Metal-Nucleotide Interactions: Crystal Structures of Alkali (Li+, Na+, K+) and Alkaline Earth (Ca2+, Mg2+) Metal Complexes of Adenosine 2'-Monophosphate

Crystal structures of lithium, sodium, potassium, calcium and magnesium salts of adenosine 2'-monophosphate (2'-AMP) have been obtained at atomic resolution by X-ray crystallographic methods. 2'-AMP.Li belongs to the monoclinic space group P21 with a = 7.472(3)Å, b = 26.853(6) Å, c = 9.184(1)Å, b = 113.36(1)Å and Z= 4. 2'-AMP.Na and 2'-AMP.K crystallize in the trigonal space groups P31 and P3121 with a = 8.762(1)Å, c = 34.630(5)Å, Z= 6 and a = 8.931(4), Åc = 34.852(9)Å and Z= 6 respectively while 2'-AMP.Ca and 2'-AMP.Mg belong to space groups P6522 and P21 with cell parameters a = 9.487(2), c = 74.622(13), Z = 12 and a = 4.973(1), b = 10.023(2), c = 16.506(2), beta = 91.1(0) and Z = 2 respectively. All the structures were solved by direct methods and refined by full matrix least-squares to final R factors of 0.033, 0.028, 0.075, 0.069 and 0.030 for 2'-AMP.Li, 2'-AMP.Na, 2'- AMP.K, 2'-AMP.Ca and 2'-AMP.Mg, respectively. The neutral adenine bases in all the structures are in syn conformation stabilized by the O5'-N3 intramolecular hydrogen bond as in free acid and ammonium complex reported earlier. In striking contrast, the adenine base is in the anti geometry (cCN = -156.4(2)°) in 2'-AMP.Mg. Ribose moieties adopt C2'-endo puckering in 2'-AMP.Li and 2'-AMP.Ca, C2'-endo-C3'-exo twist puckering in 2'-AMP.Na and 2'-AMP.K and a C3'-endo-C2'-exo twist puckering in 2'-AMP.Mg structure. The conformation about the exocyclic C4'-C5' bond is the commonly observed gauche-gauche (g+) in all the structures except the gauche- trans (g-) conformation observed in 2'-AMP.Mg structure. Lithium ions coordinate with water, ribose and phosphate oxygens at distances 1.88 to 1.99Å. Na+ ions and K+ ions interact with phosphate and ribose oxygens directly and with N7 indirectly through a water oxygen. A distinct feature of 2'-AMP.Na and 2'-AMP.K structures is the involvement of ribose O4' in metal coordination. The calcium ion situated on a two-fold axis coordinates directly with three oxygens OW1, OW2 and O2 and their symmetry mates at distances 2.18 to 2.42Å forming an octahedron. A classic example of an exception to the existence of the O5'-N3 intramolecular hydorgen bond is the 2'-AMP.Mg strucure. Magnesium ion forms an octahedral coordination with three water and three phosphate oxygens at distances ranging from 2.02 to 2.11Å. A noteworthy feature of its coordination is the indirect link with N3 through OW3 oxygen resulting in macrochelation between the base and the phosphate group. Greater affnity of metal clays towards 5' compared to 2' and 3' nucleotides (J. Lawless, E. Edelson, and L. Manring, Am. Chem. Soc. Northwest Region Meeting, Seattle. 1978) due to macrochelation infered from solution studies (S. S. Massoud, H. Sigel, Eur. J. Biochem. 179, 451-458 (1989)) and interligand hydrogen bonding induced by metals postulated from metal-nucleotide structures in solid state (V. Swaminathan and M. Sundaralingam, CRC. Crit. Rev. Biochem. 6, 245-336 (1979)) are borne out by our structures also. The stacking patterns of adenine bases of both 2'-AMP.Na and 2'-AMP.K structures resemble the 2'-AMP.NH4 structure reported in the previous article. 2'-AMP.Li, 2'-AMP.Ca and 2'-AMP.Mg structures display base-ribose O4' stacking. An overview of interaction of monovalent and divalent cations with 2' and 5'-nucleotides has been presented.

Neuronal K-Cl Cotransporter : Transcriptional Mechanisms of KCC2 Gene Regulation

K-Cl cotransporter 2 (KCC2) maintains a low intracellular Cl concentration required for fast hyperpolarizing responses of neurons to classical inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. Decreased Cl extrusion observed in genetically modified KCC2-deficient mice leads to depolarizing GABA responses, impaired brain inhibition, and as a consequence to epileptic seizures. Identification of mechanisms regulating activity of the SLC12A5 gene, which encodes the KCC2 cotransporter, in normal and pathological conditions is, thus, of extreme importance. Multiple reports have previously elucidated in details a spatio-temporal pattern of KCC2 expression. Among the characteristic features are an exclusive neuronal specificity, a dramatic upregulation during embryonic and early postnatal development, and a significant downregulation by neuronal trauma. Numerous studies confirmed these expressional features, however transcriptional mechanisms predetermining the SLC12A5 gene behaviour are still unknown. The aim of the presented thesis is to recognize such transcriptional mechanisms and, on their basis, to create a transcriptional model that would explain the established SLC12A5 gene behaviour. Up to recently, only one KCC2 transcript has been thought to exist. A particular novelty of the presented work is the identification of two SLC12A5 gene promoters (SLC12A5-1a and SLC12A5-1b) that produce at least two KCC2 isoforms (KCC2a and KCC2b) differing by their N-terminal parts. Even though a functional 86Rb+ assay reveals no significant difference between transport activities of the isoforms, consensus sites for several protein kinases, found in KCC2a but not in KCC2b, imply a distinct kinetic regulation. As a logical continuation, the current work presents a detailed analysis of the KCC2a and KCC2b expression patterns. This analysis shows an exclusively neuron-specific pattern and similar expression levels for both isoforms during embryonic and neonatal development in rodents. During subsequent postnatal development, the KCC2b expression dramatically increases, while KCC2a expression, depending on central nervous system (CNS) area, either remains at the same level or moderately decreases. In an attempt to explain both the neuronal specificity and the distinct expressional kinetics of the KCC2a and KCC2b isoforms during postnatal development, the corresponding SLC12A5-1a and SLC12A5-1b promoters have been subjected to a comprehensive bioinformatical analysis. Binding sites of several transcription factors (TFs), conserved in the mammalian SLC12A5 gene orthologs, have been identified that might shed light on the observed behaviour of the SLC12A5 gene. Possible roles of these TFs in the regulating of the SLC12A5 gene expression have been elucidated in subsequent experiments and are discussed in the current thesis.

RF Sputtered Er2O3 Thin Films as High-k Gate Dielectrics for Germanium MOS Devices

We report the material and electrical properties of Erbium Oxide (Er2O3) thin films grown on n-Ge (100) by RF sputtering. The properties of the films are correlated with the processing conditions. The structural characterization reveals that the films annealed at 550 degrees C, has densified as compared to the as-grown ones. Fixed oxide charges and interface charges, both of the order of 10(13)/cm(2) is observed.

Soft gluon k(t)-resummation and the Froissart bound

We study soft gluon k(t)-resurnmation and the relevance of InfraRed (IR) gluons for the energy dependence of total hadronic cross-sections. In our model, consistency with the Froissart bound is directly related to the ansatz that the IR behaviour of the QCD coupling constant follows an inverse power law.

On the Structure of Contractible Edges in k-connected Partial k-trees

Contraction of an edge e merges its end points into a new single vertex, and each neighbor of one of the end points of e is a neighbor of the new vertex. An edge in a k-connected graph is contractible if its contraction does not result in a graph with lesser connectivity; otherwise the edge is called non-contractible. In this paper, we present results on the structure of contractible edges in k-trees and k-connected partial k-trees. Firstly, we show that an edge e in a k-tree is contractible if and only if e belongs to exactly one (k + 1) clique. We use this characterization to show that the graph formed by contractible edges is a 2-connected graph. We also show that there are at least |V(G)| + k - 2 contractible edges in a k-tree. Secondly, we show that if an edge e in a partial k-tree is contractible then e is contractible in any k-tree which contains the partial k-tree as an edge subgraph. We also construct a class of contraction critical 2k-connected partial 2k-trees.

STEM education K-12: perspectives on integration

This commentary was stimulated by Yeping Li's first editorial (2014) citing one of the journal's goals as adding multidisciplinary perspectives to current studies of single disciplines comprising the focus of other journals. In this commentary I argue for a greater focus on STEM integration, with a more equitable representation of the four disciplines in studies purporting to advance STEM learning. The STEM acronym is often used in reference to just one of the disciplines, commonly science. Although the integration of STEM disciplines is increasingly advocated in the literature, studies that address multiple disciplines appear scant with mixed findings and inadequate directions for STEM advancement. Perspectives on how discipline integration can be achieved are varied, with reference to multidisciplinary, interdisciplinary, and transdisciplinary approaches adding to the debates. Such approaches include core concepts and skills being taught separately in each discipline but housed within a common theme; the introduction of closely linked concepts and skills from two or more disciplines with the aim of deepening understanding and skills; and the adoption of a transdisciplinary approach, where knowledge and skills from two or more disciplines are applied to real-world problems and projects with the aim of shaping the total learning experience. Research that targets STEM integration is an embryonic field with respect to advancing curriculum development and various student outcomes. For example, we still need more studies on how student learning outcomes arise not only from different forms of STEM integration but also from the particular disciplines that are being integrated. As noted in this commentary, it seems that mathematics learning benefits less than the other disciplines in programs claiming to focus on STEM integration. Factors contributing to this finding warrant more scrutiny. Likewise, learning outcomes for engineering within K-12 integrated STEM programs appear under-researched. This commentary advocates a greater focus on these two disciplines within integrated STEM education research. Drawing on recommendations from the literature, suggestions are offered for addressing the challenges of integrating multiple disciplines faced by the STEM community.

Two-level k-means clustering algorithm for k-tau relationship establishment and linear-time classification

Partitional clustering algorithms, which partition the dataset into a pre-defined number of clusters, can be broadly classified into two types: algorithms which explicitly take the number of clusters as input and algorithms that take the expected size of a cluster as input. In this paper, we propose a variant of the k-means algorithm and prove that it is more efficient than standard k-means algorithms. An important contribution of this paper is the establishment of a relation between the number of clusters and the size of the clusters in a dataset through the analysis of our algorithm. We also demonstrate that the integration of this algorithm as a pre-processing step in classification algorithms reduces their running-time complexity.

DMT of Multi-hop Cooperative Networks-Part I: K-Parallel-Path Networks

We consider single-source, single-sink multi-hop relay networks, with slow-fading Rayleigh fading links and single-antenna relay nodes operating under the half-duplex constraint. While two hop relay networks have been studied in great detail in terms of the diversity-multiplexing tradeoff (DMT), few results are available for more general networks. In this two-part paper, we identify two families of networks that are multi-hop generalizations of the two hop network: K-Parallel-Path (KPP) networks and Layered networks. In the first part, we initially consider KPP networks, which can be viewed as the union of K node-disjoint parallel paths, each of length > 1. The results are then generalized to KPP(I) networks, which permit interference between paths and to KPP(D) networks, which possess a direct link from source to sink. We characterize the optimal DMT of KPP(D) networks with K >= 4, and KPP(I) networks with K >= 3. Along the way, we derive lower bounds for the DMT of triangular channel matrices, which are useful in DMT computation of various protocols. As a special case, the DMT of two-hop relay network without direct link is obtained. Two key implications of the results in the two-part paper are that the half-duplex constraint does not necessarily entail rate loss by a factor of two, as previously believed and that, simple AF protocols are often sufficient to attain the best possible DMT.

Free vibration and wave propagation analysis of uniform and tapered rotating beams using spectrally formulated finite elements

This paper presents a formulation of an approximate spectral element for uniform and tapered rotating Euler-Bernoulli beams. The formulation takes into account the varying centrifugal force, mass and bending stiffness. The dynamic stiffness matrix is constructed using the weak form of the governing differential equation in the frequency domain, where two different interpolating functions for the transverse displacement are used for the element formulation. Both free vibration and wave propagation analysis is performed using the formulated elements. The studies show that the formulated element predicts results, that compare well with the solution available in the literature, at a fraction of the computational effort. In addition, for wave propagation analysis, the element shows superior convergence. (C) 2007 Elsevier Ltd. All rights reserved.

Phase diagram of the system Ca-Ti-O at 1200 K

Phase relations in the system Ca-Ti-O have been established by equilibration of several samples at 1200 K for prolonged periods and identification of phases in quenched samples by optical and scanning electron microscopy, XRD and EDS. Samples representing 20 compositions in the ternary system were analyzed. There was negligible solid solubility of Ca in the phases along the binary Ti-O, and of Ti in CaO. Four ternary oxides were identified: CaTiO3, Ca4Ti3O10 and Ca3Ti2O7 containing tetravalent titanium, and CaTi2O4 containing trivalent titanium. Tie-lines link calcium titanite (CaTi2O4) with the three calcium titanates (CaTiO3, Ca4Ti3O10 and Ca3Ti2O7), CaO, oxygen excess TiO1+delta and stoichiometric TiO. Tie-lines connect CaTiO3 with TiO2-x, Magneli phases TinO2n-1 (28 >= n >= 4), Ti3O5, Ti2O3 and TiO1+delta. CaO was found to coexist with TiO, and Ti-O solid solutions alpha and beta. The phase diagram is useful for understanding the mechanisms and kinetics of direct calciothermic reduction of TiO2 to metal and electrochemical reduction of TiO2 using graphite anode and molten CaCl2 electrolyte.

Avian diversification patterns across the K-Pg boundary: Influence of calibrations, datasets, and model misspecification

Birds represent the most diverse extant tetrapod clade, with ca. 10,000 extant species, and the timing of the crown avian radiation remains hotly debated. The fossil record supports a primarily Cenozoic radiation of crown birds, whereas molecular divergence dating analyses generally imply that this radiation was well underway during the Cretaceous. Furthermore, substantial differences have been noted between published divergence estimates. These have been variously attributed to clock model, calibration regime, and gene type. One underappreciated phenomenon is that disparity between fossil ages and molecular dates tends to be proportionally greater for shallower nodes in the avian Tree of Life. Here, we explore potential drivers of disparity in avian divergence dates through a set of analyses applying various calibration strategies and coding methods to a mitochondrial genome dataset and an 18-gene nuclear dataset, both sampled across 72 taxa. Our analyses support the occurrence of two deep divergences (i.e., the Palaeognathae/Neognathae split and the Galloanserae/Neoaves split) well within the Cretaceous, followed by a rapid radiation of Neoaves near the K-Pg boundary. However, 95% highest posterior density intervals for most basal divergences in Neoaves cross the boundary, and we emphasize that, barring unreasonably strict prior distributions, distinguishing between a rapid Early Paleocene radiation and a Late Cretaceous radiation may be beyond the resolving power of currently favored divergence dating methods. In contrast to recent observations for placental mammals, constraining all divergences within Neoaves to occur in the Cenozoic does not result in unreasonably high inferred substitution rates. Comparisons of nuclear DNA (nDNA) versus mitochondrial DNA (mtDNA) datasets and NT- versus RY-coded mitochondrial data reveal patterns of disparity that are consistent with substitution model misspecifications that result in tree compression/tree extension artifacts, which may explain some discordance between previous divergence estimates based on different sequence types. Comparisons of fully calibrated and nominally calibrated trees support a correlation between body mass and apparent dating error. Overall, our results are consistent with (but do not require) a Paleogene radiation for most major clades of crown birds.

Melting of an Anchored Bilayer: Molecular Dynamics Simulations of the Structural Transition in (CnH2n+1NH3)(2)PbI4 (n=12, 14, 16, 18)

The thermally driven Structural phase transition in the organic-inorganic hybrid perovskite (CnH2n+1NH3)(2)PbI4 has been investigated using molecular dynamics (MD) simulations. This system consists of positively charged alkyl-amine chains anchored to a rigid negatively charged PbI4 sheet with the chains organized as bilayers with a herringbone arrangement. Atomistic simulations were performed using ail isothermal-isobaric ensemble over a wide temperature range from 65 to 665 K for different alkyl chain lengths, n = 12, 14, 16, and 18. The simulations are able to reproduce the essential Features of the experimental observations of this system, including the existence of a transition, the linear variation of the transition temperature with alkyl chain length, and the expansion of the bilayer thickness at the transition. By use of the distance fluctuation Criteria, it is Shown that the transition is associated With a Melting of the alkyl chains of the anchored bilayer. Ail analysis of the conformation of the alkyl chains shows increased disorder in the form of gauche defects above due melting transition. Simulations also show that the melting transition is characterized by the complete disappearance of all-trans alkyl chains in the anchored bilayer, in agreement with experimental observations. A conformationally disordered chain has a larger effective cross-sectional area, and above due transition a uniformly tilted arrangement of the anchored chains call no longer be Sustained. At the melt the angular distribution of the orientation of the chains are 110 longer uniform; the chains are splayed allowing for increased space for individual chains of the anchored bilayer. This is reflected in a sharp rise in the ratio of the mean head-to-head to tail-to-tail distance of the chains of the bilayer at the transition resulting in in expansion of the bilayer thickness. The present MD simulations provide a simple explanation as to how changes in conformation of individual alkyl-chains gives rise to the observed increase in the interlayer lattice spacing of (CnH2n+1NH3)(2)PbI4 at the melting transition.

Thermodynamic activities in the Pb(Zr1-XTiX)O-3 solid solution at 1373 K

Although Pb(Zr1-XTiX)O-3 solid solution is the cornerstone of the piezoelectric ceramics, there is no information in the literature on thermodynamic activities of the component phases in the solid solution. Using inter-crystalline ion exchange equilibria between Pb(Zr1-XTiX)O-3 solid solution with cubic perovskite structure and (Zr1-YTiY)O-2 solid solutions with monoclinic and tetragonal structures, activities of PbTiO3 and PbZrO3 in the perovskite solid solution have been derived at 1373 K using the modified Gibbs-Duhem integration technique of Jacob and Jeffes. Tie-lines from the cubic solid solution are skewed towards the ZrO2 corner. Activities in the zirconia-rich (Zr1-YTiY)02 solid solutions are taken from a recent emf study. The results for the perovskite solid solution at 1373 K can be represented by a sub-regular solution model: Delta G(E.M) (J mol(-1)) = X-PbTiO3 X-PbZrO3(5280X(PbTiO3) - 1980X(PbZrO3)) where Delta G(E.M) is the excess Gibbs energy of mixing of the cubic solid solution and Xi represents the mole fraction of component i. There is a significant positive deviation from ideality for PbTiO3-rich compositions and mild negative deviation near the PbZrO3 corner. The cubic solid solution is intrinsically stable against composition fluctuations at temperatures down to 840 K. The results contrast sharply with the recent calorimetric data on enthalpy of mixing which signal instability of the cubic perovskite solid solution. (C) 2007 Elsevier B.V. All rights reserved.