Conservation Properties of the Trapezoidal Rule in Linear Time Domain Analysis of Acoustics and Structures

The trapezoidal rule, which is a special case of the Newmark family of algorithms, is one of the most widely used methods for transient hyperbolic problems. In this work, we show that this rule conserves linear and angular momenta and energy in the case of undamped linear elastodynamics problems, and an ``energy-like measure'' in the case of undamped acoustic problems. These conservation properties, thus, provide a rational basis for using this algorithm. In linear elastodynamics problems, variants of the trapezoidal rule that incorporate ``high-frequency'' dissipation are often used, since the higher frequencies, which are not approximated properly by the standard displacement-based approach, often result in unphysical behavior. Instead of modifying the trapezoidal algorithm, we propose using a hybrid finite element framework for constructing the stiffness matrix. Hybrid finite elements, which are based on a two-field variational formulation involving displacement and stresses, are known to approximate the eigenvalues much more accurately than the standard displacement-based approach, thereby either bypassing or reducing the need for high-frequency dissipation. We show this by means of several examples, where we compare the numerical solutions obtained using the displacement-based and hybrid approaches against analytical solutions.

Molecular and Functional Characterization of RecD, a Novel Member of the SF1 Family of Helicases, from Mycobacterium tuberculosis

Background: The heterotrimeric M. tuberculosis RecBCD complex, or each of its individual subunits, remains uncharacterized. Results: MtRecD exists as a homodimer in solution, catalyzes ssDNA-dependent ATP hydrolysis, unwinding of DNA replication/recombination intermediates, and interacts with RecA. Conclusion: MtRecD possesses strong 5 3- and weak 3 5-helicase activities. Significance: These findings provide insights into the mechanism underlying DSB repair and homologous recombination in mycobacteria. The annotated whole-genome sequence of Mycobacterium tuberculosis revealed the presence of a putative recD gene; however, the biochemical characteristics of its encoded protein product (MtRecD) remain largely unknown. Here, we show that MtRecD exists in solution as a stable homodimer. Protein-DNA binding assays revealed that MtRecD binds efficiently to single-stranded DNA and linear duplexes containing 5 overhangs relative to the 3 overhangs but not to blunt-ended duplex. Furthermore, MtRecD bound more robustly to a variety of Y-shaped DNA structures having 18-nucleotide overhangs but not to a similar substrate containing 5-nucleotide overhangs. MtRecD formed more salt-tolerant complexes with Y-shaped structures compared with linear duplex having 3 overhangs. The intrinsic ATPase activity of MtRecD was stimulated by single-stranded DNA. Site-specific mutagenesis of Lys-179 in motif I abolished the ATPase activity of MtRecD. Interestingly, although MtRecD-catalyzed unwinding showed a markedly higher preference for duplex substrates with 5 overhangs, it could also catalyze significant unwinding of substrates containing 3 overhangs. These results support the notion that MtRecD is a bipolar helicase with strong 5 3 and weak 3 5 unwinding activities. The extent of unwinding of Y-shaped DNA structures was approximate to 3-fold lower compared with duplexes with 5 overhangs. Notably, direct interaction between MtRecD and its cognate RecA led to inhibition of DNA strand exchange promoted by RecA. Altogether, these studies provide the first detailed characterization of MtRecD and present important insights into the type of DNA structure the enzyme is likely to act upon during the processes of DNA repair or homologous recombination.

Cyclic Cationic Peptides Containing Sugar Amino Acids Selectively Distinguishes and Inhibits Maturation of Pre-miRNAs of the Same Family

The discovery of microRNAs (miRNAs) has added a new dimension to the gene regulatory networks, making aberrantly expressed miRNAs as therapeutically important targets. Small molecules that can selectively target and modulate miRNA levels can thus serve as lead structures. Cationic cyclic peptides containing sugar amino acids represent a new class of small molecules that can target miRNA selectively. Upon treatment of these small molecules in breast cancer cell line, we profiled 96 therapeutically important miRNAs associated with cancer and observed that these peptides can selectively target paralogous miRNAs of the same seed family. This selective inhibition is of prime significance in cases when miRNAs of the same family have tissue-specific expression and perform different functions. During these conditions, targeting an entire miRNA family could lead to undesired adverse effects. The selective targeting is attributable to the difference in the three-dimensional structures of precursor miRNAs. Hence, the core structure of these peptides can be used as a scaffold for designing more potent inhibitors of miRNA maturation and hence function.

Global response sensitivity analysis of uncertain structures

The problem of characterizing global sensitivity indices of structural response when system uncertainties are represented using probabilistic and (or) non-probabilistic modeling frameworks (which include intervals, convex functions, and fuzzy variables) is considered. These indices are characterized in terms of distance measures between a fiducial model in which uncertainties in all the pertinent variables are taken into account and a family of hypothetical models in which uncertainty in one or more selected variables are suppressed. The distance measures considered include various probability distance measures (Hellinger,l(2), and the Kantorovich metrics, and the Kullback-Leibler divergence) and Hausdorff distance measure as applied to intervals and fuzzy variables. Illustrations include studies on an uncertainly parametered building frame carrying uncertain loads. (C) 2015 Elsevier Ltd. All rights reserved.

Beta-Turn Conformations In Crystal-Structures Of Model Peptides Containing Alpha,Alpha-Di-N-Propylglycine And Alpha,Alpha-Di-N-Butylglycine

The crystal state conformations of three peptides containing the alpha, alpha-dialkylated residues, alpha,alpha-di-n-propylglycine (Dpg) and alpha,alpha-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Ala-OMe (I) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II beta-turn conformations with Ala (1) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: phi = 66.2 degrees, psi = 19.3 degrees; III: phi = 66.5 degrees, psi = 21.1 degrees) deviate appreciably from ideal values for the i + 2 residue in a type II beta-turn. In both peptides the observed (N...O) distances between the Boc CO and Ala(3) NH groups are far too long (I: 3.44 Angstrom; III: 3.63 Angstrom) for an intramolecular 4 --> 1 hydrogen bond. Boc-Ala-Dpg-Ala-NHMe (II) crystallizes with two independent molecules in the asymmetric unit. Both molecules IIA and IIB adopt consecutive beta-turn (type III-III in IIA and type III-I in IIB) or incipient 3(10)-helical structures, stabilized by two intramolecular 4 --> 1 hydrogen bonds. In all four molecules the bond angle N-C-alpha-C' (tau) at the Dxg residues are greater than or equal to 110 degrees. The observation of conformational angles in the helical region of phi,psi space at these residues is consistent with theoretical predictions.

Small-angle neutron scattering study of micellar structures of dimeric surfactants

Dimeric or gemini surfactants consist of two hydrophobic chains and two hydrophilic head groups co; valently connected by a hydrocarbon spacer. Small-angle neutron scattering measurements from bis-cationic C16H33N+(CH3)(2)-(CH2)(m)-N+(CH3)(2)C(16)H(33)2Br(-) dimeric surfactants, referred to-as 16-m-16, for different length of hydrocarbon spacers m-3-6, 8, 10, and 12, are reported. The measurements have been carried out at various concentrations: C=2.5 and 10 mM for all m and C=30 and 50 mM for m greater than or equal to 5. It is found that micellar structure depends on the length of the spacer. Micelles are disks for m=3, cylindrical for m=4, and prolate ellipsoidals for other values of m. These structural results are in agreement with the theoretical predictions based on the packing parameter. It has also been observed that conformation of the spacer and the hydrophobic chains in the interior of the micelle change as the length of the spacer is increased. The concentration dependence for m greater than or equal to 5 shows that the effect of surfactant concentration on the size of the micelle is more pronounced for m=5 and 12 than for the intermediate spacers. The fractional charge on the micelle increases with the increase in spacer length and decreases when the concentration is increased.

Supersonic flutter of composite skin panels of repeated-sublaminate layup

In high-speed aerospace vehicles, supersonic flutter is a well-known phenomenon of dynamic instability to which external skin panels are prone. In theory, the instability stage is expressed by the 'flutter critical parameter' Q(crit), which is a function of the stiffness-, and dynamic pressure parameters. For a composite skin panel, Q(crit) can be maximised by lay-up optimisation. Repeated-sublaminate lay-up schemes possess good potential for economical lay-up optimisation because the corresponding effort is limited to a family of sublaminates of few layers only. When Q(crit) is obtained for all sublaminates of a family, and the sublaminates ranked accordingly, the resulting ranking reveals not only the optimum lay-up, but also the near-optimum lay-ups, which are useful design alternatives, and the inferior lay-ups which should be avoided. In this paper, we examine sublaminate-ranking characteristics for a composite panel prone to supersonic flutter. In particular, we consider a simple supported midplane-symmetrical rectangular panel of typical aspect ratio alpha and flow angle psi, and for four-layered sublaminates, obtain the Q(crit)-based rankings for a wide range of the number of repeats, r. From the rankings, we find that an optimum lay-up can exist for which the outermost layer is oriented wide of, rather than along, the flow. Furthermore, for many lay-ups other than the optimum and the inferior, we see that as r increases, Q(crit) undergoes significant change in the course of converging. To reconcile these findings, eigenvalue-coalescence characteristics are discussed in detail for specific cases.

Synthesis, X-ray structures, and spectroscopic and electrochemical properties of (mu-oxo)bis(mu-carboxylato)diruthenium complexes having six imidazole bases as terminal ligands

Complexes [Ru2O(O2CR)(2)(1-MeIm)(6)](ClO4)(2) (la-c), [Ru2O(O2CR)(2)(ImH)(6)](ClO4)(2) (2a,b), and [Ru2O(O2CR)(2)(4-MeImH)(6)](ClO4)(2) (3a,b) with a (mu-oxo)bis(mu-carboxylato)diruthenium(III) core have been prepared by reacting Ru2Cl(O2CR)(4) with the corresponding imidazole base, viz. 1-methylimidazole (1-MeIm), imidazole (ImH), and 4-methylimidazole (4-MeImH) in methanol, followed by treatment with NaClO4 in water (R: Me, a; C6H4-p-OMe, b; C6H4-p-Me, c). Diruthenium(III,IV) complexes [Ru2O(O2CR)(2)(1-MeIm)(6)](ClO4)(3) (R: Me, 4a; C6H4-p-OMe, 4b; C6H4-p-Me, 4c) have been prepared by one-electron oxidation of 1 in MeCN with K2S2O8 in water. Complexes la, 2a . 3H(2)O, and 4a . 1.5H(2)O have been structurally characterized. Crystal data for the complexes are as follows: la, orthorhombic, P2(1)2(1)2(1), a = 7.659(3) Angstrom, b = 22.366(3) Angstrom, c = 23.688(2) Angstrom, V = 4058(2) Angstrom(3), Z = 4, R = 0.0475, and R-w = 0.0467 for 2669 reflections with F-o > 2 sigma(F-o); 2a . 3H(2)O, triclinic, , a = 13.735(3) Angstrom, b = 14.428(4) Angstrom, c = 20.515(8) Angstrom, alpha = 87.13(3)degrees, beta = 87.61(3)degrees, gamma = 63.92(2)degrees, V = 3646(2) Angstrom(3), Z = 4, R = 0.0485 and R-w = 0.0583 for 10 594 reflections with F-o > 6 sigma(F-o); 4a . 1.5H(2)O triclinic, , a = 11.969(3) Angstrom, b = 12.090(6) Angstrom, c = 17.421(3) Angstrom, alpha = 108.93(2)degrees, beta = 84.42(2)degrees, gamma = 105.97(2)degrees, V = 2292(1) Angstrom(3), Z = 2, R = 0.0567, and R-w = 0.0705 for 6775 reflections with F-o > 6 sigma(F-o). The complexes have a diruthenium unit held by an oxo and two carboxylate ligands, and the imidazole ligands occupy the terminal sites of the core. The Ru-Ru distance and the Ru-O-oxo-Ru angle in la and 2a . 3H(2)O are 3.266(1), 3.272(1) Angstrom and 122.4(4), 120.5(2)degrees, while in 4a . 1.5H(2)O these values are 3.327(1) Angstrom and 133.6(2)degrees. The diruthenium(III) complexes 1-3 are blue in color and they exhibit an intense visible band in the range 560-575 nm. The absorption is charge transfer in nature involving the Ru(III)-d pi and O-oxo-p pi orbitals. The diruthenium(III,IV) complexes are red in color and show an intense band near 500 nm. The diruthenium(III) core readily gets oxidized with K2S2O8 forming quantitatively the diruthenium(III,IV) complex. The visible spectral record of the conversion shows an isosbestic point at 545 nm for 1 and at 535 nm for 2 and 3. Protonation of the oxide bridge by HClO4 in methanol yields the [Ru-2(mu-OH)(mu-O2CR)(2)](3+) core. The hydroxo species shows a visible band al 550 nm. The pK(a) value for la is 2.45. The protonated species are unstable. The 1-MeIm species converts to the diruthenium(III,IV) core, while the imidazole complex converts to [Ru(ImH)(6)](3+) and some uncharacterized products. Complex [Ru(ImH)(6)](ClO4)(3) has been structurally characterized. The diruthenium(III) complexes are essentially diamagnetic and show characteristic H-1 NMR spectra indicating the presence of the dimeric structure in solution. The diruthenium(III,IV) complexes are paramagnetic and display rhombic EPR spectral features. Complexes 1-3 are redox active. Complex 1 shows the one-electron reversible Ru-2(III)/(RuRuIV)-Ru-III, one-electron quasireversible (RuRuIV)-Ru-III/Ru-2(IV), and two-electron quasireversible Ru-2(III)/Ru-2(II) couples near 0.4, 1.5, and -1.0 V vs SCE In MeCN-0.1 M TBAP, respectively, in the cyclic and differential pulse voltammetric studies. Complexes 2 and 3 exhibit only reversible Ru-2(III)/(RuRuIV)-Ru-III and the quasireversible (RuRuIV)-Ru-III/Ru-2(IV) couples near 0.4 and 1.6 V vs SCE, respectively, The observation of a quasireversible one-step two-electron transfer reduction process in 1 is significant considering its relevance to the rapid and reversible Fe-2(III)/Fe-2(II) redox process known for the tribridged diiron core in the oxy and deoxy forms of hemerythrin.

X-ray studies on crystalline complexes involving amino acids and peptides. XXXIII. Crystal structures of L- and DL-arginine complexed with oxalic acid and a comparative study of amino acid oxalic acid complexes

The DL- and L-arginine complexes of oxalic acid are made up of zwitterionic positively charged amino acid molecules and semi-oxalate ions. The dissimilar molecules aggregate into separate alternating layers in the former. The basic unit in the arginine layer is a centrosymmetric dimer, while the semi-oxalate ions form hydrogen-bonded strings in their layer. In the L-arginine complex each semi-oxalate ion is surrounded by arginine molecules and the complex can be described as an inclusion compound. The oxalic acid complexes of basic amino acids exhibit a variety of ionization states and stoichiometry. They illustrate the effect of aggregation and chirality on ionization state and stoichiometry, and that of molecular properties on aggregation. The semi-oxalate/oxalate ions tend to be planar, but large departures from planarity are possible. The amino acid aggregation in the different oxalic acid complexes do not resemble one another significantly, but the aggregation of a particular amino acid in its oxalic acid complex tends to have similarities with its aggregation in other structures. Also, semi-oxalate ions aggregate into similar strings in four of the six oxalic acid complexes. Thus, the intrinsic aggregation propensities of individual molecules tend to be retained in the complexes.

Synthesis, crystal structures, DNA binding and cleavage activity of L-glutamine copper(II) complexes of heterocyclic bases

Ternary L-glutamine (L-gln) copper(II) complexes [Cu(L-gln)(B)(H2O)](X) (B = 2,2'-bipyridine (bpy), X = 0.5SO(4)(2-), 1; B = 1,10-phenanthroline (phen), X = ClO4-, 2) and [Cu(L-gln)(dpq)(ClO4)] (3) (dpq, dipyridoquinoxaline) are prepared and characterized by physicochemical methods. The DNA binding and cleavage activity of the complexes have been studied. Complexes 1-3 are structurally characterized by X-ray crystallography. The complexes show distorted square pyramidal (4+1) CuN3O2 coordination geometry in which the N,O-donor amino acid and the N, N-donor heterocyclic base bind at the basal plane with a H2O or perchlorate as the axial ligand. The crystal structures of the complexes exhibit chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The complexes display a d-d electronic band in the range of 610-630 nm in aqueous-dimethylformamide (DMF) solution (9:1 v/v). The quasireversible cyclic voltammetric response observed near -0.1 V versus SCE in DMF-TBAP is assignable to the Cu(II)/Cu(I) couple. The binding affinity of the complexes to calf thymus (CT) DNA follows the order: 3 (dpq) > 2 (phen) >> 1 (bpy). Complexes 2 and 3 show DNA cleavage activity in dark in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent via a mechanistic pathway forming hydroxyl radical as the reactive species. The dpq complex 3 shows efficient photoinduced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency of the DNA minor groove binding complexes follows the order:3 > 2 >> 1. The dpq complex exhibits photocleavage of DNA on irradiation with visible light of 647.1 nm. Mechanistic data on the photo-induced DNA cleavage reactions reveal the involvement of singlet oxygen (O-1(2)) as the reactive species in a type-II pathway. (C) 2008 Elsevier B.V. All rights reserved.

Mutations in STIL, Encoding a Pericentriolar and Centrosomal Protein, Cause Primary Microcephaly

Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterized by smaller-than-normal brain size and mental retardation. MCPH is genetically heterogeneous with six known loci: MCPH1-MCPH6. We report mapping of a novel locus, MCPH7, to chromosome 1p32.3-p33 between markers D1S2797 and D1S417, corresponding to a physical distance of 8.39 Mb. Heterogeneity analysis of 24 families previously excluded from linkage to the six known MCPH loci suggested linkage of five families (20.83%) to the MCPH7 locus. In addition, four families were excluded from linkage to the MCPH7 locus as well as all of the six previously known loci, whereas the remaining 15 families could not be conclusively excluded or included. The combined maximum two-point LOD score for the linked families was 5.96 at marker D1S386 at theta = 0.0. The combined multipoint LOD score was 6.97 between markers D1S2797 and D1S417. Previously, mutations in four genes, MCPH1, CDK5RAP2, ASPM, and CENPJ, that code for centrosomal proteins have been shown to cause this disorder. Three different homozygous mutations in STIL, which codes for a pericentriolar and centrosomal protein, were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the STIL protein. Further, another recently ascertained family was homozygous for the same mutation as one of the original families. There was no evidence for a common haplotype. These results suggest that the centrosome and its associated structures are important in the control of neurogenesis in the developing human brain.

Equivalent Circuit Analysis of Serpentine Folded-waveguide Slow-wave Structures for Millimeter-wave Traveling-wave Tubes

A simple equivalent circuit model for the analysis of dispersion and interaction impedance characteristics of serpentine folded-waveguide slow-wave structure was developed by considering the straight and curved portions of structure supporting the dominant TE10-mode of the rectangular waveguide. Expressions for the lumped capacitance and inductance per period of the slow-wave structure were derived in terms of the physical dimensions of the structure, incorporating the effects of the beam-hole in the lumped parameters. The lumped parameters were subsequently interpreted for obtaining the dispersion and interaction impedance characteristics of the structure. The analysis was simple yet accurate in predicting the dispersion and interaction impedance behaviour at millimeter-wave frequencies. The analysis was benchmarked against measurement as well as with 3D electromagnetic modeling using MAFIA for two typical slow-wave structures (one at the Ka-band and the other at the W-band) and close agreement observed.

Analysis of Rectangular Folded-Waveguide Millimeter-Wave Slow-wave Structures using Conformal Transformations

An analysis of rectangular folded-waveguide slow-wave structure was developed using conformal mapping technique through Schwarz's polygon transformation and closed form expressions for the lumped capacitance and inductance per period of the slow-wave structure were derived in terms of the physical dimensions of the structure, incorporating the effects of the beam hole in the lumped parameters. The lumped parameters were subsequently interpreted for obtaining the dispersion and interaction impedance characteristics of the structure. The analysis was benchmarked for two typical millimeter-wave structures, one operating in Ka-band and the other operating in Q-band, against measurement and 3D electromagnetic modeling using MAFIA.

PocketMatch: A new algorithm to compare binding sites in protein structures

Recognizing similarities and deriving relationships among protein molecules is a fundamental requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison. Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. A comparison with other site matching algorithms is also presented. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless combined with chemical nature of amino acids. Conclusion: A new algorithm has been developed to compare binding sites in accurate, efficient and high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250(th) second for one comparison on a single processor. A parallel version on BlueGene has also been implemented.

A comparative study of the energetics, structures, and mechanisms of the HCN H HNC and LiCN <-> LiNC isomerizations

The potential energy surfaces of the HCN<->HNC and LiCN<->LiNC isomerization processes were determined by ab initio theory using fully optimized triple-zeta double polarization types of basis sets. Both the MP2 corrections and the QCISD level of calculations were performed to correct for the electron correlation. Results show that electron correlation has a considerable influence on the energetics and structures. Analysis of the intramolecular bond rearrangement processes reveals that, in both cases, H (or Li+) migrates in an almost elliptic path in the plane of the molecule. In HCN<->HNC, the migrating hydrogen interacts with the in-plane pi,pi* orbitals of CN, leading to a decrease in the C-N bond order. In LiCN<->LiNC, Li+ does not interact with the corresponding pi,pi* orbitals of CN.