the elastic line and by the new parameter, Ω, which corresponds to the rotation angles of nucleosides about the elastic line, offers a considerable simplification of molecular modelling of hairpin loops. They can be varied independently from each other, since the global shape of the hairpin loop is preserved in all cases. PMID:12560506

Statistical properties of edge plasma turbulence in the Large Helical Device

NASA Astrophysics Data System (ADS)

Dewhurst, J. M.; Hnat, B.; Ohno, N.; Dendy, R. O.; Masuzaki, S.; Morisaki, T.; Komori, A.

2008-09-01

Ion saturation current (Isat) measurements made by three tips of a Langmuir probe array in the Large Helical Device are analysed for two plasma discharges. Absolute moment analysis is used to quantify properties on different temporal scales of the measured signals, which are bursty and intermittent. Strong coherent modes in some datasets are found to distort this analysis and are consequently removed from the time series by applying bandstop filters. Absolute moment analysis of the filtered data reveals two regions of power-law scaling, with the temporal scale τ ≈ 40 µs separating the two regimes. A comparison is made with similar results from the Mega-Amp Spherical Tokamak. The probability density function is studied and a monotonic relationship between connection length and skewness is found. Conditional averaging is used to characterize the average temporal shape of the largest intermittent bursts.

Recording and wear characteristics of 4 and 8 mm helical scan tapes

NASA Technical Reports Server (NTRS)

Peter, Klaus J.; Speliotis, Dennis E.

1993-01-01

Performance data of media on helical scan tape systems (4 and 8 mm) is presented and various types of media are compared. All measurements were performed on a standard MediaLogic model ML4500 Tape Evaluator System with a Flash Converter option for time based measurements. The 8 mm tapes are tested on an Exabyte 8200 drive and 4 mm tapes on an Archive Python drive; in both cases, the head transformer is directly connected to a Media Logic Read/Write circuit and test electronics. The drive functions only as a tape transport and its data recover circuits are not used. Signal to Noise, PW 50, Peak Shift and Wear Test data is used to compare the performance of MP (metal particle), BaFe, and metal evaporate (ME). ME tape is the clear winner in magnetic performance but its susceptibility to wear and corrosion, make it less than ideal for data storage.

Cavity resonance absorption in ultra-high bandwidth CRT deflection structure by a resistive load

DOEpatents

Dunham, M.E.; Hudson, C.L.

1993-05-11

An improved ultra-high bandwidth helical coil deflection structure for a cathode ray tube is described comprising a first metal member having a bore therein, the metal walls of which form a first ground plane; a second metal member coaxially mounted in the bore of the first metal member and forming a second ground plane; a helical deflection coil coaxially mounted within the bore between the two ground planes; and a resistive load disposed in one end of the bore and electrically connected to the first and second ground planes, the resistive load having an impedance substantially equal to the characteristic impedance of the coaxial line formed by the two coaxial ground planes to inhibit cavity resonance in the structure within the ultra-high bandwidth of operation. Preferably, the resistive load comprises a carbon film on a surface of an end plug in one end of the bore.

Cavity resonance absorption in ultra-high bandwidth CRT deflection structure by a resistive load

DOEpatents

Dunham, Mark E.; Hudson, Charles L.

1993-01-01

An improved ultra-high bandwidth helical coil deflection structure for a hode ray tube is described comprising a first metal member having a bore therein, the metal walls of which form a first ground plane; a second metal member coaxially mounted in the bore of the first metal member and forming a second ground plane; a helical deflection coil coaxially mounted within the bore between the two ground planes; and a resistive load disposed in one end of the bore and electrically connected to the first and second ground planes, the resistive load having an impedance substantially equal to the characteristic impedance of the coaxial line formed by the two coaxial ground planes to inhibit cavity resonance in the structure within the ultra-high bandwidth of operation. Preferably, the resistive load comprises a carbon film on a surface of an end plug in one end of the bore.

Minimum Winfree loop determines self-sustained oscillations in excitable Erdös-Rényi random networks.

PubMed

Qian, Yu; Cui, Xiaohua; Zheng, Zhigang

2017-07-18

The investigation of self-sustained oscillations in excitable complex networks is very important in understanding various activities in brain systems, among which the exploration of the key determinants of oscillations is a challenging task. In this paper, by investigating the influence of system parameters on self-sustained oscillations in excitable Erdös-Rényi random networks (EERRNs), the minimum Winfree loop (MWL) is revealed to be the key factor in determining the emergence of collective oscillations. Specifically, the one-to-one correspondence between the optimal connection probability (OCP) and the MWL length is exposed. Moreover, many important quantities such as the lower critical connection probability (LCCP), the OCP, and the upper critical connection probability (UCCP) are determined by the MWL. Most importantly, they can be approximately predicted by the network structure analysis, which have been verified in numerical simulations. Our results will be of great importance to help us in understanding the key factors in determining persistent activities in biological systems.

Network community structure and loop coefficient method

NASA Astrophysics Data System (ADS)

Vragović, I.; Louis, E.

2006-07-01

A modular structure, in which groups of tightly connected nodes could be resolved as separate entities, is a property that can be found in many complex networks. In this paper, we propose a algorithm for identifying communities in networks. It is based on a local measure, so-called loop coefficient that is a generalization of the clustering coefficient. Nodes with a large loop coefficient tend to be core inner community nodes, while other vertices are usually peripheral sites at the borders of communities. Our method gives satisfactory results for both artificial and real-world graphs, if they have a relatively pronounced modular structure. This type of algorithm could open a way of interpreting the role of nodes in communities in terms of the local loop coefficient, and could be used as a complement to other methods.

Closed-Loop and Activity-Guided Optogenetic Control

PubMed Central

Grosenick, Logan; Marshel, James H.; Deisseroth, Karl

2016-01-01

Advances in optical manipulation and observation of neural activity have set the stage for widespread implementation of closed-loop and activity-guided optical control of neural circuit dynamics. Closing the loop optogenetically (i.e., basing optogenetic stimulation on simultaneously observed dynamics in a principled way) is a powerful strategy for causal investigation of neural circuitry. In particular, observing and feeding back the effects of circuit interventions on physiologically relevant timescales is valuable for directly testing whether inferred models of dynamics, connectivity, and causation are accurate in vivo. Here we highlight technical and theoretical foundations as well as recent advances and opportunities in this area, and we review in detail the known caveats and limitations of optogenetic experimentation in the context of addressing these challenges with closed-loop optogenetic control in behaving animals. PMID:25856490

Hopf-link topological nodal-loop semimetals

NASA Astrophysics Data System (ADS)

Zhou, Yao; Xiong, Feng; Wan, Xiangang; An, Jin

2018-04-01

We construct a generic two-band model which can describe topological semimetals with multiple closed nodal loops. All the existing multi-nodal-loop semimetals, including the nodal-net, nodal-chain, and Hopf-link states, can be examined within the same framework. Based on a two-nodal-loop model, the corresponding drumhead surface states for these topologically different bulk states are studied and compared with each other. The connection of our model with Hopf insulators is also discussed. Furthermore, to identify experimentally these topologically different semimetal states, especially to distinguish the Hopf-link from unlinked ones, we also investigate their Landau levels. It is found that the Hopf-link state can be characterized by the existence of a quadruply degenerate zero-energy Landau band, regardless of the direction of the magnetic field.

A 3D chiral metal-organic framework based on left-handed helices containing 3-amino-1 H-1,2,4-triazole ligand

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Bing, E-mail: bliu_1203@163.com; Yang, Tian-Yi; Feng, Hui-Jun

2015-10-15

A chiral metal-organic framework, [Cu(atr)(OH)]·0.5H{sub 2}O·0.5en (1) (Hatr=3-amino-1 H-1,2,4-triazole, en=ethylenediamine), was constructed via diffusion reaction of the achiral Hatr ligand and CuSO{sub 4} as starting materials. Compound 1 crystallizes in the chiral space group P3{sub 2}21 and features a porous metal-organic framework with 44.1% solvent-accessible volume fabricated by left-handed helices with a pitch height of l{sub p}=10.442 Å. Six helices gather around in a cycle forming a large honeycomb channel with a 6.58 Å inner diameter. Cu(II) center and atr{sup ‒} ligand regarded as 3-connected nodes, compound 1 can be simplified to a 3-c uninodal (4.12{sup 2}) (qtz-h) topological network.more » A gradual decreasing in the magnetic moment depending on temperature decreasing indicates an antiferromagnetic interaction in 1. The powder XRD confirms the bulk sample is a single crystal pure phase, and the thermogravimetric analysis shows the thermal stability of 1 is up to ca. 240 °C. - Highlights: • The present 3D chiral MOF is built from achiral Hatr ligand. • Six left-handed helices gather into a honeycomb channel in chiral sp P3{sub 2}21. • Compound 1 shows a 3-c uninodal (4.12{sup 2}) or qtz-h topological network. • Compound 1 indicates an antiferromagnetic interaction.« less