Magnetic and superconducting phase diagrams of single-crystal Er0.8R0.2Ni2B2C (R=Tb,Lu) and ErNi1.9Co0.1B2C: Identification of pair-breaking mechanisms

NASA Astrophysics Data System (ADS)

Takeya, H.; El Massalami, M.

2004-01-01

We investigated the magnetism, superconductivity and their interplay in single crystals Er0.8R0.2Ni2B2C (R=Tb,Lu) and ErNi1.9Co0.1B2C. In contrast to Co substitution, R substitutions induce considerable modifications in the magnetism of Er sublattice: e.g., Tb (Lu) substitution enhances (reduces) TN and critical fields. Both R substitutions introduce size effects and pinning centers; the former modifies the magnon specific heat while the latter hinders the formation of a weak ferromagnetism. The superconductivity, on the other hand, is strongly (weakly) influenced by Tb and Co (Lu) substitution. Taking LuNi2B2C as a nonmagnetic superconducting limit, we analyzed their superconductivities, as well as that of ErNi2B2C, in terms of multiple pair breaking theory on dirty superconductors. Based on this analysis, many of their superconducting features can be explained: The breakdown of de Gennes scaling is due to the presence of multiple pair breakers, the anisotropy of Hc2(T) is related to the magnetic anisotropy, the absence of a structure in Hc2(T) at TN of Lu substitution (TN

Ultra-superovulation for the CRISPR-Cas9-mediated production of gene-knockout, single-amino-acid-substituted, and floxed mice.

PubMed

Nakagawa, Yoshiko; Sakuma, Tetsushi; Nishimichi, Norihisa; Yokosaki, Yasuyuki; Yanaka, Noriyuki; Takeo, Toru; Nakagata, Naomi; Yamamoto, Takashi

2016-08-15

Current advances in producing genetically modified mice using genome-editing technologies have indicated the need for improvement of limiting factors including zygote collection for microinjection and their cryopreservation. Recently, we developed a novel superovulation technique using inhibin antiserum and equine chorionic gonadotropin to promote follicle growth. This method enabled the increased production of fertilized oocytes via in vitro fertilization compared with the conventional superovulation method. Here, we verify that the ultra-superovulation technique can be used for the efficient generation of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated knockout mice by microinjection of plasmid vector or ribonucleoprotein into zygotes. We also investigated whether single-amino-acid-substituted mice and conditional knockout mice could be generated. Founder mice bearing base substitutions were generated more efficiently by co-microinjection of Cas9 protein, a guide RNA and single-stranded oligodeoxynucleotide (ssODN) than by plasmid microinjection with ssODN. The conditional allele was successfully introduced by the one-step insertion of an ssODN designed to carry an exon flanked by two loxP sequences and homology arms using a double-cut CRISPR-Cas9 strategy. Our study presents a useful method for the CRISPR-Cas9-based generation of genetically modified mice from the viewpoints of animal welfare and work efficiency. © 2016. Published by The Company of Biologists Ltd.

Comparison of Relative Binding Affinities for Trout and Human Estrogen Receptor Based upon Different Competitive Binding Assays

EPA Science Inventory

The development of a predictive model based upon a single aquatic species inevitably raises the question of whether this information is valid for other species. To partially address this question, relative binding affinities (RBA) for six alkylphenols (para-substituted, n- and b...

A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus.

PubMed Central

Ito, M; Mori, Y; Oiso, Y; Saito, H

1991-01-01

To elucidate the molecular mechanism of familial central diabetes insipidus (FDI), we sequenced the arginine vasopressin-neurophysin II (AVP-NPII) gene in 2 patients belonging to a pedigree that is consistent with an autosomal dominant mode of inheritance. 10 patients with idiopathic central diabetes insipidus (IDI) and 5 normals were also studied. The AVP-NPII gene, locating on chromosome 20, consists of three exons that encode putative signal peptide, AVP, NPII, and glycoprotein. Using polymerase chain reaction, fragments including the promoter region and all coding regions were amplified from genomic DNA and subjected to direct sequencing. Sequences of 10 patients with IDI were identical with those of normals, while in 2 patients with FDI, a single base substitution was detected in one of two alleles of the AVP-NPII gene, indicating they were heterozygotes for this mutation. It was a G----A transition at nucleotide position 1859 in the second exon, resulting in a substitution of Gly for Ser at amino acid position 57 in the NPII moiety. It was speculated that the mutated AVP-NPII precursor or the mutated NPII molecule, through their conformational changes, might be responsible for AVP deficiency. Images PMID:1840604

Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana

PubMed Central

Belfield, Eric J.; Gan, Xiangchao; Mithani, Aziz; Brown, Carly; Jiang, Caifu; Franklin, Keara; Alvey, Elizabeth; Wibowo, Anjar; Jung, Marko; Bailey, Kit; Kalwani, Sharan; Ragoussis, Jiannis; Mott, Richard; Harberd, Nicholas P.

2012-01-01

Ionizing radiation has long been known to induce heritable mutagenic change in DNA sequence. However, the genome-wide effect of radiation is not well understood. Here we report the molecular properties and frequency of mutations in phenotypically selected mutant lines isolated following exposure of the genetic model flowering plant Arabidopsis thaliana to fast neutrons (FNs). Previous studies suggested that FNs predominantly induce deletions longer than a kilobase in A. thaliana. However, we found a higher frequency of single base substitution than deletion mutations. While the overall frequency and molecular spectrum of fast-neutron (FN)–induced single base substitutions differed substantially from those of “background” mutations arising spontaneously in laboratory-grown plants, G:C>A:T transitions were favored in both. We found that FN-induced G:C>A:T transitions were concentrated at pyrimidine dinucleotide sites, suggesting that FNs promote the formation of mutational covalent linkages between adjacent pyrimidine residues. In addition, we found that FNs induced more single base than large deletions, and that these single base deletions were possibly caused by replication slippage. Our observations provide an initial picture of the genome-wide molecular profile of mutations induced in A. thaliana by FN irradiation and are particularly informative of the nature and extent of genome-wide mutation in lines selected on the basis of mutant phenotypes from FN-mutagenized A. thaliana populations. PMID:22499668

Mutational analysis of the transcriptional activator VirG of Agrobacterium tumefaciens.

PubMed Central

Scheeren-Groot, E P; Rodenburg, K W; den Dulk-Ras, A; Turk, S C; Hooykaas, P J

1994-01-01

To find VirG proteins with altered properties, the virG gene was mutagenized. Random chemical mutagenesis of single-stranded DNA containing the Agrobacterium tumefaciens virG gene led with high frequency to the inactivation of the gene. Sequence analysis showed that 29% of the mutants contained a virG gene with one single-base-pair substitution somewhere in the open reading frame. Thirty-nine different mutations that rendered the VirG protein inactive were mapped. Besides these inactive mutants, two mutants in which the vir genes were active even in the absence of acetosyringone were found on indicator plates. A VirG protein with an N54D substitution turned out to be able to induce a virB-lacZ reporter gene to a high level even in the absence of the inducer acetosyringone. A VirG protein with an I77V substitution exhibited almost no induction in the absence of acetosyringone but showed a maximum induction level already at low concentrations of acetosyringone. Images PMID:7961391

The roles of word-form frequency and phonological neighbourhood density in the acquisition of Lithuanian noun morphology.

PubMed

Savičiūtė, Eglė; Ambridge, Ben; Pine, Julian M

2018-05-01

Four- and five-year-old children took part in an elicited familiar and novel Lithuanian noun production task to test predictions of input-based accounts of the acquisition of inflectional morphology. Two major findings emerged. First, as predicted by input-based accounts, correct production rates were correlated with the input frequency of the target form, and with the phonological neighbourhood density of the noun. Second, the error patterns were not compatible with the systematic substitution of target forms by either (a) the most frequent form of that noun or (b) a single morphosyntactic default form, as might be predicted by naive versions of a constructivist and generativist account, respectively. Rather, most errors reflected near-miss substitutions of singular for plural, masculine for feminine, or nominative/accusative for a less frequent case. Together, these findings provide support for an input-based approach to morphological acquisition, but are not adequately explained by any single account in its current form.

Postgrowth tuning of the bandgap of single-layer molybdenum disulfide films by sulfur/selenium exchange.

PubMed

Ma, Quan; Isarraraz, Miguel; Wang, Chen S; Preciado, Edwin; Klee, Velveth; Bobek, Sarah; Yamaguchi, Koichi; Li, Emily; Odenthal, Patrick Michael; Nguyen, Ariana; Barroso, David; Sun, Dezheng; von Son Palacio, Gretel; Gomez, Michael; Nguyen, Andrew; Le, Duy; Pawin, Greg; Mann, John; Heinz, Tony F; Rahman, Talat Shahnaz; Bartels, Ludwig

2014-05-27

We demonstrate bandgap tuning of a single-layer MoS2 film on SiO2/Si via substitution of its sulfur atoms by selenium through a process of gentle sputtering, exposure to a selenium precursor, and annealing. We characterize the substitution process both for S/S and S/Se replacement. Photoluminescence and, in the latter case, X-ray photoelectron spectroscopy provide direct evidence of optical band gap shift and selenium incorporation, respectively. We discuss our experimental observations, including the limit of the achievable bandgap shift, in terms of the role of stress in the film as elucidated by computational studies, based on density functional theory. The resultant films are stable in vacuum, but deteriorate under optical excitation in air.

Intermolecular interactions of trifluorohalomethanes with Lewis bases in the gas phase: an ab initio study.

PubMed

Wang, Yi-Siang; Yin, Chih-Chien; Chao, Sheng D

2014-10-07

We perform an ab initio computational study of molecular complexes with the general formula CF3X-B that involve one trifluorohalomethane CF3X (X = Cl or Br) and one of a series of Lewis bases B in the gas phase. The Lewis bases are so chosen that they provide a range of electron-donating abilities for comparison. Based on the characteristics of their electron pairs, we consider the Lewis bases with a single n-pair (NH3 and PH3), two n-pairs (H2O and H2S), two n-pairs with an unsaturated bond (H2CO and H2CS), and a single π-pair (C2H4) and two π-pairs (C2H2). The aim is to systematically investigate the influence of the electron pair characteristics and the central atom substitution effects on the geometries and energetics of the formed complexes. The counterpoise-corrected supermolecule MP2 and coupled-cluster single double with perturbative triple [CCSD(T)] levels of theory have been employed, together with a series of basis sets up to aug-cc-pVTZ. The angular and radial configurations, the binding energies, and the electrostatic potentials of the stable complexes have been compared and discussed as the Lewis base varies. For those complexes where halogen bonding plays a significant role, the calculated geometries and energetics are consistent with the σ-hole model. Upon formation of stable complexes, the C-X bond lengths shorten, while the C-X vibrational frequencies increase, thus rendering blueshifting halogen bonds. The central atom substitution usually enlarges the intermolecular bond distances while it reduces the net charge transfers, thus weakening the bond strengths. The analysis based on the σ-hole model is grossly reliable but requires suitable modifications incorporating the central atom substitution effects, in particular, when interaction components other than electrostatic contributions are involved.

Intermolecular interactions of trifluorohalomethanes with Lewis bases in the gas phase: An ab initio study

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

Wang, Yi-Siang; Yin, Chih-Chien; Chao, Sheng D., E-mail: sdchao@spring.iam.ntu.edu.tw

2014-10-07

We perform an ab initio computational study of molecular complexes with the general formula CF{sub 3}X—B that involve one trifluorohalomethane CF{sub 3}X (X = Cl or Br) and one of a series of Lewis bases B in the gas phase. The Lewis bases are so chosen that they provide a range of electron-donating abilities for comparison. Based on the characteristics of their electron pairs, we consider the Lewis bases with a single n-pair (NH{sub 3} and PH{sub 3}), two n-pairs (H{sub 2}O and H{sub 2}S), two n-pairs with an unsaturated bond (H{sub 2}CO and H{sub 2}CS), and a single π-pairmore » (C{sub 2}H{sub 4}) and two π-pairs (C{sub 2}H{sub 2}). The aim is to systematically investigate the influence of the electron pair characteristics and the central atom substitution effects on the geometries and energetics of the formed complexes. The counterpoise-corrected supermolecule MP2 and coupled-cluster single double with perturbative triple [CCSD(T)] levels of theory have been employed, together with a series of basis sets up to aug-cc-pVTZ. The angular and radial configurations, the binding energies, and the electrostatic potentials of the stable complexes have been compared and discussed as the Lewis base varies. For those complexes where halogen bonding plays a significant role, the calculated geometries and energetics are consistent with the σ-hole model. Upon formation of stable complexes, the C–X bond lengths shorten, while the C–X vibrational frequencies increase, thus rendering blueshifting halogen bonds. The central atom substitution usually enlarges the intermolecular bond distances while it reduces the net charge transfers, thus weakening the bond strengths. The analysis based on the σ-hole model is grossly reliable but requires suitable modifications incorporating the central atom substitution effects, in particular, when interaction components other than electrostatic contributions are involved.« less

Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity.

PubMed

Seidman, M M; Bredberg, A; Seetharam, S; Kraemer, K H

1987-07-01

Mutagenesis was studied at the DNA-sequence level in human fibroblast and lymphoid cells by use of a shuttle vector plasmid, pZ189, containing a suppressor tRNA marker gene. In a series of experiments, 62 plasmids were recovered that had two to six base substitutions in the 160-base-pair marker gene. Approximately 20-30% of the mutant plasmids that were recovered after passing ultraviolet-treated pZ189 through a repair-proficient human fibroblast line contained these multiple mutations. In contrast, passage of ultraviolet-treated pZ189 through an excision-repair-deficient (xeroderma pigmentosum) line yielded only 2% multiple base substitution mutants. Introducing a single-strand nick in otherwise unmodified pZ189 adjacent to the marker, followed by passage through the xeroderma pigmentosum cells, resulted in about 66% multiple base substitution mutants. The multiple mutations were found in a 160-base-pair region containing the marker gene but were rarely found in an adjacent 170-base-pair region. Passing ultraviolet-treated or nicked pZ189 through a repair-proficient human B-cell line also yielded multiple base substitution mutations in 20-33% of the mutant plasmids. An explanation for these multiple mutations is that they were generated by an error-prone polymerase while filling gaps. These mutations share many of the properties displayed by mutations in the immunoglobulin hypervariable regions.

Candida kantuleensis sp. nov., a d-xylose-fermenting yeast species isolated from peat in a tropical peat swamp forest.

PubMed

Nitiyon, Sukanya; Khunnamwong, Pannida; Lertwattanasakul, Noppon; Limtong, Savitree

2018-05-24

Three strains (DMKU-XE11 T , DMKU-XE15 and DMKU-XE20) representing a single novel anamorphic and d-xylose-fermenting yeast species were obtained from three peat samples collected from Khan Thulee peat swamp forest in Surat Thani province, Thailand. The strains differed from each other by one to two nucleotide substitutions in the sequences of the D1/D2 region of the large subunit (LSU) rRNA gene and zero to one nucleotide substitution in the internal transcribed spacer (ITS) region. Phylogenetic analysis based on the combined sequences of the ITS and the D1/D2 regions showed that the three strains represented a single Candida species that was distinct from the other related species in the Lodderomyces/Candida albicans clade. The three strains form a subclade with the other Candida species including Candida sanyaensis, Candida tropicalis and Candida sojae. C. sanyaensis was the most closely related species, with 2.1-2.4 % nucleotide substitutions in the D1/D2 region of the LSU rRNA gene, and 3.8-4.0 % nucleotide substitutions in the ITS region. The three strains (DMKU-XE11 T , DMKU-XE15 and DMKU-XE20) were assigned as a single novel species, which was named Candida kantuleensis sp. nov. The type strain is DMKU-XE11 T (=CBS 15219 T =TBRC 7764 T ). The MycoBank number for C. kantuleensis sp. nov. is MB 824179.

Non-chemically amplified 193-nm top surface imaging photoresist development: polymer substituent and polydispersity effects

NASA Astrophysics Data System (ADS)

Kim, Myoung-Soo; Kim, Hyoung-Gi; Kim, Hyeong-Soo; Baik, Ki-Ho; Johnson, Donald W.; Cernigliaro, George J.; Minsek, David W.

1999-06-01

Thin film imaging processes such as top surface imaging (TSI) are candidates for sub-150 nm lithography using 193 nm lithography. Single component, non-chemically amplified, positive tone TSI photoresists based on phenolic polymers demonstrate good post-etch contrast, resolution, and minimal line edge roughness, in addition to being the most straightforward thin film imaging approach. In this approach, ArF laser exposure results directly in radiation- induced crosslinking of the phenolic polymer, followed by formation of a thin etch mask at the surface of the un- exposed regions by vapor-phase silylation, followed by reactive ion etching of the non-silylated regions. However, single component resists based on poly(para-hydroxystryene) (PHS), such as MicroChem's Nano MX-P7, suffer from slow photospeed as well as low silylation contrast which can cause reproducibility and line-edge-roughness problems. We report that selected aromatic substitution of the poly(para- hydroxystryene) polymer can increase the photospeed by up to a factor of four relative to un-substituted PHS. In this paper we report the synthesis and lithographic evaluations of four experimental TSI photoresists. MX-EX-1, MX-EX-2, MX- EX-3 and MX-EX-4 are non-chemically amplified resists based on aromatic substitutions of chloro- and hydroxymethyl- groups and PHS. We report optimized lithographic processing conditions, line edge roughness, silylation contrast, and compare the results to the parent PHS photoresist.

Typing of canine parvovirus isolates using mini-sequencing based single nucleotide polymorphism analysis.

PubMed

Naidu, Hariprasad; Subramanian, B Mohana; Chinchkar, Shankar Ramchandra; Sriraman, Rajan; Rana, Samir Kumar; Srinivasan, V A

2012-05-01

The antigenic types of canine parvovirus (CPV) are defined based on differences in the amino acids of the major capsid protein VP2. Type specificity is conferred by a limited number of amino acid changes and in particular by few nucleotide substitutions. PCR based methods are not particularly suitable for typing circulating variants which differ in a few specific nucleotide substitutions. Assays for determining SNPs can detect efficiently nucleotide substitutions and can thus be adapted to identify CPV types. In the present study, CPV typing was performed by single nucleotide extension using the mini-sequencing technique. A mini-sequencing signature was established for all the four CPV types (CPV2, 2a, 2b and 2c) and feline panleukopenia virus. The CPV typing using the mini-sequencing reaction was performed for 13 CPV field isolates and the two vaccine strains available in our repository. All the isolates had been typed earlier by full-length sequencing of the VP2 gene. The typing results obtained from mini-sequencing matched completely with that of sequencing. Typing could be achieved with less than 100 copies of standard plasmid DNA constructs or ≤10¹ FAID₅₀ of virus by mini-sequencing technique. The technique was also efficient for detecting multiple types in mixed infections. Copyright © 2012 Elsevier B.V. All rights reserved.

The effect of amino acid deletions and substitutions in the longest loop of GFP

PubMed Central

Flores-Ramírez, Gabriela; Rivera, Manuel; Morales-Pablos, Alfredo; Osuna, Joel; Soberón, Xavier; Gaytán, Paul

2007-01-01

Background The effect of single and multiple amino acid substitutions in the green fluorescent protein (GFP) from Aequorea victoria has been extensively explored, yielding several proteins of diverse spectral properties. However, the role of amino acid deletions in this protein -as with most proteins- is still unknown, due to the technical difficulties involved in generating combinatorial in-phase amino acid deletions on a target region. Results In this study, the region I129-L142 of superglo GFP (sgGFP), corresponding to the longest loop of the protein and located far away from the central chromophore, was subjected to a random amino acid deletion approach, employing an in-house recently developed mutagenesis method termed Codon-Based Random Deletion (COBARDE). Only two mutants out of 16384 possible variant proteins retained fluorescence: sgGFP-Δ I129 and sgGFP-Δ D130. Interestingly, both mutants were thermosensitive and at 30°C sgGFP-Δ D130 was more fluorescent than the parent protein. In contrast with deletions, substitutions of single amino acids from residues F131 to L142 were well tolerated. The substitution analysis revealed a particular importance of residues F131, G135, I137, L138, H140 and L142 for the stability of the protein. Conclusion The behavior of GFP variants with both amino acid deletions and substitutions demonstrate that this loop is playing an important structural role in GFP folding. Some of the amino acids which tolerated any substitution but no deletion are simply acting as "spacers" to localize important residues in the protein structure. PMID:17594481

A Rapid Method to Test for Chloroplast DNA Involvement in Atrazine Resistance

PubMed Central

McNally, Sheila; Bettini, Priscilla; Sevignac, Mireille; Darmency, Henry; Gasquez, Jacques; Dron, Michel

1987-01-01

A point mutation in the chloroplast psbA gene at codon 264 resulting in an animo acid substitution (ser-gly) manifests itself as atrazine resistance in all recognized weed species studied to date. The single base substitution overlaps a highly conserved Mae1 restriction site which is present in susceptible but not in resistant plants. This restriction enzyme, recently commercialized, has been used to show that it is now possible to discriminate rapidly between the two biotypes without the need for DNA sequencing. Images Fig. 1 PMID:16665229

New alloys to conserve critical elements

NASA Technical Reports Server (NTRS)

Stephens, J. R.

1978-01-01

Based on availability of domestic reserves, chromium is one of the most critical elements within the U.S. metal industry. New alloys having reduced chromium contents which offer potential as substitutes for higher chromium containing alloys currently in use are being investigated. This paper focuses primarily on modified Type 304 stainless steels having one-third less chromium, but maintaining comparable oxidation and corrosion properties to that of type 304 stainless steel, the largest single use of chromium. Substitutes for chromium in these modified Type 304 stainless steel alloys include silicon and aluminum plus molybdenum.

Lithium doping and vacancy effects on the structural, electronic and magnetic properties of hexagonal boron nitride sheet: A first-principles calculation

NASA Astrophysics Data System (ADS)

Fartab, Dorsa S.; Kordbacheh, Amirhossein Ahmadkhan

2018-06-01

The first-principles calculations based on spin-polarized density functional theory is carried out to investigate the structural, electronic and magnetic properties of a hexagonal boron nitride sheet (h-BNS) doped by one or two lithium atom(s). Moreover, a vacancy in the neighborhood of one Li-substituted atom is introduced into the system. All optimized structures indicate significant local deformations with Li atom(s) protruded to the exterior of the sheet. The defects considered at N site are energetically more favorable than their counterpart structures at B site. The spin-polarized impurity states appear within the bandgap region of the pristine h-BNS, which lead to a spontaneous magnetization with the largest magnetic moments of about 2 μB in where a single or two B atom(s) are replaced by Li atom(s). Furthermore, the Li substitution for a single B atom increases the density of holes compared to that of electrons forming a p-type semiconductor. More interestingly, the structure in which two Li are substituted two neighboring B atoms appears to show desired half-metallic behavior that may be applicable in spintronic. The results provide a way to enhance the conductivity and magnetism of the pristine h-BNS for potential applications in BN-based nanoscale devices.

Single genome retrieval of context-dependent variability in mutation rates for human germline.

PubMed

Sahakyan, Aleksandr B; Balasubramanian, Shankar

2017-01-13

Accurate knowledge of the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39,894 retrotransposon remnants, we reveal sequence context-dependent germline nucleotide substitution rates for the human genome. The rates are characterised through rate constants in a time-domain, and are made available through a dedicated program (Trek) and a stand-alone database. Due to the nature of the method design and the imposed stringency criteria, we expect our rate constants to be good estimates for the rates of spontaneous mutations. Benefiting from such data, we study the short-range nucleotide (up to 7-mer) organisation and the germline basal substitution propensity (BSP) profile of the human genome; characterise novel, CpG-independent, substitution prone and resistant motifs; confirm a decreased tendency of moieties with low BSP to undergo somatic mutations in a number of cancer types; and, produce a Trek-based estimate of the overall mutation rate in human. The extended set of rate constants we report may enrich our resources and help advance our understanding of genome dynamics and evolution, with possible implications for the role of spontaneous mutations in the emergence of pathological genotypes and neutral evolution of proteomes.

Deletions at short direct repeats and base substitutions are characteristic mutations for bleomycin-induced double- and single-strand breaks, respectively, in a human shuttle vector system

NASA Technical Reports Server (NTRS)

Dar, M. E.; Jorgensen, T. J.

1995-01-01

Using the radiomimetic drug, bleomycin, we have determined the mutagenic potential of DNA strand breaks in the shuttle vector pZ189 in human fibroblasts. The bleomycin treatment conditions used produce strand breaks with 3'-phosphoglycolate termini as > 95% of the detectable dose-dependent lesions. Breaks with this end group represent 50% of the strand break damage produced by ionizing radiation. We report that such strand breaks are mutagenic lesions. The type of mutation produced is largely determined by the type of strand break on the plasmid (i.e. single versus double). Mutagenesis studies with purified DNA forms showed that nicked plasmids (i.e. those containing single-strand breaks) predominantly produce base substitutions, the majority of which are multiples, which presumably originate from error-prone polymerase activity at strand break sites. In contrast, repair of linear plasmids (i.e. those containing double-strand breaks) mainly results in deletions at short direct repeat sequences, indicating the involvement of illegitimate recombination. The data characterize the nature of mutations produced by single- and double-strand breaks in human cells, and suggests that deletions at direct repeats may be a 'signature' mutation for the processing of DNA double-strand breaks.

Single-Molecule Mechanical (Un)folding of RNA Hairpins: Effects of Single A-U to A∙C Pair Substitutions and Single Proton Binding and Implications for mRNA Structure-Induced -1 Ribosomal Frameshifting.

PubMed

Yang, Lixia; Zhong, Zhensheng; Tong, Cailing; Jia, Huan; Liu, Yiran; Chen, Gang

2018-06-08

A wobble A∙C pair can be protonated at near physiological pH to form a more stable wobble A+∙C pair. Here, we constructed an RNA hairpin (rHP) and three mutants with one A-U base pair substituted with an A∙C mismatch on the top (near the loop, U22C), middle (U25C) and bottom (U29C) positions of the stem, respectively. Our results on single-molecule mechanical (un)folding using optical tweezers reveal the destabilization effect of A-U to A∙C pair substitution, and protonation-dependent enhancement of mechanical stability facilitated through an increased folding rate, or decreased unfolding rate, or both. Our data show that protonation may occur rapidly upon the formation of apparent mechanical folding transition state. Furthermore, we measured the bulk -1 ribosomal frameshifting efficiencies of the hairpins by a cell-free translation assay. For the mRNA hairpins studied, -1 frameshifting efficiency correlates with mechanical unfolding force at equilibrium and folding rate at around 15 pN. U29C has a frameshifting efficiency similar to that of rHP (~2%). Accordingly, the bottom 2-4 base pairs of U29C may not form under a stretching force at pH 7.3, which is consistent with the fact that the bottom base pairs of the hairpins may be disrupted by ribosome at the slippery site. U22C and U25C have a similar frameshifting efficiency (~1%), indicating that both unfolding and folding rates of an mRNA hairpin in a crowded environment may affect frameshifting. Our data indicate that mechanical (un)folding of RNA hairpins may mimic how mRNAs unfold and fold in the presence of translating ribosomes.

Virtual substitution scan via single-step free energy perturbation.

PubMed

Chiang, Ying-Chih; Wang, Yi

2016-02-05

With the rapid expansion of our computing power, molecular dynamics (MD) simulations ranging from hundreds of nanoseconds to microseconds or even milliseconds have become increasingly common. The majority of these long trajectories are obtained from plain (vanilla) MD simulations, where no enhanced sampling or free energy calculation method is employed. To promote the 'recycling' of these trajectories, we developed the Virtual Substitution Scan (VSS) toolkit as a plugin of the open-source visualization and analysis software VMD. Based on the single-step free energy perturbation (sFEP) method, VSS enables the user to post-process a vanilla MD trajectory for a fast free energy scan of substituting aryl hydrogens by small functional groups. Dihedrals of the functional groups are sampled explicitly in VSS, which improves the performance of the calculation and is found particularly important for certain groups. As a proof-of-concept demonstration, we employ VSS to compute the solvation free energy change upon substituting the hydrogen of a benzene molecule by 12 small functional groups frequently considered in lead optimization. Additionally, VSS is used to compute the relative binding free energy of four selected ligands of the T4 lysozyme. Overall, the computational cost of VSS is only a fraction of the corresponding multi-step FEP (mFEP) calculation, while its results agree reasonably well with those of mFEP, indicating that VSS offers a promising tool for rapid free energy scan of small functional group substitutions. This article is protected by copyright. All rights reserved. © 2016 Wiley Periodicals, Inc.

Identification of Critical Residues for the Tight Binding of Both Correct and Incorrect Nucleotides to Human DNA Polymerase λ

PubMed Central

Brown, Jessica A.; Pack, Lindsey R.; Sherrer, Shanen M.; Kshetry, Ajay K.; Newmister, Sean A.; Fowler, Jason D.; Taylor, John-Stephen; Suo, Zucai

2010-01-01

DNA polymerase λ (Pol λ) is a novel X-family DNA polymerase that shares 34% sequence identity with DNA polymerase β (Pol β). Pre-steady state kinetic studies have shown that the Pol λ•DNA complex binds both correct and incorrect nucleotides 130-fold tighter on average than the Pol β•DNA complex, although, the base substitution fidelity of both polymerases is 10−4 to 10−5. To better understand Pol λ’s tight nucleotide binding affinity, we created single- and double-substitution mutants of Pol λ to disrupt interactions between active site residues and an incoming nucleotide or a template base. Single-turnover kinetic assays showed that Pol λ binds to an incoming nucleotide via cooperative interactions with active site residues (R386, R420, K422, Y505, F506, A510, and R514). Disrupting protein interactions with an incoming correct or incorrect nucleotide impacted binding with each of the common structural moieties in the following order: triphosphate ≫ base > ribose. In addition, the loss of Watson-Crick hydrogen bonding between the nucleotide and template base led to a moderate increase in the Kd. The fidelity of Pol λ was maintained predominantly by a single residue, R517, which has minor groove interactions with the DNA template. PMID:20851705

Theoretical Effects of Substituting Butter with Margarine on Risk of Cardiovascular Disease.

PubMed

Liu, Qing; Rossouw, Jacques E; Roberts, Mary B; Liu, Simin; Johnson, Karen C; Shikany, James M; Manson, JoAnn E; Tinker, Lesley F; Eaton, Charles B

2017-01-01

Several recent articles have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal-based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). We prospectively studied 71,410 women, aged 50-79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke, and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs = 0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs = 0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results. This theoretical dietary substitution analysis suggests that substituting butter and stick margarine with tub margarine when spreadable fats are eaten may be associated with reduced risk of myocardial infarction.

Theoretical effects of substituting butter with margarine on risk of cardiovascular disease

PubMed Central

Liu, Qing; Rossouw, Jacques E.; Roberts, Mary B.; Liu, Simin; Johnson, Karen C.; Shikany, James M.; Manson, JoAnn E.; Tinker, Lesley F.; Eaton, Charles B.

2017-01-01

Background Several recent papers have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). Methods We prospectively studied 71,410 women, aged 50–79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and Year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. Results Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs=0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs=0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results. Conclusions This theoretical dietary substitution analysis suggests that substituting butter and stick margarine with tub margarine when spreadable fats are eaten may be associated with reduced risk of myocardial infarction. PMID:27648593

Theoretical exploration of structural, electro-optical and magnetic properties of gallium-doped silicon carbide nanotubes

NASA Astrophysics Data System (ADS)

Behzad, Somayeh; Chegel, Raad; Moradian, Rostam; Shahrokhi, Masoud

2014-09-01

The effects of gallium doping on the structural, electro-optical and magnetic properties of (8,0) silicon carbide nanotube (SiCNT) are investigated by using spin-polarized density functional theory. It is found from the calculation of the formation energies that gallium substitution for silicon atom is preferred. Our results show that gallium substitution at either single carbon or silicon atom site in SiCNT could induce spontaneous magnetization. The optical studies based on dielectric function indicate that new transition peaks and a blue shift are observed after gallium doping.

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

PubMed Central

Kumar, Amit; Tripathi, Amit Kumar; Kathuria, Manoj; Shree, Sonal; Tripathi, Jitendra Kumar; Purshottam, R. K.; Ramachandran, Ravishankar; Mitra, Kalyan

2016-01-01

Piscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with significant antimicrobial and antiendotoxin activities can be designed by incorporating single alanine substitutions in the piscidin-1 heptad repeat. PMID:27067326

A Linguistic Image of Nature: The Burmese Numerative Classifier System

ERIC Educational Resources Information Center

Becker, Alton L.

1975-01-01

The Burmese classifier system is coherent because it is based upon a single elementary semantic dimension: deixis. On that dimension, four distances are distinguished, distances which metaphorically substitute for other conceptual relations between people and other living beings, people and things, and people and concepts. (Author/RM)

Laser spectrometer for CO2 clumped isotope analysis

NASA Astrophysics Data System (ADS)

Prokhorov, Ivan; Kluge, Tobias; Janssen, Christof

2017-04-01

Carbon dioxide clumped isotope thermometry has proven to be a reliable method for biogeochemical and atmospheric research. We present a new laser spectroscopic instrument for doubly-substituted isotopologues analysis. In contrast to a conventional isotope ratio mass spectrometry (IRMS), tunable laser direct absorption spectroscopy (TLDAS) has the advantage of isotopologue-specific determination free of isobaric interferences. Tunable infrared laser based spectrometer for clumped isotope analysis is being developed in collaboration between Heidelberg University, Germany, and LERMA-IPSL, CNRS, France. The instrument employs two continuous intraband cascade lasers (ICL) tuned at 4439 and 4329 nm. The spectral windows covered by the lasers contain absorption lines of the six most abundant CO2 isotopologues, including the two doubly substituted species 16O13C18O and 16O13C17O, and all singly substituted isotopologues with 13C, 18O and 17O. A Herriott-type multi-pass cell provides two different absorption pathlengths to compensate the abundance difference between singly- and doubly-substituted isotopologues. We have reached the sub-permill precision required for clumped isotope measurements within the integration time of several seconds. The test version of the instrument demonstrates a performance comparable to state of the art IRMS. We highlight the following features of the instrument that are strong advantages compared to conventional mass spectrometry: measurement cycle in the minute range, simplified sample preparation routine, table-top layout with a potential for in-situ applications.

Amino Acid Substitution in Trichophyton rubrum Squalene Epoxidase Associated with Resistance to Terbinafine

PubMed Central

Osborne, Colin S.; Leitner, Ingrid; Favre, Bertrand; Ryder, Neil S.

2005-01-01

There has only been one clinically confirmed case of terbinafine resistance in dermatophytes, where six sequential Trichophyton rubrum isolates from the same patient were found to be resistant to terbinafine and cross-resistant to other squalene epoxidase (SE) inhibitors. Microsomal SE activity from these resistant isolates was insensitive to terbinafine, suggesting a target-based mechanism of resistance (B. Favre, M. Ghannoum, and N. S. Ryder, Med. Mycol. 42:525-529, 2004). In this study, we have characterized at the molecular level the cause of the resistant phenotype of these clinical isolates. Cloning and sequencing of the SE gene and cDNA from T. rubrum revealed the presence of an intron in the gene and an open reading frame encoding a protein of 489 residues, with an equivalent similarity (57%) to both yeast and mammalian SEs. The nucleotide sequences of SE from two terbinafine-susceptible strains were identical whereas those of terbinafine-resistant strains, serially isolated from the same patient, each contained the same single missense introducing the amino acid substitution L393F. Introduction of the corresponding substitution in the Candida albicans SE gene (L398F) and expression of this gene in Saccharomyces cerevisiae conferred a resistant phenotype to the transformants when compared to those expressing the wild-type sequence. Terbinafine resistance in these T. rubrum clinical isolates appears to be due to a single amino acid substitution in SE. PMID:15980358

40 CFR 419.12 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... organic carbon (TOC) based upon an analysis of any single grab or composite sample. (2) If contaminated... contaminated runoff which exceeds 15 mg/l oil and grease or 110 mg/l TOC is not commingled or treated with any... substitute TOC as a parameter in lieu of COD. A TOC effluent limitation shall be based on effluent data from...

Yeast ribonuclease III uses a network of multiple hydrogen bonds for RNA binding and cleavage.

PubMed

Lavoie, Mathieu; Abou Elela, Sherif

2008-08-19

Members of the bacterial RNase III family recognize a variety of short structured RNAs with few common features. It is not clear how this group of enzymes supports high cleavage fidelity while maintaining a broad base of substrates. Here we show that the yeast orthologue of RNase III (Rnt1p) uses a network of 2'-OH-dependent interactions to recognize substrates with different structures. We designed a series of bipartite substrates permitting the distinction between binding and cleavage defects. Each substrate was engineered to carry a single or multiple 2'- O-methyl or 2'-fluoro ribonucleotide substitutions to prevent the formation of hydrogen bonds with a specific nucleotide or group of nucleotides. Interestingly, introduction of 2'- O-methyl ribonucleotides near the cleavage site increased the rate of catalysis, indicating that 2'-OH are not required for cleavage. Substitution of nucleotides in known Rnt1p binding site with 2'- O-methyl ribonucleotides inhibited cleavage while single 2'-fluoro ribonucleotide substitutions did not. This indicates that while no single 2'-OH is essential for Rnt1p cleavage, small changes in the substrate structure are not tolerated. Strikingly, several nucleotide substitutions greatly increased the substrate dissociation constant with little or no effect on the Michaelis-Menten constant or rate of catalysis. Together, the results indicate that Rnt1p uses a network of nucleotide interactions to identify its substrate and support two distinct modes of binding. One mode is primarily mediated by the dsRNA binding domain and leads to the formation of stable RNA/protein complex, while the other requires the presence of the nuclease and N-terminal domains and leads to RNA cleavage.

Spatial Interactions in Multiple-Use Forestry and Substitution and Wealth Effects for the Single Stand

Treesearch

Stephen K. Swallow; David N. Wear

1993-01-01

Forestry models often ignore spatial relationships between forest stands. This paper isolates the effects of stand interactions in muitiple-use forestry through a straightforward extension of the single-stand model. Effects of stand interactions decompose into wealth and substitution effects and may cause time-varying patterns of resource use for a forest...

Neuraminidase inhibitor susceptibility and neuraminidase enzyme kinetics of human influenza A and B viruses circulating in Thailand in 2010-2015.

PubMed

Tewawong, Nipaporn; Marathe, Bindumadhav M; Poovorawan, Yong; Vongpunsawad, Sompong; Webby, Richard J; Govorkova, Elena A

2018-01-01

Amino acid substitutions within or near the active site of the viral neuraminidase (NA) may affect influenza virus fitness. In influenza A(H3N2) and B viruses circulating in Thailand between 2010 and 2015, we identified several NA substitutions that were previously reported to be associated with reduced inhibition by NA inhibitors (NAIs). To study the effect of these substitutions on the enzymatic properties of NA and on virus characteristics, we generated recombinant influenza viruses possessing either a wild type (WT) NA or an NA with a single I222V, S331G, or S331R substitution [in influenza A(H3N2) viruses] or a single D342S, A395T, A395V, or A395D NA substitution (in influenza B viruses). We generated recombinant (7:1) influenza A and B viruses on the genetic background of A/Puerto Rico/8/1934 (A/PR/8, H1N1) or B/Yamanashi/166/1998 (B/YAM) viruses, respectively. In contrast to the expected phenotypes, all the recombinant influenza A(H3N2) and B viruses carrying putative NA resistance substitutions were susceptible to NAIs. The Km and Vmax for the NAs of A/PR8-S331G and A/PR8-S331R viruses were higher than for the NA of WT virus, and the corresponding values for the B/YAM-D342S virus were lower than for the NA of WT virus. Although there was initial variation in the kinetics of influenza A and B viruses' replication in MDCK cells, their titers were comparable to each other and to WT viruses at later time points. All introduced substitutions were stable except for B/YAM-D342S and B/YAM-A395V which reverted to WT sequences after three passages. Our data suggest that inferring susceptibility to NAIs based on sequence information alone should be cautioned. The impact of NA substitution on NAI resistance, viral growth, and enzymatic properties is viral context dependent and should be empirically determined.

On the use of Lineal Energy Measurements to Estimate Linear Energy Transfer Spectra

NASA Technical Reports Server (NTRS)

Adams, David A.; Howell, Leonard W., Jr.; Adam, James H., Jr.

2007-01-01

This paper examines the error resulting from using a lineal energy spectrum to represent a linear energy transfer spectrum for applications in the space radiation environment. Lineal energy and linear energy transfer spectra are compared in three diverse but typical space radiation environments. Different detector geometries are also studied to determine how they affect the error. LET spectra are typically used to compute dose equivalent for radiation hazard estimation and single event effect rates to estimate radiation effects on electronics. The errors in the estimations of dose equivalent and single event rates that result from substituting lineal energy spectra for linear energy spectra are examined. It is found that this substitution has little effect on dose equivalent estimates in interplanetary quiet-time environment regardless of detector shape. The substitution has more of an effect when the environment is dominated by solar energetic particles or trapped radiation, but even then the errors are minor especially if a spherical detector is used. For single event estimation, the effect of the substitution can be large if the threshold for the single event effect is near where the linear energy spectrum drops suddenly. It is judged that single event rate estimates made from lineal energy spectra are unreliable and the use of lineal energy spectra for single event rate estimation should be avoided.

Single substitution in bacteriophage T4 RNase H alters the ratio between its exo- and endonuclease activities.

PubMed

Kholod, Natalia; Sivogrivov, Dmitry; Latypov, Oleg; Mayorov, Sergey; Kuznitsyn, Rafail; Kajava, Andrey V; Shlyapnikov, Mikhail; Granovsky, Igor

2015-11-01

The article describes substitutions in bacteriophage T4 RNase H which provide so called das-effect. Phage T4 DNA arrest suppression (das) mutations have been described to be capable of partially suppressing the phage DNA arrest phenotype caused by a dysfunction in genes 46 and/or 47 (also known as Mre11/Rad50 complex). Genetic mapping of das13 (one of the das mutations) has shown it to be in the region of the rnh gene encoding RNase H. Here we report that Das13 mutant of RNase H has substitutions of valine 43 and leucine 242 with isoleucines. To investigate the influence of these mutations on RNase H nuclease properties we have designed a novel in vitro assay that allows us to separate and quantify exo- or endonuclease activities of flap endonuclease. The nuclease assay in vitro showed that V43I substitution increased the ratio between exonuclease/endonuclease activities of RNase H whereas L242I substitution did not affect the nuclease activity of RNase H in vitro. However, both mutations were necessary for the full das effect in vivo. Molecular modelling of the nuclease structure suggests that V43I substitution may lead to disposition of H4 helix, responsible for the interaction with the first base pairs of 5'end of branched DNA. These structural changes may affect unwinding of the first base pairs of gapped or nicked DNA generating a short flap and therefore may stabilize the DNA-enzyme complex. L242I substitution did not affect the structure of RNase H and its role in providing das-effect remains unclear. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of chemically induced contraction of a coordination polyhedron on the dynamical magnetism of bis(phthalocyaninato)disprosium, a single-4f-ionic single-molecule magnet with a Kramers ground state.

PubMed

Ishikawa, Naoto; Mizuno, Yoshifumi; Takamatsu, Satoshi; Ishikawa, Tadahiko; Koshihara, Shin-ya

2008-11-17

Chemically induced longitudinal contraction of the square-antiprism coordination polyhedron of a peripherically substituted bis(phthalocyaninato)dysprosiumate(III), a dysprosium-based single-4f-ionic single-molecule magnet having a J z = +/- (13)/ 2 Kramers doublet ground state, resulted in drastic changes in dynamical magnetism including a doubling of the energy barrier, a 2-order-of-magnitude decrease of the spin reversal rate, a significant rise of the blocking temperature, and the first observation of the emergence of a large remanent magnetization.

Ab initio study of single-crystalline and polycrystalline elastic properties of Mg-substituted calcite crystals.

PubMed

Zhu, L-F; Friák, M; Lymperakis, L; Titrian, H; Aydin, U; Janus, A M; Fabritius, H-O; Ziegler, A; Nikolov, S; Hemzalová, P; Raabe, D; Neugebauer, J

2013-04-01

We employ ab initio calculations and investigate the single-crystalline elastic properties of (Ca,Mg)CO3 crystals covering the whole range of concentrations from pure calcite CaCO3 to pure magnesite MgCO3. Studying different distributions of Ca and Mg atoms within 30-atom supercells, our theoretical results show that the energetically most favorable configurations are characterized by elastic constants that nearly monotonously increase with the Mg content. Based on the first principles-derived single-crystalline elastic anisotropy, the integral elastic response of (Ca,Mg)CO3 polycrystals is determined employing a mean-field self-consistent homogenization method. As in case of single-crystalline elastic properties, the computed polycrystalline elastic parameters sensitively depend on the chemical composition and show a significant stiffening impact of Mg atoms on calcite crystals in agreement with the experimental findings. Our analysis also shows that it is not advantageous to use a higher-scale two-phase mix of stoichiometric calcite and magnesite instead of substituting Ca atoms by Mg ones on the atomic scale. Such two-phase composites are not significantly thermodynamically favorable and do not provide any strong additional stiffening effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa

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

Dryja, T.P.; Han, L.B.; Cowley, G.S.

1991-10-15

The authors searched for point mutations in every exon of the rhodopsin gene in 150 patients from separate families with autosomal dominant retinitis pigmentosa. Including the 4 mutations the authors reported previously, they found a total of 17 different mutations that correlate with the disease. Each of these mutations is a single-base substitution corresponding to a single amino acid substitution. Based on current models for the structure of rhodopsin, 3 of the 17 mutant amino acids are normally located on the cytoplasmic side of the protein, 6 in transmembrane domains, and 8 on the intradiscal side. Forty-three of the 150more » patients (29%) carry 1 of these mutations, and no patient has more than 1 mutation. In every family with a mutation so far analyzed, the mutation cosegregates with the disease. They found one instance of a mutation in an affected patient that was absent in both unaffected parents (i.e., a new germ-line mutation), indicating that some isolate cases of retinitis pigmentosa carry a mutation of the rhodopsin gene.« less

Ce and La single- and double-substitutional defects in yttrium aluminum garnet: first-principles study.

PubMed

Muñoz-García, Ana Belén; Seijo, Luis

2011-02-10

The atomistic structure, energetics, and electronic structure of single-substitutional Ce and La defects and double-substitutional Ce-La defects in Ce,La-codoped yttrium aluminum garnet (YAG) Y(3)Al(5)O(12) have been studied by means of first-principles periodic boundary conditions density functional theory calculations. Single substitution of Y by Ce or by La produces atomistic expansions around the impurities, which are significantly smaller than the ionic radii mismatches and the overall lattice distortions are found to be confined within their second coordination spheres. In double-substitutional defects, the impurities tend to be as close as possible. La-codoping Ce:YAG provokes an anisotropic expansion around Ce defects. The Ce impurity introduces 4f occupied states in the 5.0 eV computed gap of YAG, peaking 0.25 eV above the top of the valence band, and empty 4f, 5d, and 6s states starting at 3.8 eV in the gap and spreading over the conduction band. La-codoping produces very small effects on the electronic structure of Ce:YAG, the most visible one being the decrease in covalent bonding with one of the oxygen atoms, which shifts 0.05 Å away from Ce and gets 0.04 Å closer to La in the most stable Ce-La double-substitutional defect.

Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun.

PubMed

Leonard, D A; Rajaram, N; Kerppola, T K

1997-05-13

Interactions among transcription factors that bind to separate sequence elements require bending of the intervening DNA and juxtaposition of interacting molecular surfaces in an appropriate orientation. Here, we examine the effects of single amino acid substitutions adjacent to the basic regions of Fos and Jun as well as changes in sequences flanking the AP-1 site on DNA bending. Substitution of charged amino acid residues at positions adjacent to the basic DNA-binding domains of Fos and Jun altered DNA bending. The change in DNA bending was directly proportional to the change in net charge for all heterodimeric combinations between these proteins. Fos and Jun induced distinct DNA bends at different binding sites. Exchange of a single base pair outside of the region contacted in the x-ray crystal structure altered DNA bending. Substitution of base pairs flanking the AP-1 site had converse effects on the opposite directions of DNA bending induced by homodimers and heterodimers. These results suggest that Fos and Jun induce DNA bending in part through electrostatic interactions between amino acid residues adjacent to the basic region and base pairs flanking the AP-1 site. DNA bending by Fos and Jun at inverted binding sites indicated that heterodimers bind to the AP-1 site in a preferred orientation. Mutation of a conserved arginine within the basic regions of Fos and transversion of the central C:G base pair in the AP-1 site to G:C had complementary effects on the orientation of heterodimer binding and DNA bending. The conformational variability of the Fos-Jun-AP-1 complex may contribute to its functional versatility at different promoters.

Chromatographic methods for determination of S-substituted cysteine derivatives--a comparative study.

PubMed

Kubec, Roman; Dadáková, Eva

2009-10-09

A novel HPLC method for determination of a wide variety of S-substituted cysteine derivatives in Allium species has been developed and validated. This method allows simultaneous separation and quantification of S-alk(en)ylcysteine S-oxides, gamma-glutamyl-S-alk(en)ylcysteines and gamma-glutamyl-S-alk(en)ylcysteine S-oxides in a single run. The procedure is based on extraction of these amino acids and dipeptides by methanol, their derivatization by dansyl chloride and subsequent separation by reversed phase HPLC. The main advantages of the new method are simplicity, excellent stability of derivatives, high sensitivity, specificity and the ability to simultaneously analyze the whole range of S-substituted cysteine derivatives. This method was critically compared with other chromatographic procedures used for quantification of S-substituted cysteine derivatives, namely with two other HPLC methods (derivatization by o-phthaldialdehyde/tert-butylthiol and fluorenylmethyl chloroformate), and with determination by gas chromatography or capillary electrophoresis. Major advantages and drawbacks of these analytical procedures are discussed. Employing these various chromatographic methods, the content and relative proportions of individual S-substituted cysteine derivatives were determined in four most frequently consumed alliaceous vegetables (garlic, onion, shallot, and leek).

Decoding the Effect of Isobaric Substitutions on Identifying Missing Proteins and Variant Peptides in Human Proteome.

PubMed

Choong, Wai-Kok; Lih, Tung-Shing Mamie; Chen, Yu-Ju; Sung, Ting-Yi

2017-12-01

To confirm the existence of missing proteins, we need to identify at least two unique peptides with length of 9-40 amino acids of a missing protein in bottom-up mass-spectrometry-based proteomic experiments. However, an identified unique peptide of the missing protein, even identified with high level of confidence, could possibly coincide with a peptide of a commonly observed protein due to isobaric substitutions, mass modifications, alternative splice isoforms, or single amino acid variants (SAAVs). Besides unique peptides of missing proteins, identified variant peptides (SAAV-containing peptides) could also alternatively map to peptides of other proteins due to the aforementioned issues. Therefore, we conducted a thorough comparative analysis on data sets in PeptideAtlas Tiered Human Integrated Search Proteome (THISP, 2017-03 release), including neXtProt (2017-01 release), to systematically investigate the possibility of unique peptides in missing proteins (PE2-4), unique peptides in dubious proteins, and variant peptides affected by isobaric substitutions, causing doubtful identification results. In this study, we considered 11 isobaric substitutions. From our analysis, we found <5% of the unique peptides of missing proteins and >6% of variant peptides became shared with peptides of PE1 proteins after isobaric substitutions.

40 CFR 419.52 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... mg/l total organic carbon (TOC) based upon an analysis of any single grab or composite sample. (2) If... contaminated runoff which exceeds 15 mg/l oil and grease or 110 mg/l TOC is not commingled or treated with any... substitute TOC as a parameter in lieu of COD. A TOC effluent limitation shall be based on effluent data from...

Feruloylated and nonferuloylated arabino-oligosaccharides from sugar beet pectin selectively stimulate the growth of Bifidobacterium spp. in human fecal in vitro fermentations.

PubMed

Holck, Jesper; Lorentzen, Andrea; Vigsnæs, Louise K; Licht, Tine R; Mikkelsen, Jørn D; Meyer, Anne S

2011-06-22

The side chains of the rhamnogalacturonan I fraction in sugar beet pectin are particularly rich in arabinan moieties, which may be substituted with feruloyl groups. In this work the arabinan-rich fraction resulting from sugar beet pulp based pectin production was separated by Amberlite XAD hydrophobic interaction and membrane separation into four fractions based on feruloyl substitution and arabino-oligosaccharide chain length: short-chain (DP 2-10) and long-chain (DP 7-14) feruloylated and nonferuloylated arabino-oligosaccharides, respectively. HPAEC, SEC, and MALDI-TOF/TOF analyses of the fractions confirmed the presence of singly and doubly substituted feruloylated arabino-oligosaccharides in the feruloyl-substituted fractions. In vitro microbial fermentation by human fecal samples (n = 6 healthy human volunteers) showed a selective stimulation of bifidobacteria by both the feruloylated and the nonferuloylated long-chain arabino-oligosaccharides to the same extent as the prebiotic fructo-oligosaccharides control. None of the fractions stimulated the growth of the potential pathogen Clostridium difficile in monocultures. This work provides a first report on the separation of potentially bioactive feruloylated arabino-oligosaccharides from sugar beet pulp and an initial indication of the potentially larger bifidogenic effect of relatively long-chain arabino-oligosaccharides as opposed to short-chain arabino-oligosaccharides.

A-Site (MCe) Substitution Effects on the Structures and Properties of CaBi4Ti4O15 Ceramics

NASA Astrophysics Data System (ADS)

Yan, Haixue; Li, Chengen; Zhou, Jiaguang; Zhu, Weimin; He, Lianxin; Song, Yuxin

2000-11-01

We investigated the effect of A-site compound substitution on the structures and properties of Ca0.8(MCe)0.1Bi4Ti4O15 (M denotes Li, Na and K) ceramics. The samples were prepared by the conventional ceramic technique. Sintering characteristics of Ca0.8(MCe)0.1Bi4Ti4O15 and CaBi4Ti4O15 ceramics were discussed. X-ray powder diffraction patterns of the three modified CBT-based compounds show a single phase of bismuth oxide layer type structure with m=4. The hysteresis loops of polarization versus electric field of the four compounds were also measured. A-site compound substitution improves the piezoelectric properties and the high-temperature resistivity of these materials. A-site (LiCe) and (KCe) substitution not only improves the Curie temperature but also decreases the temperature coefficient of dielectric constant (TK\\varepsilon). Among the three modified ceramics, only the Curie temperature of Ca0.8(NaCe)0.1Bi4Ti4O15 is lower than that of CaBi4Ti4O15; however, its TK\\varepsilon is the lowest. As a result, all the three modified CBT-based ceramics were found to be excellent high-temperature piezoelectric materials.

The cyc1-11 mutation in yeast reverts by recombination with a nonallelic gene: composite genes determining the iso-cytochromes c.

PubMed Central

Ernst, J F; Stewart, J W; Sherman, F

1981-01-01

DNA sequence analysis of a cloned fragment directly established that the cyc1-11 mutation of iso-1-cytochrome c in the yeast Saccharomyces cerevisiae is a two-base-pair substitution that changes the CCA proline codon at amino acid position 76 to a UAA nonsense codon. Analysis of 11 revertant proteins and one cloned revertant gene showed that reversion of the cyc1-11 mutation can occur in three ways: a single base-pair substitution, which produces a serine replacement at position 76; recombination with the nonallelic CYC7 gene of iso-2-cytochrome c, which causes replacement of a segment in the cyc1-11 gene by the corresponding segment of the CYC7 gene; and either a two-base-pair substitution or recombination with the CYC7 gene, which causes the formation of the normal iso-1-cytochrome c sequence. These results demonstrate the occurrence of low frequencies of recombination between nonallelic genes having extensive but not complete homology. The formation of composite genes that share sequences from nonallelic genes may be an evolutionary mechanism for producing protein diversities and for maintaining identical sequences at different loci. Images PMID:6273865

Contribution of single amino acid and codon substitutions to the production and secretion of a lipase by Bacillus subtilis.

PubMed

Skoczinski, Pia; Volkenborn, Kristina; Fulton, Alexander; Bhadauriya, Anuseema; Nutschel, Christina; Gohlke, Holger; Knapp, Andreas; Jaeger, Karl-Erich

2017-09-25

Bacillus subtilis produces and secretes proteins in amounts of up to 20 g/l under optimal conditions. However, protein production can be challenging if transcription and cotranslational secretion are negatively affected, or the target protein is degraded by extracellular proteases. This study aims at elucidating the influence of a target protein on its own production by a systematic mutational analysis of the homologous B. subtilis model protein lipase A (LipA). We have covered the full natural diversity of single amino acid substitutions at 155 positions of LipA by site saturation mutagenesis excluding only highly conserved residues and qualitatively and quantitatively screened about 30,000 clones for extracellular LipA production. Identified variants with beneficial effects on production were sequenced and analyzed regarding B. subtilis growth behavior, extracellular lipase activity and amount as well as changes in lipase transcript levels. In total, 26 LipA variants were identified showing an up to twofold increase in either amount or activity of extracellular lipase. These variants harbor single amino acid or codon substitutions that did not substantially affect B. subtilis growth. Subsequent exemplary combination of beneficial single amino acid substitutions revealed an additive effect solely at the level of extracellular lipase amount; however, lipase amount and activity could not be increased simultaneously. Single amino acid and codon substitutions can affect LipA secretion and production by B. subtilis. Several codon-related effects were observed that either enhance lipA transcription or promote a more efficient folding of LipA. Single amino acid substitutions could improve LipA production by increasing its secretion or stability in the culture supernatant. Our findings indicate that optimization of the expression system is not sufficient for efficient protein production in B. subtilis. The sequence of the target protein should also be considered as an optimization target for successful protein production. Our results further suggest that variants with improved properties might be identified much faster and easier if mutagenesis is prioritized towards elements that contribute to enzymatic activity or structural integrity.

Expansion of inverted repeat does not decrease substitution rates in Pelargonium plastid genomes.

PubMed

Weng, Mao-Lun; Ruhlman, Tracey A; Jansen, Robert K

2017-04-01

For species with minor inverted repeat (IR) boundary changes in the plastid genome (plastome), nucleotide substitution rates were previously shown to be lower in the IR than the single copy regions (SC). However, the impact of large-scale IR expansion/contraction on plastid nucleotide substitution rates among closely related species remains unclear. We included plastomes from 22 Pelargonium species, including eight newly sequenced genomes, and used both pairwise and model-based comparisons to investigate the impact of the IR on sequence evolution in plastids. Ten types of plastome organization with different inversions or IR boundary changes were identified in Pelargonium. Inclusion in the IR was not sufficient to explain the variation of nucleotide substitution rates. Instead, the rate heterogeneity in Pelargonium plastomes was a mixture of locus-specific, lineage-specific and IR-dependent effects. Our study of Pelargonium plastomes that vary in IR length and gene content demonstrates that the evolutionary consequences of retaining these repeats are more complicated than previously suggested. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Balanced design for the feasible super rocket fuels: A first-principle study on gauche CHN7 and CHN3.

PubMed

Yu, Tao; Lin, Maohua; Wu, Bo; Wang, Jintian; Tsai, Chi-Tay

2018-05-16

On the basis of the framework of cubic gauche nitrogen (cg-N), six one-eighth methanetriyl groups (>CH-) substitutes and fifteen one-fourth >CH- substitutes were optimized using the first-principle calculations based on density functional theory (DFT). Both one-eighth and one-fourth substitutes still keep the gauche structures with the simple formula CHN 7 and CHN 3 , respectively. The most thermodynamic stable gauche CHN 7 and CHN 3 are P2 1 qtg-C 2 H 2 N 14 I and P2 1 qtg-C 4 H 4 N 12 III, respectively. No probability density of C-C single bonds and high probability densities of C-N-C structures were found in the two substitutes. Although gauche CHN 7 and CHN 3 lose energy density in contrast to cg-N, they win kinetic stability and combustion temperature (T c ). Thus, they are more feasible than cg-N, and more effective than the traditional rocket fuels. Copyright © 2018 Elsevier Inc. All rights reserved.

The antigenic surface of staphylococcal nuclease. II. Analysis of the N-1 epitope by site-directed mutagenesis.

PubMed

Smith, A M; Benjamin, D C

1991-02-15

Previous studies in our laboratory on the production and isolation of a panel of mAb to staphylococcal nuclease allowed us to define a series of eight overlapping epitopes. Using site-directed mutagenesis of the nuclease coding sequences we were able to map the nonoverlapping epitopes recognized by two members of this panel. In the study reported here, we report the generation and analysis of a number of single amino acid substitutions for seven surface residues predicted to lie within one of these two epitopes. Immunochemical analysis showed that one or more substitutions at each of these seven positions had a major effect on mAb binding, whereas other substitutions had none. Based on the nature of these substitutions and the chemical and physical properties of the variant molecules, we believe that any structural effects induced by these substitutions are local and do not result in long-range structural alterations that indirectly influence antibody reactivity. Therefore, we conclude that disruption of mAb binding can be directly attributed to changes in amino acid side chains and that not only are all seven of the residues studied part of the epitope but all seven make contact with the antibody combining site. These studies demonstrate the advantages of using site-directed mutagenesis to study antigen structure and emphasize the importance of constructing the examining multiple substitutions for any given amino acid.

A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

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

Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko

2010-09-01

We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinantmore » AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.« less

Elimination of single-beam substitution error in diffuse reflectance measurements using an integrating sphere.

PubMed

Vidovic, Luka; Majaron, Boris

2014-02-01

Diffuse reflectance spectra (DRS) of biological samples are commonly measured using an integrating sphere (IS). To account for the incident light spectrum, measurement begins by placing a highly reflective white standard against the IS sample opening and collecting the reflected light. After replacing the white standard with the test sample of interest, DRS of the latter is determined as the ratio of the two values at each involved wavelength. However, such a substitution may alter the fluence rate inside the IS. This leads to distortion of measured DRS, which is known as single-beam substitution error (SBSE). Barring the use of more complex experimental setups, the literature states that only approximate corrections of the SBSE are possible, e.g., by using look-up tables generated with calibrated low-reflectivity standards. We present a practical method for elimination of SBSE when using IS equipped with an additional reference port. Two additional measurements performed at this port enable a rigorous elimination of SBSE. Our experimental characterization of SBSE is replicated by theoretical derivation. This offers an alternative possibility of computational removal of SBSE based on advance characterization of a specific DRS setup. The influence of SBSE on quantitative analysis of DRS is illustrated in one application example.

A spectroscopic investigation of the Schiff base reprotonation mechanism of bacteriorhodopsin

NASA Astrophysics Data System (ADS)

Russell, Terence Stephen

This thesis reports time-resolved visible spectroscopy experiments performed on the light-driven proton pumping protein, bacteriorhodopsin (bR), and a number of artificially produced analogs. These analogs comprise a variety of single and double amino acid substitutions produced in several of the residues previously implicated in proton transport in bR. Also addressed are the results of resonance Raman and FTIR difference spectroscopy which provide information about the vibrational modes of the protein. The results from these experiments confirm aspects of both structural and functional models of bR based on previous electron diffraction and spectroscopic data. During a phase of the proton pumping photocycle in bR known as Schiff base reprotonation (also referred to as M intermediate decay), a proton is transferred over a 12 A distance from a proton donor residue (Asp-96) to the light-absorbing active site. The behavior of the M intermediate was monitored by time-resolved visible spectroscopy. In the single substitution known as D96N, the Asp-96 residue was replaced with a less efficient proton donor, asparagine. This mutant exhibited an M intermediate which decayed slowly in comparison to that of wild-type bR. However, this effect was reversed with the double substitution, T46D/D96N. This result indicates that the proton donor group can be moved to another nearby location and still yield a system functionally similar to the native protein. Replacement of the donor group with a histidine, His-96, resulted in a photocycle similar to D96N above pH 7. However, below this pH, the M intermediate is not detected. FTIR difference spectroscopy indicates that the protonation state of the substituted His-96 residue influences the structure of the active site of bR which suggests that a proton that is associated with His-96 may move towards the active site and thereby block M intermediate formation. Finally, the residue Thr-89 was replaced with an asparagine. This substitution altered not only the vibrational modes of the protein but also its visible absorption, which indicates that Thr-89 interacts directly with the active site of bR. These results are used to correct and extend an overall molecular model of the proton transport mechanism in bacteriorhodopsin.

The Electronic and Optical Properties of Au Doped Single-Layer Phosphorene

NASA Astrophysics Data System (ADS)

Zhu, Ziqing; Chen, Changpeng; Liu, Jiayi; Han, Lu

2018-01-01

The electronic properties and optical properties of single and double Au-doped phosphorene have been comparatively investigated using the first-principles plane-wave pseudopotential method based on density functional theory. The decrease from direct band gap 0.78 eV to indirect band gap 0.22 and 0.11 eV are observed in the single and double Au-doped phosphorene, respectively. The red shifts of absorbing edge occur in both doped systems, which consequently enhance the absorbing of infrared light in phosphorene. Band gap engineering can, therefore, be used to directly tune the optical absorption of phosphorene system by substitutional Au doping.

Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man.

PubMed Central

Stöckler, S.; Isbrandt, D.; Hanefeld, F.; Schmidt, B.; von Figura, K.

1996-01-01

In two children with an accumulation of guanidinoacetate in brain and a deficiency of creatine in blood, a severe deficiency of guanidinoacetate methyltransferase (GAMT) activity was detected in the liver. Two mutant GAMT alleles were identified that carried a single base substitution within a 5' splice site or a 13-nt insertion and gave rise to four mutant transcripts. Three of the transcripts encode truncated polypeptides that lack a residue known to be critical for catalytic activity of GAMT. Deficiency of GAMT is the first inborn error of creatine metabolism. It causes a severe developmental delay and extrapyramidal symptoms in early infancy and is treatable by oral substitution with creatine. Images Figure 2 PMID:8651275

Optical Sensing Properties of Pyrene-Schiff Bases toward Different Acids.

PubMed

Babgi, Bandar A; Alzahrani, Asma

2016-07-01

A set of (4-substituted-phenyl)-pyren-1-ylmethylene-amine (PMA) was prepared by the reaction of pyrene-1-carboxaldehyde and the corresponding 4-substituted aniline. The structure of the PMA compounds were confirmed by spectroscopic data (IR, (1)HNMR, (13)CNMR, ISI-MS and elemental analysis. The structure of (4-bromo-phenyl)-pyren-1-ylmethylene-amine (BrPMA) was further confirmed by the single X-ray crystallography. The absorption and emission spectroscopic behaviors were investigated in variant acids. The compounds showed dramatic spectroscopic changes upon acidifying with strong acids and negligible effects when weak acids are used in the acidifications. Hence, the PMA compounds can be used as sensors to distinguish between weak and strong acids.

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case.

PubMed

Mroczyńska, Karina; Kaczorowska, Małgorzata; Kolehmainen, Erkki; Grubecki, Ireneusz; Pietrzak, Marek; Ośmiałowski, Borys

2015-01-01

The association of substituted benzoates and naphthyridine dianions was used to study the complexation of dibutyltriuret. The title molecule is the simplest molecule able to form two intramolecular hydrogen bonds. The naphthyridine salt was used to break two intramolecular hydrogen bonds at a time while with the use of substituted benzoates the systematic approach to study association was achieved. Both, titrations and variable temperature measurements shed the light on the importance of conformational equilibrium and its influence on association in solution. Moreover, the associates were observed by mass spectrometry. The DFT-based computations for complexes and single bond rotational barriers supports experimental data and helps understanding the properties of multiply hydrogen bonded complexes.

The comparative chloroplast genomic analysis of photosynthetic orchids and developing DNA markers to distinguish Phalaenopsis orchids.

PubMed

Jheng, Cheng-Fong; Chen, Tien-Chih; Lin, Jhong-Yi; Chen, Ting-Chieh; Wu, Wen-Luan; Chang, Ching-Chun

2012-07-01

The chloroplast genome of Phalaenopsis equestris was determined and compared to those of Phalaenopsis aphrodite and Oncidium Gower Ramsey in Orchidaceae. The chloroplast genome of P. equestris is 148,959 bp, and a pair of inverted repeats (25,846 bp) separates the genome into large single-copy (85,967 bp) and small single-copy (11,300 bp) regions. The genome encodes 109 genes, including 4 rRNA, 30 tRNA and 75 protein-coding genes, but loses four ndh genes (ndhA, E, F and H) and seven other ndh genes are pseudogenes. The rate of inter-species variation between the two moth orchids was 0.74% (1107 sites) for single nucleotide substitution and 0.24% for insertions (161 sites; 1388 bp) and deletions (189 sites; 1393 bp). The IR regions have a lower rate of nucleotide substitution (3.5-5.8-fold) and indels (4.3-7.1-fold) than single-copy regions. The intergenic spacers are the most divergent, and based on the length variation of the three intergenic spacers, 11 native Phalaenopsis orchids could be successfully distinguished. The coding genes, IR junction and RNA editing sites are relatively more conserved between the two moth orchids than between those of Phalaenopsis and Oncidium spp. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Probing Single Pt Atoms in Complex Intermetallic Al13Fe4.

PubMed

Yamada, Tsunetomo; Kojima, Takayuki; Abe, Eiji; Kameoka, Satoshi; Murakami, Yumi; Gille, Peter; Tsai, An Pang

2018-03-21

The atomic structure of a 0.2 atom % Pt-doped complex metallic alloy, monoclinic Al 13 Fe 4 , was investigated using a single crystal prepared by the Czochralski method. High-angle annular dark-field scanning transmission electron microscopy showed that the Pt atoms were dispersed as single atoms and substituted at Fe sites in Al 13 Fe 4 . Single-crystal X-ray structural analysis revealed that the Pt atoms preferentially substitute at Fe(1). Unlike those that have been reported, Pt single atoms in the surface layers showed lower activity and selectivity than those of Al 2 Pt and bulk Pt for propyne hydrogenation, indicating that the active state of a given single-atom Pt site is strongly dominated by the bonding to surrounding Al atoms.

Charge-coupled Substituted Garnets (Y3-xCa0.5xM0.5x)Fe5O12 (M = Ce, Th): Structure and Stability as Crystalline Nuclear Waste Forms

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

Guo, Xiaofeng; Kukkadapu, Ravi K.; Lanzirotti, Anthony

2015-04-20

The garnet structure has been proposed as a potential crystalline nuclear waste form for accommodation of actinide elements, especially uranium (U). In this study, yttrium iron garnet (YIG) as a model garnet host was studied for the incorporation of U analogs, cerium (Ce), and thorium (Th), incorporated by a charge-coupled substitution with calci-um (Ca) for yttrium (Y) in YIG, namely 2Y3+ = Ca2+ + M4+, where M4+ = Ce4+ or Th4+. Single phase garnets Y3-xCa0.5xM0.5xFe5O12, synthesized by the citrate-nitrate combustion method, were obtained up to x = 0.7. Ce was confirmed to be tetravalent by X-ray absorption spectroscopy and X-raymore » photoelectron spectroscopy. X-ray diffraction and 57Fe-Mössbauer spectroscopy indicated that the samples are single phase, M4+ and Ca2+ cations are restricted to the c-site, the nature of M4+ has only a minor effect on the structure, and the local environments of both the tetrahedral and octahedral Fe3+ are systematically affected by the extent of substitution, especially on the tetrahedral sublattice. The charge coupled substitution has advantages in incorporating Ce/Th and in stabilizing the substituted phases, compared to a single substitution strategy. Enthalpies of formation of garnets were obtained by high temperature oxide melt solution calorimetry, and the enthalpies of substitution of Ce and Th were determined. The thermodynamic analysis demonstrates that the substituted garnets are entropically rather than energetically stabilized. This suggests that such garnets may form and persist in repositories at high temperature but might decompose near room temperature. These structural and thermodynamic findings shed light on possible incorporation of U in this garnet system.« less

40 CFR 419.33 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (TOC) based upon an analysis of any single grab or composite sample. (2) If contaminated runoff is... which exceeds 110 mg/l TOC is not commingled or treated with any other type of wastewater, the quantity... (1,000 ppm), the permitting authority may substitute TOC as a parameter in lieu of COD. A TOC...

40 CFR 419.53 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (TOC) based upon an analysis of any single grab or composite sample. (2) If contaminated runoff is... which exceeds 110 mg/l TOC is not commingled or treated with any other type of wastewater, the quantity... (1,000 ppm), the permitting authority may substitute TOC as a parameter in lieu of COD. A TOC...

40 CFR 419.23 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (TOC) based upon an analysis of any single grab or composite sample. (2) If contaminated runoff is... which exceeds 110 mg/l TOC is not commingled or treated with any other type of wastewater, the quantity... (1,000 ppm), the permitting authority may substitute TOC as a parameter in lieu of COD. A TOC...

Sequence polymorphism in an insect RNA virus field population: A snapshot from a single point in space and time reveals stochastic differences among and within individual hosts

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

Stenger, Drake C., E-mail: drake.stenger@ars.usda.

Population structure of Homalodisca coagulata Virus-1 (HoCV-1) among and within field-collected insects sampled from a single point in space and time was examined. Polymorphism in complete consensus sequences among single-insect isolates was dominated by synonymous substitutions. The mutant spectrum of the C2 helicase region within each single-insect isolate was unique and dominated by nonsynonymous singletons. Bootstrapping was used to correct the within-isolate nonsynonymous:synonymous arithmetic ratio (N:S) for RT-PCR error, yielding an N:S value ~one log-unit greater than that of consensus sequences. Probability of all possible single-base substitutions for the C2 region predicted N:S values within 95% confidence limits of themore » corrected within-isolate N:S when the only constraint imposed was viral polymerase error bias for transitions over transversions. These results indicate that bottlenecks coupled with strong negative/purifying selection drive consensus sequences toward neutral sequence space, and that most polymorphism within single-insect isolates is composed of newly-minted mutations sampled prior to selection. -- Highlights: •Sampling protocol minimized differential selection/history among isolates. •Polymorphism among consensus sequences dominated by negative/purifying selection. •Within-isolate N:S ratio corrected for RT-PCR error by bootstrapping. •Within-isolate mutant spectrum dominated by new mutations yet to undergo selection.« less

Structural And Electrical Properties oF (La{sub 0.5-x}Pr{sub x}Ba{sub 0.5})(Mn{sub 0.5}Ti{sub 0.5})O{sub 3} Perovskite

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

Alias, Nor Hayati; Department of Physics, Faculty Science, University Putra of Malaysia; Shaari, Abdul Halim

2010-01-05

A single phase monoclinic new perovskite based titano-manganite (La{sub 0.5-x}Pr{sub x}Ba{sub 0.5})(Mn{sub 0.5}Ti{sub 0.5})O{sub 3} has been successfully prepared by ceramic solid-state technique at sintering temperature of 1300 deg. C. The concentration of Pr (Praseodymium), x, in molar proportion in A site has been varied as x = 0, 0.02 and 0.2. Analysis has been carried out to determine the electrical properties of the synthesized material at frequency ranging from 5 Hz to 1 MHz; and at temperature range between 25 deg. C to 200 deg. C. It is found that Pr addition promoted liquid phase sintering diffusion, porosity andmore » agglomeration formation at 1300 deg. C. Dual relaxation is observed in unsubstituted Pr sample x = 0 and high Pr substituted sample x = 0.2. This phenomenon was a combinational contribution from a quasi dc (QDC) or low frequency dispersion (LFD), two cole-cole relaxational responses and a resistor. While low concentrated Pr substituted sampled x = 0.02 shows a combinational contribution from a quasi dc (QDC) or low frequency dispersion (LFD), single cole-cole relaxational response and a resistor at room temperature. Pr substitution at x = 0(max 12000) and x = 0.2(max 16000) showed high dielectric values compared to low substituted sample x = 0.02. Variation of dielectric loss tangent (tan delta) are observed for all samples at temperature ranged studied.« less

Modified nucleotides reveal the indirect role of the central base pairs in stabilizing the lac repressor-operator complex.

PubMed Central

Zhang, X; Gottlieb, P A

1995-01-01

Guanine residues in the lac operator were replaced by 2-aminopurine or purine analogues, pairing the modified nucleotides with C. The observed equilibrium dissociation constants for lac repressor binding to substituted operators were measured in 10 mM Tris, 150 mM KCl, 0.1 mM EDTA, 0.1 mM DTE, pH 7.6 at 25 degrees C. These measurements revealed five positions that destabilized the complex when substituted with either analogue. Two positions, which are related by a 2-fold symmetry, are in the major groove of the operator thought to directly interact with the protein. Three sites were in the central region of the operator. A purine analogue at a sixth site perturbed the local DNA structure and destabilized the complex. Alkylation interference experiments of the 2-aminopurine substituted operators demonstrated that, of the five affected, two substitutions displayed altered phosphate interference patterns at the phosphate adjacent to the substituted base. For these operators, complex formation was measured in different concentrations of KCl to assess the contribution of counterion release to the bimolecular process. The results indicated that both complexes were similar to wild-type, although minor changes were observed. The Kobs of the complex was then measured when 2-aminopurine or purine analogues were paired with uracil nucleotide, a base pair that serves to stabilize the DNA. The introduction of the new base pairs revealed two effects on the bimolecular interaction. For those operator sites that are thought to perturb the interaction directly, the affinity of the complex was weakened to levels observed for the singly-substituted operators. In contrast, the nucleotides of 2-aminopurine paired with uracil positioned in the central region of the operator served to enhance the stability of the complex. The purine-uracil base pair substitution on the other hand had a significant destabilizing effect on the interaction. We propose that the central base pairs modulate binding of the complex by altering the intrinsic properties of the DNA. Two specific attributes are required to achieve the lowest free energy of interaction. The DNA must have two interstrand hydrogen bonds to stabilize the duplex and it must have properties associated with directional bending or unwinding. This analysis does not rule out contributions by direct interactions between the protein and the central region of the operator but underscores how indirect effects play a major role in complex formation in this system. Images PMID:7784203

Fluorescence Visual Detection of Herbal Product Substitutions at Terminal Herbal Markets by CCP-based FRET technique.

PubMed

Jiang, Chao; Yuan, Yuan; Yang, Guang; Jin, Yan; Liu, Libing; Zhao, Yuyang; Huang, Luqi

2016-10-21

Inaccurate labeling of materials used in herbal products may compromise the therapeutic efficacy and may pose a threat to medicinal safety. In this paper, a rapid (within 3 h), sensitive and visual colorimetric method for identifying substitutions in terminal market products was developed using cationic conjugated polymer-based fluorescence resonance energy transfer (CCP-based FRET). Chinese medicinal materials with similar morphology and chemical composition were clearly distinguished by the single-nucleotide polymorphism (SNP) genotyping method. Assays using CCP-based FRET technology showed a high frequency of adulterants in Lu-Rong (52.83%) and Chuan-Bei-Mu (67.8%) decoction pieces, and patented Chinese drugs (71.4%, 5/7) containing Chuan-Bei-Mu ingredients were detected in the terminal herbal market. In comparison with DNA sequencing, this protocol simplifies procedures by eliminating the cumbersome workups and sophisticated instruments, and only a trace amount of DNA is required. The CCP-based method is particularly attractive because it can detect adulterants in admixture samples with high sensitivity. Therefore, the CCP-based detection system shows great potential for routine terminal market checks and drug safety controls.

Identification of acidic and aromatic residues in the Zta activation domain essential for Epstein-Barr virus reactivation.

PubMed

Deng, Z; Chen, C J; Zerby, D; Delecluse, H J; Lieberman, P M

2001-11-01

Epstein-Barr virus (EBV) lytic cycle transcription and DNA replication require the transcriptional activation function of the viral immediate-early protein Zta. We describe a series of alanine substitution mutations in the Zta activation domain that reveal two functional motifs based on amino acid composition. Alanine substitution of single or paired hydrophobic aromatic amino acid residues resulted in modest transcription activation defects, while combining four substitutions of aromatic residues (F22/F26/W74/F75) led to more severe transcription defects. Substitution of acidic amino acid residue E27, D35, or E54 caused severe transcription defects on most viral promoters. Promoter- and cell-specific defects were observed for some substitution mutants. Aromatic residues were required for Zta interaction with TFIIA-TFIID and the CREB-binding protein (CBP) and for stimulation of CBP histone acetyltransferase activity in vitro. In contrast, acidic amino acid substitution mutants interacted with TFIIA-TFIID and CBP indistinguishably from the wild type. The nuclear domain 10 (ND10) protein SP100 was dispersed by most Zta mutants, but acidic residue mutations led to reduced, while aromatic substitution mutants led to increased SP100 nuclear staining. Acidic residue substitution mutants had more pronounced defects in transcription activation of endogenous viral genes in latently infected cells and for viral replication, as measured by the production of infectious virus. One mutant, K12/F13, was incapable of stimulating EBV lytic replication but had only modest transcription defects. These results indicate that Zta stimulates viral reactivation through two nonredundant structural motifs, one of which interacts with general transcription factors and coactivators, and the other has an essential but as yet not understood function in lytic transcription.

Substitute CT generation from a single ultra short time echo MRI sequence: preliminary study

NASA Astrophysics Data System (ADS)

Ghose, Soumya; Dowling, Jason A.; Rai, Robba; Liney, Gary P.

2017-04-01

In MR guided radiation therapy planning both MR and CT images for a patient are acquired and co-registered to obtain a tissue specific HU map. Generation of the HU map directly from the MRI would eliminate the CT acquisition and may improve radiation therapy planning. In this preliminary study of substitute CT (sCT) generation, two porcine leg phantoms were scanned using a 3D ultrashort echo time (PETRA) sequence and co-registered to corresponding CT images to build tissue specific regression models. The model was created from one co-registered CT-PETRA pair to generate the sCT for the other PETRA image. An expectation maximization based clustering was performed on the co-registered PETRA image to identify the soft tissues, dense bone and air class membership probabilities. A tissue specific non linear regression model was built from one registered CT-PETRA pair dataset to predict the sCT of the second PETRA image in a two-fold cross validation schema. A complete substitute CT is generated in 3 min. The mean absolute HU error for air was 0.3 HU, bone was 95 HU, fat was 30 HU and for muscle it was 10 HU. The mean surface reconstruction error for the bone was 1.3 mm. The PETRA sequence enabled a low mean absolute surface distance for the bone and a low HU error for other classes. The sCT generated from a single PETRA sequence shows promise for the generation of fast sCT for MRI based radiation therapy planning.

Proline Substitution of Dimer Interface β-strand Residues as a Strategy for the Design of Functional Monomeric Proteins

PubMed Central

Joseph, Prem Raj B.; Poluri, Krishna Mohan; Gangavarapu, Pavani; Rajagopalan, Lavanya; Raghuwanshi, Sandeep; Richardson, Ricardo M.; Garofalo, Roberto P.; Rajarathnam, Krishna

2013-01-01

Proteins that exist in monomer-dimer equilibrium can be found in all organisms ranging from bacteria to humans; this facilitates fine-tuning of activities from signaling to catalysis. However, studying the structural basis of monomer function that naturally exists in monomer-dimer equilibrium is challenging, and most studies to date on designing monomers have focused on disrupting packing or electrostatic interactions that stabilize the dimer interface. In this study, we show that disrupting backbone H-bonding interactions by substituting dimer interface β-strand residues with proline (Pro) results in fully folded and functional monomers, by exploiting proline’s unique feature, the lack of a backbone amide proton. In interleukin-8, we substituted Pro for each of the three residues that form H-bonds across the dimer interface β-strands. We characterized the structures, dynamics, stability, dimerization state, and activity using NMR, molecular dynamics simulations, fluorescence, and functional assays. Our studies show that a single Pro substitution at the middle of the dimer interface β-strand is sufficient to generate a fully functional monomer. Interestingly, double Pro substitutions, compared to single Pro substitution, resulted in higher stability without compromising native monomer fold or function. We propose that Pro substitution of interface β-strand residues is a viable strategy for generating functional monomers of dimeric, and potentially tetrameric and higher-order oligomeric proteins. PMID:24048001

Lectins and substitution for helper function in anti-hapten responses in Xenopus laevis.

PubMed

Clothier, R H; James, H S; Ruben, L N; Balls, M

1984-08-01

Substitution by lectins for the carrier-priming requirement in thymus-dependent, antigen-binding responses in Xenopus laevis has been examined. Concanavalin A (Con A) was found to substitute for carrier priming in control, early-thymectomized and adult-thymectomized animals, but not in animals given a single, high dose of N-methyl-N-nitrosourea, which has a permanent effect on certain thymus-dependent functions in this species. Lipopolysaccharide and other lectins, such as peanut agglutinin and wheat germ agglutinin, were unable to substitute for carrier priming. These effects of Con A are discussed in terms of substitution via amplifier T cells or a helper T cell subset.

Reduction of Werner Syndrome Protein Enhances G:C → A:T Transition by O6-Methylguanine in Human Cells.

PubMed

Suzuki, Tetsuya; Kuramoto, Yoshie; Kamiya, Hiroyuki

2018-05-21

O 6 -Methylguanine ( O 6 -MeG) is a damaged base produced by methylating reagents. The Werner syndrome protein (WRN) is a cancer-related human DNA helicase. The effects of WRN reduction on O 6 -MeG-caused mutagenesis were assessed by an siRNA-mediated knockdown in human U2OS cells, using a shuttle plasmid with a single O 6 -MeG base in the supF gene. The plasmid DNA was replicated in the cells, isolated, and electroporated into an Escherichia coli indicator strain. The lowered amount of WRN increased the frequency of mutations induced by O 6 -MeG, mainly G:C → A:T substitution. The increased mutation rate suggested that the cancer-related WRN suppresses the G:C → A:T substitution by O 6 -MeG in human cells.

FISHER'S GEOMETRIC MODEL WITH A MOVING OPTIMUM

PubMed Central

Matuszewski, Sebastian; Hermisson, Joachim; Kopp, Michael

2014-01-01

Fisher's geometric model has been widely used to study the effects of pleiotropy and organismic complexity on phenotypic adaptation. Here, we study a version of Fisher's model in which a population adapts to a gradually moving optimum. Key parameters are the rate of environmental change, the dimensionality of phenotype space, and the patterns of mutational and selectional correlations. We focus on the distribution of adaptive substitutions, that is, the multivariate distribution of the phenotypic effects of fixed beneficial mutations. Our main results are based on an “adaptive-walk approximation,” which is checked against individual-based simulations. We find that (1) the distribution of adaptive substitutions is strongly affected by the ecological dynamics and largely depends on a single composite parameter γ, which scales the rate of environmental change by the “adaptive potential” of the population; (2) the distribution of adaptive substitution reflects the shape of the fitness landscape if the environment changes slowly, whereas it mirrors the distribution of new mutations if the environment changes fast; (3) in contrast to classical models of adaptation assuming a constant optimum, with a moving optimum, more complex organisms evolve via larger adaptive steps. PMID:24898080

Peripheral Substitution: An Easy Way to Tuning the Magnetic Behavior of Tetrakis(phthalocyaninato) Dysprosium(III) SMMs

PubMed Central

Shang, Hong; Zeng, Suyuan; Wang, Hailong; Dou, Jianmin; Jiang, Jianzhuang

2015-01-01

Two tetrakis(phthalocyaninato) dysprosium(III)-cadmium(II) single-molecule magnets (SMMs) with different extent of phthalocyanine peripheral substitution and therefore different coordination geometry for the Dy ions were revealed to exhibit different SMM behavior, providing an easy way to tuning and controlling the molecular structure and in turn the magnetic properties of tetrakis(tetrapyrrole) lanthanide SMMs through simple tetrapyrrole peripheral substitution. PMID:25744587

DFT study of the effect of substituents on the absorption and emission spectra of Indigo

PubMed Central

2012-01-01

Background Theoretical analyses of the indigo dye molecule and its derivatives with Chlorine (Cl), Sulfur (S), Selenium (Se) and Bromine (Br) substituents, as well as an analysis of the Hemi-Indigo molecule, were performed using the Gaussian 03 software package. Results Calculations were performed based on the framework of density functional theory (DFT) with the Becke 3- parameter-Lee-Yang-Parr (B3LYP) functional, where the 6-31 G(d,p) basis set was employed. The configuration interaction singles (CIS) method with the same basis set was employed for the analysis of excited states and for the acquisition of the emission spectra. Conclusions The presented absorption and emission spectra were affected by the substitution position. When a hydrogen atom of the molecule was substituted by Cl or Br, practically no change in the absorbed and emitted energies relative to those of the indigo molecule were observed; however, when N was substituted by S or Se, the absorbed and emitted energies increased. PMID:22809100

Mutation analysis of GLDC, AMT and GCSH in cataract captive-bred vervet monkeys (Chlorocebus aethiops).

PubMed

Chauke, Chesa G; Magwebu, Zandisiwe E; Sharma, Jyoti R; Arieff, Zainunisha; Seier, Jürgen V

2016-08-01

Non-ketotic hyperglycinaemia (NKH) is an autosomal recessive inborn error of glycine metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. This study describes the first screening of NKH in cataract captive-bred vervet monkeys (Chlorocebus aethiops). Glycine dehydrogenase (GLDC), aminomethyltransferase (AMT) and glycine cleavage system H protein (GCSH) were prioritized. Mutation analysis of the complete coding sequence of GLDC and AMT revealed six novel single-base substitutions, of which three were non-synonymous missense and three were silent nucleotide changes. Although deleterious effects of the three amino acid substitutions were not evaluated, one substitution of GLDC gene (S44R) could be disease-causing because of its drastic amino acid change, affecting amino acids conserved in different primate species. This study confirms the diagnosis of NKH for the first time in vervet monkeys with cataracts. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ab initio studies of isolated boron substitutional defects in graphane

NASA Astrophysics Data System (ADS)

Mapasha, R. E.; Chetty, N.

2017-10-01

We have systematically studied energetics, structural and electronic properties of different configurations of the B atoms substituting C-H pairs located on a single hexagonal ring in a graphane system using the first-principles density functional theory (DFT). A total number of 12 distinct B dopants configurations were identified and characterized. Based on the formation energy analysis, we found that relative stability of B dopants depends greatly on the defect configurations. Our results suggest that the B substitutions prefer to be distributed randomly but avoiding the formation of homo-elemental B-B bonds in a graphane system, at any concentration. Generally, the values of band gap decrease as the number of B dopants increases, but the low energy configurations have large band gaps compared to those that have homo-elemental bonds. As a result, the band gap of graphane can be fine tuned through the change in the structural arrangement of B atoms. The adequate control of the electronic structure of graphane through doping should be essential for technological device applications.

Simulation analysis of formycin 5?-monophosphate analog substrates in the ricin A-chain active site

NASA Astrophysics Data System (ADS)

Olson, Mark A.; Scovill, John P.; Hack, Dallas C.

1995-06-01

Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A-chain active site.

PubMed

Olson, M A; Scovill, J P; Hack, D C

1995-06-01

Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

Activation and reactivation of the RNA polymerase II trigger loop for intrinsic RNA cleavage and catalysis

PubMed Central

Čabart, Pavel; Jin, Huiyan; Li, Liangtao; Kaplan, Craig D

2014-01-01

In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process. Here we show that a single amino-acid substitution in the trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of intrinsic cleavage activity where the substituted tyrosine appears to participate in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl transfer. We extensively characterize this TL substitution for each of these reactions by examining the responses RNAP II enzymes to catalytic metals, altered pH, and factor inputs. We demonstrate that TFIIF stimulation of the first phosphodiester bond formation by RNAP II requires wild type TL function and that H1085Y substitution within the TL compromises or alters RNAP II responsiveness to both TFIIB and TFIIF. Finally, Mn2+ stimulation of H1085Y RNAP II reveals possible allosteric effects of TFIIB on the active center and cooperation between TFIIB and TFIIF. PMID:25764335

Palladium-catalyzed double carbonylation using near stoichiometric carbon monoxide: expedient access to substituted 13C2-labeled phenethylamines.

PubMed

Nielsen, Dennis U; Neumann, Karoline; Taaning, Rolf H; Lindhardt, Anders T; Modvig, Amalie; Skrydstrup, Troels

2012-07-20

A novel and general approach for (13)C(2)- and (2)H-labeled phenethylamine derivatives has been developed, based on a highly convergent single-step assembly of the carbon skeleton. The efficient incorporation of two carbon-13 isotopes into phenethylamines was accomplished using a palladium-catalyzed double carbonylation of aryl iodides with near stoichiometric carbon monoxide.

40 CFR 419.22 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (TOC) based upon an analysis of any single grab or composite sample. (2) If contaminated runoff is... which exceeds 15 mg/l oil and grease or 110 mg/l TOC is not commingled or treated with any other type of... the effluent exceeds 1,000 mg/l (1,000 ppm), the permitting authority may substitute TOC as a...

40 CFR 419.43 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 110 mg/l total organic carbon (TOC) based upon an analysis of any single grab or composite sample. (2... solely of contaminated runoff which exceeds 110 mg/l TOC is not commingled or treated with any other type... effluent exceeds 1,000 mg/l (1,000 ppm), the permitting authority may substitute TOC as a parameter in lieu...

Protein Adhesion and Ion Substitution (on/in)to Minerals

NASA Astrophysics Data System (ADS)

Charlet, L.; Fernandez Martinez, A.; Chapron, Y.; Sahai, N.; Cuello, G.; Brendle, J.; Marichal, C.

2008-12-01

Arsenic and pathogenic prion protein-scrapie (PrPsc) are important contaminants which may soil and water for decades, unless they are removed by sorption. Two sorption mechanisms will be discussed, namely the organics (Prp and single aminoacid) adsorption on clay and the arsenic substitution in gypsum. The elucidation of these contrasted mechanisms will be shown to request complementary molecular-mechanical simulations with experimental spectroscopic investigations. As first example, structural studies performed at ILL/ESRF on As-doped gypsum (CaSO4 2H2O) using neutron and X-ray diffraction data and EXAFS were performed to determine how As fits into the bulk of gypsum structure. The combined Rietveld analysis of neutron and X-ray diffraction data shows an expansion of the unit cell volume proportional to the As concentration within the samples. to-sulfate substitution mechanisms were used as simulation starting hypotheses. DFT-based simulations (Mulliken analysis) were used to interpret charge distribution and to show that among the possible mechanisms, a sulphate substitution by either protonated, or fully deprotonated, arsenate ion, only the protonated arsenate substitution could best fit the EXAFS data. In the second example, we used Molecular Dynamics to understand the mechanism of strong binding of the pathogenic PrP peptide with clay mineral surfaces. We modeled only the infectious moiety, PrP92-138, of the whole PrPsc structure, with explicitly solvating water molecules in contact with the cleavage plane of pyrophillite, as a model for montmorillonite without any cationic substitution. Partial residual negative charges on the cleavage plane were balanced with K+ ions. The peptide anchored to the clay surface via up to 10 hydrogen bonds from lysine and histidine residues to oxygen atoms of the siloxane cavities, and a total adsorption energy of 3465 KJ.mol-1 was obtained. Our results were compared to the one obtained by chemical and thermal analysis, 23Na, 1H, 13C solid state NMR and MD computation on sorption of single lysine amino acid on model synthetic Na-montmorillonite. Our data provide further insight about interactions between lysine and montmorillonite which depend strongly on lysine concentration.

Synthesis and characterization of a novel schiff base of 1,2-diaminopropane with substituted salicyaldehyde and its transition metal complexes: Single crystal structures and biological activities

NASA Astrophysics Data System (ADS)

Tadavi, Samina K.; Yadav, Abhijit A.; Bendre, Ratnamala S.

2018-01-01

A novel schiff base H2L derived from simple condensation of 2-hydroxy-6-isopropyl-3-methyl benzaldehyde and 1,2-diaminopropane in 2:1 M ratio and its [MnL], [CoL] and [NiL]2 complexes have been prepared and characterized by spectroscopic technique, elemental analysis, SEM-EDX analysis, and cyclic voltammetry. Additionally, single crystal X-ray diffraction technique has been applied to the schiff base ligand H2L and its nickel complex. The structure of nickel complex exhibited dimeric form with formula [NiL]2 with distorted square planar geometry around each nickel center. Furthermore, all the synthesized compounds were screened for their antimicrobial and antioxidant and DNA cleavage activities.

Formation of the nitrogen aggregates in annealed diamond by neutron irradiation

NASA Astrophysics Data System (ADS)

Mita, Y.; Nisida, Y.; Okada, M.

2018-02-01

Neutron heavy irradiation was performed on synthetic diamonds contain nitrogen atoms in isolated substitutional form (called "type Ib diamond") and they were annealed under a pressure of 6 GPa. A large number of nitrogen B-aggregate which consists of four substitutional nitrogen atoms symmetrically surrounding a vacancy was formed within 30 m from single nitrogen atoms. Furthermore it is observed that, in these diamonds, single nitrogen atoms coexist with the B-aggregates, which is unexplainable by the simple nitrogen aggregation model.

Designing Antibacterial Peptides with Enhanced Killing Kinetics

PubMed Central

Waghu, Faiza H.; Joseph, Shaini; Ghawali, Sanket; Martis, Elvis A.; Madan, Taruna; Venkatesh, Kareenhalli V.; Idicula-Thomas, Susan

2018-01-01

Antimicrobial peptides (AMPs) are gaining attention as substitutes for antibiotics in order to combat the risk posed by multi-drug resistant pathogens. Several research groups are engaged in design of potent anti-infective agents using natural AMPs as templates. In this study, a library of peptides with high sequence similarity to Myeloid Antimicrobial Peptide (MAP) family were screened using popular online prediction algorithms. These peptide variants were designed in a manner to retain the conserved residues within the MAP family. The prediction algorithms were found to effectively classify peptides based on their antimicrobial nature. In order to improve the activity of the identified peptides, molecular dynamics (MD) simulations, using bilayer and micellar systems could be used to design and predict effect of residue substitution on membranes of microbial and mammalian cells. The inference from MD simulation studies well corroborated with the wet-lab observations indicating that MD-guided rational design could lead to discovery of potent AMPs. The effect of the residue substitution on membrane activity was studied in greater detail using killing kinetic analysis. Killing kinetics studies on Gram-positive, negative and human erythrocytes indicated that a single residue change has a drastic effect on the potency of AMPs. An interesting outcome was a switch from monophasic to biphasic death rate constant of Staphylococcus aureus due to a single residue mutation in the peptide. PMID:29527201

High coercivity Gd-substituted Ba hexaferrites, prepared by chemical coprecipitation

NASA Astrophysics Data System (ADS)

Litsardakis, G.; Manolakis, I.; Serletis, C.; Efthimiadis, K. G.

2008-04-01

A series of Gd-substituted Ba hexaferrites with nominal formula (Ba1-xGdx)Oṡ5.25 Fe2O3 (x=0-0.30) were prepared by the chemical coprecipitation method from nitrate precursors and heating at T =800-1200°C for 2h. The samples have been examined by x-ray diffraction, vibrating-sample magnetometer, and scanning electron microscopy methods. Gd substituted samples form single phase materials with the M-type hexaferrite structure at all heating temperatures, in the range of x ⩽0.10-0.20. The saturation magnetization (at 1.8T) varies slightly with x in most cases and, for x =0.05-0.10, it increases up to 66.7Am2/kg, exceeding the value of the unsubstituted hexaferrite. A strong enhancement of the coercivity is observed for all substituted samples, with maximum values Hc=457kA/m for the single-phase x =0.10 sample annealed at 1000°C and Hc=477kA/m for the x =0.25 sample annealed at 1100°C which contains Fe2O3 and GdFeO3 impurities. As the variation of coercivity with either substitution rate (x ) or annealing temperature is not monotonic, three different factors may account for the high coercivities that are obtained: (a) an inhibition of grain growth due to the presence of Gd, (b) a possible inherent effect on magnetocrystalline anisotropy, especially for single phase samples, and (c) a microstructural effect of secondary phases.

Enhanced water purification: a single atom makes a difference.

PubMed

Stewart, Tom A; Trudell, Daniel E; Alam, Todd M; Ohlin, C André; Lawler, Christian; Casey, William H; Jett, Stephen; Nyman, May

2009-07-15

The aluminum Keggin polycation (Al13) has been identified as an effective specie for neutralization and coagulation of anionic contaminants in water. In this study, we compare efficacy of the aluminum Keggin-ion to the analogues containing a single Ga-atom or single Ge-atom (GaAl12 and GeAl12, respectively) substituted into the center of the polycation in water-treatment studies. We investigated removal of bacteriophage (model viruses), Cryptosporidium, dissolved organic carbon (DOC), and turbidity. In every study, the order of contaminant removal efficacy trends GaAl12 > Al13 > GeAl12. By ESI MS (electrospray ionization mass spectrometry), we noted the GaAl12 deprotonates least of the three aluminum polycations, and thus probably carries the highest charge, and also optimal contaminant-neutralization ability. The ESI MS studies of the aluminum polycation solutions, as well as solid-state characterization of their resulting precipitates both reveal some conversion of Al13 to larger polycations, Al30 for instance. The GaAl12 does not show any evidence for this alteration that is responsible for poor shelf life of commercial prehydrolyzed aluminum coagulants such as polyaluminum chloride. Based on these studies, we conclude that substitution of a single Ga-atom in the center of the aluminum Keggin polycation produces an optimal water-treatment product due to enhanced shelf life and efficacy in neutralization of anionic contaminants.

Comparison among methods of effective energy evaluation of corn silage for beef cattle.

PubMed

Wei, Ming; Chen, Zhiqiang; Wei, Shengjuan; Geng, Guangduo; Yan, Peishi

2018-06-01

This study was conducted to compare different methods on effective energy evaluation of corn silage for beef cattle. Twenty Wandong bulls (Chinese indigenous yellow cattle) with initial body weight of 281±15.6 kg, were assigned to 1 of 5 dietary treatments with 4 animals per treatment in a randomized complete block design. Five dietary treatments included group 1 with corn silage only diet, group 2 with corn silage-concentrate basal diet (BD) and 3 groups with 3 test diets, which were the BD partly substituted by corn silage at 10%, 30%, and 60%. The total collection digestion trial was conducted for 5 d for each block after a 10-d adaptation period, and then an open-circuit respiratory cage was used to measure the gas exchange of each animal in a consecutive 4-d period. The direct method-derived metabolizable energy and net energy of corn silage were 8.86 and 5.15 MJ/kg dry matter (DM), expressed as net energy requirement for maintenance and gain were 5.28 and 2.90 MJ/kg DM, respectively; the corresponding regression method-derived estimates were 8.96, 5.34, 5.37, and 2.98 MJ/kg DM, respectively. The direct method-derived estimates were not different (p>0.05) from those obtained using the regression method. Using substitution method, the nutrient apparent digestibility and effective energy values of corn silage varied with the increased corn silage substitution ratio (p<0.05). In addition, the corn silage estimates at the substitution ratio of 30% were similar to those estimated by direct and regression methods. In determining the energy value of corn silage using substitution method, there was a discrepancy between different substitution ratios, and the substitution ratio of 30% was more appropriate than 10% or 60% in the current study. The regression method based on multiple point substitution was more appropriate than single point substitution on energy evaluation of feedstuffs for beef cattle.

West Nile virus (WNV) genome RNAs with up to three adjacent mutations that disrupt long distance 5'-3' cyclization sequence basepairs are viable

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

Basu, Mausumi; Brinton, Margo A., E-mail: mbrinton@gsu.ed

2011-03-30

Mosquito-borne flavivirus genomes contain conserved 5' and 3' cyclization sequences (CYC) that facilitate long distance RNA-RNA interactions. In previous studies, flavivirus replicon RNA replication was completely inhibited by single or multiple mismatching CYC nt substitutions. In the present study, full-length WNV genomes with one, two or three mismatching CYC substitutions showed reduced replication efficiencies but were viable and generated revertants with increased replication efficiency. Several different three adjacent mismatching CYC substitution mutant RNAs were rescued by a second site mutation that created an additional basepair (nts 147-10913) on the internal genomic side of the 5'-3' CYC. The finding that full-lengthmore » genomes with up to three mismatching CYC mutations are viable and can be rescued by a single nt spontaneous mutation indicates that more than three adjacent CYC basepair substitutions would be required to increase the safety of vaccine genomes by creating mismatches in inter-genomic recombinants.« less

A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

PubMed Central

Florio, Marta; Namba, Takashi; Pääbo, Svante; Hiller, Michael; Huttner, Wieland B.

2016-01-01

The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex. PMID:27957544

Proline substitution of dimer interface β-strand residues as a strategy for the design of functional monomeric proteins.

PubMed

Joseph, Prem Raj B; Poluri, Krishna Mohan; Gangavarapu, Pavani; Rajagopalan, Lavanya; Raghuwanshi, Sandeep; Richardson, Ricardo M; Garofalo, Roberto P; Rajarathnam, Krishna

2013-09-17

Proteins that exist in monomer-dimer equilibrium can be found in all organisms ranging from bacteria to humans; this facilitates fine-tuning of activities from signaling to catalysis. However, studying the structural basis of monomer function that naturally exists in monomer-dimer equilibrium is challenging, and most studies to date on designing monomers have focused on disrupting packing or electrostatic interactions that stabilize the dimer interface. In this study, we show that disrupting backbone H-bonding interactions by substituting dimer interface β-strand residues with proline (Pro) results in fully folded and functional monomers, by exploiting proline's unique feature, the lack of a backbone amide proton. In interleukin-8, we substituted Pro for each of the three residues that form H-bonds across the dimer interface β-strands. We characterized the structures, dynamics, stability, dimerization state, and activity using NMR, molecular dynamics simulations, fluorescence, and functional assays. Our studies show that a single Pro substitution at the middle of the dimer interface β-strand is sufficient to generate a fully functional monomer. Interestingly, double Pro substitutions, compared to single Pro substitution, resulted in higher stability without compromising native monomer fold or function. We propose that Pro substitution of interface β-strand residues is a viable strategy for generating functional monomers of dimeric, and potentially tetrameric and higher-order oligomeric proteins. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Modulation of DNA-Polyamide Interaction by β-alanine Substitutions: A Study of Positional Effects on Binding Affinity, Kinetics and Thermodynamics

PubMed Central

Wang, Shuo; Aston, Karl; Koeller, Kevin J.; Harris, G. Davis; Rath, Nigam P.

2014-01-01

Hairpin polyamides (PAs) are an important class of sequence-specific DNA minor groove binders, and frequently employ a flexible motif, β-alanine (β), to reduce the molecular rigidity to maintain the DNA recognition register. To better understand the diverse effects β can have on DNA-PA binding affinity, selectivity, and especially kinetics, which have rarely been reported, we have initiated a detailed study for an eight-heterocyclic hairpin PA and its β derivatives with their cognate and mutant sequences. With these derivatives, all internal pyrroles of the parent PA are systematically substituted with single or double βs. A set of complementary experiments have been conducted to evaluate the molecular interactions in detail: UV-melting, biosensor-surface plasmon resonance, circular dichroism and isothermal titration calorimetry. The β substitutions generally weaken the binding affinities of these PAs with cognate DNA, and have large and diverse influences on PA binding kinetics in a position- and number-dependent manner. The DNA base mutations have also shown positional effects on binding of a single PA. Besides the β substitutions, the monocationic Dp group [3-(dimethylamino) propylamine] in parent PA has been modified into a dicationic Ta group (3, 3'-Diamino-N-methyldipropylamine) to minimize the frequently observed PA aggregation with ITC experiments. The results clearly show that the Ta modification not only maintains the DNA binding mode and affinity of PA, but also significantly reduces PA aggregation and allows the complete thermodynamic signature of eight-ring hairpin PA to be determined for the first time. This combined set of results significantly extends our understanding of the energetic basis of specific DNA recognition by PAs. PMID:25141096

Solid oral forms availability in children: a cost saving investigation

PubMed Central

Lajoinie, Audrey; Henin, Emilie; Kassai, Behrouz; Terry, David

2014-01-01

Aim To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. Method Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. Results Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of £5K and £8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of £238K and £410K (single institution). Conclusion Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules. PMID:24965935

Ultraviolet mutagenesis in a plasmid vector replicated in lymphoid cells from patient with the melanoma-prone disorder dysplastic nevus syndrome

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

Seetharam, S.; Waters, H.L.; Seidman, M.M.

The hereditary dysplastic nevus syndrome (DNS) is an autosomal dominant disorder in which affected individuals have increased numbers of dysplastic (premalignant) nevi and a greater than 100-fold increased risk of developing cutaneous melanoma. Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with hereditary DNS have been shown to be hypermutable to UV radiation. To examine the mechanism involved in this UV hypermutability, we used a shuttle vector plasmid, pZ189, which carries a 160-base pair marker gene, supF, and can replicate in human cells. pZ189 was treated with UV radiation and transfected into DNS6BE, a lymphoblastoid cell line from a patient withmore » hereditary DNS. Plasmid survival after UV was similar with the DNS6BE line and with a lymphoblastoid cell line from a normal donor. Plasmid mutation frequency was greater with the DNS line in accord with the DNS cellular hypermutability. Base sequence analysis was performed on 69 mutated plasmids recovered from the DNS line. There were significantly more plasmids with single base substitution mutations (P less than 0.01) in comparison to UV-treated plasmids passed through normal fibroblasts. pZ189 hypermutability and an increased frequency of single base substitutions was previously found with a cell line from a melanoma-prone xeroderma pigmentosum patient. These differences may be related to the increased melanoma susceptibility in both DNS and xeroderma pigmentosum.« less

Sugar Substitutes

MedlinePlus

... Substitutes Share Print Sugar substitutes are chemical or plant-based substances used to sweeten or enhance the ... made with saccharin. Stevia sweeteners Stevia is a plant-based sugar substitute that has no calories. The ...

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

PubMed

Soler, Miguel A; de Marco, Ario; Fortuna, Sara

2016-10-10

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

NASA Astrophysics Data System (ADS)

Soler, Miguel A.; De Marco, Ario; Fortuna, Sara

2016-10-01

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Magnetic moment in single crystalline BaFe2-xZnxAs2

NASA Astrophysics Data System (ADS)

Guo, Yanfeng; Wang, Xia; Li, Jun; Yamaura, Kazunari; Takayama-Muromachi, Eiji

2012-02-01

Nature of the magnetism for iron-based superconductors (FeSCs) has been actively studied since the discovery of this new family of compounds in 2008, largely owing to its significance for interpreting the paring mechanism. The approach through impurity substitution to shed light into this issue is always one of major ways. The substitution shows distinct responses to species of impurities, where partially replacement of Fe in parent FeSCs with a variety of d-metals like Co, Ni Ru, Rh, Pd, Ir, and Pt generally results in superconductivity, while recent progress in Zn doped FeSCs gives rather contrary result, where Zn severely degenerates the TC. Herein we show the magnetic and electrical studies on BaFe2-xZnxAs2 single crystals. Nonmagnetic Zn doping progressively suppresses the SDW without resulting in superconductivity, while it alternatively develops the spin-glass state, possibly suggestive of local magnetic moment around the Fe sites induced by Zn. The characterizations by X-ray diffraction, magnetic and electrical transport properties, specific heat capacity, and Hall coefficient have been done and the results will be discussed in detail.

Is dibotermin alfa a cost-effective substitute for autologous iliac crest bone graft in single level lumbar interbody spine fusion?

PubMed

Svedbom, Axel; Paech, Daniel; Leonard, Catherine; Donnell, David; Song, Fujian; Boszcyk, Bronek; Rothenfluh, Dominique A; Lloyd, Andrew; Borgman, Benny

2015-11-01

To evaluate the cost-effectiveness of dibotermin alfa compared with autologous iliac crest bone graft (ICBG) for patients undergoing single level lumbar interbody spinal fusion in a UK hospital setting. An individual patient data (IPD) meta-analysis of six randomized controlled clinical trials and two single arm trials compared dibotermin alfa on an absorbable collagen implantation matrix (ACIM) (n = 456) and ICBG (n = 244) on resource use, re-operation rates, and SF-6D (Short form 6-dimension) health utility (total N = 700). Failure-related second surgery, operating time, post-operative hospital stay, and quality-adjusted life years (QALYs) derived from the IPD meta-analysis were included as inputs in an economic evaluation undertaken to assess the cost-effectiveness of dibotermin alfa/ACIM versus ICBG for patients undergoing single level lumbar interbody spinal fusion. A four year time horizon and the United Kingdom (UK) National Health Service (NHS) and Personal Social Services (PSS) perspective was adopted in the base case, with sensitivity analyses performed to gauge parameter uncertainty. In the base case analysis, patients treated using dibotermin alfa/ACIM (12 mg pack) accrued 0.055 incremental QALYs at an incremental cost of £ 737, compared with patients treated with ICBG. This resulted in an incremental cost-effectiveness ratio (ICER) of £ 13,523, indicating that at a willingness-to-pay threshold of £ 20,000, dibotermin alfa/ACIM is a cost-effective intervention relative to ICBG from the NHS and PSS perspective. In a UK hospital setting, dibotermin alfa/ACIM is a cost-effective substitute for ICBG for patients who require lumbar interbody arthrodesis.

Photophysical investigation of cyano-substituted terrylenediimide derivatives.

PubMed

Kennes, Koen; Baeten, Yannick; Vosch, Tom; Sempels, Wouter; Yordanov, Stoyan; Stappert, Sebastian; Chen, Long; Müllen, Klaus; Hofkens, Johan; Van der Auweraer, Mark; Fron, Eduard

2014-12-18

Two new terrylenediimide (TDI) chromophores with cyano substituents in the bay and core area (BCN-TDI and OCN-TDI, respectively) have been characterized by a wide range of techniques, and their applicability for stimulated emission depletion (STED) microscopy has been tested. By cyano substitution an increase of the fluorescence quantum yield and a decrease of the nonradiative rate constant is achieved and attributed to a reduced charge-transfer character of the excited state due to a lower electron density of the TDI core. For BCN-TDI, the substitution in the bay area induces a strong torsional twist in the molecule which, similar to phenoxy bay-perylenediimide (PDI), has a strong effect on the fluorescence lifetime but appears to prevent the aggregation that is observed for OCN-TDI. The single-molecule photobleaching stability of BCN- and OCN-TDI is lower than that of a reference TDI without cyano substitution (C7-TDI), although less so for OCN-TDI. The photophysical properties of the excited singlet state are only slightly influenced by the cyano groups. The observed intense stimulated emission, the pump-dump-probe experiments, and STED single-molecule imaging indicate that STED experiments with the cyano-substituted TDIs are possible. However, because of aggregation and more efficient photobleaching, the performance of BCN- and OCN-TDI is worse than that of the reference compound without cyano groups (C7-TDI). Bay-substituted TDIs are less suitable for STED microscopy.

Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks

PubMed Central

Belotserkovskii, Boris P.; Neil, Alexander J.; Saleh, Syed Shayon; Shin, Jane Hae Soo; Mirkin, Sergei M.; Hanawalt, Philip C.

2013-01-01

The ability of DNA to adopt non-canonical structures can affect transcription and has broad implications for genome functioning. We have recently reported that guanine-rich (G-rich) homopurine-homopyrimidine sequences cause significant blockage of transcription in vitro in a strictly orientation-dependent manner: when the G-rich strand serves as the non-template strand [Belotserkovskii et al. (2010) Mechanisms and implications of transcription blockage by guanine-rich DNA sequences., Proc. Natl Acad. Sci. USA, 107, 12816–12821]. We have now systematically studied the effect of the sequence composition and single-stranded breaks on this blockage. Although substitution of guanine by any other base reduced the blockage, cytosine and thymine reduced the blockage more significantly than adenine substitutions, affirming the importance of both G-richness and the homopurine-homopyrimidine character of the sequence for this effect. A single-strand break in the non-template strand adjacent to the G-rich stretch dramatically increased the blockage. Breaks in the non-template strand result in much weaker blockage signals extending downstream from the break even in the absence of the G-rich stretch. Our combined data support the notion that transcription blockage at homopurine-homopyrimidine sequences is caused by R-loop formation. PMID:23275544

Imaging of Al/Fe ratios in synthetic Al-goethite revealed by nanoscale secondary ion mass spectrometry.

PubMed

Pohl, Lydia; Kölbl, Angelika; Werner, Florian; Mueller, Carsten W; Höschen, Carmen; Häusler, Werner; Kögel-Knabner, Ingrid

2018-04-30

Aluminium (Al)-substituted goethite is ubiquitous in soils and sediments. The extent of Al-substitution affects the physicochemical properties of the mineral and influences its macroscale properties. Bulk analysis only provides total Al/Fe ratios without providing information with respect to the Al-substitution of single minerals. Here, we demonstrate that nanoscale secondary ion mass spectrometry (NanoSIMS) enables the precise determination of Al-content in single minerals, while simultaneously visualising the variation of the Al/Fe ratio. Al-substituted goethite samples were synthesized with increasing Al concentrations of 0.1, 3, and 7 % and analysed by NanoSIMS in combination with established bulk spectroscopic methods (XRD, FTIR, Mössbauer spectroscopy). The high spatial resolution (50-150 nm) of NanoSIMS is accompanied by a high number of single-point measurements. We statistically evaluated the Al/Fe ratios derived from NanoSIMS, while maintaining the spatial information and reassigning it to its original localization. XRD analyses confirmed increasing concentration of incorporated Al within the goethite structure. Mössbauer spectroscopy revealed 11 % of the goethite samples generated at high Al concentrations consisted of hematite. The NanoSIMS data show that the Al/Fe ratios are in agreement with bulk data derived from total digestion and demonstrated small spatial variability between single-point measurements. More advantageously, statistical analysis and reassignment of single-point measurements allowed us to identify distinct spots with significantly higher or lower Al/Fe ratios. NanoSIMS measurements confirmed the capacity to produce images, which indicated the uniform increase in Al-concentrations in goethite. Using a combination of statistical analysis with information from complementary spectroscopic techniques (XRD, FTIR and Mössbauer spectroscopy) we were further able to reveal spots with lower Al/Fe ratios as hematite. Copyright © 2018 John Wiley & Sons, Ltd.

Charge-coupled substituted garnets (Y 3–x Ca 0.5x M 0.5x )Fe₅O₁₂ (M = Ce, Th): Structure and stability as crystalline nuclear waste forms

DOE PAGES

Guo, Xiaofeng; Kukkadapu, Ravi K.; Lanzirotti, Antonio; ...

2015-04-20

The garnet structure has been proposed as a potential crystalline nuclear waste form for accommodation of actinide elements, especially uranium (U). In this study, yttrium iron garnet (YIG) as a model garnet host was studied for the incorporation of U analogs, cerium (Ce) and thorium (Th), incorporated by a charge-coupled substitution with calcium (Ca) for yttrium (Y) in YIG, namely, 2Y³⁺ = Ca²⁺ + M⁴⁺, where M⁴⁺ = Ce⁴⁺ or Th⁴⁺. Single-phase garnets Y 3–xCa 0.5xM 0.5xFe₅O₁₂ (x = 0.1–0.7) were synthesized by the citrate–nitrate combustion method. Ce was confirmed to be tetravalent by X-ray absorption spectroscopy and X-ray photoelectronmore » spectroscopy. X-ray diffraction and ⁵⁷Fe–Mössbauer spectroscopy indicated that M⁴⁺ and Ca²⁺ cations are restricted to the c site, and the local environments of both the tetrahedral and the octahedral Fe³⁺ are systematically affected by the extent of substitution. The charge-coupled substitution has advantages in incorporating Ce/Th and in stabilizing the substituted phases compared to a single substitution strategy. Enthalpies of formation of garnets were obtained by high-temperature oxide melt solution calorimetry, and the enthalpies of substitution of Ce and Th were determined. The thermodynamic analysis demonstrates that the substituted garnets are entropically rather than energetically stabilized. This suggests that such garnets may form and persist in repositories at high temperature but might decompose near room temperature.« less

Screening for Novel Germline Rare Mutations Associated with Aggressive Prostate Cancer

DTIC Science & Technology

2015-12-01

amino acid substitution from Threonine (Thr) to Proline (Pro); while rs61756080 results to the amino acid substitution from Glycine (Gly) to Glutamic...Single nucleotide polymorphisms 20 in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes . Diabetologia. 2005 Jul;48(7

Site-selective substitutional doping with atomic precision on stepped Al (111) surface by single-atom manipulation

PubMed Central

2014-01-01

In fabrication of nano- and quantum devices, it is sometimes critical to position individual dopants at certain sites precisely to obtain the specific or enhanced functionalities. With first-principles simulations, we propose a method for substitutional doping of individual atom at a certain position on a stepped metal surface by single-atom manipulation. A selected atom at the step of Al (111) surface could be extracted vertically with an Al trimer-apex tip, and then the dopant atom will be positioned to this site. The details of the entire process including potential energy curves are given, which suggests the reliability of the proposed single-atom doping method. PMID:24899871

Site-selective substitutional doping with atomic precision on stepped Al (111) surface by single-atom manipulation.

PubMed

Chen, Chang; Zhang, Jinhu; Dong, Guofeng; Shao, Hezhu; Ning, Bo-Yuan; Zhao, Li; Ning, Xi-Jing; Zhuang, Jun

2014-01-01

In fabrication of nano- and quantum devices, it is sometimes critical to position individual dopants at certain sites precisely to obtain the specific or enhanced functionalities. With first-principles simulations, we propose a method for substitutional doping of individual atom at a certain position on a stepped metal surface by single-atom manipulation. A selected atom at the step of Al (111) surface could be extracted vertically with an Al trimer-apex tip, and then the dopant atom will be positioned to this site. The details of the entire process including potential energy curves are given, which suggests the reliability of the proposed single-atom doping method.

Mapping the neutralizing epitopes on the glycoprotein of infectious haematopoietic necrosis virus, a fish rhabdovirus

USGS Publications Warehouse

Huang, C.; Chien, M.S.; Landolt, M.L.; Batts, W.; Winton, J.

1996-01-01

Twelve neutralizing monoclonal antibodies (MAbs) against the fish rhabdovirus, infectious haematopoietic necrosis virus (IHNV), were used to select 20 MAb escape mutants. The nucleotide sequence of the entire glycoprotein (G) gene was determined for six mutants representing differing cross-neutralization patterns and each had a single nucleotide change leading to a single amino acid substitution within one of three regions of the protein. These data were used to design nested PCR primers to amplify portions of the G gene of the 14 remaining mutants. When the PCR products from these mutants were sequenced, they also had single nucleotide substitutions coding for amino acid substitutions at the same, or nearby, locations. Of the 20 mutants for which all or part of the glycoprotein gene was sequenced, two MAbs selected mutants with substitutions at amino acids 230-231 (antigenic site I) and the remaining MAbs selected mutants with substitutions at amino acids 272-276 (antigenic site II). Two MAbs that selected mutants mapping to amino acids 272-276, selected other mutants that mapped to amino acids 78-81, raising the possibility that this portion of the N terminus of the protein was part of a discontinuous epitope defining antigenic site II. CLUSTAL alignment of the glycoproteins of rabies virus, vesicular stomatitis virus and IHNV revealed similarities in the location of the neutralizing epitopes and a high degree of conservation among cysteine residues, indicating that the glycoproteins of three different genera of animal rhabdoviruses may share a similar three-dimensional structure in spite of extensive sequence divergence.

Tuning the Origin of Magnetic Relaxation by Substituting the 3d or Rare-Earth Ions into Three Isostructural Cyano-Bridged 3d-4f Heterodinuclear Compounds.

PubMed

Zhang, Yan; Guo, Zhen; Xie, Shuang; Li, Hui-Li; Zhu, Wen-Hua; Liu, Li; Dong, Xun-Qing; He, Wei-Xun; Ren, Jin-Chao; Liu, Ling-Zhi; Powell, Annie K

2015-11-02

Three isostructural cyano-bridged 3d-4f compounds, [YFe(CN)6(hep)2(H2O)4] (1), [DyFe(CN)6(hep)2(H2O)4] (2), and [DyCo(CN)6(hep)2(H2O)4] (3), were successfully assembled by site-targeted substitution of the 3d or rare-earth ions. All compounds have been structurally characterized to display slightly distorted pentagonal-bipyramidal local coordination geometry around the rare-earth ions. Magnetic analyses revealed negligible magnetic coupling in compound 1, antiferromagnetic intradimer interaction in 2, and weak ferromagnetic coupling through dipolar-dipolar interaction in 3. Under an applied direct-current (dc) field, 1 (Hdc = 2.5 kOe, τ0 = 1.3 × 10(-7) s, and Ueff/kB = 23 K) and 3 (Hdc = 2.0 kOe, τ0 = 7.1 × 10(-11) s, and Ueff/kB = 63 K) respectively indicated magnetic relaxation behavior based on a single [Fe(III)]LS ion and a Dy(III) ion; nevertheless, 2 (Hdc = 2.0 kOe, τ0 = 9.7 × 10(-8) s, and Ueff/kB = 23 K) appeared to be a single-molecule magnet based on a cyano-bridged DyFe dimer. Compound 1, which can be regarded as a single-ion magnet of the [Fe(III)]LS ion linked to a diamagnetic Y(III) ion in a cyano-bridged heterodimer, represents one of the rarely investigated examples based on a single Fe(III) ion explored in magnetic relaxation behavior. It demonstrated that the introduction of intradimer magnetic interaction of 2 through a cyano bridge between Dy(III) and [Fe(III)]LS ions negatively affects the energy barrier and χ″(T) peak temperature compared to 3.

Sugar-modified G-quadruplexes: effects of LNA-, 2′F-RNA– and 2′F-ANA-guanosine chemistries on G-quadruplex structure and stability

PubMed Central

Li, Zhe; Lech, Christopher Jacques; Phan, Anh Tuân

2014-01-01

G-quadruplex-forming oligonucleotides containing modified nucleotide chemistries have demonstrated promising pharmaceutical potential. In this work, we systematically investigate the effects of sugar-modified guanosines on the structure and stability of a (4+0) parallel and a (3+1) hybrid G-quadruplex using over 60 modified sequences containing a single-position substitution of 2′-O-4′-C-methylene-guanosine (LNAG), 2′-deoxy-2′-fluoro-riboguanosine (FG) or 2′-deoxy-2′-fluoro-arabinoguanosine (FANAG). Our results are summarized in two parts: (I) Generally, LNAG substitutions into ‘anti’ position guanines within a guanine-tetrad lead to a more stable G-quadruplex, while substitutions into ‘syn’ positions disrupt the native G-quadruplex conformation. However, some interesting exceptions to this trend are observed. We discover that a LNAG modification upstream of a short propeller loop hinders G-quadruplex formation. (II) A single substitution of either FG or FANAG into a ‘syn’ position is powerful enough to perturb the (3+1) G-quadruplex. Substitution of either FG or FANAG into any ‘anti’ position is well tolerated in the two G-quadruplex scaffolds. FANAG substitutions to ‘anti’ positions are better tolerated than their FG counterparts. In both scaffolds, FANAG substitutions to the central tetrad layer are observed to be the most stabilizing. The observations reported herein on the effects of LNAG, FG and FANAG modifications on G-quadruplex structure and stability will enable the future design of pharmaceutically relevant oligonucleotides. PMID:24371274

Transition metal-substituted lead halide perovskite absorbers

DOE PAGES

Sampson, M. D.; Park, J. S.; Schaller, R. D.; ...

2017-01-27

Here, lead halide perovskites have proven to be a versatile class of visible light absorbers that allow rapid access to the long minority carrier lifetimes and diffusion lengths desirable for traditional single-junction photovoltaics. We explore the extent to which the attractive features of these semiconductors may be extended to include an intermediate density of states for future application in multi-level solar energy conversion systems capable of exceeding the Shockley–Queisser limit. We computationally and experimentally explore the substitution of transition metals on the Pb site of MAPbX 3 (MA = methylammonium, X = Br or Cl) to achieve a tunable densitymore » of states within the parent gap. Computational screening identified both Fe- and Co-substituted MAPbBr 3 as promising absorbers with a mid-gap density of states, and the later films were synthesized via conventional solution-based processing techniques. First-principles density functional theory (DFT) calculations support the existence of mid-gap states upon Co incorporation and enhanced sub-gap absorption, which are consistent with UV-visible-NIR absorption spectroscopy. Strikingly, steady state and time-resolved PL studies reveal no sign of self-quenching for Co-substitution up to 25%, which suggest this class of materials to be a worthy candidate for future application in intermediate band photovoltaics.« less

Modification of the band offset in boronitrene

NASA Astrophysics Data System (ADS)

Obodo, K. O.; Andrew, R. C.; Chetty, N.

2011-10-01

Using density functional methods within the generalized gradient approximation implemented in the Quantum Espresso codes, we modify the band offset in a single layer of boronitrene by substituting a double line of carbon atoms. This effectively introduces a line of dipoles at the interface. We considered various junctions of this system within the zigzag and armchair orientations. Our results show that the “zigzag-short” structure is energetically most stable, with a formation energy of 0.502 eV and with a band offset of 1.51 eV. The “zigzag-long” structure has a band offset of 1.99 eV. The armchair structures are nonpolar, while the zigzag-single structures show a charge accumulation for the C-substituted B and charge depletion for the C-substituted N at the junction. Consequently there is no shifting of the bands.

Cu1–xFexO: hopping transport and ferromagnetism

PubMed Central

Nasir, Mohd.; Islam, Rakibul; Ahmed, Md. A; Ayaz, Saniya; Kumar, Gautham; Kumar, Sunil; Prajapat, C. L.; Roussel, Frederick; Biring, Sajal

2017-01-01

Single phase, sol–gel prepared Cu1–xFexO (0 ≤ x ≤ 0.125) powders are characterized in terms of structural, electronic and magnetic properties. Using dielectric and magnetic studies we investigate the coupling of electron and spin. The electrical conductivities and activation energies are studied with increasing Fe content. Modelling of experimental conductivity data emphasizes a single hopping mechanism for all samples except x = 0.125, which have two activation energies. Hole doping is confirmed by confirming a majority Fe3+ substitution of Cu2+ in CuO from X-ray photoelectron spectroscopy studies (XPS). Such a substitution results in stabilized ferromagnetism. Fe substitution introduces variation in coercivity as an intrinsic magnetic property in Fe-doped CuO, and not as a secondary impurity phase. PMID:28989741

Two-Dimensional Protein Pattern Recognition in Chemical Toxicity

DTIC Science & Technology

1994-04-20

reverse it aces"ry and identfy by b•€ number) FILDO GRtouP UsB. aR.- rat liver, rat kidney, rat testis, perfluorcarboxylic acid peroxisome proliferator, 2D...cellular proteins in a single sample, first based on their content of acidic and basic amino acids (isoelectric focusing) and second by molecular...as phosphorylation, ribosylation, conjugation or amino acid substitutions resulting from point mutations in the genome. Regardless of the type of

Identification of four novel mutations in the COL4A5 gene of patients with Alport syndrome

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

Lemmink, H.H.; Schroeder, C.H.; Brunner, H.G.

1993-08-01

The type IV collagen [alpha]5 chain (COL4A5) genes of patients with Alport syndrome were tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA clones as probes. In addition, individual exons were screened for small mutations by single-strand conformation polymorphism (SSCP) analysis. Four new COL4A5 mutations were detected. A duplication of the nine most 3[prime] located nucleotides of exon 49 and the first nucleotide of intron 49 was identified in the COL4A5 gene of one patient. Two patients displayed single base substitutions leading to, respectively, a proline to threonine and an arginine to glutamine substitution in the C-terminalmore » end. Both substitutions involve amino acids conserved through evolution. In COL4A5 intron 41 a mutation changing the splice acceptor site from AG to AA was identified. All mutations cosegregate with the clinical phenotype of Alport syndrome in affected family members. In a control population of 50 individuals tested by PCR-SSCP these mutations were never identified. Together with two mutations reported previously, a total of six mutations were found in 26 patients with Alport syndrome (23%) after systematic screening of about 30% of the COL4A5 coding region. The clinical features of these six patients are described in detail. 21 refs., 2 figs., 3 tabs.« less

UV-Vis Spectroscopy and Dynamic Light Scattering Study of Gold Nanorods Aggregation

PubMed Central

Kanjanawarut, Roejarek; Yuan, Bo

2013-01-01

Gold nanorods (AuNRs) were used as spectroscopic sensing elements to detect specific DNA sequences with a single-base mismatch sensitivity. The assay was based on the observation that the stabilizing repulsive forces between CTA+-coated AuNRs can be removed by citrate ions, which causes aggregation among AuNRs; whereas nucleic acids of different structures[ i.e., peptide nucleic acid (PNA), single-stranded DNA (ssDNA), PNA-DNA complex, and double-stranded DNA (dsDNA)] can retard the aggregation. Moreover, the dsDNA PNA-DNA duplexes provide larger retardation than that by unhybridized ssDNA and PNA probe. This assay can differentiate single-base mismatched targets with base substitution at different locations (center and end) with AuNRs of a larger aspect ratio. Besides ultraviolet–visable spectroscopy measurement of particle assembly-induced plasmonic coupling that in turn provides a spectroscopic detection of the specific DNA, dynamic light scattering and transmission electron microscope (TEM) were used to measure smaller degree of aggregation that can reveal sodium citrate– and dsDNA–AuNRs interactions in fine detail. PMID:23902360

UV-vis spectroscopy and dynamic light scattering study of gold nanorods aggregation.

PubMed

Kanjanawarut, Roejarek; Yuan, Bo; XiaoDi, Su

2013-08-01

Gold nanorods (AuNRs) were used as spectroscopic sensing elements to detect specific DNA sequences with a single-base mismatch sensitivity. The assay was based on the observation that the stabilizing repulsive forces between CTA(+)-coated AuNRs can be removed by citrate ions, which causes aggregation among AuNRs; whereas nucleic acids of different structures[ i.e., peptide nucleic acid (PNA), single-stranded DNA (ssDNA), PNA-DNA complex, and double-stranded DNA (dsDNA)] can retard the aggregation. Moreover, the dsDNA PNA-DNA duplexes provide larger retardation than that by unhybridized ssDNA and PNA probe. This assay can differentiate single-base mismatched targets with base substitution at different locations (center and end) with AuNRs of a larger aspect ratio. Besides ultraviolet-visable spectroscopy measurement of particle assembly-induced plasmonic coupling that in turn provides a spectroscopic detection of the specific DNA, dynamic light scattering and transmission electron microscope (TEM) were used to measure smaller degree of aggregation that can reveal sodium citrate- and dsDNA-AuNRs interactions in fine detail.

Comparative study of 2mol% Li- and Mn-substituted lead-free potassium sodium niobate ceramics

NASA Astrophysics Data System (ADS)

Dahiya, Asha; Thakur, O. P.; Juneja, J. K.; Singh, Sangeeta; Dipti

2014-12-01

The effect of Li and Mn substitution on the dielectric, ferroelectric and piezoelectric properties of lead free K0.5Na0.5NbO3 (KNN) was investigated. Samples were prepared using a conventional solid state reaction method. The sintering temperature for all the samples was 1050°C. The optimum doping concentration for the enhancement of different properties without the introduction of any other co-dopants such as Ti, Sb, and La was investigated. X-ray diffraction analysis confirmed that all the samples crystallize in a single phase perovskite structure. The dielectric properties were investigated as a function of temperature and applied electric field frequency. Compared with Li-substituted KNN (KLNN), Mn-substituted KNN (KMNN) exhibited a higher dielectric constant ɛ max (i.e., 4840) at its critical transition temperature T c (i.e., 421°C) along with a lower value of tangent loss at 10 kHz and greater values of saturation polarisation P s (i.e., 20.14 μC/cm2) and remnant polarisation P r (i.e., 15.48 μC/cm2). The piezoelectric constant ( d 33) of KMNN was 178 pC/N, which is comparable to that of lead-based hard ceramics. The results presented herein suggest that B-site or Mn substitution at the optimum concentration results in good enhancement of different properties required for materials used in memory devices and other applications.

Intrinsically modified thermoelectric performance of alkaline-earth isovalently substituted [Bi2AE2O4][CoO2]y single crystals

NASA Astrophysics Data System (ADS)

Sun, N.; Dong, S. T.; Zhang, B. B.; Chen, Y. B.; Zhou, J.; Zhang, S. T.; Gu, Z. B.; Yao, S. H.; Chen, Y. F.

2013-07-01

Alkaline-earth elements isovalently substituted into a [Bi2AE2O4][CoO2]y (AE2 = Ca2, Sr2, and CaSr) single crystal with a layered structure were grown by the optical floating zone method. Structural characterization by X-ray diffraction and electron microscopy showed that the layers were oriented perpendicular to the c-axis, as well as the growth of direction was parallel to the ab-plane. The thermoelectric properties, including the Seebeck effect, electrical conductivity and thermal conductivity were investigated. The results of the thermoelectric measurements showed that the full substitution of Ca for Sr in [Bi2Sr2-xCaxO4][CoO2]y has the best overall thermoelectric performance. Compared with the other two cases studied, the full Ca substituted crystal [Bi2Ca2O4][CoO2]y exhibits both reduced resistivity and thermal conductivity, but not a reduced Seebeck coefficient. The enhanced thermoelectric property in [Bi2Ca2O4][CoO2]y is mainly due to lower structural symmetry, which is confirmed by electron microscopy characterization. This work demonstrates that even isovalently substitution can play a crucial role in the thermoelectric effect of layered cobalt oxides.

Plastome-Wide Nucleotide Substitution Rates Reveal Accelerated Rates in Papilionoideae and Correlations with Genome Features Across Legume Subfamilies.

PubMed

Schwarz, Erika N; Ruhlman, Tracey A; Weng, Mao-Lun; Khiyami, Mohammad A; Sabir, Jamal S M; Hajarah, Nahid H; Alharbi, Njud S; Rabah, Samar O; Jansen, Robert K

2017-04-01

This study represents the most comprehensive plastome-wide comparison of nucleotide substitution rates across the three subfamilies of Fabaceae: Caesalpinioideae, Mimosoideae, and Papilionoideae. Caesalpinioid and mimosoid legumes have large, unrearranged plastomes compared with papilionoids, which exhibit varying levels of rearrangement including the loss of the inverted repeat (IR) in the IR-lacking clade (IRLC). Using 71 genes common to 39 legume taxa representing all the three subfamilies, we show that papilionoids consistently have higher nucleotide substitution rates than caesalpinioids and mimosoids, and rates in the IRLC papilionoids are generally higher than those in the IR-containing papilionoids. Unsurprisingly, this pattern was significantly correlated with growth habit as most papilionoids are herbaceous, whereas caesalpinioids and mimosoids are largely woody. Both nonsynonymous (dN) and synonymous (dS) substitution rates were also correlated with several biological features including plastome size and plastomic rearrangements such as the number of inversions and indels. In agreement with previous reports, we found that genes in the IR exhibit between three and fourfold reductions in the substitution rates relative to genes within the large single-copy or small single-copy regions. Furthermore, former IR genes in IR-lacking taxa exhibit accelerated rates compared with genes contained in the IR.

Generic substitution of antiepileptic drugs.

PubMed

Sander, Josemir W; Ryvlin, Philippe; Stefan, Hermann; Booth, Daniel R; Bauer, Jürgen

2010-12-01

Substitution of antiepileptic drugs with generic formulations may affect individual people, as well as healthcare systems. Analyses of large medical claims databases suggest that generic substitution of antiepileptic drugs is associated with increased morbidity and greater use of healthcare resources. While a single brand-to-generic switch may be associated with a slight increase in overall medical costs, multiple switches may be associated with higher costs, perhaps because different generic agents are not required to be bioequivalent to each other. Generic substitution also affects the individual: along with the possible increased risk of seizures or adverse events, inconsistency of supply may make the medication appear unfamiliar, thus discouraging adherence. Importantly, substitution is often carried out at the dispensing level, without the knowledge or consent of physicians and affected individuals. Therefore, regulatory and professional bodies advocate that substitution should not be carried out without specific counseling of the individual by healthcare professionals on the details and implications of the change.

High-pressure electronic phase diagrams in FeSe1-xSx superconductors

NASA Astrophysics Data System (ADS)

Matsuura, Kohei; Arai, Yuki; Hosoi, Suguru; Ishida, Kousuke; Mizukami, Yuta; Watashige, Tatsuya; Kasahara, Shigeru; Matsuda, Yuji; Maejima, Naoyuki; Machida, Akihiko; Watanuki, Tetsu; Fukuda, Tatsuo; Uwatoko, Yoshiya; Shibauchi, Takasada

The spin fluctuations are believed to be related to the mechanism of the unconventional superconductors. On the other hand, many recent studies suggest that the nematic order that spontaneously breaks rotational symmetry of the system exists in the Fe-based superconductors and its quantum fluctuations may play an essential role for the superconductivity. However, this remains unclear because the nematic order usually coexists with the magnetic order. To solve this issue, FeSe exhibiting a nonmagnetic nematic order is a key system. Under pressure, this order is suppressed and concurrently magnetic order appears, which competes with high-Tc superconducting phase. In isovalent substitution system FeSe1-xSx, we found a nonmagnetic nematic quantum critical point. Here we report our recent high-pressure studies in high-quality single-crystalline FeSe1-xSx up to 8 GPa. We find a systematic change of the pressure phase diagram in FeSe by the S-substitution. Our results imply that the respective role of nematic and magnetic fluctuations can be elucidated from the precise control of pressure and substitution in this system.

Al3+ ions dependent structural and magnetic properties of Co-Ni nano-alloys.

PubMed

Kadam, R H; Alone, Suresh T; Gaikwad, Anil S; Birajdar, A P; Shirsath, Sagar E

2014-06-01

Ferrite samples with a chemical formula Co0.5Ni0.5Al(x)Fe(2-x)O4 (where x = 0.0, 0.25, 0.5, 0.75 and 1.0) were synthesized by sol-gel auto-combustion method. The synthesized samples were annealed at 600 degrees C for 4 h. An analysis of X-ray diffraction (XRD) patterns reveals the formation of single phase cubic spinel structure. The lattice parameter decreased linearly with the increasing Al content x. Nano size of the powders were confirmed by the transmission electron micrographs (TEM). Particle size, bulk density decreased whereas specific surface area and porosity of the samples increased with the Al substitution. Cation distribution of constituent ions shows linear dependence of Al substitution. Based on the cation distribution obtained from XRD data, structural parameters such as lattice parameters, ionic radii of available sites and the oxygen parameter 'u' is calculated. Saturation magnetization (M(s)), magneton number (n(B)) and coercivity (H(c)) decreased with the Al substitution. Possible explanation for the observed structural and magnetic behavior with various Al content are discussed.

Interchangeability of biosimilar and biological reference product: updated regulatory positions and pre- and post-marketing evidence.

PubMed

Trifirò, Gianluca; Marcianò, Ilaria; Ingrasciotta, Ylenia

2018-03-01

Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity. Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state. Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence.

[Characterization of puroindolines in the control of endosperm texture in common wheat lines with substitutions of homeologous group-5 chromosomes].

PubMed

Obukhova, L V; Efremova, T T; Shumnyĭ, V K

2013-03-01

The genetic control of grain hardness and its association with the specific friabilin content on starch granules of common wheat cultivars and lines with intervarietal substitutions of homeologous group-5 chromosomes were studied. A significant correlation was revealed between the technological parameters of grain hardness (mean size of flour particles) and the specific content of puroindolines on the starch surface estimated in terms of starch doses. The results obtained allowed the method of starch doses to be used to identify soft and hard wheat cultivars and lines based on an analysis of a single grain. The biochemical analysis confirmed the previously obtained estimates of flour-grinding properties of wheat cultivars and substitution lines, which allowed specific genotypes to be characterized according to the composition of puroindolines. The influence of chromosomes 5D and 5A of donor wheat cultivars on the activity of the Ha loci of recipient cultivars was revealed and found to be associated with the composition of PIN products and with the expression of the Pina-D1 and Pinb-D1 genes.

Rheological and thermal performance of newly developed binder systems for ceramic injection molding

NASA Astrophysics Data System (ADS)

Hausnerova, Berenika; Kasparkova, Vera; Hnatkova, Eva

2016-05-01

In a novel binder system, carnauba wax was considered to replace the synthetic backbone polymers (polyolefins) enhancing the environmental sustainability of Ceramic Injection Molding (CIM) technology. The paper presents comparison of the rheological performance and thermal behavior of the aluminum oxide CIM feedstocks based on a binder containing carnauba wax with those consisting of a commercial binder. Further, acrawax (N, N'-Ethylene Bis-stearamide) has been considered as another possible substitute of polyolefins. For both proposed substitutes there is a significant reduction in viscosity, and in case of carnauba wax based feedstock also in processing temperature, which is essential for injection molding of reactive powders. Thermal characterization comprised analyses of single neat binders, their mixtures and mixtures with aluminum oxide. The presence of powder lowered melting temperatures of all tested binders except of polyolefin. Further depression in melting point of poly(ethylene glycol) is observed in combination with polyolefin in the presence of powder, and it is related to changes in size of the crystalline domains.

Electrical conduction mechanism in La3Ta0.5Ga5.3Al0.2O14 single crystals

PubMed Central

Yaokawa, Ritsuko; Aota, Katsumi; Uda, Satoshi

2013-01-01

The electrical conduction mechanism in La3Ta0.5Ga5.3Al0.2O14 (LTGA) single crystals was studied by nonstoichiometric defect formation during crystal growth. Since stoichiometric LTGA is not congruent, the single crystal grown from the stoichiometric melt was Ta-poor and Al-rich, where Al atoms were substituted not only in Ga sites but also in Ta sites. The population of the substitutional Al in Ta sites increased with increasing oxygen partial pressure during growth (growth-pO2) in the range from 0.01 to 1 atm. Below 600 °C, substitutional Al atoms in Ta sites were ionized to yield holes, and thus the electrical conductivity of the LTGA crystal depended on temperature and the growth-pO2. The dependence of the electrical conductivity on the growth-pO2 decreased as temperature increased. The temperature rise increases ionic conductivity, for which the dominant carriers are oxygen defects formed by the anion Frenkel reaction. PMID:24396153

Genomic variation and DNA repair associated with soybean transgenesis: a comparison to cultivars and mutagenized plants.

PubMed

Anderson, Justin E; Michno, Jean-Michel; Kono, Thomas J Y; Stec, Adrian O; Campbell, Benjamin W; Curtin, Shaun J; Stupar, Robert M

2016-05-12

The safety of mutagenized and genetically transformed plants remains a subject of scrutiny. Data gathered and communicated on the phenotypic and molecular variation induced by gene transfer technologies will provide a scientific-based means to rationally address such concerns. In this study, genomic structural variation (e.g. large deletions and duplications) and single nucleotide polymorphism rates were assessed among a sample of soybean cultivars, fast neutron-derived mutants, and five genetically transformed plants developed through Agrobacterium based transformation methods. On average, the number of genes affected by structural variations in transgenic plants was one order of magnitude less than that of fast neutron mutants and two orders of magnitude less than the rates observed between cultivars. Structural variants in transgenic plants, while rare, occurred adjacent to the transgenes, and at unlinked loci on different chromosomes. DNA repair junctions at both transgenic and unlinked sites were consistent with sequence microhomology across breakpoints. The single nucleotide substitution rates were modest in both fast neutron and transformed plants, exhibiting fewer than 100 substitutions genome-wide, while inter-cultivar comparisons identified over one-million single nucleotide polymorphisms. Overall, these patterns provide a fresh perspective on the genomic variation associated with high-energy induced mutagenesis and genetically transformed plants. The genetic transformation process infrequently results in novel genetic variation and these rare events are analogous to genetic variants occurring spontaneously, already present in the existing germplasm, or induced through other types of mutagenesis. It remains unclear how broadly these results can be applied to other crops or transformation methods.

Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite

PubMed Central

Friederichs, Robert J.; Chappell, Helen F.; Shepherd, David V.; Best, Serena M.

2015-01-01

Experimental chemistry and atomic modelling studies were performed here to investigate a novel ionic co-substitution in hydroxyapatite (HA). Zinc, silicate co-substituted HA (ZnSiHA) remained phase pure after heating to 1100°C with Zn and Si amounts of 0.6 wt% and 1.2 wt%, respectively. Unique lattice expansions in ZnSiHA, silicate Fourier transform infrared peaks and changes to the hydroxyl IR stretching region suggested Zn and silicate co-substitution in ZnSiHA. Zn and silicate insertion into HA was modelled using density functional theory (DFT). Different scenarios were considered where Zn substituted for different calcium sites or at a 2b site along the c-axis, which was suspected in singly substituted ZnHA. The most energetically favourable site in ZnSiHA was Zn positioned at a previously unreported interstitial site just off the c-axis near a silicate tetrahedron sitting on a phosphate site. A combination of experimental chemistry and DFT modelling provided insight into these complex co-substituted calcium phosphates that could find biomedical application as a synthetic bone mineral substitute. PMID:26040597

Allelic variation of soybean flower color gene W4 encoding dihydroflavonol 4-reductase 2.

PubMed

Yan, Fan; Di, Shaokang; Rojas Rodas, Felipe; Rodriguez Torrico, Tito; Murai, Yoshinori; Iwashina, Tsukasa; Anai, Toyoaki; Takahashi, Ryoji

2014-03-06

Flower color of soybean is primarily controlled by six genes, viz., W1, W2, W3, W4, Wm and Wp. This study was conducted to investigate the genetic and chemical basis of newly-identified flower color variants including two soybean mutant lines, 222-A-3 (near white flower) and E30-D-1 (light purple flower), a near-isogenic line (Clark-w4), flower color variants (T321 and T369) descended from the w4-mutable line and kw4 (near white flower, Glycine soja). Complementation tests revealed that the flower color of 222-A-3 and kw4 was controlled by the recessive allele (w4) of the W4 locus encoding dihydroflavonol 4-reductase 2 (DFR2). In 222-A-3, a single base was deleted in the first exon resulting in a truncated polypeptide consisting of 24 amino acids. In Clark-w4, base substitution of the first nucleotide of the fourth intron abolished the 5' splice site, resulting in the retention of the intron. The DFR2 gene of kw4 was not expressed. The above results suggest that complete loss-of-function of DFR2 gene leads to near white flowers. Light purple flower of E30-D-1 was controlled by a new allele at the W4 locus, w4-lp. The gene symbol was approved by the Soybean Genetics Committee. In E30-D-1, a single-base substitution changed an amino acid at position 39 from arginine to histidine. Pale flowers of T369 had higher expression levels of the DFR2 gene. These flower petals contained unique dihydroflavonols that have not yet been reported to occur in soybean and G. soja. Complete loss-of-function of DFR2 gene leads to near white flowers. A new allele of the W4 locus, w4-lp regulates light purple flowers. Single amino acid substitution was associated with light purple flowers. Flower petals of T369 had higher levels of DFR2 gene expression and contained unique dihydroflavonols that are absent in soybean and G. soja. Thus, mutants of the DFR2 gene have unique flavonoid compositions and display a wide variety of flower color patterns in soybean, from near white, light purple, dilute purple to pale.

Role of a single amino acid substitution of VP3 H142D for increased acid resistance of foot-and-mouth disease virus serotype A.

PubMed

Biswal, Jitendra K; Das, Biswajit; Sharma, Gaurav K; Khulape, Sagar A; Pattnaik, Bramhadev

2016-04-01

Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their dissociation into pentamers at pH value below 6.5. After the uptake of FMDV by receptor-mediated endocytosis, the acid-dependent dissociation process is required for the release of FMDV genome inside endosomes. Nevertheless, dissociation of FMDV particles in mildly acidic conditions renders the inactivated FMD vaccine less effective. To improve the acid stability of inactivated FMD vaccine during the manufacturing process, a serotype A IND 40/2000 (in-use vaccine strain) mutant with increased resistance to acid inactivation was generated through reverse genetics approach. Based upon the earlier reports, the crucial amino acid residue, H142 of VP3 capsid protein was substituted separately to various amino acid residues Arg (R), Phe (F), Ala (A), and Asp (D) on the full-genome length cDNA clone. While the H142 → R or H142 → F or H142 → A substitutions resulted in non-infectious FMDV, H142 → D mutation on VP3 protein (H3142D) resulted in the generation of mutant virus with enhanced resistance to acid-induced inactivation. In addition, H3142D substitution did not alter the replication ability and antigenicity of mutant as compared to the parental virus. However, the virus competition experiments revealed that the H3142D substitution conferred a loss of fitness for the mutant virus. Results from this study demonstrate that the H3142D substitution is the molecular determinant of acid-resistant phenotype in FMDV serotype A.

A Comparison of Two Single-Stranded DNA Binding Models by Mutational Analysis of APOBEC3G

PubMed Central

Shindo, Keisuke; Li, Ming; Gross, Phillip J.; Brown, William L.; Harjes, Elena; Lu, Yongjian; Matsuo, Hiroshi; Harris, Reuben S.

2012-01-01

APOBEC3G is the best known of several DNA cytosine deaminases that function to inhibit the replication of parasitic genetic elements including the lentivirus HIV. Several high-resolution structures of the APOBEC3G catalytic domain have been generated, but none reveal how this enzyme binds to substrate single-stranded DNA. Here, we constructed a panel of APOBEC3G amino acid substitution mutants and performed a series of biochemical, genetic, and structural assays to distinguish between “Brim” and “Kink” models for single-strand DNA binding. Each model predicts distinct sets of interactions between surface arginines and negatively charged phosphates in the DNA backbone. Concordant with both models, changing the conserved arginine at position 313 to glutamate abolished both catalytic and restriction activities. In support of the Brim model, arginine to glutamate substitutions at positions 213, 215, and 320 also compromised these APOBEC3G activities. Arginine to glutamate substitutions at Kink model residues 374 and 376 had smaller effects. These observations were supported by A3G catalytic domain-ssDNA chemical shift perturbation experiments. The overall data set is most consistent with the Brim model for single-stranded DNA binding by APOBEC3G. PMID:24832226

Influence of Samarium Substitution on Dielectric Properties of Barium Titanate Based Ceramics

NASA Astrophysics Data System (ADS)

Kumar, Parveen; Singh, Sangeeta; Juneja, J. K.; Prakash, Chandra; Raina, K. K.

In this paper we report samarium substituted Ba0.80Pb0.20Ti0.90Zr0.10O3 (BPZT) ceramics. The material series with compositional formula Ba0.80-xSmxPb0.20Ti0.90Zr0.10O3 with x varying from 0 to 0.01 in the steps of 0.0025 was chosen for investigations. The material was synthesized by solid state reaction method. Reacted powders compacted in the form of circular discs were sintered at 1325°C. All the samples were subjected to X-ray analysis and found to be single phase. Dielectric behavior was studied as a function of frequency and temperature and Curie temperature (Tc) was determined. Tc was found to decrease with increasing x. The details are discussed and presented here.

Ferroelectric Properties of La Substituted PZT Ceramics

NASA Astrophysics Data System (ADS)

Rani, Rekha; Juneja, J. K.; Raina, K. K.; Prakash, Chandra

2011-11-01

For the present study, La substituted PZT ceramics having compositional formula Pb1-3x/2LaxZr0.65Ti0.35O3 were prepared by conventional solid state method. La content was varied from x = 0 to 0.03 in the steps of 0.01. XRD analyses of all the samples were done and were found to have single phase with rhombohedral structure. In this paper, we are reporting the variation in ferroelectric properties of Pb1-3x/2LaxZr0.65Ti0.35O3 by varying La content. P-E hysteresis loops were recorded using P-E loop tracer based on Sawyer- Tower circuit for all the samples at 20 Hz. Increase in coercive field (Ec), remanant polarization (Pr), saturation polarization (Ps) and squareness ratio (Pr/Ps) was observed with increase in x.

Half-metallicity and electronic structures for carbon-doped group III-nitrides: Calculated with a modified Becke-Johnson potential

NASA Astrophysics Data System (ADS)

Fan, Shuai-wei; Wang, Ri-gao; Xu, Pemg

2016-09-01

The electronic structures and magnetism for carbon-doped group III-nitrides are investigated by utilizing the first principle method with the modified Becke-Johnson potential. Calculations show that carbon substituting cations (anions) would induce the group III-nitrides to be paramagnetic metals (half-metallic ferromagnets). Single carbon substituting nitrogen could produce 1.00μB magnetic moment. Electronic structures indicate that the carriers-mediated double-exchange interaction plays a crucial role in forming the ferromagnetism. Based on the mean-field theory, the Curie temperature for carbon-doped group III-nitrides would be above the room temperature. Negative chemical pair interactions imply that carbon dopants tend to form clustering distribution in group III-nitrides. The nitrogen vacancy would make the carbon-doped group III-nitrides lose the half-metallic ferromagnetism.

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

PubMed Central

Josefík, František; Svobodová, Markéta; Bertolasi, Valerio

2013-01-01

Summary Easily obtainable cyclic enaminones (piperidin-2-ylidenealkanones) can be transformed into substituted bicyclic pyridazinium tetrafluoroborates upon treatment with corresponding diazonium salts. The transformation can be performed either in a one-pot way or in a two-step process with the isolation of single azo-coupled enaminone as the intermediate. The former method is superior. Under the optimized conditions, a number of pyridazinium salts substituted with both electron-donating and electron-withdrawing substituents was easily synthesized. A mechanism of the formation of the pyridazinium salts is suggested. A partial drawback is the possibility of the formation of a mixture of products when using a different diazonium salt in each step due to a reversibility of the azo coupling. This can be suppressed by using a more reactive diazonium salt before a less reactive one. PMID:23946844

Protected DNA strand displacement for enhanced single nucleotide discrimination in double-stranded DNA.

PubMed

Khodakov, Dmitriy A; Khodakova, Anastasia S; Huang, David M; Linacre, Adrian; Ellis, Amanda V

2015-03-04

Single nucleotide polymorphisms (SNPs) are a prime source of genetic diversity. Discriminating between different SNPs provides an enormous leap towards the better understanding of the uniqueness of biological systems. Here we report on a new approach for SNP discrimination using toehold-mediated DNA strand displacement. The distinctiveness of the approach is based on the combination of both 3- and 4-way branch migration mechanisms, which allows for reliable discrimination of SNPs within double-stranded DNA generated from real-life human mitochondrial DNA samples. Aside from the potential diagnostic value, the current study represents an additional way to control the strand displacement reaction rate without altering other reaction parameters and provides new insights into the influence of single nucleotide substitutions on 3- and 4-way branch migration efficiency and kinetics.

Emergence of Avian Influenza Viruses with Enhanced Transcription Activity by a Single Amino Acid Substitution in the Nucleoprotein during Replication in Chicken Brains ▿

PubMed Central

Tada, Tatsuya; Suzuki, Koutaro; Sakurai, Yu; Kubo, Masanori; Okada, Hironao; Itoh, Toshihiro; Tsukamoto, Kenji

2011-01-01

To explore the genetic basis of the pathogenesis and adaptation of avian influenza viruses (AIVs) to chickens, the A/duck/Yokohama/aq10/2003 (H5N1) (DkYK10) virus was passaged five times in the brains of chickens. The brain-passaged DkYK10-B5 caused quick death of chickens through rapid and efficient replication in tissues, accompanied by severe apoptosis. Genome sequence comparison of two viruses identified a single amino acid substitution at position 109 in NP from isoleucine to threonine (NP I109T). By analyzing viruses constructed by the reverse-genetic method, we established that the NP I109T substitution also contributed to increased viral replication and polymerase activity in chicken embryo fibroblasts, but not in duck embryo fibroblasts. Real-time RT-PCR analysis demonstrated that the NP I109T substitution enhances mRNA synthesis quickly and then cRNA and viral RNA (vRNA) synthesis slowly. Next, to determine the mechanism underlying the appearance of the NP I109T substitution during passages, four H5N1 highly pathogenic AIVs (HPAIVs) were passaged in the lungs and brains of chicken embryos. Single-nucleotide polymorphism analysis, together with a database search, suggests that the NP I109T mutation would be induced frequently during replication of HPAIVs in brains, but not in lungs. These results demonstrate that the amino acid at position 109 in NP enhances viral RNA synthesis and the pathogenicity of highly pathogenic avian influenza viruses in chickens and that the NP mutation emerges quickly during replication of the viruses in chicken brains. PMID:21795332

Mutational analysis of immunoglobulin E-binding epitopes of beta-casein and beta-lactoglobulin showed a heterogeneous pattern of critical amino acids between individual patients and pooled sera.

PubMed

Cocco, R R; Järvinen, K-M; Han, N; Beyer, K; Sampson, H A

2007-06-01

For immunotherapeutic approaches, 'critical' amino acids (AAs) within allergenic epitopes are replaced with alternate AAs to eliminate IgE antibody binding. To determine the critical AAs for IgE binding in beta-casein and beta-lactoglobulin (BLG). Peptides of 10-14 AAs in length were synthesized on a derivatized cellulose membrane with single AA substitutions (alanine or glycine) at each position. Membranes were incubated with a pool of sera from 15 cow's milk-allergic patients and individual sera from six of the 15 patients. In cases where no decrease in binding occurred with a single AA substitution, peptides with two AA substitutions were generated and labelled. Using pooled patient sera, single AA substitutions led to complete elimination of binding to six of 11 peptides for beta-casein and to all six peptides for BLG. Substituting two AAs led to an elimination of binding to four of the remaining five beta-casein epitopes. However, in three of the 11 modified beta-casein peptides and five of the six BLG peptides, no decrease in IgE binding occurred in at least one individual patient. For these patients, critical AAs other than those defined by the patient serum pool were identified, indicating a heterogeneous pattern of IgE recognition. These results indicate that AAs critical for IgE binding are more heterogeneous than initially defined by pooled milk-allergic patient sera. For future immunotherapeutic interventions with mutated peptides, critical AAs should also be identified with individual patient sera to account for heterogeneity of IgE binding between patients.

A large-scale study of the random variability of a coding sequence: a study on the CFTR gene.

PubMed

Modiano, Guido; Bombieri, Cristina; Ciminelli, Bianca Maria; Belpinati, Francesca; Giorgi, Silvia; Georges, Marie des; Scotet, Virginie; Pompei, Fiorenza; Ciccacci, Cinzia; Guittard, Caroline; Audrézet, Marie Pierre; Begnini, Angela; Toepfer, Michael; Macek, Milan; Ferec, Claude; Claustres, Mireille; Pignatti, Pier Franco

2005-02-01

Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (n(g) approximately 100-150 genes). In the present investigation, a large random European population sample (average n(g) approximately 1500) was studied for a single gene, the CFTR (Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q > 0.005), much lower than that of the synonymous (S) substitutions, but they showed a similar rate of subpolymorphic (q < 0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.

Chapter 8: Pyrolysis Mechanisms of Lignin Model Compounds Using a Heated Micro-Reactor

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

Robichaud, David J.; Nimlos, Mark R.; Ellison, G. Barney

2015-10-03

Lignin is an important component of biomass, and the decomposition of its thermal deconstruction products is important in pyrolysis and gasification. In this chapter, we investigate the unimolecular pyrolysis chemistry through the use of singly and doubly substituted benzene molecules that are model compounds representative of lignin and its primary pyrolysis products. These model compounds are decomposed in a heated micro-reactor, and the products, including radicals and unstable intermediates, are measured using photoionization mass spectrometry and matrix isolation infrared spectroscopy. We show that the unimolecular chemistry can yield insight into the initial decomposition of these species. At pyrolysis and gasificationmore » severities, singly substituted benzenes typically undergo bond scission and elimination reactions to form radicals. Some require radical-driven chain reactions. For doubly substituted benzenes, proximity effects of the substituents can change the reaction pathways.« less

Investigation of the thermophilic mechanism in the genus Porphyrobacter by comparative genomic analysis.

PubMed

Xu, Lin; Wu, Yue-Hong; Zhou, Peng; Cheng, Hong; Liu, Qian; Xu, Xue-Wei

2018-05-23

Type strains of the genus Porphyrobacter belonging to the family Erythrobacteraceae and the class Alphaproteobacteria have been isolated from various environments, such as swimming pools, lake water and hot springs. P. cryptus DSM 12079 T and P. tepidarius DSM 10594 T out of all Erythrobacteraceae type strains, are two type strains that have been isolated from geothermal environments. Next-generation sequencing (NGS) technology offers a convenient approach for detecting situational types based on protein sequence differences between thermophiles and mesophiles; amino acid substitutions can lead to protein structural changes, improving the thermal stabilities of proteins. Comparative genomic studies have revealed that different thermal types exist in different taxa, and few studies have been focused on the class Alphaproteobacteria, especially the family Erythrobacteraceae. In this study, eight genomes of Porphyrobacter strains were compared to elucidate how Porphyrobacter thermophiles developed mechanisms to adapt to thermal environments. P. cryptus DSM 12079 T grew optimally at 50 °C, which was higher than the optimal growth temperature of other Porphyrobacter type strains. Phylogenomic analysis of the genus Porphyrobacter revealed that P. cryptus DSM 12079 T formed a distinct and independent clade. Comparative genomic studies uncovered that 1405 single-copy genes were shared by Porphyrobacter type strains. Alignments of single-copy proteins showed that various types of amino acid substitutions existed between P. cryptus DSM 12079 T and the other Porphyrobacter strains. The primary substitution types were changes from glycine/serine to alanine. P. cryptus DSM 12079 T was the sole thermophile within the genus Porphyrobacter. Phylogenomic analysis and amino acid frequencies indicated that amino acid substitutions might play an important role in the thermophily of P. cryptus DSM 12079 T . Bioinformatic analysis revealed that major amino acid substitutional types, such as changes from glycine/serine to alanine, increase the frequency of α-helices in proteins, promoting protein thermostability in P. cryptus DSM 12079 T . Hence, comparative genomic analysis broadens our understanding of thermophilic mechanisms in the genus Porphyrobacter and may provide a useful insight in the design of thermophilic enzymes for agricultural, industrial and medical applications.

"I Run My Classes along the Lines of Dad's Army"

ERIC Educational Resources Information Center

Stanistreet, Paul

2011-01-01

Few artists are as closely associated with a single educational institution as Maggi Hambling--still fewer with an institution that specialises in the education of adults. Her relationship with Morley College began more than 40 years ago, but soon blossomed into enduring mutual affection. She was a substitute for a substitute on a Monday afternoon…

Straightforward Entry toward Highly Substituted 2,3-Dihydrobenz[ b]oxepines by Ring Expansion of Benzopyryliums with Donor-Acceptor Diazo Compounds.

PubMed

Courant, Thibaut; Pasco, Morgane; Lecourt, Thomas

2018-05-04

Ylide-type reactivity of diazo compounds is exploited in a new way to prepare benzo[ b]oxepines thanks to the formation of three chemical bonds and two contiguous and highly substituted stereocenters in a single pot. This cationic reaction cascade first involves addition of a donor-acceptor-substituted diazo compound to a benzopyrylium. Selective 1,2 migration of the endocyclic C-C bond then results in a ring-expansion and generates a second oxocarbenium that is trapped by a nucleophile added sequentially.

Gα and regulator of G-protein signaling (RGS) protein pairs maintain functional compatibility and conserved interaction interfaces throughout evolution despite frequent loss of RGS proteins in plants.

PubMed

Hackenberg, Dieter; McKain, Michael R; Lee, Soon Goo; Roy Choudhury, Swarup; McCann, Tyler; Schreier, Spencer; Harkess, Alex; Pires, J Chris; Wong, Gane Ka-Shu; Jez, Joseph M; Kellogg, Elizabeth A; Pandey, Sona

2017-10-01

Signaling pathways regulated by heterotrimeric G-proteins exist in all eukaryotes. The regulator of G-protein signaling (RGS) proteins are key interactors and critical modulators of the Gα protein of the heterotrimer. However, while G-proteins are widespread in plants, RGS proteins have been reported to be missing from the entire monocot lineage, with two exceptions. A single amino acid substitution-based adaptive coevolution of the Gα:RGS proteins was proposed to enable the loss of RGS in monocots. We used a combination of evolutionary and biochemical analyses and homology modeling of the Gα and RGS proteins to address their expansion and its potential effects on the G-protein cycle in plants. Our results show that RGS proteins are widely distributed in the monocot lineage, despite their frequent loss. There is no support for the adaptive coevolution of the Gα:RGS protein pair based on single amino acid substitutions. RGS proteins interact with, and affect the activity of, Gα proteins from species with or without endogenous RGS. This cross-functional compatibility expands between the metazoan and plant kingdoms, illustrating striking conservation of their interaction interface. We propose that additional proteins or alternative mechanisms may exist which compensate for the loss of RGS in certain plant species. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts

PubMed Central

Saini, Natalie; Chan, Kin; Grimm, Sara A.; Dai, Shuangshuang; Fargo, David C.; Kaufmann, William K.; Taylor, Jack A.; Lee, Eunjung; Cortes-Ciriano, Isidro; Park, Peter J.; Schurman, Shepherd H.; Malc, Ewa P.; Mieczkowski, Piotr A.

2016-01-01

Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration ClinicalTrials.gov NCT01087307 PMID:27788131

Screening of Possible Re-Substitutional Elements in Single-Crystal Ni-Based Superalloys: A Viewpoint From Interdiffusion Coefficients in Ni-Al-X Ternaries

NASA Astrophysics Data System (ADS)

Chen, Juan; Zhang, Lijun; Lu, Xiao-Gang

2018-07-01

A popular area of research in the field of high-temperature alloys concerns the search of substitutional elements for Re in order to manufacture single-crystal Ni-based superalloys with less or even no Re addition. To find the elements with similar or even lower diffusion coefficients than Re is an effective strategy. Based on 29 fcc diffusion couples in ternary Ni-Al-X (X = Re, Os, and Ir) systems, high-throughput measurement of composition- and temperature-dependent interdiffusivity matrices was performed using our recently developed numerical inverse method implemented in HitDIC software. The reliability of the determined interdiffusivities was validated by comprehensively comparing the model-predicted composition/interdiffusion flux profiles for each diffusion couple with the corresponding experimental data. Moreover, we also conducted a comparison with the interdiffusivities evaluated using the traditional Matano-Kirkaldy method as well as those from the literature and in boundary binary systems. After that, a comprehensive comparison of the interdiffusion coefficients in fcc Ni-2 wt pct Al-6 wt pct X (X = Ti, Co, Ni, Nb, Mo, Ru, Rh, Ta, W, Re, Os, Ir, and Pt) alloys at 1423 K to 1573 K was conducted. Results indicate that the diffusion rate of Re is lower than that of Os at 1473 K and 1523 K; but higher at 1573 K, while the diffusion rate of Ir is always slightly higher than those of Os and Re at 1473 K to 1573 K. Further analysis of the magnitude of the interdiffusion coefficient correlates with the alloying concentration, activation energy, atomic number, and atomic radius of different diffusing transition metal species ( i.e., Ti, Co, Ni, Nb, Mo, Ru, Rh, Ta, W, Re, Os, Ir, and Pt) was conducted, which is expected to provide useful information regarding element choice in the development of new-generation Ni-based single-crystal superalloys.

Screening of Possible Re-Substitutional Elements in Single-Crystal Ni-Based Superalloys: A Viewpoint From Interdiffusion Coefficients in Ni-Al-X Ternaries

NASA Astrophysics Data System (ADS)

Chen, Juan; Zhang, Lijun; Lu, Xiao-Gang

2018-05-01

A popular area of research in the field of high-temperature alloys concerns the search of substitutional elements for Re in order to manufacture single-crystal Ni-based superalloys with less or even no Re addition. To find the elements with similar or even lower diffusion coefficients than Re is an effective strategy. Based on 29 fcc diffusion couples in ternary Ni-Al-X (X = Re, Os, and Ir) systems, high-throughput measurement of composition- and temperature-dependent interdiffusivity matrices was performed using our recently developed numerical inverse method implemented in HitDIC software. The reliability of the determined interdiffusivities was validated by comprehensively comparing the model-predicted composition/interdiffusion flux profiles for each diffusion couple with the corresponding experimental data. Moreover, we also conducted a comparison with the interdiffusivities evaluated using the traditional Matano-Kirkaldy method as well as those from the literature and in boundary binary systems. After that, a comprehensive comparison of the interdiffusion coefficients in fcc Ni-2 wt pct Al-6 wt pct X (X = Ti, Co, Ni, Nb, Mo, Ru, Rh, Ta, W, Re, Os, Ir, and Pt) alloys at 1423 K to 1573 K was conducted. Results indicate that the diffusion rate of Re is lower than that of Os at 1473 K and 1523 K; but higher at 1573 K, while the diffusion rate of Ir is always slightly higher than those of Os and Re at 1473 K to 1573 K. Further analysis of the magnitude of the interdiffusion coefficient correlates with the alloying concentration, activation energy, atomic number, and atomic radius of different diffusing transition metal species (i.e., Ti, Co, Ni, Nb, Mo, Ru, Rh, Ta, W, Re, Os, Ir, and Pt) was conducted, which is expected to provide useful information regarding element choice in the development of new-generation Ni-based single-crystal superalloys.

Alkyne Benzannulation Reactions for the Synthesis of Novel Aromatic Architectures.

PubMed

Hein, Samuel J; Lehnherr, Dan; Arslan, Hasan; J Uribe-Romo, Fernando; Dichtel, William R

2017-11-21

Aromatic compounds and polymers are integrated into organic field effect transistors, light-emitting diodes, photovoltaic devices, and redox-flow batteries. These compounds and materials feature increasingly complex designs, and substituents influence energy levels, bandgaps, solution conformation, and crystal packing, all of which impact performance. However, many polycyclic aromatic hydrocarbons of interest are difficult to prepare because their substitution patterns lie outside the scope of current synthetic methods, as strategies for functionalizing benzene are often unselective when applied to naphthalene or larger systems. For example, cross-coupling and nucleophilic aromatic substitution reactions rely on prefunctionalized arenes, and even directed metalation methods most often modify positions near Lewis basic sites. Similarly, electrophilic aromatic substitutions access single regioisomers under substrate control. Cycloadditions provide a convergent route to densely functionalized aromatic compounds that compliment the above methods. After surveying cycloaddition reactions that might be used to modify the conjugated backbone of poly(phenylene ethynylene)s, we discovered that the Asao-Yamamoto benzannulation reaction is notably efficient. Although this reaction had been reported a decade earlier, its scope and usefulness for synthesizing complex aromatic systems had been under-recognized. This benzannulation reaction combines substituted 2-(phenylethynyl)benzaldehydes and substituted alkynes to form 2,3-substituted naphthalenes. The reaction tolerates a variety of sterically congested alkynes, making it well-suited for accessing poly- and oligo(ortho-arylene)s and contorted hexabenzocoronenes. In many cases in which asymmetric benzaldehyde and alkyne cycloaddition partners are used, the reaction is regiospecific based on the electronic character of the alkyne substrate. Recognizing these desirable features, we broadened the substrate scope to include silyl- and halogen-substituted alkynes. Through a combined experimental and computational approach, we have elucidated mechanistic insight and key principles that govern the regioselectivity outcome of the benzannulation of structurally diverse alkynes. We have applied these methods to prepare sterically hindered, shape-persistent aromatic systems, heterocyclic aromatic compounds, functionalized 2-aryne precursors, polyheterohalogenated naphthalenes, ortho-arylene foldamers, and graphene nanoribbons. As a result of these new synthetic avenues, aromatic structures with interesting properties were uncovered such as ambipolar charge transport in field effect transistors based on our graphene nanoribbons, conformational aspects of ortho-arylene architectures resulting from intramolecular π-stacking, and modulation of frontier molecular orbitals via protonation of heteroatom containing aromatic systems. Given the availability of many substituted 2-(phenylethynyl)benzaldehydes and the regioselectivity of the benzannulation reaction, naphthalenes can be prepared with control of the substitution pattern at seven of the eight substitutable positions. Researchers in a range of fields are likely to benefit directly from newly accessible molecular and polymeric systems derived from polyfunctionalized naphthalenes.

Single-cone finite-difference schemes for the (2+1)-dimensional Dirac equation in general electromagnetic textures

NASA Astrophysics Data System (ADS)

Pötz, Walter

2017-11-01

A single-cone finite-difference lattice scheme is developed for the (2+1)-dimensional Dirac equation in presence of general electromagnetic textures. The latter is represented on a (2+1)-dimensional staggered grid using a second-order-accurate finite difference scheme. A Peierls-Schwinger substitution to the wave function is used to introduce the electromagnetic (vector) potential into the Dirac equation. Thereby, the single-cone energy dispersion and gauge invariance are carried over from the continuum to the lattice formulation. Conservation laws and stability properties of the formal scheme are identified by comparison with the scheme for zero vector potential. The placement of magnetization terms is inferred from consistency with the one for the vector potential. Based on this formal scheme, several numerical schemes are proposed and tested. Elementary examples for single-fermion transport in the presence of in-plane magnetization are given, using material parameters typical for topological insulator surfaces.

Archival Isolates Confirm a Single Topotype of West Nile Virus in Australia

PubMed Central

Huang, Bixing; Prow, Natalie A; van den Hurk, Andrew F.; Allcock, Richard J. N.; Moore, Peter R.; Doggett, Stephen L.; Warrilow, David

2016-01-01

West Nile virus is globally wide-spread and causes significant disease in humans and animals. The evolution of West Nile virus Kunjin subtype in Australia (WNVKUN) was investigated using archival samples collected over a period of 50 years. Based on the pattern of fixed amino acid substitutions and time-stamped molecular clock analyses, a single long-term lineage (or topotype) was inferred. This implies that a bottleneck exists such that regional strains eventually die out and are replaced with strains from a single source. This was consistent with current hypotheses regarding the distribution of WNVKUN, whereby the virus is enzootic in northern Australia and is disseminated to southern states by water-birds or mosquitoes after flooding associated with above average rainfall. In addition, two previous amino acid changes associated with pathogenicity, an N-Y-S glycosylation motif in the envelope protein and a phenylalanine at amino acid 653 in the RNA polymerase, were both detected in all isolates collected since the 1980s. Changes primarily occurred due to stochastic drift. One fixed substitution each in NS3 and NS5, subtly changed the chemical environment of important functional groups, and may be involved in fine-tuning RNA synthesis. Understanding these evolutionary changes will help us to better understand events such as the emergence of the virulent strain in 2011. PMID:27906966

NMR analysis of cleaved Escherichia coli thioredoxin (1-73/74-108) and its P76A variant: cis/trans peptide isomerization.

PubMed Central

Yu, W. F.; Tung, C. S.; Wang, H.; Tasayco, M. L.

2000-01-01

Inspection of high resolution three-dimensional (3D) structures from the protein database reveals an increasing number of cis-Xaa-Pro and cis-Xaa-Yaa peptide bonds. However, we are still far from being able to predict whether these bonds will remain cis upon single-site substitution of Pro or Yaa and/or cleavage of a peptide bond close to it in the sequence. We have chosen oxidized Escherichia coli thioredoxin (Trx), a member of the Trx superfamily with a single alpha/beta domain and cis P76 to determine the effect of single-site substitution and/or cleavage on this isomer. Standard two-dimensional (2D) NMR analysis were performed on cleaved Trx (1-73/74-108) and its P76A variant. Analysis of the NOE connectivities indicates remarkable similarity between the secondary and supersecondary structure of the noncovalent complexes and Trx. Analysis of the 2D version of the HCCH-TOCSY and HMQC-NOESY-HMQC and 13C-filtered HMQC-NOESY spectra of cleaved Trx with uniformly 13C-labeled 175 and P76 shows surprising conservation of both cis P76 and packing of 175 against W31. A similar NMR analysis of its P76A variant provides no evidence for cis A76 and shows only subtle local changes in both the packing of 175 and the interstrand connectivities between its most protected hydrophobic strands (beta2 and beta4). Indeed, a molecular simulation model for the trans P76A variant of Trx shows only subtle local changes around the substitution site. In conclusion, cleavage of R73 is insufficient to provoke cis/trans isomerization of P76, but cleavage and single-site substitution (P76A) favors the trans isomer. PMID:10739243

An Escherichia coli Expression Assay and Screen for Human Immunodeficiency Virus Protease Variants with Decreased Susceptibility to Indinavir

PubMed Central

Melnick, Laurence; Yang, Shiow-Shong; Rossi, Rick; Zepp, Charlie; Heefner, Donald

1998-01-01

We have developed a recombinant Escherichia coli screening system for the rapid detection and identification of amino acid substitutions in the human immunodeficiency virus (HIV) protease associated with decreased susceptibility to the protease inhibitor indinavir (MK-639; Merck & Co.). The assay depends upon the correct processing of a segment of the HIV-1 HXB2 gag-pol polyprotein followed by detection of HIV reverse transcriptase activity by a highly sensitive, colorimetric enzyme-linked immunosorbent assay. The highly sensitive system detects the contributions of single substitutions such as I84V, L90M, and L63P. The combination of single substitutions further decreases the sensitivity to indinavir. We constructed a library of HIV protease variant genes containing dispersed mutations and, using the E. coli recombinant system, screened for mutants with decreased indinavir sensitivity. The discovered HIV protease variants contain amino acid substitutions commonly associated with indinavir resistance in clinical isolates, including the substitutions L90M, L63P, I64V, V82A, L24I, and I54T. One substitution, W6R, is also frequently found by the screen and has not been reported elsewhere. Of a total of 12,000 isolates that were screened, 12 protease variants with decreased sensitivity to indinavir were found. The L63P substitution, which is also associated with indinavir resistance, increases the stability of the isolated protease relative to that of the native HXB2 protease. The rapidity, sensitivity, and accuracy of this screen also make it useful for screening for novel inhibitors. We have found the approach described here to be useful for the detection of amino acid substitutions in HIV protease that have been associated with drug resistance as well as for the screening of novel compounds for inhibitory activity. PMID:9835523

Evaluation of stability region for scandium-containing rare-earth garnet single crystals and their congruent-melting compositions

NASA Astrophysics Data System (ADS)

Kaurova, I. A.; Domoroshchina, E. N.; Kuz'micheva, G. M.; Rybakov, V. B.

2017-06-01

Single crystals of scandium-containing rare-earth garnets in system R-Sc-C-O (R3+=Y, Gd; C3+=Al, Ga) have been grown by the Czochralski technique. X-ray diffraction analysis has been used to refine crystal compositions. The fundamental difference between the melt compositions and compositions of grown crystals has been found (except for compositions of congruent-melting compounds, CMC). The specific features of garnet solid solution formation have been established and the ternary diagrams with real or hypothetical phases have been built. The dinamics of coordination polyhedra changes with the formation of substitutional solid solutions have been proposed based on the mathematical modeling and experimental data. Possible existence of CMC with garnet structure in different systems as well as limit content of Sc ions in dodecahedral and octahedral sites prior to their partial substitution of ions, located in other sites, have been evaluated. It was established that the redistribution of cations over crystallographic sites (antistructural point defects) due to system self-organization to maintain its stability may be accompanied by cation ordering and the symmetry change of individual polyhedrons and/or the whole crystal.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder.

PubMed

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder

PubMed Central

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered. PMID:22934180

Effect of Fe and Co substitution on the martensitic stability and the elastic, electronic, and magnetic properties of Mn2NiGa : Insights from ab initio calculations

NASA Astrophysics Data System (ADS)

Kundu, Ashis; Ghosh, Sheuly; Ghosh, Subhradip

2017-11-01

We investigate the effects of Fe and Co substitutions on the phase stability of the martensitic phase and mechanical, electronic, and magnetic properties of the magnetic shape memory system Mn2NiGa by first-principles density functional theory calculations. The evolution of these aspects upon substitution of Fe and Co at different crystallographic sites is investigated by computing the electronic structure, mechanical properties (tetragonal shear constant, Pugh ratio, and Cauchy pressure), and magnetic exchange parameters. We find that the austenite phase of Mn2NiGa gradually stabilizes with increase in concentration of Fe/Co due to the weakening of the minority spin hybridization of Ni and Mn atoms occupying crystallographically equivalent sites. The interplay between relative structural stability and the compositional changes is understood from the variations in the elastic moduli and electronic structures. We find that like in the Ni2MnGa -based systems, the elastic shear modulus C' can be considered as a predictor of composition dependence of martensitic transformation temperature Tm in substituted Mn2NiGa , thus singling it out as the universally acceptable predictor for martensitic transformation in Ni-Mn-Ga compounds over a wide composition range. The magnetic properties of Mn2NiGa are found to be greatly improved by the substitutions due to stronger ferromagnetic interactions in the compounds. The gradually weaker (stronger) Jahn-Teller distortion (covalent bonding) in the minority spin densities of states due to substitutions leads to a half-metallic-like gap in these compounds resulting in materials with high spin polarization when the substitutions are complete. The substitutions at the Ga site result in the two compounds Mn2NiFe and Mn2NiCo with very high magnetic moments and Curie temperatures. Thus, our work indicates that although the substitutions destroy the martensitic transformation and thus the possibility of realization of shape memory properties in Mn2NiGa , magnetic materials with very good magnetic parameters that are potentially useful for novel magnetic applications can be obtained. This can trigger interest in the experimental community in further research on substituted Mn2NiGa .

Antibody specificities of children living in a malaria endemic area to inhibitory and blocking epitopes on MSP-1 19 of Plasmodium falciparum.

PubMed

Omosun, Y O; Adoro, S; Anumudu, C I; Odaibo, A B; Uthiapibull, C; Holder, A A; Nwagwu, M; Nwuba, R I

2009-03-01

Merozoite surface protein-1(19) (MSP-1(19)) specific antibodies which include processing inhibitory, blocking and neutral antibodies have been identified in individuals exposed to Plasmodium falciparum. Here we intend to look at the effect of single and multiple amino acid substitutions of MSP-1(19) on the recognition by polyclonal antibodies from children living in Igbo-Ora, Nigeria. This would provide us with information on the possibility of eliciting mainly processing inhibitory antibodies with a recombinant MSP-1(19) vaccine. Blood was collected from children in the rainy season and binding of anti-MSP-1(19) antibodies to modified mutants of MSP-1(19) was analysed by ELISA. The MSP-1(19) mutant proteins with single substitutions at positions 22 (Leu-->Arg), 43 (Glu-->Leu) and 53 (Asn-->Arg) and the MSP-1(19) mutant protein with multiple substitutions at positions 27+31+34+43 (Glu-->Tyr, Leu-->Arg, Tyr-->Ser, Glu-->Leu); which had inhibitory epitopes; had the highest recognition. Children recognised both sets of mutants with different age groups having different recognition levels. The percentage of malaria positive individuals (32-80%) with antibodies that bound to the mutants MSP-1(19) containing epitopes that recognise only processing inhibitory and not blocking antibodies, were significantly different from those with antibodies that did not bind to these mutants (21-28%). The amino acid substitutions that abolished the binding of blocking antibodies without affecting the binding of inhibitory antibodies are of particular interest in the design of MSP-1(19) based malaria vaccines. Although these MSP-1(19) mutants have not been found in natural population, their recognition by polyclonal antibodies from humans naturally infected with malaria is very promising for the future use of MSP-1(19) mutants in the design of a malaria vaccine.

Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite.

PubMed

Friederichs, Robert J; Chappell, Helen F; Shepherd, David V; Best, Serena M

2015-07-06

Experimental chemistry and atomic modelling studies were performed here to investigate a novel ionic co-substitution in hydroxyapatite (HA). Zinc, silicate co-substituted HA (ZnSiHA) remained phase pure after heating to 1100 °C with Zn and Si amounts of 0.6 wt% and 1.2 wt%, respectively. Unique lattice expansions in ZnSiHA, silicate Fourier transform infrared peaks and changes to the hydroxyl IR stretching region suggested Zn and silicate co-substitution in ZnSiHA. Zn and silicate insertion into HA was modelled using density functional theory (DFT). Different scenarios were considered where Zn substituted for different calcium sites or at a 2b site along the c-axis, which was suspected in singly substituted ZnHA. The most energetically favourable site in ZnSiHA was Zn positioned at a previously unreported interstitial site just off the c-axis near a silicate tetrahedron sitting on a phosphate site. A combination of experimental chemistry and DFT modelling provided insight into these complex co-substituted calcium phosphates that could find biomedical application as a synthetic bone mineral substitute. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Modal gating of muscle nicotinic acetylcholine receptors

NASA Astrophysics Data System (ADS)

Vij, Ridhima

Many ion channels exhibit multiple patterns of kinetic activity in single-channel currents. This behavior is rare in WT mouse muscle nicotinic acetylcholine receptors (AChRs), where A2C↔A2O gating events are well-described by single exponentials. Also, single-channel open probability (PO) is essentially homogeneous at a given agonist concentration in the WT receptors. Here I report that perturbations of almost all the residues in loop C (alpha188-alpha199, at the agonist binding site) generate heterogeneity in PO ('modes'). Such unsettled activity was apparent with an alanine substitution at all positions in loop C (except alphaY190 and alphaY198) and with different side chain substitutions at alphaP197 for both adult- and fetal-type AChRs. I used single channel electrophysiology along with site-directed mutagenesis to study modal gating in AChRs consequent to mutations/deletions in loop C. The multiple patterns of kinetic activity arose from the difference in agonist affinity rather than in intrinsic AChR gating. Out of the four different agonists used to study the modal behavior, acetylcholine (ACh) showed a higher degree of kinetic heterogeneity compared to others. The time constant for switching between modes was long (~mins), suggesting that they arise from alternative, stable protein conformations. By studying AChRs having only 1 functional binding site, I attempted to find the source of the affinity difference, which was traced mainly to the alphadelta agonist site. Affinity at the neurotransmitter binding site is mainly determined by a core of five aromatic residues (alphaY93, alphaW149, alphaY190, alphaY198 and deltaW57). Phenylalanine substitutions at all aromatic residues except alphaY93 resulted in elimination of modes. Modes were also eliminated by alanine mutation at deltaW57 on the complementary side but not at other aromatics. Also, by substituting four gamma subunit residues into the delta subunit on the complementary beta sheet, I found that modes were reduced. Based on our results, we propose that WT loop C has an important role in determining resting affinity, in part by making stable interactions with the complementary surface of the alphadelta binding pocket. We suggest a possible structural basis for the fluctuations caused by loop C perturbations and propose that at the alphadelta agonist binding site, both loop C and the complementary subunit surface can adopt alternative conformations and interact with each other with respect to the aromatic core, to cause the variations in affinity.

Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

PubMed

Hernández, Armando R; Peterson, Larryn W; Kool, Eric T

2012-08-17

Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modified siRNAs have been reported, relatively few studies with modified nucleobases exist. Here we describe the synthesis and hybridization properties of siRNAs bearing size-expanded RNA (xRNA) nucleobases and their use as a novel and systematic set of steric probes in RNAi. xRNA nucleobases are expanded by 2.4 Å using benzo-homologation and retain canonical Watson-Crick base-pairing groups. Our data show that the modified siRNA duplexes display small changes in melting temperature (+1.4 to -5.0 °C); substitutions near the center are somewhat destabilizing to the RNA duplex, while substitutions near the ends are stabilizing. RNAi studies in a dual-reporter luciferase assay in HeLa cells revealed that xRNA nucleobases in the antisense strand reduce activity at some central positions near the seed region but are generally well tolerated near the ends. Most importantly, we observed that xRNA substitutions near the 3'-end increased activity over that of wild-type siRNAs. The data are analyzed in terms of site-dependent steric effects in RISC. Circular dichroism experiments show that single xRNA substitutions do not significantly distort the native A-form helical structure of the siRNA duplex, and serum stability studies demonstrated that xRNA substitutions protect siRNAs against nuclease degradation.

Steric Restrictions of RISC in RNA Interference Identified with Size-Expanded RNA Nucleobases

PubMed Central

Hernández, Armando R.; Peterson, Larryn W.; Kool, Eric T.

2012-01-01

Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC) – the key protein complex of RNA interference (RNAi) – is of great importance to the development of siRNAs with improved biological, and potentially therapeutic, function. Although various chemically modified siRNAs have been reported, relatively few studies with modified nucleobases exist. Here we describe the synthesis and hybridization properties of siRNAs bearing size-expanded RNA (xRNA) nucleobases, and their use as a novel and systematic set of steric probes in RNAi. xRNA nucleobases are expanded by 2.4 Å using benzo-homologation and retain canonical Watson-Crick base-pairing groups. Our data show that the modified siRNA duplexes display small changes in melting temperature (+1.4 to −5.0 °C); substitutions near the center are somewhat destabilizing to the RNA duplex, while substitutions near the ends are stabilizing. RNAi studies in a dual-reporter luciferase assay in HeLa cells revealed that xRNA nucleobases in the antisense strand reduce activity at some central positions near the seed region, but are generally well tolerated near the ends. Most importantly, we observed that xRNA substitutions near the 3′-end increased activity over wild-type siRNAs. The data are analyzed in terms of site-dependent steric effects in RISC. Circular dichroism experiments show that single xRNA substitutions do not significantly distort the native A-form helical structure of the siRNA duplex, and serum stability studies demonstrated that xRNA substitutions protect siRNAs against nuclease degradation. PMID:22646660

2Flux growth and characterization of Ce-substituted Nd 2 Fe 14 B single crystals

DOE PAGES

Susner, Michael A.; Conner, Benjamin S.; Saparov, Bayrammurad I.; ...

2016-10-27

Single crystals of (Nd 1-xCe x) 2Fe 14B are grown out of Fe-(Nd,Ce) flux. Chemical and structural analysis of the crystals indicate that (Nd 1-xCe x) 2Fe 14B forms a solid solution until at least x = 0.38 with a Vegard-like variation of the lattice constants with x. Refinements of single crystal neutron diffraction data indicate that Ce has a slight site preference (7:3) for the 4g rare earth site over the 4f site. Magnetization measurements at 300 K show only small decreases with increasing Ce content in saturation magnetization (M s) and anisotropy field (H A), and Curie temperaturemore » (T C). First principles calculations are carried out to understand the effect of Ce substitution on the electronic and magnetic properties. For a multitude of applications, it is expected that the advantage of incorporating lower-cost and more abundant Ce will outweigh the small adverse effects on magnetic properties. In conclusion, Ce-substituted Nd 2Fe 14B is therefore a potential high-performance permanent magnet material with substantially reduced Nd content.« less

Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution.

PubMed

Gumbs, Pearl D; Verschuren, W M Monique; Souverein, Patrick C; Mantel-Teeuwisse, Aukje K; de Wit, G Ardine; de Boer, Anthonius; Klungel, Olaf H

2007-11-01

To assess the potential annual savings due to generic and therapeutic substitution of statin therapy for the general Dutch population, taking the patients medical history into account. We conducted a population-based costing study using the PHARMO Record Linkage System (RLS). PHARMO RLS contains drug dispensing records from a representative sample of pharmacies located in more than 50 regions in the Netherlands. We selected all statin users in the database since 2003. The cost-savings of generic substitution of statin therapy for all simvastatin and pravastatin users, and of therapeutic substitution of statin therapy for other statin users were calculated. Substituting current users and new users of statins were considered separately. Therapeutic substitution was based on the medical history of the individual patient. Patients were only substituted if there was an appropriate substitute available. The appropriateness of substitution was based on drug-drug interactions between statins and possible comedication and the availability of an equipotent alternative. Substituting (generic and therapeutic) statin therapy for all current users would lead to potential annual savings of approximately 87 million euros. Substituting (generic and therapeutic) all starters on statin therapy would lead to potential annual savings of around 51 million euros. In the case of generic substitution only, the potential annual savings for all current simvastatin and pravastatin users would be 2.4 million euros and for the new users about 1.8 million euros. From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution.

The Idiographic Study of Leadership Behavior in Natural Settings: An Empirical Analysis Using a Single Case Experimental Design.

DTIC Science & Technology

1982-08-01

Management , 1977, 1, 105-109. LAuthans, F. Leadership : A proposal for a social learning theory base and observational and functional analysis...Manz, C.C., & Sims, H.P. Self management as a substitute for leadership : A social learning theory perspective. Academy of Management Review, 1980, 5...AD-AI19 89 NEBRASKA UNIV LINCOLN DEPT OF MANAGEMENT F/G 5/1 THE IDIOGRAPHIC STUDY OF LEADERSHIP BEHAVIOR IN NATURAL SETTING-ETCIU)AUG 82 T R DAVI , F

One-pot microwave assisted synthesis and structural elucidation of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates with larvicidal activity against Anopheles arabiensis

NASA Astrophysics Data System (ADS)

Chandrashekharappa, Sandeep; Venugopala, Katharigatta N.; Nayak, Susanta K.; Gleiser, Raquel M.; García, Daniel A.; Kumalo, Hezekiel M.; Kulkarni, Rashmi S.; Mahomoodally, Fawzi M.; Venugopala, Rashmi; Mohan, Mahendra K.; Odhav, Bharti

2018-03-01

In the present investigation a series of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates was achieved by microwave assisted one-pot method. The purity of the compounds was ascertained by HPLC and structural elucidation of the title compounds was achieved by FT-IR, NMR (1H and 13C), LC-MS and elemental analysis. One randomly selected compound from the series was further studied by single crystal X-ray method for intra and intermolecular interactions. Larvicidal properties of the characterized compounds were evaluated against Anopheles arabiensis and it was found that indolizine pharmacophore influences larvicidal activity as we can see larvicidal activity for all the analogues. The synthesized analogues (2j, 2m and 2f) were the most potent compounds based on the functional groups on the indolizine pharmacophore for larvicidal assay.

The chlorophyll-deficient golden leaf mutation in cucumber is due to a single nucleotide substitution in CsChlI for magnesium chelatase I subunit.

PubMed

Gao, Meiling; Hu, Liangliang; Li, Yuhong; Weng, Yiqun

2016-10-01

The cucumber chlorophyll-deficient golden leaf mutation is due to a single nucleotide substitution in the CsChlI gene for magnesium chelatase I subunit which plays important roles in the chlorophyll biosynthesis pathway. The Mg-chelatase catalyzes the insertion of Mg(2+) into the protoporphyrin IX in the chlorophyll biosynthesis pathway, which is a protein complex encompassing three subunits CHLI, CHLD, and CHLH. Chlorophyll-deficient mutations in genes encoding the three subunits have played important roles in understanding the structure, function and regulation of this important enzyme. In an EMS mutagenesis population, we identified a chlorophyll-deficient mutant C528 with golden leaf color throughout its development which was viable and able to set fruits and seeds. Segregation analysis in multiple populations indicated that this leaf color mutation was recessively inherited and the green color showed complete dominance over golden color. Map-based cloning identified CsChlI as the candidate gene for this mutation which encoded the CHLI subunit of cucumber Mg-chelatase. The 1757-bp CsChlI gene had three exons and a single nucleotide change (G to A) in its third exon resulted in an amino acid substitution (G269R) and the golden leaf color in C528. This mutation occurred in the highly conserved nucleotide-binding domain of the CHLI protein in which chlorophyll-deficient mutations have been frequently identified. The mutant phenotype, CsChlI expression pattern and the mutated residue in the CHLI protein suggested the mutant allele in C528 is unique among mutations identified so far in different species. This golden leaf mutant not only has its potential in cucumber breeding, but also provides a useful tool in understanding the CHLI function and its regulation in the chlorophyll biosynthesis pathway as well as chloroplast development.

A single amino acid substitution in the Bombyx-specific mucin-like membrane protein causes resistance to Bombyx mori densovirus.

PubMed

Ito, Katsuhiko; Kidokoro, Kurako; Katsuma, Susumu; Sezutsu, Hideki; Uchino, Keiro; Kobayashi, Isao; Tamura, Toshiki; Yamamoto, Kimiko; Mita, Kazuei; Shimada, Toru; Kadono-Okuda, Keiko

2018-05-09

Bombyx mori densovirus type 1 (BmDV) is a pathogen that causes flacherie disease in the silkworm. The absolute nonsusceptibility to BmDV among certain silkworm strains is determined independently by two genes, nsd-1 and Nid-1. However, neither of these genes has been molecularly identified to date. Here, we isolated the nsd-1 gene by positional cloning and characterized the properties of its product, NSD-1. Sequence and biochemical analyses revealed that this gene encodes a Bombyx-specific mucin-like glycoprotein with a single transmembrane domain. The NSD-1 protein was specifically expressed in the larval midgut epithelium, the known infection site of BmDV. Sequence analysis of the nsd-1 gene from 13 resistant and 12 susceptible strains suggested that a specific arginine residue in the extracellular tail of the NSD-1 protein was common among susceptible strains. Germline transformation of the susceptible-type nsd-1 (with a single nucleotide substitution) conferred partial susceptibility to resistant larvae, indicating that the +  nsd-1 gene is required for the susceptibility of B. mori larvae to BmDV and the susceptibility is solely a result of the substitution of a single amino acid with arginine. Taken together, our results provide striking evidence that a novel membrane-bound mucin-like protein functions as a cell-surface receptor for a densovirus.

Structural analysis of aluminium substituted nickel ferrite nanoparticles

NASA Astrophysics Data System (ADS)

Singh, H. S.; Sangwa, Neha

2018-05-01

Aluminium substituted nickel ferrite nanoparticles were synthesized by High Energy Ball milling (HEBM) of the mixture of α-NiO, α-Al2O3 and α-Fe2O3 followed by annealing at 1000˚C. X-ray diffraction (XRD) and Energy dispersive spectroscopy analysis (EDS) characterization was done for Aluminium substituted nickel ferrite. The structural analysis reveals the formation of the single phase compound. The average grain size was estimated by X-ray diffraction technique ranges from 30 to 10 nm with the increasing concentration of Aluminium. EDS spectra conforms the homogeneous mixing and purity of ferrite.

Synthesis and structure elucidation of fluoro substituted guanidines as potential therapeutic agents

NASA Astrophysics Data System (ADS)

Ullah, Waseem; Imtiaz-ud-Din; Raheel, Ahmad; Badshah, Amin; Tahir, Muhammad Nawaz

2017-09-01

Six new fluoro -substituted guanidines (1-6) were synthesized and characterized by 1H and 13C NMR spectroscopy to ascertain the structures in solution (DMSO) besides the solid state information collected through FT IR and single crystal X-ray spectroscopy. The XRD data for (1-3) show that molecules are stabilized by strong intramolecular hydrogen bonding. The compounds were also preliminary bio-assayed for anti-microbial studies and show good to moderate activities. The anti-oxidant data revealed that o and p-substituted fluoro-guanidines enhances their DPPH scavenging ability significantly.

The Rotational Spectrum of Singly and Doubly 13C-SUBSTITUTED Dimethylether

NASA Astrophysics Data System (ADS)

Koerber, Monika; Endres, Christian P.; Lewen, Frank; Giesen, Thomas F.; Schlemmer, Stephan; Pohl, Roland; Klein, Axel

2010-06-01

Dimethylether (DME) is a nearly prolate asymmetric top with two internal rotors (methyl groups) which undergo periodic large amplitude motions and show a complicated torsional splitting of each rotational energy level. Due to its complex spectrum and its high abundance in hot cores such as Orion KL or Sagittarius B2 at temperatures exceeding 100 K, DME is very prominent in astronomical line surveys and contributes to spectral line confusion of such sources. The interpretation of astronomical observations therefore depends on the knowledge of accurate rest frequencies and reliable intensities. Precise predictions for the ground state of DME's main isotopologue are now available up to 2.1 THz In contrast, very little is known about 13C-substituted DME. Only a few data are available on singly 13C-substituted DME, 12CH_3O13CH_3. However, no data are available on doubly 13C-substituted DME, (13CH_3)_2O, yet. While in (13CH_3)_2O the two internal rotating methyl groups are equivalent and the splitting of rotational energy levels into four substates is comparable to the main isotopologue, singly 13C-substituted DME has two non-equivalent internal rotors resulting in torsional splitting of rotational energy levels into five substates. The purpose of our new laboratory measurements is to extend the knowledge on the astrophysically relevant species 12CH_3O13CH_3. To analyze the complicated spectrum resulting from a 13C-enriched sample of DME, containing all different 13C-substituted species as well as the main isotopologue, also precise data on doubly 13C-substituted DME are inevitable. We performed measurements in the frequency region 35-120 GHz using an all solid state spectrometer. Rotational as well as torsional parameters have been obtained for (13CH_3)_2O as well as 12CH_3O13CH_3 by fitting the assigned transitions to an effective rotational Hamiltonian introduced by Peter Groner. C. Comito et al., Astrophys. J. Suppl. Ser. 156, 127-167 (2005) C. P. Endres et al., Astronomy & Astrophysics 504, 635-640 (2009) Y. Niide and M. Hayashi, J. Mol. Spectrosc. 220, 65-79 (2003) P. Groner, J. Chem. Phys. 107, 4483-4498 (1997).

A first-principles study of carbon-related energy levels in GaN. I. Complexes formed by substitutional/interstitial carbons and gallium/nitrogen vacancies

NASA Astrophysics Data System (ADS)

Matsubara, Masahiko; Bellotti, Enrico

2017-05-01

Various forms of carbon based complexes in GaN are studied with first-principles calculations employing Heyd-Scuseria-Ernzerhof hybrid functionals within the framework of the density functional theory. We consider carbon complexes made of the combinations of single impurities, i.e., CN-CGa, CI-CN , and CI-CGa , where CN, CGa , and CI denote C substituting nitrogen, C substituting gallium, and interstitial C, respectively, and of neighboring gallium/nitrogen vacancies ( VGa / VN ), i.e., CN-VGa and CGa-VN . Formation energies are computed for all these configurations with different charge states after full geometry optimizations. From our calculated formation energies, thermodynamic transition levels are evaluated, which are related to the thermal activation energies observed in experimental techniques such as deep level transient spectroscopy. Furthermore, the lattice relaxation energies (Franck-Condon shift) are computed to obtain optical activation energies, which are observed in experimental techniques such as deep level optical spectroscopy. We compare our calculated values of activation energies with the energies of experimentally observed C-related trap levels and identify the physical origins of these traps, which were unknown before.

Substitution structure of cyanogen, NCCN, from high-resolution far infrared spectra

NASA Astrophysics Data System (ADS)

Grecu, John C.; Winnewisser, Brenda P.; Winnewisser, Manfred

2003-04-01

The lowest lying vibrational bands of the gas-phase spectra of cyanogen, NCCN, and four of its isotopomers, 15NCCN, N13CCN, 15NCC15N, and N13C13CN, were recorded with a Fourier transform interferometer. The resolution was limited by the maximum optical path difference (MOPD) attainable with the interferometer to FWHM=0.0012 cm-1. Rovibrational transitions of the ν5 ( ≈230 cm-1) and also the ν2- ν5 ( ≈610 cm-1) band systems were assigned for all five isotopomers. The use of an effective Hamiltonian for linear molecules to fit the data yielded precise spectroscopic vibrational and rotational constants for the vibrational states ( v1v2v3v4v5) or ( v4v5)=(00), (01), (02), (03), and (01000). These data include the first rotationally resolved transitions involving (01000). Complete substitution ( rs) structures of cyanogen, based on both single and double isotopic substitution of the parent species, were calculated. The derived structure is rCC=138.48(17) pm and rCN=115.66(13) pm. The two rs structures coincide within the errors due to remaining contributions of zero-point vibrations.

A revised timescale for human evolution based on ancient mitochondrial genomes

PubMed Central

Johnson, Philip L.F.; Bos, Kirsten; Lari, Martina; Bollongino, Ruth; Sun, Chengkai; Giemsch, Liane; Schmitz, Ralf; Burger, Joachim; Ronchitelli, Anna Maria; Martini, Fabio; Cremonesi, Renata G.; Svoboda, Jiří; Bauer, Peter; Caramelli, David; Castellano, Sergi; Reich, David; Pääbo, Svante; Krause, Johannes

2016-01-01

Summary Background Recent analyses of de novo DNA mutations in modern humans have suggested a nuclear substitution rate that is approximately half that of previous estimates based on fossil calibration. This result has led to suggestions that major events in human evolution occurred far earlier than previously thought. Result Here we use mitochondrial genome sequences from 10 securely dated ancient modern humans spanning 40,000 years as calibration points for the mitochondrial clock, thus yielding a direct estimate of the mitochondrial substitution rate. Our clock yields mitochondrial divergence times that are in agreement with earlier estimates based on calibration points derived from either fossils or archaeological material. In particular, our results imply a separation of non-Africans from the most closely related sub-Saharan African mitochondrial DNAs (haplogroup L3) of less than 62,000-95,000 years ago. Conclusion Though single loci like mitochondrial DNA (mtDNA) can only provide biased estimates of population split times, they can provide valid upper bounds; our results exclude most of the older dates for African and non-African split times recently suggested by de novo mutation rate estimates in the nuclear genome. PMID:23523248

A revised timescale for human evolution based on ancient mitochondrial genomes.

PubMed

Fu, Qiaomei; Mittnik, Alissa; Johnson, Philip L F; Bos, Kirsten; Lari, Martina; Bollongino, Ruth; Sun, Chengkai; Giemsch, Liane; Schmitz, Ralf; Burger, Joachim; Ronchitelli, Anna Maria; Martini, Fabio; Cremonesi, Renata G; Svoboda, Jiří; Bauer, Peter; Caramelli, David; Castellano, Sergi; Reich, David; Pääbo, Svante; Krause, Johannes

2013-04-08

Recent analyses of de novo DNA mutations in modern humans have suggested a nuclear substitution rate that is approximately half that of previous estimates based on fossil calibration. This result has led to suggestions that major events in human evolution occurred far earlier than previously thought. Here, we use mitochondrial genome sequences from ten securely dated ancient modern humans spanning 40,000 years as calibration points for the mitochondrial clock, thus yielding a direct estimate of the mitochondrial substitution rate. Our clock yields mitochondrial divergence times that are in agreement with earlier estimates based on calibration points derived from either fossils or archaeological material. In particular, our results imply a separation of non-Africans from the most closely related sub-Saharan African mitochondrial DNAs (haplogroup L3) that occurred less than 62-95 kya. Though single loci like mitochondrial DNA (mtDNA) can only provide biased estimates of population divergence times, they can provide valid upper bounds. Our results exclude most of the older dates for African and non-African population divergences recently suggested by de novo mutation rate estimates in the nuclear genome. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multiplex PCR method for use in real-time PCR for identification of fish fillets from grouper (Epinephelus and Mycteroperca species) and common substitute species.

PubMed

Trotta, Michele; Schönhuth, Susana; Pepe, Tiziana; Cortesi, M Luisa; Puyet, Antonio; Bautista, José M

2005-03-23

Mitochondrial 16S rRNA sequences from morphological validated grouper (Epinephelus aeneus, E. caninus, E. costae, and E. marginatus; Mycteroperca fusca and M. rubra), Nile perch (Lates niloticus), and wreck fish (Polyprion americanus) were used to develop an analytical system for group diagnosis based on two alternative Polymerase Chain Reaction (PCR) approaches. The first includes conventional multiplex PCR in which electrophoretic migration of different sizes of bands allowed identification of the fish species. The second approach, involving real-time PCR, produced a single amplicon from each species that showed different Tm values allowing the fish groups to be directly identified. Real-time PCR allows the quick differential diagnosis of the three groups of species and high-throughput screening of multiple samples. Neither PCR system cross-reacted with DNA samples from 41 common marketed fish species, thus conforming to standards for species validation. The use of these two PCR-based methods makes it now possible to discriminate grouper from substitute fish species.

Magnetic properties of co-precipitated hexaferrite powders with Sm-Co substitutions optimized with the molten flux method

NASA Astrophysics Data System (ADS)

Serletis, C.; Litsardakis, G.; Pavlidou, E.; Efthimiadis, K. G.

2017-11-01

In this work, using the chemical coprecipitation method, Sr1-xSmxFe12-xCoxO19 (x = 0, 0.1, 0.2) hexaferrite powders were prepared. Major magnetization loops were recorded at room temperature in order to determine the correct calcination temperature for optimum hard magnetic properties. It is found that a small degree of substitution increases substantially the coercive field. Also, the use of the molten flux calcination method increases the remanent magnetization. SEM/EDXS and XRD measurements were performed at the calcined powders: the results show that a single hexaferrite phase is formed and that the substituted powders consist of an assembly of grains with a mean diameter of 40 nm. Measurements of minor magnetization loops and of the temperature and time dependence of the magnetization confirm that the powders consist of a non-oriented single domain magnetic particles assembly. The results indicate that Sm could be a viable replacement for La in the manufacturing of hexaferrites with a high-energy product.

Effect of Fe-substitution on the structure and magnetism of single crystals Mn2-xFexBO4

NASA Astrophysics Data System (ADS)

Platunov, M. S.; Kazak, N. V.; Knyazev, Yu. V.; Bezmaternykh, L. N.; Moshkina, E. M.; Trigub, A. L.; Veligzhanin, A. A.; Zubavichus, Y. V.; Solovyov, L. A.; Velikanov, D. A.; Ovchinnikov, S. G.

2017-10-01

Single crystalline Mn2-xFexBO4 with x = 0.3, 0.5, 0.7 grown by the flux method have been studied by means of X-ray diffraction and X-ray absorption spectroscopy at both Mn and Fe K edges. The compounds were found to crystallize in an orthorhombic warwickite structure (sp. gr. Pnam). The lattice parameters change linearly with x thus obeying the Vegard's law. The Fe3+ substitution for Mn3+ has been deduced from the X-ray absorption near-edge structure (XANES) spectra. Two energy positions of the absorption edges have been observed in Mn K-edge XANES spectra indicating the presence of manganese in two different oxidation states. Extended X-ray absorption fine structure (EXAFS) analysis has shown the reduction of local structural distortions upon Fe substitution. The magnetization data have revealed a spin-glass transition at TSG = 11, 14 and 18 K for x = 0.3, 0.5 and 0.7, respectively.

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

Structure variations of TBA G-quadruplex induced by 2'-O-methyl nucleotide in K+ and Ca2+ environments.

PubMed

Zhao, Xiaoyang; Liu, Bo; Yan, Jing; Yuan, Ying; An, Liwen; Guan, Yifu

2014-10-01

Thrombin binding aptamer (TBA), a 15-mer oligonucleotide of d(GGTTGGTGTGGTTGG) sequence, folds into a chair-type antiparallel G-quadruplex in the K(+) environment, and each of two G-tetrads is characterized by a syn-anti-syn-anti glycosidic conformation arrangement. To explore its folding topology and structural stability, 2'-O-methyl nucleotide (OMe) with the C3'-endo sugar pucker conformation and anti glycosidic angle was used to selectively substitute for the guanine residues of G-tetrads of TBA, and these substituted TBAs were characterized using a circular dichroism spectrum, thermally differential spectrum, ultraviolet stability analysis, electrophoresis mobility shift assay, and thermodynamic analysis in K(+) and Ca(2+) environments. Results showed that single substitutions for syn-dG residues destabilized the G-quadruplex structure, while single substitutions for anti-dG residues could preserve the G-quadruplex in the K(+) environment. When one or two G-tetrads were modified with OMe, TBA became unstructured. In contrast, in Ca(2+) environment, the native TBA appeared to be unstructured. When two G-tetrads were substituted with OMe, TBA seemed to become a more stable parallel G-4 structure. Further thermodynamic data suggested that OMe-substitutions were an enthalpy-driven event. The results in this study enrich our understanding about the effects of nucleotide derivatives on the G-quadruplex structure stability in different ionic environments, which will help to design G-quadruplex for biological and medical applications. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Photoisomerization of Trans Ortho-, Meta-, Para-Nitro Diarylbutadienes: A Case of Regioselectivity.

PubMed

Agnihotri, Harsha; Paramasivam, Mahalingavelar; Palakollu, Veerabhadraiah; Kanvah, Sriram

2015-11-01

A series of ortho-, meta- and para-substituted trans-nitro aryl (phenyl and pyridyl) butadienes have been synthesized and characterized. The effect of substitution and positional selectivity on their fluorescence and photoisomerization were systematically investigated. Among all dienes, meta- and para-nitro phenyl-substituted derivatives exhibit remarkable solvatochromic emission shifts due to intramolecular charge transfer. On the other hand, ortho derivatives undergo regioselective isomerization upon photoexcitation in contrast to inefficient isomerization of para and meta nitro-substituted dienes. Single crystal X-ray analysis revealed existence of intramolecular hydrogen bonding between the nitro group and the hydrogen of the proximal double bond. This restricts the rotation of the proximal double bond thereby allowing regioselective isomerization. The observations were also supported by NMR spectroscopic studies. © 2015 The American Society of Photobiology.

The study of structure-activity relationships among substituted N-benzoyl derivatives of phenylalanine and its analogs in a microbial antitumor prescreen: II. Derivatives of m-fluoro-DL-phenylalanine.

PubMed

Otani, T T; Briley, M R

1983-05-01

The fluoro-, chloro-, methoxy- and nitro-substituted benzoyl derivatives of m-fluoro-DL-phenylalanine, substituted singly at the ortho, meta or para position of the benzoyl phenyl ring, were prepared and tested for growth-inhibitory activity in a Lactobacillus casei system used as an antitumor prescreen. The substituted benzoyl derivatives that were previously found to be the most active for o-fluoro-DL-phenylalanine were also the most active for the m-fluoro-DL-phenylalanine. The position of the fluorine substituent in the phenylalanine also appeared to be important for inhibitory activity as the derivatives of m-fluoro-phenylalanine were in general better inhibitors than those of the corresponding o-fluorophenylalanine.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle

PubMed Central

Serre, Stéphanie B. N.; Jensen, Sanne B.; Ghanem, Lubna; Humes, Daryl G.; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens

2016-01-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. PMID:27021330

Effects of Xylan Side-Chain Substitutions on Xylan-Cellulose Interactions and Implications for Thermal Pretreatment of Cellulosic Biomass.

PubMed

Pereira, Caroline S; Silveira, Rodrigo L; Dupree, Paul; Skaf, Munir S

2017-04-10

Lignocellulosic biomass is mainly constituted by cellulose, hemicellulose, and lignin and represents an important resource for the sustainable production of biofuels and green chemistry materials. Xylans, a common hemicellulose, interact with cellulose and often exhibit various side chain substitutions including acetate, (4-O-methyl) glucuronic acid, and arabinose. Recent studies have shown that the distribution of xylan substitutions is not random, but follows patterns that are dependent on the plant taxonomic family and cell wall type. Here, we use molecular dynamics simulations to investigate the role of substitutions on xylan interactions with the hydrophilic cellulose face, using the recently discovered xylan decoration pattern of the conifer gymnosperms as a model. The results show that α-1,2-linked substitutions stabilize the binding of single xylan chains independently of the nature of the substitution and that Ca 2+ ions can mediate cross-links between glucuronic acid substitutions of two neighboring xylan chains, thus stabilizing binding. At high temperature, xylans move from the hydrophilic to the hydrophobic cellulose surface and are also stabilized by Ca 2+ cross-links. Our results help to explain the role of substitutions on xylan-cellulose interactions, and improve our understanding of the plant cell wall architecture and the fundamentals of biomass pretreatments.

Structural, optical, mechanical and dielectric studies of pure and doped L-Prolinium trichloroacetate single crystals.

PubMed

Renuka, N; Ramesh Babu, R; Vijayan, N; Vasanthakumar, Geetha; Krishna, Anuj; Ramamurthi, K

2015-02-25

In the present work, pure and metal substituted L-Prolinium trichloroacetate (LPTCA) single crystals were grown by slow evaporation method. The grown crystals were subjected to single crystal X-ray diffraction (XRD), powder X-ray diffraction, FTIR, UV-Visible-NIR, hardness, photoluminescence and dielectric studies. The dopant concentration in the crystals was measured by inductively coupled plasma (ICP) analysis. Single crystal X-ray diffraction studies of the pure and metal substituted LPTCA revealed that the grown crystals belong to the trigonal system. Ni(2+) and Co(2+) doping slightly altered the lattice parameters of LPTCA without affecting the basic structure of the crystal. FTIR spectral analysis confirms the presence of various functional groups in the grown crystals. The mechanical behavior of pure and doped crystals was analyzed by Vickers's microhardness test. The optical transmittance, dielectric and photoluminescence properties of the pure and doped crystals were analyzed. Copyright © 2014 Elsevier B.V. All rights reserved.

Halogeno-substituted 2-aminobenzoic acid derivatives for negative ion fragmentation studies of N-linked carbohydrates.

PubMed

Harvey, David J

2005-01-01

Negative ion electrospray mass spectra of high-mannose N-linked glycans derivatised with 2-aminobenzoic acids and ionised from solutions containing ammonium hydroxide gave prominent [M-H](-) ions accompanied by weaker [M-2H](2-) ions. Fragmentation of both types of ions gave prominent singly charged glycosidic cleavage ions containing the derivatised reducing terminus and ions from the non-reducing terminus that appeared to be products of cross-ring cleavages. Differentiation of these two groups of ions was conveniently achieved in a single spectrum by use of chloro- or bromo-substituted benzoic acids in order to label ions containing the derivative with an atom with a distinctive isotope pattern. Fragmentation of the doubly charged ions gave more abundant fragments, both singly and doubly charged, than did fragmentation of the singly charged ions, but information of chain branching was masked by the appearance of prominent ions produced by internal cleavages. Copyright (c) 2005 John Wiley & Sons, Ltd.

Fundamental Studies on Donor-acceptor Conjugated Polymers Containing 'Heavy' Group 14 and Group 16 Elements

NASA Astrophysics Data System (ADS)

Gibson, Gregory Laird

One advantage of conjugated polymers as organic materials is that their properties may be readily tuned through covalent modifications. This thesis presents studies on the structure-property relationships resulting from single- and double-atom substitutions on an alternating donor-acceptor conjugated polymer. Specifically, single selenium and tellurium atoms have been incorporated into the acceptor monomer in place of sulfur; silicon and germanium atoms have been substituted in place of carbon at the donor monomer bridge position. The carbon-donor/ tellurium-acceptor polymer was synthesized by a post-polymerization reaction sequence and demonstrated the utility of heavy group 16 atoms to red shift a polymer absorption spectrum. Density functional theory calculations point to a new explanation for this result invoking the lower heavy atom ionization energy and reduced aromaticity of acceptor monomers containing selenium and tellurium compared to sulfur. Absorption and emission experiments demonstrate that both silicon and germanium substitutions in the donor slightly blue shift the polymer absorption spectrum. Polymers containing sulfur in the acceptor are the strongest light absorbers of all polymers studied here. Molecular weight and phenyl end capping studies show that molecular weight appears to affect polymer absorption to the greatest degree in a medium molecular weight regime and that these effects have a significant aggregation component. Solar cell devices containing either the silicon- or germanium-donor/selenium-acceptor polymer display improved red light harvesting or hole mobility relative to their structural analogues. Overall, these results clarify the effects of single atom substitution on donor-acceptor polymers and aid in the future design of polymers containing heavy atoms.

Influence of La3+ Substitution on Structure, Morphology and Magnetic Properties of Nanocrystalline Ni-Zn Ferrite

PubMed Central

Dasan, Y. K.; Guan, B. H.; Zahari, M. H.; Chuan, L. K.

2017-01-01

Lanthanum substituted Ni-Zn ferrite nanoparticles (Ni0.5Zn0.5LaxFe1-xO4; 0.00 ≤x≤ 1.00) synthesized by sol-gel method were presented. X-ray diffraction patterns reveal the typical single phase spinel cubic ferrite structure, with the traces of secondary phase for lanthanum substituted nanocrystals. In addition, the structural analysis also demonstrates that the average crystallite size varied in the range of 21–25 nm. FTIR spectra present the two prominent absorption bands in the range of 400 to 600 cm-1 which are the fingerprint region of all ferrites. Surface morphology of both substituted and unsubstituted Ni-Zn ferrite nanoparticle samples was studied using FESEM technique and it indicates a significant increase in the size of spherical shaped particles with La3+ substitution. Magnetic properties of all samples were analyzed using vibrating sample magnetometer (VSM). The results revealed that saturation magnetization (Ms) and coercivity (Hc) of La3+ substituted samples has decreased as compared to the Ni-Zn ferrite samples. Hence, the observed results affirm that the lanthanum ion substitution has greatly influenced the structural, morphology and magnetic properties of Ni-Zn ferrite nanoparticles. PMID:28081257

Influence of La3+ Substitution on Structure, Morphology and Magnetic Properties of Nanocrystalline Ni-Zn Ferrite.

PubMed

Dasan, Y K; Guan, B H; Zahari, M H; Chuan, L K

2017-01-01

Lanthanum substituted Ni-Zn ferrite nanoparticles (Ni0.5Zn0.5LaxFe1-xO4; 0.00 ≤x≤ 1.00) synthesized by sol-gel method were presented. X-ray diffraction patterns reveal the typical single phase spinel cubic ferrite structure, with the traces of secondary phase for lanthanum substituted nanocrystals. In addition, the structural analysis also demonstrates that the average crystallite size varied in the range of 21-25 nm. FTIR spectra present the two prominent absorption bands in the range of 400 to 600 cm-1 which are the fingerprint region of all ferrites. Surface morphology of both substituted and unsubstituted Ni-Zn ferrite nanoparticle samples was studied using FESEM technique and it indicates a significant increase in the size of spherical shaped particles with La3+ substitution. Magnetic properties of all samples were analyzed using vibrating sample magnetometer (VSM). The results revealed that saturation magnetization (Ms) and coercivity (Hc) of La3+ substituted samples has decreased as compared to the Ni-Zn ferrite samples. Hence, the observed results affirm that the lanthanum ion substitution has greatly influenced the structural, morphology and magnetic properties of Ni-Zn ferrite nanoparticles.

Magnesium- and strontium-co-substituted hydroxyapatite: the effects of doped-ions on the structure and chemico-physical properties.

PubMed

Aina, Valentina; Lusvardi, Gigliola; Annaz, Basil; Gibson, Iain R; Imrie, Flora E; Malavasi, Gianluca; Menabue, Ledi; Cerrato, Giuseppina; Martra, Gianmario

2012-12-01

The present study is aimed at investigating the contribution of two biologically important cations, Mg(2+) and Sr(2+), when substituted into the structure of hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2),HA). The substituted samples were synthesized by an aqueous precipitation method that involved the addition of Mg(2+)- and Sr(2+)-containing precursors to partially replace Ca(2+) ions in the apatite structure. Eight substituted HA samples with different concentrations of single (only Mg(2+)) or combined (Mg(2+) and Sr(2+)) substitution of cations have been investigated and the results compared with those of pure HA. The obtained materials were characterized by X-ray powder diffraction, specific surface area and porosity measurements (N(2) adsorption at 77 K), FT-IR and Raman spectroscopies and scanning electron microscopy. The results indicate that the co-substitution gives rise to the formation of HA and β-TCP structure types, with a variation of their cell parameters and of the crystallinity degree of HA with varying levels of substitution. An evaluation of the amount of substituents allows us to design and prepare BCP composite materials with a desired HA/β-TCP ratio.

Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenazi Jewish patients with Tarui disease.

PubMed Central

Vasconcelos, O; Sivakumar, K; Dalakas, M C; Quezado, M; Nagle, J; Leon-Monzon, M; Dubnick, M; Gajdusek, D C; Goldfarb, L G

1995-01-01

Mutations in the human phosphofructokinase muscle subunit gene (PFKM) are known to cause myopathy classified as glycogenosis type VII (Tarui disease). Previously described molecular defects include base substitutions altering encoded amino acids or resulting in abnormal splicing. We report a mutation resulting in phosphofructokinase deficiency in three patients from an Ashkenazi Jewish family. Using a reverse transcription PCR assay, PFKM subunit transcripts differing by length were detected in skeletal muscle tissue of all three affected subjects. In the longer transcript, an insertion of 252 nucleotides totally homologous to the structure of the 10th intron of the PFKM gene was found separating exon 10 from exon 11. In addition, two single base transitions were identified by direct sequencing: [exon 6; codon 95; CGA (Arg) to TGA (stop)] and [exon 7; codon 172; ACC (Thr) to ACT (Thr)] in either transcript. Single-stranded conformational polymorphism and restriction enzyme analyses confirmed the presence of these point substitutions in genomic DNA and strongly suggested homozygosity for the pathogenic allele. The nonsense mutation at codon 95 appeared solely responsible for the phenotype in these patients, further expanding genetic heterogeneity of Tarui disease. Transcripts with and without intron 10 arising from identical mutant alleles probably resulted from differential pre-mRNA processing and may represent a novel message from the PFKM gene. Images Fig. 2 Fig. 4 Fig. 5 PMID:7479776

Nodeless multiband superconductivity in stoichiometric single-crystalline CaKFe 4 As 4

DOE PAGES

Cho, Kyuil; Fente, A.; Teknowijoyo, S.; ...

2017-03-08

Measurements of the London penetration depth Δλ(T) and tunneling conductance in single crystals of the recently discovered stoichiometric iron-based superconductor CaKFe 4As 4 (CaK1144) show nodeless, two-effective-gap superconductivity with a larger gap of about 6–10 meV and a smaller gap of about 1–4 meV. Having a critical temperature T c,onset ≈ 35.8 K, this material behaves similar to slightly overdoped (Ba 1–xK x)Fe 2As 2 (e.g., x = 0.54,T c ≈ 34 K), a known multigap s ± superconductor. Here, we conclude that the superconducting behavior of stoichiometric CaK1144 demonstrates that two-gap s± superconductivity is an essential property of high-temperaturemore » superconductivity in iron-based superconductors, independent of the degree of substitutional disorder.« less

Quantitation of base substitutions in eukaryotic 5S rRNA: selection for the maintenance of RNA secondary structure.

PubMed

Curtiss, W C; Vournakis, J N

1984-01-01

Eukaryotic 5S rRNA sequences from 34 diverse species were compared by the following method: (1) The sequences were aligned; (2) the positions of substitutions were located by comparison of all possible pairs of sequences; (3) the substitution sites were mapped to an assumed general base pairing model; and (4) the R-Y model of base stacking was used to study stacking pattern relationships in the structure. An analysis of the sequence and structure variability in each region of the molecule is presented. It was found that the degree of base substitution varies over a wide range, from absolute conservation to occurrence of over 90% of the possible observable substitutions. The substitutions are located primarily in stem regions of the 5S rRNA secondary structure. More than 88% of the substitutions in helical regions maintain base pairing. The disruptive substitutions are primarily located at the edges of helical regions, resulting in shortening of the helical regions and lengthening of the adjacent nonpaired regions. Base stacking patterns determined by the R-Y model are mapped onto the general secondary structure. Intrastrand and interstrand stacking could stabilize alternative coaxial structures and limit the conformational flexibility of nonpaired regions. Two short contiguous regions are 100% conserved in all species. This may reflect evolutionary constraints imposed at the DNA level by the requirement for binding of a 5S gene transcription initiation factor during gene expression.

Absolute configuration and crystal packing chirality for three conglomerate-forming ortho-halogen substituted phenyl glycerol ethers

NASA Astrophysics Data System (ADS)

Bredikhin, Alexander A.; Gubaidullin, Aidar T.; Bredikhina, Zemfira A.

2010-06-01

Three conglomerate-forming ortho-Hal (Hal = Cl, Br, I) substituted phenyl glycerol ethers 1- 3 were investigated by single-crystal X-ray analysis, and the absolute configuration for all substances was established. The molecular structures and crystal packing details for halogen derivatives were compared with the same characteristics for ortho-OCH 3 and ortho-CH 3 analogues. Two different types of crystal packing were evaluated for these very much alike compounds. The interplay of the supramolecular crystal organization chirality sense and the single molecule absolute configuration was demonstrated. Some stabilizing and destabilizing interactions involving the ortho-substituents were revealed. The resolution of rac-2 by entrainment procedure was successfully realized.

Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues.

PubMed

Peng, Tao; Huang, Bingzhen; Sun, Yao; Lu, Yongbo; Bonewald, Lynda; Chen, Shuo; Butler, William T; Feng, Jerry Q; D'Souza, Rena N; Qin, Chunlin

2009-01-01

Dentin matrix protein 1 (DMP1) is present in the extracellular matrix (ECM) of dentin and bone as processed NH(2)- and COOH-terminal fragments, resulting from proteolytic cleavage at the NH(2) termini of 4 aspartic acid residues during rat DMP1 processing. One cleavage site residue, Asp(181) (corresponding to Asp(197) of mouse DMP1), and its flanking region are highly conserved across species. We speculate that cleavage at the NH(2) terminus of Asp(197) of mouse DMP1 represents an initial, first-step scission in the whole cascade of proteolytic processing. To test if Asp(197) is critical for initiating the proteolytic processing of mouse DMP1, we substituted Asp(197) with Ala(197) by mutating the corresponding nucleotides of mouse cDNA that encode this amino acid residue. This mutant DMP1 cDNA was cloned into a pcDNA3.1 vector. Data from transfection experiments indicated that this single substitution blocked the proteolytic processing of mouse DMP1 in HEK-293 cells, indicating that cleavage at the NH(2) terminus of Asp(197) is essential for exposing other cleavage sites for the conversion of DMP1 to its fragments. The NH(2)-terminal fragment of DMP1 occurs as a proteoglycan form (DMP1-PG) that contains a glycosaminoglycan (GAG) chain. Previously, we showed that a GAG chain is linked to Ser(74) in rat DMP1 (Ser(89) in mouse DMP1). To confirm that mouse DMP1-PG possesses a single GAG chain attached to Ser(89), we substituted Ser(89) by Gly(89). Data from transfection analysis indicated that this substitution completely prevented formation of the GAG-containing form, confirming that DMP1-PG contains a single GAG chain attached to Ser(89) in mouse DMP1. Copyright 2008 S. Karger AG, Basel.

"Anticlumping" and Other Combinatorial Effects on Clumped Isotopes: Implications for Tracing Biogeochemical Cycling

NASA Astrophysics Data System (ADS)

Yeung, L.

2015-12-01

I present a mode of isotopic ordering that has purely combinatorial origins. It can be important when identical rare isotopes are paired by coincidence (e.g., they are neighbors on the same molecule), or when extrinsic factors govern the isotopic composition of the two atoms that share a chemical bond. By itself, combinatorial isotope pairing yields products with isotopes either randomly distributed or with a deficit relative to a random distribution of isotopes. These systematics arise because of an unconventional coupling between the formation of singly- and multiply-substituted isotopic moieties. In a random distribution, rare isotopes are symmetrically distributed: Single isotopic substitutions (e.g., H‒D and D‒H in H2) occur with equal probability, and double isotopic substitutions (e.g., D2) occur according to random chance. The absence of symmetry in a bond-making complex can yield unequal numbers of singly-substituted molecules (e.g., more H‒D than D‒H in H2), which is recorded in the product molecule as a deficit in doubly-substituted moieties and an "anticlumped" isotope distribution (i.e., Δn < 0). Enzymatic isotope pairing reactions, which can have site-specific isotopic fractionation factors and atom reservoirs, should express this class of combinatorial isotope effect. Chemical-kinetic isotope effects, which are related to the bond-forming transition state, arise independently and express second-order combinatorial effects. In general, both combinatorial and chemical factors are important for calculating and interpreting clumped-isotope signatures of individual reactions. In many reactions relevant to geochemical oxygen, carbon, and nitrogen cycling, combinatorial isotope pairing likely plays a strong role in the clumped isotope distribution of the products. These isotopic signatures, manifest as either directly bound isotope clumps or as features of a molecule's isotopic anatomy, could be exploited as tracers of biogeochemistry that can relate molecular mechanisms to signals observable at environmentally relevant spatial scales.

A Critical Analysis of Concentration and Competition in the Indian Pharmaceutical Market.

PubMed

Mehta, Aashna; Hasan Farooqui, Habib; Selvaraj, Sakthivel

2016-01-01

It can be argued that with several players marketing a large number of brands, the pharmaceutical market in India is competitive. However, the pharmaceutical market should not be studied as a single market but, as a sum total of a large number of individual sub-markets. This paper examines the methodological issues with respect to defining the relevant market involved in studying concentration in the pharmaceutical market in India. Further, we have examined whether the Indian pharmaceutical market is competitive. Indian pharmaceutical market was studied using PharmaTrac, the sales audit data from AIOCD-AWACS, that organises formulations into 5 levels of therapeutic classification based on the EphMRA system. The Herfindahl-Hirschman Index (HHI) was used as the indicator of market concentration. We calculated HHI for the entire pharmaceutical market studied as a single market as well as at the five different levels of therapeutic classification. Whereas the entire pharmaceutical market taken together as a single market displayed low concentration (HHI = 226.63), it was observed that if each formulation is defined as an individual sub-market, about 69 percent of the total market in terms of market value displayed at least moderate concentration. Market should be defined taking into account the ease of substitutability. Since, patients cannot themselves substitute the formulation prescribed by the doctor with another formulation with the same indication and therapeutic effect, owing to information asymmetry, it is appropriate to study market concentration at the narrower levels of therapeutic classification.

Cobalt ferrite based magnetostrictive materials for magnetic stress sensor and actuator applications

NASA Technical Reports Server (NTRS)

Jiles, David C. (Inventor); Paulsen, Jason A. (Inventor); Snyder, John E. (Inventor); Lo, Chester C. H. (Inventor); Ring, Andrew P. (Inventor); Bormann, Keith A. (Inventor)

2008-01-01

Magnetostrictive material based on cobalt ferrite is described. The cobalt ferrite is substituted with transition metals (such manganese (Mn), chromium (Cr), zinc (Zn) and copper (Cu) or mixtures thereof) by substituting the transition metals for iron or cobalt to form substituted cobalt ferrite that provides mechanical properties that make the substituted cobalt ferrite material effective for use as sensors and actuators. The substitution of transition metals lowers the Curie temperature of the material (as compared to cobalt ferrite) while maintaining a suitable magnetostriction for stress sensing applications.

Pressure effects on magnetic pair-breaking in Mn- and Eu-substituted BaFe{sub 2}As{sub 2}

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

Rosa, P. F. S., E-mail: ferrari@ifi.unicamp.br; University of California, Irvine, California 92697-4574; Garitezi, T. M.

2014-05-07

We report a combined study of hydrostatic pressure (P ≤ 25 kbar) and chemical substitution on the magnetic pair-breaking effect in Eu- and Mn-substituted BaFe{sub 2}As{sub 2} single crystals. At ambient pressure, both substitutions suppress the superconducting (SC) transition temperature (T{sub c}) of BaFe{sub 2–x}Co{sub x}As{sub 2} samples slightly under the optimally doped region, indicating the presence of a pair-breaking effect. At low pressures, an increase of T{sub c} is observed for all studied compounds followed by an expected decrease at higher pressures. However, in the Eu dilute system, T{sub c} further increases at higher pressure along with a narrowingmore » of the SC transition, suggesting that a pair-breaking mechanism reminiscent of the Eu Kondo single impurity regime is being suppressed by pressure. Furthermore, Electron Spin Resonance (ESR) measurements indicate the presence of Mn{sup 2+} and Eu{sup 2+} local moments and the microscopic parameters extracted from the ESR analysis reveal that the Abrikosov–Gor'kov expression for magnetic pair-breaking in a conventional sign-preserving superconducting state cannot describe the observed reduction of T{sub c}.« less

Ion channel stabilization of synthetic alamethicin analogs by rings of inter-helix H-bonds.

PubMed Central

Molle, G; Dugast, J Y; Spach, G; Duclohier, H

1996-01-01

Rings of inter-helix H-bonds due to Gln at position 7, a highly conserved residue in all pore-forming peptaibols, have been suggested to play an important role in the stabilization of alamethicin channels. In an attempt to test this hypothesis, experimental studies have been undertaken on four synthetic alamethicin non-Aib analogs (Alm-dUL) in which the Gln at position 7 (Q7) is substituted by Ala, Asn, or Ser (Q7A, Q7N, or Q7S). Voltage-dependent pore formation by these analogs in planar lipid bilayers is compared at the macroscopic and single-channel conductance levels. As anticipated, the Q7A substitution abolished all channel-forming activity. The voltage dependence of macroscopic current-voltage curves was conserved with the Q7N substitution but reduced in the Q7S analog. Normalized single-channel conductance ratios between substates follow the same pattern, with the Q7S analog yielding the highest unit conductances. Channel lifetimes were the most significantly modulated parameter with markedly faster kinetics when Gln or Asn was replaced by Ser. The effect of the Q7S substitution on channel lifetimes may be explained through a reduced stabilization of bundles by inter-helix H-bonds. PMID:8785325

Calibration of Multiple Poliovirus Molecular Clocks Covering an Extended Evolutionary Range▿ †

PubMed Central

Jorba, Jaume; Campagnoli, Ray; De, Lina; Kew, Olen

2008-01-01

We have calibrated five different molecular clocks for circulating poliovirus based upon the rates of fixation of total substitutions (Kt), synonymous substitutions (Ks), synonymous transitions (As), synonymous transversions (Bs), and nonsynonymous substitutions (Ka) into the P1/capsid region (2,643 nucleotides). Rates were determined over a 10-year period by analysis of sequences of 31 wild poliovirus type 1 isolates representing a well-defined phylogeny derived from a common imported ancestor. Similar rates were obtained by linear regression, the maximum likelihood/single-rate dated-tip method, and Bayesian inference. The very rapid Kt [(1.03 ± 0.10) × 10−2 substitutions/site/year] and Ks [(1.00 ± 0.08) × 10−2] clocks were driven primarily by the As clock [(0.96 ± 0.09) × 10−2], the Bs clock was ∼10-fold slower [(0.10 ± 0.03) × 10−2], and the more stochastic Ka clock was ∼30-fold slower [(0.03 ± 0.01) × 10−2]. Nonsynonymous substitutions at all P1/capsid sites, including the neutralizing antigenic sites, appeared to be constrained by purifying selection. Simulation of the evolution of third-codon positions suggested that saturation of synonymous transitions would be evident at 10 years and complete at ∼65 years of independent transmission. Saturation of synonymous transversions was predicted to be minimal at 20 years and incomplete at 100 years. The rapid evolution of the Kt, Ks, and As clocks can be used to estimate the dates of divergence of closely related viruses, whereas the slower Bs and Ka clocks may be used to explore deeper evolutionary relationships within and across poliovirus genotypes. PMID:18287242

Identification of single amino acid substitutions (SAAS) in neuraminidase from influenza a virus (H1N1) via mass spectrometry analysis coupled with de novo peptide sequencing.

PubMed

Peng, Qisheng; Wang, Zijian; Wu, Donglin; Li, Xiaoou; Liu, Xiaofeng; Sun, Wanchun; Liu, Ning

2016-08-01

Amino acid substitutions in the neuraminidase of the influenza virus are the main cause of the emergence of resistance to zanamivir or oseltamivir during seasonal influenza treatment; they are the result of non-synonymous mutations in the viral genome that can be successfully detected by polymer chain reaction (PCR)-based approaches. There is always an urgent need to detect variation in amino acid sequences directly at the protein level. Mass spectrometry coupled with de novo sequencing has been explored as an alternative and straightforward strategy for detecting amino acid substitutions, as well - this approach is the primary focus of the present study. Influenza virus (A/Puerto Rico/8/1934 H1N1) propagated in embryonated chicken eggs was purified by ultracentrifugation, followed by PNGase F treatment. The deglycosylated virion was lysed and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The gel band corresponding to neuraminidase was picked up and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. LC-MS/MS analyses, coupled with manual de novo sequencing, allowed the determination of three amino acid substitutions: R346K, S349 N, and S370I/L, in the neuraminidase from the influenza virus (A/Puerto Rico/8/1934 H1N1), which were located in three mutated peptides of the neuraminidase: YGNGVWIGK, TKNHSSR, and PNGWTETDI/LK, respectively. We found that the amino acid substitutions in the proteins of RNA viruses (including influenza A virus) resulting from non-synonymous gene mutations can indeed be directly analyzed via mass spectrometry, and that manual interpretation of the MS/MS data may be beneficial. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Recycling of plastic: accounting of greenhouse gases and global warming contributions.

PubMed

Astrup, Thomas; Fruergaard, Thilde; Christensen, Thomas H

2009-11-01

Major greenhouse gas (GHG) emissions related to plastic waste recycling were evaluated with respect to three management alternatives: recycling of clean, single-type plastic, recycling of mixed/contaminated plastic, and use of plastic waste as fuel in industrial processes. Source-separated plastic waste was received at a material recovery facility (MRF) and processed for granulation and subsequent downstream use. In the three alternatives, plastic was assumed to be substituting virgin plastic in new products, wood in low-strength products (outdoor furniture, fences, etc.), and coal or fuel oil in the case of energy utilization. GHG accounting was organized in terms of indirect upstream emissions (e.g. provision of energy, fuels, and materials), direct emissions at the MRF (e.g. fuel combustion), and indirect downstream emissions (e.g. avoided emissions from production of virgin plastic, wood, or coal/oil). Combined, upstream and direct emissions were estimated to be roughly between 5 and 600 kg CO(2)-eq. tonne( -1) of plastic waste depending on treatment at the MRF and CO(2) emissions from electricity production. Potential downstream savings arising from substitution of virgin plastic, wood, and energy fuels were estimated to be around 60- 1600 kg CO(2)-eq. tonne( -1) of plastic waste depending on substitution ratios and CO(2) emissions from electricity production. Based on the reviewed data, it was concluded that substitution of virgin plastic should be preferred. If this is not viable due to a mixture of different plastic types and/or contamination, the plastic should be used for energy utilization. Recycling of plastic waste for substitution of other materials such as wood provided no savings with respect to global warming.

A study of enhancing critical current densities (J(sub c)) and critical temperature (T(sub c)) of high-temperature superconductors

NASA Technical Reports Server (NTRS)

Vlasse, Marcus

1992-01-01

The development of pure phase 123 and Bi-based 2223 superconductors has been optimized. The pre-heat processing appears to be a very important parameter in achieving optimal physical properties. The synthesis of pure phases in the Bi-based system involves effects due to oxygen partial pressure, time, and temperature. Orientation/melt-sintering effects include the extreme c-axis orientation of Yttrium 123 and Bismuth 2223, 2212, and 2201 phases. This orientation is conductive to increasing critical currents. A procedure was established to substitute Sr for Ba in Y-123 single crystals.

Amino acid substitutions of conserved residues in the carboxyl-terminal domain of the [alpha]I(X) chain of type X collagen occur in two unrelated families with metaphyseal chondrodysplasia type Schmid

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

Wallis, G.A.; Rash, B.; Sweetman, W.A.

1994-02-01

Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix component that is specifically and transiently synthesized by hypertrophic chondrocytes at the site of endochondral ossification. The precise function of type X collagen is not known, but its specific pattern of expression suggests that mutations within the encoding gene (COL10A1) that alter the structure or synthesis of the protein may cause heritable forms of chondrodysplasia. The authors used the PCR and the SSCP techniques to analyze the coding and upstream promoter regions of the COL10A1 gene in a number of individuals with forms of chondrodysplasia. Using this approach, they identified twomore » individuals with metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated that the individuals were heterozygous for two unique single-base-pair transitions that led to the substitution of the highly conserved amino acid residue tyrosine at position 598 by aspartic acid in one person and of leucine at position 614 by proline in the other. The substitution at residue 598 segregated with the phenotype in a family of eight (five affected and three unaffected) related persons. The substitutions at residue 614 occurred in a sporadically affected individual but not in her unaffected mother and brother. Additional members of this family were not available for further study. These results suggest that certain amino acid substitutions within the carboxyl-terminal domain of the chains of the type X collagen molecule cause MCDS. These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development. 36 refs., 5 figs.« less

The influence of specific neighboring bases on substitution bias in noncoding regions of the plant chloroplast genome.

PubMed

Morton, B R; Oberholzer, V M; Clegg, M T

1997-09-01

Substitutions occurring in noncoding sequences of the plant chloroplast genome violate the independence of sites that is assumed by substitution models in molecular evolution. The probability that a substitution at a site is a transversion, as opposed to a transition, increases significantly with increasing A + T content of the two adjacent nucleotides. In the present study, this dependency of substitutions on local context is examined further in a number of noncoding regions from the chloroplast genome of members of the grass family (Poaceae). Two features were examined; the influence of specific neighboring bases, as opposed to the general A + T content, on transversion proportion and an influence on substitutions by nucleotides other than the two immediately adjacent to the site of substitution. In both cases, a significant effect was found. In the case of specific nucleotides, transversion proportion is significantly higher at sites with a pyrimidine immediately 5' on either strand. Substitutions at sites of the type YNR, where N is the site of substitution, have the highest rate of transversion. This specific effect is secondary to the A + T content effect such that, in terms of proportion of substitutions that are transversions, the nucleotides are ranked T > A > C > G as to their effect when they are immediately 5' to the site of substitution. In the case of nucleotides other than the immediate neighbors, a significant influence on substitution dynamics is observed in the case where the two neighboring bases are both A and/or T. Thus, substitutions are primarily, but not exclusively, influenced by the composition of the two nucleotides that are immediately adjacent. These results indicate that the pattern of molecular evolution of the plant chloroplast genome is extremely complex as a result of a variety of inter-site dependencies.

Arenium ions are not obligatory intermediates in electrophilic aromatic substitution

PubMed Central

Galabov, Boris; Koleva, Gergana; Simova, Svetlana; Hadjieva, Boriana; Schaefer, Henry F.; Schleyer, Paul von Ragué

2014-01-01

Our computational and experimental investigation of the reaction of anisole with Cl2 in nonpolar CCl4 solution challenges two fundamental tenets of the traditional SEAr (arenium ion) mechanism of aromatic electrophilic substitution. Instead of this direct substitution process, the alternative addition–elimination (AE) pathway is favored energetically. This AE mechanism rationalizes the preferred ortho and para substitution orientation of anisole easily. Moreover, neither the SEAr nor the AE mechanisms involve the formation of a σ-complex (Wheland-type) intermediate in the rate-controlling stage. Contrary to the conventional interpretations, the substitution (SEAr) mechanism proceeds concertedly via a single transition state. Experimental NMR investigations of the anisole chlorination reaction course at various temperatures reveal the formation of tetrachloro addition by-products and thus support the computed addition–elimination mechanism of anisole chlorination in nonpolar media. The important autocatalytic effect of the HCl reaction product was confirmed by spectroscopic (UV-visible) investigations and by HCl-augmented computational modeling. PMID:24972792

Synthesis and Properties of Size-expanded DNAs: Toward Designed, Functional Genetic Systems

PubMed Central

Krueger, Andrew T.; Lu, Haige; Lee, Alex H. F.; Kool, Eric T.

2008-01-01

We describe the design, synthesis, and properties of DNA-like molecules in which the base pairs are expanded by benzo homologation. The resulting size-expanded genetic helices are called xDNA (“expanded DNA”) and yDNA (“wide DNA”). The large component bases are fluorescent, and they display high stacking affinity. When singly substituted into natural DNA, they are destabilizing because the benzo-expanded base pair size is too large for the natural helix. However, when all base pairs are expanded, xDNA and yDNA form highly stable, sequence-selective double helices. The size-expanded DNAs are candidates for components of new, functioning genetic systems. In addition, the fluorescence of expanded DNA bases makes them potentially useful in probing nucleic acids. PMID:17309194

The Synthesis of Methyl-Substituted Spirocyclic Piperidine-Azetidine (2,7-Diazaspiro[3.5]nonane) and Spirocyclic Piperidine-Pyrrolidine (2,8-Diazaspiro[4.5]decane) Ring Systems.

PubMed

Smith, Aaron C; Cabral, Shawn; Kung, Daniel W; Rose, Colin R; Southers, James A; García-Irizarry, Carmen N; Damon, David B; Bagley, Scott W; Griffith, David A

2016-05-06

The synthesis of a series of pharmaceutically important N-protected methyl-substituted spirocyclic piperidine-azetidine (2,7-diazaspiro[3.5]nonane) and spirocyclic piperidine-pyrrolidine (2,8-diazaspiro[4.5]decane) ring systems was developed. These motifs contain two differentiated sites (protected secondary amines) to allow for further functionalization via reductive amination, amidation, or other chemistry. The methyl-substituted spiroazetidine ring systems were accessed using nitrile lithiation/alkylation chemistry while the methyl-substituted spiropyrrolidines were synthesized by 1,4-addition reactions with nitroalkanes, followed by reduction and cyclization. These conditions were then scaled for the synthesis of 1-methyl spirocyclic piperidine-pyrrolidine with a classical resolution of the product using a tartaric acid derivative to isolate a single enantiomer.

Photovoltaic devices based on high density boron-doped single-walled carbon nanotube/n-Si heterojunctions

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

Saini, Viney; Li, Zhongrui; Bourdo, Shawn

2011-01-13

A simple and easily processible photovoltaic device has been developed based on borondoped single-walled carbon nanotubes (B-SWNTs) and n-type silicon (n-Si) heterojunctions. The single-walled carbon nanotubes (SWNTs) were substitutionally doped with boron atoms by thermal annealing, in the presence of B 2O 3. The samples used for these studies were characterized by Raman spectroscopy, thermal gravimetric analysis (TGA), transmission electron microscopy (TEM), and x-ray photoelectron spectroscopy (XPS). The fully functional solar cell devices were fabricated by airbrush deposition that generated uniform B-SWNT films on top of the n-Si substrates. The carbon nanotube films acted as exciton-generation sites, charge collection andmore » transportation, while the heterojunctions formed between B-SWNTs and n-Si acted as charge dissociation centers. The current-voltage characteristics in the absence of light and under illumination, as well as optical transmittance spectrum are reported here. It should be noted that the device fabrication process can be made amenable to scalability by depositing direct and uniform films using airbrushing, inkjet printing, or spin-coating techniques.« less

Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

PubMed

Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

2016-01-18

A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

Nano- and micro-scale Bi-substituted iron garnet films for photonics and magneto-optic eddy current defectoscopy

NASA Astrophysics Data System (ADS)

Berzhansky, V. N.; Karavainikov, A. V.; Mikhailova, T. V.; Prokopov, A. R.; Shaposhnikov, A. N.; Shumilov, A. G.; Lugovskoy, N. V.; Semuk, E. Yu.; Kharchenko, M. F.; Lukienko, I. M.; Kharchenko, Yu. M.; Belotelov, V. I.

2017-10-01

Synthesis technology of nano-scale Bi-substituted iron garnets films with high magneto-optic activity for photonics and plasmonics applications were proposed. The micro-scale single-crystal garnet films with different types of magnetic anisotropy as a magneto-optic sensors were synthesized. It was shown that easy-axis anisotropy films demonstrated the best results for visualization of redistribution eddy current magnetic field near defects.

One-Dimensional Multichromophor Arrays Based on DNA: From Self-Assembly to Light-Harvesting.

PubMed

Ensslen, Philipp; Wagenknecht, Hans-Achim

2015-10-20

Light-harvesting complexes collect light energy and deliver it by a cascade of energy and electron transfer processes to the reaction center where charge separation leads to storage as chemical energy. The design of artificial light-harvesting assemblies faces enormous challenges because several antenna chromophores need to be kept in close proximity but self-quenching needs to be avoided. Double stranded DNA as a supramolecular scaffold plays a promising role due to its characteristic structural properties. Automated DNA synthesis allows incorporation of artificial chromophore-modified building blocks, and sequence design allows precise control of the distances and orientations between the chromophores. The helical twist between the chromophores, which is induced by the DNA framework, controls energy and electron transfer and thereby reduces the self-quenching that is typically observed in chromophore aggregates. This Account summarizes covalently multichromophore-modified DNA and describes how such multichromophore arrays were achieved by Watson-Crick-specific and DNA-templated self-assembly. The covalent DNA systems were prepared by incorporation of chromophores as DNA base substitutions (either as C-nucleosides or with acyclic linkers as substitutes for the 2'-deoxyribofuranoside) and as DNA base modifications. Studies with DNA base substitutions revealed that distances but more importantly relative orientations of the chromophores govern the energy transfer efficiencies and thereby the light-harvesting properties. With DNA base substitutions, duplex stabilization was faced and could be overcome, for instance, by zipper-like placement of the chromophores in both strands. For both principal structural approaches, DNA-based light-harvesting antenna could be realized. The major disadvantages, however, for covalent multichromophore DNA conjugates are the poor yields of synthesis and the solubility issues for oligonucleotides with more than 5-10 chromophore modifications in a row. A logical alternative approach is to leave out the phosphodiester bridges between the chromophores and let chromophore-nucleoside conjugates self-assemble specifically along single stranded DNA as template. The self-organization of chromophores along the DNA template based on canonical base pairing would be advantageous because sequence selective base pairing could provide a structural basis for programmed complexity within the chromophore assembly. The self-assembly is governed by two interactions. The chromophore-nucleoside conjugates as guest molecules are recognized via hydrogen bonds to the corresponding counter bases in the single stranded DNA template. Moreover, the π-π interactions between the stacked chromophores stabilize these self-assembled constructs with increasing length. Longer DNA templates are more attractive for self-assembled antenna. The helicity in the stack of porphyrins as guest molecules assembled on the DNA template can be switched by environmental changes, such as pH variations. DNA-templated stacks of ethynyl pyrene and nile red exhibit left-handed chirality, which stands in contrast to similar covalent multichromophore-DNA conjugates with enforced right-handed helicity. With ethynyl nile red, it is possible to occupy every available binding site on the templates. Mixed assemblies of ethynyl pyrene and nile red show energy transfer and thereby provide a proof-of-principle that simple light-harvesting antennae can be obtained in a noncovalent and self-assembled fashion. With respect to the next important step, chemical storage of the absorbed light energy, future research has to focus on the coupling of sophisticated DNA-based light-harvesting antenna to reaction centers.

Experimental rugged fitness landscape in protein sequence space.

PubMed

Hayashi, Yuuki; Aita, Takuyo; Toyota, Hitoshi; Husimi, Yuzuru; Urabe, Itaru; Yomo, Tetsuya

2006-12-20

The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18-24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.

Experimental Rugged Fitness Landscape in Protein Sequence Space

PubMed Central

Hayashi, Yuuki; Aita, Takuyo; Toyota, Hitoshi; Husimi, Yuzuru; Urabe, Itaru; Yomo, Tetsuya

2006-01-01

The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12–130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7×104-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18–24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region. PMID:17183728

Characteristics of oxidative homolytic alkylation of imidazoles and organic-inorganic hybrid extended networks from large aromatic building blocks

NASA Astrophysics Data System (ADS)

Li, Kunhao

The discovery of the dramatic in vitro antimalarial activity of 2-iodo-L-histidine and 2-fluoro-L-histidine, as well as their in vivo limitations, has prompted a systematic search for novel 2-substituted imidazoles and bioimidazoles as agents against human malaria. Previous research has shown that the regioselective alkyl free radical substitution on imidazoles and bioimidazoles could serve as a simple and efficient route to a wide variety of 2-alkylimidazoles. In this research, this methodology was successfully extended to include alkyl radicals substituted with various functional groups such as amide or ester. While this novel methodology should be of some synthetic utility when tertiary radicals are used, poorer yields are usually encountered in the cases of primary radicals. In the second part of this dissertation, a series of novel ligands containing multiple ortho-bis(organothio) groups were synthesized and their coordination and network forming properties were studied in the context of crystalline organic-inorganic hybrid extended networks. For the syntheses of HRTTs [2,3,6,7,10,11-hexakis(alkylthio)triphenylenes], a simpler, safer and higher yielding one-pot process was developed. Quenching the hexa-anions (formed when sodium methylthiolate was refluxed with hexabromotriphenylene) with alkyl halides or acid chlorides afforded HRTTs. This newly developed process was also successfully expanded to the pyrene system. In the syntheses of unsymmetrically substituted triphenlyenes, it was shown for the first time that the oxidative cyclization process is applicable to thioether containing systems, pointing to a novel strategy for the preparation of this type of unsymmetrically substituted triphenlyenes. Treating these novel ligands with various metal salts [i.e. bismuth(III) chloride and bismuth(III) bromide] under carefully controlled conditions resulted in a series of air-stable semiconductive coordination networks. Their single crystal structures were determined by X-ray diffraction and properties such as semiconductivity and solution processability, as well as the structure-property relationship, were also studied. As a reasonable extension of this research, two phenylacetylene-based thioether containing ligands L1 and L2, were prepared. Similar to the triphenylene-based ligands, they also formed semiconductive extended networks with bismuth(III) bromide. The preparation of HArTTs [2,3,6,7,10,11-hexakis-(arylthio)triphenlyenes] and a series of crystalline extended networks based on the coordination of these ligands and various silver salts are reported in Chapter 5.

Energetics of Single Substitutional Impurities in NiTi

NASA Technical Reports Server (NTRS)

Good, Brian S.; Noebe, Ronald

2003-01-01

Shape-memory alloys are of considerable current interest, with applications ranging from stents to Mars rover components. In this work, we present results on the energetics of single substitutional impurities in B2 NiTi. Specifically, energies of Pd, Pt, Zr and Hf impurities at both Ni and Ti sites are computed. All energies are computed using the CASTEP ab initio code, and, for comparison, using the quantum approximate energy method of Bozzolo, Ferrante and Smith. Atomistic relaxation in the vicinity of the impurities is investigated via quantum approximate Monte Carlo simulation, and in cases where the relaxation is found to be important, the resulting relaxations are applied to the ab initio calculations. We compare our results with available experimental work.

Competitive fitness of influenza B viruses with neuraminidase inhibitor-resistant substitutions in a coinfection model of the human airway epithelium.

PubMed

Burnham, Andrew J; Armstrong, Jianling; Lowen, Anice C; Webster, Robert G; Govorkova, Elena A

2015-04-01

Influenza A and B viruses are human pathogens that are regarded to cause almost equally significant disease burdens. Neuraminidase (NA) inhibitors (NAIs) are the only class of drugs available to treat influenza A and B virus infections, so the development of NAI-resistant viruses with superior fitness is a public health concern. The fitness of NAI-resistant influenza B viruses has not been widely studied. Here we examined the replicative capacity and relative fitness in normal human bronchial epithelial (NHBE) cells of recombinant influenza B/Yamanashi/166/1998 viruses containing a single amino acid substitution in NA generated by reverse genetics (rg) that is associated with NAI resistance. The replication in NHBE cells of viruses with reduced inhibition by oseltamivir (recombinant virus with the E119A mutation generated by reverse genetics [rg-E119A], rg-D198E, rg-I222T, rg-H274Y, rg-N294S, and rg-R371K, N2 numbering) or zanamivir (rg-E119A and rg-R371K) failed to be inhibited by the presence of the respective NAI. In a fluorescence-based assay, detection of rg-E119A was easily masked by the presence of NAI-susceptible virus. We coinfected NHBE cells with NAI-susceptible and -resistant viruses and used next-generation deep sequencing to reveal the order of relative fitness compared to that of recombinant wild-type (WT) virus generated by reverse genetics (rg-WT): rg-H274Y > rg-WT > rg-I222T > rg-N294S > rg-D198E > rg-E119A ≫ rg-R371K. Based on the lack of attenuated replication of rg-E119A in NHBE cells in the presence of oseltamivir or zanamivir and the fitness advantage of rg-H274Y over rg-WT, we emphasize the importance of these substitutions in the NA glycoprotein. Human infections with influenza B viruses carrying the E119A or H274Y substitution could limit the therapeutic options for those infected; the emergence of such viruses should be closely monitored. Influenza B viruses are important human respiratory pathogens contributing to a significant portion of seasonal influenza virus infections worldwide. The development of resistance to a single class of available antivirals, the neuraminidase (NA) inhibitors (NAIs), is a public health concern. Amino acid substitutions in the NA glycoprotein of influenza B virus not only can confer antiviral resistance but also can alter viral fitness. Here we used normal human bronchial epithelial (NHBE) cells, a model of the human upper respiratory tract, to examine the replicative capacities and fitness of NAI-resistant influenza B viruses. We show that virus with an E119A NA substitution can replicate efficiently in NHBE cells in the presence of oseltamivir or zanamivir and that virus with the H274Y NA substitution has a relative fitness greater than that of the wild-type NAI-susceptible virus. This study is the first to use NHBE cells to determine the fitness of NAI-resistant influenza B viruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Adsorption and separation of reactive aromatic isomers and generation and stabilization of their radicals within cadmium(II)-triazole metal-organic confined space in a single-crystal-to-single-crystal fashion.

PubMed

Liu, Qi-Kui; Ma, Jian-Ping; Dong, Yu-Bin

2010-05-26

A series of reactive group functionalized aromatics, namely 2-furaldehyde, 3-furaldehyde, 2-thenaldehyde, 3-thenaldehyde, o-toluidine, m-toluidine, p-toluidine, and aniline, can be absorbed by a CdL(2) (1; L = 4-amino-3,5-bis(4-pyridyl-3-phenyl)-1,2,4-triazole) porous framework in both vapor and liquid phases to generate new G(n) [symbol: see text] CdL(2) (n = 1, 2) host-guest complexes. In addition, the CdL(2) framework can be a shield to protect the active functional group (-CHO and -NH(2)) substituted guests from reaction with the outside medium containing their reaction partners. That is, aldehyde-substituted guests within the CdL(2) host become "stable" in the aniline phase and vice versa. Moreover, 1 displays a very strict selectivity for these reactive group substituted aromatic isomers and can completely separate these guest isomers under mild conditions (i.e., 2-furaldehyde vs 3-furaldehyde, 2-thenaldehyde vs 3-thenaldehyde, and o-toluidine vs m-toluidine vs p-toluidine). All adsorptions and separations are directly performed on the single crystals of 1. More interestingly, these reactive group substituted aromatics readily transform to the corresponding radicals within the CdL(2) host upon ambient light or UV light (355 nm) irradiation. Furthermore, the generated organic radicals are alive for 1 month within the interior cavity in air under ambient conditions. Simple organic radicals are highly reactive short-lived species, and they cannot be generally isolated and conserved under ambient conditions. Thus, the CdL(2) host herein could be considered as a radical generator and storage vessel.

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

PubMed Central

Hamasy, A; Wang, Q; Blomberg, K E M; Mohammad, D K; Yu, L; Vihinen, M; Berglöf, A; Smith, C I E

2017-01-01

Irreversible Bruton tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib have demonstrated remarkable clinical responses in multiple B-cell malignancies. Acquired resistance has been identified in a sub-population of patients in which mutations affecting BTK predominantly substitute cysteine 481 in the kinase domain for catalytically active serine, thereby ablating covalent binding of inhibitors. Activating substitutions in the BTK substrate phospholipase Cγ2 (PLCγ2) instead confers resistance independent of BTK. Herein, we generated all six possible amino acid substitutions due to single nucleotide alterations for the cysteine 481 codon, in addition to threonine, requiring two nucleotide substitutions, and performed functional analysis. Replacement by arginine, phenylalanine, tryptophan or tyrosine completely inactivated the catalytic activity, whereas substitution with glycine caused severe impairment. BTK with threonine replacement was catalytically active, similar to substitution with serine. We identify three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. Glycine and tryptophan variants were not yet reported but likely also provide resistance. PMID:27282255

Equivalent-Continuum Modeling With Application to Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Odegard, Gregory M.; Gates, Thomas S.; Nicholson, Lee M.; Wise, Kristopher E.

2002-01-01

A method has been proposed for developing structure-property relationships of nano-structured materials. This method serves as a link between computational chemistry and solid mechanics by substituting discrete molecular structures with equivalent-continuum models. It has been shown that this substitution may be accomplished by equating the vibrational potential energy of a nano-structured material with the strain energy of representative truss and continuum models. As important examples with direct application to the development and characterization of single-walled carbon nanotubes and the design of nanotube-based devices, the modeling technique has been applied to determine the effective-continuum geometry and bending rigidity of a graphene sheet. A representative volume element of the chemical structure of graphene has been substituted with equivalent-truss and equivalent continuum models. As a result, an effective thickness of the continuum model has been determined. This effective thickness has been shown to be significantly larger than the interatomic spacing of graphite. The effective thickness has been shown to be significantly larger than the inter-planar spacing of graphite. The effective bending rigidity of the equivalent-continuum model of a graphene sheet was determined by equating the vibrational potential energy of the molecular model of a graphene sheet subjected to cylindrical bending with the strain energy of an equivalent continuum plate subjected to cylindrical bending.

Is sensorimotor BCI performance influenced differently by mono, stereo, or 3-D auditory feedback?

PubMed

McCreadie, Karl A; Coyle, Damien H; Prasad, Girijesh

2014-05-01

Imagination of movement can be used as a control method for a brain-computer interface (BCI) allowing communication for the physically impaired. Visual feedback within such a closed loop system excludes those with visual problems and hence there is a need for alternative sensory feedback pathways. In the context of substituting the visual channel for the auditory channel, this study aims to add to the limited evidence that it is possible to substitute visual feedback for its auditory equivalent and assess the impact this has on BCI performance. Secondly, the study aims to determine for the first time if the type of auditory feedback method influences motor imagery performance significantly. Auditory feedback is presented using a stepped approach of single (mono), double (stereo), and multiple (vector base amplitude panning as an audio game) loudspeaker arrangements. Visual feedback involves a ball-basket paradigm and a spaceship game. Each session consists of either auditory or visual feedback only with runs of each type of feedback presentation method applied in each session. Results from seven subjects across five sessions of each feedback type (visual, auditory) (10 sessions in total) show that auditory feedback is a suitable substitute for the visual equivalent and that there are no statistical differences in the type of auditory feedback presented across five sessions.

Phylodynamic Analysis of Clinical and Environmental Vibrio cholerae Isolates from Haiti Reveals Diversification Driven by Positive Selection

PubMed Central

Azarian, Taj; Ali, Afsar; Johnson, Judith A.; Mohr, David; Prosperi, Mattia; Veras, Nazle M.; Jubair, Mohammed; Strickland, Samantha L.; Rashid, Mohammad H.; Alam, Meer T.; Weppelmann, Thomas A.; Katz, Lee S.; Tarr, Cheryl L.; Colwell, Rita R.

2014-01-01

ABSTRACT Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. PMID:25538191

Effect of BDNF Val66Met polymorphism on digital working memory and spatial localization in a healthy Chinese Han population.

PubMed

Gong, Pingyuan; Zheng, Anyun; Chen, Dongmei; Ge, Wanhua; Lv, Changchao; Zhang, Kejin; Gao, Xiaocai; Zhang, Fuchang

2009-07-01

Cognitive abilities are complex human traits influenced by genetic factors. Brain-derived neurotrophic factor (BDNF), a unique polypeptide growth factor, has an influence on the differentiation and survival of neurons in the nervous system. A single-nucleotide polymorphism (rs6265) in the human gene, resulting in a valine to methionine substitution in the pro-BDNF protein, was thought to associate with psychiatric disorders and might play roles in the individual difference of cognitive abilities. However, the specific roles of the gene in cognition remain unclear. To investigate the relationships between the substitution and cognitive abilities, a healthy population-based study and the PCR-SSCP method were performed. The results showed the substitution was associated with digital working memory (p = 0.02) and spatial localization (p = 0.03), but not with inhibition, shifting, updating, visuo-spatial working memory, long-term memory, and others (p > 0.05) among the compared genotype groups analyzed by general linear model. On the other hand, the participants with BDNF (GG) had higher average performance in digital working memory and spatial localization than the ones with BDNF (AA). The findings of the present work implied that the variation in BDNF might play positive roles in human digital working memory and spatial localization.

Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases.

PubMed

Schaafsma, Gerard C P; Vihinen, Mauno

2017-07-01

Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitutions (AASs) in nine representative protein groups by using the PON-P2 method. The effects on 996 proteins were studied and vast differences were noticed. Proteins in the cancer group harbor the largest proportion of harmful variants (42.1%), whereas the non-disease group of proteins not known to have a disease association and not involved in the housekeeping functions had the lowest number of harmful variants (4.2%). Differences in the proportions of the harmful and benign variants are wide within each group, but they still show clear differences between the groups. Frequently appearing protein domains show a wide spectrum of variant frequencies, whereas no major protein structural class-specific differences were noticed. AAS types in the original and variant residues showed distinctive patterns, which are shared by all the protein groups. The observations are relevant for understanding genetic bases of diseases, variation interpretation, and for the development of methods for that purpose. © 2017 Wiley Periodicals, Inc.

Improvement of thermostability and halostability of β-1,3-1,4-glucanase by substituting hydrophobic residue for Lys48.

PubMed

Lee, Jong Min; Moon, Soo Young; Kim, Yu-Ri; Kim, Kang Woong; Lee, Bong-Joo; Kong, In-Soo

2017-01-01

The aim of this study was to improve the stability of β-1,3-1,4-glucanase by substituting hydrophobic residue for specific amino acid. The results indicated that the catalytic efficiency, thermostability and halostability were enhanced simultaneously by replacement of Lys48 with Ala (K48A) or Leu (K48L). Comparison of kinetic parameters revealed that catalytic efficiency of mutants is enhanced as a result of the increase in substrate affinity. A great improvement in thermostability and halostability was observed. The half-lives of mutants significantly increased (up to ∼7-fold) at 60-70°C. Moreover, relative enzymatic activities of mutants were observed more than 80% even in the presence of 30% NaCl, and half-lives were increased to 3-fold that of wild-type. Based on above results, when applied to ionic liquid, mutants were more active and stable compared to wild-type. These were the results from improvement of protein functions by the substitution of hydrophobic single residue in adjacent with forming carbohydrate binding cavity. Therefore, this report could be helpful for improvement of the enzyme property and for biotechnological application as well. Copyright © 2016 Elsevier B.V. All rights reserved.

Nucleophilic substitution reaction for post-functionalization of polyoxometalates

DOE PAGES

Yin, Panchao; Li, Qiang; Zhang, Jin; ...

2015-07-06

In this study, a hexamolybdate-based organic inorganic hybrid molecule containing a chloralkane fragment is synthesized and its Cl atom can be substituted by iodine and nitrate through nucleophilic substitution reactions in high yields, which provide a post-functionalization protocol to bring in various additional functional groups into polyoxometalate-based hybrid materials under mild conditions.

6-Thioguanine alters the structure and stability of duplex DNA and inhibits quadruplex DNA formation.

PubMed

Marathias, V M; Sawicki, M J; Bolton, P H

1999-07-15

The ability to chemically synthesize biomolecules has opened up the opportunity to observe changes in structure and activity that occur upon single atom substitution. In favorable cases this can provide information about the roles of individual atoms. The substitution of 6-thioguanine (6SG) for guanine is a potentially very useful single atom substitution as 6SG has optical, photocrosslinking, metal ion binding and other properties of potential utility. In addition, 6-mercaptopurine is a clinically important pro-drug that is activated by conversion into 6SG by cells. The results presented here indicate that the presence of 6SG blocks the formation of quadruplex DNA. The presence of 6SG alters the structure and lowers the thermal stability of duplex DNA, but duplex DNA can be formed in the presence of 6SG. These results indicate that some of the cytotoxic activity of 6SG may be due to disruption of the quadruplex structures formed by telomere and other DNAs. This additional mode of action is consistent with the delayed onset of cytotoxicity.

Complete chloroplast genome of Tetragonia tetragonioides: Molecular phylogenetic relationships and evolution in Caryophyllales.

PubMed

Choi, Kyoung Su; Kwak, Myounghai; Lee, Byoungyoon; Park, SeonJoo

2018-01-01

The chloroplast genome of Tetragonia tetragonioides (Aizoaceae; Caryophyllales) was sequenced to provide information for studies on phylogeny and evolution within Caryophyllales. The chloroplast genome of Tetragonia tetragonioides is 149,506 bp in length and includes a pair of inverted repeats (IRs) of 24,769 bp that separate a large single copy (LSC) region of 82,780 bp and a small single copy (SSC) region of 17,188 bp. Comparative analysis of the chloroplast genome showed that Caryphyllales species have lost many genes. In particular, the rpl2 intron and infA gene were not found in T. tetragonioides, and core Caryophyllales lack the rpl2 intron. Phylogenetic analyses were conducted using 55 genes in 16 complete chloroplast genomes. Caryophyllales was found to divide into two clades; core Caryophyllales and noncore Caryophyllales. The genus Tetragonia is closely related to Mesembryanthemum. Comparisons of the synonymous (Ks), nonsynonymous (Ka), and Ka/Ks substitution rates revealed that nonsynonymous substitution rates were lower than synonymous substitution rates and that Ka/Ks rates were less than 1. The findings of the present study suggest that most genes are a purified selection.

Evolution of London penetration depth with scattering in single crystals of K1-xNaxFe2As2

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

Kim, H; Tanatar, M A; Liu, Yong

2014-05-01

London penetration depth, λ(T), was measured in single crystals of K1-xNaxFe2As2, x=0 and 0.07, down to temperatures of 50 mK, ~Tc/50. Isovalent substitution of Na for K significantly increases impurity scattering, with ρ(Tc) rising from 0.2 to 2.2 μΩ cm, and leads to a suppression of Tc from 3.5 to 2.8 K. At the same time, a close to T-linear Δλ(T) in pure samples changes to almost T2 in the substituted samples. The behavior never becomes exponential as expected for the accidental nodes, as opposed to T2 dependence in superconductors with symmetry imposed line nodes. The superfluid density in themore » full temperature range follows a simple clean and dirty d-wave dependence, for pure and substituted samples, respectively. This result contradicts suggestions of multiband scenarios with strongly different gap structure on four sheets of the Fermi surface.« less

Structure analysis on synthetic emerald crystals

NASA Astrophysics Data System (ADS)

Lee, Pei-Lun; Lee, Jiann-Shing; Huang, Eugene; Liao, Ju-Hsiou

2013-05-01

Single crystals of emerald synthesized by means of the flux method were adopted for crystallographic analyses. Emerald crystals with a wide range of Cr3+-doping content up to 3.16 wt% Cr2O3 were examined by X-ray single crystal diffraction refinement method. The crystal structures of the emerald crystals were refined to R 1 (all data) of 0.019-0.024 and w R 2 (all data) of 0.061-0.073. When Cr3+ substitutes for Al3+, the main adjustment takes place in the Al-octahedron and Be-tetrahedron. The effect of substitution of Cr3+ for Al3+ in the beryl structure results in progressively lengthening of the Al-O distance, while the length of the other bonds remains nearly unchanged. The substitution of Cr3+ for Al3+ may have caused the expansion of a axis, while keeping the c axis unchanged in the emerald lattice. As a consequence, the Al-O-Si and Al-O-Be bonding angles are found to decrease, while the angle of Si-O-Be increases as the Al-O distance increases during the Cr replacement.

(13)C NMR substituent-induced chemical shifts in 4-(substituted phenyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-ones (thiones).

PubMed

Kara, Yesim Saniye

2015-01-01

In the present, study mostly novel ten 4-(substituted phenyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-ones and ten 4-(substituted phenyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-thiones were synthesized. These oxadiazole derivatives were characterized by IR, (1)H NMR, (13)C NMR and elemental analyses. Their (13)C NMR spectra were measured in Deuterochloroform (CDCl3). The correlation analysis for the substituent-induced chemical shift (SCS) with Hammett substituent constants (σ), Brown Okamoto substituent constants (σ(+), σ(-)), inductive substituent constants (σI) and different of resonance substituent constants (σR, σR(o)) were performed using SSP (single substituent parameter), DSP (dual substituent parameter) and DSP-NLR (dual substituent parameter-non-linear resonance) methods, as well as single and multiple regression analysis. Negative ρ values were found for all correlations (reverse substituent effect). The results of all statistical analyses, (13)C NMR chemical shift of CN, CO and CS carbon of oxadiazole rings have shown satisfactory correlation. Copyright © 2015 Elsevier B.V. All rights reserved.

Exploring the Limits of DNA Size: Naphtho-homologated DNA Bases and Pairs

PubMed Central

Lee, Alex H. F.; Kool, Eric T.

2008-01-01

A new design for DNA bases and base pairs is described in which the pyrimidine bases are widened by naphtho-homologation. Two naphtho-homologated deoxyribosides, dyyT (1) and dyyC (2) were synthesized and could be incorporated into oligonucleotides as suitably protected phosphoramidite derivatives. The deoxyribosides were found to be fluorescent, with emission maxima at 446 and 433 nm, respectively. Studies with single substitutions of 1 and 2 in the natural DNA context revealed exceptionally strong base stacking propensity for both. Sequences containing multiple substitutions of 1 and 2 paired opposite adenine and guanine were subsequently mixed and studied by several analytical methods. Data from UV mixing experiments, FRET measurements, fluorescence quenching experiments, and hybridizations on beads suggest that complementary “doublewide DNA” (yyDNA) strands may self-assemble into helical complexes with 1:1 stoichiometry. Data from thermal denaturation plots and CD spectra were less conclusive. Control experiments in one sequence context gave evidence that yyDNA helices, if formed, are preferentially antiparallel and are sequence selective. Hypothesized base pairing schemes are analogous to Watson-Crick pairing, but with glycosidic C1′-C1′ distances widened by over 45%, to ca. 15.2 Å. The possible self-assembly of the double-wide DNA helix establishes a new limit for the size of information-encoding, DNA-like molecules, and the fluorescence of yyDNA bases suggests uses as reporters in monomeric and oligomeric forms. PMID:16834396

Solvent-free synthesis, spectral correlations and antimicrobial activities of some aryl E 2-propen-1-ones

NASA Astrophysics Data System (ADS)

Sathiyamoorthi, K.; Mala, V.; Sakthinathan, S. P.; Kamalakkannan, D.; Suresh, R.; Vanangamudi, G.; Thirunarayanan, G.

2013-08-01

Totally 38 aryl E 2-propen-1-ones including nine substituted styryl 4-iodophenyl ketones have been synthesised using solvent-free SiO2-H3PO4 catalyzed Aldol condensation between respective methyl ketones and substituted benzaldehydes under microwave irradiation. The yields of the ketones are more than 80%. The synthesised chalcones were characterized by their analytical, physical and spectroscopic data. The spectral frequencies of synthesised substituted styryl 4-iodophenyl ketones have been correlated with Hammett substituent constants, F and R parameters using single and multi-linear regression analysis. The antimicrobial activities of 4-iodophenyl chalcones have been studied using Bauer-Kirby method.

Investigation on gas sensing properties of Ag doped BiFeO3

NASA Astrophysics Data System (ADS)

Bagwaiya, Toshi; Khade, Poonam; Reshi, Hilal Ahmad; Bhattacharya, Shovit; Shelke, Vilas; Kaur, Manmeet; Debnath, A. K.; Muthe, K. P.; Gadkari, S. C.

2018-04-01

Bismuth ferrite (BFO) and Ag substituted Bismuth ferrite with perovskite structure have been synthesized using sol-gel method and investigated for their gas sensing properties. Single phase and rhombohedral crystal structure of the samples were confirmed from XRD pattern. Oxidation state of the elements is confirmed using X-Ray Photoelectron Spectroscopy (XPS). Since Ag substituted Bismuth ferrite exhibited pronounced response to H2S gas as compared to other gases, H2S gas sensing properties of Bismuth ferrite (BFO) and Ag substituted Bismuth ferrite were investigated in detail. Bi0.9Ag0.1FeO3 (BAFO) exhibits enhanced sensitivity, quick response and selectivity towards H2S as compared to BFO.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.

PubMed

Serre, Stéphanie B N; Jensen, Sanne B; Ghanem, Lubna; Humes, Daryl G; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens; Gottwein, Judith M

2016-06-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The electric field gradient in natural iron-doped chrysoberyl Al2BeO4 and sinhalite MgAlBO4 single crystals

NASA Astrophysics Data System (ADS)

Lottermoser, Werner; Redhammer, Günther J.; Weber, Sven-Ulf; Litterst, Fred Jochen; Tippelt, Gerold; Dlugosz, Stephen; Bank, Hermann; Amthauer, Georg; Grodzicki, Michael

2011-12-01

This work reports on the evaluation of the electric field gradient (EFG) in natural chrysoberyl Al2BeO4 and sinhalite MgAlBO4 using two different procedures: (1) experimental, with single crystal Mössbauer spectroscopy (SCMBS) on the three principal sections of each sample and (2) a "fully quantitative" method with cluster molecular orbital calculations based on the density functional theory. Whereas the experimental and theoretical results for the EFG tensor are in quantitative agreement, the calculated isomer shifts and optical d-d-transitions exhibit systematic deviations from the measured values. These deviations indicate that the substitution of Al and Mg with iron should be accompanied by considerable local expansion of the coordination octahedra.

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

PubMed Central

2017-01-01

Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred syn or anti N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the in vitro action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events. PMID:29181193

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

PubMed

Parrella, P; Xiao, Y; Fliss, M; Sanchez-Cespedes, M; Mazzarelli, P; Rinaldi, M; Nicol, T; Gabrielson, E; Cuomo, C; Cohen, D; Pandit, S; Spencer, M; Rabitti, C; Fazio, V M; Sidransky, D

2001-10-15

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Soy-based polyols

DOEpatents

Suppes, Galen; Lozada, Zueica; Lubguban, Arnold

2013-06-25

The invention provides processes for preparing soy-based oligomeric polyols or substituted oligomeric polyols, as well as urethane bioelasteromers comprising the oligomeric polyols or substituted oligomeric polyols.

Neutron diffraction studies on cobalt substituted BiFeO3

NASA Astrophysics Data System (ADS)

Ray, J.; Biswal, A. K.; Acharya, S.; Babu, P. D.; Siruguri, V.; Vishwakarma, P. N.

2013-02-01

A dilute concentration of single phase Cobalt substituted Bismuth ferrite, BiFe1-XCoXO3; (x=0, 0.02) is prepared by sol-gel auto combustion method. Room temperature neutron diffraction patterns show no change in the crystal and magnetic structure upon cobalt doping. The calculation of magnetic moments shows 3.848 μB for Fe+ and 2.85 μB for Co3+. The cobalt is found to be in intermediate spin state.

Packaging waste prevention activities: A life cycle assessment of the effects on a regional waste management system.

PubMed

Nessi, Simone; Rigamonti, Lucia; Grosso, Mario

2015-09-01

A life cycle assessment was carried out to evaluate the effects of two packaging waste prevention activities on the overall environmental performance of the integrated municipal waste management system of Lombardia region, Italy. The activities are the use of refined tap water instead of bottled water for household consumption and the substitution of liquid detergents packaged in single-use containers by those distributed 'loose' through self-dispensing systems and refillable containers. A 2020 baseline scenario without waste prevention is compared with different waste prevention scenarios, where the two activities are either separately or contemporaneously implemented, by assuming a complete substitution of the traditional product(s). The results show that, when the prevention activities are carried out effectively, a reduction in total waste generation ranging from 0.14% to 0.66% is achieved, corresponding to a 1-4% reduction of the affected packaging waste fractions (plastics and glass). However, the improvements in the overall environmental performance of the waste management system can be far higher, especially when bottled water is substituted. In this case, a nearly 0.5% reduction of the total waste involves improvements ranging mostly between 5 and 23%. Conversely, for the substitution of single-use packaged liquid detergents (0.14% reduction of the total waste), the achieved improvements do not exceed 3% for nearly all impact categories. © The Author(s) 2015.

Electronic and magnetic behaviors of B, N, and 3d transition metal substitutions in germanium carbide monolayer

NASA Astrophysics Data System (ADS)

Xu, Zhuo; Li, Yangping; Liu, Zhengtang; Liu, Shengzhong (Frank)

2018-04-01

The structural, electronic, and magnetic behaviors of two-dimensional GeC (2D-GeC) with single vacancy, substitutional B, N, and 3d transition metal atoms (Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) are investigated based on the density functional theory. These impurities are tightly bonded to the surrounding atoms and found energetically more favorable at Ge sub-lattice site. In addition, the electronic band structures and magnetic properties of the doped systems indicate that (i) tunable electronic structures and magnetic moments of 2D-GeC can be obtained depending on different dopant species and sub-lattice sites, (ii) systems such as VC@Sc, VC@Fe, VC@Co, VGe@Fe, and VGe@Co are found to be half-metals, while the other systems all show semiconductor behavior. Simple models of the impurity-vacancy interaction is put forwards to illustrate the origin of the electronic structures and magnetic moments.

Multiferroics BiMn1-xAlxO3 nanoparticles: Synthesis, characterization and evaluation of various structural, physical, electrical and dielectric parameters

NASA Astrophysics Data System (ADS)

Ahmad, Bashir; Raissat, Rabia; Mumtaz, Saleem; Ahmad, Zahoor; Sadiq, Imran; Ashiq, Muhammad Naeem; Najam-ul-Haq, Muhammad

2017-07-01

The aluminium substituted bismuth based manganates with nominal composition BiMn1-xAlxO3 (x = 0.0, 0.2, 0.4, 0.6 and 0.8) were prepared by the simple microemulsion method. The alteration in their structural, electrical and dielectric parameters due to Al substitution has been investigated. The X-ray diffraction analysis (XRD) confirms the formation of single phase orthorhombic with crystallite size ranges from 32 to 52 nm. The morphological features and particle size were determined by using scanning electron microscopy (SEM). The dc electrical resistivity increased from 6 × 108 to 8 × 109 Ω cm with the increase in substituent concentration. The dielectric constant, dielectric loss tangent and dielectric loss factor decreased with the increase in frequency. The increase in electrical resistivity makes the synthesized materials paramount over other materials and can be useful for technological applications in microwave devices.

Induction of relaxor state in ordinary ferroelectrics by isovalent ion substitution: A pretransitional martensitic texture case

NASA Astrophysics Data System (ADS)

Lente, M. H.; Moreira, E. N.; Garcia, D.; Eiras, J. A.; Neves, P. P.; Doriguetto, A. C.; Mastelaro, V. R.; Mascarenhas, Y. P.

2006-02-01

The understanding of the structural origin of relaxor ferroelectrics has been doubtlessly a long-standing puzzle in the field of ferroelectricity. Thus, motivated by the interest in improving the comprehension of this important issue, it a framework is proposed for explaining the origin of the relaxor state in ordinary ferroelectrics induced via the isovalent-ion substitution. Based on the martensitic transformation concepts, it is proposed that the continuous addition of isovalent ions in a so-called normal ferroelectric decreases considerably the elastic strain energy. This results in a gradual transformation of ferroelectric domain patterns from a micrometer polydomain structure (twins), through single domains, to nanometer-polar-“tweed” structures with glasslike behavior, that are, in turn, strongly driven by point defects and surface effects. The electrical interaction between these weakly coupled polar-tweed structures leads to a wide spectrum of relaxation times, thus resulting in a dielectric relaxation process, the signature of relaxor ferroelectrics.

Effective oligonucleotide-mediated gene disruption in ES cells lacking the mismatch repair protein MSH3.

PubMed

Dekker, M; Brouwers, C; Aarts, M; van der Torre, J; de Vries, S; van de Vrugt, H; te Riele, H

2006-04-01

We have previously demonstrated that site-specific insertion, deletion or substitution of one or two nucleotides in mouse embryonic stem cells (ES cells) by single-stranded deoxyribo-oligonucleotides is several hundred-fold suppressed by DNA mismatch repair (MMR) activity. Here, we have investigated whether compound mismatches and larger insertions escape detection by the MMR machinery and can be effectively introduced in MMR-proficient cells. We identified several compound mismatches that escaped detection by the MMR machinery to some extent, but could not define general rules predicting the efficacy of complex base-pair substitutions. In contrast, we found that four-nucleotide insertions were largely subject to suppression by the MSH2/MSH3 branch of MMR and could be effectively introduced in Msh3-deficient cells. As these cells have no overt mutator phenotype and Msh3-deficient mice do not develop cancer, Msh3-deficient ES cells can be used for oligonucleotide-mediated gene disruption. As an example, we present disruption of the Fanconi anemia gene Fancf.

Best Hiding Capacity Scheme for Variable Length Messages Using Particle Swarm Optimization

NASA Astrophysics Data System (ADS)

Bajaj, Ruchika; Bedi, Punam; Pal, S. K.

Steganography is an art of hiding information in such a way that prevents the detection of hidden messages. Besides security of data, the quantity of data that can be hidden in a single cover medium, is also very important. We present a secure data hiding scheme with high embedding capacity for messages of variable length based on Particle Swarm Optimization. This technique gives the best pixel positions in the cover image, which can be used to hide the secret data. In the proposed scheme, k bits of the secret message are substituted into k least significant bits of the image pixel, where k varies from 1 to 4 depending on the message length. The proposed scheme is tested and results compared with simple LSB substitution, uniform 4-bit LSB hiding (with PSO) for the test images Nature, Baboon, Lena and Kitty. The experimental study confirms that the proposed method achieves high data hiding capacity and maintains imperceptibility and minimizes the distortion between the cover image and the obtained stego image.

Influence of cobalt, tantaum and tungsten on the high temperature mechanical properties of single crystal nickel-base superalloys. Ph.D. Thesis - Case Western Reserve Univ.

NASA Technical Reports Server (NTRS)

Nathal, M. V.

1984-01-01

For alloys with the baseline refractory metal level of 3 percent Ta and 10 percent W, decreases in Co level from 10 to 0 percent resulted in increased tensile strength and creep resistance. Substitution of W for Ta resulted in decreased creep life at high stresses but improved life at low stresses. Substitution of Ni for Ta caused large reductions in tensile strength and creep resistance, and corresponding increases in ductility. For these alloys with low Ta plus W totals, strength was independent of Co level. The increases in tensile strength with increases in refractory metal content were related to the increases in gamma volume fraction and solid solution hardening. Increases in strength as Co level decreased were considered to be the result of coherency strain hardening from the increased lattice mismatch. Dislocation shear through the gamma-gamma interface is considered to be the rate limiting step in the deformation process.

M3Ag17(SPh)12 Nanoparticles and Their Structure Prediction.

PubMed

Wickramasinghe, Sameera; Atnagulov, Aydar; Conn, Brian E; Yoon, Bokwon; Barnett, Robert N; Griffith, Wendell P; Landman, Uzi; Bigioni, Terry P

2015-09-16

Although silver nanoparticles are of great fundamental and practical interest, only one structure has been determined thus far: M4Ag44(SPh)30, where M is a monocation, and SPh is an aromatic thiolate ligand. This is in part due to the fact that no other molecular silver nanoparticles have been synthesized with aromatic thiolate ligands. Here we report the synthesis of M3Ag17(4-tert-butylbenzene-thiol)12, which has good stability and an unusual optical spectrum. We also present a rational strategy for predicting the structure of this molecule. First-principles calculations support the structural model, predict a HOMO-LUMO energy gap of 1.77 eV, and predict a new "monomer mount" capping motif, Ag(SR)3, for Ag nanoparticles. The calculated optical absorption spectrum is in good correspondence with the measured spectrum. Heteroatom substitution was also used as a structural probe. First-principles calculations based on the structural model predicted a strong preference for a single Au atom substitution in agreement with experiment.

Distinct molecular structures and hydrogen bond patterns of α,α-diethyl-substituted cyclic imide, lactam, and acetamide derivatives in the crystalline phase

NASA Astrophysics Data System (ADS)

Krivoshein, Arcadius V.; Ordonez, Carlos; Khrustalev, Victor N.; Timofeeva, Tatiana V.

2016-10-01

α,α-Dialkyl- and α-alkyl-α-aryl-substituted cyclic imides, lactams, and acetamides show promising anticonvulsant, anxiolytic, and anesthetic activities. While a number of crystal structures of various α-substituted cyclic imides, lactams, and acetamides were reported, no in-depth comparison of crystal structures and solid-state properties of structurally matched compounds have been carried out so far. In this paper, we report molecular structure and intermolecular interactions of three α,α-diethyl-substituted compounds - 3,3-diethylpyrrolidine-2,5-dione, 3,3-diethylpyrrolidin-2-one, and 2,2-diethylacetamide - in the crystalline phase, as studied using single-crystal X-ray diffraction and IR spectroscopy. We found considerable differences in the patterns of H-bonding and packing of the molecules in crystals. These differences correlate with the compounds' melting points and are of significance to physical pharmacy and formulation development of neuroactive drugs.

Effects of Gd substitution on the structural and magnetic properties of strontium hexaferrites

NASA Astrophysics Data System (ADS)

Litsardakis, G.; Manolakis, I.; Serletis, C.; Efthimiadis, K. G.

2007-09-01

The effect of Gd substitution in M-type strontium hexaferrites has been examined in two series of samples, (Sr1-xGdx)O·5.25Fe2O3 and Sr1-xGdxFe12-xCoxO19, both prepared by the ceramic method, where x=0-0.40. The samples have been characterized by XRD, VSM and SEM-EDAX techniques. All substituted samples present primarily the hexaferrite structure. Sample (Sr0.95Gd)O·5.25Fe2O3 is single phase. Formation of impurity phases is affected by stoichiometry and presence of Co. In Sr-Gd samples, coercivity showed a maximum value of 305 kA/m (3.8 kOe) for x=0.20, while remanence and saturation magnetization did not decrease. Coercivity and magnetization in the Sr-Gd-Co series decreased steadily with substitution degree.

Single and couple doping ZnO nanocrystals characterized by positron techniques

NASA Astrophysics Data System (ADS)

Pasang, Tenzin; Namratha, Keerthiraj; Guagliardo, Paul; Byrappa, Kullaiah; Ranganathaiah, Chikkakuntappa; Samarin, S.; Williams, J. F.

2015-04-01

Zinc oxide (ZnO) nanocrystals have been synthesized using a mild hydrothermal process using low temperatures and pressures with the advantages of free growth catalyst, low cost and alternative technology. Positron annihilation lifetime spectroscopy and coincidence Doppler broadening (CDB) spectroscopic methods have been used to investigate the roles of single- and co-dopants and native defects of the ZnO nanocrystals controlled by the synthesis process. It is shown that single Ag1+ and Pd2+ dopants occupy interstitial sites of the ZnO lattice and single Ru3+ doping replaces Zn vacancies substitutionally with a significant effect on the CDB momentum ratio curves when compared using ZnO as the reference spectrum. The co-doping of the ZnO lattice with (Sn4+ + Co2+) shows similar CDB ratios as Ru3+ single-doping. Also co-doping with (Ag1+ + Pd2+) or (Ag1+ + W6+) shows significant decreases in the band gap energy up to about 12.6% compared to single doping. The momentum ratio curves, referenced to undoped ZnO, indicate dopants in interstitial and substitutional sites. The presence of transition metal ions interstitially will trap electrons which resist the recombination of electrons and in turn affect the conductivity of the material.

Improving the assessment of prescribing: use of a 'substitution index'.

PubMed

Kunisawa, Susumu; Otsubo, Tetsuya; Lee, Jason; Imanaka, Yuichi

2013-07-01

To analyse the current and potential utilization of generic drugs in Japan, to examine the maximum possible cost savings from generic drug use and to develop a fairer measure to assess the level of generic drug substitution. We conducted a cross-sectional retrospective analysis of nine million dispensing records during January to March 2010 in Kyoto Prefecture. Maximum potential quantity-based shares were defined as the quantity of generic drugs used plus the quantity of branded drugs that could have been replaced by generic drugs divided by the quantity of all drugs dispensed. We developed a 'substitution index', defined as the proportion of generic drugs out of the total drugs substitutable with generic drugs (based on quantity rather than cost). Generic drugs had a quantity-based share of 17.9%, a cost-based share of 8.9% and a maximum potential quantity-based share of 50.1%, which is lower than the actual generic drug shares of some other countries. The maximum possible cost savings as a result of generic drug substitution was 16.5%. We also observed wide variations in maximum potential quantity-based shares between health care sectors and health care institutions. Simple comparisons based on quantity-based shares may misrepresent the actual generic drug use. A substitution index that takes into account the maximum potential quantity-based share of generic drugs as a fairer measure may promote more realistic goals and encourage generic drug usage.

Unique Determinants of Neuraminidase Inhibitor Resistance among N3, N7, and N9 Avian Influenza Viruses.

PubMed

Song, Min-Suk; Marathe, Bindumadhav M; Kumar, Gyanendra; Wong, Sook-San; Rubrum, Adam; Zanin, Mark; Choi, Young-Ki; Webster, Robert G; Govorkova, Elena A; Webby, Richard J

2015-11-01

Human infections with avian influenza viruses are a serious public health concern. The neuraminidase (NA) inhibitors (NAIs) are the frontline anti-influenza drugs and are the major option for treatment of newly emerging influenza. Therefore, it is essential to identify the molecular markers of NAI resistance among specific NA subtypes of avian influenza viruses to help guide clinical management. NAI-resistant substitutions in NA subtypes other than N1 and N2 have been poorly studied. Here, we identified NA amino acid substitutions associated with NAI resistance among influenza viruses of N3, N7, and N9 subtypes which have been associated with zoonotic transmission. We applied random mutagenesis and generated recombinant influenza viruses carrying single or double NA substitution(s) with seven internal genes from A/Puerto Rico/8/1934 (H1N1) virus. In a fluorescence-based NA inhibition assay, we identified three categories of NA substitutions associated with reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir): (i) novel subtype-specific substitutions in or near the enzyme catalytic site (R152W, A246T, and D293N, N2 numbering), (ii) subtype-independent substitutions (E119G/V and/or D and R292K), and (iii) substitutions previously reported in other subtypes (Q136K, I222M, and E276D). Our data show that although some markers of resistance are present across NA subtypes, other subtype-specific markers can only be determined empirically. The number of humans infected with avian influenza viruses is increasing, raising concerns of the emergence of avian influenza viruses resistant to neuraminidase (NA) inhibitors (NAIs). Since most studies have focused on NAI-resistance in human influenza viruses, we investigated the molecular changes in NA that could confer NAI resistance in avian viruses grown in immortalized monolayer cells, especially those of the N3, N7, and N9 subtypes, which have caused human infections. We identified not only numerous NAI-resistant substitutions previously reported in other NA subtypes but also several novel changes conferring reduced susceptibility to NAIs, which are subtype specific. The findings indicate that some resistance markers are common across NA subtypes, but other markers need to be determined empirically for each subtype. The study also implies that antiviral surveillance monitoring could play a critical role in the clinical management of influenza virus infection and an essential component of pandemic preparedness. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Synthesis and Characterization of a Heterometallic Extended Architecture Based on a Manganese(II)-Substituted Sandwich-Type Polyoxotungstate

PubMed Central

Ibrahim, Masooma; Moreno-Pineda, Eufemio; Anson, Christopher E.; Powell, Annie K.

2018-01-01

The reaction of [α-P2W15O56]12− with MnII and DyIII in an aqueous basic solution led to the isolation of an all inorganic heterometallic aggregate Na10(OH2)42[{Dy(H2O)6}2Mn4P4W30O112(H2O)2]·17H2O (Dy2Mn4-P2W15). Single-crystal X-ray diffraction revealed that Dy2Mn4-P2W15 crystallizes in the triclinic system with space group P1¯, and consists of a tetranuclear manganese(II)-substituted sandwich-type phosphotungstate [Mn4(H2O)2(P2W15O56)2]16− (Mn4-P2W15), Na, and DyIII cations. Compound Dy2Mn4-P2W15 exhibits a 1D ladder-like chain structure based on sandwich-type segments and dysprosium cations as linkers, which are further connected into a three-dimensional open framework by sodium cations. The title compound was structurally and compositionally characterized in solid state by single-crystal XRD, powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA), and elemental analyses. Further, the absorption and emission electronic spectra in aqueous solutions of Dy2Mn4-P2W15 and Mn4-P2W15 were studied. Also, magnetic properties were studied and compared with the magnetic behavior of [Mn4(H2O)2(P2W15O56)2]16−. PMID:29342122

Different mutational function of low- and high-linear energy transfer heavy-ion irradiation demonstrated by whole-genome resequencing of Arabidopsis mutants.

PubMed

Kazama, Yusuke; Ishii, Kotaro; Hirano, Tomonari; Wakana, Taeko; Yamada, Mieko; Ohbu, Sumie; Abe, Tomoko

2017-12-01

Heavy-ion irradiation is a powerful mutagen that possesses high linear energy transfer (LET). Several studies have indicated that the value of LET affects DNA lesion formation in several ways, including the efficiency and the density of double-stranded break induction along the particle path. We assumed that the mutation type can be altered by selecting an appropriate LET value. Here, we quantitatively demonstrate differences in the mutation type induced by irradiation with two representative ions, Ar ions (LET: 290 keV μm -1 ) and C ions (LET: 30.0 keV μm -1 ), by whole-genome resequencing of the Arabidopsis mutants produced by these irradiations. Ar ions caused chromosomal rearrangements or large deletions (≥100 bp) more frequently than C ions, with 10.2 and 2.3 per mutant genome under Ar- and C-ion irradiation, respectively. Conversely, C ions induced more single-base substitutions and small indels (<100 bp) than Ar ions, with 28.1 and 56.9 per mutant genome under Ar- and C-ion irradiation, respectively. Moreover, the rearrangements induced by Ar-ion irradiation were more complex than those induced by C-ion irradiation, and tended to accompany single base substitutions or small indels located close by. In conjunction with the detection of causative genes through high-throughput sequencing, selective irradiation by beams with different effects will be a powerful tool for forward genetics as well as studies on chromosomal rearrangements. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.

PubMed

Tang, Xian; Guo, Jia; Cheng, Lin; Sun, Caijun; Liu, Li; Zuo, Teng; Wang, Hui; Chen, Ling; Zhang, Linqi; Chen, Zhiwei

2017-05-02

An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIV mac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain. Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively. Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity. ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer. Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIV mac239 . Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Critical Analysis of Concentration and Competition in the Indian Pharmaceutical Market

PubMed Central

Mehta, Aashna; Hasan Farooqui, Habib; Selvaraj, Sakthivel

2016-01-01

Objectives It can be argued that with several players marketing a large number of brands, the pharmaceutical market in India is competitive. However, the pharmaceutical market should not be studied as a single market but, as a sum total of a large number of individual sub-markets. This paper examines the methodological issues with respect to defining the relevant market involved in studying concentration in the pharmaceutical market in India. Further, we have examined whether the Indian pharmaceutical market is competitive. Methods Indian pharmaceutical market was studied using PharmaTrac, the sales audit data from AIOCD-AWACS, that organises formulations into 5 levels of therapeutic classification based on the EphMRA system. The Herfindahl-Hirschman Index (HHI) was used as the indicator of market concentration. We calculated HHI for the entire pharmaceutical market studied as a single market as well as at the five different levels of therapeutic classification. Results and Discussion Whereas the entire pharmaceutical market taken together as a single market displayed low concentration (HHI = 226.63), it was observed that if each formulation is defined as an individual sub-market, about 69 percent of the total market in terms of market value displayed at least moderate concentration. Market should be defined taking into account the ease of substitutability. Since, patients cannot themselves substitute the formulation prescribed by the doctor with another formulation with the same indication and therapeutic effect, owing to information asymmetry, it is appropriate to study market concentration at the narrower levels of therapeutic classification. PMID:26895269

Anomalous electron doping independent two-dimensional superconductivity

NASA Astrophysics Data System (ADS)

Zhou, Wei; Xing, Xiangzhuo; Zhao, Haijun; Feng, Jiajia; Pan, Yongqiang; Zhou, Nan; Zhang, Yufeng; Qian, Bin; Shi, Zhixiang

2017-07-01

Transition metal (Co and Ni) co-doping effects are investigated on an underdoped Ca0.94La0.06Fe2As2 compound. It is discovered that electron doping from substituting Fe with transition metal (TM = Co, Ni) can trigger high-{T}{{c}} superconductivity around 35 K, which emerges abruptly before the total suppression of the innate spin-density-wave/anti-ferromagnetism (SDW/AFM) state. Remarkably, the critical temperature for the high-{T}{{c}} superconductivity remains constant against a wide range of TM doping levels. And the net electron doping density dependence of the superconducting {T}{{c}} based on the rigid band model can be nicely scaled into a single curve for Co and Ni substitutions, in stark contrast to the case of Ba(Fe1-x TM x )2As2. This carrier density independent superconductivity and the unusual scaling behavior are presumably resulted from the interface superconductivity based on the similarity with the interface superconductivity in a La2-x Sr x CuO4-La2CuO4 bilayer. Evidence of the two-dimensional character of the superfluid by angle-resolved magneto-resistance measurements can further strengthen the interface nature of the high-{T}{{c}} superconductivity.

DNA-binding studies of a tetraalkyl-substituted porphyrin and the mutually adaptive distortion principle.

PubMed

Ghimire, Srijana; Fanwick, Phillip E; McMillin, David R

2014-10-20

This investigation explores DNA-binding interactions of various forms of an alkyl-substituted cationic porphyrin, H2TC3 (5,10,15,20-tetra[3-(3'-methylimidazolium-1'-yl)]porphyrin). The motivating idea is that incorporating alkyl rather than aryl substituents in the meso positions will enhance the prospects for intercalative as well as external binding to DNA hosts. The ligands may also be applicable for photodynamic and/or anticancer therapy. Methods employed include absorbance, circular dichroism, and emission spectroscopies, as well as viscometry and X-ray crystallography. By comparison with the classical H2T4 system, H2TC3 exhibits a higher molar extinction coefficient but is more prone to self-association. Findings of note include that the copper(II)-containing form Cu(TC3) is adept at internalizing into single-stranded as well as B-form DNA, regardless of the base composition. Surprisingly, however, external binding of H2TC3 occurs within domains that are rich in adenine-thymine base pairs. The difference in the deformability of H2TC3 versus Cu(TC3) probably accounts for the reactivity difference. Finally, Zn(TC3) binds externally, as the metal center remains five-coordinate.

Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer.

PubMed

Bogdanowicz, Brian S; Hoch, Matthew A; Hartranft, Megan E

2017-04-01

Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.

A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase.

PubMed Central

Fox, T.; Coll, J. T.; Xie, X.; Ford, P. J.; Germann, U. A.; Porter, M. D.; Pazhanisamy, S.; Fleming, M. A.; Galullo, V.; Su, M. S.; Wilson, K. P.

1998-01-01

Mitogen-activated protein (MAP) kinases are serine/threonine kinases that mediate intracellular signal transduction pathways. Pyridinyl imidazole compounds block pro-inflammatory cytokine production and are specific p38 kinase inhibitors. ERK2 is related to p38 in sequence and structure, but is not inhibited by pyridinyl imidazole inhibitors. Crystal structures of two pyridinyl imidazoles complexed with p38 revealed these compounds bind in the ATP site. Mutagenesis data suggested a single residue difference at threonine 106 between p38 and other MAP kinases is sufficient to confer selectivity of pyridinyl imidazoles. We have changed the equivalent residue in human ERK2, Q105, into threonine and alanine, and substituted four additional ATP binding site residues. The single residue change Q105A in ERK2 enhances the binding of SB202190 at least 25,000-fold compared to wild-type ERK2. We report enzymatic analyses of wild-type ERK2 and the mutant proteins, and the crystal structure of a pyridinyl imidazole, SB203580, bound to an ERK2 pentamutant, I103L, Q105T, D106H, E109G. T110A. These ATP binding site substitutions induce low nanomolar sensitivity to pyridinyl imidazoles. Furthermore, we identified 5-iodotubercidin as a potent ERK2 inhibitor, which may help reveal the role of ERK2 in cell proliferation. PMID:9827991

Synthesis and characterization of p-type conductivity dopant 2-(3-(adamantan-1-yl)propyl)-3,5,6-trifluoro-7,7,8,8-tetracyanoquinodimethane

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

Rainbolt, James E.; Koech, Phillip K.; Polikarpov, Evgueni

2013-01-22

We report the synthesis and characterization of 2-(3-(adamantan-1-yl)propyl)-3,5,6-trifluoro-7,7,8,8-tetracyanoquinodimethane (F3TCNQ-Ad1), a substituted analog of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), designed for p-type conductivity doping. The dopant is designed as a model for substituted alternatives to F4TCNQ that maintain similar electronic properties with the goal of engineering dopants with superior fabrication characteristics over F4TCNQ. We describe the design strategy for F3TCNQ-Ad1 based on molecular modeling predictions that substitution of a single fluorine atom of F4TCNQ has little effect on the electronic properties of the molecule. Photophysical and electrochemical characterization reveal that the adamantyl substituent in F3TCNQ-Ad1 does not significantly alter the electronic properties of themore » substituted dopant relative to F4TCNQ. Unfortunately, F3TCNQ-Ad1 degrades under standard sublimation conditions, preventing sublimation deposition processing. Instead, hole-only devices were made via solution-processing of the p-doped films with the structure glass/ITO/2.3 x103Å PVK:(MTDATA:dopant)/2.0x102Å Au/1.0x103Å Al, where dopant is either F4TCNQ or F3TCNQ-Ad1. We demonstrate that F3TCNQ-Ad1 increased the conductivity of the films by at least 1,000 times compared to an undoped device.« less

Prediction of equilibrium distributions of isotopologues for methane, ethane and propane using density functional theory

NASA Astrophysics Data System (ADS)

Piasecki, Alison; Sessions, Alex; Peterson, Brian; Eiler, John

2016-10-01

Many previous studies have examined abundances of deuterium (D) and 13C within small organic molecules. Recent advances in analytical instrumentation add the abilities to measure site-specific and multiply substituted isotopologues of natural organics. Here we perform first-principles calculations of the equilibrium distributions of 13C and D in the volatile alkanes (including both single and multiple substitutions), as a guide to the interpretation of current measurements and as a basis for anticipating isotope effects that might be examined with future analytical techniques. The models we present illustrate several common themes of the isotopic structures of the small alkanes, including; temperature dependent enrichment of clumped isotope species, with amplitudes in the order D-D > 13C-D > 13C-13C; similarity in strength of such clumped isotope effects between different molecules (e.g., 13C-D clumping is ∼5‰ enriched at 300 K in methane, ethane and propane); a ∼10× contrast between the amplitudes of stronger adjacent substitution of two heavy isotopes vs. weaker non-adjacent substitution; temperature-dependent site-specific fractionation of D and 13C into interior positions of molecules relative to terminal methyl groups; and a relatively simple additive effect to the overall amplitude of enrichment when clumped and site specific effects combine in the same isotopologue. We suggest that the most promising tools suggested by our results are isotopic thermometers based on site-specific distribution of deuterium, which exhibits strong (∼100‰), highly temperature dependent fractionation between methyl groups and methylene carbon positions in propane (and likely other larger n-alkanes).

Combined effect of fuel-design and after-treatment system on reduction of local and global emissions from CI engine.

PubMed

Thiyagarajan, S; Geo, V Edwin; Martin, Leenus Jesu; Nagalingam, B

2018-03-22

This experimental study aims to mitigate harmful emissions from a CI engine using bio-energy with carbon capture and storage (BECCS) approach. The engine used for this experimental work is a single cylinder CI engine with a rated power of 5.2 kW at a constant speed of 1500 rpm. The BECCS approach is a combination of plant-based biofuels and carbon capture and storage (CCS) system. The whole investigation was done in four phases: (1) Substituting diesel with Karanja oil methyl ester (KOME) (2) Equal volume blending of Orange oil (ORG) with KOME (3) 20% blending of n-butanol (B) with KOME-ORG blend (4) CCS system with zeolite based non-selective catalytic reduction (NSCR) and mono ethanolamine (MEA) based selective non-catalytic reduction (SNCR) system with KOME-ORG + B20 blend. The experimental results show that substitution of diesel with KOME reduces smoke emission, but increases NO and CO 2 emission. KOME-ORG blend reduces CO 2 and smoke emissions with high NO emission due to combustion improvement. In comparison with the sole combustion of KOME at full load condition, the combination of KOME-ORG + B20 as bio-fuel with zeolite based post-combustion treatment system resulted in a maximum reduction of NO, smoke and CO 2 emission by 41%, 19% and 15% respectively.

pKa prediction from an ab initio bond length: part 3--benzoic acids and anilines.

PubMed

Harding, A P; Popelier, P L A

2011-06-21

The prediction of pK(a) from a single ab initio bond length has been extended to provide equations for benzoic acids and anilines. The HF/6-31G(d) level of theory is used for all geometry optimisations. Similarly to phenols (Part 2 of this series of publications), the meta-/para-substituted benzoic acids can be predicted from a single model constructed from one bond length. This model had an impressive RMSEP of 0.13 pK(a) units. The prediction of ortho-substituted benzoic acids required the identification of high-correlation subsets, where the compounds in the same subset have at least one of the same (e.g. halogens, hydroxy) ortho substituent. Two pK(a) equations are provided for o-halogen benzoic acids and o-hydroxybenzoic acids, where the RMSEP values are 0.19 and 0.15 pK(a) units, respectively. Interestingly, the bond length that provided the best model differed between these two high-correlation subsets. This demonstrates the importance of investigating the most predictive bond length, which is not necessarily the bond involving the acid hydrogen. Three high-correlation subsets were identified for the ortho-substituted anilines. These were o-halogen, o-nitro and o-alkyl-substituted aniline high-correlation subsets, where the RMSEP ranged from 0.23 to 0.44 pK(a) units. The RMSEP for the meta-/para-substituted aniline model was 0.54 pK(a) units. This value exceeded our threshold of 0.50 pK(a) units and was higher than both the m-/p-benzoic acids in this work and the m-/p-phenols (RMSEP = 0.43) of Part 2. Constructing two separate models for the meta- and para- substituted anilines, where RMSEP values of 0.63 and 0.33 pK(a) units were obtained respectively, revealed it was the meta-substituted anilines that caused the large RMSEP value. For unknown reasons the RMSEP value increased with the addition of a further twenty meta-substituted anilines to this model. The C-N bond always produced the best correlations with pK(a) for all the high-correlation subsets. A higher level of theory and an ammonia probe improved the statistics only marginally for the hydroxybenzoic acid high-correlation subsets.

Extending substructure based iterative solvers to multiple load and repeated analyses

NASA Technical Reports Server (NTRS)

Farhat, Charbel

1993-01-01

Direct solvers currently dominate commercial finite element structural software, but do not scale well in the fine granularity regime targeted by emerging parallel processors. Substructure based iterative solvers--often called also domain decomposition algorithms--lend themselves better to parallel processing, but must overcome several obstacles before earning their place in general purpose structural analysis programs. One such obstacle is the solution of systems with many or repeated right hand sides. Such systems arise, for example, in multiple load static analyses and in implicit linear dynamics computations. Direct solvers are well-suited for these problems because after the system matrix has been factored, the multiple or repeated solutions can be obtained through relatively inexpensive forward and backward substitutions. On the other hand, iterative solvers in general are ill-suited for these problems because they often must restart from scratch for every different right hand side. In this paper, we present a methodology for extending the range of applications of domain decomposition methods to problems with multiple or repeated right hand sides. Basically, we formulate the overall problem as a series of minimization problems over K-orthogonal and supplementary subspaces, and tailor the preconditioned conjugate gradient algorithm to solve them efficiently. The resulting solution method is scalable, whereas direct factorization schemes and forward and backward substitution algorithms are not. We illustrate the proposed methodology with the solution of static and dynamic structural problems, and highlight its potential to outperform forward and backward substitutions on parallel computers. As an example, we show that for a linear structural dynamics problem with 11640 degrees of freedom, every time-step beyond time-step 15 is solved in a single iteration and consumes 1.0 second on a 32 processor iPSC-860 system; for the same problem and the same parallel processor, a pair of forward/backward substitutions at each step consumes 15.0 seconds.

In Situ XAS and XRD Studies of Substituted Spinel Lithium Manganese Oxides in the 4-5 V Region

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

McBreen, J.; Mukerjee, S.; Yang, X. Q.

Partial substitution of Mn in lithium manganese oxide spinel materials by Cu and Ni greatly affects the electrochemistry and the phase behavior of the cathode. Substitution with either metal or with a combination of both shortens the 4.2 V plateau and results in higher voltage plateaus. In situ x-ray absorption (XAS) studies indicate that the higher voltage plateaus are related to redox processes on the substituents. In situ x-ray diffraction (XRD) on LiCu{sub 0.5}Mn{sub 1.5}O{sub 4} shows single phase behavior during the charge and discharge process. Three phases are observed for LiNi{sub 0.5}Mn{sub 1.5}O{sub 4} and two phases are observedmore » in the case of LiNi{sub 0.25}Cu{sub 0.25}Mn{sub 1.5}O{sub 4}. The electrolyte stability is dependent on both the operating voltage and the cathode composition. Even though Ni substituted materials have lower voltages, the electrolyte is more stable in cells with the Cu substituted materials.« less

Drastic effect of the Mn-substitution in the strongly correlated semiconductor FeSb2.

NASA Astrophysics Data System (ADS)

Kassem, Mohamed A.; Tabata, Yoshikazu; Waki, Takeshi; Nakamura, Hiroyuki

2017-06-01

We report the effects of Mn substitution, corresponding to hole doping, on the electronic properties of the narrow gap semiconductor, FeSb2, using single crystals of Fe1- x Mn x Sb2 grown by the Sb flux method. The orthorhombic Pnnm structure was confirmed by powder X-ray diffraction (XRD) for the pure and Mn-substituted samples. Their crystal structure parameters were refined using the Rietveld method. The chemical composition was investigated by wavelength-dispersive X-ray spectroscopy (WDX). The solubility limit of Mn in FeSb2 is x max ˜ 0.05 and the lattice constants change monotonically with increasing the actual Mn concentration. A drastic change from semiconducting to metallic electronic transports was found at very low Mn concentration at x ˜ 0.01. Our experimental results and analysis indicate that the substitution of a small amount of Mn changes drastically the electronic state in FeSb2 as well as the Co-substitution does: closing of the narrow gap and emergence of the density of states (DOS) at the Fermi level.

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals.

PubMed

Sarker, Suprovath Kumar; Islam, Md Tarikul; Eckhoff, Grace; Hossain, Mohammad Amir; Qadri, Syeda Kashfi; Muraduzzaman, A K M; Bhuyan, Golam Sarower; Shahidullah, Mohammod; Mannan, Mohammad Abdul; Tahura, Sarabon; Hussain, Manzoor; Akhter, Shahida; Nahar, Nazmun; Shirin, Tahmina; Qadri, Firdausi; Mannoor, Kaiissar

2016-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh.

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals

PubMed Central

Sarker, Suprovath Kumar; Hossain, Mohammad Amir; Qadri, Syeda Kashfi; Muraduzzaman, A. K. M.; Bhuyan, Golam Sarower; Shahidullah, Mohammod; Mannan, Mohammad Abdul; Tahura, Sarabon; Hussain, Manzoor; Akhter, Shahida; Nahar, Nazmun; Shirin, Tahmina; Qadri, Firdausi; Mannoor, Kaiissar

2016-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh. PMID:27880809

Electron spin resonance (ESR) of magnetic sublattices in Sc-substituted barium hexaferrite

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

Díaz-Pardo, Rebeca; Monjaras, Raúl Valenzuela; Bierlich, Silvia

2016-05-15

The partial substitution of Fe{sup 3+} by Sc{sup 3+} in barium hexaferrite has shown to be an effective method to tailor anisotropy for many novel microwave applications. Some basic studies have revealed that this substitution leads to unusual interactions among the magnetic sublattices of the ferrite. In order to investigate these interactions, samples with formula BaSc{sub x}Fe{sub 12-x}O{sub 19} (1 ≤x ≤ 2) were prepared by sintering (1300°C, 6h). After structural characterization by x-ray diffraction, their ferromagnetic resonance spectra were measured in the X-band (9.4 GHz), in the 100-500 K temperature range. For x = 2, a single, broad resonancemore » peak was observed at the low temperatures (103 K), exhibiting a progressive splitting into two peaks for increasing T, to finally coalesce again into a single (paramagnetic) narrow peak at 473 K. These results are interpreted in terms of a substitution of Fe{sup 3+} by Sc{sup 3+} ions in the 4f{sub vi} and 2b sublattices; the diamagnetic cations disrupt the superexchange interactions and produce a splitting of the 12k sublattice (which interacts directly with the 4f{sub vi} sublattice) into two sublattices with different canting angles, and different thermal dependence. As a result, the fraction of the 12k sublattices that are nearest neighbours of substituted 4f{sub vi} sites can behave as an independent sublattice for some temperature ranges. A similar behavior is observed for all the compositions with varying degrees of amplitude, but it is more evident for x = 2. A deconvolution of peaks has been attempted, in order to shed more light into this behavior.« less

Retuning Rieske-type Oxygenases to Expand Substrate Range

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

Mohammadi, Mahmood; Viger, Jean-François; Kumar, Pravindra

2012-09-17

Rieske-type oxygenases are promising biocatalysts for the destruction of persistent pollutants or for the synthesis of fine chemicals. In this work, we explored pathways through which Rieske-type oxygenases evolve to expand their substrate range. BphAE{sub p4}, a variant biphenyl dioxygenase generated from Burkholderia xenovorans LB400 BphAE{sub LB400} by the double substitution T335A/F336M, and BphAE{sub RR41}, obtained by changing Asn{sup 338}, Ile{sup 341}, and Leu{sup 409} of BphAE{sub p4} to Gln{sup 338}, Val{sup 341}, and Phe{sup 409}, metabolize dibenzofuran two and three times faster than BphAE{sub LB400}, respectively. Steady-state kinetic measurements of single- and multiple-substitution mutants of BphAE{sub LB400} showed thatmore » the single T335A and the double N338Q/L409F substitutions contribute significantly to enhanced catalytic activity toward dibenzofuran. Analysis of crystal structures showed that the T335A substitution relieves constraints on a segment lining the catalytic cavity, allowing a significant displacement in response to dibenzofuran binding. The combined N338Q/L409F substitutions alter substrate-induced conformational changes of protein groups involved in subunit assembly and in the chemical steps of the reaction. This suggests a responsive induced fit mechanism that retunes the alignment of protein atoms involved in the chemical steps of the reaction. These enzymes can thus expand their substrate range through mutations that alter the constraints or plasticity of the catalytic cavity to accommodate new substrates or that alter the induced fit mechanism required to achieve proper alignment of reaction-critical atoms or groups.« less

A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization.

PubMed Central

Duquesnoy, P; Sobrier, M L; Duriez, B; Dastot, F; Buchanan, C R; Savage, M O; Preece, M A; Craescu, C T; Blouquit, Y; Goossens, M

1994-01-01

Growth hormone (GH) elicits a variety of biological activities mainly mediated by the GH receptor (GHR), a transmembrane protein that, based on in vitro studies, seemed to function as a homodimer. To test this hypothesis directly, we investigated patients displaying the classic features of Laron syndrome (familial GH resistance characterized by severe dwarfism and metabolic dysfunction), except for the presence of normal binding activity of the plasma GH-binding protein, a molecule that derives from the exoplasmic-coding domain of the GHR gene. In two unrelated families, the same GHR mutation was identified, resulting in the substitution of a highly conserved aspartate residue by histidine at position 152 (D152H) of the exoplasmic domain, within the postulated interface sequence involved in homodimerization. The recombinant mutated receptor protein was correctly expressed at the plasma membrane. It displayed subnormal GH-binding activity, a finding in agreement with the X-ray crystal structure data inferring this aspartate residue outside the GH-binding domain. However, mAb-based studies suggested the critical role of aspartate 152 in the proper folding of the interface area. We show that a recombinant soluble form of the mutant receptor is unable to dimerize, the D152H substitution also preventing the formation of heterodimers of wild-type and mutant molecules. These results provide in vivo evidence that monomeric receptors are inactive and that receptor dimerization is involved in the primary signalling of the GH-associated growth-promoting and metabolic actions. Images PMID:8137822

A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization.

PubMed

Duquesnoy, P; Sobrier, M L; Duriez, B; Dastot, F; Buchanan, C R; Savage, M O; Preece, M A; Craescu, C T; Blouquit, Y; Goossens, M

1994-03-15

Growth hormone (GH) elicits a variety of biological activities mainly mediated by the GH receptor (GHR), a transmembrane protein that, based on in vitro studies, seemed to function as a homodimer. To test this hypothesis directly, we investigated patients displaying the classic features of Laron syndrome (familial GH resistance characterized by severe dwarfism and metabolic dysfunction), except for the presence of normal binding activity of the plasma GH-binding protein, a molecule that derives from the exoplasmic-coding domain of the GHR gene. In two unrelated families, the same GHR mutation was identified, resulting in the substitution of a highly conserved aspartate residue by histidine at position 152 (D152H) of the exoplasmic domain, within the postulated interface sequence involved in homodimerization. The recombinant mutated receptor protein was correctly expressed at the plasma membrane. It displayed subnormal GH-binding activity, a finding in agreement with the X-ray crystal structure data inferring this aspartate residue outside the GH-binding domain. However, mAb-based studies suggested the critical role of aspartate 152 in the proper folding of the interface area. We show that a recombinant soluble form of the mutant receptor is unable to dimerize, the D152H substitution also preventing the formation of heterodimers of wild-type and mutant molecules. These results provide in vivo evidence that monomeric receptors are inactive and that receptor dimerization is involved in the primary signalling of the GH-associated growth-promoting and metabolic actions.

Maple Syrup Urine Disease in Cypriot Families: Identification of Three Novel Mutations and Biochemical Characterization of the p.Thr211Met Mutation in the E1α Subunit

PubMed Central

Georgiou, Theodoros; Chuang, Jacinta L.; Wynn, R. Max; Stylianidou, Goula; Korson, Mark; Chuang, David T.

2009-01-01

We report five mutations, three of them novel, responsible for maple syrup urine disease in four unrelated Cypriot families. The five children studied are the first cases of classic maple syrup urine disease to be reported among Cypriots. The first novel mutation identified is a single-base deletion in exon 6 of the Elα gene (c.718delG), which leads to a frameshift after Ala240 and to a stop codon 89 residues further downstream. The other two novel mutations identified are in the Elβ subunit: a two-base deletion in exon 6, c.662_663delCC, which leads to a frameshift after Ala221 and creates a stop codon 17 residues further downstream, as well as a splice mutation, IVS3[+3]delA, which results in the skipping of exon 3. The two known mutations identified are in the Elα gene: the G > C transversion at the 3′-splice acceptor site, (IVS5-1G > C), which results in the deletion of the entire exon 6, and the missense mutation in exon 5 (c.632C > T), which corresponds to a p.Thr211Met substitution. The p.Thr211Met substitution is located in a potassium-ion pocket in the E1 component required for stability of the bound cofactor thiamine diphosphate. The mutant E1 protein harboring the p.Thr211Met substitution was shown unable to bind thiamine diphosphate, leading to undetectable E1 activity. PMID:19715473

Re-engineering an artificial sweetener: transforming sucralose residuals in water via advanced oxidation.

PubMed

Keen, Olya S; Linden, Karl G

2013-07-02

Sucralose is an artificial sweetener persistently present in wastewater treatment plant effluents and aquatic environments impacted by human activity. It has a potential to accumulate in the water cycle due to its resistance to common water and wastewater treatment processes. This study examined UV/H2O2 advanced oxidation and found that hydroxyl substitution of the chlorine atoms on the sucralose molecule can form a carbohydrate consisting of fructose and sugar alcohol, very similar to environmentally benign sucrose. The second-order reaction rate constant for loss of parent molecule via reaction with hydroxyl radical was determined to be (1.56 ± 0.03)·10(9) M(-1)s(-1). The degradation pathway involves substitution of a single chlorine by a hydroxyl group, with cyclic moiety being a preferential site for initial dechlorination. Further reaction leads to full dechlorination of the molecule, presumably via hydroxyl group substitution as well. No direct photolysis by UV wavelengths above 200 nm was observed. Because of its photostability when exposed to UV wavelengths ≥200 nm, known stability with ozone, limits of quantification by mass spectrometry close to or below environmental concentrations (<5 μg/L) without preconcentration, and otherwise stable nature, sucralose can be used as an in situ hydroxyl radical probe for UV-based and ozone-based AOP processes. As a compound safe for human consumption, sucralose makes a suitable full scale hydroxyl radical probe fit even for drinking water treatment plant applications. Its main drawback as a probe is lack of UV detection and as a result a need for mass spectrometry analysis.

Microsatellite Interruptions Stabilize Primate Genomes and Exist as Population-Specific Single Nucleotide Polymorphisms within Individual Human Genomes

PubMed Central

Ananda, Guruprasad; Hile, Suzanne E.; Breski, Amanda; Wang, Yanli; Kelkar, Yogeshwar; Makova, Kateryna D.; Eckert, Kristin A.

2014-01-01

Interruptions of microsatellite sequences impact genome evolution and can alter disease manifestation. However, human polymorphism levels at interrupted microsatellites (iMSs) are not known at a genome-wide scale, and the pathways for gaining interruptions are poorly understood. Using the 1000 Genomes Phase-1 variant call set, we interrogated mono-, di-, tri-, and tetranucleotide repeats up to 10 units in length. We detected ∼26,000–40,000 iMSs within each of four human population groups (African, European, East Asian, and American). We identified population-specific iMSs within exonic regions, and discovered that known disease-associated iMSs contain alleles present at differing frequencies among the populations. By analyzing longer microsatellites in primate genomes, we demonstrate that single interruptions result in a genome-wide average two- to six-fold reduction in microsatellite mutability, as compared with perfect microsatellites. Centrally located interruptions lowered mutability dramatically, by two to three orders of magnitude. Using a biochemical approach, we tested directly whether the mutability of a specific iMS is lower because of decreased DNA polymerase strand slippage errors. Modeling the adenomatous polyposis coli tumor suppressor gene sequence, we observed that a single base substitution interruption reduced strand slippage error rates five- to 50-fold, relative to a perfect repeat, during synthesis by DNA polymerases α, β, or η. Computationally, we demonstrate that iMSs arise primarily by base substitution mutations within individual human genomes. Our biochemical survey of human DNA polymerase α, β, δ, κ, and η error rates within certain microsatellites suggests that interruptions are created most frequently by low fidelity polymerases. Our combined computational and biochemical results demonstrate that iMSs are abundant in human genomes and are sources of population-specific genetic variation that may affect genome stability. The genome-wide identification of iMSs in human populations presented here has important implications for current models describing the impact of microsatellite polymorphisms on gene expression. PMID:25033203

Effects of scandium substitution on the crystal structure and luminescence properties of LuBO{sub 3}: Ce{sup 3+}

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

Wu, Yuntao, E-mail: caswyt@hotmail.com; Ren, Guohao, E-mail: rgh@mail.sic.ac.cn; Ding, Dongzhou

2012-10-15

The calcite phase of LuBO{sub 3} and ScBO{sub 3} polycrystalline powders were synthesized by solid state reaction method, and the Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce (x=0.2, 0.5, 0.7) single crystals were grown by the Czochralski method. A large composition deviation between the initial polycrystalline powders and final single crystal was confirmed by electron probe micro-analysis. Raman spectroscopy revealed that moderate lattice disorder was induced by scandium substitution. However, based on the single crystal X-ray study, we finally concluded that the crystal structure of lutetium scandium orthoborate still crystallized in the rhombohedral system belonging to R3{sup -}c. Furthermore, the relationship between themore » energies of the five 5d levels of Ce{sup 3+} and the crystalline environment was revealed. The total redshift, total crystal field splitting, and centroid shift of Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce{sup 3+} were calculated based on their VUV excitation spectra. The variations trend of these observed spectroscopic parameters was in accordance with the predicted ones. - Graphical abstract: The crystal structure of Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce is rhombohedral system with R3{sup -}c space group. The relationship between the energies of the five Ce{sup 3+} 5d levels and the crystalline environment is established. Highlights: Black-Right-Pointing-Pointer Moderate lattice disorder is induced by scandium doping. Black-Right-Pointing-Pointer The crystal structure of Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce is rhombohedral system with R3{sup -}c space group. Black-Right-Pointing-Pointer Relationship between energies of Ce{sup 3+} 5d levels and crystalline environment is established. Black-Right-Pointing-Pointer The spectroscopic parameters are experimentally and theoretically calculated.« less

Strain Aging Behavior in NiAl Microalloyed with Interstitial and Substitutional Solutes

NASA Technical Reports Server (NTRS)

Weaver, M. L.; Noebe R. D.; Kaufman, M. J.

1997-01-01

Dynamic strain aging has been investigated in polycrystalline NiAl alloys containing combined additions of interstitial and substitutional impurities. The results indicate that strain aging can be enhanced in polycrystalline alloys containing concentrations of silicon or iron in excess of 0.15 at.% in addition to conventional levels of carbon. This co-doping leads to very dramatic strain aging events, comparable to those typically observed in single crystals. This effect will be discussed with respect to conventional theories of strain aging.

Development of mono- and di-AcO substituted BODIPYs on the boron center.

PubMed

Jiang, Xin-Dong; Zhang, Jian; Furuyama, Taniyuki; Zhao, Weili

2012-01-06

Mono- and di-AcO substituted BODIPYs (1 and 2) were synthesized from TM-BDP. The structures of 1 and 2 were supported by single crystal X-ray analysis. Both 1 and 2 possess a large absorption coefficient, high fluorescence quantum yield, and high light stability. Compound 2 has much improved water solubility which is highly desirable for biological applications. Theoretical calculation supports our observations in X-ray analysis, absorption, and cyclic voltammetry. © 2011 American Chemical Society

Synthesis, characterization and biological activities of semicarbazones and their copper complexes.

PubMed

Venkatachalam, Taracad K; Bernhardt, Paul V; Noble, Chris J; Fletcher, Nicholas; Pierens, Gregory K; Thurecht, Kris J; Reutens, David C

2016-09-01

Substituted semicarbazones/thiosemicarbazones and their copper complexes have been prepared and several single crystal structures examined. The copper complexes of these semicarbazone/thiosemicarbazones were prepared and several crystal structures examined. The single crystal X-ray structure of the pyridyl-substituted semicarbazone showed two types of copper complexes, a monomer and a dimer. We also found that the p-nitrophenyl semicarbazone formed a conventional 'magic lantern' acetate-bridged dimer. Electron Paramagnetic Resonance (EPR) of several of the copper complexes was consistent with the results of single crystal X-ray crystallography. The EPR spectra of the p-nitrophenyl semicarbazone copper complex in dimethylsulfoxide (DMSO) showed the presence of two species, confirming the structural information. Since thiosemicarbazones and semicarbazones have been reported to exhibit anticancer activity, we examined the anticancer activity of several of the derivatives reported in the present study and interestingly only the thiosemicarbazone showed activity while the semicarbazones were not active indicating that introduction of sulphur atom alters the biological profile of these thiosemicarbazones. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective Se-for-S substitution in Cs-bearing uranyl compounds

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

Gurzhiy, Vladislav V., E-mail: vladgeo17@mail.ru; Tyumentseva, Olga S.; Krivovichev, Sergey V.

Phase formation in the mixed sulfate-selenate aqueous system of uranyl nitrate and cesium nitrate has been investigated. Two types of crystalline compounds have been obtained and characterized using a number of experimental (single crystal XRD, FTIR, SEM) and theoretical (information-based complexity calculations, topological analysis) techniques. No miscibility gaps have been observed for Cs{sub 2}[(UO{sub 2}){sub 2}(TO{sub 4}){sub 3}] (T= S, Se), which crystallizes in tetragonal system, P-42{sub 1}m, a =9.616(1)–9.856(2), c =8.105(1)–8.159(1) Å, V =749.6(2)–792.5(3) Å{sup 3}. Nine phases with variable amount of S and Se have been structurally characterized. The structures of the Cs{sub 2}[(UO{sub 2}){sub 2}(TO{sub 4}){sub 3}]more » (T= S, Se) compounds are based upon the [(UO{sub 2}){sub 2}(TO{sub 4}){sub 3}]{sup 2-} layers of corner-sharing uranyl pentagonal bipyramids and TO{sub 4} tetrahedra. The layers contain two types of tetrahedral sites: T1 (3-connected, i.e. having three O atoms shared by adjacent uranyl polyhedra) and T2 (4-connected). The Se-for-S substitution in tetrahedral sites is highly selective with smaller S{sup 6+} cation showing a strong preference for the more tightly bonded T2 site. Crystallization in the pure Se system starts with the formation of Cs{sub 2}[(UO{sub 2})(SeO{sub 4}){sub 2}(H{sub 2}O)](H{sub 2}O) crystals, its subsequent dissolution and formation of Cs{sub 2}[(UO{sub 2}){sub 2}(SeO{sub 4}){sub 3}]. The information-based structural complexity calculations for these two phases support the rule that more topologically complex structures form at the latest stages of crystallization. - Graphical abstract: Nine phases representing the Cs{sub 2}[(UO{sub 2}){sub 2}(TO{sub 4}){sub 3}] (T= S, Se) solid solution series with variable amount of S and Se have been prepared by isothermal evaporation from aqueous solutions and characterized using a number of experimental and theoretical techniques. No immiscibility is observed between the pure sulfate and selenate compounds. The Se-for-S substitution in tetrahedral sites is highly selective with smaller S{sup 6+} cation showing a strong preference for the more tightly bonded 4-connected site. - Highlights: • Single crystals of novel mixed sulfate-selenate uranyl oxysalts were prepared by evaporation method. • Topological analysis and information-based complexity calculations were used for structure description. • The selective Se-for-S substitution was observed. • Evolution of phase formation in the aqueous Cs{sup +}–UO{sub 2}{sup 2+}–SO{sub 4}{sup 2–}–SeO{sub 4}{sup 2–} system was analyzed.« less

Porous single-phase NiTi processed under Ca reducing vapor for use as a bone graft substitute.

PubMed

Bertheville, Bernard

2006-03-01

Porous nickel-titanium alloys (NiTi, nitinol) have recently attracted attention in clinical surgery because they are a very interesting alternative to the more brittle and less machinable conventional porous Ca-based ceramics. The main remaining limitations come from the chemical homogeneity of the as-processed porous nickel-titanium alloys, which always contain undesired secondary Ti- and Ni-rich phases. These are known to weaken the NiTi products, to favor their cavitation corrosion and to decrease their biocompatibility. Elemental nickel must also be avoided because it could give rise to several adverse tissue reactions. Therefore, the synthesis of porous single-phase NiTi alloys by using a basic single-step sintering procedure is an important step towards the processing of safe implant materials. The sintering process used in this work is based on a vapor phase calciothermic reduction operating during the NiTi compound formation. The as-processed porous nickel-titanium microstructure is single-phase and shows a uniformly open pore distribution with porosity of about 53% and pore diameters in the range 20-100 microm. Furthermore, due to the process, fine CaO layers grow on the NiTi outer and inner surfaces, acting as possible promoting agents for the ingrowth of bone cells at the implantation site.

Poly(3-hydroxybutyrate) anabolism in Cupriavidus necator cultivated at various carbon-to-nitrogen ratios: insights from single-cell Raman spectroscopy

NASA Astrophysics Data System (ADS)

Tao, Zhanhua; Zhang, Pengfei; Qin, Zhaojun; Li, Yong-Qing; Wang, Guiwen

2016-09-01

Cupriavidus necator accumulates large amounts of poly(3-hydroxybutyrate) (PHB), a biodegradable substitute for petroleum-based plastics, under certain nutrient conditions. Conventional solvent-extraction-based methods for PHB quantification only obtain average information from cell populations and, thus, mask the heterogeneity among individual cells. Laser tweezers Raman spectroscopy (LTRS) was used to monitor dynamic changes in the contents of PHB, nucleic acids, and proteins in C. necator at the population and single-cell levels when the microorganism cells were cultivated at various carbon-to-nitrogen ratios. The biosynthetic activities of nucleic acids and proteins were maintained at high levels, and only a small amount of PHB was produced when the bacterial cells were cultured under balanced growth conditions. By contrast, the syntheses of nucleic acids and proteins were blocked, and PHB was accumulated in massive amount inside the microbial cells under nitrogen-limiting growth circumstances. Single-cell analysis revealed a relatively high heterogeneity in PHB level at the early stage of the bacterial growth. Additionally, bacterial cells in populations at certain cultivation stages were composed of two or three subpopulations on the basis of their PHB abundance. Overall, LTRS is a reliable single-cell analysis tool that can provide insights into PHB fermentation.

Hyperfine Interactions in the Electron Paramagnetic Resonance Spectra of Point Defects in Wide-Band-Gap Semiconductors

DTIC Science & Technology

2014-09-18

compensation) during growth due to their preferred trivalent charge states. The electron paramagnetic resonance spectrum of the singly ionized chromium ...neutral nitrogen acceptor in ZnO . . . . . . . . . . . . . . . . . . 45 16 Spectrum of the singly ionized chromium acceptor in TiO2 . . . . . . . . . 49...is a single crystal of magnesium oxide that has been doped with chromium . Chromium Cr3+ substitutes for magnesium Mg2+ and creates a paramagnetic

Single step signal group-imidazole labeling of organic phosphate groups under aqueous conditions

DOEpatents

Giese, Roger W.; Wang, Poguang

1996-01-01

Compounds and methods for single step, covalent labeling of the phosphate group of an organic substance under aqueous conditions are described. The labeling compound includes any kind of detectable signal group covalently bound to an imidazole moiety, which can be imidazole or a substituted imidazole. A preferred labeling compound has the formula ##STR1##

Enhancing the performance of single-chambered microbial fuel cell using manganese/palladium and zirconium/palladium composite cathode catalysts.

PubMed

Jadhav, Dipak A; Deshpande, Parag A; Ghangrekar, Makarand M

2017-08-01

Application of ZrO 2 , MnO 2 , palladium, palladium-substituted-zirconium oxide (Zr 0.98 Pd 0.02 O 2 ) and palladium-substituted-manganese oxide (Mn 0.98 Pd 0.02 O 2 ) cathode catalysts in a single-chambered microbial fuel cell (MFC) was explored. The highest power generation (1.28W/m 3 ) was achieved in MFC with Mn 0.98 Pd 0.02 O 2 catalyst, which was higher than that with MnO 2 (0.58W/m 3 ) alone; whereas, MFC having Zr 0.98 Pd 0.02 O 2 catalyzed cathode and non-catalyzed cathode produced powers of 1.02 and 0.23W/m 3 , respectively. Also, low-cost zirconium-palladium-composite showed better catalytic activity and capacitance over ZrO 2 with 20A/m 3 current production and demonstrated its suitability for MFC applications. Cyclic voltammetry analyses showed higher well-defined redox peaks in composite catalysts (Mn/Zr-Pd-C) over other catalyzed MFCs containing MnO 2 or ZrO 2 . Electrochemical behaviour of composite catalysts on cathode showed higher availability of adsorption sites for oxygen reduction and, hence, enhanced the rate of cathodic reactions. Thus, Mn/Zr-Pd-C-based composite catalysts exhibited superior cathodic performance and could be proposed as alternatives to costly Pd-catalyst for field applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

LASER BIOLOGY AND MEDICINE: Application of laser fluorimetry for determining the influence of a single amino-acid substitution on the individual photophysical parameters of a fluorescent form of a fluorescent protein mRFP1

NASA Astrophysics Data System (ADS)

Banishev, A. A.; Vrzheshch, E. P.; Shirshin, E. A.

2009-03-01

Individual photophysical parameters of the chromophore of a fluorescent protein mRFP1 and its two mutants (amino-acid substitution at position 66 - mRFP1/ Q66C and mRFP1/Q66S proteins) are determined. For this purpose, apart from conventional methods of fluorimetry and spectrophotometry, nonlinear laser fluorimetry is used. It is shown that the individual extinction coefficients of the chromophore of proteins correlate (correlation coefficient above 0.9) with the volume of the substituted amino-acid residue at position 66 (similar to the positions of the absorption, fluorescence excitation and emission maxima).

Accounting for substitution and spatial heterogeneity in a labelled choice experiment.

PubMed

Lizin, S; Brouwer, R; Liekens, I; Broeckx, S

2016-10-01

Many environmental valuation studies using stated preferences techniques are single-site studies that ignore essential spatial aspects, including possible substitution effects. In this paper substitution effects are captured explicitly in the design of a labelled choice experiment and the inclusion of different distance variables in the choice model specification. We test the effect of spatial heterogeneity on welfare estimates and transfer errors for minor and major river restoration works, and the transferability of river specific utility functions, accounting for key variables such as site visitation, spatial clustering and income. River specific utility functions appear to be transferable, resulting in low transfer errors. However, ignoring spatial heterogeneity increases transfer errors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

PubMed Central

Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

2015-01-01

ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses. PMID:25609810

Dynamical simulation of electron transfer processes in self-assembled monolayers at metal surfaces using a density matrix approach.

PubMed

Prucker, V; Bockstedte, M; Thoss, M; Coto, P B

2018-03-28

A single-particle density matrix approach is introduced to simulate the dynamics of heterogeneous electron transfer (ET) processes at interfaces. The characterization of the systems is based on a model Hamiltonian parametrized by electronic structure calculations and a partitioning method. The method is applied to investigate ET in a series of nitrile-substituted (poly)(p-phenylene)thiolate self-assembled monolayers adsorbed at the Au(111) surface. The results show a significant dependence of the ET on the orbital symmetry of the donor state and on the molecular and electronic structure of the spacer.

Strategy for an Extensible Microcomputer-Based Mumps System for Private Practice

PubMed Central

Walters, Richard F.; Johnson, Stephen L.

1979-01-01

A macro expander technique has been adopted to generate a machine independent single user version of ANSI Standard MUMPS running on an 8080 Microcomputer. This approach makes it possible to have the medically oriented MUMPS language available on inexpensive systems suitable for small group practice settings. Substitution of another macro expansion set allows the same interpreter to be implemented on another computer, thereby providing compatibility with comparable or larger scale systems. Furthermore, since the global file handler can be separated from the interpreter, this approach permits development of a distributed MUMPS system with no change in applications software.

Structural and spectral comparisons between isomeric benzisothiazole and benzothiazole based aromatic heterocyclic dyes

NASA Astrophysics Data System (ADS)

Wang, Yin-Ge; Wang, Yue-Hua; Tao, Tao; Qian, Hui-Fen; Huang, Wei

2015-09-01

A pair of isomeric heterocyclic compounds, namely 3-amino-5-nitro-[2,1]-benzisothiazole and 2-amino-6-nitrobenzothiazole, are used as the diazonium components to couple with two N-substituted 4-aminobenzene derivatives. As a result, two pairs of isomeric aromatic heterocyclic azo dyes have been produced and they are structurally and spectrally characterized and compared including single-crystal structures, electronic spectra, solvatochromism and reversible acid-base discoloration, thermal stability and theoretically calculations. It is concluded that both benzisothiazole and benzothiazole based dyes show planar molecular structures and offset π-π stacking interactions, solvatochromism and reversible acid-base discoloration. Furthermore, benzisothiazole based aromatic heterocyclic dyes exhibit higher thermal stability, larger solvatochromic effects and maximum absorption wavelengths than corresponding benzothiazole based ones, which can be explained successfully by the differences of their calculated isomerization energy, dipole moment and molecular band gaps.

A Rapid Method for Optimizing Running Temperature of Electrophoresis through Repetitive On-Chip CE Operations

PubMed Central

Kaneda, Shohei; Ono, Koichi; Fukuba, Tatsuhiro; Nojima, Takahiko; Yamamoto, Takatoki; Fujii, Teruo

2011-01-01

In this paper, a rapid and simple method to determine the optimal temperature conditions for denaturant electrophoresis using a temperature-controlled on-chip capillary electrophoresis (CE) device is presented. Since on-chip CE operations including sample loading, injection and separation are carried out just by switching the electric field, we can repeat consecutive run-to-run CE operations on a single on-chip CE device by programming the voltage sequences. By utilizing the high-speed separation and the repeatability of the on-chip CE, a series of electrophoretic operations with different running temperatures can be implemented. Using separations of reaction products of single-stranded DNA (ssDNA) with a peptide nucleic acid (PNA) oligomer, the effectiveness of the presented method to determine the optimal temperature conditions required to discriminate a single-base substitution (SBS) between two different ssDNAs is demonstrated. It is shown that a single run for one temperature condition can be executed within 4 min, and the optimal temperature to discriminate the SBS could be successfully found using the present method. PMID:21845077

Single-Stranded γPNAs for In Vivo Site-Specific Genome Editing via Watson-Crick Recognition

PubMed Central

Bahal, Raman; Quijano, Elias; McNeer, Nicole Ali; Liu, Yanfeng; Bhunia, Dinesh C.; López-Giráldez, Francesco; Fields, Rachel J.; Saltzman, W. Mark; Ly, Danith H.; Glazer, Peter M.

2014-01-01

Triplex-forming peptide nucleic acids (PNAs) facilitate gene editing by stimulating recombination of donor DNAs within genomic DNA via site-specific formation of altered helical structures that further stimulate DNA repair. However, PNAs designed for triplex formation are sequence restricted to homopurine sites. Herein we describe a novel strategy where next generation single-stranded gamma PNAs (γPNAs) containing miniPEG substitutions at the gamma position can target genomic DNA in mouse bone marrow at mixed-sequence sites to induce targeted gene editing. In addition to enhanced binding, γPNAs confer increased solubility and improved formulation into poly(lactic-co-glycolic acid) (PLGA) nanoparticles for efficient intracellular delivery. Single-stranded γPNAs induce targeted gene editing at frequencies of 0.8% in mouse bone marrow cells treated ex vivo and 0.1% in vivo via IV injection, without detectable toxicity. These results suggest that γPNAs may provide a new tool for induced gene editing based on Watson-Crick recognition without sequence restriction. PMID:25174576

Single-stranded γPNAs for in vivo site-specific genome editing via Watson-Crick recognition.

PubMed

Bahal, Raman; Quijano, Elias; McNeer, Nicole A; Liu, Yanfeng; Bhunia, Dinesh C; Lopez-Giraldez, Francesco; Fields, Rachel J; Saltzman, William M; Ly, Danith H; Glazer, Peter M

2014-01-01

Triplex-forming peptide nucleic acids (PNAs) facilitate gene editing by stimulating recombination of donor DNAs within genomic DNA via site-specific formation of altered helical structures that further stimulate DNA repair. However, PNAs designed for triplex formation are sequence restricted to homopurine sites. Herein we describe a novel strategy where next generation single-stranded gamma PNAs (γPNAs) containing miniPEG substitutions at the gamma position can target genomic DNA in mouse bone marrow at mixed-sequence sites to induce targeted gene editing. In addition to enhanced binding, γPNAs confer increased solubility and improved formulation into poly(lactic-co-glycolic acid) (PLGA) nanoparticles for efficient intracellular delivery. Single-stranded γPNAs induce targeted gene editing at frequencies of 0.8% in mouse bone marrow cells treated ex vivo and 0.1% in vivo via IV injection, without detectable toxicity. These results suggest that γPNAs may provide a new tool for induced gene editing based on Watson-Crick recognition without sequence restriction.

A single point mutation in Tomato spotted wilt virus NSs protein is sufficient to overcome Tsw-gene-mediated resistance in pepper.

PubMed

Almási, Asztéria; Nemes, Katalin; Csömör, Zsófia; Tóbiás, István; Palkovics, László; Salánki, Katalin

2017-06-01

The nonstructural protein (NSs) of Tomato spotted wilt virus (TSWV) was previously identified as an avirulence determinant for Tsw-based resistance on pepper. The NSs of wild-type (WT) and resistance-breaking (RB) TSWV strains isolated in Hungary had only two amino acid substitutions (104, 461). We have analysed the ability of the NSs and their point mutant variants to trigger Tsw-mediated hypersensitive responses and RNA silencing suppressor (RSS) activity in patch assays. We identified a single amino acid change at position 104 (T-A) that was responsible for the necrosis induction or loss, while a significant difference was not detected in the RSS activity of the two parental strains. We have successfully complemented the infection of the WT strain on resistant pepper cultivar with the infectious S RNA transcript of the RB strain and the WT-T104A point mutant. Our work provides direct evidence that a single amino acid change can induce an RB phenotype.

Photoinduced electron-transfer in perylenediimide triphenylamine-based dendrimers: single photon timing and femtosecond transient absorption spectroscopy.

PubMed

Fron, Eduard; Pilot, Roberto; Schweitzer, Gerd; Qu, Jianqiang; Herrmann, Andreas; Müllen, Klaus; Hofkens, Johan; Van der Auweraer, Mark; De Schryver, Frans C

2008-05-01

The excited state dynamics of two generations perylenediimide chromophores substituted in the bay area with dendritic branches bearing triphenylamine units as well as those of the respective reference compounds are investigated. Using single photon timing and multi-pulse femtosecond transient absorption experiments a direct proof of a reversible charge transfer occurring from the peripheral triphenylamine to the electron acceptor perylenediimide core is revealed. Femtosecond pump-dump-probe experiments provide evidence for the ground state dynamics by populating excited vibronic levels. It is found by the means of both techniques that the rotational isomerization of the dendritic branches occurs on a time scale that ranges up to 1 ns. This time scale of the isomerization depends on the size of the dendritic arms and is similar both in the ground and excited state.

Anisotropic upper critical fields up to 63 T in CaKFe 4As 4 single crystals

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

Kong, T.; Balakirev, Fedor Fedorovich; Meier, W. R.

2017-02-13

The discovery of Fe-based superconductors (FBS) has intensified research on mechanisms of hightemperature superconductivity as well as searches for materials with higher superconducting transition temperatures, Tc. Among many different classes of FBS, the so called “122” family is one of the most well studied systems. However, superconductivity in “122” systems is often stabilized via chemical substitution, which inevitably invites chemical disorder. Recently, a new compound, CaKFe 4As 4, with a well ordered structure that is essentially composed of alternating “122” layers, was discovered with a T c of 35 K. We were able to perform the first single crystal studymore » and measured the anisotropic upper critical fields, H c2, up to 63 T.« less

Asymmetric mutations in the tetrameric R67 dihydrofolate reductase reveal high tolerance to active-site substitutions.

PubMed

Ebert, Maximilian C C J C; Morley, Krista L; Volpato, Jordan P; Schmitzer, Andreea R; Pelletier, Joelle N

2015-04-01

Type II R67 dihydrofolate reductase (DHFR) is a bacterial plasmid-encoded enzyme that is intrinsically resistant to the widely-administered antibiotic trimethoprim. R67 DHFR is genetically and structurally unrelated to E. coli chromosomal DHFR and has an unusual architecture, in that four identical protomers form a single symmetrical active site tunnel that allows only one substrate binding/catalytic event at any given time. As a result, substitution of an active-site residue has as many as four distinct consequences on catalysis, constituting an atypical model of enzyme evolution. Although we previously demonstrated that no single residue of the native active site is indispensable for function, library selection here revealed a strong bias toward maintenance of two native protomers per mutated tetramer. A variety of such "half-native" tetramers were shown to procure native-like catalytic activity, with similar KM values but kcat values 5- to 33-fold lower, illustrating a high tolerance for active-site substitutions. The selected variants showed a reduced thermal stability (Tm ∼12°C lower), which appears to result from looser association of the protomers, but generally showed a marked increase in resilience to heat denaturation, recovering activity to a significantly greater extent than the variant with no active-site substitutions. Our results suggest that the presence of two native protomers in the R67 DHFR tetramer is sufficient to provide native-like catalytic rate and thus ensure cellular proliferation. © 2014 The Protein Society.

Chemical substitution study on magnetism and superconductivity in Ce1-xSmxCoIn5

NASA Astrophysics Data System (ADS)

Jang, Sooyoung; White, B. D.; Yazici, D.; Wong, A. S.; Maple, M. B.

2015-03-01

We have investigated the system Ce1-xSmxCoIn5 (0 < x < 1) by means of x-ray diffraction, electrical resistivity, specific heat, and magnetization measurements. We observe a crossover from a coherent Kondo lattice exhibiting superconductivity to a single-ion impurity Kondo effect coexisting with magnetic order on the Sm-rich side of the phase diagram. The superconducting transition temperature, Tc, and Kondo lattice coherence temperature, Tcoh, are suppressed near x ~ 0.2 and x ~ 0.5, respectively, which is consistent with the effect of substitution with other rare-earth (RE) ions on CeCoIn5. After Tcoh is suppressed to 0 K, a single-ion impurity Kondo effect is observed for 0.5 < x <= 0.85. The compound SmCoIn5 exhibits three distinct magnetic phase transitions at roughly 8, 10, and 12 K, which are presumably associated with magnetic order; similar features are observed in the related compound SmIn3. These transition temperatures are gradually suppressed by Ce substitution and completely vanish near x ~ 0.2. We establish the phase diagram of the system Ce1-xSmxCoIn5 and compare our results with those obtained from chemical substitution studies of CeCoIn5 involving other RE ions. Research at UCSD was supported by the U.S. Department of Energy, Office of Basic Energy Science, Division of Material Science and Engineering under Grant No. DE-FG02-04-ER46105.

Tunable ferromagnetic resonance in La-Co substituted barium hexaferrites at millimeter wave frequencies

NASA Astrophysics Data System (ADS)

Korolev, Konstantin A.; Wu, Chuanjian; Yu, Zhong; Sun, Ke; Afsar, Mohammed N.; Harris, Vincent G.

2018-05-01

Transmittance measurements have been performed on La-Co substituted barium hexaferrites in millimeter waves. Broadband millimeter-wave measurements have been carried out using the free space quasi-optical spectrometer, equipped with a set of high power backward wave oscillators covering the frequency range of 30 - 120 GHz. Strong absorption zones have been observed in the millimeter-wave transmittance spectra of all La-Co substituted barium hexaferrites due to the ferromagnetic resonance. Linear shift of ferromagnetic resonance frequency as functions of La-Co substitutions have been found. Real and imaginary parts of dielectric permittivity of La-Co substituted barium hexaferrites have been calculated using the analysis of recorded high precision transmittance spectra. Frequency dependences of magnetic permeability of La-Co substituted barium hexaferrites, as well as saturation magnetization and anisotropy field have been determined based on Schlömann's theory for partially magnetized ferrites. La-Co substituted barium hexaferrites have been further investigated by DC magnetization to assess magnetic behavior and compare with millimeter wave data. Consistency of saturation magnetization determined independently by both millimeter wave absorption and DC magnetization have been found for all La-Co substituted barium hexaferrites. These materials seem to be quite promising as tunable millimeter wave absorbers, filters, circulators, based on the adjusting of their substitution parameters.

Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions.

PubMed

Kelly, Jarod C; Sullivan, John L; Burnham, Andrew; Elgowainy, Amgad

2015-10-20

This study examines the vehicle-cycle and vehicle total life-cycle impacts of substituting lightweight materials into vehicles. We determine part-based greenhouse gas (GHG) emission ratios by collecting material substitution data and evaluating that alongside known mass-based GHG ratios (using and updating Argonne National Laboratory's GREET model) associated with material pair substitutions. Several vehicle parts are lightweighted via material substitution, using substitution ratios from a U.S. Department of Energy report, to determine GHG emissions. We then examine fuel-cycle GHG reductions from lightweighting. The fuel reduction value methodology is applied using FRV estimates of 0.15-0.25, and 0.25-0.5 L/(100km·100 kg), with and without powertrain adjustments, respectively. GHG breakeven values are derived for both driving distance and material substitution ratio. While material substitution can reduce vehicle weight, it often increases vehicle-cycle GHGs. It is likely that replacing steel (the dominant vehicle material) with wrought aluminum, carbon fiber reinforced plastic (CRFP), or magnesium will increase vehicle-cycle GHGs. However, lifetime fuel economy benefits often outweigh the vehicle-cycle, resulting in a net total life-cycle GHG benefit. This is the case for steel replaced by wrought aluminum in all assumed cases, and for CFRP and magnesium except for high substitution ratio and low FRV.

Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.

PubMed

Ruiz, Federico M; Scholz, Barbara A; Buzamet, Eliza; Kopitz, Jürgen; André, Sabine; Menéndez, Margarita; Romero, Antonio; Solís, Dolores; Gabius, Hans-Joachim

2014-03-01

Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence for association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically to rheumatoid arthritis, we here initiate the study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. We apply a strategically combined set of structural and cell biological techniques for comparing properties of the wild-type and variant proteins. The overall hydrodynamic behavior of the full-length protein and of the separate N-domain is not noticeably altered, but displacements in the F0 β-strand of the β-sandwich fold in the N-domain are induced, as evidenced by protein crystallography. Analysis of thermal stability by circular dichroism spectroscopy revealed perceptible differences for the full-length proteins, pointing to an impact of the substitution beyond the N-domain. In addition, small differences in thermodynamic parameters of carbohydrate binding are detected. On the level of two types of tumor cells, characteristics of binding appeared rather similar. In further comparison of the influence on proliferation, the variant proved to be more active as growth regulator in the six tested lines of neuroblastoma, erythroleukemia and colon adenocarcinoma. The seemingly subtle structural change identified here thus has functional implications in vitro, encouraging further analysis in autoimmune regulation and, in a broad context, in work with other natural single-site variants, using the documented combined strategy. The atomic coordinates and structure factors (codes 4BMB, 4BME) have been deposited in the Protein Data Bank. © 2014 FEBS.

Unraveling the Complex Delithiation Mechanisms of Olivine-Type Cathode Materials, LiFe x Co 1–x PO 4

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

Strobridge, Fiona C.; Liu, Hao; Leskes, Michal

2016-06-14

The delithiation mechanisms occurring within the olivine-type class of cathode materials for Li-ion batteries have received considerable attention owing to the good capacity retention at high rates for LiFePO4. A comprehensive mechanistic study of the (de)lithiation reactions that occur when the substituted olivine-type cathode materials LiFexCo1-xPO4 (x = 0, 0.05, 0.125, 0.25, 0.5, 0.75, 0.875, 0.95 and 1) are electrochemically cycled is reported here, using in situ X-ray diffraction (XRD) data. On the first charge, two intermediate phases are observed and identified: Li1-x(Fe3+)x(Co2+)1- xPO4 for 0 < x < 1 (i.e. after oxidation of Fe2+ => Fe3+) and Li2/3FexCo1-xPO4 formore » 0 ≤ x ≤ 0.5 (i.e. the Co-majority materials). For the Fe-rich materials, we study how nonequilibrium, single-phase mechanisms that occur discretely in single particles, as observed for LiFePO4 at high rates, is affected by Co substitution. In the Co-majority materials, a two-phase mechanism with a coherent interface is observed, as was seen in LiCoPO4, and we discuss how it is manifested in the XRD patterns. We then compare the nonequilibrium, single-phase mechanism with the bulk single-phase and the coherent interface two-phase mechanisms. Despite the apparent differences between these mechanisms, we discuss how they are related and interconverted as a function of Fe/Co substitution and the potential implications for the electrochemistry of this system.« less

Structural, morphological and electrical properties of Sn-substituted Ni-Zn ferrites synthesized by double sintering technique

NASA Astrophysics Data System (ADS)

Ali, M. A.; Uddin, M. M.; Khan, M. N. I.; Chowdhury, F.-U.-Z.; Haque, S. M.

2017-02-01

The Sn-substituted Ni-Zn ferrites, (0.0≤x≤0.30), have been synthesized by the standard double sintering technique from the oxide nanopowders of Ni, Zn, Fe and Sn. The structural and electrical properties have been investigated by the X-ray diffraction (XRD), scanning electron microscopy (SEM), DC resistivity and dielectric measurements. From XRD data, the single cubic spinel phase has been confirmed for x≤0.1, whereas for x>0.1 an extra intermediate phase has been detected along with the cubic spinel phase of Ni-Zn ferrite. The grain size is increased due to Sn substitution in Ni-Zn ferrites. DC resistivity as a function of temperature has been measured by two probe method. The semiconducting nature has been found operative in the samples. The DC resistivity was found to decrease whilst the dielectric constant increased with increasing Sn content in Ni-Zn ferrites. The unusual behavior of the dielectric loss factor of the ferrites was explained by the Rezlescu model. The electrical relaxation of the ferrites has been studied in terms of electric modulus formalism and the time for dielectric relaxation was calculated. The contribution of grain resistance has been studied from the Cole-Cole plot. The suitability to use the as prepared samples in the miniaturized memory devices based capacitive components or energy storage principles are confirmed from the values of dielectric constant.

Central online hemodiafiltration in Japan: management of water quality and practice.

PubMed

Yamashita, Akihiro C; Sato, Takashi

2009-01-01

Hemodiafiltration (HDF) includes a variety of technologies and preparation of ultrapure dialysis fluid has made it possible to perform online HDF and its extensive alternatives. According to current statistics, 5.8% of ESRD patients are treated with HDF in Japan. The majority of these HDF treatments are performed using the central dialysis fluid delivery system (CDDS), this is because most Japanese clinicians and researchers consider that with CDDS it is easier to prepare substitution fluid; moreover, CDDS has economical advantages against single-patient dialysis machine (SPDM)-based counterparts. The water quality at each patient station (dialysis console) is regularly validated by bacterial culture (colony-forming units) and by measuring endotoxin concentration (ET). Since ET measurement takes much less time than bacterial culture, ET is often used as an indicator to verify the water quality for online use. Dialysis fluid with ET below the detection level (usually <0.001 EU/ml) is used for online substitution. In CDDS online HDF, since dialysis clinics must prepare not only the dialysis fluid but also the substitution fluid, they need to satisfy almost the same requirements as pharmaceutical water treatment factories do. The Japanese Society for Dialysis Therapy (JSDT) together with the Japanese Society for Hemodiafiltration (JS-HDF) is now preparing guidelines to meet all these necessary requirements on a worldwide basis. (c) 2009 S. Karger AG, Basel.

An ab initio mechanism for efficient population of triplet states in cytotoxic sulfur substituted DNA bases: the case of 6-thioguanine.

PubMed

Martínez-Fernández, Lara; González, Leticia; Corral, Inés

2012-02-18

The deactivation mechanism of the cytotoxic 6-thioguanine, the 6-sulfur-substituted analogue of the canonical DNA base, is unveiled by ab initio calculations. Oxygen-by-sulfur substitution leads to efficient population of triplet states-the first step for generating singlet oxygen-which is responsible for its cytotoxicity. This journal is © The Royal Society of Chemistry 2012

Effect of Chlorine Substitution on Sulfide Reactivity with OH Radicals

DTIC Science & Technology

2008-09-01

Single point energy: MP2/6-311+G(3df,2p) (LRG) • Zero Point Energy from a vibrational frequency analysis: MP2/6-31++G** ( ZPE ) • Extrapolated energy...E(QCI) + E(LARG) – E(SML) + ZPE • Characterize the TS • Use a three-point fit methodology – fit a harmonic potential to three CCSD single point

Single crystal growth and characterization of kagomé-lattice shandites Co3Sn2-xInxS2

NASA Astrophysics Data System (ADS)

Kassem, Mohamed A.; Tabata, Yoshikazu; Waki, Takeshi; Nakamura, Hiroyuki

2015-09-01

Single crystals of the shandite-type half metallic ferromagnet Co3Sn2S2, and its In-substituted compounds, Co3Sn2-xInxS2 (0

Optimized alumina coagulants for water treatment

DOEpatents

Nyman, May D [Albuquerque, NM; Stewart, Thomas A [Albuquerque, NM

2012-02-21

Substitution of a single Ga-atom or single Ge-atom (GaAl.sub.12 and GeAl.sub.12 respectively) into the center of an aluminum Keggin polycation (Al.sub.13) produces an optimal water-treatment product for neutralization and coagulation of anionic contaminants in water. GaAl.sub.12 consistently shows .about.1 order of magnitude increase in pathogen reduction, compared to Al.sub.13. At a concentration of 2 ppm, GaAl.sub.12 performs equivalently to 40 ppm alum, removing .about.90% of the dissolved organic material. The substituted GaAl.sub.12 product also offers extended shelf-life and consistent performance. We also synthesized a related polyaluminum chloride compound made of pre-hydrolyzed dissolved alumina clusters of [GaO.sub.4Al.sub.12(OH).sub.24(H.sub.2O).sub.12].sup.7+.

NBOMe and 2C substitute phenylethylamine exposures reported to the National Poison Data System.

PubMed

Srisuma, Sahaphume; Bronstein, Alvin C; Hoyte, Christopher O

2015-01-01

Hallucinogenic designer drugs, especially NBOMe and the 2C substitute phenylethylamine series, have been increasing ubiquitous in past years. The purpose of this study is to characterize and compare clinical features of NBOMe and 2C exposures in humans. This is a retrospective cohort study of all single agent exposures to NBOMe and 2C substitute phenylethlamine reported to the National Poison Data System (NPDS) from 1st September 2012 to 30th September 2014. Over the study period, there were a total 341 cases including 148 NBOMe exposures and 193 2C exposures. The majority cases involved men (73.9%); median age was 18 years (Interquartile-range, 16-21). Similar clinical effects were reported in both groups including tachycardia (45.2%), agitation/irritable (44.3%), hallucination/delusion (32.0%), confusion (19.1%) and hypertension (18.5%). There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe exposures (40.5%, 8.8% and 50.0%respectively) than those of 2C exposures (25.4%, 3.1%, and 32.6% respectively). There were 2.3% death; no difference between two groups. The higher rate of symptoms in NBOMe is consistent with the higher 5HT2A agonistic effects of NBOMe described in both molecular and animal studies. Common clinical effects of NBOMe and 2C exposures were tachycardia, agitation/irritable, hallucination/delusion, confusion, and hypertension. There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe.

The effect of fluorine substitutions on the refractive index properties for π-conjugated calamitic nematic materials

NASA Astrophysics Data System (ADS)

Arakawa, Yuki; Tsuji, Hideto

2017-06-01

In order to reveal the effect of fluorine substitutions on the refractive index properties for calamitic nematic materials, we carried out a comparative study with respect to non-fluorinated and two types of laterally fluorinated 1,4-bis[4-(hexyloxy)phenyl]ethynylbenzene molecules. Phase transition behaviours were investigated by differential scanning calorimetry and polarised optical microscopy. Additionally, extraordinary and ordinary refractive index and birefringence were evaluated from each single component system. All the analogues exhibited high birefringence values beyond 0.3 at 550 nm, of which an analogue with a fluorine substitution at the central benzene ring showed the highest Δn-value of 0.43. With respect to an analogue with the highest level of fluorination, Δn as well as ne and no values were declined due to decreased order parameter and diluted molecular density. Not only the mesomorphic behaviours but also optical properties strongly relied on the manner of fluorine substitution including the number and position.

Alkaline earth metallocenes coordinated with ester pendants: synthesis, structural characterization, and application in metathesis reactions.

PubMed

Li, Heng; Zhang, Wen-Xiong; Xi, Zhenfeng

2013-09-16

A variety of ester-substituted cyclopentadiene derivatives have been synthesized by one-pot reactions of 1,4-dilithio-1,3-butadienes, CO, and acid chlorides. Direct deprotonation of the ester-substituted cyclopentadienes with Ae[N(SiMe3 )2 ]2 (Ae=Ca, Sr, Ba) efficiently generated members of a new class of heavier alkaline earth (Ca, Sr, Ba) metallocenes in good to excellent yields. Single-crystal X-ray structural analysis demonstrated that these heavier alkaline earth metallocenes incorporated two intramolecularly coordinated ester pendants and multiply-substituted cyclopentadienyl ligands. The corresponding transition metal metallocenes, such as ferrocene derivatives and half-sandwich cyclopentadienyl tricarbonylrhenium complexes, could be generated highly efficiently by metathesis reactions. The multiply-substituted cyclopentadiene ligands bearing an ester pendant, and the corresponding heavier alkaline earth and transition-metal metallocenes, may have further applications in coordination chemistry, organometallic chemistry, and organic synthesis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Web service substitution method based on service cluster nets

NASA Astrophysics Data System (ADS)

Du, YuYue; Gai, JunJing; Zhou, MengChu

2017-11-01

Service substitution is an important research topic in the fields of Web services and service-oriented computing. This work presents a novel method to analyse and substitute Web services. A new concept, called a Service Cluster Net Unit, is proposed based on Web service clusters. A service cluster is converted into a Service Cluster Net Unit. Then it is used to analyse whether the services in the cluster can satisfy some service requests. Meanwhile, the substitution methods of an atomic service and a composite service are proposed. The correctness of the proposed method is proved, and the effectiveness is shown and compared with the state-of-the-art method via an experiment. It can be readily applied to e-commerce service substitution to meet the business automation needs.

A leucine repeat motif in AbiA is required for resistance of Lactococcus lactis to phages representing three species.

PubMed

Dinsmore, P K; O'Sullivan, D J; Klaenhammer, T R

1998-05-28

The abiA gene encodes an abortive bacteriophage infection mechanism that can protect Lactococcus species from infection by a variety of bacteriophages including three unrelated phage species. Five heptad leucine repeats suggestive of a leucine zipper motif were identified between residues 232 and 266 in the predicted amino acid sequence of the AbiA protein. The biological role of residues in the repeats was investigated by incorporating amino acid substitutions via site-directed mutagenesis. Each mutant was tested for phage resistance against three phages, phi 31, sk1, and c2, belonging to species P335, 936, and c2, respectively. The five residues that comprise the heptad repeats were designated L234, L242, A249, L256, and L263. Three single conservative mutations of leucine to valine in positions L235, L242, and L263 and a double mutation of two leucines (L235 and L242) to valines did not affect AbiA activity on any phages tested. Non-conservative single substitutions of charged amino acids for three of the leucines (L235, L242, and L256) virtually eliminated AbiA activity on all phages tested. Substitution of the alanine residue in the third repeat (A249) with a charged residue did not affect AbiA activity. Replacement of L242 with an alanine elimination phage resistance against phi 31, but partial resistance to sk1 and c2 remained. Two single proline substitutions for leucines L242 and L263 virtually eliminated AbiA activity against all phages, indicating that the predicted alpha-helical structure of this region is important. Mutations in an adjacent region of basic amino acids had various effects on phage resistance, suggesting that these basic residues are also important for AbiA activity. This directed mutagenesis analysis of AbiA indicated that the leucine repeat structure is essential for conferring phage resistance against three species of lactococcal bacteriophages.

Basecalling with LifeTrace

PubMed Central

Walther, Dirk; Bartha, Gábor; Morris, Macdonald

2001-01-01

A pivotal step in electrophoresis sequencing is the conversion of the raw, continuous chromatogram data into the actual sequence of discrete nucleotides, a process referred to as basecalling. We describe a novel algorithm for basecalling implemented in the program LifeTrace. Like Phred, currently the most widely used basecalling software program, LifeTrace takes processed trace data as input. It was designed to be tolerant to variable peak spacing by means of an improved peak-detection algorithm that emphasizes local chromatogram information over global properties. LifeTrace is shown to generate high-quality basecalls and reliable quality scores. It proved particularly effective when applied to MegaBACE capillary sequencing machines. In a benchmark test of 8372 dye-primer MegaBACE chromatograms, LifeTrace generated 17% fewer substitution errors, 16% fewer insertion/deletion errors, and 2.4% more aligned bases to the finished sequence than did Phred. For two sets totaling 6624 dye-terminator chromatograms, the performance improvement was 15% fewer substitution errors, 10% fewer insertion/deletion errors, and 2.1% more aligned bases. The processing time required by LifeTrace is comparable to that of Phred. The predicted quality scores were in line with observed quality scores, permitting direct use for quality clipping and in silico single nucleotide polymorphism (SNP) detection. Furthermore, we introduce a new type of quality score associated with every basecall: the gap-quality. It estimates the probability of a deletion error between the current and the following basecall. This additional quality score improves detection of single basepair deletions when used for locating potential basecalling errors during the alignment. We also describe a new protocol for benchmarking that we believe better discerns basecaller performance differences than methods previously published. PMID:11337481

The Fate of Arabidopsis thaliana Homeologous CNSs and Their Motifs in the Paleohexaploid Brassica rapa

PubMed Central

Subramaniam, Sabarinath; Wang, Xiaowu; Freeling, Michael; Pires, J. Chris

2013-01-01

Following polyploidy, duplicate genes are often deleted, and if they are not, then duplicate regulatory regions are sometimes lost. By what mechanism is this loss and what is the chance that such a loss removes function? To explore these questions, we followed individual Arabidopsis thaliana–A. thaliana conserved noncoding sequences (CNSs) into the Brassica ancestor, through a paleohexaploidy and into Brassica rapa. Thus, a single Brassicaceae CNS has six potential orthologous positions in B. rapa; a single Arabidopsis CNS has three potential homeologous positions. We reasoned that a CNS, if present on a singlet Brassica gene, would be unlikely to lose function compared with a more redundant CNS, and this is the case. Redundant CNSs go nondetectable often. Using this logic, each mechanism of CNS loss was assigned a metric of functionality. By definition, proved deletions do not function as sequence. Our results indicated that CNSs that go nondetectable by base substitution or large insertion are almost certainly still functional (redundancy does not matter much to their detectability frequency), whereas those lost by inferred deletion or indels are approximately 75% likely to be nonfunctional. Overall, an average nondetectable, once-redundant CNS more than 30 bp in length has a 72% chance of being nonfunctional, and that makes sense because 97% of them sort to a molecular mechanism with “deletion” in its description, but base substitutions do cause loss. Similarly, proved-functional G-boxes go undetectable by deletion 82% of the time. Fractionation mutagenesis is a procedure that uses polyploidy as a mutagenic agent to genetically alter RNA expression profiles, and then to construct testable hypotheses as to the function of the lost regulatory site. We show fractionation mutagenesis to be a “deletion machine” in the Brassica lineage. PMID:23493633

Single base substitution causing the fragrant phenotype and development of a type-specific marker in aromatic coconut (Cocos nucifera).

PubMed

Vongvanrungruang, A; Mongkolsiriwatana, C; Boonkaew, T; Sawatdichaikul, O; Srikulnath, K; Peyachoknagul, S

2016-09-19

The fragrance gene, betaine aldehyde dehydrogenase 2 (Badh2), has been well studied in many plant species. The objectives of this study were to clone Badh2 and compare the sequences between aromatic and non-aromatic coconuts. The complete coding region was cloned from cDNA of both aromatic and non-aromatic coconuts. The nucleotide sequences were highly homologous to Badh2 genes of other plants. Badh2 consisted of a 1512-bp open reading frame encoding 503 amino acids. A single nucleotide difference between aromatic and non-aromatic coconuts resulted in the conversion of alanine (non-aromatic) to proline (aromatic) at position 442, which was the substrate binding site of BADH2. The ring side chain of proline could destabilize the structure leading to a non-functional enzyme. Badh2 genomic DNA was cloned from exon 1 to 4, and from exon 5 to 15 from the two coconut types, except for intron 4 that was very long. The intron sequences of the two coconut groups were highly homologous. No differences in Badh2 expression were found among the tissues of aromatic coconut or between aromatic and non-aromatic coconuts. The amino acid sequences of BADH2 from coconut and other plants were compared and the genetic relationship was analyzed using MEGA 7.0. The phylogenetic tree reconstructed by the Bayesian information criterion consisted of two distinct groups of monocots and dicots. Among the monocots, coconut (Cocos nucifera) and oil palm (Elaeis guineensis) were the most closely related species. A marker for coconut differentiation was developed from one-base substitution site and could be successfully used.

Synthesis and pharmacological evaluation of N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide as cyclooxygenase inhibitors.

PubMed

Rambabu, D; Mulakayala, Naveen; Ismail; Kumar, K Ravi; Kumar, G Pavan; Mulakayala, Chaitanya; Kumar, Chitta Suresh; Kalle, Arunasree M; Rao, M V Basaveswara; Oruganti, Srinivas; Pal, Manojit

2012-11-01

A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives were synthesized via converting the readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and then reacting with different substituted amines. The molecular structures of two representative compounds, that is, 3 and 5l were confirmed by single crystal X-ray diffraction study. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. The compound 5i showed balanced selectivity towards COX-2 over COX-1 inhibition and good docking scores when docked into the COX-2 protein. Copyright © 2012 Elsevier Ltd. All rights reserved.

Broadening the functionality of a J-protein/Hsp70 molecular chaperone system.

PubMed

Schilke, Brenda A; Ciesielski, Szymon J; Ziegelhoffer, Thomas; Kamiya, Erina; Tonelli, Marco; Lee, Woonghee; Cornilescu, Gabriel; Hines, Justin K; Markley, John L; Craig, Elizabeth A

2017-10-01

By binding to a multitude of polypeptide substrates, Hsp70-based molecular chaperone systems perform a range of cellular functions. All J-protein co-chaperones play the essential role, via action of their J-domains, of stimulating the ATPase activity of Hsp70, thereby stabilizing its interaction with substrate. In addition, J-proteins drive the functional diversity of Hsp70 chaperone systems through action of regions outside their J-domains. Targeting to specific locations within a cellular compartment and binding of specific substrates for delivery to Hsp70 have been identified as modes of J-protein specialization. To better understand J-protein specialization, we concentrated on Saccharomyces cerevisiae SIS1, which encodes an essential J-protein of the cytosol/nucleus. We selected suppressors that allowed cells lacking SIS1 to form colonies. Substitutions changing single residues in Ydj1, a J-protein, which, like Sis1, partners with Hsp70 Ssa1, were isolated. These gain-of-function substitutions were located at the end of the J-domain, suggesting that suppression was connected to interaction with its partner Hsp70, rather than substrate binding or subcellular localization. Reasoning that, if YDJ1 suppressors affect Ssa1 function, substitutions in Hsp70 itself might also be able to overcome the cellular requirement for Sis1, we carried out a selection for SSA1 suppressor mutations. Suppressing substitutions were isolated that altered sites in Ssa1 affecting the cycle of substrate interaction. Together, our results point to a third, additional means by which J-proteins can drive Hsp70's ability to function in a wide range of cellular processes-modulating the Hsp70-substrate interaction cycle.

Modeling the SOA Forming Potential of Substituted Dihydrofurans from Alkane + OH Reactions in the Atmosphere

NASA Astrophysics Data System (ADS)

Jordan, C. E.; Griffin, R. J.; Lim, Y. B.; Ziemann, P. J.; Atkinson, R.; Arey, J.

2005-12-01

Recent laboratory studies show that δ-hydroxycarbonyls formed in the atmosphere via OH-initiated reactions with alkanes can cyclize then dehydrate to form substituted dihydrofurans. These dihydrofurans are highly reactive, with lifetimes in the atmosphere of 1.3 h (OH), 24 s (NO3), and 7 min (O3). The ability of the δ-hydroxycarbonyls to cyclize and dehydrate has been shown to increase with increasing carbon number. Recent laboratory results show that the secondary organic aerosol (SOA) yields from alkanes also increase with carbon number reaching ~53% for C15. The reaction mechanism proposed based on the chamber results is the basis of the modeling study presented here. We have incorporated this proposed mechanism into the Caltech Atmospheric Chemistry Mechanism (CACM). For computational reasons, similar compounds are lumped together and represented by a single suitable compound. In the present case, alkanes are lumped into 3 groups: short chains (≤C6), medium chains (C7 - C12), and long chains (≥C13). SOA yields obtained in chamber studies increase dramatically from 0.5% for C8 to 25% for C12. The most dramatic increase is observed from C11 (8%) to C13 (~50%). This is attributed to the low volatility of first generation products contributing to the SOA from longer chain alkanes. Here we have studied OH reactions with the substituted dihydrofurans for medium (represented by C10) and long (represented by C16) chain alkanes using CACM along with the aerosol partitioning module MPMPO (Model to Predict the Multi-phase Partitioning of Organics). We will present the results of this modeling study, characterizing the influence of substituted dihydrofurans on the SOA forming potential of alkanes.

The role of proline-containing peptide triads in β-sheet formation: A kinetic study.

PubMed

Takor, Gaius A; Higashiya, Seiichiro; Sikirzhytski, Vitali K; Seeley, Jason P; Lednev, Igor K; Welch, John T

2015-06-01

The design of biomimetic materials through molecular self-assembly is a growing area of modern nanotechnology. With problems of protein folding, self-assembly, and sequence-structure relationships as essential in nanotechnology as in biology, the effect of the nucleation of β-hairpin formation by proline on the folding process has been investigated in model studies. Previously such studies were limited to investigations of the influence of proline on the formation of turns in short peptide sequences. The effect of proline-based triads on the folding of an 11-kDa amyloidogenic peptide GH6[(GA)3GY(GA)3GE]8 GAH6 (YE8) was investigated by selective substitution of the proline-substituted triads at the γ-turn sites. The folding and fibrillation of the singly proline-substituted polypeptides, e.g., GH6-[(GA)3GY(GA)3GE]7(GA)3GY(GA)3PD-GAH6 (8PD), and doubly proline-substituted polypeptides, e.g., GH6-[(GA)3GY(GA)3GE]3(GA)3GY(GA)3PD[(GA)3GY(GA)3GE]3(GA)3GY(GA)3PD-GAH6 (4,8PD), were directly monitored by circular dichroism and deep UV resonance Raman and fluorescence spectroscopies. These findings were used to identify the essential folding domains, i.e., the minimum number of β-strands necessary for stable folding. These experimental findings may be especially useful in the design and construction of peptidic materials for a wide range of applications as well as in understanding the mechanisms of folding critical to fibril formation. © 2015 Wiley Periodicals, Inc.

Rotational characterization of methyl methacrylate: Internal dynamics and structure determination

NASA Astrophysics Data System (ADS)

Herbers, Sven; Wachsmuth, Dennis; Obenchain, Daniel A.; Grabow, Jens-Uwe

2018-01-01

Rotational constants, Watson's S centrifugal distortion coefficients, and internal rotation parameters of the two most stable conformers of methyl methacrylate were retrieved from the microwave spectrum. Splittings of rotational energy levels were caused by two non equivalent methyl tops. Constraining the centrifugal distortion coefficients and internal rotation parameters to the values of the main isotopologues, the rotational constants of all single substituted 13C and 18O isotopologues were determined. From these rotational constants the substitution structures and semi-empirical zero point structures of both conformers were precisely determined.

Synthesis of isochromene-type scaffolds via single-flask Diels-Alder-[4 + 2]-annulation sequence of a silyl-substituted diene with menadione.

PubMed

Lee, Jihoon; Panek, James S

2014-06-20

A sequential Diels-Alder reaction/silicon-directed [4 + 2]-annulation was developed to assemble hydroisochromene-type ring systems from menadione 2. In the first step, a Diels-Alder of the 1-silyl-substituted butadiene 1 with 2 furnished an intermediate cyclic allylsilane. Subsequently, TMSOTf promoted a [4 + 2]-annulation through trapping of an oxonium, generated by condensation between an aldehyde and the TBS protected alcohol resulted in the formation of a cis-fused hydroisochromene 13.

Explicit Substitutions and All That

NASA Technical Reports Server (NTRS)

Ayala-Rincon, Mauricio; Munoz, Cesar

2000-01-01

Explicit substitution calculi are extensions of the lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda sigma- and lambda S(e)-calculi.

Explicit Substitutions and All That

NASA Technical Reports Server (NTRS)

Ayala-Rincon, Mauricio; Munoz, Cesar; Busnell, Dennis M. (Technical Monitor)

2000-01-01

Explicit substitution calculi are extensions of the Lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda(sigma)- and lambda(s(e))-calculi.

Raman study of the Hg0.7Cr0.3Sr2CuO4+δ superconductors

NASA Astrophysics Data System (ADS)

Lee, S.-Y.; Chang, B.-Y.; Yang, I.-S.; Gwak, J.-H.; Kim, S.-J.; Choi, J.-H.; Lee, S.-I.; Yakhmi, J. V.; Mandal, J. B.; Bandyopadhyay, B.; Ghosh, B.

1997-08-01

The local environment of the apical oxygens (OA) in the Sr-substituted mercury-based superconductor Hg0.7Cr0.3Sr2CuO4+δ is investigated using Raman spectroscopy. Raman spectra from the Sr-substituted Hg-1201 samples show broad OA A1g double peaks at 553 and 583 cm-l, which are 10 - 20 cm-1 lower than the pristine Hg-1201. The existence of, and lower shift of, the double peaks in the Raman spectra of the Sr-substituted Hg-1201 superconductors indicate changes in the environment of OA in the Sr-substituted mercury-based superconductors.

Photochemistry of nucleic acid bases and their thio- and aza-analogues in solution.

PubMed

Pollum, Marvin; Martínez-Fernández, Lara; Crespo-Hernández, Carlos E

2015-01-01

The steady-state and time-resolved photochemistry of the natural nucleic acid bases and their sulfur- and nitrogen-substituted analogues in solution is reviewed. Emphasis is given to the experimental studies performed over the last 3-5 years that showcase topical areas of scientific inquiry and those that require further scrutiny. Significant progress has been made toward mapping the radiative and nonradiative decay pathways of nucleic acid bases. There is a consensus that ultrafast internal conversion to the ground state is the primary relaxation pathway in the nucleic acid bases, whereas the mechanism of this relaxation and the level of participation of the (1)πσ*, (1) nπ*, and (3)ππ* states are still matters of debate. Although impressive research has been performed in recent years, the microscopic mechanism(s) by which the nucleic acid bases dissipate excess vibrational energy to their environment, and the role of the N-glycosidic group in this and in other nonradiative decay pathways, are still poorly understood. The simple replacement of a single atom in a nucleobase with a sulfur or nitrogen atom severely restricts access to the conical intersections responsible for the intrinsic internal conversion pathways to the ground state in the nucleic acid bases. It also enhances access to ultrafast and efficient inter-system crossing pathways that populate the triplet manifold in yields close to unity. Determining the coupled nuclear and electronic pathways responsible for the significantly different photochemistry in these nucleic acid base analogues serves as a convenient platform to examine the current state of knowledge regarding the photodynamic properties of the DNA and RNA bases from both experimental and computational perspectives. Further investigations should also aid in forecasting the prospective use of sulfur- and nitrogen-substituted base analogues in photochemotherapeutic applications.

Cd(II)-coordination polymers based on tetracarboxylic acid and diverse bis(imidazole) ligands: Synthesis, structural diversity and photoluminescence properties

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

Arıcı, Mürsel, E-mail: marici@ogu.edu.tr; Yeşilel, Okan Zafer; Taş, Murat

Three new Cd(II)-coordination polymers, namely, ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,5-bipe){sub 2}]·2H{sub 2}O){sub n} (1), ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,4-bix){sub 2}]{sub n}·2DMF) (2) and ([Cd{sub 2}(μ{sub 8}-abtc)(μ-1,4-betix)]·DMF·H{sub 2}O){sub n} (3) (ao{sub 2}btc=di-oxygenated form of 3,3′,5,5′-azobenzenetetracarboxylate, 1,5-bipe: 1,5-bis(imidazol-1yl)pentane, 1,4-bix=1,4-bis(imidazol-1ylmethyl)benzene, 1,4-betix=1,4-bis(2-ethylimidazol-1ylmethyl)benzene) were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the raremore » sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. Moreover, thermal and photoluminescence properties of the complexes were determined in detailed. - Graphical abstract: In this study, three novel Cd(II)-coordination polymers were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. - Highlights: • Three new Cd(II)-coordination polymers with azobenzenetetracarboxylic acid and diverse bis(imidazole) linkers. • Complex 1 is 2D structure with 3,6L18 topology. • 3D pillar-layered framework of 2 with the rare sqc27 topology. • 3D framework of 3 with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type SBU.« less

Modeled Dietary Impact of Pizza Reformulations in US Children and Adolescents.

PubMed

Masset, Gabriel; Mathias, Kevin C; Vlassopoulos, Antonis; Mölenberg, Famke; Lehmann, Undine; Gibney, Mike; Drewnowski, Adam

2016-01-01

Approximately 20% of US children and adolescents consume pizza on any given day; and pizza intake is associated with higher intakes of energy, sodium, and saturated fat. The reformulation of pizza products has yet to be evaluated as a viable option to improve diets of the US youth. This study modeled the effect on nutrient intakes of two potential pizza reformulation strategies based on the standards established by the Nestlé Nutritional Profiling System (NNPS). Dietary intakes were retrieved from the first 24hr-recall of the National Health and Nutrition Examination Survey (NHANES) 2011-12, for 2655 participants aged 4-19 years. The composition of pizzas in the NHANES food database (n = 69) were compared against the NNPS standards for energy, total fat, saturated fat, sodium, added sugars, and protein. In a reformulation scenario, the nutrient content of pizzas was adjusted to the NNPS standards if these were not met. In a substitution scenario, pizzas that did not meet the standards were replaced by the closest pizza, based on nutrient content, that met all of the NNPS standards. Pizzas consistent with all the NNPS standards (29% of all pizzas) were significantly lower in energy, saturated fat and sodium than pizzas that were not. Among pizza consumers, modeled intakes in the reformulation and substitution scenarios were lower in energy (-14 and -45kcal, respectively), saturated fat (-1.2 and -2.7g), and sodium (-143 and -153mg) compared to baseline. Potential industry wide reformulation of a single food category or intra-category food substitutions may positively impact dietary intakes of US children and adolescents. Further promotion and support of these complimentary strategies may facilitate the adoption and implementation of reformulation standards.

Modeled Dietary Impact of Pizza Reformulations in US Children and Adolescents

PubMed Central

Masset, Gabriel; Mathias, Kevin C.; Vlassopoulos, Antonis; Mölenberg, Famke; Lehmann, Undine; Gibney, Mike; Drewnowski, Adam

2016-01-01

Background and Objective Approximately 20% of US children and adolescents consume pizza on any given day; and pizza intake is associated with higher intakes of energy, sodium, and saturated fat. The reformulation of pizza products has yet to be evaluated as a viable option to improve diets of the US youth. This study modeled the effect on nutrient intakes of two potential pizza reformulation strategies based on the standards established by the Nestlé Nutritional Profiling System (NNPS). Methods Dietary intakes were retrieved from the first 24hr-recall of the National Health and Nutrition Examination Survey (NHANES) 2011–12, for 2655 participants aged 4–19 years. The composition of pizzas in the NHANES food database (n = 69) were compared against the NNPS standards for energy, total fat, saturated fat, sodium, added sugars, and protein. In a reformulation scenario, the nutrient content of pizzas was adjusted to the NNPS standards if these were not met. In a substitution scenario, pizzas that did not meet the standards were replaced by the closest pizza, based on nutrient content, that met all of the NNPS standards. Results Pizzas consistent with all the NNPS standards (29% of all pizzas) were significantly lower in energy, saturated fat and sodium than pizzas that were not. Among pizza consumers, modeled intakes in the reformulation and substitution scenarios were lower in energy (-14 and -45kcal, respectively), saturated fat (-1.2 and -2.7g), and sodium (-143 and -153mg) compared to baseline. Conclusions Potential industry wide reformulation of a single food category or intra-category food substitutions may positively impact dietary intakes of US children and adolescents. Further promotion and support of these complimentary strategies may facilitate the adoption and implementation of reformulation standards. PMID:27706221

Pan-Arctic modelling of net ecosystem exchange of CO2

PubMed Central

Shaver, G. R.; Rastetter, E. B.; Salmon, V.; Street, L. E.; van de Weg, M. J.; Rocha, A.; van Wijk, M. T.; Williams, M.

2013-01-01

Net ecosystem exchange (NEE) of C varies greatly among Arctic ecosystems. Here, we show that approximately 75 per cent of this variation can be accounted for in a single regression model that predicts NEE as a function of leaf area index (LAI), air temperature and photosynthetically active radiation (PAR). The model was developed in concert with a survey of the light response of NEE in Arctic and subarctic tundras in Alaska, Greenland, Svalbard and Sweden. Model parametrizations based on data collected in one part of the Arctic can be used to predict NEE in other parts of the Arctic with accuracy similar to that of predictions based on data collected in the same site where NEE is predicted. The principal requirement for the dataset is that it should contain a sufficiently wide range of measurements of NEE at both high and low values of LAI, air temperature and PAR, to properly constrain the estimates of model parameters. Canopy N content can also be substituted for leaf area in predicting NEE, with equal or greater accuracy, but substitution of soil temperature for air temperature does not improve predictions. Overall, the results suggest a remarkable convergence in regulation of NEE in diverse ecosystem types throughout the Arctic. PMID:23836790

Structure-based design of NS2 mutants for attenuated influenza A virus vaccines.

PubMed

Akarsu, Hatice; Iwatsuki-Horimoto, Kiyoko; Noda, Takeshi; Kawakami, Eiryo; Katsura, Hiroaki; Baudin, Florence; Horimoto, Taisuke; Kawaoka, Yoshihiro

2011-01-01

We previously characterised the matrix 1 (M1)-binding domain of the influenza A virus NS2/nuclear export protein (NEP), reporting a critical role for the tryptophan (W78) residue that is surrounded by a cluster of glutamate residues in the C-terminal region that interacts with the M1 protein (Akarsu et al., 2003). To gain further insight into the functional role of this interaction, here we used reverse genetics to generate a series of A/WSN/33 (H1N1)-based NS2/NEP mutants for W78 or the C-terminal glutamate residues and assessed their effect on virus growth. We found that simultaneous mutations at three positions (E67S/E74S/E75S) of NS2/NEP were important for inhibition of influenza viral polymerase activity, although the W78S mutant and other glutamate mutants with single substitutions were not. In addition, double and triple substitutions in the NS2/NEP glutamine residues, which resulted in the addition of seven amino acids to the C-terminus of NS1 due to gene overlapping, resulted in virus attenuation in mice. Animal studies with this mutant suggest a potential benefit to incorporating these NS mutations into live vaccines. Copyright © 2010 Elsevier B.V. All rights reserved.

A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH.

PubMed

Klotsman, M; Weinberg, C R; Davis, K; Binnie, C G; Hartmann, K E

2004-01-01

In men with a clinical diagnosis of benign prostatic hyperplasia (BPH), polytomous logistic regression analysis was conducted to evaluate associations between two silent polymorphisms in SRD5A1 (codon positions 30 and 116), two polymorphisms in SRD5A2 (Val89Leu substitution and C to T transition in intron 1), a trinucleotide (CAG)n repeat in androgen receptor (AR), and an Arg492Cys substitution in ADRA1A and clinical parameters that characterize severity of BPH. Candidate gene selection was based on two mechanistic pathways targeted by pharmacotherapy for BPH: (1) androgen metabolic loci contributing to prostate growth (static obstruction); and (2) factors affecting smooth muscle tone (dynamic obstruction). Polymorphisms in SRD5A2 were not associated with severity of BPH; however, SRD5A1 polymorphisms were associated with severity of BPH. The process(es) in which these silent single-nucleotide polymorphisms (SNPs) influence BPH phenotypes is unknown and additional studies will be needed to assess whether these SNPs have direct functional consequences. The characterization of additional molecular factors that contribute to static and dynamic obstruction may help predict response to pharmacotherapy and serve to identify novel drug targets for the clinical management of BPH.

Managing Substitute Teaching.

ERIC Educational Resources Information Center

Jones, Kevin R.

1999-01-01

This news brief presents information on managing substitute teaching. The information is based on issues discussed at a summit meeting which included public school administrators and personnel directors from around the nation. The main topics of concern focused around four core components related to the management of substitute teaching:…

Strain tuning of electronic structure in Bi 4Ti 3O 12-LaCoO 3 epitaxial thin films

DOE PAGES

Choi, Woo Seok; Lee, Ho Nyung

2015-05-08

In this study, we investigated the crystal and electronic structures of ferroelectric Bi 4Ti 3O 12 single-crystalline thin films site-specifically substituted with LaCoO 3 (LCO). The epitaxial films were grown by pulsed laser epitaxy on NdGaO 3 and SrTiO 3 substrates to vary the degree of strain. With increasing the LCO substitution, we observed a systematic increase in the c-axis lattice constant of the Aurivillius phase related with the modification of pseudo-orthorhombic unit cells. These compositional and structural changes resulted in a systematic decrease in the band gap, i.e., the optical transition energy between the oxygen 2p and transition-metal 3dmore » states, based on a spectroscopic ellipsometry study. In particular, the Co 3d state seems to largely overlap with the Ti t 2g state, decreasing the band gap. Interestingly, the applied tensile strain facilitates the band-gap narrowing, demonstrating that epitaxial strain is a useful tool to tune the electronic structure of ferroelectric transition-metal oxides.« less

Syntheses and characterizations of transition-metal-substituted aluminophosphate molecular sieves |(C3N2H5) 8|[M8Al16P24O96] (M = Co, Mn, Zn) with zeotype LAU topology.

PubMed

Song, Xiaowei; Li, Jiyang; Guo, Yanan; Pan, Qinhe; Gan, Lin; Yu, Jihong; Xu, Ruren

2009-01-05

Three transitional-metal-substituted aluminophosphate molecular sieves, |(C3N2H5)8|[M8Al16P24O96] (denoted MAPO-LAU, M = Co, Mn, Zn), have been synthesized under solvothermal conditions in the presence of imidazole as the structure-directing agent. Their structures are determined by single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, inductively coupled plasma, thermogravimetric, and diffuse reflectance spectroscopy (UV-vis) analyses. The structure of MAPO-LAU is based on the strict alternation of MO4/AlO4 tetrahedra and PO4 tetrahedra through vertex oxygen atoms. Their frameworks are analogous to the zeotype LAU structure in which 33% of the aluminum sites are replaced by transitional-metal ions. The protonated imidazole cations resided in the 10-ring channels. These compounds show photoluminescent properties due to the existence of imidazole molecules in the structures. Magnetic measurements reveal that there is very weak antiferromagnetic interaction among the metal centers of MnAPO-LAU.

Charge transport kinetics in a robust radical-substituted polymer/nanocarbon composite electrode

NASA Astrophysics Data System (ADS)

Sato, Kan; Oyaizu, Kenichi; Nishide, Hiroyuki

We have reported a series of organic radical-substituted polymers as new-type charge storage and transport materials which could be used for energy related devices such as batteries and solar cells. Redox-active radical moieties introduced to the non-conjugated polymer backbones enable the rapid electron transfer among the adjacent radical sites, and thus large diffusive flux of electrical charge at a bulk scale. Here we present the elucidated charge transport kinetics in a radical polymer/single-walled carbon nanotube (SWNT) composite electrode. The synergetic effect of electrical conduction by a three-dimensional SWNT network and electron self-exchange reaction by radical polymers contributed to the 105-fold (per 1 g of added SWNT) boosting of electrochemical reactions and exceptionally large current density (greater than 1 A/cm2) as a rechargeable electrode. A totally organic-based secondary battery with a submicron thickness was fabricated to demonstrate the splendid electrochemical performances. Grants-in-Aid for Scientific Research (No. 24225003, 15J00888) and the Leading Graduate Program in Science and Engineering, from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT).

The Cladophora complex (Chlorophyta): new views based on 18S rRNA gene sequences.

PubMed

Bakker, F T; Olsen, J L; Stam, W T; van den Hoek, C

1994-12-01

Evolutionary relationships among species traditionally ascribed to the Siphonocladales/Cladophorales have remained unclear due to a lack of phylogenetically informative characters and extensive morphological plasticity resulting in morphological convergence. This study explores some of the diversity within the generic complex Cladophora and its siphonocladalaen allies. Twelve species of Cladophora representing 6 of the 11 morphological sections recognized by van den Hoek were analyzed along with 8 siphonocladalaen species using 18S rRNA gene sequences. The final alignment consisted of 1460 positions containing 92 phylogenetically informative substitutions. Weighting schemes (EOR weighting, combinatorial weighting) were applied in maximum parsimony analysis to correct for substitution bias. Stem characters were weighted 0.66 relative to single-stranded characters to correct for secondary structural constraints. Both weighting approaches resulted in greater phylogenetic resolution. Results confirm that there is no basis for the independent recognition of the Cladophorales and Siphonocladales. The Siphonocladales is polyphyletic, and Cladophora is paraphyletic. All analyses support two principal lineages, of which one contains predominantly tropical members including almost all siphonocladalean taxa, while the other lineage consists of mostly warm- to cold-temperate species of Cladophora.

5-Fluoro pyrimidines: labels to probe DNA and RNA secondary structures by 1D 19F NMR spectroscopy

PubMed Central

Puffer, Barbara; Kreutz, Christoph; Rieder, Ulrike; Ebert, Marc-Olivier; Konrat, Robert; Micura, Ronald

2009-01-01

19F NMR spectroscopy has proved to be a valuable tool to monitor functionally important conformational transitions of nucleic acids. Here, we present a systematic investigation on the application of 5-fluoro pyrimidines to probe DNA and RNA secondary structures. Oligonucleotides with the propensity to adapt secondary structure equilibria were chosen as model systems and analyzed by 1D 19F and 1H NMR spectroscopy. A comparison with the unmodified analogs revealed that the equilibrium characteristics of the bistable DNA and RNA oligonucleotides were hardly affected upon fluorine substitution at C5 of pyrimidines. This observation was in accordance with UV spectroscopic melting experiments which demonstrated that single 5-fluoro substitutions in double helices lead to comparable thermodynamic stabilities. Thus, 5-fluoro pyrimidine labeling of DNA and RNA can be reliably applied for NMR based nucleic acid secondary structure evaluation. Furthermore, we developed a facile synthetic route towards 5-fluoro cytidine phosphoramidites that enables their convenient site-specific incorporation into oligonucleotides by solid-phase synthesis. PMID:19843610

5-Fluoro pyrimidines: labels to probe DNA and RNA secondary structures by 1D 19F NMR spectroscopy.

PubMed

Puffer, Barbara; Kreutz, Christoph; Rieder, Ulrike; Ebert, Marc-Olivier; Konrat, Robert; Micura, Ronald

2009-12-01

(19)F NMR spectroscopy has proved to be a valuable tool to monitor functionally important conformational transitions of nucleic acids. Here, we present a systematic investigation on the application of 5-fluoro pyrimidines to probe DNA and RNA secondary structures. Oligonucleotides with the propensity to adapt secondary structure equilibria were chosen as model systems and analyzed by 1D (19)F and (1)H NMR spectroscopy. A comparison with the unmodified analogs revealed that the equilibrium characteristics of the bistable DNA and RNA oligonucleotides were hardly affected upon fluorine substitution at C5 of pyrimidines. This observation was in accordance with UV spectroscopic melting experiments which demonstrated that single 5-fluoro substitutions in double helices lead to comparable thermodynamic stabilities. Thus, 5-fluoro pyrimidine labeling of DNA and RNA can be reliably applied for NMR based nucleic acid secondary structure evaluation. Furthermore, we developed a facile synthetic route towards 5-fluoro cytidine phosphoramidites that enables their convenient site-specific incorporation into oligonucleotides by solid-phase synthesis.

Control of magnetic, nonmagnetic, and superconducting states in annealed Ca(Fe 1–xCo x)₂As₂

DOE PAGES

Ran, S.; Bud'ko, S. L.; Straszheim, W. E.; ...

2012-06-22

We have grown single-crystal samples of Co substituted CaFe₂As₂ using an FeAs flux and systematically studied the effects of annealing/quenching temperature on the physical properties of these samples. Whereas the as-grown samples (quenched from 960°C) all enter the collapsed tetragonal phase upon cooling, annealing/quenching temperatures between 350 and 800°C can be used to tune the system to low-temperature antiferromagnetic/orthorhomic or superconducting states as well. The progression of the transition temperature versus annealing/quenching temperature (T-T anneal) phase diagrams with increasing Co concentration shows that, by substituting Co, the antiferromagnetic/orthorhombic and the collapsed tetragonal phase lines are separated and bulk superconductivity ismore » revealed. We established a 3D phase diagram with Co concentration and annealing/quenching temperature as two independent control parameters. At ambient pressure, for modest x and T anneal values, the Ca(Fe₁₋ xCox)₂As₂ system offers ready access to the salient low-temperature states associated with Fe-based superconductors: antiferromagnetic/orthorhombic, superconducting, and nonmagnetic/collapsed tetragonal.« less

Substitutional Growth of Methylammonium Lead Iodide Perovskites in Alcohols

DOE PAGES

Acik, Muge; Alam, Todd M.; Guo, Fangmin; ...

2017-09-29

Methylammonium lead iodide (MAPbI 3) perovskites are organic–inorganic semiconductors with long carrier diffusion lengths serving as the light-harvesting component in optoelectronics. Through a substitutional growth of MAPbI 3 catalyzed by polar protic alcohols, evidence is shown in this paper for their substrate- and annealing-free production and use of toxic solvents and high temperature is prevented. The resulting variable-sized crystals (≈100 nm–10 µm) are found to be tetragonally single-phased in alcohols and precipitated as powders that are metallic-lead-free. A comparatively low MAPbI 3 yield in toluene supports the role of alcohol polarity and the type of solvent (protic vs aprotic). Themore » theoretical calculations suggest that overall Gibbs free energy in alcohols is lowered due to their catalytic impact. Based on this alcohol-catalyzed approach, MAPbI 3 is obtained, which is chemically stable in air up to ≈1.5 months and thermally stable (≤300 °C). Finally, this method is amendable to large-scale manufacturing and ultimately can lead to energy-efficient, low-cost, and stable devices.« less

Rapid Multistep Synthesis of 1,2,4-Oxadiazoles in a Single Continuous Microreactor Sequence

PubMed Central

Grant, Daniel; Dahl, Russell; Cosford, Nicholas D. P.

2009-01-01

A general method for the synthesis of bis-substituted 1,2,4-oxadiazoles from readily available arylnitriles and activated carbonyls in a single continuous microreactor sequence is described. The synthesis incorporates three sequential microreactors to produce 1,2,4-oxadiazoles in ~30 min in quantities (40–80 mg) sufficient for full characterization and rapid library supply. PMID:18687005

Single step signal group-imidazole labeling of organic phosphate groups under aqueous conditions

DOEpatents

Giese, R.W.; Wang, P.

1996-04-30

Compounds and methods for single step, covalent labeling of the phosphate group of an organic substance under aqueous conditions are described. The labeling compound includes any kind of detectable signal group covalently bound to an imidazole moiety, which can be imidazole or a substituted imidazole. A preferred labeling compound has the formula shown in the accompanying diagram. 4 figs.

Structural and catalytic effects of an invariant purine substitution in the hammerhead ribozyme: implications for the mechanism of acid–base catalysis

PubMed Central

Schultz, Eric P.; Vasquez, Ernesto E.; Scott, William G.

2014-01-01

The hammerhead ribozyme catalyzes RNA cleavage via acid–base catalysis. Whether it does so by general acid–base catalysis, in which the RNA itself donates and abstracts protons in the transition state, as is typically assumed, or by specific acid–base catalysis, in which the RNA plays a structural role and proton transfer is mediated by active-site water molecules, is unknown. Previous biochemical and crystallographic experiments implicate an invariant purine in the active site, G12, as the general base. However, G12 may play a structural role consistent with specific base catalysis. To better understand the role of G12 in the mechanism of hammerhead catalysis, a 2.2 Å resolution crystal structure of a hammerhead ribozyme from Schistosoma mansoni with a purine substituted for G12 in the active site of the ribozyme was obtained. Comparison of this structure (PDB entry 3zd4), in which A12 is substituted for G, with three previously determined structures that now serve as important experimental controls, allows the identification of structural perturbations that are owing to the purine substitution itself. Kinetic measurements for G12 purine-substituted schistosomal hammerheads confirm a previously observed dependence of rate on the pK a of the substituted purine; in both cases inosine, which is similar to G in pK a and hydrogen-bonding properties, is unexpectedly inactive. Structural comparisons indicate that this may primarily be owing to the lack of the exocyclic 2-amino group in the G12A and G12I substitutions and its structural effect upon both the nucleotide base and phosphate of A9. The latter involves the perturbation of a previously identified and well characterized metal ion-binding site known to be catalytically important in both minimal and full-length hammerhead ribozyme sequences. The results permit it to be suggested that G12 plays an important role in stabilizing the active-site structure. This result, although not inconsistent with the potential role of G12 as a general base, indicates that an alternative hammerhead cleavage mechanism involving specific base catalysis may instead explain the observed rate dependence upon purine substitutions at G12. The crystallographic results, contrary to previous assumptions, therefore cannot be interpreted to favor the general base catalysis mecahnism over the specific base catalysis mechanism. Instead, both of these mutually exclusive mechanistic alternatives must be considered in light of the current structural and biochemical data. PMID:25195740

Structural and catalytic effects of an invariant purine substitution in the hammerhead ribozyme: implications for the mechanism of acid-base catalysis.

PubMed

Schultz, Eric P; Vasquez, Ernesto E; Scott, William G

2014-09-01

The hammerhead ribozyme catalyzes RNA cleavage via acid-base catalysis. Whether it does so by general acid-base catalysis, in which the RNA itself donates and abstracts protons in the transition state, as is typically assumed, or by specific acid-base catalysis, in which the RNA plays a structural role and proton transfer is mediated by active-site water molecules, is unknown. Previous biochemical and crystallographic experiments implicate an invariant purine in the active site, G12, as the general base. However, G12 may play a structural role consistent with specific base catalysis. To better understand the role of G12 in the mechanism of hammerhead catalysis, a 2.2 Å resolution crystal structure of a hammerhead ribozyme from Schistosoma mansoni with a purine substituted for G12 in the active site of the ribozyme was obtained. Comparison of this structure (PDB entry 3zd4), in which A12 is substituted for G, with three previously determined structures that now serve as important experimental controls, allows the identification of structural perturbations that are owing to the purine substitution itself. Kinetic measurements for G12 purine-substituted schistosomal hammerheads confirm a previously observed dependence of rate on the pK(a) of the substituted purine; in both cases inosine, which is similar to G in pK(a) and hydrogen-bonding properties, is unexpectedly inactive. Structural comparisons indicate that this may primarily be owing to the lack of the exocyclic 2-amino group in the G12A and G12I substitutions and its structural effect upon both the nucleotide base and phosphate of A9. The latter involves the perturbation of a previously identified and well characterized metal ion-binding site known to be catalytically important in both minimal and full-length hammerhead ribozyme sequences. The results permit it to be suggested that G12 plays an important role in stabilizing the active-site structure. This result, although not inconsistent with the potential role of G12 as a general base, indicates that an alternative hammerhead cleavage mechanism involving specific base catalysis may instead explain the observed rate dependence upon purine substitutions at G12. The crystallographic results, contrary to previous assumptions, therefore cannot be interpreted to favor the general base catalysis mecahnism over the specific base catalysis mechanism. Instead, both of these mutually exclusive mechanistic alternatives must be considered in light of the current structural and biochemical data.

Feature-based classification of amino acid substitutions outside conserved functional protein domains.

PubMed

Gemovic, Branislava; Perovic, Vladimir; Glisic, Sanja; Veljkovic, Nevena

2013-01-01

There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to determination of their functional effects. We have developed feature-based algorithm for the detection of mutations outside conserved functional domains (CFDs) and compared its classification efficacy with the most commonly used phylogeny-based tools, PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum method (ISM), a feature-based technique, and statistical analysis. Our dataset contained neutral polymorphisms and mutations associated with myeloid malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. On the other hand, only ISM algorithm showed statistically significant classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and 13%, respectively. These results suggest that feature-based methods, like ISM, are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools.

Perfluorinated Polyalkylether Based Lubricant Composition.

DTIC Science & Technology

phosphorus atoms are substituted by aromatic groups and the carbon atom is substituted by a perfluoroalkyl or perfluoroalkylether moiety. (Author)...A lubricant composition comprising a perfluorinated polyalkylether base fluid and a minor amount of a diphospha-s-triazine in which the two

Electronic structure of Pt-substituted clathrate silicides Ba{sub 8}Pt{sub x}Si{sub 46–x}(x = 4–6)

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

Borshch, N. A., E-mail: n.a.borshch@ya.ru

The results of calculation of the electronic structure of Si-based Pt-substituted clathrates are reported. Calculation is carried out by the linearized-augmented-plane-wave method. The effect of the number of substitutions and their crystallographic position in the unit cell on the electron-energy spectrum and the electronic properties of Pt-substituted clathrates is analyzed.

Fast synthesis of La-substituted apatite by the dry mechanochemical method and analysis of its structure

NASA Astrophysics Data System (ADS)

Bulina, Natalia V.; Chaikina, Marina V.; Prosanov, Igor Yu.; Dudina, Dina V.; Solovyov, Leonid A.

2017-08-01

Compared to pure apatite, La-substituted apatites have improved thermal, mechanical and biological characteristics. In this article, a fast synthesis of La-substituted apatites by a dry mechanochemical method is presented. Structural studies by X-ray diffraction and Fourier transform infrared spectroscopy indicated the formation of a single-phase nanosized product after 30 min of high-energy ball milling of the reaction mixtures. The dry mechanochemical method is technologically attractive for the preparation of La-substituted apatites, as it allows reducing the processing time down to half an hour and does not require prolonged high-temperature annealing normally used in the synthesis practice of the substituted apatite. As the mechanochemically synthesized samples are nanosized, it is difficult to determine the details of their crystal structure by the Rietveld refinement method. Therefore, a series of the mechanochemically synthesized samples with different concentrations of lanthanum were annealed at 1000°C for 5 h. It was found that the annealed powders are microcrystalline La-substituted apatites Ca10-xLax(PO4)6Ox(OH)2-x, where 0 ≤ x ≤2. In their structure, the Ca2+ ions are replaced by the La3+ ions localized near the Ca2 sites, and the OH- groups are replaced by the O2- ions in the hexagonal channels.

Investigations of the effect of nonmagnetic Ca substitution for magnetic Dy on spin-freezing in Dy₂Ti₂O₇.

PubMed

Anand, V K; Tennant, D A; Lake, B

2015-11-04

Physical properties of partially Ca substituted hole-doped Dy2Ti2O7 have been investigated by ac magnetic susceptibility χ(ac)(T), dc magnetic susceptibility χ(T), isothermal magnetization M(H) and heat capacity C(p)(T) measurements on Dy1.8Ca0.2Ti2O7. The spin-ice system Dy2Ti2O7 exhibits a spin-glass type freezing behavior near 16 K. Our frequency dependent χ(ac)(T) data of Dy1.8Ca0.2Ti2O7 show that the spin-freezing behavior is significantly influenced by Ca substitution. The effect of partial nonmagnetic Ca(2+) substitution for magnetic Dy(3+) is similar to the previous study on nonmagnetic isovalent Y(3+) substituted Dy(2-x)Y(x) Ti2O7 (for low levels of dilution), however the suppression of spin-freezing behavior is substantially stronger for Ca than Y. The Cole-Cole plot analysis reveals semicircular character and a single relaxation mode in Dy1.8Ca0.2Ti2O7 as for Dy2Ti2O7. No noticeable change in the insulating behavior of Dy2Ti2O7 results from the holes produced by 10% Ca(2+) substitution for Dy(3+) ions.

Tunable microwave absorbing nano-material for X-band applications

NASA Astrophysics Data System (ADS)

Sadiq, Imran; Naseem, Shahzad; Ashiq, Muhammad Naeem; Khan, M. A.; Niaz, Shanawer; Rana, M. U.

2016-03-01

The effect of rare earth elements substitution in Sr1.96RE0.04Co2Fe27.80Mn0.2O46 (RE=Ce, Gd, Nd, La and Sm) X-type hexagonal ferrites prepared by using sol gel autocombustion method was studied. The XRD and FTIR analysis show the single phase of the prepared material. The lattice constants a (Å) and c (Å) varies with the additives. The particle size measured by Scherer formula for all the samples varies in the range of 54-100 nm and confirmed by the TEM analysis. The average grain size measured by SEM analysis lies in the range of 0.672-1.01 μm for all the samples. The Gd-substituted ferrite has higher value of coercivity (526.06 G) among all the samples which could be a good material for longitudinal recording media. The results also indicate that the Gd-substituted sample has maximum reflection loss of -25.2 dB at 11.878 GHz, can exhibit the best microwave absorption properties among all the substituted samples. Furthermore, the minimum value of reflection loss shifts towards the lower and higher frequencies with the substitution of rare earth elements which confirms that the microwave absorption properties can be tuned with the substitution of rare earth elements in pure ferrites. The peak value of attenuation constant at higher frequency agrees well the reflection loss data.

X-ray crystal structure and properties of Phanta, a weakly fluorescent photochromic GFP-like protein

DOE PAGES

Paul, Craig Don; Traore, Daouda A. K.; Olsen, Seth; ...

2015-04-29

Phanta is a reversibly photoswitching chromoprotein (Φ F, 0.003), useful for pcFRET, that was isolated from a mutagenesis screen of the bright green fluorescent eCGP123 (Φ F, 0.8). We have investigated the contribution of substitutions at positions His193, Thr69 and Gln62, individually and in combination, to the optical properties of Phanta. Single amino acid substitutions at position 193 resulted in proteins with very low Φ F, indicating the importance of this position in controlling the fluorescence efficiency of the variant proteins. The substitution Thr69Val in Phanta was important for supressing the formation of a protonated chromophore species observed in somemore » His193 substituted variants, whereas the substitution Gln62Met did not significantly contribute to the useful optical properties of Phanta. X-ray crystal structures for Phanta (2.3 Å), eCGP123 T69V (2.0 Å) and eCGP123 H193Q (2.2 Å) in their non-photoswitched state were determined, revealing the presence of a cis-coplanar chromophore. We conclude that changes in the hydrogen-bonding network supporting the cis-chromophore, and its contacts with the surrounding protein matrix, are responsible for the low fluorescence emission of eCGP123 variants containing a His193 substitution.« less

Base-promoted one-pot tandem reaction of 3-(1-alkynyl)chromones under microwave irradiation to functionalized amino-substituted xanthones.

PubMed

Liu, Yang; Huang, Liping; Xie, Fuchun; Hu, Youhong

2010-09-17

A base-promoted one-pot tandem reaction has been developed from 3-(1-alkynyl)chromones with various acetonitriles to afford functionalized amino-substituted xanthones 3 under microwave irradiation. This tandem process involves multiple reactions, such as Michael addition/cyclization/1,2-addition, without a transition metal catalyst. This method provides an efficient approach to build up natural product-like diversified amino-substituted xanthone scaffolds rapidly.

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

PubMed

Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-09-21

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units ([Formula: see text]) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into [Formula: see text] was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of [Formula: see text] corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

NASA Astrophysics Data System (ADS)

Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-10-01

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units (HU ) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into HU was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of 4~mm corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

Appendix C demand elasticities for highway travel.

DOT National Transportation Integrated Search

2000-04-12

An elasticity summarizes a large amount of information in a single number. Levels and : distribution of incomes, price levels of the specific good and of substitute and complementary : goods, preferences and tastes, transaction costs, etc., can, cete...

Working with Missing Values

ERIC Educational Resources Information Center

Acock, Alan C.

2005-01-01

Less than optimum strategies for missing values can produce biased estimates, distorted statistical power, and invalid conclusions. After reviewing traditional approaches (listwise, pairwise, and mean substitution), selected alternatives are covered including single imputation, multiple imputation, and full information maximum likelihood…

Superconductivity induced by In substitution into the topological crystalline insulator Pb0.5Sn0.5Te

NASA Astrophysics Data System (ADS)

Zhong, R. D.; Schneeloch, J. A.; Liu, T. S.; Camino, F. E.; Tranquada, J. M.; Gu, G. D.

2014-07-01

Indium substitution turns the topological crystalline insulator (TCI) Pb0.5Sn0.5Te into a possible topological superconductor. To investigate the effect of the indium concentration on the crystal structure and superconducting properties of (Pb0.5Sn0.5)1-xInxTe, we have grown high-quality single crystals using a modified floating-zone method and have performed systematic studies for indium content in the range 0≤x≤0.35. We find that the single crystals retain the rocksalt structure up to the solubility limit of indium (x ˜0.30). Experimental dependencies of the superconducting transition temperature (Tc) and the upper critical magnetic field (Hc2) on the indium content x have been measured. The maximum Tc is determined to be 4.7 K at x =0.30, with μ0Hc2(T =0)≈5 T.

A Ka-band chirped-pulse Fourier transform microwave spectrometer

NASA Astrophysics Data System (ADS)

Zaleski, Daniel P.; Neill, Justin L.; Muckle, Matt T.; Seifert, Nathan A.; Brandon Carroll, P.; Widicus Weaver, Susanna L.; Pate, Brooks H.

2012-10-01

The design and performance of a new chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer operating from 25 to 40 GHz (Ka-band) is presented. This spectrometer is well-suited for the study of complex organic molecules of astronomical interest in the size range of 6-10 atoms that have strong rotational transitions in Ka-band under pulsed jet sample conditions (Trot = 1-10 K). The spectrometer permits acquisition of the full spectral band in a single data acquisition event. Sensitivity is enhanced by using two pulsed jet sources and acquiring 10 broadband measurements for each sample injection cycle. The spectrometer performance is benchmarked by measuring the pure rotational spectrum of several isotopologues of acetaldehyde in natural abundance. The rotational spectra of the singly substituted 13C and 18O isotopologues of the two lowest energy conformers of ethyl formate have been analyzed and the resulting substitution structures for these conformers are compared to electronic structure theory calculations.

Substituent effect study on experimental ¹³C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene)diacetate derivatives.

PubMed

Kara, Yesim S

2015-12-05

Eleven novel (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene) diacetate derivatives were synthesized in the present study. These dihydroisoxazole derivatives were characterized by IR, (1)H NMR, (13)C NMR and elemental analyses. Their (13)C NMR spectra were measured in Deuterochloroform (CDCl3). The correlation analysis for the substituent-induced chemical shift (SCS) with Hammett substituent constant (σ), inductive substituent constant (σI), different of resonance substituent constants (σR, σR(o)) and Swain-Lupton substituent parameters (F, R) were performed using SSP (single substituent parameter), and DSP (dual substituent parameter) methods, as well as single and multiple regression analysis. From the result of regression analysis, the effect of substituent on the (13)C NMR chemical shifts was explained. Copyright © 2015 Elsevier B.V. All rights reserved.

Self-assembly of [UO{sub 2}X{sub 4}]{sup 2−} (X=Cl, Br) dianions with γ substituted pyridinium cations: Structural systematics and fluorescence properties

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

Surbella, Robert G.; Andrews, Michael B.; Cahill, Christopher L., E-mail: cahill@gwu.edu

2016-04-15

Room temperature self-assembly of [UO{sub 2}X{sub 4}]{sup 2−} (X=Cl, Br) with γ substituted pyridinium cations has resulted in the formation of twelve compounds that were studied via single crystal X-ray diffraction and fluorescence spectroscopy. Systematic variation of electron donating groups on the pyridinium species is shown to influence the presence and/or strength of various supramolecular synthons, including hydrogen bonding and pi interactions. Combinations of such non-covalent interactions (NCIs) have given rise to a range of supramolecular assemblies, and are shown to influence uranyl emission by way of second sphere coordination to equatorial ligands. - Graphical abstract: Supramolecular assembly of themore » [UO{sub 2}Cl{sub 4}]{sup 2−} dianion with pyridinium cations is a viable synthetic route to the growth of uranyl containing single crystals.« less

Silicon Qubits

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

Ladd, Thaddeus D.; Carroll, Malcolm S.

2018-02-28

Silicon is a promising material candidate for qubits due to the combination of worldwide infrastructure in silicon microelectronics fabrication and the capability to drastically reduce decohering noise channels via chemical purification and isotopic enhancement. However, a variety of challenges in fabrication, control, and measurement leaves unclear the best strategy for fully realizing this material’s future potential. In this article, we survey three basic qubit types: those based on substitutional donors, on metal-oxide-semiconductor (MOS) structures, and on Si/SiGe heterostructures. We also discuss the multiple schema used to define and control Si qubits, which may exploit the manipulation and detection of amore » single electron charge, the state of a single electron spin, or the collective states of multiple spins. Far from being comprehensive, this article provides a brief orientation to the rapidly evolving field of silicon qubit technology and is intended as an approachable entry point for a researcher new to this field.« less

Carboxymethylcellulose adsorption on molybdenite: the effect of electrolyte composition on adsorption, bubble-surface collisions, and flotation.

PubMed

Kor, Mohammad; Korczyk, Piotr M; Addai-Mensah, Jonas; Krasowska, Marta; Beattie, David A

2014-10-14

The adsorption of carboxymethylcellulose polymers on molybdenite was studied using spectroscopic ellipsometry and atomic force microscopy imaging with two polymers of differing degrees of carboxyl group substitution and at three different electrolyte conditions: 1 × 10(-2) M KCl, 2.76 × 10(-2) M KCl, and simulated flotation process water of multicomponent electrolyte content, with an ionic strength close to 2.76 × 10(-2) M. A higher degree of carboxyl substitution in the adsorbing polymer resulted in adsorbed layers that were thinner and with more patchy coverage; increasing the ionic strength of the electrolyte resulted in increased polymer layer thickness and coverage. The use of simulated process water resulted in the largest layer thickness and coverage for both polymers. The effect of the adsorbed polymer layer on bubble-particle attachment was studied with single bubble-surface collision experiments recorded with high-speed video capture and image processing and also with single mineral molybdenite flotation tests. The carboxymethylcellulose polymer with a lower degree of substitution resulted in almost complete prevention of wetting film rupture at the molybdenite surface under all electrolyte conditions. The polymer with a higher degree of substitution prevented rupture only when adsorbed from simulated process water. Molecular kinetic theory was used to quantify the effect of the polymer on the dewetting dynamics for collisions that resulted in wetting film rupture. Flotation experiments confirmed that adsorbed polymer layer properties, through their effect on the dynamics of bubble-particle attachment, are critical to predicting the effectiveness of polymers used to prevent mineral recovery in flotation.

Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia

PubMed Central

Rios, Jonathan; Stein, Evan; Shendure, Jay; Hobbs, Helen H.; Cohen, Jonathan C.

2010-01-01

Whole-genome sequencing is a potentially powerful tool for the diagnosis of genetic diseases. Here, we used sequencing-by-ligation to sequence the genome of an 11-month-old breast-fed girl with xanthomas and very high plasma cholesterol levels (1023 mg/dl). Her parents had normal plasma cholesterol levels and reported no family history of hypercholesterolemia, suggesting either an autosomal recessive disorder or a de novo mutation. Known genetic causes of severe hypercholesterolemia were ruled out by sequencing the responsible genes (LDLRAP, LDLR, PCSK9, APOE and APOB), and sitosterolemia was ruled out by documenting a normal plasma sitosterol:cholesterol ratio. Sequencing revealed 3 797 207 deviations from the reference sequence, of which 9726 were nonsynonymous single-nucleotide substitutions. A total of 9027 of the nonsynonymous substitutions were present in dbSNP or in 21 additional individuals from whom complete exonic sequences were available. The 699 novel nonsynonymous substitutions were distributed among 604 genes, 23 of which were single-copy genes that each contained 2 nonsynonymous substitutions consistent with an autosomal recessive model. One gene, ABCG5, had two nonsense mutations (Q16X and R446X). This finding indicated that the infant has sitosterolemia. Thus, whole-genome sequencing led to the diagnosis of a known disease with an atypical presentation. Diagnosis was confirmed by the finding of severe sitosterolemia in a blood sample obtained after the infant had been weaned. These findings demonstrate that whole-genome (or exome) sequencing can be a valuable aid to diagnose genetic diseases, even in individual patients. PMID:20719861

Antimicrobial Drug Resistance of Salmonella enterica Serovar Typhi in Asia and Molecular Mechanism of Reduced Susceptibility to the Fluoroquinolones▿

PubMed Central

Chau, Tran Thuy; Campbell, James Ian; Galindo, Claudia M.; Van Minh Hoang, Nguyen; Diep, To Song; Nga, Tran Thu Thi; Van Vinh Chau, Nguyen; Tuan, Phung Quoc; Page, Anne Laure; Ochiai, R. Leon; Schultsz, Constance; Wain, John; Bhutta, Zulfiqar A.; Parry, Christopher M.; Bhattacharya, Sujit K.; Dutta, Shanta; Agtini, Magdarina; Dong, Baiqing; Honghui, Yang; Anh, Dang Duc; Canh, Do Gia; Naheed, Aliya; Albert, M. John; Phetsouvanh, Rattanaphone; Newton, Paul N.; Basnyat, Buddha; Arjyal, Amit; La, Tran Thi Phi; Rang, Nguyen Ngoc; Phuong, Le Thi; Van Be Bay, Phan; von Seidlein, Lorenz; Dougan, Gordon; Clemens, John D.; Vinh, Ha; Hien, Tran Tinh; Chinh, Nguyen Tran; Acosta, Camilo J.; Farrar, Jeremy; Dolecek, Christiane

2007-01-01

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83→Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions. PMID:17908946

Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F

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

Yagi, T.; Tatsumi-Miyajima, J.; Sato, M.

1991-06-15

To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (W138-VA13), UV-treated pZ189 passed through the XP-A (XP2OS(SV))more » or XP-F (XP2YO(SV)) cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C----A:T transition with all three cell lines. The XP-A and XP-F cells revealed a higher frequency of G:C----A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5{prime}-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features.« less

Growth and structure of a new photonic crystal: Chlorine substituted chalcone

NASA Astrophysics Data System (ADS)

Sarveshwara, H. P.; Raghavendra, S.; A, Jayarama; Menezes, Anthoni Praveen; Dharmaprakash, S. M.

2015-06-01

A new organic photonic material 3-(2, 4-dichlorophenyl)-1-(2,5-dimethylthiophen-3-yl)propan-1-one(DMTP) has been synthesized and crystallised in acetone solution. The functional groups present in the new material were identified by FTIR spectroscopy. The material is optically transparent in the wavelength range of 400-1100 nm. The crystal structure of DMTP was determined by single crystal X-ray diffraction. The title compound crystallizes in monoclinic system with a centrosymmetric space group P21/c. The Z-scan study revealed that the optical limiting property exhibited by the DMTP molecule is based on the reverse saturable absorption phenomena.

Endo-Fullerene and Doped Diamond Nanocrystallite Based Models of Qubits for Solid-State Quantum Computers

NASA Technical Reports Server (NTRS)

Park, Seongjun; Srivastava, Deepak; Cho, Kyeongjae; Biegel, Bryan (Technical Monitor)

2001-01-01

Models of encapsulated 1/2 nuclear spin H-1 and P-31 atoms in fullerene and diamond nanocrystallite, respectively, are proposed and examined with ab-initio local density functional method for possible applications as single quantum bits (qubits) in solid-state quantum computers. A H-1 atom encapsulated in a fully deuterated fullerene, C(sub 20)D(sub 20), forms the first model system and ab-initio calculation shows that H-1 atom is stable in atomic state at the center of the fullerene with a barrier of about 1 eV to escape. A P-31 atom positioned at the center of a diamond nanocrystallite is the second model system, and 3 1P atom is found to be stable at the substitutional site relative to interstitial sites by 15 eV, Vacancy formation energy is 6 eV in diamond so that substitutional P-31 atom will be stable against diffusion during the formation mechanisms within the nanocrystallite. The coupling between the nuclear spin and weakly bound (valance) donor electron coupling in both systems is found to be suitable for single qubit applications, where as the spatial distributions of (valance) donor electron wave functions are found to be preferentially spread along certain lattice directions facilitating two or more qubit applications. The feasibility of the fabrication pathways for both model solid-state qubit systems within practical quantum computers is discussed with in the context of our proposed solid-state qubits.

Molecular adaptation in the world's deepest-living animal: Insights from transcriptome sequencing of the hadal amphipod Hirondellea gigas.

PubMed

Lan, Yi; Sun, Jin; Tian, Renmao; Bartlett, Douglas H; Li, Runsheng; Wong, Yue Him; Zhang, Weipeng; Qiu, Jian-Wen; Xu, Ting; He, Li-Sheng; Tabata, Harry G; Qian, Pei-Yuan

2017-07-01

The Challenger Deep in the Mariana Trench is the deepest point in the oceans of our planet. Understanding how animals adapt to this harsh environment characterized by high hydrostatic pressure, food limitation, dark and cold is of great scientific interest. Of the animals dwelling in the Challenger Deep, amphipods have been captured using baited traps. In this study, we sequenced the transcriptome of the amphipod Hirondellea gigas collected at a depth of 10,929 m from the East Pond of the Challenger Deep. Assembly of these sequences resulted in 133,041 contigs and 22,046 translated proteins. Functional annotation of these contigs was made using the go and kegg databases. Comparison of these translated proteins with those of four shallow-water amphipods revealed 10,731 gene families, of which 5659 were single-copy orthologs. Base substitution analysis on these single-copy orthologs showed that 62 genes are positively selected in H. gigas, including genes related to β-alanine biosynthesis, energy metabolism and genetic information processing. For multiple-copy orthologous genes, gene family expansion analysis revealed that cold-inducible proteins (i.e., transcription factors II A and transcription elongation factor 1) as well as zinc finger domains are expanded in H. gigas. Overall, our results indicate that genetic adaptation to the hadal environment by H. gigas may be mediated by both gene family expansion and amino acid substitutions of specific proteins. © 2017 John Wiley & Sons Ltd.

Genome-Wide Spectra of Transcription Insertions and Deletions Reveal That Slippage Depends on RNA:DNA Hybrid Complementarity.

PubMed

Traverse, Charles C; Ochman, Howard

2017-08-29

Advances in sequencing technologies have enabled direct quantification of genome-wide errors that occur during RNA transcription. These errors occur at rates that are orders of magnitude higher than rates during DNA replication, but due to technical difficulties such measurements have been limited to single-base substitutions and have not yet quantified the scope of transcription insertions and deletions. Previous reporter gene assay findings suggested that transcription indels are produced exclusively by elongation complex slippage at homopolymeric runs, so we enumerated indels across the protein-coding transcriptomes of Escherichia coli and Buchnera aphidicola , which differ widely in their genomic base compositions and incidence of repeat regions. As anticipated from prior assays, transcription insertions prevailed in homopolymeric runs of A and T; however, transcription deletions arose in much more complex sequences and were rarely associated with homopolymeric runs. By reconstructing the relocated positions of the elongation complex as inferred from the sequences inserted or deleted during transcription, we show that continuation of transcription after slippage hinges on the degree of nucleotide complementarity within the RNA:DNA hybrid at the new DNA template location. IMPORTANCE The high level of mistakes generated during transcription can result in the accumulation of malfunctioning and misfolded proteins which can alter global gene regulation and in the expenditure of energy to degrade these nonfunctional proteins. The transcriptome-wide occurrence of base substitutions has been elucidated in bacteria, but information on transcription insertions and deletions-errors that potentially have more dire effects on protein function-is limited to reporter gene constructs. Here, we capture the transcriptome-wide spectrum of insertions and deletions in Escherichia coli and Buchnera aphidicola and show that they occur at rates approaching those of base substitutions. Knowledge of the full extent of sequences subject to transcription indels supports a new model of bacterial transcription slippage, one that relies on the number of complementary bases between the transcript and the DNA template to which it slipped. Copyright © 2017 Traverse and Ochman.

Synthetic versatility of 2-substituted-6-methyl 2,3-dihydropyridinones in the synthesis of polyfunctional piperidine-based compounds and related β amino acid derivatives.

PubMed

Yang, Yang; Hardman, Clayton

2017-10-18

Chiral 2-substituted-6-methyl 2,3-dihydropyidinones 9, which can be facilely obtained from an asymmetric vinylogous Mannich reaction (VMR) with 1,3-bis-trimethysily enol ether, were used as versatile intermediates in constructing chiral polyfunctional piperidine-based compounds. The 6-methyl group of such compounds can be conveniently functionalized via alkylation and acylation reactions to provide efficient entries to the synthesis of a variety of chiral multi-substituted piperidine-based compounds. Further elaboration of the corresponding intermediates also provided access to polyfunctional indolizidine-based compounds. These methods were showcased in an asymmetric synthesis of 2,6-di-substituted piperidine compound 13, reported as the key intermediate in the synthesis of (+)-calvine and a natural alkaloid (-)-indolizidine 209D. Furthermore, selective C5 iodination of compound 9 enabled the installation of additional functional groups at this position. Finally, we demonstrated that the oxidative cleavage of 2-substituted-6-methyl-2,3-dihydropyidinones is a practical and efficient method for the enantioselective synthesis of β-amino acids, which can undergo further intra-molecular cyclization to give the corresponding chiral four-membered β-lactam derivatives.

Recombination–deletion between homologous cassettes in retrovirus is suppressed via a strategy of degenerate codon substitution

PubMed Central

Im, Eung Jun; Bais, Anthony J; Yang, Wen; Ma, Qiangzhong; Guo, Xiuyang; Sepe, Steven M; Junghans, Richard P

2014-01-01

Transduction and expression procedures in gene therapy protocols may optimally transfer more than a single gene to correct a defect and/or transmit new functions to recipient cells or organisms. This may be accomplished by transduction with two (or more) vectors, or, more efficiently, in a single vector. Occasionally, it may be useful to coexpress homologous genes or chimeric proteins with regions of shared homology. Retroviridae include the dominant vector systems for gene transfer (e.g., gamma-retro and lentiviruses) and are capable of such multigene expression. However, these same viruses are known for efficient recombination–deletion when domains are duplicated within the viral genome. This problem can be averted by resorting to two-vector strategies (two-chain two-vector), but at a penalty to cost, convenience, and efficiency. Employing a chimeric antigen receptor system as an example, we confirm that coexpression of two genes with homologous domains in a single gamma-retroviral vector (two-chain single-vector) leads to recombination–deletion between repeated sequences, excising the equivalent of one of the chimeric antigen receptors. Here, we show that a degenerate codon substitution strategy in the two-chain single-vector format efficiently suppressed intravector deletional loss with rescue of balanced gene coexpression by minimizing sequence homology between repeated domains and preserving the final protein sequence. PMID:25419532

A study of a tissue equivalent gelatine based tissue substitute

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

Spence, J.L.

1992-11-01

A study of several tissue substitutes for use as volumetric dosimeters was performed. The tissue substitutes studied included tissue substitutes from previous studies and from ICRU 44. The substitutes were evaluated for an overall match to Reference Man which was used as a basis for this study. The evaluation was based on the electron stopping power, the mass attenuation coefficient, the electron density, and the specific gravity. The tissue substitute chosen also had to be capable of changing from a liquid into a solid form to maintain an even distribution of thermoluminesent dosimetry (TLD) powder and then back to amore » liquid for recovery of the TLD powder without adversely effecting the TLD powder. The gelatine mixture provided the closest match to the data from Reference Man tissue. The gelatine mixture was put through a series of test to determine it's usefulness as a reliable tissue substitute. The TLD powder was cast in the gelatine mixture and recovered to determine if the TLD powder was adversely effected. The distribution of the TLD powder after being cast into the gelatin mixture was tested in insure an even was maintained.« less

A study of a tissue equivalent gelatine based tissue substitute

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

Spence, Jody L.

1992-11-01

A study of several tissue substitutes for use as volumetric dosimeters was performed. The tissue substitutes studied included tissue substitutes from previous studies and from ICRU 44. The substitutes were evaluated for an overall match to Reference Man which was used as a basis for this study. The evaluation was based on the electron stopping power, the mass attenuation coefficient, the electron density, and the specific gravity. The tissue substitute chosen also had to be capable of changing from a liquid into a solid form to maintain an even distribution of thermoluminesent dosimetry (TLD) powder and then back to amore » liquid for recovery of the TLD powder without adversely effecting the TLD powder. The gelatine mixture provided the closest match to the data from Reference Man tissue. The gelatine mixture was put through a series of test to determine it`s usefulness as a reliable tissue substitute. The TLD powder was cast in the gelatine mixture and recovered to determine if the TLD powder was adversely effected. The distribution of the TLD powder after being cast into the gelatin mixture was tested in insure an even was maintained.« less

Gas-solid reactions of single crystals: A study of reactions of NH 3 and NO 2 with single crystalline organic substrates by infrared microspectroscopy

NASA Astrophysics Data System (ADS)

Jenkins, Samantha L.; Almond, Matthew J.; Atkinson, Samantha D. M.; Hollins, Peter; Knowles, John P.

2005-12-01

Reaction of single crystals of benzoic and trans-cinnamic acids with 200 Torr pressure of ammonia gas in a sealed glass bulb at 20 °C generates the corresponding ammonium salts; there is no sign of any 1:2 adduct as has been reported previously for related systems. Isotopic substitution using ND 3 has been used to aid identification of the products. Adipic acid likewise reacts with NH 3 gas to form a product in which ammonium salts are formed at both carboxylic acid groups. Reaction of 0.5 Torr pressure of NO 2 gas with single crystals of 9-methylanthracene and 9-anthracenemethanol in a flow system generates nitrated products where the nitro group appears to be attached at the 10-position, i.e. the position trans to the methyl or methoxy substituent on the central ring. Isotopic substitution using 15NO 2 has been used to confirm the identity of the bands arising from the coordinated NO 2 group. The products formed when single crystals of hydantoin are reacted with NO 2 gas under similar conditions depend on the temperature of the reaction. At 20 °C, a nitrated product is formed, but at 65 °C this gives way to a product containing no nitro groups. The findings show the general applicability of infrared microspectroscopy to a study of gas-solid reactions of organic single crystals.

A multi-material coating containing chemically-modified apatites for combined enhanced bioactivity and reduced infection via a drop-on-demand micro-dispensing technique.

PubMed

Lim, Poon Nian; Wang, Zuyong; Chang, Lei; Konishi, Toshiisa; Choong, Cleo; Ho, Bow; Thian, Eng San

2017-01-01

Prevention of infection and enhanced osseointegration are closely related, and required for a successful orthopaedic implant, which necessitate implant designs to consider both criteria in tandem. A multi-material coating containing 1:1 ratio of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite as the top functional layer, and hydroxyapatite as the base layer, was produced via the drop-on-demand micro-dispensing technique, as a strategic approach in the fight against infection along with the promotion of bone tissue regeneration. The homogeneous distribution of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets at alternate position in silicon-substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite coating delayed the exponential growth of Staphylococcus aureus for up to 24 h, and gave rise to up-regulated expression of alkaline phosphatase activity, type I collagen and osteocalcin as compared to hydroxyapatite and silver-substituted hydroxyapatite coatings. Despite containing reduced amounts of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets over the coated area than silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite coatings, silicon-substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite coating exhibited effective antibacterial property with enhanced bioactivity. By exhibiting good controllability of distributing silicon-substituted hydroxyapatite, silver-substituted hydroxyapatite and hydroxyapatite micro-droplets, it was demonstrated that drop-on-demand micro-dispensing technique was capable in harnessing the advantages of silver-substituted hydroxyapatite, silicon-substituted hydroxyapatite and hydroxyapatite to produce a multi-material coating along with enhanced bioactivity and reduced infection.

Electronic Structure of Ethynyl Substituted Cyclobutadienes

NASA Astrophysics Data System (ADS)

Emmert, Frank Lee Emmert, III; Thompson, Stephanie J.; Slipchenko, Lyudmila V.

2011-06-01

We investigated the effects of ethynyl substitution on the electronic structure of cyclobutadiene. These species are involved in Bergman Cyclization reactionsand are possible intermediates in the formation of fullerenes and graphite sheets. Prediction of the electronic energy of cyclobutadiene is challenging for single-reference ab initio methods such as HF, MP2 or DFT because of Jahn-Teller distortions and the diradical character of the singlet state. We determined the vertical and adiabatic singlet-triplet energy splittings, the natural charges and spin densities in substituted cyclobutadienes, using the equations of motion spin flip coupled cluster with single and double excitations (EOM-SF-CCSD) method that accurately describes diradical states. The adiabatic singlet-triplet gaps decrease upon substituent addition, but the singlet state is always lower in energy. However, we found that the results are affected by spin-contamination of the reference state and deteriorate when an unrestricted HF reference is employed. O. L. Chapman, C. L. McIntosh, J. Pacansky, "Cyclobutadiene" J. Am. Chem. Soc. 1973, 95, (2), 614-617. N. S. Goroff, "Mechanism of Fullerene Formation." Acc. Chem. Res. 1996, 29, (2), 77-83. L.V. Slipchenko and A.I. Krylov, "Singlet-triplet gaps in diradicals by the Spin-Flip approach: A benchmark study", J. Chem. Phys. 2002, 117, 4694-4708.

A Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds

PubMed Central

Martín-Acebes, Miguel A.; Blázquez, Ana-Belén; de Oya, Nereida Jiménez; Escribano-Romero, Estela; Shi, Pei-Yong; Saiz, Juan-Carlos

2013-01-01

West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses. PMID:23874963

Home-based intermediate care program vs hospitalization: Cost comparison study.

PubMed

Armstrong, Catherine Deri; Hogg, William E; Lemelin, Jacques; Dahrouge, Simone; Martin, Carmel; Viner, Gary S; Saginur, Raphael

2008-01-01

To explore whether a home-based intermediate care program in a large Canadian city lowers the cost of care and to look at whether such home-based programs could be a solution to the increasing demands on Canadian hospitals. Single-arm study with historical controls. Department of Family Medicine at the Ottawa Hospital (Civic campus) in Ontario. Patients requiring hospitalization for acute care. Participants were matched with historical controls based on case-mix, most responsible diagnosis, and level of complexity. Placement in the home-based intermediate care program. Daily home visits from the nurse practitioner and 24-hour access to care by telephone. Multivariate regression models were used to estimate the effect of the program on 5 outcomes: length of stay in hospital, cost of care substituted for hospitalization (Canadian dollars), readmission for a related diagnosis, readmission for any diagnosis, and costs incurred by community home-care services for patients following discharge from hospital. The outcomes of 43 hospital admissions were matched with those of 363 controls. Patients enrolled in the program stayed longer in hospital (coefficient 3.3 days, P < .001), used more community care services following discharge (coefficient $729, P = .007), and were more likely to be readmitted to hospital within 3 months of discharge (coefficient 17%, P = .012) than patients treated in hospital. Total substituted costs of home-based care were not significantly different from the costs of hospitalization (coefficient -$501, P = .11). While estimated cost savings were not statistically significant, the limitations of our study suggest that we underestimated these savings. In particular, the economic inefficiencies of a small immature program and the inability to control for certain factors when selecting historical controls affected our results. Further research is needed to determine the economic effect of mature home-based programs.

Foods for Special Dietary Needs: Non-dairy Plant-based Milk Substitutes and Fermented Dairy-type Products.

PubMed

Mäkinen, Outi Elina; Wanhalinna, Viivi; Zannini, Emanuele; Arendt, Elke Karin

2016-01-01

A growing number of consumers opt for plant-based milk substitutes for medical reasons or as a lifestyle choice. Medical reasons include lactose intolerance, with a worldwide prevalence of 75%, and cow's milk allergy. Also, in countries where mammal milk is scarce and expensive, plant milk substitutes serve as a more affordable option. However, many of these products have sensory characteristics objectionable to the mainstream western palate. Technologically, plant milk substitutes are suspensions of dissolved and disintegrated plant material in water, resembling cow's milk in appearance. They are manufactured by extracting the plant material in water, separating the liquid, and formulating the final product. Homogenization and thermal treatments are necessary to improve the suspension and microbial stabilities of commercial products that can be consumed as such or be further processed into fermented dairy-type products. The nutritional properties depend on the plant source, processing, and fortification. As some products have extremely low protein and calcium contents, consumer awareness is important when plant milk substitutes are used to replace cow's milk in the diet, e.g. in the case of dairy intolerances. If formulated into palatable and nutritionally adequate products, plant-based substitutes can offer a sustainable alternative to dairy products.

AUTO-MUTE 2.0: A Portable Framework with Enhanced Capabilities for Predicting Protein Functional Consequences upon Mutation.

PubMed

Masso, Majid; Vaisman, Iosif I

2014-01-01

The AUTO-MUTE 2.0 stand-alone software package includes a collection of programs for predicting functional changes to proteins upon single residue substitutions, developed by combining structure-based features with trained statistical learning models. Three of the predictors evaluate changes to protein stability upon mutation, each complementing a distinct experimental approach. Two additional classifiers are available, one for predicting activity changes due to residue replacements and the other for determining the disease potential of mutations associated with nonsynonymous single nucleotide polymorphisms (nsSNPs) in human proteins. These five command-line driven tools, as well as all the supporting programs, complement those that run our AUTO-MUTE web-based server. Nevertheless, all the codes have been rewritten and substantially altered for the new portable software, and they incorporate several new features based on user feedback. Included among these upgrades is the ability to perform three highly requested tasks: to run "big data" batch jobs; to generate predictions using modified protein data bank (PDB) structures, and unpublished personal models prepared using standard PDB file formatting; and to utilize NMR structure files that contain multiple models.

Ultrasensitive Laser Spectroscopy in Solids: Single-Molecule Detection

DTIC Science & Technology

1989-10-25

spite of detection intensity constraints necessary to avoid power broadening, the optical absorption spectrum of single molecules of pentacene In p...molecule detection, or SMD) would provide a useful tool for the study of local host-absorber interactions where tihe absorbing ,ontor is essentially at...modulation techniques 7. 8 for the model system composed of pentacene substitutional impurities in p-terphenyl crystals at 1.5K. The pontacene molecules can

Electronic structure of alloys

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

Ehrenreich, H.; Schwartz, L.M.

1976-01-01

The description of electronic properties of binary substitutional alloys within the single particle approximation is reviewed. Emphasis is placed on a didactic exposition of the equilibrium properties of the transport and magnetic properties of such alloys. Topics covered include: multiple scattering theory; the single band alloy; formal extensions of the theory; the alloy potential; realistic model state densities; the s-d model; and the muffin tin model. 43 figures, 3 tables, 151 references. (GHT)

Performance of PIN-PMN-PT Single Crystal Piezoelectric versus PZT8 Piezoceramic Materials in Ultrasonic Transducers

NASA Astrophysics Data System (ADS)

DeAngelis, D. A.; Schulze, G. W.

The recent advancements in the manufacturing of single crystal PIN-PMN-PT piezoelectric materials now make them a cost-competitive alternative to PZT4 and PZT8 (Navy Types I and III) piezoceramic materials, which have been the workhorse of power ultrasonic applications (e.g., welding, cutting, sonar, etc.) for over 50 years. Although there are great benefits to the use of single crystal materials with respect to high output, as well as added actuating and sensing abilities, many transducer designers are still reluctant to explore these materials due to inadequate design guidelines for substituting the familiar PZT materials; for example, what are the implications of the higher capacitance, sensitivity to chipping/cracks, aging effects, frequency shifts, or how much preload can be used are all common questions. This research is a case study on the performance of identical ultrasonic transducer bodies, used for semiconductor wire bonding, assembled with either PZT8 or PIN-PMN-PT piezo material. The main purpose of the study is to establish rule-of-thumb design guidelines for direct substitution of single crystal materials in existing PZT8 transducer designs, along with a side-by-side performance comparison to highlight benefits. Several metrics are investigated such as impedance, frequency, displacement gain, quality factor and electromechanical coupling factor.

Co-solvents with high coulombic efficiency in propylene carbonate based electrolytes

DOEpatents

Liu, Gao; Zhao, Hui; Park, Sang-Jae

2017-06-27

A homologous series of cyclic carbonate or propylene carbonate (PC) analogue solvents with increasing length of linear alkyl substitutes were synthesized and used as co-solvents with PC for graphite based lithium ion half cells. A graphite anode reaches a capacity around 310 mAh/g in PC and its analogue co-solvents with 99.95% Coulombic efficiency. Cyclic carbonate co-solvents with longer alkyl chains are able to prevent exfoliation of graphite when used as co-solvents with PC. The cyclic carbonate co-solvents of PC compete for solvation of Li ion with PC solvent, delaying PC co-intercalation. Reduction products of PC on graphite surfaces via single-electron path form a stable Solid Electrolyte Interphase (SEI), which allows the reversible cycling of graphite.

Self-assembly of Terbium(III)-based metal-organic complexes with two-photon absorbing active

NASA Astrophysics Data System (ADS)

Li, Dandan; Shao, Nanqi; Sun, Xianshun; Zhang, Guocui; Li, Shengli; Zhou, Hongping; Wu, Jieying; Tian, Yupeng

2014-12-01

Hybrid complexes based on D-π-A type dyes p-aminostyryl-pyridinum and Terbium(III) complex anion (1, 2) have been synthesized by ionic exchange reaction. Meanwhile two different alkyl-substituted amino groups were used as electron donors in organic dyes cations. The synthesized complexes were characterized by element analysis. In addition, the structural features of them were systematic studied by single crystal X-ray diffraction analysis. Their linear properties have been systematically investigated by absorption spectra and fluorescence, the results show that the energy transfer takes place from the trans-4-[4‧-(N,N-diethylamino)styryl]-N-methyl pyridinium (2‧) cation to Tb(III). In addition, complex 2 exhibit a large two-photon absorption coefficient β: 0.044 cm/GW at 710 nm.

Study of structure and dielectric properties of 1:2 type modified Barium Niobates in bulk and thin film forms

NASA Astrophysics Data System (ADS)

Bishnoi, Bhagwanti Ben S.

In view of the processing and environmental issues pertaining to lead based ferroelectric materials, investigations on lead free ferroelectrics are carried intensively in recent years. These materials are interesting because, they are flexible with respect to structural changes and functional properties. These materials have potential device applications such as capacitors, sensors, actuators, and memory storage and microwave devices. This thesis is an attempt to elucidate the effect of substitution of isovalent ions (Sr, Ca) at the 'A' site of Hexagonal structured Barium Magnesium Niobate Ba(Mgl/3Nb 2/3)O3 (BMN) as well as effect of simultaneous substitution of divalent ions (Co2+ and Cu2+) on the 'B'-site' of Ba(Mg1/3Nb2/3)O3 (BMN) and Sr(Mg 1/3Nb2/3)O3 (SMN). Their structural, morphological, dielectric, impedance and optical properties are investigated. The XRD study on the ceramic compositions (SMN) showed single phase monoclinic hexagonal perovskite structure at room temperature. The SEM micrograph shows that the grains are uniformly distributed throughout the surface and the average grain size decreases with the substitution of divalent ion doping in Sr(Mg 1/3Nb2/3)O3 ceramic. The diffusivity of ceramics increases with increase in divalent ions substitution. The dielectric study confirmed that the relaxor nature is introduced in the Barium Niobate on replacement by other divalent ions at the A- or B'-site. Among various compositions in Sr(Cu1/3Nb2/3)O3 we obtained most promising dielectric properties. The impedance and modulus spectroscopy were employed to evaluate the different electrical properties of the grain and grain boundary of the ceramics. Ac Conductivity shows the two types of hopping conduction mechanism in frequency exponent vs temperature plots after the divalent ions replacement. The optical band gaps were calculated from UV-Visible spectroscopy ceramic suggested the presence of intermediately energy levels within the band gap. The single phase thin films of various compositions with A- and B'-site substitutions were successfully made using Pulsed laser deposition technique. Over all properties of films are identical to the respective bulk compositions except for some of the samples which exhibited relaxor behaviour only in the film form. Compared to O7+ irradiation the Ag15+ irradiation due to type of defects it created is more effective in reducing lattice strain induced dielectric losses along with marginal loss of dielectric constant. Significant increase in dielectric constant with low loss, on O 7+ as well as Ag15+ ion irradiation, may enhance the electro-optical properties which in turn increase compounds tuneablility for device applications.

The impact of CRISPR repeat sequence on structures of a Cas6 protein-RNA complex

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

Wang, Ruiying; Zheng, Han; Preamplume, Gan

The repeat-associated mysterious proteins (RAMPs) comprise the most abundant family of proteins involved in prokaryotic immunity against invading genetic elements conferred by the clustered regularly interspaced short palindromic repeat (CRISPR) system. Cas6 is one of the first characterized RAMP proteins and is a key enzyme required for CRISPR RNA maturation. Despite a strong structural homology with other RAMP proteins that bind hairpin RNA, Cas6 distinctly recognizes single-stranded RNA. Previous structural and biochemical studies show that Cas6 captures the 5' end while cleaving the 3' end of the CRISPR RNA. Here, we describe three structures and complementary biochemical analysis of amore » noncatalytic Cas6 homolog from Pyrococcus horikoshii bound to CRISPR repeat RNA of different sequences. Our study confirms the specificity of the Cas6 protein for single-stranded RNA and further reveals the importance of the bases at Positions 5-7 in Cas6-RNA interactions. Substitutions of these bases result in structural changes in the protein-RNA complex including its oligomerization state.« less

Molecular spectrum of somaclonal variation in regenerated rice revealed by whole-genome sequencing.

PubMed

Miyao, Akio; Nakagome, Mariko; Ohnuma, Takako; Yamagata, Harumi; Kanamori, Hiroyuki; Katayose, Yuichi; Takahashi, Akira; Matsumoto, Takashi; Hirochika, Hirohiko

2012-01-01

Somaclonal variation is a phenomenon that results in the phenotypic variation of plants regenerated from cell culture. One of the causes of somaclonal variation in rice is the transposition of retrotransposons. However, many aspects of the mechanisms that result in somaclonal variation remain undefined. To detect genome-wide changes in regenerated rice, we analyzed the whole-genome sequences of three plants independently regenerated from cultured cells originating from a single seed stock. Many single-nucleotide polymorphisms (SNPs) and insertions and deletions (indels) were detected in the genomes of the regenerated plants. The transposition of only Tos17 among 43 transposons examined was detected in the regenerated plants. Therefore, the SNPs and indels contribute to the somaclonal variation in regenerated rice in addition to the transposition of Tos17. The observed molecular spectrum was similar to that of the spontaneous mutations in Arabidopsis thaliana. However, the base change ratio was estimated to be 1.74 × 10(-6) base substitutions per site per regeneration, which is 248-fold greater than the spontaneous mutation rate of A. thaliana.

Multiple Genetic Pathways Involving Amino Acid Position 143 of HIV-1 Integrase Are Preferentially Associated with Specific Secondary Amino Acid Substitutions and Confer Resistance to Raltegravir and Cross-Resistance to Elvitegravir

PubMed Central

Frantzell, Arne; Fransen, Signe; Petropoulos, Christos J.

2013-01-01

Y143C,R substitutions in HIV-1 integrase define one of three primary raltegravir (RAL) resistance pathways. Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL treatment. Integrase amino acid sequences and RAL susceptibility were characterized in 117 patient isolates submitted for drug resistance testing and contained Y143 amino acid changes. The influence of specific Y143 substitutions on RAL susceptibility and their preferential association with particular secondary substitutions were further defined by evaluating the composition of patient virus populations along with a large panel of site-directed mutants. Our observations demonstrate that the RAL resistance profiles of Y143A,G,H,S viruses and their association with specific secondary substitutions are similar to the well-established Y143C profile but distinct from the Y143R profile. Y143R viruses differ from Y143A,C,G,H,S viruses in that Y143R confers a greater reduction in RAL susceptibility as a single substitution, consistent with a lower resistance barrier. Among Y143A,C,G,H,S viruses, the higher prevalence of Y143C viruses is the result of a lower genetic barrier than that of the Y143A,G,S viruses and a lower resistance barrier than that of the Y143H viruses. In addition, Y143A,C,G,H,S viruses require multiple secondary substitutions to develop large reductions in RAL susceptibility. Patient-derived viruses containing Y143 substitutions exhibit cross-resistance to elvitegravir. PMID:23733474

Site specific ligand substitution in cubane-type Mo3FeS(4)(4+) clusters: kinetics and mechanism of reaction and isolation of mixed ligand Cl/SPh complexes.

PubMed

Algarra, Andrés G; Basallote, Manuel G; Fernandez-Trujillo, M J; Llusar, Rosa; Pino-Chamorro, Jose A; Sorribes, Ivan; Vicent, Cristian

2010-04-21

The synthesis, crystal structure and solution characterization of the cubane-type [Mo(3)(FeCl)S(4)(dmpe)(3)Cl(3)] (1) (dmpe = 1,2-bis(dimethylphophane-ethane)) cluster are reported and the ligand substitution processes of chloride by thiophenolate investigated. The kinetics and the intimate mechanism of these substitutions reveal that compound 1 undergoes a number of Fe and Mo site specific ligand substitution reactions in acetonitrile solutions. In particular, PhS(-) coordination at the tetrahedral Fe site proceeds in a single resolved kinetic step whereas such substitutions at the Mo sites proceed more slowly. The effect of the presence of acids in the reaction media is also investigated and reveals that an acid excess hinders substitution reactions both at the Fe and Mo sites; however, an acid-promoted solvolysis of the Fe-Cl bonds is observed. Electrospray ionization (ESI) and tandem (ESI-MS/MS) mass spectrometry allow the identification of all the reaction intermediates proposed on the basis of stopped-flow measurements. The distinctive site specific reactivity made it possible to isolate two new clusters of the Mo(3)FeS(4)(4+) family featuring mixed chlorine/thiophenolate ligands, namely Mo(3)S(4)(FeSPh)(dmpe)(3)Cl(3) (2) and [Mo(3)S(4)(FeSPh)(dmpe)(3)(SPh)(3)] (3). A detailed computational study has also been carried out to understand the details of the mechanism of substitution at the M-Cl (M = Mo and Fe) bonds as well as the solvolysis at the Fe-Cl sites, with particular emphasis on the role of acids on the substitution process. The results of the calculations are in agreement with the experimental observations, thus justifying the non-existence of an accelerating effect of acids on the thiophenolate substitution reaction, which differs from previous proposals for the Fe(4)S(4) and MoFe(3)S(4) clusters and some related compounds.

The Questionable Economic Case for Value-Based Drug Pricing in Market Health Systems.

PubMed

Pauly, Mark V

2017-02-01

This article investigates the economic theory and interpretation of the concept of "value-based pricing" for new breakthrough drugs with no close substitutes in a context (such as the United States) in which a drug firm with market power sells its product to various buyers. The interpretation is different from that in a country that evaluates medicines for a single public health insurance plan or a set of heavily regulated plans. It is shown that there will not ordinarily be a single value-based price but rather a schedule of prices with different volumes of buyers at each price. Hence, it is incorrect to term a particular price the value-based price, or to argue that the profit-maximizing monopoly price is too high relative to some hypothesized value-based price. When effectiveness of treatment or value of health is heterogeneous, the profit-maximizing price can be higher than that associated with assumed values of quality-adjusted life-years. If the firm sets a price higher than the value-based price for a set of potential buyers, the optimal strategy of the buyers is to decline to purchase that drug. The profit-maximizing price will come closer to a unique value-based price if demand is less heterogeneous. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Dielectric properties of rare earth (Sm and La) substituted lead zirconate titanate (PZT) ceramics

NASA Astrophysics Data System (ADS)

Dipti, Singh, Sangeeta; Juneja, J. K.; Raina, K. K.; Prakash, Chandra

2013-06-01

In the present paper, we are reporting the studies on dielectric properties of Lanthanum (La) and Samarium (Sm) substituted Lead Zirconate Titanate with compositional formula Pb(1.02-x)SmxZr0.55Ti0.45O3 and Pb(1.02-x)LaxZr0.55Ti0.45O3 with x = 0.00, 0.01, 0.02, 0.03. The materials were synthesized by solid state reaction route. XRD analysis shows that all the samples be in single phase with tetragonal structure. Dielectric properties were studied as a function of temperature.

Palladium-catalyzed Kumada coupling reaction of bromoporphyrins with silylmethyl Grignard reagents: preparation of silylmethyl-substituted porphyrins as a multipurpose synthon for fabrication of porphyrin systems.

PubMed

Sugita, Noriaki; Hayashi, Satoshi; Hino, Fumio; Takanami, Toshikatsu

2012-12-07

We have developed an efficient method for preparing silylmethyl-substituted porphyrins via the palladium-catalyzed Kumada cross-coupling reaction of bromoporphyrins with silylmethyl Grignard reagents. We demonstrated the synthetic utility of these silylmethylporphyrins as a multipurpose synthon for fabricating porphyrin derivatives through a variety of transformations of the silylmethyl groups, including the DDQ-promoted oxidative conversion to CHO, CH(2)OH, CH(2)OMe, and CH(2)F functionalities and the fluoride ion-mediated desilylative introduction of carbon-carbon single and double bonds.

Syntheses, structural characterization, and basic properties of unsymmetrically substituted biphenoquinones

NASA Astrophysics Data System (ADS)

Fujii, Ryotaro; Sugiura, Ken-ichi

2018-03-01

Unsymmetrically substituted biphenoquinones, 3,5-dimethyl-3‧,5‧-diphenylbiphenoquinone and 3,5-di-tert-butyl-3‧,5‧-diphenylbiphenoquinone, were prepared by a mixed oxidative coupling reaction of the corresponding phenols with potassium permanganate in CHCl3. The properties of the quinones such as reduction potential and visible light absorption were measured and positively shifted reduction potentials and bathochromic shifts as a result of light absorption were found to be characteristic of the π-expanded quinones. We also carried out single-crystal diffraction study and uncovered a unique packing motif attributable to their unsymmetrical structures.

Fast and Selective Two-Stage Ratiometric Fluorescent Probes for Imaging of Glutathione in Living Cells.

PubMed

Gong, Deyan; Han, Shi-Chong; Iqbal, Anam; Qian, Jing; Cao, Ting; Liu, Wei; Liu, Weisheng; Qin, Wenwu; Guo, Huichen

2017-12-19

Two fluorescent, m-nitrophenol-substituted difluoroboron dipyrromethene dyes have been designed by nucleophilic substitution reaction of 3,5-dichloro-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY). Nonsymmetric and symmetric probes, that is. BODIPY 1 (with one nitrophenol group at the position 3) and BODIPY 2 (with two nitrophenol groups at the positions 3 and 5) were applied to ratiometric fluorescent glutathione detection. The detection is based on the two-step nucleophilic aromatic substitution of the nitrophenol groups of the probes by glutathione in buffer solution containing CTAB. In the first stage, probe 1 showed ratiometric fluorescent color change from green (λ em = 530 nm) to yellow (λ em = 561 nm) because of monosubstitution with glutathione (I 561nm /I 530nm ). Addition of excess glutathione caused the second stage of ratiometric fluorescent color change from yellow to reddish orange (λ em = 596 nm, I 596nm /I 561nm ) due to disubstitution with glutathione. Therefore, different concentration ranges of glutathione (from less to excess) could be rapidly detected by the two-stage ratiometric fluorescent probe 1 in 5 min. While, probe 2 shows single-stage ratiometric fluorescent detection to GSH (from green to reddish orange, I 596nm /I 535nm ). Probes 1 and 2 exhibit excellent properties with sensitive, specific colorimetric response and ratiometric fluorescent response to glutathione over other sulfur nucleophiles. Application to cellular ratiometric fluorescence imaging indicated that the probes were highly responsive to intracellular glutathione.

Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: Evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta

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

Spotila, L.D.; Constantinou, C.D.; Sereda, L.

Mutations in the two genes for type I collagen (COL1A1 or COL1A2) cause osteogenesis imperfecta (OI), a heritable disease characterized by moderate to extreme brittleness of bone early in life. Here, the authors show that a 52-year-old post menopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the {alpha}2(I) chain of type I collagen (COL1A2) similar to mutations that cause OI. cDNA was prepared from the woman's skin fibroblast RNA and assayed for the presence of a mutation by treating DNA heteroduplexes with carbodiimide. The results indicated a sequencemore » variation in the region encoding amino acid residues 660-667 of the {alpha}2(I) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the {alpha}2(I) triple-helical domain. The substitution produced posttranslational overmodification of the collagen triple helix, as is seen with most glycine substitutions that cause OI. The patient had a history of five previous fractures, slightly blue sclerae, and slight hearing loss. Therefore, the results suggest that there may be phenotypic and genotypic overlap between mild osteogenesis imperfecta and postmenopausal osteoporosis, and that a subset of women with postmenopausal osteoporosis may have mutations in the genes for type I procollagen.« less

Cd(II)-coordination polymers based on tetracarboxylic acid and diverse bis(imidazole) ligands: Synthesis, structural diversity and photoluminescence properties

NASA Astrophysics Data System (ADS)

Arıcı, Mürsel; Yeşilel, Okan Zafer; Taş, Murat

2017-01-01

Three new Cd(II)-coordination polymers, namely, {[Cd2(μ6-ao2btc)(μ-1,5-bipe)2]·2H2O}n (1), {[Cd2(μ6-ao2btc)(μ-1,4-bix)2]n·2DMF} (2) and {[Cd2(μ8-abtc)(μ-1,4-betix)]·DMF·H2O}n (3) (ao2btc=di-oxygenated form of 3,3‧,5,5‧-azobenzenetetracarboxylate, 1,5-bipe: 1,5-bis(imidazol-1yl)pentane, 1,4-bix=1,4-bis(imidazol-1ylmethyl)benzene, 1,4-betix=1,4-bis(2-ethylimidazol-1ylmethyl)benzene) were synthesized with 3,3‧,5,5‧-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1-3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd2(CO2)4-type binuclear SBU. Moreover, thermal and photoluminescence properties of the complexes were determined in detailed.

Impedance and AC conductivity studies of Sm3+ substituted 0.8Ba0.2(Bi0.5K0.5)TiO3 lead free ceramics

NASA Astrophysics Data System (ADS)

Sastry, C. V. S. S.; Ramesh, M. N. V.; Ramesh, K. V.

2017-07-01

Samarium substituted 0.8Ba0.2(Bi0.5K0.5)TiO3 (here after abbreviated as BTBKT-20) lead free ceramics with composition 0.8Ba0.2(Bi0.5(1-x)Sm0.5xK0.5)TiO3 (where x=0.01,0.03,0.05) lead free ceramics have been prepared by solid state reaction and followed by high energy ball milling process. The present paper focuses the impedance and ac conductivity studies of Sm substituted BTBKT-20 lead free ceramics. Impedance spectroscopic studies revealthat temperature dependent relaxation process. Single depressed semi circle was observed in Cole-Cole plots, indicates non-Debye kind of relaxation process. Maximum grain resistance was observed for x=0.03 Sm substituted BTBKT-20 sample. Frequency and temperature dependent AC conductivity was calculated and it found to obey the universal Jonscher's power law and the values of activation energies suggest that conduction is ionic in nature.

Phylogenetic incongruence and the evolutionary origins of cardenolide-resistant forms of Na+,K+-ATPase in Danaus butterflies

PubMed Central

Aardema, Matthew L.; Andolfatto, Peter

2016-01-01

Many distantly-related insect species are specialized feeders of cardenolide-containing host plants such as milkweed (Asclepias spp.). Studies have revealed frequent, parallel substitution of a functionally important amino acid substitution (N122H) in the alpha subunit of Na+,K+-ATPase (N122H) in many of these species. This substitution facilitates the ability of these insects to feed on their toxic hosts. Among milkweed butterflies of the genus Danaus, the previously established phylogeny for this group suggests that N122H arose independently and fixed in two distinct lineages. We re-evaluate this conclusion by examining Danaus phylogenetic relationships using >400 orthologous gene sequences assembled from transcriptome data. Our results indicate that the three Danaus species known to harbor the N122H substitution are more closely related than previously thought, consistent with a single, common origin for N122H. However, we also find evidence of both incomplete lineage sorting and post-speciation genetic exchange among these butterfly species, raising the possibility of collateral evolution of cardenolide-insensitivity in this species group. PMID:27405795

Enumerating Substituted Benzene Isomers of Tree-Like Chemical Graphs.

PubMed

Li, Jinghui; Nagamochi, Hiroshi; Akutsu, Tatsuya

2018-01-01

Enumeration of chemical structures is useful for drug design, which is one of the main targets of computational biology and bioinformatics. A chemical graph with no other cycles than benzene rings is called tree-like, and becomes a tree possibly with multiple edges if we contract each benzene ring into a single virtual atom of valence 6. All tree-like chemical graphs with a given tree representation are called the substituted benzene isomers of . When we replace each virtual atom in with a benzene ring to obtain a substituted benzene isomer, distinct isomers of are caused by the difference in arrangements of atom groups around a benzene ring. In this paper, we propose an efficient algorithm that enumerates all substituted benzene isomers of a given tree representation . Our algorithm first counts the number of all the isomers of the tree representation by a dynamic programming method. To enumerate all the isomers, for each , our algorithm then generates the th isomer by backtracking the counting phase of the dynamic programming. We also implemented our algorithm for computational experiments.

The Effect of Terminal Substitution on the Helical Carbon Structure of Fluoro-Alkane Chains: a Pure Rotational Study of CH2OH-Cn-1F2n-1 (n = 4, 5,& 6)

NASA Astrophysics Data System (ADS)

Schwartz, Aaron Z. A.; Maturo, Mark P.; Obenchain, Daniel A.; Cooke, S. A.

2016-06-01

Continuing a series of studies to investigate the change in structure of hydrocarbons as the amount of fluorination is increased to varying degrees of substitution, we present a survey on the change in the helical nature of the fluorinated carbon backbone when a -CH2OH group is substituted for a terminal - CF3 group. Spectra for 1H,1H-heptafluorobutan-1-ol, 1H,1H-nonafluoropentan-1-ol, and 1H,1H-undecafluorohexan-1-ol were collected separately using a chirped-pulse FTMW spectrometer in the range of 7-13 GHz. Only one conformation was observed for each molecule. Additional measurements of the 1H,1H-heptafluorobutan-1-ol were completed using a Balle-Flygare cavity instrument. Assignments of the singly-substituted 13C isotopologues of the 1H,1H-heptafluorobutan-1-ol were also measured. A comparison of both ab initio and experimental structures will be presented.

Structural and electrochemical properties of annealed La1-xYxNi3.55Mno.4Alo.3Coo.75 hydrogen storage alloys.

PubMed

Du, Yulei; Li, Wei

2011-06-01

The effects of the annealing and partial substitution of Y for La on the structural and electrochemical properties of La1-xYxNi3.55Mno.4Alo.3Cro.75 (x = 0, 0.1 and 0.2) alloys were reported in the present work. The single-phased CaCu5-type structure was retained after La was partially substituted by Y. However, the increase of Y content leads to decrease of the lattice parameters and the unit-cell volume. The annealed Lao.9Yo.1Ni3.55Mno.4Alo.3Coo.75 alloys shows typical isometric microstructure, indicating that the composition segregation is improved by annealing. Y substitution for La in the alloys is effective to improve the electrochemical properties at both room temperature and high temperature. A critical substitution content of Y is found at x = 0.1. Copyright © 2011 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Structural, electrical and magnetic study of Nd-Ni substituted W-type Hexaferrite

NASA Astrophysics Data System (ADS)

Khan, Imran; Sadiq, Imran; Ali, Irshad; Rana, Mazhar-Ud-Din; Najam-Ul-Haq, Muhammad; Shah, Afzal; Shakir, Imran; Naeem Ashiq, Muhammad

2016-01-01

A series of Nd-Ni substituted W-type hexaferrites with composition Sr1-xNdxCo2NiyFe16-yO27 (where x=0.0, 0.025, 0.050, 0.075, 0.1 and y=0.0, 0.25, 0.50, 0.75, 1) has been prepared by the chemical co-precipitation method. The effect of rare earth Nd substitution at strontium site while Ni at iron site on microstructure, electrical and magnetic properties has been investigated. All the XRD patterns of the synthesized materials show single W-type hexagonal phase without any other intermediate phases. SEM images show that the particles are homogeneous and hexagonal platelet-like shape. DC electrical resistivity measurements were carried out in temperature range of 298-673 K showing metal-to-semiconductor transition when doped with Nd-Ni. The magnetic properties such as saturation magnetization, remanence, squareness ratio and coercivity were calculated from hysteresis loops and were observed to increase with the increase in Nd-Ni concentration up to a certain substitution level which is beneficial for high density recording media.

Applying School Administrators' Authentic Leadership Skills in Conflict Situations: The Perceptions of Substitute Teachers

ERIC Educational Resources Information Center

Demirdag, Seyithan; Kalafat, Sezai

2016-01-01

This study mainly aimed to determine the relationships between conflict management strategies and authentic leadership attitudes of primary school administrators based on the perception of substitute teachers, who were in pedagogical proficiency classes at a university. This quantitative study included 456 substitute teachers. Two instruments were…

Coarse graining of atactic polystyrene and its derivatives

NASA Astrophysics Data System (ADS)

Agrawal, Anupriya; Perahia, Dvora; Grest, Gary S.

2014-03-01

Capturing large length scales in polymers and soft matter while retaining atomistic properties is imperative to computational studies of dynamic systems. Here we present a new methodology developing coarse-grain model based on atomistic simulation of atactic polystyrene (PS). Similar to previous work by Fritz et al., each monomer is described by two coarse grained beads. In contrast to this earlier work where intramolecular potentials were based on Monte Carlo simulation of both isotactic and syndiotactic single PS molecule to capture stereochemistry, we obtained intramolecular interactions from a single molecular dynamics simulation of an all-atom atactic PS melts. The non-bonded interactions are obtained using the iterative Boltzmann inversion (IBI) scheme. This methodology has been extended to coarse graining of poly-(t-butyl-styrene) (PtBS). An additional coarse-grained bead is used to describe the t-butyl group. Similar to the process for PS, the intramolecular interactions are obtained from a single all atom atactic melt simulation. Starting from the non-bonded interactions for PS, we show that the IBI method for the non-bonded interactions of PtBS converges relatively fast. A generalized scheme for substituted PS is currently in development. We would like to acknowledge Prof. Kurt Kremer for helpful discussions during this work.

Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli

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

Burnouf, D.; Fuchs, R.P.P.; Gauthier, C.

1990-08-01

The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP(d(ApG)) adducts, although they account for only 25% of the lesions formed are {approx}5 times more mutagenic than the major GG adduct. The authors report the construction of vectors bearing a single cisDDP(d(ApG)) lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5{prime} base of the adduct.more » Single A {yields} T transversions are mainly observed (80%), whereas A {yields} G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5{prime} to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP(d(ApG)) adducts are not blocking lesions. The high mutation specificity of cisDDP-(d(ApG))-induced mutagenesis is discussed in relation to structural data.« less

Complete Genome Sequence of ER2796, a DNA Methyltransferase-Deficient Strain of Escherichia coli K-12.

PubMed

Anton, Brian P; Mongodin, Emmanuel F; Agrawal, Sonia; Fomenkov, Alexey; Byrd, Devon R; Roberts, Richard J; Raleigh, Elisabeth A

2015-01-01

We report the complete sequence of ER2796, a laboratory strain of Escherichia coli K-12 that is completely defective in DNA methylation. Because of its lack of any native methylation, it is extremely useful as a host into which heterologous DNA methyltransferase genes can be cloned and the recognition sequences of their products deduced by Pacific Biosciences Single-Molecule Real Time (SMRT) sequencing. The genome was itself sequenced from a long-insert library using the SMRT platform, resulting in a single closed contig devoid of methylated bases. Comparison with K-12 MG1655, the first E. coli K-12 strain to be sequenced, shows an essentially co-linear relationship with no major rearrangements despite many generations of laboratory manipulation. The comparison revealed a total of 41 insertions and deletions, and 228 single base pair substitutions. In addition, the long-read approach facilitated the surprising discovery of four gene conversion events, three involving rRNA operons and one between two cryptic prophages. Such events thus contribute both to genomic homogenization and to bacteriophage diversification. As one of relatively few laboratory strains of E. coli to be sequenced, the genome also reveals the sequence changes underlying a number of classical mutant alleles including those affecting the various native DNA methylation systems.

Complete Genome Sequence of ER2796, a DNA Methyltransferase-Deficient Strain of Escherichia coli K-12

PubMed Central

Anton, Brian P.; Mongodin, Emmanuel F.; Agrawal, Sonia; Fomenkov, Alexey; Byrd, Devon R.; Roberts, Richard J.; Raleigh, Elisabeth A.

2015-01-01

We report the complete sequence of ER2796, a laboratory strain of Escherichia coli K-12 that is completely defective in DNA methylation. Because of its lack of any native methylation, it is extremely useful as a host into which heterologous DNA methyltransferase genes can be cloned and the recognition sequences of their products deduced by Pacific Biosciences Single-Molecule Real Time (SMRT) sequencing. The genome was itself sequenced from a long-insert library using the SMRT platform, resulting in a single closed contig devoid of methylated bases. Comparison with K-12 MG1655, the first E. coli K-12 strain to be sequenced, shows an essentially co-linear relationship with no major rearrangements despite many generations of laboratory manipulation. The comparison revealed a total of 41 insertions and deletions, and 228 single base pair substitutions. In addition, the long-read approach facilitated the surprising discovery of four gene conversion events, three involving rRNA operons and one between two cryptic prophages. Such events thus contribute both to genomic homogenization and to bacteriophage diversification. As one of relatively few laboratory strains of E. coli to be sequenced, the genome also reveals the sequence changes underlying a number of classical mutant alleles including those affecting the various native DNA methylation systems. PMID:26010885

The Sequences of 1504 Mutants in the Model Rice Variety Kitaake Facilitate Rapid Functional Genomic Studies

PubMed Central

Pham, Nikki T.; Wei, Tong; Schackwitz, Wendy S.; Lipzen, Anna M.; Duong, Phat Q.; Jones, Kyle C.; Ruan, Deling; Bauer, Diane; Peng, Yi; Schmutz, Jeremy

2017-01-01

The availability of a whole-genome sequenced mutant population and the cataloging of mutations of each line at a single-nucleotide resolution facilitate functional genomic analysis. To this end, we generated and sequenced a fast-neutron-induced mutant population in the model rice cultivar Kitaake (Oryza sativa ssp japonica), which completes its life cycle in 9 weeks. We sequenced 1504 mutant lines at 45-fold coverage and identified 91,513 mutations affecting 32,307 genes, i.e., 58% of all rice genes. We detected an average of 61 mutations per line. Mutation types include single-base substitutions, deletions, insertions, inversions, translocations, and tandem duplications. We observed a high proportion of loss-of-function mutations. We identified an inversion affecting a single gene as the causative mutation for the short-grain phenotype in one mutant line. This result reveals the usefulness of the resource for efficient, cost-effective identification of genes conferring specific phenotypes. To facilitate public access to this genetic resource, we established an open access database called KitBase that provides access to sequence data and seed stocks. This population complements other available mutant collections and gene-editing technologies. This work demonstrates how inexpensive next-generation sequencing can be applied to generate a high-density catalog of mutations. PMID:28576844

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

Li, Guotian; Jain, Rashmi; Chern, Mawsheng

The availability of a whole-genome sequenced mutant population and the cataloging of mutations of each line at a single-nucleotide resolution facilitate functional genomic analysis. To this end, we generated and sequenced a fast-neutron-induced mutant population in the model rice cultivar Kitaake (Oryza sativa ssp japonica), which completes its life cycle in 9 weeks. We sequenced 1504 mutant lines at 45-fold coverage and identified 91,513 mutations affecting 32,307 genes, i.e., 58% of all rice genes. We detected an average of 61 mutations per line. Mutation types include single-base substitutions, deletions, insertions, inversions, translocations, and tandem duplications. We observed a high proportionmore » of loss-of-function mutations. We identified an inversion affecting a single gene as the causative mutation for the short-grain phenotype in one mutant line. This result reveals the usefulness of the resource for efficient, cost-effective identification of genes conferring specific phenotypes. To facilitate public access to this genetic resource, we established an open access database called KitBase that provides access to sequence data and seed stocks. This population complements other available mutant collections and gene-editing technologies. In conclusion, this work demonstrates how inexpensive next-generation sequencing can be applied to generate a high-density catalog of mutations.« less

Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

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

Brown, M.D.; Shoffner, J.M.; Wallace, D.C.

1996-01-22

The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients ormore » 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.« less

Steroidogenic activity of fragments of adrenocorticotropin with arginine in residue positions 3 and 5.

PubMed Central

Jean-Baptiste, E; Draper, M W; Rizack, M A

1977-01-01

The maximal steroidogenic response (Smax) to adrenocorticotropin (ACTH) is enhanced by the substitution of arginine in position 3. Though the Smax of adrenocorticotropin-(3-10)-octapeptide [ACTH-(3-10)] is only 20% of ACTH-(1-24) in isolated rabbit adrenal cells and 10% in rat cells, [Arg3]ACTH-(3-10) has an Smax comparable to that of the longer peptide. Activity determined from the midpoints of dose-response curves (A50), however, is several orders of magnitude less. The Smax of ACTH-(4-10) is not significantly different from that of the 3-10 analog. Substitution of arginine in the 5 position of ACTH-(4-10) decreases activity for rabbit cells, but does not affect activity for rat cells. The substitution of arginine in the 5 position of ACTH-(1-20) markedly decreases Smax in rabbit but not rat cells. The Smax of [Arg 3,5)]ACTH-(3-10), containing both substitutions, is greater than that of ACTH-(3-10), but much less than that of [Arg3]acth-(3-10) in both species studied. These findings contrast with those in the rabbit adipocyte, where both arginine-containing ACTH analogs have enhanced activity and the effects of both substitutions in a single peptide are additive. PMID:200914

Spin-state responses to light impurity substitution in low-spin perovskite LaCoO3

NASA Astrophysics Data System (ADS)

Tomiyasu, Keisuke; Kubota, Yuuki; Shimomura, Saya; Onodera, Mitsugi; Koyama, Syun-Ichi; Nojima, Tsutomu; Ishihara, Sumio; Nakao, Hironori; Murakami, Youichi

2013-06-01

We studied the spin-state responses to light impurity substitution in low-spin perovskite LaCoO3 (Co3+: d6) through magnetization, x-ray fluorescence, and electrical resistivity measurements of single-crystal LaCo0.99M0.01O3 (M = Cr, Mn, Fe, Ni). In the magnetization curves measured at 1.8 K, a change in the spin-state was not observed for Cr, Mn, or Fe substitution but was observed for Ni substitution. Strong magnetic anisotropy was also found in the Ni-substituted sample. The fluorescence measurements revealed that the valences were roughly estimated to be Cr3+, Mn(4-δ)+, Fe(3+δ')+, and Ni3+. From the observed chemical trends, we propose that the chemical potential is a key factor in inducing the change of the low-spin state. By expanding a model of the ferromagnetic spin-state heptamer generated by hole doping [Podlesnyak , Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.101.247603 101, 247603 (2008)], the emergence of highly anisotropic spin-state molecular ferromagnets induced by low-spin Ni3+ with Jahn-Teller activity is suggested. We also discuss applicability of the present results to other materials with Fe (d6).

A Dicobalt Complex with an Unsymmetrical Quinonoid Bridge Isolated in Three Units of Charge: A Combined Structural, (Spectro)electrochemical, Magnetic and Spectroscopic Study.

PubMed

van der Meer, Margarethe; Rechkemmer, Yvonne; Frank, Uta; Breitgoff, Frauke D; Hohloch, Stephan; Su, Cheng-Yong; Neugebauer, Petr; Marx, Raphael; Dörfel, María; van Slageren, Joris; Sarkar, Biprajit

2016-09-19

Quinonoid ligands are excellent bridges for generating redox-rich dinuclear assemblies. A large majority of these bridges are symmetrically substituted, with examples of unsymmetrically substituted quinonoid bridges being extremely rare. We present here a dicobalt complex in its various redox states with an unsymmetrically substituted quinonoid bridging ligand. Two homovalent forms and one mixed-valent form have been isolated and characterized by single crystal X-ray diffraction. The complex displays a large comproportionation constant for the mixed-valent state which is three orders of magnitude higher than that observed for the analogous complex with a symmetrically substituted bridge. Results from electrochemistry, UV/Vis/NIR spectroelectrochemistry, SQUID magnetometry, multi-frequency EPR spectroscopy and FIR spectroscopy are used to probe the electronic structures of these complexes. FIR provides direct evidence of exchange coupling. The results presented here display the advantages of using an unsymmetrically substituted bridge: site specific redox chemistry, high thermodynamic stabilization of the mixed-valent form, isolation and crystallization of various redox forms of the complex. This work represents an important step on the way to generating heterodinuclear complexes for use in cooperative catalysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrochemical properties of LaNi{sub 5{minus}x}Ge{sub x} alloys in Ni-MH batteries

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

Witham, C.; Hightower, A.; Fultz, B.

1997-11-01

Electrochemical studies were performed on LaNi{sub 5{minus}x}Ge{sub x} metal hydride alloys with 0 {le} x {le} 0.5. The authors carried out single-electrode studies to understand the effects of the Ge substituent on the hydrogen absorption characteristics, the electrochemical capacity, and the electrochemical kinetics of hydrogen absorption and desorption. The electrochemical characteristics of the Ge-substituted alloys are compared to those of the Sn-substituted alloys reported earlier. LaNi{sub 5{minus}x}Ge{sub x} alloys show compositional trends similar to LaNi{sub 5{minus}x}Sn{sub x} alloys, but unlike the Sn-substituted alloys, Ge-substituted alloys continue to exhibit facile kinetics for hydrogen absorption/desorption at high solute concentrations. Cycle lives ofmore » LaNi{sub 5{minus}x}Ge{sub x} electrodes were measured in 300 mAh laboratory test cells and were found to be superior to the Sn-substituted LaNi{sub 5} and comparable to a Mm(Ni, Co, Mn, Al){sub 5} alloy. The optimum Ge content for LaNi{sub 5{minus}x}Ge{sub x} metal hydride alloys in alkaline rechargeable cells is in the range 0.4 {le} x {le} 0.5.« less

Characterization of 2-Oxindole Forming Heme Enzyme MarE, Expanding the Functional Diversity of the Tryptophan Dioxygenase Superfamily.

PubMed

Zhang, Yuyang; Zou, Yi; Brock, Nelson L; Huang, Tingting; Lan, Yingxia; Wang, Xiaozheng; Deng, Zixin; Tang, Yi; Lin, Shuangjun

2017-08-30

3-Substituted 2-oxindoles are important structural motifs found in many biologically active natural products and pharmaceutical lead compounds. Here, we report an enzymatic formation of the 3-substituted 2-oxindoles catalyzed by MarE in the maremycin biosynthetic pathway in Streptomyces sp. B9173. MarE is a homologue of Fe II /heme-dependent tryptophan 2,3-dioxygenases (TDOs). Typical TDOs usually catalyze the insertion of two oxygen atoms from O 2 into an indole ring to generate N-formylkynurenine (NFK)-like products. In contrast, MarE catalyzes the insertion of a single oxygen atom from O 2 into an indole ring, to probably generate an epoxyindole intermediate that undergoes an unprecedented 2,3-hydride migration to form 2-oxindole structure. MarE shows substrate robustness to catalyze the conversion of a series of 3-substituted indoles into their corresponding 3-substituted 2-oxindoles. Although containing most key amino acid residues conserved in well-known TDO homologues, MarE falls into a separate new subgroup in the phylogenetic tree. The characterization of MarE and its homologue enriches the functional diversities of TDO superfamily and provides a new strategy for discovering novel natural products containing 3-substituted 2-oxindole pharmacophores by genome mining.

Entropy Beacon: A Hairpin-Free DNA Amplification Strategy for Efficient Detection of Nucleic Acids

PubMed Central

2015-01-01

Here, we propose an efficient strategy for enzyme- and hairpin-free nucleic acid detection called an entropy beacon (abbreviated as Ebeacon). Different from previously reported DNA hybridization/displacement-based strategies, Ebeacon is driven forward by increases in the entropy of the system, instead of free energy released from new base-pair formation. Ebeacon shows high sensitivity, with a detection limit of 5 pM target DNA in buffer and 50 pM in cellular homogenate. Ebeacon also benefits from the hairpin-free amplification strategy and zero-background, excellent thermostability from 20 °C to 50 °C, as well as good resistance to complex environments. In particular, based on the huge difference between the breathing rate of a single base pair and two adjacent base pairs, Ebeacon also shows high selectivity toward base mutations, such as substitution, insertion, and deletion and, therefore, is an efficient nucleic acid detection method, comparable to most reported enzyme-free strategies. PMID:26505212

Review: Potential Strength of Fly Ash-Based Geopolymer Paste with Substitution of Local Waste Materials with High-Temperature Effect

NASA Astrophysics Data System (ADS)

Subekti, S.; Bayuaji, R.; Darmawan, M. S.; Husin, N. A.; Wibowo, B.; Anugraha, B.; Irawan, S.; Dibiantara, D.

2017-11-01

This research provided an overview of the potential fly ash based geopolymer paste for application in building construction. Geopolymer paste with various variations of fly ash substitution with local waste material and high-temperature influence exploited with the fresh and hardened condition. The local waste material which utilized for this study were sandblasting waste, carbide waste, shell powder, bagasse ash, rice husk and bottom ash. The findings of this study indicated that fly-based geopolymer paste with local waste material substitution which had high-temperature influence ash showed a similar nature of OPC binders potentially used in civil engineering applications.

Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange

PubMed Central

Hmelo, Laura R.; Borlee, Bradley R.; Almblad, Henrik; Love, Michelle E.; Randall, Trevor E.; Tseng, Boo Shan; Lin, Chuyang; Irie, Yasuhiko; Storek, Kelly M.; Yang, Jaeun Jane; Siehnel, Richard J.; Howell, P. Lynne; Singh, Pradeep K.; Tolker-Nielsen, Tim; Parsek, Matthew R.; Schweizer, Herbert P.; Harrison, Joe J.

2016-01-01

Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knockins, as well as single nucleotide insertions, deletions and substitutions in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selection are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNA. The entire procedure requires ~2 weeks. PMID:26492139

Catalytic hydrodeoxygenation of methyl-substituted phenols: correlations of kinetic parameters with molecular properties.

PubMed

Massoth, F E; Politzer, P; Concha, M C; Murray, J S; Jakowski, J; Simons, Jack

2006-07-27

The hydrodeoxygenation of methyl-substituted phenols was carried out in a flow microreactor at 300 degrees C and 2.85 MPa hydrogen pressure over a sulfided CoMo/Al(2)O(3) catalyst. The primary reaction products were methyl-substituted benzene, cyclohexene, cyclohexane, and H(2)O. Analysis of the results suggests that two independent reaction paths are operative, one leading to aromatics and the other to partially or completely hydrogenated cyclohexanes. The reaction data were analyzed using Langmuir-Hinshelwood kinetics to extract the values of the reactant-to-catalyst adsorption constant and of the rate constants characterizing the two reaction paths. The adsorption constant was found to be the same for both reactions, suggesting that a single catalytic site center is operative in both reactions. Ab initio electronic structure calculations were used to evaluate the electrostatic potentials and valence orbital ionization potentials for all of the substituted phenol reactants. Correlations were observed between (a) the adsorption constant and the two reaction rate constants measured for various methyl-substitutions and (b) certain moments of the electrostatic potentials and certain orbitals' ionization potentials of the isolated phenol molecules. On the basis of these correlations to intrinsic reactant-molecule properties, a reaction mechanism is proposed for each pathway, and it is suggested that the dependencies of adsorption and reaction rates upon methyl-group substitution are a result of the substituents' effects on the electrostatic potential and orbitals rather than geometric (steric) effects.

Preparation and characterization of fusion processed solid dispersions containing a viscous thermally labile polymeric carrier.

PubMed

Hughey, Justin R; Keen, Justin M; Miller, Dave A; Brough, Chris; McGinity, James W

2012-11-15

The primary aim of the present study was to investigate the ability of hydroxypropyl and methoxyl substituted cellulose ethers to stabilize supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak base, after an acid-to-neutral pH transition. A secondary aim of the study was to evaluate the effect of fusion processes on polymer stability and molecular weight. Polymer screening studies showed that stabilization of ITZ supersaturation was related to the molecular weight of the polymer and levels of hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is characterized as having a high melt viscosity, was selected for solid dispersion formulation studies. Hot-melt extrusion processing of E50LV based compositions resulted in high torque loads, low material throughput and polymer degradation. KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as a method to prepare the solid dispersions with reduced levels of polymer degradation. An experimental design revealed that polymer molecular weight was sensitive to shearing forces and high temperatures. However, optimal processing conditions resulted in significantly reduced E50LV degradation relative to HME processing. The technique was effectively utilized to prepare homogenous solid solutions of E50LV and ITZ, characterized as having a single glass transition temperature over a wide range of drug loadings. All prepared compositions provided for a high degree of ITZ supersaturation stabilization. Copyright © 2012 Elsevier B.V. All rights reserved.

Scaling Reward Value with Demand Curves versus Preference Tests

PubMed Central

Schwartz, Lindsay P.; Silberberg, Alan; Casey, Anna H.; Paukner, Annika; Suomi, Stephen J.

2016-01-01

In Experiment 1, six capuchins lifted a weight during a 10-minute session to receive a food piece. Across conditions, the weight was increased across six different amounts for three different food types. The number of food pieces obtained as a function of the weight lifted was fitted by a demand equation that is hypothesized to quantify food value. For most subjects, this analysis showed that the three food types differed little in value. In Experiment 2, these monkeys were given pairwise choices among these food types. In 13 of 18 comparisons, preferences at least equaled a 3-to-1 ratio; in seven comparisons, preference was absolute. There was no relation between values based on degree of preference versus values based on the demand equation. When choices in the present report were compared to similar data with these subjects from another study, between-study lability in preference emerged. This outcome contrasts with the finding in demand analysis that test-retest reliability is high. We attribute the unreliability and extreme assignment of value based on preference tests to high substitutability between foods. We suggest use of demand analysis instead of preference tests for studies that compare the values of different foods. A better strategy might be to avoid manipulating value by using different foods. Where possible, value should be manipulated by varying amounts of a single food type because, over an appropriate range, more food is consistently more valuable than less. Such an approach would be immune to problems in between-food substitutability. PMID:26908005

Novel high contrast electrochromic polymer materials based on 3,4-propylenedioxythiophene

NASA Astrophysics Data System (ADS)

Sahoo, Rabindra; Mishra, Sarada P.; Kumar, Anil; Sindhu, S.; Narasimha Rao, K.; Gopal, E. S. R.

2007-09-01

Mono and di allyl and napthyl substituted 3,4-propylenedioxythiophenes were synthesized and polymerized electrochemically. All the monomers were characterized for their molecular structures, and the polymers were characterized for their electrochemical properties. The disubstituted derivatives showed higher contrast than the corresponding mono substituted derivatives. The allyl substituted polymers showed higher contrast and faster switching time than corresponding napthyl substituted derivatives. The presence of the allyl group as the pendant can be used for further functionalization of the polymer.

Influence of mandatory generic substitution on pharmaceutical sales patterns: a national study over five years.

PubMed

Andersson, Karolina A; Petzold, Max G; Allebeck, Peter; Carlsten, Anders

2008-02-29

Mandatory generic substitution was introduced in Sweden in October 2002 in order to try to curb escalating pharmaceutical expenditure. The aim of this study was to investigate how sales patterns for substitutable and non-substitutable pharmaceuticals have developed since the introduction of mandatory generic substitution; furthermore, to compare sales patterns in different groups of the population, based on patients' age and gender. Five therapeutic groups comprising both substitutable and non-substitutable pharmaceuticals were included. The study period was from January 2000 to June 2005. National sales data were used, covering volumes of dispensed prescription medicines (expressed in defined daily doses per 1000 inhabitants and day) of each pharmacological substance in the therapeutic groups for each age and gender group. Sales patterns for substitutable and non-substitutable pharmaceuticals were compared using a descriptive approach. In most therapeutic groups there has been an increase in the volumes of substitutable pharmaceuticals sold since the introduction of the reform, ranging from one third to three times the initial volume; whereas the volumes of non-substitutable pharmaceuticals have levelled out or declined. There were few gender differences in sales patterns of substitutable and non-substitutable drugs. In three therapeutic groups, sales patterns differed across different age groups, and there was a tendency for volumes of recently introduced non-substitutable pharmaceuticals to be proportionally higher in the youngest age groups. Since the introduction of the reform, there has been a proportionally larger increase in sales of substitutable pharmaceuticals compared with sales of non-substitutable pharmaceuticals. This indicates that the reform might have contributed to larger sales of less expensive pharmaceuticals.

Cannabis as a substitute for alcohol and other drugs

PubMed Central

2009-01-01

Background Substitution can be operationalized as the conscious choice to use one drug (legal or illicit) instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Methods Anonymous survey data were collected at the Berkeley Patient's Group (BPG), a medical cannabis dispensary in Berkeley, CA. (N = 350) The sample was 68% male, 54% single, 66% White, mean age was 39; 74% have health insurance (including MediCal), 41% work full time, 81% have completed at least some college, 55% make less than $40,000 a year. Seventy one percent report having a chronic medical condition, 52% use cannabis for a pain related condition, 75% use cannabis for a mental health issue. Results Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%), better symptom management (57%), and less withdrawal potential (34%) with cannabis. Conclusion The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs. PMID:19958538

Cationic Gold Clusters Ligated with Differently Substituted Phosphines: Effect of Substitution on Ligand Reactivity and Binding

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

Johnson, Grant E.; Olivares, Astrid M.; Hill, David E.

2015-01-01

We present a systematic study of the effect of the number of methyl (Me) and cyclohexyl (Cy) functional groups in monodentate phosphine ligands on the solution-phase synthesis of ligated sub-nanometer gold clusters and their gas-phase fragmentation pathways. Small mixed ligand cationic gold clusters were synthesized using ligand exchange reactions between pre-formed triphenylphosphine ligated (PPh3) gold clusters and monodentate Me- and Cy-substituted ligands in solution and characterized using electrospray ionization mass spectrometry (ESI-MS) and collision-induced dissociation (CID) experiments. Under the same experimental conditions, larger gold-PPh3 clusters undergo efficient exchange of unsubstituted PPh3 ligands for singly Me- and Cy-substituted PPh2Me and PPh2Cymore » ligands. The efficiency of ligand exchange decreases with an increasing number of Me or Cy groups in the substituted phosphine ligands. CID experiments performed for a series of ligand-exchanged gold clusters indicate that loss of a neutral Me-substituted ligand is preferred over loss of a neutral PPh¬3 ligand while the opposite trend is observed for Cy-substituted ligands. The branching ratio of the competing ligand loss channels is strongly correlated with the electron donating ability of the phosphorous lone pair as determined by the relative proton affinity of the ligand. The results indicate that the relative ligand binding energies increase in the order PMe3 < PPhMe2 < PPh2Me < PPh3< PPh2Cy < PPhCy2< PCy3. Furthermore, the difference in relative ligand binding energies increases with the number of substituted PPh3-mMem or PPh3-mCym ligands (L) exchanged onto each cluster. This study provides the first experimental determination of the relative binding energies of ligated gold clusters containing differently substituted monophosphine ligands, which are important to controlling their synthesis and reactivity in solution. The results also indicate that ligand substitution is an important parameter that must be considered in theoretical modeling of these complex systems« less

Cannabis as a substitute for alcohol and other drugs.

PubMed

Reiman, Amanda

2009-12-03

Substitution can be operationalized as the conscious choice to use one drug (legal or illicit) instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Anonymous survey data were collected at the Berkeley Patient's Group (BPG), a medical cannabis dispensary in Berkeley, CA. (N = 350) The sample was 68% male, 54% single, 66% White, mean age was 39; 74% have health insurance (including MediCal), 41% work full time, 81% have completed at least some college, 55% make less than $40,000 a year. Seventy one percent report having a chronic medical condition, 52% use cannabis for a pain related condition, 75% use cannabis for a mental health issue. Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%), better symptom management (57%), and less withdrawal potential (34%) with cannabis. The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.

Image processing for a tactile/vision substitution system using digital CNN.

PubMed

Lin, Chien-Nan; Yu, Sung-Nien; Hu, Jin-Cheng

2006-01-01

In view of the parallel processing and easy implementation properties of CNN, we propose to use digital CNN as the image processor of a tactile/vision substitution system (TVSS). The digital CNN processor is used to execute the wavelet down-sampling filtering and the half-toning operations, aiming to extract important features from the images. A template combination method is used to embed the two image processing functions into a single CNN processor. The digital CNN processor is implemented on an intellectual property (IP) and is implemented on a XILINX VIRTEX II 2000 FPGA board. Experiments are designated to test the capability of the CNN processor in the recognition of characters and human subjects in different environments. The experiments demonstrates impressive results, which proves the proposed digital CNN processor a powerful component in the design of efficient tactile/vision substitution systems for the visually impaired people.

Enhanced energy storage density in lead free (Na0.5Bi0.48Eu0.02)Ti1-xNbxO3(x=0.00, 0.01 & 0.02) ceramics

NASA Astrophysics Data System (ADS)

Yanamandra, Radha; Kandula, Kumara Raja; Bandi, Posidevi; Reddy, H. Satish Kumar; Asthana, Saket; Patri, Tirupathi

2018-05-01

Eco friendly (Na0.5Bi0.48Eu0.02) Ti1-xNbxO3 ceramics were synthesized with help of conventional solid state reaction by using high energy ball milling. The room temperature XRD of Nb5+ substituted NBET ceramics were stabilized in single phase pervoskite structure without any secondary phase. Polarization study reflects long range ferroelectric order for pure NBET ceramics and coercive field enhance with the substitution of Nb5+ ion at Ti site. Further, the substitution of Nb5+ ≥ 0.02 composition induced relaxor future. The energy density calculation shows the maximum energy storage density of 1.02 J/cm3 for x=0.02 ceramics. These results confirms a small fraction of Nb5+ doped NBET ceramics should be good candidates for energy storage applications.

Optical properties of Y and Ti co-substituted BiFeO{sub 3} multiferroics

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

Singh, Vikash, E-mail: rk.dwivedi@jiit.ac.in; Sharma, Subhash, E-mail: rk.dwivedi@jiit.ac.in; Kumar, Manoj, E-mail: rk.dwivedi@jiit.ac.in

2014-04-24

Pure and co substituted Bi{sub 1−x}Y{sub x}Fe{sub 1−x}Ti{sub x}O{sub 3} (x ≤ 0.24) ceramics were synthesized by solid state reaction method. X-ray diffraction patterns of Y and Ti codoped samples have shown single phase formation. Increasing Y and Ti concentration reveals structural transition from rhombohedral phase (R3c) for x ≤ 0.16 to orthorhombic phase (Pnma) for x = 0.24. FT-IR spectra exhibit broad absorption bands, which may be due to the overlapping of Fe-O and Bi-O vibrations. UV-visible spectroscopy results show strong absorption of light in the spectral range of 400-720 nm, indicating optical band gap in the visible regionmore » for these samples. These interesting optical properties of co-substituted BFO samples in visible region may find potential applications in optoelectronic devices.« less

Effect of hyperthermia on the repair of sublethal radiation damage in normal and membrane fatty acid substituted fibroblasts

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

Wolters, H.; Kelholt, D.; Konings, A.W.

1987-02-01

The interaction of heat and X irradiation was studied in normal and polyunsaturated fatty acid (PUFA) substituted mouse fibroblast LM cells. As a result of the substitution the membranes of the PUFA cells were more fluid than the membranes of the normal cells. Three different heat doses were applied (60 min 42 degrees C, 20 min 43 degrees C, and 10 min 44 degrees C) in combination with single or split doses of X rays. Heat radiosensitization was the largest for the 60 min 42 degrees C treatment. Heat radiosensitization and the heat-induced inhibition of the rate of sublethal damagemore » repair were the same for the normal and the PUFA cells. It is concluded from the experiments reported that the processes of hyperthermic inhibition of SLD repair and hyperthermic radiosensitization are independent of membrane fluidity and membrane fatty acid composition.« less

Influence of La-Mn substitutions on magnetic properties of M-type strontium hexaferrites

NASA Astrophysics Data System (ADS)

Zi, Z. F.; Ma, X. H.; Wei, Y. Y.; Liu, Q. C.; Zhang, M.; Zhu, X. B.; Sun, Y. P.

2018-05-01

M-type strontium hexaferrites of Sr1-xLaxFe12-xMnxO19 (0.0≤x≤0.4) were synthesized by the chemical coprecipitation method. X-ray diffraction (XRD) studies indicate that the samples are single-phase with the space group of P63/mmc. The results of field-emission scanning electronic microscopy (FE-SEM) show that the grains are regular hexagonal platelets with sizes from 0.7 to 1.4 μm. It is observed that the value of Hc increases at low substitution (x ≤ 0.1), reaches a maximum at x = 0.1 and then decreases at x ≥ 0.1, while the value of Ms decreases monotonously with increasing x. The variations of magnetic properties can be tentatively attributed to the effects of La-Mn substitutions. The results above indicate that our samples might be promising candidates for permanent magnets in the future.

Synthesis of Aryl-Substituted 2,4-Dinitrophenylamines: Nucleophilic Aromatic Substitution as a Problem-Solving and Collaborative-Learning Approach

ERIC Educational Resources Information Center

Santos, Elvira Santos; Garcia, Irma Cruz Gavilan; Gomez, Eva Florencia Lejarazo; Vilchis-Reyes, Miguel Angel

2010-01-01

A series of experiments based on problem-solving and collaborative-learning pedagogies are described that encourage students to interpret results and draw conclusions from data. Different approaches including parallel library synthesis, solvent variation, and leaving group variation are used to study a nucleophilic aromatic substitution of…

A Safer, Discovery-Based Nucleophilic Substitution Experiment

ERIC Educational Resources Information Center

Horowitz, Gail

2009-01-01

A discovery-based nucleophilic substitution experiment is described in which students compare the reactivity of chloride and iodide ions in an S[subscript N]2 reaction. This experiment improves upon the well-known "Competing Nucleophiles" experiment in that it does not involve the generation of hydrogen halide gas. The experiment also introduces…

Function of specific 2'-hydroxyl groups of guanosines in a hammerhead ribozyme probed by 2' modifications.

PubMed Central

Williams, D M; Pieken, W A; Eckstein, F

1992-01-01

The importance of the 2'-hydroxyl group of several guanosine residues for the catalytic efficiency of a hammerhead ribozyme has been investigated. Five ribozymes in which single guanosine residues were substituted with 2'-amino-, 2'-fluoro-, or 2'-deoxyguanosine were chemically synthesized. The comparison of the catalytic activity of the three 2' modifications at a specific position allows conclusions about the functional role of the parent 2'-hydroxyl group. Substitutions of nonconserved nucleotides within the ribozyme caused little alteration in the catalytic activity relative to that obtained with the unmodified ribozyme. In contrast, when either of the guanosines within the single-stranded loop between stem I and stem II of the ribozyme was replaced by 2'-deoxyguanosine or 2'-fluoro-2'-deoxyguanosine, the catalytic activities of the resulting ribozymes were reduced by factors of at least 150. The catalytic activities of the corresponding ribozymes containing 2'-amino-2'-deoxyguanosine substitutions at these positions, however, were both reduced by factors of 15. These effects resulted from decreases in the respective kcat values, whereas variations in the Km values were comparatively small. A different pattern of reactivity of the three 2' modifications was observed at the guanosine immediately 3' to stem II of the ribozyme. Whereas both 2'-deoxyguanosine and 2'-amino-2'-deoxyguanosine at this position showed catalytic activity similar to that of the unmodified ribozyme, the activity of the corresponding 2'-fluoro-2'-deoxyguanosine-containing ribozyme was reduced by a factor of 15. The implications of these substitution-specific reactivities on the functional role of the native 2'-hydroxyl groups are discussed. Images PMID:1736306

Structural requirements for interleukin-8 function identified by design of analogs and CXC chemokine hybrids.

PubMed

Clark-Lewis, I; Dewald, B; Loetscher, M; Moser, B; Baggiolini, M

1994-06-10

Structure-activity relationships of human interleukin-8 (IL-8) were probed using chemically synthesized analogs with single or double amino acid substitutions, as well as hybrids derived by substituting IL-8 regions into IP10, a related protein that lacks IL-8 activity. The analogs were tested for functional activity by measuring induction of elastase release from human neutrophils and competition for binding of radiolabeled IL-8. The hybrid studies indicated that Gly31 and Pro32, as well as the NH2-terminal region from IL-8 are required to convert IP10 into a fully functional protein, suggesting that these elements are critical for IL-8 activity. Both disulfide bridges, linking residue 7 to 34 and residue 9 to 50, were critical for function, as shown by substituting the cysteine pairs with alpha-aminobutyric acid. Single conservative substitutions were generally accepted into the 10-22 region of IL-8, which contrasts with the ELR motif (residues 4-6), previously shown to be essential for activity. The importance of residues within the 10-15 region and the 17-22 region was demonstrated with hybrids. In addition, some of the 4-22 residues have structural roles that may be important; for example, Tyr13, Phe17, and Phe21 are involved in aromatic interactions in the IL-8 structure, and are also moderately sensitive to modification. Except for Cys50, the results argue against a role for the 36-72 region, including the COOH-terminal alpha-helix, in receptor binding. We conclude that the disulfide bridges and 30-35 turn provide a structural scaffold for the NH2-terminal region which includes the primary receptor-binding site (the ELR motif) and secondary binding and conformational determinants between residues 10 and 22.

Spectroscopic, single crystal X-ray, Hirshfeld, in vitro and in silico biological evaluation of a new series of potent thiazole nucleus integrated with pyrazoline scaffolds

NASA Astrophysics Data System (ADS)

Salian, Vinutha V.; Narayana, Badiadka; Sarojini, Balladka K.; Kumar, Madan S.; Nagananda, Govinahalli S.; Byrappa, Kullaiah; Kudva, Avinash K.

2017-03-01

In the present study, the spectroscopic characterization of a new series of substituted thiazole linked pyrazoline scaffolds 4a-l was performed. The formation of 4a-l from the intermediate 3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2 and substituted 2-bromo-1-phenylethanone 3a-l was evidenced through the changes in FTIR, 1H NMR, 13C NMR, LCMS data. The X-ray diffraction studies revealed that compound 2 and 4g crystallized in monoclinic crystal system with P21/n space group. Compound 4j crystallized in triclinic system, P1¯ space group with Z = 4. The percentage of intermolecular contacts and distribution of electrostatic potential of molecular crystal structures was resolved by Hirshfeld surface analysis with 2D finger plots and electrostatic potential map. The newly synthesized derivatives were screened for their in vitro antioxidant and antimicrobial activity. The single crystal studies revealed that, for compounds 2, 4g and 4j the isopropyl phenyl ring is positioned at near right angle with the other rings. Due to the lack of planarity of bulkier group substituted to phenyl ring (ring B), all the synthesized molecules showed weak to moderate radical scavenging capacity owing to the destabilization of the radical formed during oxidation. Also, on performing molecular docking studies to explore the interactions of ligand with the target pyrimidine nucleoside hydrolase YbeK with bound ribose complex (PNH, PDB ID-3GHW), disclosed that active compounds emerged for in vitro studies also bound to PNH more efficiently. The compounds with polar group substitution interacted through hydrogen bonding while other molecules with non-covalent interactions.

Substitutions at residues 300 and 389 of the VP2 capsid protein serve as the minimal determinant of attenuation for canine parvovirus vaccine strain 9985-46.

PubMed

Sehata, Go; Sato, Hiroaki; Yamanaka, Morimasa; Takahashi, Takuo; Kainuma, Risa; Igarashi, Tatsuhiko; Oshima, Sho; Noro, Taichi; Oishi, Eiji

2017-11-01

Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell-Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells. Using an infectious molecular clone system, we constructed isogenic CPVs of the parental virulent 9985 strain carrying single or double mutations. We observed that only a single amino acid substitution in VP2, G300V or T389N, attenuated the virulent parental virus. Combinations of these mutations further attenuated CPV to a level comparable to that of 9985-46. Strains with G300V/T389N substitutions did not induce clinical symptoms in experimentally infected pups, and their ability to infect canine cells was highly restricted. We found that another G300V/V562L double mutation decreased affinity of the virus for canine cells, although its pathogenicity to dogs was maintained. These results indicate that mutation of residue 300, which plays a critical role in host tropism, is not sufficient for viral attenuation in vivo, and that attenuation of 9985-46 strain is defined by at least two mutations in residues 300 and 389 of the VP2 capsid protein. This finding is relevant for quality control of the vaccine and provides insight into the rational design of second-generation live attenuated vaccine candidates.

A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice▿ †

PubMed Central

Fornek, Jamie L.; Gillim-Ross, Laura; Santos, Celia; Carter, Victoria; Ward, Jerrold M.; Cheng, Lily I.; Proll, Sean; Katze, Michael G.; Subbarao, Kanta

2009-01-01

The transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid 627 in the PB2 protein exhibited an increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T-cell receptor activation was impaired at 2 days postinfection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not attributable solely to differences in viral replication in the lungs but to an inefficient immune response early in infection as well. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. The disruption of these factors by a single-amino-acid substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites. PMID:19692471

The Effect of Iron and Aluminium Incorporation on the Single-Crystal Elasticity of Bridgmanite at High Pressure.

NASA Astrophysics Data System (ADS)

Kurnosov, A.; Marquardt, H.; Boffa Ballaran, T.; Frost, D. J.

2015-12-01

MgSiO3 bridgmanite constitutes about 70% by volume of the Earth's lower mantle and likely governs the physical behavior of this region. Chemical substitutions in MgSiO3 bridgmanite involving Al and Fe may explain seismic velocity anomalies observed in the Earth's lower mantle [1-3]. However, the effects of these substitutions on the anisotropic elastic properties of bridgmanite at high pressure and temperature are still experimentally unconstrained. Here, we present data of internally consistent measurements of the single-crystal elastic properties of Mg0.88Fe0.12Si0.09Al0.11O3 bridgmanite at high-pressures. Two differently oriented single-crystals of brigmanite have been double-side polished and cut as two semi-disks using a FEI Scios Focused Ion Beam (FIB) machine [4]. Two semi-disks, one for each of the crystallographic orientations, were loaded together in the pressure chamber of a diamond anvil cell with helium as a pressure-transmitting medium. Simultaneous measurements of density and sound velocities have been made on both crystals at high pressures using single-crystal X-ray diffraction and Brillouin spectroscopy in order to obtain self-consistent data, which do not depend on a secondary pressure scale. The Brillouin data at each pressure were fitted for both crystals simultaneously in order to reduce correlations among the elastic constants Cij. Our approach allows determining the single-crystal elastic properties of bridgmanite as a function of pressure, derived independently of a secondary pressure. We will use our results for Al-Fe-bearing bridgmanite to discuss the effects of chemical substitution on the high-pressure elasticity of bridgmanite and implications for the interpretation of seismic heterogeneities in Earth's lower mantle. [1] Ni et al. (2005), Geophys. J. Int. 161, 283-294. [2] Masters et al. (2000), AGU Monograph Series, 117, 63-87. [3] Garnero et al. (2005), The Geological Society of America Special Paper, 430, 79-101. [4] Marquardt et al. (2012), American Mineralogist, 97, 299-304.

Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients.

PubMed

Lucas, Philippe; Walsh, Zach

2017-04-01

In 2014 Health Canada replaced the Marihuana for Medical Access Regulations (MMAR) with the Marihuana for Medical Purposes Regulations (MMPR). One of the primary changes in the new program has been to move from a single Licensed Producer (LP) of cannabis to multiple Licensed Producers. This is the first comprehensive survey of patients enrolled in the MMPR. Patients registered to purchase cannabis from Tilray, a federally authorized Licenced Producer (LP) within the MMPR, were invited to complete an online survey consisting of 107 questions on demographics, patterns of use, and cannabis substitution effect. The survey was completed by 271 respondents. Cannabis is perceived to be an effective treatment for diverse conditions, with pain and mental health the most prominent. Findings include high self-reported use of cannabis as a substitute for prescription drugs (63%), particularly pharmaceutical opioids (30%), benzodiazepines (16%), and antidepressants (12%). Patients also reported substituting cannabis for alcohol (25%), cigarettes/tobacco (12%), and illicit drugs (3%). A significant percentage of patients (42%) reported accessing cannabis from illegal/unregulated sources in addition to access via LPs, and over half (55%) were charged to receive a medical recommendation to use cannabis, with nearly 25% paying $300 or more. The finding that patients report its use as a substitute for prescription drugs supports prior research on medical cannabis users; however, this study is the first to specify the classes of prescription drugs for which cannabis it is used as a substitute, and to match this substitution to specific diagnostic categories. The findings that some authorized patients purchase cannabis from unregulated sources and that a significant percentage of patients were charged for medical cannabis recommendations highlight ongoing policy challenges for this federal program. Copyright © 2017 Elsevier B.V. All rights reserved.

Hannaella phyllophila sp. nov., a basidiomycetous yeast species associated with plants in Thailand and Taiwan.

PubMed

Surussawadee, Janjira; Jindamorakot, Sasitorn; Nakase, Takashi; Lee, Ching-Fu; Limtong, Savitree

2015-07-01

Five strains representing one novel anamorphic yeast species were isolated from plant leaves collected in Thailand (strains DMKU-SP186(T), ST-111 and ST-201) and Taiwan (strains FN20L02 and SM13L16). On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics and sequence analysis of the D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, they were assigned to a single novel species of the genus Hannaella. The sequences of the D1/D2 regions of the LSU rRNA genes of four of the strains (DMKU-SP186(T), ST-111, FN20L02 and SM13L16) were identical, while differing from strain ST-201 by 2 substitutions and 2 gaps. The nucleotide sequence of the ITS regions of the five strains differed from each other by between 0 and 3 nucleotide substitutions. The novel species was most closely related to Hannaella luteola, but showed 1.0-1.3% nucleotide substitutions (between 6 substitutions out of 568-606 nt and 8 substitutions, and 2 gaps out of 597 nt) in the D1/D2 region of the LSU rRNA gene and 1.4-2.0% nucleotide substitutions (6-9 substitutions out of 435 nt) in the ITS region. Ballistospores were produced by three of the strains on cornmeal agar at 15 and 20 °C after 4 weeks, while H. luteola did not produce ballistospores. The name Hannaella phyllophila sp. nov. is proposed. The type strain is DMKU-SP186(T) ( = BCC 69500(T) = NBRC 110428(T) = CBS 13921(T)).

A combined calorimetric and computational study of the energetics of rare earth substituted UO 2 systems

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

Zhang, Lei; Solomon, Jonathan M.; Asta, Mark

2015-09-01

The energetics of rare earth substituted UO2 solid solutions (U1-xLnxO2-0.5x+y, where Ln = La, Y, and Nd) are investigated employing a combination of calorimetric measurements and density functional theory based computations. Calculated and measured formation enthalpies agree within 10 kJ/mol for stoichiometric oxygen/metal compositions. To better understand the factors governing the stability and defect binding in rare earth substituted urania solid solutions, systematic trends in the energetics are investigated based on the present results and previous computational and experimental thermochemical studies of rare earth substituted fluorite oxides (A1-xLnxO2-0.5x, where A = Hf, Zr, Ce, and Th). A consistent trend towardsmore » increased energetic stability with larger size mismatch between the smaller host tetravalent cation and the larger rare earth trivalent cation is found for both actinide and non-actinide fluorite oxide systems where aliovalent substitution of Ln cations is compensated by oxygen vacancies. However, the large exothermic oxidation enthalpy in the UO2 based systems favors oxygen rich compositions where charge compensation occurs through the formation of uranium cations with higher oxidation states.« less

One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections

PubMed Central

Mingo, Janire; Erramuzpe, Asier; Luna, Sandra; Aurtenetxe, Olaia; Amo, Laura; Diez, Ibai; Schepens, Jan T. G.; Hendriks, Wiljan J. A. J.; Cortés, Jesús M.; Pulido, Rafael

2016-01-01

Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one-tube-only standardized SDM approach that generates comprehensive collections of amino acid substitution variants, including scanning- and single site-multiple mutations. The approach combines unified mutagenic primer design with the mixing of multiple distinct primer pairs and/or plasmid templates to increase the yield of a single inverse-PCR mutagenesis reaction. Also, a user-friendly program for automatic design of standardized primers for Ala-scanning mutagenesis is made available. Experimental results were compared with a modeling approach together with stochastic simulation data. For single site-multiple mutagenesis purposes and for simultaneous mutagenesis in different plasmid backgrounds, combination of primer sets and/or plasmid templates in a single reaction tube yielded the distinct mutations in a stochastic fashion. For scanning mutagenesis, we found that a combination of overlapping primer sets in a single PCR reaction allowed the yield of different individual mutations, although this yield did not necessarily follow a stochastic trend. Double mutants were generated when the overlap of primer pairs was below 60%. Our results illustrate that one-tube-only SDM effectively reduces the number of reactions required in large-scale mutagenesis strategies, facilitating the generation of comprehensive collections of protein variants suitable for functional analysis. PMID:27548698

Analysis of the breast milk of giant pandas (Ailuropoda melanoleuca) and the preparation of substitutes

PubMed Central

ZHANG, Zhihe; HOU, Rong; LAN, Jingchao; WANG, Hairui; KUROKAWA, Hiroyuki; TAKATSU, Zenta; KOBAYASHI, Toyokazu; KOIE, Hiroshi; KAMATA, Hiroshi; KANAYAMA, Kiichi; WATANABE, Toshi

2016-01-01

The first milk substitute for giant panda cubs was developed in 1988 based on limited data about giant panda breast milk and that of certain types of bear. Mixtures of other formulas have also been fed to cubs at some facilities. However, they are not of sufficient nutritional quality for promoting growth in panda cubs. Here, we report analysis of giant panda breast milk and propose new milk substitutes for cubs, which were developed based on the results of our analysis. The Chengdu Research Base of Giant Panda Breeding obtained breast milk samples from three giant pandas. Up to 30 ml of breast milk were collected from each mother by hand. Then, the milk samples were frozen and sent to Nihon University. The levels of protein, fat, carbohydrates, ash, moisture, vitamins, minerals, total amino acids, fatty acids, lactose and other carbohydrates in the milk were analyzed. The breast milk samples exhibited the following nutritional values: protein: 6.6–8.5%, fat: 6.9–16.4%, carbohydrates: 2.5–9.1%, ash: 0.9–1.0% and moisture: 67–83%. We designed two kinds of milk substitutes based on the data obtained and the nutritional requirements of dogs, cats and rodents. The nutritional composition of the milk substitutes for the first and second stages was as follows: protein: 38 and 26%, fat: 40 and 40%, carbohydrates: 13 and 25%, ash: 6 and 6% and moisture: 3 and 3%, respectively. In addition, the substitutes contained vitamins, minerals, taurine, docosahexaenoic acid, lactoferrin, nucleotides and other nutrients. PMID:26781707

Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation.

PubMed

Leisegang, Matthias; Engels, Boris; Schreiber, Karin; Yew, Poh Yin; Kiyotani, Kazuma; Idel, Christian; Arina, Ainhoa; Duraiswamy, Jaikumar; Weichselbaum, Ralph R; Uckert, Wolfgang; Nakamura, Yusuke; Schreiber, Hans

2016-06-01

Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic nonsynonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T-cell receptor (TCR) that is specific for a single AAS. By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intratumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T-cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer, but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. Clin Cancer Res; 22(11); 2734-43. ©2015 AACRSee related commentary by Liu, p. 2602. ©2015 American Association for Cancer Research.

Host Genetic Variation Does Not Determine Spatio-Temporal Patterns of European Bat 1 Lyssavirus

PubMed Central

Picard-Meyer, Evelyne; Dellicour, Simon; Casademont, Isabelle; Kergoat, Lauriane; Lepelletier, Anthony; Dacheux, Laurent; Baele, Guy; Monchâtre-Leroy, Elodie; Cliquet, Florence; Lemey, Philippe

2017-01-01

Abstract The majority of bat rabies cases in Europe are attributed to European bat 1 lyssavirus (EBLV-1), circulating mainly in serotine bats (Eptesicus serotinus). Two subtypes have been defined (EBLV-1a and EBLV-1b), each associated with a different geographical distribution. In this study, we undertake a comprehensive sequence analysis based on 80 newly obtained EBLV-1 nearly complete genome sequences from nine European countries over a 45-year period to infer selection pressures, rates of nucleotide substitution, and evolutionary time scale of these two subtypes in Europe. Our results suggest that the current lineage of EBLV-1 arose in Europe ∼600 years ago and the virus has evolved at an estimated average substitution rate of ∼4.19×10−5 subs/site/year, which is among the lowest recorded for RNA viruses. In parallel, we investigate the genetic structure of French serotine bats at both the nuclear and mitochondrial level and find that they constitute a single genetic cluster. Furthermore, Mantel tests based on interindividual distances reveal the absence of correlation between genetic distances estimated between viruses and between host individuals. Taken together, this indicates that the genetic diversity observed in our E. serotinus samples does not account for EBLV-1a and -1b segregation and dispersal in Europe. PMID:29165566

Improved xylose uptake in Saccharomyces cerevisiae due to directed evolution of galactose permease Gal2 for sugar co-consumption.

PubMed

Reznicek, O; Facey, S J; de Waal, P P; Teunissen, A W R H; de Bont, J A M; Nijland, J G; Driessen, A J M; Hauer, B

2015-07-01

Saccharomyces cerevisiae does not express any xylose-specific transporters. To enhance the xylose uptake of S. cerevisiae, directed evolution of the Gal2 transporter was performed. Three rounds of error-prone PCR were used to generate mutants with improved xylose-transport characteristics. After developing a fast and reliable high-throughput screening assay based on flow cytometry, eight mutants were obtained showing an improved uptake of xylose compared to wild-type Gal2 out of 41 200 single yeast cells. Gal2 variant 2·1 harbouring five amino acid substitutions showed an increased affinity towards xylose with a faster overall sugar metabolism of glucose and xylose. Another Gal2 variant 3·1 carrying an additional amino acid substitution revealed an impaired growth on glucose but not on xylose. Random mutagenesis of the S. cerevisiae Gal2 led to an increased xylose uptake capacity and decreased glucose affinity, allowing improved co-consumption. Random mutagenesis is a powerful tool to evolve sugar transporters like Gal2 towards co-consumption of new substrates. Using a high-throughput screening system based on flow-through cytometry, various mutants were identified with improved xylose-transport characteristics. The Gal2 variants in this work are a promising starting point for further engineering to improve xylose uptake from mixed sugars in biomass. © 2015 The Society for Applied Microbiology.

Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm

PubMed Central

Öhrmalm, Christina; Jobs, Magnus; Eriksson, Ronnie; Golbob, Sultan; Elfaitouri, Amal; Benachenhou, Farid; Strømme, Maria; Blomberg, Jonas

2010-01-01

One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes. PMID:20864443

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract.

PubMed

Law, J C; Whiteside, T L; Gollin, S M; Weissfeld, J; El-Ashmawy, L; Srivastava, S; Landreneau, R J; Johnson, J T; Ferrell, R E

1995-07-01

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer. Tumor-associated p53 mutations often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational frequency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract). Mutations were identified at a frequency of 30% in upper respiratory tract (URT) tumors and 31% in lung tumors. All 29 identified mutations were single-base substitutions. Comparison of the frequency of specific base substitutions between lung and URT showed a striking difference. Transitions occurred at a frequency of 68% in URT, but only 30% in lung. Mutations involving G:C-->A:T transitions, which are commonly reported in gastric and esophageal tumors, were the most frequently identified alteration in URT (11/19). Mutations involving G:C-->T:A transversions, which were relatively common in lung tumors (3/10) and are representative of tobacco smoke-induced mutations were rare in URT tumors (1/19). Interestingly, G:C-->A:T mutations at CpG sites, which are characteristic of endogenous processes, were observed frequently in URT tumors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed differences in mutational spectra between the upper and lower respiratory systems.

Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus

PubMed Central

Tuplin, A.; Evans, D. J.; Buckley, A.; Jones, I. M.; Gould, E. A.; Gritsun, T. S.

2011-01-01

We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents. PMID:21622960

Vitreous Substitutes: Old and New Materials in Vitreoretinal Surgery

PubMed Central

Panico, Claudio; Eandi, Chiara M.

2017-01-01

Recent developments in vitreoretinal surgery have increased the need for suitable vitreous substitutes. A successful substitute should maintain all the physical and biochemical properties of the original vitreous, be easy to manipulate, and be long lasting. Substitutes can be gaseous or liquid, both of which have associated advantages and disadvantages related to their physical properties and use. Furthermore, new surgical techniques with smaller vitreoretinal instruments have driven the use of more viscous substitutes. In this review, we analyze and discuss the most frequently used vitreous substitutes and look ahead to future alternatives. We classify these compounds based on their composition and structure, discuss their clinical use with respect to their associated advantages and disadvantages, and analyze how new vitreoretinal surgical techniques have modified their use. PMID:28785482

A gene duplication/loss event in the ribulose-1,5-bisphosphate-carboxylase/oxygenase (rubisco) small subunit gene family among accessions of Arabidopsis thaliana.

PubMed

Schwarte, Sandra; Tiedemann, Ralph

2011-06-01

Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39), the most abundant protein in nature, catalyzes the assimilation of CO(2) (worldwide about 10(11) t each year) by carboxylation of ribulose-1,5-bisphosphate. It is a hexadecamer consisting of eight large and eight small subunits. Although the Rubisco large subunit (rbcL) is encoded by a single gene on the multicopy chloroplast genome, the Rubisco small subunits (rbcS) are encoded by a family of nuclear genes. In Arabidopsis thaliana, the rbcS gene family comprises four members, that is, rbcS-1a, rbcS-1b, rbcS-2b, and rbcS-3b. We sequenced all Rubisco genes in 26 worldwide distributed A. thaliana accessions. In three of these accessions, we detected a gene duplication/loss event, where rbcS-1b was lost and substituted by a duplicate of rbcS-2b (called rbcS-2b*). By screening 74 additional accessions using a specific polymerase chain reaction assay, we detected five additional accessions with this duplication/loss event. In summary, we found the gene duplication/loss in 8 of 100 A. thaliana accessions, namely, Bch, Bu, Bur, Cvi, Fei, Lm, Sha, and Sorbo. We sequenced an about 1-kb promoter region for all Rubisco genes as well. This analysis revealed that the gene duplication/loss event was associated with promoter alterations (two insertions of 450 and 850 bp, one deletion of 730 bp) in rbcS-2b and a promoter deletion (2.3 kb) in rbcS-2b* in all eight affected accessions. The substitution of rbcS-1b by a duplicate of rbcS-2b (i.e., rbcS-2b*) might be caused by gene conversion. All four Rubisco genes evolve under purifying selection, as expected for central genes of the highly conserved photosystem of green plants. We inferred a single positive selected site, a tyrosine to aspartic acid substitution at position 72 in rbcS-1b. Exactly the same substitution compromises carboxylase activity in the cyanobacterium Anacystis nidulans. In A. thaliana, this substitution is associated with an inferred recombination. Functional implications of the substitution remain to be evaluated.

The Molecular Basis of Muscular Dystrophy in the mdx Mouse: A Point Mutation

NASA Astrophysics Data System (ADS)

Sicinski, Piotr; Geng, Yan; Ryder-Cook, Allan S.; Barnard, Eric A.; Darlison, Mark G.; Barnard, Pene J.

1989-06-01

The mdx mouse is an X-linked myopathic mutant, an animal model for human Duchenne muscular dystrophy. In both mouse and man the mutations lie within the dystrophin gene, but the phenotypic differences of the disease in the two species confer much interest on the molecular basis of the mdx mutation. The complementary DNA for mouse dystrophin has been cloned, and the sequence has been used in the polymerase chain reaction to amplify normal and mdx dystrophin transcripts in the area of the mdx mutation. Sequence analysis of the amplification products showed that the mdx mouse has a single base substitution within an exon, which causes premature termination of the polypeptide chain.

Synthesis of substituted pyrazines

DOEpatents

Pagoria, Philip F.; Zhang, Mao Xi

2016-10-04

A method for synthesizing a pyrazine-containing material according to one embodiment includes contacting an iminodiacetonitrile derivative with a base and a reagent selected from a group consisting of hydroxylamine, a hydroxylamine salt, an aliphatic primary amine, a secondary amine, an aryl-substituted alkylamine a heteroaryl-substituted alkyl amine, an alcohol, an alkanolamine and an aryl alcoholamine. Additional methods and several reaction products are presented. ##STR00001##

Classification of group B streptococci with reduced β-lactam susceptibility (GBS-RBS) based on the amino acid substitutions in PBPs.

PubMed

Kimura, Kouji; Nagano, Noriyuki; Arakawa, Yoshichika

2015-01-01

All clinical isolates of group B Streptococcus (GBS; Streptococcus agalactiae) are considered uniformly susceptible to β-lactams, including penicillins. However, GBS with reduced penicillin susceptibility (PRGBS) were first identified by our group in Japan and have also been reported from North America. PRGBS are non-susceptible to penicillin because of acquisition of amino acid substitutions near the conserved active-site motifs in PBP2X. In particular, V405A and Q557E are considered the key amino acid substitutions responsible for penicillin non-susceptibility. We revealed that in addition to the substitutions in PBP2X, an amino acid substitution in PBP1A confers high-level cephalosporin resistance in GBS. As the number of publications on GBS with reduced β-lactam susceptibility (GBS-RBS), especially PRGBS, and concomitantly the need for a systematic classification of GBS-RBS is increasing, we propose here a classification of GBS-RBS based on the amino acid substitutions in their PBPs. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

Kelly, Jarod C.; Sullivan, John L.; Burnham, Andrew

This study examines the vehicle-cycle impacts associated with substituting lightweight materials for those currently found in light-duty passenger vehicles. We determine part-based energy use and greenhouse gas (GHG) emission ratios by collecting material substitution data from both the literature and automotive experts and evaluating that alongside known mass-based energy use and GHG emission ratios associated with material pair substitutions. Several vehicle parts, along with full vehicle systems, are examined for lightweighting via material substitution to observe the associated impact on GHG emissions. Results are contextualized by additionally examining fuel-cycle GHG reductions associated with mass reductions relative to the baseline vehiclemore » during the use phase and also determining material pair breakeven driving distances for GHG emissions. The findings show that, while material substitution is useful in reducing vehicle weight, it often increases vehicle-cycle GHGs depending upon the material substitution pair. However, for a vehicle’s total life cycle, fuel economy benefits are greater than the increased burdens associated with the vehicle manufacturing cycle, resulting in a net total life-cycle GHG benefit. The vehicle cycle will become increasingly important in total vehicle life-cycle GHGs, since fuel-cycle GHGs will be gradually reduced as automakers ramp up vehicle efficiency to meet fuel economy standards.« less

Interaction of influenza virus polymerase with viral RNA in the 'corkscrew' conformation.

PubMed

Flick, R; Hobom, G

1999-10-01

The influenza virus RNA (vRNA) promoter structure is known to consist of the 5'- and 3'-terminal sequences of the RNA, within very narrow boundaries of 16 and 15 nucleotides, respectively. A complete set of single nucleotide substitutions led to the previously proposed model of a binary hooked or 'corkscrew' conformation for the vRNA promoter when it interacts with the viral polymerase. This functional structure is confirmed here with a complete set of complementary double substitutions, of both the regular A:U and G:C type and also the G:U type of base-pair exchanges. The proposed structure consists of a six base-pair RNA rod in the distal element in conjunction with two stem-loop structures of two short-range base-pairs (positions 2-9; 3-8). These support an exposed tetranucleotide loop within each branch of the proximal element, in an overall oblique organization due to a central unpaired A residue at position 10 in the 5' sequence. Long-range base-pairing between the entire 5' and 3' branches, as required for an unmodified 'panhandle' model, has been excluded for the proximal element, while it is known to represent the mode of interaction within the distal element. A large number of short-range base-pair exchanges in the proximal element constitute promoter-up mutations, which show activities several times above that of the wild-type in reporter gene assays. The unique overall conformation and rather few invariant nucleotides appear to be the core elements in vRNA recognition by polymerase and also in viral ribonucleoprotein packaging, to allow discrimination against the background of other RNA molecules in the cell.

The complete chloroplast genome sequence of Aster spathulifolius (Asteraceae); genomic features and relationship with Asteraceae.

PubMed

Choi, Kyoung Su; Park, SeonJoo

2015-11-10

Aster spathulifolius, a member of the Asteraceae family, is distributed along the coast of Japan and Korea. This plant is used for medicinal and ornamental purposes. The complete chloroplast (cp) genome of A. sphathulifolius consists of 149,473 bp that include a pair of inverted repeats of 24,751 bp separated by a large single copy region of 81,998 bp and a small single copy region of 17,973 bp. The chloroplast genome contains 78 coding genes, four rRNA genes and 29 tRNA genes. When compared to other cpDNA sequences of Asteraceae, A. spathulifolius showed the closest relationship with Jacobaea vulgaris, and its atpB gene was found to be a pseudogene, unlike J. vulgaris. Furthermore, evaluation of the gene compositions of J. vulgaris, Helianthus annuus, Guizotia abyssinica and A. spathulifolius revealed that 13.6-kb showed inversion from ndhF to rps15, unlike Lactuca of Asteraceae. Comparison of the synonymous (Ks) and nonsynonymous (Ka) substitution rates with J. vulgaris revealed that synonymous genes related to a small subunit of the ribosome showed the highest value (0.1558), while nonsynonymous rates of genes related to ATP synthase genes were highest (0.0118). These findings revealed that substitution has occurred at similar rates in most genes, and the substitution rates suggested that most genes is a purified selection. Copyright © 2015 Elsevier B.V. All rights reserved.

The Study of Substitution and Elimination Reactions Using Gas Chromatography: An Examination of the Effects of Alkane and Base Structure on Product Distributions

ERIC Educational Resources Information Center

Wharry, Donald L.

2011-01-01

An experiment that compares product distribution obtained by either substitution or elimination utilizing alkyl bromides and methoxide, ethoxide, or t-butoxide as the base (or nucleophile) is described. The change in product distribution caused by steric effects of the base and substrate are readily apparent. Prior work on this experiment focused…

24 CFR 290.21 - Computing annual number of units eligible for substitution of tenant-based assistance or...

Code of Federal Regulations, 2010 CFR

2010-04-01

... PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY MORTGAGES Disposition of Multifamily Projects § 290.21 Computing annual number of units eligible for substitution of tenant-based... the fiscal year, taking into consideration the total number of units in multifamily housing projects...

24 CFR 290.21 - Computing annual number of units eligible for substitution of tenant-based assistance or...

Code of Federal Regulations, 2011 CFR

2011-04-01

... PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY MORTGAGES Disposition of Multifamily Projects § 290.21 Computing annual number of units eligible for substitution of tenant-based... the fiscal year, taking into consideration the total number of units in multifamily housing projects...

24 CFR 290.21 - Computing annual number of units eligible for substitution of tenant-based assistance or...

Code of Federal Regulations, 2012 CFR

2012-04-01

... PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY MORTGAGES Disposition of Multifamily Projects § 290.21 Computing annual number of units eligible for substitution of tenant-based... the fiscal year, taking into consideration the total number of units in multifamily housing projects...

24 CFR 290.21 - Computing annual number of units eligible for substitution of tenant-based assistance or...

Code of Federal Regulations, 2014 CFR

2014-04-01

... PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY MORTGAGES Disposition of Multifamily Projects § 290.21 Computing annual number of units eligible for substitution of tenant-based... the fiscal year, taking into consideration the total number of units in multifamily housing projects...

Wood Substitutes; A Base Syllabus on Wood Technology.

ERIC Educational Resources Information Center

Eastern Kentucky Univ., Richmond.

This curriculum guide is for use by college instructors concerned with expanding traditional woodworking programs. It was developed in a National Defense Education Act summer institute and is based on an outline provided by members of a previous institute. The content concerns wood substitutes which are made to resemble wood and are often used…

Development of navy bean-soybean milk substitute beverages and evaluation of its nutritional and physical properties

USDA-ARS?s Scientific Manuscript database

As health-conscious consumers are increasingly looking for plant-based milk substitute beverages for weight management, cancer prevention, and overall cardiovascular health, we are exploring pulse based healthful beverages with soybean-navy bean blends of 100:0, 80:20, 60:40, 20:80, and 0:100 ratios...

Molecular Mechanism of Terbinafine Resistance in Saccharomyces cerevisiae

PubMed Central

Leber, Regina; Fuchsbichler, Sandra; Klobučníková, Vlasta; Schweighofer, Natascha; Pitters, Eva; Wohlfarter, Kathrin; Lederer, Mojca; Landl, Karina; Ruckenstuhl, Christoph; Hapala, Ivan; Turnowsky, Friederike

2003-01-01

Ten mutants of the yeast Saccharomyces cerevisiae resistant to the antimycotic terbinafine were isolated after chemical or UV mutagenesis. Molecular analysis of these mutants revealed single base pair exchanges in the ERG1 gene coding for squalene epoxidase, the target of terbinafine. The mutants did not show cross-resistance to any of the substrates of various pleiotropic drug resistance efflux pumps tested. The ERG1 mRNA levels in the mutants did not differ from those in the wild-type parent strains. Terbinafine resistance was transmitted with the mutated alleles in gene replacement experiments, proving that single amino acid substitutions in the Erg1 protein were sufficient to confer the resistance phenotype. The amino acid changes caused by the point mutations were clustered in two regions of the Erg1 protein. Seven mutants carried the amino acid substitutions F402L (one mutant), F420L (one mutant), and P430S (five mutants) in the C-terminal part of the protein; and three mutants carried an L251F exchange in the central part of the protein. Interestingly, all exchanges identified involved amino acids which are conserved in the squalene epoxidases of yeasts and mammals. Two mutations that were generated by PCR mutagenesis of the ERG1 gene and that conferred terbinafine resistance mapped in the same regions of the Erg1 protein, with one resulting in an L251F exchange and the other resulting in an F433S exchange. The results strongly indicate that these regions are responsible for the interaction of yeast squalene epoxidase with terbinafine. PMID:14638499

In Silico and In Vitro Investigations of the Mutability of Disease-Causing Missense Mutation Sites in Spermine Synthase

PubMed Central

Zhang, Zhe; Norris, Joy; Schwartz, Charles; Alexov, Emil

2011-01-01

Background Spermine synthase (SMS) is a key enzyme controlling the concentration of spermidine and spermine in the cell. The importance of SMS is manifested by the fact that single missense mutations were found to cause Snyder-Robinson Syndrome (SRS). At the same time, currently there are no non-synonymous single nucleoside polymorphisms, nsSNPs (harmless mutations), found in SMS, which may imply that the SMS does not tolerate amino acid substitutions, i.e. is not mutable. Methodology/Principal Findings To investigate the mutability of the SMS, we carried out in silico analysis and in vitro experiments of the effects of amino acid substitutions at the missense mutation sites (G56, V132 and I150) that have been shown to cause SRS. Our investigation showed that the mutation sites have different degree of mutability depending on their structural micro-environment and involvement in the function and structural integrity of the SMS. It was found that the I150 site does not tolerate any mutation, while V132, despite its key position at the interface of SMS dimer, is quite mutable. The G56 site is in the middle of the spectra, but still quite sensitive to charge residue replacement. Conclusions/Significance The performed analysis showed that mutability depends on the detail of the structural and functional factors and cannot be predicted based on conservation of wild type properties alone. Also, harmless nsSNPs can be expected to occur even at sites at which missense mutations were found to cause diseases. PMID:21647366

Ultraviolet-induced sister chromatid exchanges in V-79 cells with normal and BrdUrd-substituted DNA and the influence of intercalating substances and cysteine

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

Speit, G.; Mehnert, K.; Wolf, M.

1982-06-01

The influence of intercalating substances (proflavine, ethidium bromide) and of an SH compound (L-cysteine) on uv-induced sister chromatid exchanges (SCEs) was investigated in V-79 cells with normal and BrdUrd-substituted DNA. The results are discussed in relation to the primary damages leading to SCE induction produced by uv irradiation. The data indicate that neither the pyrimidine dimers nor DNA single-strand breaks are the primary cause of SCE induction, and that the damages leading to SCEs by uv irradiation differ from those which cause chromosome aberrations.

Chemical pressure tuning of URu2Si2 via isoelectronic substitution of Ru with Fe

NASA Astrophysics Data System (ADS)

Das, Pinaki; Kanchanavatee, N.; Helton, J. S.; Huang, K.; Baumbach, R. E.; Bauer, E. D.; White, B. D.; Burnett, V. W.; Maple, M. B.; Lynn, J. W.; Janoschek, M.

2015-02-01

We have used specific heat and neutron diffraction measurements on single crystals of URu2 -xFexSi2 for Fe concentrations x ≤0.7 to establish that chemical substitution of Ru with Fe acts as "chemical pressure" Pc h as previously proposed by Kanchanavatee et al. [Phys. Rev. B 84, 245122 (2011), 10.1103/PhysRevB.84.245122] based on bulk measurements on polycrystalline samples. Notably, neutron diffraction reveals a sharp increase of the uranium magnetic moment at x =0.1 , reminiscent of the behavior at the "hidden order" to large-moment-antiferromagnetic phase transition observed at a pressure Px≈0.5 -0.7 GPa in URu2Si2 . Using the unit-cell volume determined from our measurements and an isothermal compressibility κT=5.2 ×10-3 GPa-1 for URu2Si2 , we determine the chemical pressure Pc h in URu2 -xFexSi2 as a function of x . The resulting temperature (T )-chemical pressure (Pc h) phase diagram for URu2 -xFexSi2 is in agreement with the established temperature (T )-external pressure (P ) phase diagram of URu2Si2 .