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Jung, In Young, David Boettiger, Wingwai Wong, Man Po Lee, Sasisopin Kiertiburanakul, Romanee Chaiwarith, Anchalee Avihingsanon, et al. "The Safety of Substitution of Antiretroviral Regimen in Non-Clinical Trial Settings in Asian Countries." Open Forum Infectious Diseases 4, suppl_1 (2017): S432. http://dx.doi.org/10.1093/ofid/ofx163.1091.
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Abstract Background Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the safety of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. Methods HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD) were included in this analysis if they started combination antiretroviral therapy (cART) after 2002, were being treated at a center that documented a median rate of viral load (VL) monitoring ≥ 1 tests/patient/year, and experienced a minor or major treatment substitution while on virally suppressive cART (VL < 200 copies/mL). Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. Virologic failure was defined as having had two viral load measurements > 400 copies/mL. The patterns of substitutions and rate of virologic failure after substitutions were analyzed. Results Of 3,994 adults who started ART after 2002, 3,119 (78.1%) had at least one period of virological suppression. Among these, 1,170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of virological failure were 1.48/100person years (95% CI 1.14–1.91) in the minor substitution group and 2.85/100person years (95% CI 1.88–4.33) in the major substitution group, and 2.53/100person years (95% CI 2.20–2.92) among patients that did not undergo a treatment substitution. Conclusion The rate of virological failure was relatively low in both major and minor substitution groups, showing that regimen substitution is generally safe in non-clinical trial settings in Asian countries. Disclosures All authors: No reported disclosures.
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Smith, Nick G. C., and Laurence D. Hurst. "The Effect of Tandem Substitutions on the Correlation Between Synonymous and Nonsynonymous Rates in Rodents." Genetics 153, no. 3 (November 1, 1999): 1395–402. http://dx.doi.org/10.1093/genetics/153.3.1395.
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Abstract Nonsynonymous substitutions in DNA cause amino acid substitutions while synonymous substitutions in DNA leave amino acids unchanged. The cause of the correlation between the substitution rates at nonsynonymous (KA) and synonymous (KS) sites in mammals is a contentious issue, and one that impacts on many aspects of molecular evolution. Here we use a large set of orthologous mammalian genes to investigate the causes of the KA-KS correlation in rodents. The strength of the KA-KS correlation exceeds the neutral theory expectation when substitution rates are estimated using algorithmic methods, but not when substitution rates are estimated by maximum likelihood. Irrespective of this methodological uncertainty the strength of the KA-KS correlation appears mostly due to tandem substitutions, an excess of which is generated by substitutional nonindependence. Doublet mutations cannot explain the excess of tandem synonymous-nonsynonymous substitutions, and substitution patterns indicate that selection on silent sites is the likely cause. We find no evidence for selection on codon usage. The nature of the relationship between synonymous divergence and base composition is unclear because we find a significant correlation if we use maximum-likelihood methods but not if we use algorithmic methods. Finally, we find that KS is reduced at the start of genes, which suggests that selection for RNA structure may affect silent sites in mammalian protein-coding genes.
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Zhang, Lei, Jiale Mao, Shuang Wang, and Yiting Zheng. "Synthesis and thermal properties of phenol- and amine-capped main-chain benzoxazine oligomers with multiple methyl substitutions." High Performance Polymers 32, no. 7 (February 11, 2020): 823–34. http://dx.doi.org/10.1177/0954008320905362.
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A series of main-chain benzoxazine oligomers with different methyl substitutions are successfully synthesized. Chemical structures are analyzed by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and gel permeation chromatography. Effects of methyl substitutions on chemical shifts of protons in oxazine ring and thermal properties, including glass transition temperature, thermal stability, and char yield, are discussed. The influences of methyl substitutions on different positions are demonstrated: (i) substitution on phenols induces obvious increase in curing temperature while substitution on amine does not show apparent impact; (ii) substitution at different positions results in T g variation, following the sequence of none-substitution > substitution at end-capping > substitution on diamines in main-chain > substitution on bisphenols in main-chain; and (iii) substitution at end-capping would cause apparent deterioration in thermal stability while substitution on diamines in main-chain would benefit thermal stability and char yield. Experimental results and related explanations are provided in detail.
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BEZUGLYI, S., J. KWIATKOWSKI, and K. MEDYNETS. "Aperiodic substitution systems and their Bratteli diagrams." Ergodic Theory and Dynamical Systems 29, no. 1 (February 2009): 37–72. http://dx.doi.org/10.1017/s0143385708000230.
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AbstractWe study aperiodic substitution dynamical systems arising from non-primitive substitutions. We prove that the Vershik homeomorphism φ of a stationary ordered Bratteli diagram is topologically conjugate to an aperiodic substitution system if and only if no restriction of φ to a minimal component is conjugate to an odometer. We also show that every aperiodic substitution system generated by a substitution with nesting property is conjugate to the Vershik map of a stationary ordered Bratteli diagram. It is proved that every aperiodic substitution system is recognizable. The classes of m-primitive substitutions and derivative substitutions associated with them are studied. We discuss also the notion of expansiveness for Cantor dynamical systems of finite rank.
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Rust, Dan. "Periodic points in random substitution subshifts." Monatshefte für Mathematik 193, no. 3 (August 26, 2020): 683–704. http://dx.doi.org/10.1007/s00605-020-01458-9.
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Abstract We study various aspects of periodic points for random substitution subshifts. In order to do so, we introduce a new property for random substitutions called the disjoint images condition. We provide a procedure for determining the property for compatible random substitutions—random substitutions for which a well-defined abelianisation exists. We find some simple necessary criteria for primitive, compatible random substitutions to admit periodic points in their subshifts. In the case that the random substitution further has disjoint images and is of constant length, we provide a stronger criterion. A method is outlined for enumerating periodic points of any specified length in a random substitution subshift.
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MALONEY, GREGORY R., and DAN RUST. "Beyond primitivity for one-dimensional substitution subshifts and tiling spaces." Ergodic Theory and Dynamical Systems 38, no. 3 (September 20, 2016): 1086–117. http://dx.doi.org/10.1017/etds.2016.58.
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We study the topology and dynamics of subshifts and tiling spaces associated to non-primitive substitutions in one dimension. We identify a property of a substitution, which we call tameness, in the presence of which most of the possible pathological behaviours of non-minimal substitutions cannot occur. We find a characterization of tameness, and use this to prove a slightly stronger version of a result of Durand, which says that the subshift of a minimal substitution is topologically conjugate to the subshift of a primitive substitution. We then extend to the non-minimal setting a result obtained by Anderson and Putnam for primitive substitutions, which says that a substitution tiling space is homeomorphic to an inverse limit of a certain finite graph under a self-map induced by the substitution. We use this result to explore the structure of the lattice of closed invariant subspaces and quotients of a substitution tiling space, for which we compute cohomological invariants that are stronger than the Čech cohomology of the tiling space alone.
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Bulmer, M. "Estimating the variability of substitution rates." Genetics 123, no. 3 (November 1, 1989): 615–19. http://dx.doi.org/10.1093/genetics/123.3.615.
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Abstract Suppose that amino acid or nucleotide data are available for a homologous gene in several species which diverged from a common ancestor at about the same time and that substitution rates between all pairs of species are calculated, correcting as necessary for multiple substitutions and for back and parallel substitutions. The variances and covariances of these corrected substitution rates are evaluated, and are used to construct a new test for uniformity (constancy of the molecular clock) and to find the best estimates of substitution rates in individual lineages with their standard errors. A substantial bias may arise if the effect of correcting the pairwise substitution rates is ignored.
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Overton, Tim, Eleanor G. F. Reid, Robin Foxall, Harry Smith, Stephen J. W. Busby, and Jeffrey A. Cole. "Transcription Activation at Escherichia coli FNR-Dependent Promoters by the Gonococcal FNR Protein: Effects of a Novel S18F Substitution and Comparisons with the Corresponding Substitution in E. coli FNR." Journal of Bacteriology 185, no. 16 (August 15, 2003): 4734–47. http://dx.doi.org/10.1128/jb.185.16.4734-4747.2003.
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ABSTRACT The Neisseria gonorrhoeae genome encodes a homologue of the Escherichia coli FNR protein (the fumarate and nitrate reductase regulator). Despite its similarity to E. coli FNR, the gonococcal FNR only partially complemented an E. coli fnr mutation. After error-prone PCR mutagenesis of the gonococcal fnr gene, we identified four mutant fnr derivatives carrying the same S18F substitution, and we showed that the mutant FNR could activate transcription from a range of class I and class II FNR-dependent promoters in E. coli. Prompted by the similarities between gonococcal and E. coli FNR, we made changes in gonococcal fnr that created substitutions that are equivalent to previously characterized substitutions in E. coli FNR. First, our experiments showed that cysteine, C116, in the gonococcal FNR, equivalent to C122 in E. coli FNR, is essential, presumably because, as in E. coli FNR, it binds to an iron-sulfur center. Second, the L22H and D148A substitutions in gonococcal FNR were made. These changes are equivalent to the L28H and D154A changes in E. coli FNR, which had been shown to increase FNR activity in the presence of oxygen. We show that the effects of these substitutions in gonococcal FNR are distinct from those of the S18F substitution. Similarly, substitutions in the putative activating regions of gonococcal FNR were made. We show that the activity of gonococcal FNR in E. coli can be increased by transplanting certain activating regions from E. coli FNR. The effects of these substitutions are additive to those due to S18F. From these data, we conclude that the effects of the S18F substitution in gonococcal FNR are distinct from the effects of the other substitutions. S18 is immediately adjacent to one of three N-terminal cysteine residues that coordinate the iron-sulfur center, and thus the S18F substitution is most likely to stabilize this center. Support for this came from complementary experiments in which we created the S24F substitution in E. coli FNR, which is equivalent to the S18F substitution in gonococcal FNR. Our results show that the S24F substitution changes the activity of E. coli FNR and that the changes are distinct from those due to previously characterized substitutions.
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Rahman, Shakibur, Sergei L. Kosakovsky Pond, Andrew Webb, and Jody Hey. "Weak selection on synonymous codons substantially inflates dN/dS estimates in bacteria." Proceedings of the National Academy of Sciences 118, no. 20 (May 10, 2021): e2023575118. http://dx.doi.org/10.1073/pnas.2023575118.
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Synonymous codon substitutions are not always selectively neutral as revealed by several types of analyses, including studies of codon usage patterns among genes. We analyzed codon usage in 13 bacterial genomes sampled from across a large order of bacteria, Enterobacterales, and identified presumptively neutral and selected classes of synonymous substitutions. To estimate substitution rates, given a neutral/selected classification of synonymous substitutions, we developed a flexible dN/dS substitution model that allows multiple classes of synonymous substitutions. Under this multiclass synonymous substitution (MSS) model, the denominator of dN/dS includes only the strictly neutral class of synonymous substitutions. On average, the value of dN/dS under the MSS model was 80% of that under the standard codon model in which all synonymous substitutions are assumed to be neutral. The indication is that conventional dN/dS analyses overestimate these values and thus overestimate the frequency of positive diversifying selection and underestimate the strength of purifying selection. To quantify the strength of selection necessary to explain this reduction, we developed a model of selected compensatory codon substitutions. The reduction in synonymous substitution rate, and thus the contribution that selection makes to codon bias variation among genes, can be adequately explained by very weak selection, with a mean product of population size and selection coefficient, Ns=0.8.
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Kolodiazhnyi, Oleg I. "Stereochemistry of electrophilic and nucleophilic substitutions at phosphorus." Pure and Applied Chemistry 91, no. 1 (January 28, 2019): 43–57. http://dx.doi.org/10.1515/pac-2018-0807.
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Abstract Nucleophilic and electrophilic substitutions are the most often applied reactions in organophosphorus chemistry. They are closely interrelated, because in a reacting pair always one reagent is an electrophile, and another nucleophile. The reactions of electrophilic and nucleophilic substitutions at the phosphorus center proceed via the formation of a pentacoordinated intermediate. The mechanism of nucleophilic substitution involves the exchange of ligands in the pentacoordinate phosphorane intermediate, leading to the more stable stereomer under the thermodynamic control. Electrophilic substitution proceeds with retention of absolute configuration, whereas nucleophilic substitution with inversion of configuration at the phosphorus center.
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Smith-Maxwell, Catherine J., Jennifer L. Ledwell, and Richard W. Aldrich. "Uncharged S4 Residues and Cooperativity in Voltage-dependent Potassium Channel Activation." Journal of General Physiology 111, no. 3 (March 1, 1998): 421–39. http://dx.doi.org/10.1085/jgp.111.3.421.
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Substitution of the S4 of Shaw into Shaker alters cooperativity in channel activation by slowing a cooperative transition late in the activation pathway. To determine the amino acids responsible for the functional changes in Shaw S4, we created several mutants by substituting amino acids from Shaw S4 into Shaker. The S4 amino acid sequences of Shaker and Shaw S4 differ at 11 positions. Simultaneous substitution of just three noncharged residues from Shaw S4 into Shaker (V369I, I372L, S376T; ILT) reproduces the kinetic and voltage-dependent properties of Shaw S4 channel activation. These substitutions cause very small changes in the structural and chemical properties of the amino acid side chains. In contrast, substituting the positively charged basic residues in the S4 of Shaker with neutral or negative residues from the S4 of Shaw S4 does not reproduce the shallow voltage dependence or other properties of Shaw S4 opening. Macroscopic ionic currents for ILT could be fit by modifying a single set of transitions in a model for Shaker channel gating (Zagotta, W.N., T. Hoshi, and R.W. Aldrich. 1994. J. Gen. Physiol. 103:321–362). Changing the rate and voltage dependence of a final cooperative step in activation successfully reproduces the kinetic, steady state, and voltage-dependent properties of ILT ionic currents. Consistent with the model, ILT gating currents activate at negative voltages where the channel does not open and, at more positive voltages, they precede the ionic currents, confirming the existence of voltage-dependent transitions between closed states in the activation pathway. Of the three substitutions in ILT, the I372L substitution is primarily responsible for the changes in cooperativity and voltage dependence. These results suggest that noncharged residues in the S4 play a crucial role in Shaker potassium channel gating and that small steric changes in these residues can lead to large changes in cooperativity within the channel protein.
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Leggatt, Graham R., Anne Hosmalin, C. David Pendleton, Anita Kumar, Stephen Hoffman, and Jay A. Berzofsky. "The Importance of Pairwise Interactions Between Peptide Residues in the Delineation of TCR Specificity." Journal of Immunology 161, no. 9 (November 1, 1998): 4728–35. http://dx.doi.org/10.4049/jimmunol.161.9.4728.
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Abstract A minimal, nonamer epitope (TEMEKEGKI) from the reverse transcriptase protein of HIV-1, restricted by H-2Kk, was identified and the function of individual residues determined. Besides classical anchor residues at positions 2 and 9, methionine at position 3 was identified as an important MHC anchor and improved binding of a different (malarial) nonamer epitope to H-2Kk, albeit while also abolishing CTL recognition. Lysine at position 5 was replaceable by alanine for CTL raised against wild-type peptide but abolished recognition for CTL raised against the variant 5ALA peptide, indicating a unidirectional cross-reactivity. Interestingly, one CTL line raised against the 5ALA substituted peptide was permissive for a double substitution at positions 5 and 6, in which lysine was permissive at position 5 only if the adjacent glutamic acid was replaced by alanine. Extensive analysis revealed three distinct patterns of responses with peptides doubly substituted in this region: recognition of both single substitutions but not the double substitution, recognition of only one single substitution but also the double substitution, or recognition of both single substitutions and the double substitution. A second complementary substitution can therefore restore function lost through a first substitution. Thus, no residue acts independently of its neighbors, and pairs of substitutions may give results not predictable from the effects of each taken singly. This finding may have bearing on viral infections (such as HIV), in which the accumulation of two mutations in the epitope may lead to the reengagement of memory CTL previously silenced by the initial mutation.
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Bielawski, Joseph P., and John R. Gold. "Mutation Patterns of Mitochondrial H- and L-Strand DNA in Closely Related Cyprinid Fishes." Genetics 161, no. 4 (August 1, 2002): 1589–97. http://dx.doi.org/10.1093/genetics/161.4.1589.
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Abstract Mitochondrial genome replication is asymmetric. Replication starts from the origin of heavy (H)-strand replication, displacing the parental H-strand as it proceeds along the molecule. The H-strand remains single stranded until light (L)-strand replication is initiated from a second origin of replication. It has been suggested that single-stranded H-strand DNA is more sensitive to mutational damage, giving rise to substitutional rate differences between the two strands and among genes in mammalian mitochondrial DNA. In this study, we analyzed sequences of the cytochrome b, ND4, ND4L, and COI genes of cyprinid fishes to investigate rates and patterns of nucleotide substitution in the mitochondrial genome. To test for strand-asymmetric mutation pressure, a likelihood-ratio test was developed and applied to the cyprinid sequences. Patterns of substitution and levels of strand-asymmetric mutation pressure were largely consistent with a mutation gradient between the H- and L-strand origins of replication. Significant strand bias was observed among rates of transitional substitution. However, biological interpretation of the direction and strength of strand asymmetry for specific classes of substitutions is problematic. The problem occurs because the rate of any single class of substitution inferred from one strand is actually a sum of rates on two strands. The validity of the likelihood-ratio test is not affected by this problem.
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Liang, Jiaming, Thibault Mesplède, Maureen Oliveira, Kaitlin Anstett, and Mark A. Wainberg. "The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance." Journal of Virology 89, no. 22 (August 26, 2015): 11269–74. http://dx.doi.org/10.1128/jvi.01881-15.
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ABSTRACTThe R263K substitution in integrase has been selected in tissue culture with dolutegravir (DTG) and has been reported for several treatment-experienced individuals receiving DTG as part of salvage therapy. The R263K substitution seems to be incompatible with the presence of common resistance mutations associated with raltegravir (RAL), a different integrase strand transfer inhibitor (INSTI). T66I is a substitution that is common in individuals who have developed resistance against a different INSTI termed elvitegravir (EVG), but it is not known whether these two mutations might be compatible in the context of resistance against DTG or what impact the combination of these substitutions might have on resistance against INSTIs. E138K is a common secondary substitution observed with various primary resistance substitutions in RAL- and EVG-treated individuals. Viral infectivity, replicative capacity, and resistance against INSTIs were measured in cell-based assays. Strand transfer and 3′ processing activities were measured biochemically. The combination of the R263K and T66I substitutions decreased HIV-1 infectivity, replicative capacity, and strand transfer activity. The addition of the E138K substitution partially compensated for these deficits and resulted in high levels of resistance against EVG but not against DTG or RAL. These findings suggest that the presence of the T66I substitution will not compromise the activity of DTG and may also help to prevent the additional generation of the R263K mutation. Our observations support the use of DTG in second-line therapy for individuals who experience treatment failure with EVG due to the T66I substitution.IMPORTANCEThe integrase strand transfer inhibitors (INSTIs) elvitegravir and dolutegravir are newly developed inhibitors against human immunodeficiency virus type 1 (HIV-1). HIV drug-resistant mutations in integrase that can arise in individuals treated with elvitegravir commonly include the T66I substitution, whereas R263K is a signature resistance substitution against dolutegravir. In order to determine how different combinations of integrase resistance mutations can influence the outcome of therapy, we report here the effects of the T66I, E138K, and R263K substitutions, alone and in combination, on viral replicative capacity and resistance to integrase inhibitors. Our results show that the addition of R263K to the T66I substitution diminishes viral replicative capacity and strand transfer activity while not compromising susceptibility to dolutegravir. This supports the use of dolutegravir in second-line therapy for patients failing elvitegravir therapy who harbor the T66I resistance substitution.
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Meyer, Johannes, and Stefanie Klatt. "Impact of One Additional Substitution on Player Load and Coaching Tactics in Elite Football." Applied Sciences 11, no. 16 (August 20, 2021): 7676. http://dx.doi.org/10.3390/app11167676.
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Professional football players, coaches, and researchers have discussed additional substitutions in football to reduce player load for a while. However, the effects of additional substitutions on the game have not yet been investigated in detail. The aim of this paper is to determine whether an additional substitution in (1) extra time and (2) regular time would be beneficial and would lead to (a) greater tactical influence of coaches on the match, (b) load reduction during one match, and (c) load reduction during one season. The methodological approach adopted includes two studies, both of which involve data analysis of substitution times (Study 1: n = 3060; Study 2: n = 1153) as well as a survey of football coaches (Study 1: n = 37; Study 2: n = 25). For assessing the effect of an additional substitution in regular time and in extra time, the substitutions made in the Bundesliga, U19-Bundesliga West, DFB-Cup, and 2018 World Cup were evaluated. The findings of this research clearly indicate the potential of an additional substitution by enabling almost 50% of additional load reduction in regular time and 27% in extra time. However, in practice, the findings showed the limits of an additional substitution in extra time on long-term load reduction.
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Furqon, Ahmad. "Penukaran tanah wakaf masjid agung Semarang dalam perspektif fikih istibdal." Ijtihad : Jurnal Wacana Hukum Islam dan Kemanusiaan 17, no. 1 (June 30, 2017): 39. http://dx.doi.org/10.18326/ijtihad.v17i1.39-60.
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Substitution of waqf land is one of nazir (waqf fund manager) efforts to make waqf lands managedmore productive. Semarang Mosque Welfare Council (BKM), as nazir, has made three substitutions ofSemarang Grand Mosque waqf lands. Those three-time substitutions leaved problems causing to poorresults of the waqf lands managed. This study is aimed at finding out the substitution process ofSemarang Grand Mosque waqf lands and the pespective of Istibdal Fiqh on substitutions of SemarangGrand Mosque waqf lands. This study is a case study. The data collection techniques are observation,interview, and documentation. The interview is conducted to parties who know the substitution caseof Semarang Grand Mosque waqf lands. The data collected are analyzed descriptively. The results of thisstudy are: 1) the first substitution of Semarang Grand Mosque waqf lands, made with PT Sambirejo, isnot based on in-depth research especially on land replacement. The party invited to conduct the transaction,Cipto Siswoyo from PT. Sambirejo, his testimony is categorized unacceptable due to fraud. 2) Thesecond substitution of Semarang Grand Mosque waqf lands, which is in the form of money to establishMa’had Aly, is less rocommended by fiqh scholars since the money value tends to decline, and isprone to corrupt and abuse. Moreover, Ma’had Aly has not established yet during the substitutionprocess happened in 2008 to 2016. 3) The third substitution of Semarang Grand Mosque waqf landsemploys substitute money used to purchase substitute lands. This is considered appropriate and theprice of the substitute lands refers to the market price.
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Fernandez, Javier, Deborah Taylor, Duncan R. Morhardt, Kathleen Mihalik, Montserrat Puig, Charles M. Rice, Stephen M. Feinstone, and Marian E. Major. "Long-Term Persistence of Infection in Chimpanzees Inoculated with an Infectious Hepatitis C Virus Clone Is Associated with a Decrease in the Viral Amino Acid Substitution Rate and Low Levels of Heterogeneity." Journal of Virology 78, no. 18 (September 15, 2004): 9782–89. http://dx.doi.org/10.1128/jvi.78.18.9782-9789.2004.
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ABSTRACT Two chimpanzees, 1535 and 1536, became persistently infected following inoculation with RNA transcripts from cDNA clones of hepatitis C virus (HCV). Analysis of the HCV genomes from both animals showed an accumulation of amino acid substitutions over time. The appearance of substitutions in the envelope genes was associated with increased antienvelope antibody titers. However, extensive mutations were not incorporated into hypervariable region 1 (HVR1). A comparison of the nonsynonymous substitution rate/synonymous substitution rate was made at various time points to analyze selective pressure. The highest level of selective pressure occurred during the acute phase and decreased as the infection continued. The nonsynonymous substitution rate was initially higher than the synonymous substitution rate but decreased over time from 3.3 × 10−3 (chimpanzee 1535) and 3.2 × 10−3 (chimpanzee 1536) substitutions/site/year at week 26 to 1.4 × 10−3 (chimpanzee 1535) and 1.7 × 10−3 (chimpanzee 1536) at week 216, while the synonymous substitution rate remained steady at ∼1 × 10−3 substitutions/site/year. Analysis of PCR products using single-stranded conformational polymorphism indicated a low level of heterogeneity in the viral genome. The results of these studies confirm that the persistence of infection is not solely due to changes in HVR1 or heterogeneity and that the majority of variants observed in natural infections could not arise simply through mutation during the time period most humans and chimpanzees are observed. These data also indicate that immune pressure and selection continue throughout the chronic phase.
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Zheng, Jiali, Tianren Zhu, Guanghuan Yang, Longgang Zhao, Fangyu Li, Yong-Moon Park, Fred K. Tabung, Susan E. Steck, Xiaoguang Li, and Hui Wang. "The Isocaloric Substitution of Plant-Based and Animal-Based Protein in Relation to Aging-Related Health Outcomes: A Systematic Review." Nutrients 14, no. 2 (January 9, 2022): 272. http://dx.doi.org/10.3390/nu14020272.
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Plant-based and animal-based protein intake have differential effects on various aging-related health outcomes, but less is known about the health effect of isocaloric substitution of plant-based and animal-based protein. This systematic review summarized current evidence of the isocaloric substitutional effect of plant-based and animal-based protein on aging-related health outcomes. PubMed and Embase databases were searched for epidemiologic observational studies published in English up to 15 March 2021. Studies that included adults ≥18 years old; use of a nutritional substitution model to define isocaloric substitution of plant protein and animal protein; health outcomes covering mortality, aging-related diseases or indices; and reported association estimates with corresponding 95% confidence intervals were included. Nine cohort studies and 3 cross-sectional studies were identified, with a total of 1,450,178 subjects included in this review. Consistent and significant inverse association of substituting plant protein for various animal proteins on all-cause mortality was observed among 4 out of 5 studies with relative risks (RRs) from 0.54 to 0.95 and on cardiovascular disease (CVD) mortality among all 4 studies with RRs from 0.58 to 0.91. Among specific animal proteins, the strongest inverse association on all-cause and CVD mortality was identified when substituting plant protein for red and/or processed meat protein, with the effect mainly limited to bread, cereal, and pasta protein when replacing red meat protein. Isocaloric substitution of plant-based protein for animal-based protein might prevent all-cause and CVD-specific mortality. More studies are needed on this topic, particularly for cancer incidence and other specific aging-related diseases.
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Giraudeau, Alain, and Lana El Kahef. "β-Substitution de la méso-tétraphénylporphyrine de zinc par voie électrochimique." Canadian Journal of Chemistry 69, no. 7 (July 1, 1991): 1161–65. http://dx.doi.org/10.1139/v91-173.
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The electrochemical oxidation of the zinc tetraphenylporphyrin complex in a mixed acetonitrile–dichloroethane solution in the presence of nucleophiles (Py, 3-Pic, [Formula: see text], SCN−) leads to the formation of the corresponding monosubstituted metalloporphyrin. For each of these nucleophiles the substitution occurs at a pyrrole carbon atom (β-substitution). The electrochemical conditions of these substitutions are discussed and an overall reaction is proposed. Key words: porphyrins, electrochemical reactions, nucleophilic substitution.
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Tillier, Elisabeth R. M., and Richard A. Collins. "High Apparent Rate of Simultaneous Compensatory Base-Pair Substitutions in Ribosomal RNA." Genetics 148, no. 4 (April 1, 1998): 1993–2002. http://dx.doi.org/10.1093/genetics/148.4.1993.
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Abstract We present a model for the evolution of paired bases in RNA sequences. The new model allows for the instantaneous rate of substitution of both members of a base pair in a compensatory substitution (e.g., A-U→G-C) and expands our previous work by allowing for unpaired bases or noncanonical pairs. We implemented the model with distance and maximum likelihood methods to estimate the rates of simultaneous substitution of both bases, αd, vs. rates of substitution of individual bases, αs in rRNA. In the rapidly evolving D2 expansion segments of Drosophila large subunit rRNA, we estimate a low ratio of αd/αs, indicating that most compensatory substitutions involve a G-U intermediate. In contrast, we find a surprisingly high ratio of αd/αs in the core small subunit rRNA, indicating that the evolution of the slowly evolving rRNA sequences is modeled much more accurately if simultaneous substitution of both members of a base pair is allowed to occur approximately as often as substitution of individual bases. Using simulations, we have ruled out several potential sources of error in the estimation of αd/αs. We conclude that in the core rRNA sequences compensatory substitutions can be fixed so rapidly as to appear to be instantaneous.
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Imrie, Flora E., Marta Corno, Piero Ugliengo, and Iain R. Gibson. "Computational Studies of Magnesium and Strontium Substitution in Hydroxyapatite." Key Engineering Materials 529-530 (November 2012): 123–28. http://dx.doi.org/10.4028/www.scientific.net/kem.529-530.123.
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The properties of hydroxyapatite can be improved by substitution of biologically relevant ions, such as magnesium (Mg) and strontium (Sr), into its structure. Previous work in the literature has not reached agreement as to site preferences in these substitutions, and there are suggestions that these may change with differing levels of substitution. The current work adopted a quantum mechanical approach based on density functional theory using the CRYSTAL09 code to investigate the structural changes relating to, and site preferences of, magnesium and strontium substitution (to 10 mol%) in hydroxyapatites and also to predict the corresponding vibrational spectra in the harmonic approximation. The structures underwent full geometrical optimisation within the P63 space group, indicating an energetic site preference for the Ca (2) site in the case of Mg substitution, and the Ca (1) site in the case of Sr. Shrinkage of the unit cell was observed in the case of Mg substitution, and expansion in the case of Sr substitution, in agreement with the corresponding ionic radii. Thermodynamic properties of the structures obtained from the harmonic vibrational frequency calculations confirmed that the structures were minima on the potential energy surface. Isotopic substitutions indicated that the main contribution of Sr and Mg to vibrational modes is at frequencies < 400 cm-1.
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Shafer, Robert W., Phillip Hsu, Amy K. Patick, Charles Craig, and Volker Brendel. "Identification of Biased Amino Acid Substitution Patterns in Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Protease Inhibitors." Journal of Virology 73, no. 7 (July 1, 1999): 6197–202. http://dx.doi.org/10.1128/jvi.73.7.6197-6202.1999.
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ABSTRACT Human immunodeficiency virus type 1 (HIV-1) amino acid substitutions observed during antiretroviral drug therapy may be caused by drug selection, non-drug-related evolution, or sampling error introduced by the sequencing process. We analyzed HIV-1 sequences from 371 untreated patients and from 178 patients receiving a single protease inhibitor. Amino acid substitution patterns during treatment were compared with inferred substitution patterns arising evolutionarily without treatment. Our results suggest that most treatment-associated amino acid substitutions are caused by selective drug pressure, including substitutions not previously associated with drug resistance.
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Martin, Jean-Rémy, and François Le Corre. "Sensory Substitution is Substitution." Mind & Language 30, no. 2 (April 2015): 209–33. http://dx.doi.org/10.1111/mila.12078.
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Forsbach-Rothman, Terri, Fernando F. Padró, and Jennifer Rice-Mason. "Course Substitution Practices, Policies, and Implications for Students with Disabilities." NACADA Journal 25, no. 1 (March 1, 2005): 17–25. http://dx.doi.org/10.12930/0271-9517-25.1.17.
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Data from 65 colleges and universities across the United State were used to study course substitution practices for postsecondary students with disabilities. Data indicate that the majority of surveyed institutions (90.8%) allow course substitutions, yet only 50% had written policies directing substitution decisions. At responding institutions (N = 65), foreign language and math are the most common courses requested for substitution. In addition, at surveyed institutions, students with learning disabilities are more likely than other students with disabilities to request and be offered substitutions. These findings are discussed in regard to §504 of the Rehabilitation Act of 1973, subsequent legislation, and two key cases, Southeastern Community College v. Davis (1979) and Guckenberger et al. v. Boston University (1998).
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Hu, Qiang, and Jiaji Shen. "A Cluster and Process Collaboration-Aware Method to Achieve Service Substitution in Cloud Service Processes." Scientific Programming 2020 (August 1, 2020): 1–12. http://dx.doi.org/10.1155/2020/1298513.
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Some cloud services may be invalid since they are located in a dynamically changing network environment. Service substitution is necessary when a cloud service cannot be used. Existing work mainly concerned on service function and quality in service substitution. To select a more suitable substitutive service, process collaboration similarity needs to be considered. This paper proposes a cluster and process collaboration-aware method to achieve service substitution. To compute the process collaboration similarity, we use logic Petri nets to model service processes. All the service processes are transformed into path strings. Service vectors for cloud services are generated by Word2Vec from these path strings. Process collaboration similarity of two cloud services is obtained by computing the cosine value of their service vectors. Meanwhile, similar cloud services are classified as a service cluster. By calculating function similarity and quality matching, a candidate set for services substitution is generated. The service with the highest process collaboration similarity to invalid one in the candidate set is chosen as the substitutive one. Simulation experiments show the proposed method is less time-consuming than traditional methods in finding substitutive service. Meanwhile, the substitutive one has a high cooccurrence rate with neighboring services of the invalid cloud service. Thus, the proposed method is efficient and integrates process collaboration well in service substitution.
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Si-Ahmed, Mohammed, Said Kenai, and Elhem Ghorbel. "Performance of cement mortar with waste ground clay brick." MRS Advances 3, no. 34-35 (2018): 2041–50. http://dx.doi.org/10.1557/adv.2018.291.
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ABSTRACTAn effective way to reduce the impact of cement production on the environment is to use supplementary cementitious materials (SCM) as a partial substitution to cement. In addition to the reduction in cost and energy saving, the use of SCM in cement for the manufacture of mortar and concrete offers technical advantages. In this paper, cement was partially substituted by fines obtained from crushed recycled bricks recovered from a brick plant. The level of substitution was either 0%, 5%, 10% or 15% by weight of cement. The results show that cement substitution by brick fines resulted in a slight loss of workability with the increase of the substitution rate. Substitutions rates of 5% and 10% produced at long-term comparable strength as control mortars. The differential thermal analysis (DTA) and thermo-gravimetric analysis (TGA) results show cement hydration improved significantly with different rates of substitutions at 28 and 180 days of age.
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Comeron, Josep M., and Martin Kreitman. "The Correlation Between Synonymous and Nonsynonymous Substitutions in Drosophila: Mutation, Selection or Relaxed Constraints?" Genetics 150, no. 2 (October 1, 1998): 767–75. http://dx.doi.org/10.1093/genetics/150.2.767.
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Abstract Codon usage bias, the preferential use of particular codons within each codon family, is characteristic of synonymous base composition in many species, including Drosophila, yeast, and many bacteria. Preferential usage of particular codons in these species is maintained by natural selection acting largely at the level of translation. In Drosophila, as in bacteria, the rate of synonymous substitution per site is negatively correlated with the degree of codon usage bias, indicating stronger selection on codon usage in genes with high codon bias than in genes with low codon bias. Surprisingly, in these organisms, as well as in mammals, the rate of synonymous substitution is also positively correlated with the rate of nonsynonymous substitution. To investigate this correlation, we carried out a phylogenetic analysis of substitutions in 22 genes between two species of Drosophila, Drosophila pseudoobscura and D. subobscura, in codons that differ by one replacement and one synonymous change. We provide evidence for a relative excess of double substitutions in the same species lineage that cannot be explained by the simultaneous mutation of two adjacent bases. The synonymous changes in these codons also cannot be explained by a shift to a more preferred codon following a replacement substitution. We, therefore, interpret the excess of double codon substitutions within a lineage as being the result of relaxed constraints on both kinds of substitutions in particular codons.
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Say-awen, April Lynne D., Ma Louise Antonette N. De Las Peñas, and Dirk Frettlöh. "Primitive substitution tilings with rotational symmetries." Acta Crystallographica Section A Foundations and Advances 74, no. 4 (July 1, 2018): 388–98. http://dx.doi.org/10.1107/s2053273318006745.
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This work introduces the idea of symmetry order, which describes the rotational symmetry types of tilings in the hull of a given substitution. Definitions are given of the substitutions σ6 and σ7 which give rise to aperiodic primitive substitution tilings with dense tile orientations and which are invariant under six- and sevenfold rotations, respectively; the derivation of the symmetry orders of their hulls is also presented.
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VandenBerg, Amy M. "Automatic therapeutic substitution in a psychiatric hospital." Mental Health Clinician 3, no. 4 (October 1, 2013): 180–84. http://dx.doi.org/10.9740/mhc.n172343.
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Automatic therapeutic substitution protocols have become common practice in health care systems in the last ten to fifteen years. These protocols can help formulary management, simplify pharmacy inventory, and reduce costs. To date, psychotropics continue to be absent from the most common automatic substitution policies. This article will describe the rationale for select psychotropic substitutions.
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Martynova, Inna A. "METHODOLOGICAL SUPPORT FOR THE DIVIDING OF FACTORIAL SETS SUBSTITUTIONS." АВТОМАТИЗАЦИЯ ПРОЦЕССОВ УПРАВЛЕНИЯ 63, no. 1 (2021): 91–97. http://dx.doi.org/10.35752/1991-2927-2021-1-63-91-97.
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The substitution and permutation functions are the main functions of information cryptographic systems that provide diffusion and mixing of information. It is required to analyze these cryptographic primitives while creating new algorithms for data transformation using such functions. A new scale of notation has been proposed for performing such analysis. This is the factorial sets statistical series notation scale. This scale of notation helps to index the factorial sets statistical series elements and establish a one-to-one correspondence between the number and a specific type of substitution. The use of this system provides a way to find new characteristics and properties of substitutions. Since substitutions of the factorial sets form a cyclic group, the operation on elements of this group can be determined. In the general case, the operation used is a multiplication of substitutions, but this paper suggests another operation for group determination. The article presents a capability for dividing the factorial sets substitutions. Two methods for implementing the substitution division operations are proposed such as a method of successive transition and a method of group transition, which are implemented through non commutative operation of multiplying on inverted substitutions.
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Pánková, K., Z. Milec, M. Leverington-Waite, S. Chebotar, and J. W. Snape. "Characterization of inter-varietal chromosome substitution lines of wheat using molecular markers." Czech Journal of Genetics and Plant Breeding 44, No. 1 (March 28, 2008): 22–29. http://dx.doi.org/10.17221/1329-cjgpb.
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Several sets of wheat inter-varietal chromosome substitution lines (SLs) have been produced over the last fifty years at the CRI (formerly RICP) in Prague-Ruzyně, based on cytogenetic manipulations using aneuploids. Lines with defined genes have been obtained which significantly influence growth habit and flowering time and these have been used particularly in the study of the genetics and physiology of flowering. The sets of lines include substitutions of homoeologous group 5 chromosomes carrying Vrn genes that control vernalisation response, homoeologous group 2 chromosomes with Ppd genes controlling photoperiodic sensitivity, and some other substitutions, particularly those with chromosome 3B of the Czech alternative variety Česká Přesívka where a novel flowering time effect was located. Although the phenotypic and cytological analysis of substitution lines has been continually carried out during backcrossing generations, only the use of molecular markers can allow an unambiguous characterization to verify that substitutions are correct and complete. This analysis has allowed incorrect substitutions or partial substitutions to be identified and discarded. This paper summarizes the results of recent molecular checks of the substitution line collections at CRI.
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Chalimah, Chalimah, and Sumarlam Sumarlam. "SUBSTITUTION ON THE FAMOUS INDONESIAN NOVEL “AYAT AYAT CINTA” WRITTEN BY HABIBURRAHMAN SAEROZI." Jo-ELT (Journal of English Language Teaching) Fakultas Pendidikan Bahasa & Seni Prodi Pendidikan Bahasa Inggris IKIP 4, no. 1 (February 28, 2020): 18. http://dx.doi.org/10.33394/jo-elt.v4i1.2435.
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After being explained about substitution by one of my lecturers, professor Sumarlam, I am interested in investigating the substitution on a famous novel. I choose “Ayat Ayat Cinta” a novel written by Habiburrahman Saerozi. It is very famous in Indonesia and it is not only interesting to read but also it gives us education and the way to love someone seen from Moslem side. There are so many some moral values given there. The novel tells us about true love, honesty, pride, and struggle. The data which I analyzed was only in the sub title “Gadis Mesir Itu Bernama Maria”. The aim of this study is to describe the substitution used by the great writer. I am definitely sure that it will give good contribution on understanding about substitution. The ground theory which I use is from (Sudaryanto, 1993:15). He stated that there were four kinds of substitution, such as: equal quality substitution, definite readdressing substitution, nominal predicative substitution, pronominal substitution. I analyzed the data by describing the substitution used based on substitution theory. There are four findings which I can get after investigating the substitution used in the novel, namely: 1) there is no nominal predicative substitutions but the pronominal substitution is mostly used, 2) one word can substitute two words, 3) the writer differs the calling between friends and teachers to show respect, 4) aku (I) as subject sometimes are not fully written in Indonesian.
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Sudita, I. Dewa Nyoman, I. Gusti Agus Maha Putra Sanjaya, Ni Ketut Sri Rukmini, and Stefanus Nahak. "Substitution of fermented coffee skin in commercial feed on the growth of pigs aged 1-3 months." AJARCDE (Asian Journal of Applied Research for Community Development and Empowerment) 7, no. 2 (May 15, 2023): 51–54. http://dx.doi.org/10.29165/ajarcde.v7i2.259.
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Catur Kintamani Village is one of the village areas in Kintamani-Bangli District, besides its cool climate as an Arabica coffee producing area and has received a Geographical Indication Certificate (GIS). Several coffee processing companies have developed, one of which is UPP. Catur Paramita is a business unit of Subak Abian Kenjung Sari. The problem is that coffee skin waste has not been utilized which can disrupt the environment. One alternative solution to the problem is processing coffee husk waste through fermentation using local microorganism (LMO) probiotics from coffee husks for animal feed. The purpose of this study was to determine the extent to which the appearance response of sows given fermented coffee husk waste as a substitute for commercial feed can affect the appearance of sows in the growth phase. The method used to achieve this goal is the experimental design method and the design used in this study was a completely randomized design (CRD) with 3 treatments, namely: Po (without coffee husk waste), P1 (5% substitution of coffee husk waste), and P2 (substitution of 10% coffee husk waste). Each treatment was repeated 3 times. The results showed a significant effect (P<0.05) substitution of fermented coffee husk waste in commercial feed on the growth of pigs aged 1-3 months. The greater the number of substitutions for coffee skin waste up to 10% (P2) had a significant effect (P<0.05) with an increase in body weight of 12.76 kg compared to without substitution (Po) only 7.89 kg and substitution of coffee skin waste 5% (P1) of 10.98 kg. Still, between P1 and Po the difference was not significantly (P>0.05). It can be concluded that substituting commercial feed with fermented coffee husk waste using local microorganisms (LMO) coffee skin as much as 10% significantly improves body weight gain at 1-3 months.
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Wilkinson, D. J., T. V. Strong, M. K. Mansoura, D. L. Wood, S. S. Smith, F. S. Collins, and D. C. Dawson. "CFTR activation: additive effects of stimulatory and inhibitory phosphorylation sites in the R domain." American Journal of Physiology-Lung Cellular and Molecular Physiology 273, no. 1 (July 1, 1997): L127—L133. http://dx.doi.org/10.1152/ajplung.1997.273.1.l127.
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To investigate the functional significance of individual consensus phosphorylation sites within the R domain of cystic fibrosis transmembrane conductance regulator (CFTR), serines were eliminated by substituting them with alanine. Included in this analysis were serine-660, -670, -686, -700, -712, -737, -768, -795, and -813, which lie within protein kinase A consensus sequences, and serine-641, which does not. Elimination of single potential phosphorylation sites altered the sensitivity of CFTR (expressed in Xenopus oocytes) to activating conditions in a manner that was highly site dependent. Substitution at serine-660, -670, -700, -795, or -813 significantly increased the half-maximal activation constant (KA) for activation by 3-isobutyl-1-methylxanthine, which is consistent with the hypothesis that phosphorylation at any of these sites promotes CFTR activation. The effect of substitution at serine-813 was significantly greater than at the other sites. In contrast, alanine substitution at serine-737 or -768 actually decreased the KA for activation, suggesting that phosphorylation at either of these sites is inhibitory. Substitution at serine-641, -686, and -712 had no significant effect on activation sensitivity. The effects of multiple serine to alanine substitutions were consistent with the notion that phosphorylation at individual sites produced roughly additive effects, suggesting that the effect produced by phosphorylation of any one serine was not dependent on the phosphorylation state of other serines. These results are consistent with the notion that, although none of the phosphorylation sites studied here are absolutely necessary for activation of CFTR, individual sites contribute differently to the gating of the channel.
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R.K., Migunova, Todrin A.F, and Kaprelyants A.S. "Freeze Substitution for EM-Studies Time Measuring." Microscopy and Microanalysis 5, S2 (August 1999): 450–51. http://dx.doi.org/10.1017/s1431927600015579.
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We conducted physical and mathematical modelling of the process of substituion of ice with organic solvent. The result was a relationship between the time of freeze-substitution and the sample thickness. The model is based on the solution of mass exchange problem between a porous plate (frozen tissue) filled with a solid matter (ice) and an organic solvent (alcohol, acetone) that is contained in an apparatus with an active fluid circulation. The model takes in account porousness of tissue, dissolving of ice with solvent that produces a new medium, dissolving of that medium and its substitutions with solvent after solvent concentration exceeds evtectic concentration for the given temperature. Our results (fig. 1) agree with previously published results [1].We also conducted experiments using original device [2] that implements freeze-substitution method. The device is made of the desk apparatus, comprising cryogenic and electron parts. Cryochamber ( Fig. 2 ) contains cylindrical unit (1), central channel (2) and located around it cylindrical vessels (3), connected by means of upper (4) and lower (5) channels with the central one. Perforated containers (6) with frozen bioobjects are adjusted on metal rack (7). The flux inducer (8) provides the circulation of substituting medium. The cold-conduct or (9) is submerged into a liquid nitrogen. Temperature control is performed be the thermogauge (10). The range of operating temperatures stabilization is from +20° to −120° C.
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Yang, Yunhan, Fenji Li, Cuicui Yang, Lijuan Jia, Lijuan Yang, Futing Xia, and Jinhui Peng. "Effect of Substitution for Insertion of CO2 into Epoxides and Aziridines: An Ab Initio Study." Australian Journal of Chemistry 73, no. 1 (2020): 30. http://dx.doi.org/10.1071/ch19296.
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The insertion of CO2 into epoxides and aziridines has been studied using density functional theory (B3LYP) and ab initio (MP2) methods, and the effect of substitution for the two reactions are further explored. It is found that the reactivity of epoxides and aziridines are similar, and insertion of CO2 proceeds through a concerted mechanism. The substitutions of methyl and phenyl does not change the reaction mechanism, but the transition state for the substitution on the attacking position becomes loose with a lower free energy barrier. The substitutions of methyl and phenyl decrease the free energy barrier, with phenyl substitution having a greater affect. The results also show that the free energy barriers for the insertions of CO2 into aziridines are ~10kcalmol−1 lower than the corresponding reactions of CO2 with epoxides.
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Hastings, Alan. "Substitution Rates Under Stabilizing Selection." Genetics 116, no. 3 (July 1, 1987): 479–86. http://dx.doi.org/10.1093/genetics/116.3.479.
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ABSTRACT Allelic substitutions under stabilizing phenotypic selection on quantitative traits are studied in Monte Carlo simulations of 8 and 16 loci. The results are compared and contrasted to analytical models based on work of M. Kimura for two and "infinite" loci. Selection strengths of S = 4Nes approximately four (which correspond to reasonable strengths of selection for quantitative characters) can retard substitution rates tenfold relative to rates under neutrality. An important finding is a strong dependence of per locus substitution rates on the number of loci.
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Berbee, Mary L., and John W. Taylor. "Dating the evolutionary radiations of the true fungi." Canadian Journal of Botany 71, no. 8 (August 1, 1993): 1114–27. http://dx.doi.org/10.1139/b93-131.
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In this paper we construct a relative time scale for the origin and radiation of major lineages of the true fungi, using the 18S ribosomal RNA gene sequence data of 37 fungal species, and then calibrate the time scale using fossil evidence. Of the sequences, 28 were from the literature or data banks and the remaining 9 are new. To estimate the order of origin of fungal lineages we reconstructed the phylogeny of the fungi using aligned sequence data. To compensate for the differences in nucleotide substitution rates among various fungal lineages, we normalized the pairwise substitution data before estimating the relative timing of fungal divergences. We divided the fungi into nine groups. We then calculated the average percent substitution for each group, and also the average for all the groups, for the time period beginning when the fungi diverged from a common ancestor and ending at the present. We used the ratios of group-specific percent substitutions to the average percent substitution to normalize our pairwise substitution data matrix. To infer the relative timing of the origin of lineages we superimposed the normalized percentages of nucleotide substitutions onto the parsimony-based phylogeny. Calibrating the rate of sequence change involved relating the normalized percent substitution associated with phylogenetic events to fungal fossils, the ages of fungus hosts, and ages of symbionts. These calibration points were consistent with a substitution rate of 1% per lineage per 100 Ma. Based on phylogeny and calibrated percent substitution, the terrestrial fungi diverged from the chytrids approximately 550 Ma ago. After plants invaded the land approximately 400 Ma ago, ascomycetes split from basidiomycetes. Mushrooms, many ascomycetous yeasts, and common molds in the genera Penicillium and Aspergillus may have evolved after the origin of angiosperm plants and in the last 200 Ma. Key words: fungus evolution, molecular clock, ascomycete phylogeny, basidiomycete phylogeny, 18S rRNA.
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Mattson, D. H., N. Shimojo, E. P. Cowan, J. J. Baskin, R. V. Turner, B. D. Shvetsky, J. E. Coligan, W. L. Maloy, and W. E. Biddison. "Differential effects of amino acid substitutions in the beta-sheet floor and alpha-2 helix of HLA-A2 on recognition by alloreactive viral peptide-specific cytotoxic T lymphocytes." Journal of Immunology 143, no. 4 (August 15, 1989): 1101–7. http://dx.doi.org/10.4049/jimmunol.143.4.1101.
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Abstract Crystallographic studies of the HLA-A2 molecule have led to the assignment of a putative peptide binding site that consists of a groove with a beta-pleated sheet floor bordered by two alpha-helices. A CTL-defined variant of HLA-A2, termed HLA-A2.2F, differs from the common A2.1 molecule by three amino acids: a Leu to Trp substitution at position 156 in the alpha-2 helix, a Val to Leu substitution at position 95 in the beta-sheet floor of the groove, and a Gln to Arg substitution at position 43 in a loop outside of the groove. Another HLA-A2 variant, termed CLA, has a single Phe to Tyr substitution at position 9 that is sterically located adjacent to position 95 in the beta-sheet floor of the groove. We have determined which of the amino acid substitutions at positions 9, 43, 95, or 156 could individually affect recognition by panels of A2.1 allospecific and A2.1-restricted influenza viral matrix peptide-specific CTL lines, using a panel of site-directed mutants and CLA. Recognition by allospecific CTL lines was generally unaffected by any one of the amino acid substitutions, but was eliminated by the double substitution at positions 95 and 156. Allorecognition by some CTL lines was eliminated by a single substitution at position 9 or 95. In contrast, recognition by A2.1-restricted matrix peptide specific CTL was totally eliminated by a single substitution at position 9 or 156. The substitution at position 43 in a loop away from the peptide binding groove had no effect on allorecognition or matrix peptide recognition. These results indicate that amino acid residues in the floor or alpha-2 helical wall of the peptide binding groove of the HLA-A2 molecule can differentially affect allorecognition and viral peptide recognition.
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Bielawski, Joseph P., Katherine A. Dunn, and Ziheng Yang. "Rates of Nucleotide Substitution and Mammalian Nuclear Gene Evolution: Approximate and Maximum-Likelihood Methods Lead to Different Conclusions." Genetics 156, no. 3 (November 1, 2000): 1299–308. http://dx.doi.org/10.1093/genetics/156.3.1299.
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Abstract Rates and patterns of synonymous and nonsynonymous substitutions have important implications for the origin and maintenance of mammalian isochores and the effectiveness of selection at synonymous sites. Previous studies of mammalian nuclear genes largely employed approximate methods to estimate rates of nonsynonymous and synonymous substitutions. Because these methods did not account for major features of DNA sequence evolution such as transition/transversion rate bias and unequal codon usage, they might not have produced reliable results. To evaluate the impact of the estimation method, we analyzed a sample of 82 nuclear genes from the mammalian orders Artiodactyla, Primates, and Rodentia using both approximate and maximum-likelihood methods. Maximum-likelihood analysis indicated that synonymous substitution rates were positively correlated with GC content at the third codon positions, but independent of nonsynonymous substitution rates. Approximate methods, however, indicated that synonymous substitution rates were independent of GC content at the third codon positions, but were positively correlated with nonsynonymous rates. Failure to properly account for transition/transversion rate bias and unequal codon usage appears to have caused substantial biases in approximate estimates of substitution rates.
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Zhao, Mingyue, Lingyi Zhang, Zhitong Feng, and Yu Fang. "Physicians’ Knowledge, Attitude and Practice of Generic Substitution in China: A Cross-Sectional Online Survey." International Journal of Environmental Research and Public Health 18, no. 15 (July 21, 2021): 7749. http://dx.doi.org/10.3390/ijerph18157749.
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The purpose of this study is to investigate physicians’ knowledge, attitudes and practice of generic medicine substitutions in China. We conducted a cross-sectional online questionnaire survey on physicians from secondary or tertiary hospitals in China from 2020 December to 2021 April. Descriptive statistical and ordered logistic regression were used for analysis. A total of 1225 physicians were included in the final analysis, and only 330 (26.94%) of them scored 4 or above in the knowledge part, which means that the physicians have a good knowledge of generic substitutions. Of the total, 586 (47.83%) agreed or strongly agreed that generic drugs could be substituted for originator drugs and 585 (47.75%) always or often prescribed generic medicines. The percentage of physicians with a positive attitude toward or that practice prescribing generic medicine is below 50%, which needs to be improved in China. Physicians’ knowledge, their attitude toward generic substitution, if familiar with the policy of generic substitution, and incentives for prescribing generic medicines are influencing factors for the practice of generic substitution. Our studies show that the practice of generic substitution by physicians could be improved by several measures in China. We suggested that the physicians should be taught more about the bulk-buy policy and the generic-originator equivalence evaluation policy. Moreover, government incentives to promote generic substitution should be established. Our study also suggested that physicians with less working experience and female physicians should learn more about generic substitution.
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Iglesias, Blanca, Juan M. García-Ceberino, Javier García-Rubio, and Sergio J. Ibáñez. "How Do Player Substitutions Influence Men’s UEFA Champions League Soccer Matches?" Applied Sciences 12, no. 22 (November 9, 2022): 11371. http://dx.doi.org/10.3390/app122211371.
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Coaches’ player substitution strategies can change the tactical behavior and the final result of matches. This empirical study aims to describe the relationship/association of player substitution variables with the results of men’s UEFA Champions League matches during the 2018–2019 season. A total of 125 matches were analyzed using an ad hoc observation sheet created for this purpose. To measure the degree and strength of association between the variables studied, Chi-square and Cramer’s V tests were used, respectively. In turn, the Adjusted Standardized Residuals from the contingency tables were calculated to detect patterns of association. Likewise, a decision tree, in particular, the CHAID method, was used to predict and identify interactions. Player substitutions affect the final result and the findings prove it. An own team’s goal after 5–10 min of player substitution was win-related (positive impact) (90.40%, ASRs = 10.40), while an opposing team’s goal after 5–10 min of player substitution was loss-related (negative impact) (90.30%, ASRs = 10.30). Regardless of the match status, the positive impact increased the winning percentage. Furthermore, the match status was postulated as an indicator of the need to make player substitutions. It showed that player substitutions could determine the final result when teams were tying. On the other hand, the match location was not a differentiating factor between winning and losing teams, although the winning percentage was somewhat higher for home teams. Coaches could use this information to establish player substitution strategies that would allow them to perform at their best.
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Thiele, V., R. A. Pickering, G. Melz, and W. Pohler. "Identification of Hordeum bulbosum chromosomes in H. vulgare – H. bulbosum substitutions using isozyme markers." Genome 35, no. 3 (June 1, 1992): 454–60. http://dx.doi.org/10.1139/g92-067.
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Hordeum bulbosum chromosomes 1Hb, 4Hb, 6Hb, and 7Hb were identified in five monosomic and one double monosomic H. vulgare – H. bulbosum substitution using 11 isozyme systems. In all substitutions analyzed, diagnostic isozyme bands for H. bulbosum chromosomes were found in the same isozyme systems and zones having diagnostic value for the homoeologous H. vulgare chromosomes. However, bands that are normally diagnostic for the 3Hv region appeared in one 6Hv substitution and in one selfed progeny from another 6Hv substitution.Key words: Hordeum vulgare, Hordeum bulbosum, alien chromosome substitutions, isozymes, chromosome identification, homoeologous relationships.
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Miller, T. E., S. M. Reader, and C. C. Ainsworth. "A chromosome of Hordeum chilense homoeologous to group 7 of wheat." Canadian Journal of Genetics and Cytology 27, no. 1 (February 1, 1985): 101–4. http://dx.doi.org/10.1139/g85-016.
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Individual substitution lines have been produced with Hordeum chilense chromosome A substituted in turn for chromosome 7A, 7B, or 7D of Triticum aestivum. Telocentric substitutions with the α arm, substituted for chromosome 7A or 7D, or the β arm substituted for chromosome 7B have also been produced. The substitutions have been confirmed by the presence of a purple straw marker, by gel isoelectric focusing of α-amylase isozymes, and cytologically using telocentric chromosome markers. Chromosome A has consequently been designated 7Hch.Key words: Hordeum chilense, wheat, chromosome substitution, homoeology, α-amylase.
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Margiotti, K., F. Sangiuolo, A. De Luca, F. Froio, C. L. Pearce, V. Ricci-Barbini, F. Micali, et al. "Evidence for an Association between the SRD5A2 (Type II Steroid 5α-Reductase) Locus and Prostate Cancer in Italian Patients." Disease Markers 16, no. 3-4 (2000): 147–50. http://dx.doi.org/10.1155/2000/683607.
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We have investigated the contributions of three polymorphic markers in the SRD5A2 gene to prostate cancer in a group of Italian patients. We have genotyped cases and controls for a polymorphic (TA)ndinucleotide repeat and two functional substitutions, A49T and V89L, substituting respectively alanine with threonine at codon 49, and valine to leucine at codon 89. We found a substantially increased but not significant risk associated with the 49T mutation and a reduction of risk for the V89L substitution. In conclusion, we report on preliminary evidence for both increased and decreased risk associated with separate markers at this locus.
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Briales, A., J. M. Rodríguez-Martínez, C. Velasco, P. Díaz de Alba, J. Domínguez-Herrera, J. Pachón, and A. Pascual. "In VitroEffect ofqnrA1,qnrB1, andqnrS1Genes on Fluoroquinolone Activity against IsogenicEscherichia coliIsolates with Mutations ingyrAandparC." Antimicrobial Agents and Chemotherapy 55, no. 3 (December 20, 2010): 1266–69. http://dx.doi.org/10.1128/aac.00927-10.
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ABSTRACTThis article provides an analysis of thein vitroeffect ofqnrA1,qnrB1, andqnrS1genes, combined with quinolone-resistant Ser83Leu substitutions in GyrA and/or Ser80Arg in ParC, on fluoroquinolone (FQ) resistance in isogenicEscherichia colistrains. The association of Ser83Leu substitution in GyrA, Ser80Arg substitution in ParC, andqnrgene expression increased the MIC of ciprofloxacin to 2 μg/ml.qnrgenes present inE. colithat harbored a Ser83Leu substitution in GyrA increased mutant prevention concentration (MPC) values to 8 to 32 μg/ml.qnrgene expression inE. colimay play an important role in selecting for one-step FQ-resistant mutants.
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Bystrov, Vladimir S., Ekaterina V. Paramonova, Leon A. Avakyan, Natalya V. Eremina, Svetlana V. Makarova, and Natalia V. Bulina. "Effect of Magnesium Substitution on Structural Features and Properties of Hydroxyapatite." Materials 16, no. 17 (August 30, 2023): 5945. http://dx.doi.org/10.3390/ma16175945.
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Hydroxyapatite (HAP) is the main mineral component of bones and teeth. It is widely used in medicine as a bone filler and coating for implants to promote new bone growth. Ion substitutions into the HAP structure highly affect its properties. One of the most important substituents is magnesium. This paper presents new results obtained using high-precision hybrid density functional theory calculations for Mg/Ca substitutions in HAP in a wide magnesium concentration range within a 2 × 2 × 2 supercell model. Experimental data on the mechanochemical synthesis of HAP-Mg samples with different Mg concentrations are also presented. A comparison between the experiment and the theory showed good agreement: the HAP-Mg unit cell parameters and volume decreased with increasing degree of Mg/Ca substitution. The changes in the distances between the Ca and O, Ca and H, and Mg and O ions upon Mg/Ca substitution in different calcium positions was analyzed. The resulting asymmetry and distortion of the cell parameters were evaluated. It was shown that bulk modulus, energy levels, and band gap depend on the degree of Mg substitutions in the Ca1 and Ca2 positions. The formation energies of Mg/Ca substitutions showed non-monotonic behavior that was different for Ca1 and Ca2 positions. The Ca2 position had a slightly higher probability (~5 meV/f.u.) of substitution than Ca1 position at a Mg concentration x = 0.5. At x = 1, substitution in both positions can coexist. The simulated IR spectra for different Mg/Ca substitutions showed that Mg in the Ca2 position changes the IR spectrum more significantly than Mg in the Ca1 position. Similar changes were recorded in the IR spectra of the synthesized samples. The electronic structure is shown to be sensitive to the number and position of substitutions, which may be used to tweak the optical properties of the HAP-Mg material.
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Rakov, L. T., V. Yu Prokofiev, and L. D. Zorina. "Impurity elements in quartz from gold deposits of the Darasun ore field (Eastern Transbaikalia, Russia): electron paramagnetic resonance data." Геология рудных месторождений 61, no. 2 (May 8, 2019): 72–92. http://dx.doi.org/10.31857/s0016-777061272-92.
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The distribution of substitutional Al, Ti, and Ge impurities in quartz samples from the Darasun, Teremkinskoe and Talatui gold deposits, located in the Darasun orefield, were studied using the electron paramagnetic resonance method. Relationship between the isomorphic substitution and the dynamic recrystallization of quartz was studied by optical and scanning electron microscopy.
Analysis of the plots of interdependency between the concentrations of various substitutional impurities in quartz (isogens) provided an opportunity to detect isomorphic substitution development trends. Two isomorphic substitution stages were recognized, one associated with mineral crystallization and the other, with its subsequent dynamic recrystallization. The first stage leads to Al impurity incorporation into the quartz crystal lattice, and the second, to Ti impurity incorporation. The Ge impurity is the isomorphic substitution catalyst, and its concentrations vary widely. It is noted that the second stage plays a decisive role, because it accounts for the incorporation of the larger part of substitutional impurities. This process is facilitated by the dynamic recrystallization of quartz.
Four quartz genetic groups, which are described by individual isogens, have been recognized in the Darasun orefield. Two of them correspond to the quartz crystallized from a magmatogenic fluid directly or redeposited with its participation, and the other two correspond to the quartz crystallized from an altered fluid. The facts that substitutional Al concentrations are retained in quartz after redeposition, whereas substitutional Ti impurity concentrations fall dramatically, are demonstrated.
Mineral formation processes at each gold deposit are discussed. Two types of temperature zoning, the normal and the reverse, have been recognized at the Darasun deposit. Each zoning is characterized by an individual quartz genetic group and the extent of mineralization system closedness. The genetically similar magmatogenic quartz samples found at the Darasun and Talatui deposits attest to the uniformity of mineralization process in the Darasun orefield. The established trends of isomorphic substitution in quartz are applicable in the studies of ore formation histories of gold and other ore deposits.
Keywords: Darasun; Teremkinskoe; and Talatui deposits of the Darasun orefield; mineral formation; auriferous quartz; dynamic recrystallization; substitutional impurities; genetic analysis; isogens; isomorphic substitution stages; quartz redeposition; temperature zoning; EPR method; scanning electron microscopy
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Kumar, Raj, Suganya Natarajan, Rahul Singh, Vinod Singh Rajput, Ganesh Babu Loganathan, Sanjeev Kumar, T. Sakthi, and Akter Meem Mahseena. "Investigation on Mechanical Durability Properties of High-Performance Concrete with Nanosilica and Copper Slag." Journal of Nanomaterials 2022 (August 24, 2022): 1–8. http://dx.doi.org/10.1155/2022/7030680.
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Mineral admixtures are frequently utilized as cement substitution materials in high-performance concrete (HPC), and so many studies have explored the influence of mineral admixtures on the rheological behavior of HPC. Investigations were done to examine the impact of nanosilica less than 100 nm on HPC by substituting copper slag at a fixed substitution of forty percent for fine aggregate. Concrete samples were cast by substituting cement with nanosilica at (0.5, 1, 1.5, 2, 2.5, and 3) percentages. Examinations on mechanical properties and durability were done on specimens. The above tests demonstrated an increase in water demand because of the increase in the nanosilica substitution percentage. Mechanical and durability properties were improved at a larger rate with the incorporation of nanosilica. The outcomes indicated that colloidal nanosilica is an effective material that enhances the microstructure and acts as a catalyst for pozzolanic activity. The incorporation of nanosilica improves the strength up to two percentage substitution level.
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Dror, Yehudit. "Cohesive substitution in the Qurʼān." Lingua Posnaniensis 59, no. 2 (December 1, 2017): 41–52. http://dx.doi.org/10.1515/linpo-2017-0011.
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Abstract This article describes the use of cohesive substitution in the Qurʼān. In Halliday and Hasan’s model of cohesion, this term refers to the replacement of one syntactic item by another; this article asks several questions in this regard: How is cohesive substitution realized in the Qurʼān? What items does it replace? Why is it used? The study finds that there are only a few cases of cohesive substitution in the Qurʼān, and the nominal and verbal substitution operate in the Qurʼān as they do in English. In that language, the forms one and the same are employed for nominal substitution. In the Qurʼān the forms ʼaḥad “one” (sg. masc.), ʼiḥdā “one” (sg. fem.) and miṯlu ḏālika “the same” can be considered equivalent to the English form one and the same. Verbal substitution in Arabic is realized by the verb yaf’alu “he will do,” “he does” (and is not followed by the anaphoric pronoun ḏālika “that”), replacing only the verb without its complement. No occurrences of clausal substitutions were found because usually variations of anaphoric reference (e.g., ḏālika “that” or ka-ḏālika “like that”) were used instead. From a pragmatic viewpoint, cohesive substitution is used to prevent repetition of the same word found in the immediately preceding clause.