Shear tests of rivet fastened rectangular hollow flange channel beams

The intermittently rivet fastened Rectangular Hollow Flange Channel Beam (RHFCB) is a new cold-formed hollow section proposed as an alternative to welded hollow flange channel beams. It is a monosymmetric channel section made by intermittently rivet fastening two torsionally rigid rectangular hollow flanges to a web plate. This process enables the end users to choose an effective combination of different web and flange plate sizes to achieve optimum design capacities. Recent research studies focused mainly on the shear behaviour of the most commonly used lipped channel beam and welded hollow flange beam sections. However, the shear behaviour of rivet fastened RHFCB has not been investigated. Therefore a detailed experimental study involving 24 shear tests was undertaken to investigate the shear behaviour and capacities of rivet fastened RHFCBs. Simply supported test specimens of RHFCB with aspect ratios of 1.0 and 1.5 were loaded at mid-span until failure. Comparison of experimental shear capacities with corresponding predictions from the current Australian cold-formed steel design rules showed that the current design rules are very conservative for the shear design of rivet fastened RHFCBs. Significant improvements to web shear buckling occurred due to the presence of rectangular hollow flanges while considerable post-buckling strength was also observed. Such enhancements to the shear behaviour and capacity were achieved with a rivet spacing of 100 mm. Improved design rules were proposed for rivet fastened RHFCBs based on the current shear design equations in AISI S100 and the direct strength method. This paper presents the details of this experimental investigation and the results.

Shear tests of rivet fastened rectangular hollow flange channel beams with web openings

The rivet-fastened rectangular hollow flange channel beam (RHFCB) is a new cold-formed hollow section proposed as an alternative to welded hollow flange steel beams. No research has been undertaken on the shear behaviour and strength of rivet fastened RHFCBs with web openings. Hence a detailed experimental study involving 30 shear tests was undertaken to investigate the shear behaviour and strength of rivet fastened RHFCBs with web openings. Experimental results showed that the current design rules are inadequate for the shear design of Rivet fastened RHFCBs with web openings. Improved design equations have been proposed for the shear strength of rivet fastened RHFCBs with web openings.

Web crippling tests of rivet fastened rectangular hollow flange channel beams under two-flange load cases

The rivet-fastened rectangular hollow flange channel beam (RHFCB) is a new cold-formed hollow section proposed as an alternative to welded hollow flange steel beams. To date, no investigation has been conducted on their web crippling behaviour and strengths. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of rivet fastened RHFCBs under End Two Flange (ETF) and Interior Two Flange (ITF) load cases. Experimental results showed that the current design rules are unconservative for rivet fastened RHFCB sections under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of rivet fastened RHFCBs.

Deciphering the Distinct Role for the Metal Coordination Motif in the Catalytic Activity of Mycobacterium smegmatis Topoisomerase I

Mycobacterium smegmatis topoisomerase I (Mstopol) is distinct from typical type IA topoisomerases. The enzyme binds to both single- and double-stranded DNA with high affinity, making specific contacts. The enzyme comprises conserved regions similar to type IA topoisomerases from Escherichia coli and other eubacteria but lacks the typically found zinc fingers in the carboxy-terminal domain. The enzyme can perform DNA cleavage m the absence of Mg2+ but religation needs exogenously added Mg2+. One molecule of Mg2+ tightly bound to the enzyme has no role in DNA cleavage but is needed only for the religation reaction. The toprim. (topoisomerase-primase) domain in MstopoI comprising the Mg2+ binding pocket, conserved in both type IA and type II topoisomerases, was subjected to mutagenesis to understand the role of Mg2+, in different steps of the reaction. The residues D108, D110, and E112 of the enzyme, which form the acidic triad in the DXDXE motif, were changed to alanines. D108A mutation resulted in an enzyme that is Mg2+ dependent for DNA cleavage unlike Mstopol and exhibited enhanced DNA cleavage property and reduced religation activity. The mutant was toxic for cell growth, most likely due to the imbalance in cleavage-religation equilibrium. In contrast, the E112A mutant behaved like wild-type enzyme, cleaving DNA in a Mg2+-independent fashion, albeit to a reduced extent. Intra- and intermolecular religation assays indicated specific roles for D108 and E112 residues during the reaction. Together, these results indicate that the D108 residue has a major role during cleavage and religation, while E112 is important for enhancing the efficiency of cleavage. Thus, although architecturally and mechanistically similar to topoisomerase I from E. coli, the metal coordination pattern of the mycobacterial enzyme is distinct, opening up avenues to exploit the enzyme to develop inhibitors.

Increased Efficacies of an Individual Catalytic Site in Clustered Multivalent Dendritic Catalysts

In the studies reported so far on dendrimer-mediated catalysis, the efficacies of the catalytic units were studied and compared primarily across the generations. In order to identify the efficacy of an individual catalytic unit with respect to the number of such units present within a given generation, a series of catalysts were prepared within a generation. Dendrimers incorporated with phosphinemetal complexes were chosen for the study and as many as 11 catalysts within three generations were synthesized. The C-C bond-forming reactions, namely, the Heck and the Suzuki coupling reactions, were then selected to study the catalytic efficiencies of the series of partially and fully phosphine-metal complex functionalized dendrimers. The efficacies of the formation of cinnamate and biphenyl. catalyzed by the dendritic catalysts, were compared. The comparative analyses show that an individual catalytic site is far more effective in its catalytic activity when presented in multiple numbers, i.e., in a multivalent dendritic system, than as a single unit within the same generation, i.e., in a monovalent dendritic system. The study identifies the beneficial effects of the multivalent presentation of the catalytic moieties, both within and across the dendrimer generations.

Mutations of mitochondrial DNA polymerase gamma: an important cause of neurological disorders

Thesis focuses on mutations of POLG1 gene encoding catalytic subunit polγ-α of mitochondrial DNA polymerase gamma holoenzyme (polG) and the association of mutations with different clinical phenotypes. In addition, particular defective mutant variants of the protein were characterized biochemically in vitro. PolG-holoenzyme is the sole DNA polymerase found in mitochondria. It is involved in replication and repair of the mitochondrial genome, mtDNA. Holoenzyme also includes the accessory subunit polγ-β, which is required for the enhanced processivity of polγ-α. Defective polγ-α causes accumulation of secondary mutations on mtDNA, which leads to a defective oxidative phosphorylation system. The clinical consequences of such mutations are variable, affecting nervous system, skeletal muscles, liver and other post-mitotic tissues. The aims of the studies included: 1) Determination of the role of POLG1 mutations in neurological syndromes with features of mitochondrial dysfunction and an unknown molecular cause. 2) Development and set up of diagnostic tests for routine clinical purposes. 3) Biochemical characterization of the functional consequences of the identified polγ-α variants. Studies describe new neurological phenotypes in addition to PEO caused by POLG1 mutations, including parkinsonism, premature amenorrhea, ataxia and Parkinson s disease (PD). POLG1 mutations and polymorphisms are both common and/or potential genetic risk factors at least among the Finnish population. The major findings and applications reported here are: 1) POLG1 mutations cause parkinsonism and premature menopause in PEO families in either a recessive or a dominant manner. 2) A common recessive POLG1 mutations (A467T and W748S) in the homozygous state causes severe adult or juvenile-onset ataxia without muscular symptoms or histological or mtDNA abnormalities in muscles. 3) A common recessive pathogenic change A467T can also cause a mild dominant disease in heterozygote carriers. 4) The A467T variant shows reduced polymerase activity due to defective template binding. 5) Rare polyglutamine tract length variants of POLG1 are significantly enriched in Finnish idiopathic Parkinson s disease patients. 6) Dominant mutations are clearly restricted to the highly conserved polymerase domain motifs, whereas recessive ones are more evenly distributed along the protein. The present results highlight and confirm the new role of mitochondria in parkinsonism/Parkinson s disease and describe a new mitochondrial ataxia. Based on these results, a POLG1 diagnostic routine has been set up in Helsinki University Central Hospital (HUSLAB).

Substrate specificity plays an important role in uncoupling the catalytic and scaffolding activities of rat testis DNA topoisomerase IIalpha

Topoisomerase II (topo II) is a dyadic enzyme found in all eukaryotic cells. Topo II is involved in a number of cellular processes related to DNA metabolism, including DNA replication, recombination and the maintenance of genomic stability. We discovered a correlation between the development of postnatal testis and increased binding of topo IIalpha to the chromatin fraction. We used this observation to characterize DNA-binding specificity and catalytic properties of purified testis topo IIalpha. The results indicate that topo IIalpha binds a substrate containing the preferred site with greater affinity and, consequently, catalyzes the conversion of form I to form IV DNA more efficiently in contrast to substrates lacking such a site. Interestingly, topo IIalpha displayed high-affinity and cooperativity in binding to the scaffold associated region. In contrast to the preferred site, however, high-affinity binding of topo IIalpha to the scaffold-associated region failed to result in enhanced catalytic activity. Intriguingly, competition assays involving scaffold-associated region revealed an additional DNA-binding site within the dyadic topo IIalpha. These results implicate a dual role for topo IIalpha in vivo consistent with the notion that its sequestration to the chromatin might play a role in chromosome condensation and decondensation during spermatogenesis.

Electronic coupling and catalytic effect on H2 evolution of MoS2/graphene nanocatalyst

Inorganic nano-graphene hybrid materials that are strongly coupled via chemical bonding usually present superior electrochemical performance. However, how the chemical bond forms and the synergistic catalytic mechanism remain fundamental questions. In this study, the chemical bonding of the MoS2 nanolayer supported on vacancy mediated graphene and the hydrogen evolution reaction of this nanocatalyst system were investigated. An obvious reduction of the metallic state of the MoS2 nanolayer is noticed as electrons are transferred to form a strong contact with the reduced graphene support. The missing metallic state associated with the unsaturated atoms at the peripheral sites in turn modifies the hydrogen evolution activity. The easiest evolution path is from the Mo edge sites, with the presence of the graphene resulting in a decrease in the energy barrier from 0.17 to 0.11 eV. Evolution of H2 from the S edge becomes more difficult due to an increase in the energy barrier from 0.43 to 0.84 eV. The clarification of the chemical bonding and catalytic mechanisms for hydrogen evolution using this strongly coupled MoS2/graphene nanocatalyst provide a valuable source of reference and motivation for further investigation for improved hydrogen evolution using chemically active nanocoupled systems.

An Insight to the Dynamics of Conserved Water Molecular Triad in IMPDH II (Human): Recognition of Cofactor and Substrate to Catalytic Arg 322

Inosine 5' monophosphate dehydrogenase (IMPDH II) is a key enzyme involved in the de novo biosynthesis pathway of purine nucleotides and is also considered to be an excellent target for cancer inhibitor design. The conserve R 322 residue (in human) is thought to play some role in the recognition of inhibitor and cofactor through the catalytic D 364 and N 303. The 15 ns simulation and the water dynamics of the three different PDB structures (1B3O, 1NF7, and 1NFB) of human IMPDH by CHARMM force field have clearly indicated the involvement of three conserved water molecules (W-L, W-M, and W-C) in the recognition of catalytic residues (R 322, D 364, and N 303) to inhibitor and cofactor. Both the guanidine nitrogen atoms (NH1 and NH 2) of the R 322 have anchored the di- and mono-nucleotide (cofactor and inhibitor) binding domains via the conserved W-C and W-L water molecules. Another conserved water molecule W-M seems to bridge the two domains including the R 322 and also the W-C and W-L through seven centers H-bonding coordination. The conserved water molecular triad (W-C - W-M - W-L) in the protein complex may thought to play some important role in the recognition of inhibitor and cofactor to the protein through R 322 residue.

Catalytic cyclopropanation of olefins using copper(I) diphosphinoamines

Catalytic cyclopropanation reactions of olefins with ethyl diazoacetate were carried out using copper(I) diphosphinoamine (PPh2)(2)N(R) (R = Pr-i, H, Ph and -CH2-C6H4-CH=CH2) complexes at 40 degrees C in chloroform. High yields of the cyclopropanes were obtained in all cases. The rate of the reaction was influenced by the nuclearity of the complex and the binding mode of the ligand which was either bridging or chelating. Comparison of isostructural complexes shows that the rate follows the order R = Pr-i > H > Ph, where R is the substituent on the N. However, cyclopropane formation versus dimerization of the carbene, and trans to cis ratios of cyclopropane was similar in all cases. The nearly identical selectivity for different products formed was indicative of a common catalytic intermediate. A labile "copper-olefin" complex which does not involve the phosphine or the counterion is the most likely candidate. The differences in the reaction rates for different complexes are attributed to differences in the concentration of the catalytically active species which are in equilibrium with the catalytically inactive copper-phosphinoamine complex. To test the hypothesis a diphosphinoamine polymer complexed to copper(I) was used as a heterogeneous catalyst. Leaching of copper(I) and deactivation of the catalyst confirmed the proposed mechanism. (C) 2008 Elsevier B. V. All rights reserved.

Hydrocarbon oxidation and three-way catalytic activity on a single step directly coated cordierite monolith: High catalytic activity of Ce0.98Pd0.02O2−δ

Catalytic activity of cordierite honeycomb by a completely new coating method for the oxidation of major hydrocarbons in exhaust gas is reported here. The new coating process consists of (a) dipping and growing γ-Al2O3 on cordierite by combustion of monolith dipped in the aqueous solution of Al(NO3)3 and oxalyldihydrazide (ODH) (or glycine) at 600 °C and active catalyst phase Ce0.98Pd0.02O2−δ on γ-Al2O3-coated cordierite again by combustion of monolith dipped in the aqueous solution of ceric ammonium nitrate, ODH and 1.2 × 10−3 M PdCl2 solution at 500 °C. Weight of active catalyst can be varied from 0.02 wt% to 2 wt% which is sufficient but can be loaded even up to 12 wt% by repeating dip dry combustion. Adhesion of catalyst to cordierite surface is via oxide growth, which is very strong. ‘HC’ oxidation over the monolith catalyst is carried out with a mixture having the composition, 470 ppm of both propene and propane and 870 ppm of both ethylene and acetylene with the varying amount of O2. Three-way catalytic test is done by putting hydrocarbon mixture along with CO (10 000 ppm), NO (2000 ppm) and O2 (15 000 ppm). Below 350 °C full conversion is achieved. In this method, handling of nano-material powder is avoided.

Conditional Probability-Based Significance Tests for Sequential Patterns in Multineuronal Spike Trains

We consider the problem of detecting statistically significant sequential patterns in multineuronal spike trains. These patterns are characterized by ordered sequences of spikes from different neurons with specific delays between spikes. We have previously proposed a data-mining scheme to efficiently discover such patterns, which occur often enough in the data. Here we propose a method to determine the statistical significance of such repeating patterns. The novelty of our approach is that we use a compound null hypothesis that not only includes models of independent neurons but also models where neurons have weak dependencies. The strength of interaction among the neurons is represented in terms of certain pair-wise conditional probabilities. We specify our null hypothesis by putting an upper bound on all such conditional probabilities. We construct a probabilistic model that captures the counting process and use this to derive a test of significance for rejecting such a compound null hypothesis. The structure of our null hypothesis also allows us to rank-order different significant patterns. We illustrate the effectiveness of our approach using spike trains generated with a simulator.