Sequence diversity and molecular evolutionary rates between buffalo and cattle.

PubMed

Moaeen-ud-Din, M; Bilal, G

2015-02-01

Identification of genes of importance regarding production traits in buffalo is impaired by a paucity of genomic resources. Choice to fill this gap is to exploit data available for cow. The cross-species application of comparative genomics tools is potential gear to investigate the buffalo genome. However, this is dependent on nucleotide sequences similarity. In this study, gene diversity between buffalo and cattle was determined using 86 gene orthologues. There was approximately 3% difference in all genes in terms of nucleotide diversity and 0.267 ± 0.134 in amino acids, indicating the possibility for successfully using cross-species strategies for genomic studies. There were significantly higher non-synonymous substitutions both in cattle and buffalo; however, there was similar difference in terms of dN- dS (4.414 versus 4.745) in buffalo and cattle, respectively. Higher rate of non-synonymous substitutions at similar level in buffalo and cattle indicated a similar positive selection pressure. Results for relative rate test were assessed with the chi-squared test. There was no significance difference on unique mutations between cattle and buffalo lineages at synonymous sites. However, there was a significance difference on unique mutations for non-synonymous sites, indicating ongoing mutagenic process that generates substitutional mutation at approximately the same rate at silent sites. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of cattle and buffalo. This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae. © 2014 Blackwell Verlag GmbH.

Whole-Gene Positive Selection, Elevated Synonymous Substitution Rates, Duplication, and Indel Evolution of the Chloroplast clpP1 Gene

PubMed Central

Erixon, Per; Oxelman, Bengt

2008-01-01

Background Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. Methodology/Principle Findings We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family) and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family). Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying) selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. Conclusions/Significance We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the controversial issue of whether negative or positive selection is to be expected after gene duplications by providing evidence for the latter alternative. The observed increase in synonymous substitution rates in some of the lineages indicates that the detection of positive selection may be obscured under such circumstances. Future studies are required to explore the functional significance of the large inserted repeated amino acid motifs, as well as the possibility that synonymous substitution rates may be affected by positive selection. PMID:18167545

The nearly neutral and selection theories of molecular evolution under the fisher geometrical framework: substitution rate, population size, and complexity.

PubMed

Razeto-Barry, Pablo; Díaz, Javier; Vásquez, Rodrigo A

2012-06-01

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population's phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models.

The Nearly Neutral and Selection Theories of Molecular Evolution Under the Fisher Geometrical Framework: Substitution Rate, Population Size, and Complexity

PubMed Central

Razeto-Barry, Pablo; Díaz, Javier; Vásquez, Rodrigo A.

2012-01-01

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population’s phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models. PMID:22426879

Are Synonymous Substitutions in Flowering Plant Mitochondria Neutral?

PubMed

Wynn, Emily L; Christensen, Alan C

2015-10-01

Angiosperm mitochondrial genes appear to have very low mutation rates, while non-gene regions expand, diverge, and rearrange quickly. One possible explanation for this disparity is that synonymous substitutions in plant mitochondrial genes are not truly neutral and selection keeps their occurrence low. If this were true, the explanation for the disparity in mutation rates in genes and non-genes needs to consider selection as well as mechanisms of DNA repair. Rps14 is co-transcribed with cob and rpl5 in most plant mitochondrial genomes, but in some genomes, rps14 has been duplicated to the nucleus leaving a pseudogene in the mitochondria. This provides an opportunity to compare neutral substitution rates in pseudogenes with synonymous substitution rates in the orthologs. Genes and pseudogenes of rps14 have been aligned among different species and the mutation rates have been calculated. Neutral substitution rates in pseudogenes and synonymous substitution rates in genes are significantly different, providing evidence that synonymous substitutions in plant mitochondrial genes are not completely neutral. The non-neutrality is not sufficient to completely explain the exceptionally low mutation rates in land plant mitochondrial genomes, but selective forces appear to play a small role.

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

PubMed Central

GUZMÁN-URIBE, Daniela; ALVARADO-ESTRADA, Keila Neri; PIERDANT-PÉREZ, Mauricio; TORRES-ÁLVAREZ, Bertha; SÁNCHEZ-AGUILAR, Jesus Martin; ROSALES-IBÁÑEZ, Raúl

2017-01-01

Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%), meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues. PMID:28403359

FRAGS: estimation of coding sequence substitution rates from fragmentary data

PubMed Central

Swart, Estienne C; Hide, Winston A; Seoighe, Cathal

2004-01-01

Background Rates of substitution in protein-coding sequences can provide important insights into evolutionary processes that are of biomedical and theoretical interest. Increased availability of coding sequence data has enabled researchers to estimate more accurately the coding sequence divergence of pairs of organisms. However the use of different data sources, alignment protocols and methods to estimate substitution rates leads to widely varying estimates of key parameters that define the coding sequence divergence of orthologous genes. Although complete genome sequence data are not available for all organisms, fragmentary sequence data can provide accurate estimates of substitution rates provided that an appropriate and consistent methodology is used and that differences in the estimates obtainable from different data sources are taken into account. Results We have developed FRAGS, an application framework that uses existing, freely available software components to construct in-frame alignments and estimate coding substitution rates from fragmentary sequence data. Coding sequence substitution estimates for human and chimpanzee sequences, generated by FRAGS, reveal that methodological differences can give rise to significantly different estimates of important substitution parameters. The estimated substitution rates were also used to infer upper-bounds on the amount of sequencing error in the datasets that we have analysed. Conclusion We have developed a system that performs robust estimation of substitution rates for orthologous sequences from a pair of organisms. Our system can be used when fragmentary genomic or transcript data is available from one of the organisms and the other is a completely sequenced genome within the Ensembl database. As well as estimating substitution statistics our system enables the user to manage and query alignment and substitution data. PMID:15005802

Using multinomial logistic regression analysis to understand anglers willingness to substitute other fishing locations

Treesearch

Woo-Yong Hyun; Robert B. Ditton

2007-01-01

The concept of recreation substitutability has been a continuing research topic for outdoor recreation researchers. This study explores the relationships among variables regarding the willingness to substitute one location for another location. The objectives of the study are 1) to ascertain and predict the extent to which saltwater anglers were willing to substitute...

A survey of nuclear ribosomal internal transcribed spacer substitution rates across angiosperms: an approximate molecular clock with life history effects

PubMed Central

Kay, Kathleen M; Whittall, Justen B; Hodges, Scott A

2006-01-01

Background A full understanding of the patterns and processes of biological diversification requires the dating of evolutionary events, yet the fossil record is inadequate for most lineages under study. Alternatively, a molecular clock approach, in which DNA or amino acid substitution rates are calibrated with fossils or geological/climatic events, can provide indirect estimates of clade ages and diversification rates. The utility of this approach depends on the rate constancy of molecular evolution at a genetic locus across time and across lineages. Although the nuclear ribosomal internal transcribed spacer region (nrITS) is increasingly being used to infer clade ages in plants, little is known about the sources or magnitude of variation in its substitution rate. Here, we systematically review the literature to assess substitution rate variation in nrITS among angiosperms, and we evaluate possible correlates of the variation. Results We summarize 28 independently calibrated nrITS substitution rates ranging from 0.38 × 10-9 to 8.34 × 10-9 substitutions/site/yr. We find that herbaceous lineages have substitution rates almost twice as high as woody plants, on average. We do not find any among-lineage phylogenetic constraint to the rates, or any effect of the type of calibration used. Within life history categories, both the magnitude of the rates and the variance among rates tend to decrease with calibration age. Conclusion Angiosperm nrITS substitution rates vary by approximately an order of magnitude, and some of this variation can be attributed to life history categories. We make cautious recommendations for the use of nrITS as an approximate plant molecular clock, including an outline of more appropriate phylogenetic methodology and caveats against over interpretation of results. We also suggest that for lineages with independent calibrations, much of the variation in nrITS substitution rates may come from uncertainty in calibration date estimates, highlighting the importance of accurate and/or multiple calibration dates. PMID:16638138

Sample substitution can be an acceptable data-collection strategy: the case of the Belgian Health Interview Survey.

PubMed

Demarest, Stefaan; Molenberghs, Geert; Van der Heyden, Johan; Gisle, Lydia; Van Oyen, Herman; de Waleffe, Sandrine; Van Hal, Guido

2017-11-01

Substitution of non-participating households is used in the Belgian Health Interview Survey (BHIS) as a method to obtain the predefined net sample size. Yet, possible effects of applying substitution on response rates and health estimates remain uncertain. In this article, the process of substitution with its impact on response rates and health estimates is assessed. The response rates (RR)-both at household and individual level-according to the sampling criteria were calculated for each stage of the substitution process, together with the individual accrual rate (AR). Unweighted and weighted health estimates were calculated before and after applying substitution. Of the 10,468 members of 4878 initial households, 5904 members (RRind: 56.4%) of 2707 households (RRhh: 55.5%) participated. For the three successive (matched) substitutes, the RR dropped to 45%. The composition of the net sample resembles the one of the initial samples. Applying substitution did not produce any important distorting effects on the estimates. Applying substitution leads to an increase in non-participation, but does not impact the estimations.

Comparative Analysis of the Mitochondrial Genomes of Callitettixini Spittlebugs (Hemiptera: Cercopidae) Confirms the Overall High Evolutionary Speed of the AT-Rich Region but Reveals the Presence of Short Conservative Elements at the Tribal Level

PubMed Central

Liu, Jie; Bu, Cuiping; Wipfler, Benjamin; Liang, Aiping

2014-01-01

The present study compares the mitochondrial genomes of five species of the spittlebug tribe Callitettixini (Hemiptera: Cercopoidea: Cercopidae) from eastern Asia. All genomes of the five species sequenced are circular double-stranded DNA molecules and range from 15,222 to 15,637 bp in length. They contain 22 tRNA genes, 13 protein coding genes (PCGs) and 2 rRNA genes and share the putative ancestral gene arrangement of insects. The PCGs show an extreme bias of nucleotide and amino acid composition. Significant differences of the substitution rates among the different genes as well as the different codon position of each PCG are revealed by the comparative evolutionary analyses. The substitution speeds of the first and second codon position of different PCGs are negatively correlated with their GC content. Among the five species, the AT-rich region features great differences in length and pattern and generally shows a 2–5 times higher substitution rate than the fastest PCG in the mitochondrial genome, atp8. Despite the significant variability in length, short conservative segments were identified in the AT-rich region within Callitettixini, although absent from the other groups of the spittlebug superfamily Cercopoidea. PMID:25285442

Generation time, life history and the substitution rate of neutral mutations.

PubMed

Lehtonen, Jussi; Lanfear, Robert

2014-11-01

Our understanding of molecular evolution is hampered by a lack of quantitative predictions about how life-history (LH) traits should correlate with substitution rates. Comparative studies have shown that neutral substitution rates vary substantially between species, and evidence shows that much of this diversity is associated with variation in LH traits. However, while these studies often agree, some unexplained and contradictory results have emerged. Explaining these results is difficult without a clear theoretical understanding of the problem. In this study, we derive predictions for the relationships between LH traits and substitution rates in iteroparous species by using demographic theory to relate commonly measured life-history traits to genetic generation time, and by implication to neutral substitution rates. This provides some surprisingly simple explanations for otherwise confusing patterns, such as the association between fecundity and substitution rates. The same framework can be applied to more complex life histories if full life-tables are available. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Evolutionary constraints and the neutral theory. [mutation-caused nucleotide substitutions in DNA

NASA Technical Reports Server (NTRS)

Jukes, T. H.; Kimura, M.

1984-01-01

The neutral theory of molecular evolution postulates that nucleotide substitutions inherently take place in DNA as a result of point mutations followed by random genetic drift. In the absence of selective constraints, the substitution rate reaches the maximum value set by the mutation rate. The rate in globin pseudogenes is about 5 x 10 to the -9th substitutions per site per year in mammals. Rates slower than this indicate the presence of constraints imposed by negative (natural) selection, which rejects and discards deleterious mutations.

Aromatherapy Benefits Autonomic Nervous System Regulation for Elementary School Faculty in Taiwan

PubMed Central

Chang, Kang-Ming; Shen, Chuh-Wei

2011-01-01

Workplace stress-related illness is a serious issue, and consequently many stress reduction methods have been investigated. Aromatherapy is especially for populations that work under high stress. Elementary school teachers are a high-stress working population in Taiwan. In this study, fifty-four elementary school teachers were recruited to evaluate aromatherapy performance on stress reduction. Bergamot essential oil was used for aromatherapy spray for 10 minutes. Blood pressure and autonomic nervous system parameters were recorded 5 minutes before and after the application of the aroma spray. Results showed that there were significant decreases in blood pressure, heart rate, LF power percentage, and LF/HF while there were increases in heart rate variability and HF power percentage (P < .001∗∗∗) after application of the aromatherapy spray. Further analysis was investigated by dividing subjects into three background variables (position variables, age variables, gender variables) and anxiety degree groups. All parameters were significantly different for most subgroups, except for the substitute teachers and the light-anxiety group. Parasympathetic nervous system activation was measured after aromatherapy in this study. It encouraged further study for other stress working population by aromatherapy. PMID:21584196

Aromatherapy benefits autonomic nervous system regulation for elementary school faculty in taiwan.

PubMed

Chang, Kang-Ming; Shen, Chuh-Wei

2011-01-01

Workplace stress-related illness is a serious issue, and consequently many stress reduction methods have been investigated. Aromatherapy is especially for populations that work under high stress. Elementary school teachers are a high-stress working population in Taiwan. In this study, fifty-four elementary school teachers were recruited to evaluate aromatherapy performance on stress reduction. Bergamot essential oil was used for aromatherapy spray for 10 minutes. Blood pressure and autonomic nervous system parameters were recorded 5 minutes before and after the application of the aroma spray. Results showed that there were significant decreases in blood pressure, heart rate, LF power percentage, and LF/HF while there were increases in heart rate variability and HF power percentage (P < .001(∗∗∗)) after application of the aromatherapy spray. Further analysis was investigated by dividing subjects into three background variables (position variables, age variables, gender variables) and anxiety degree groups. All parameters were significantly different for most subgroups, except for the substitute teachers and the light-anxiety group. Parasympathetic nervous system activation was measured after aromatherapy in this study. It encouraged further study for other stress working population by aromatherapy.

Assessing the greenhouse impact of natural gas

NASA Astrophysics Data System (ADS)

Cathles, L. M.

2012-06-01

The global warming impact of substituting natural gas for coal and oil is currently in debate. We address this question here by comparing the reduction of greenhouse warming that would result from substituting gas for coal and some oil to the reduction which could be achieved by instead substituting zero carbon energy sources. We show that substitution of natural gas reduces global warming by 40% of that which could be attained by the substitution of zero carbon energy sources. At methane leakage rates that are ˜1% of production, which is similar to today's probable leakage rate of ˜1.5% of production, the 40% benefit is realized as gas substitution occurs. For short transitions the leakage rate must be more than 10 to 15% of production for gas substitution not to reduce warming, and for longer transitions the leakage must be much greater. But even if the leakage was so high that the substitution was not of immediate benefit, the 40%-of-zero-carbon benefit would be realized shortly after methane emissions ceased because methane is removed quickly from the atmosphere whereas CO2 is not. The benefits of substitution are unaffected by heat exchange to the ocean. CO2 emissions are the key to anthropogenic climate change, and substituting gas reduces them by 40% of that possible by conversion to zero carbon energy sources. Gas substitution also reduces the rate at which zero carbon energy sources must eventually be introduced.

Nonsynonymous substitution rate heterogeneity in the peptide-binding region among different HLA-DRB1 lineages in humans.

PubMed

Yasukochi, Yoshiki; Satta, Yoko

2014-05-02

An extraordinary diversity of amino acid sequences in the peptide-binding region (PBR) of human leukocyte antigen [HLA; human major histocompatibility complex (MHC)] molecules has been maintained by balancing selection. The process of accumulation of amino acid diversity in the PBR for six HLA genes (HLA-A, B, C, DRB1, DQB1, and DPB1) shows that the number of amino acid substitutions in the PBR among alleles does not linearly correlate with the divergence time of alleles at the six HLA loci. At these loci, some pairs of alleles show significantly less nonsynonymous substitutions at the PBR than expected from the divergence time. The same phenomenon was observed not only in the HLA but also in the rat MHC. To identify the cause for this, DRB1 sequences, a representative case of a typical nonlinear pattern of substitutions, were examined. When the amino acid substitutions in the PBR were placed with maximum parsimony on a maximum likelihood tree based on the non-PBR substitutions, heterogeneous rates of nonsynonymous substitutions in the PBR were observed on several branches. A computer simulation supported the hypothesis that allelic pairs with low PBR substitution rates were responsible for the stagnation of accumulation of PBR nonsynonymous substitutions. From these observations, we conclude that the nonsynonymous substitution rate at the PBR sites is not constant among the allelic lineages. The deceleration of the rate may be caused by the coexistence of certain pathogens for a substantially long time during HLA evolution. Copyright © 2014 Yasukochi and Satta.

A stochastic evolution model for residue Insertion-Deletion Independent from Substitution.

PubMed

Lèbre, Sophie; Michel, Christian J

2010-12-01

We develop here a new class of stochastic models of gene evolution based on residue Insertion-Deletion Independent from Substitution (IDIS). Indeed, in contrast to all existing evolution models, insertions and deletions are modeled here by a concept in population dynamics. Therefore, they are not only independent from each other, but also independent from the substitution process. After a separate stochastic analysis of the substitution and the insertion-deletion processes, we obtain a matrix differential equation combining these two processes defining the IDIS model. By deriving a general solution, we give an analytical expression of the residue occurrence probability at evolution time t as a function of a substitution rate matrix, an insertion rate vector, a deletion rate and an initial residue probability vector. Various mathematical properties of the IDIS model in relation with time t are derived: time scale, time step, time inversion and sequence length. Particular expressions of the nucleotide occurrence probability at time t are given for classical substitution rate matrices in various biological contexts: equal insertion rate, insertion-deletion only and substitution only. All these expressions can be directly used for biological evolutionary applications. The IDIS model shows a strongly different stochastic behavior from the classical substitution only model when compared on a gene dataset. Indeed, by considering three processes of residue insertion, deletion and substitution independently from each other, it allows a more realistic representation of gene evolution and opens new directions and applications in this research field. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of heat moisture treatment (HMT) on product quality of sorghum starch

NASA Astrophysics Data System (ADS)

Haryani, Kristinah; Hadiyanto, Handayani, Noera; Nugraheni, Dwi; Suryanto

2015-12-01

Sorghum is a cereal plant that rich of nutrition contents. The high content of carbohydrate in sorghum make this plant can be processed into one of the processed food i.e vermicelli. To give better quality, it is necessary to use flour substitution from sorghum starch. The aim of this study was to evaluate the treatment of natural sorghum starch substitution, the addition of CMC, and a comparison of the natural starch with starch sorghum forage sorghum against solid losses value, rehydration weight and texture profiles. The variable used in this study: amount of natural sorghum starch subtituion (10%, 20%, 30%, 40%, 50%), the addition of CMC (0.1%; 0.2%; 0.3%; 0.4%; 0.5%) and substituting sorghum starch Natural: HMT sorghum starch (1: 1; 1: 2; 1: 3; 1: 4; 1: 5) and the quality parameters were evaluated. The result indicated that to substitute sorghum starch naturally at a rate of 50% had the best results with a value of solid losses 5.1% (white sorghum) 5.83% (red sorghum) and weighing rehydration 301.82% (white sorghums) 293.16% (red sorghum), the addition of CMC with 0.5% concentration of 3.96% solid losses value (red sorghum) 4:21% (white sorghums) and weight rehydration 252.71% (white sorghums) 244.45% (red sorghums).

Anisotropic scattering rate in Fe-substituted Bi 2Sr 2Ca(Cu 1-xFex) 2O 8+δ

DOE PAGES

Naamneh, M.; Lubashevsky, Y.; Lahoud, E.; ...

2015-05-27

We measured the electronic structure of Fe substituted Bi2212 using Angle Resolved Photoemission Spectroscopy (ARPES). We find that the substitution does not change the momentum dependence of the superconducting gap but induces a very anisotropic enhancement of the scattering rate. A comparison of the effect of Fe substitution to that of Zn substitution suggests that the Fe reduces T c so effectively because it supresses very strongly the coherence weight around the anti-nodes.

Do Changes in Hospital Outpatient Payments Affect the Setting of Care?

PubMed Central

He, Daifeng; Mellor, Jennifer M

2013-01-01

Objective To examine whether decreases in Medicare outpatient payment rates under the Outpatient Prospective Payment System (OPPS) caused outpatient care to shift toward the inpatient setting. Data Sources/Study Setting Hospital inpatient and outpatient discharge files from the Florida Agency for Health Care Administration from 1997 through 2008. Study Design This study focuses on inguinal hernia repair surgery, one of the most commonly performed surgical procedures in the United States. We estimate multivariate regressions of inguinal hernia surgery counts in the outpatient setting and in the inpatient setting. The key explanatory variable is the time-varying Medicare payment rate specific to the procedure and hospital. Control variables include time-varying hospital and county characteristics and hospital and year-fixed effects. Principal Findings Outpatient hernia surgeries fell in response to OPPS-induced rate cuts. The volume of inpatient hernia repair surgeries did not increase in response to reductions in the outpatient reimbursement rate. Conclusions Potential substitution from the outpatient setting to the inpatient setting does not pose a serious threat to Medicare's efforts to contain hospital outpatient costs. PMID:23701048

Adaptive Molecular Evolution for 13,000 Phage Generations

PubMed Central

Wichman, Holly A.; Millstein, Jack; Bull, J. J.

2005-01-01

Bacteriophage φX174 was evolved on a continuous supply of sensitive hosts for 180 days (∼13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell. PMID:15687276

Differentiation of Xylella fastidiosa Strains via Multilocus Sequence Analysis of Environmentally Mediated Genes (MLSA-E)

PubMed Central

Parker, Jennifer K.; Havird, Justin C.

2012-01-01

Isolates of the plant pathogen Xylella fastidiosa are genetically very similar, but studies on their biological traits have indicated differences in virulence and infection symptomatology. Taxonomic analyses have identified several subspecies, and phylogenetic analyses of housekeeping genes have shown broad host-based genetic differences; however, results are still inconclusive for genetic differentiation of isolates within subspecies. This study employs multilocus sequence analysis of environmentally mediated genes (MLSA-E; genes influenced by environmental factors) to investigate X. fastidiosa relationships and differentiate isolates with low genetic variability. Potential environmentally mediated genes, including host colonization and survival genes related to infection establishment, were identified a priori. The ratio of the rate of nonsynonymous substitutions to the rate of synonymous substitutions (dN/dS) was calculated to select genes that may be under increased positive selection compared to previously studied housekeeping genes. Nine genes were sequenced from 54 X. fastidiosa isolates infecting different host plants across the United States. Results of maximum likelihood (ML) and Bayesian phylogenetic (BP) analyses are in agreement with known X. fastidiosa subspecies clades but show novel within-subspecies differentiation, including geographic differentiation, and provide additional information regarding host-based isolate variation and specificity. dN/dS ratios of environmentally mediated genes, though <1 due to high sequence similarity, are significantly greater than housekeeping gene dN/dS ratios and correlate with increased sequence variability. MLSA-E can more precisely resolve relationships between closely related bacterial strains with low genetic variability, such as X. fastidiosa isolates. Discovering the genetic relationships between X. fastidiosa isolates will provide new insights into the epidemiology of populations of X. fastidiosa, allowing improved disease management in economically important crops. PMID:22194287

Differentiation of Xylella fastidiosa strains via multilocus sequence analysis of environmentally mediated genes (MLSA-E).

PubMed

Parker, Jennifer K; Havird, Justin C; De La Fuente, Leonardo

2012-03-01

Isolates of the plant pathogen Xylella fastidiosa are genetically very similar, but studies on their biological traits have indicated differences in virulence and infection symptomatology. Taxonomic analyses have identified several subspecies, and phylogenetic analyses of housekeeping genes have shown broad host-based genetic differences; however, results are still inconclusive for genetic differentiation of isolates within subspecies. This study employs multilocus sequence analysis of environmentally mediated genes (MLSA-E; genes influenced by environmental factors) to investigate X. fastidiosa relationships and differentiate isolates with low genetic variability. Potential environmentally mediated genes, including host colonization and survival genes related to infection establishment, were identified a priori. The ratio of the rate of nonsynonymous substitutions to the rate of synonymous substitutions (dN/dS) was calculated to select genes that may be under increased positive selection compared to previously studied housekeeping genes. Nine genes were sequenced from 54 X. fastidiosa isolates infecting different host plants across the United States. Results of maximum likelihood (ML) and Bayesian phylogenetic (BP) analyses are in agreement with known X. fastidiosa subspecies clades but show novel within-subspecies differentiation, including geographic differentiation, and provide additional information regarding host-based isolate variation and specificity. dN/dS ratios of environmentally mediated genes, though <1 due to high sequence similarity, are significantly greater than housekeeping gene dN/dS ratios and correlate with increased sequence variability. MLSA-E can more precisely resolve relationships between closely related bacterial strains with low genetic variability, such as X. fastidiosa isolates. Discovering the genetic relationships between X. fastidiosa isolates will provide new insights into the epidemiology of populations of X. fastidiosa, allowing improved disease management in economically important crops.

Cassava brown streak virus has a rapidly evolving genome: implications for virus speciation, variability, diagnosis and host resistance

PubMed Central

Alicai, Titus; Ndunguru, Joseph; Sseruwagi, Peter; Tairo, Fred; Okao-Okuja, Geoffrey; Nanvubya, Resty; Kiiza, Lilliane; Kubatko, Laura; Kehoe, Monica A.; Boykin, Laura M.

2016-01-01

Cassava is a major staple food for about 800 million people in the tropics and sub-tropical regions of the world. Production of cassava is significantly hampered by cassava brown streak disease (CBSD), caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). The disease is suppressing cassava yields in eastern Africa at an alarming rate. Previous studies have documented that CBSV is more devastating than UCBSV because it more readily infects both susceptible and tolerant cassava cultivars, resulting in greater yield losses. Using whole genome sequences from NGS data, we produced the first coalescent-based species tree estimate for CBSV and UCBSV. This species framework led to the finding that CBSV has a faster rate of evolution when compared with UCBSV. Furthermore, we have discovered that in CBSV, nonsynonymous substitutions are more predominant than synonymous substitution and occur across the entire genome. All comparative analyses between CBSV and UCBSV presented here suggest that CBSV may be outsmarting the cassava immune system, thus making it more devastating and harder to control. PMID:27808114

Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs.

PubMed Central

Horai, S; Hayasaka, K; Kondo, R; Tsugane, K; Takahata, N

1995-01-01

We analyzed the complete mitochondrial DNA (mtDNA) sequences of three humans (African, European, and Japanese), three African apes (common and pygmy chimpanzees, and gorilla), and one orangutan in an attempt to estimate most accurately the substitution rates and divergence times of hominoid mtDNAs. Nonsynonymous substitutions and substitutions in RNA genes have accumulated with an approximately clock-like regularity. From these substitutions and under the assumption that the orangutan and African apes diverged 13 million years ago, we obtained a divergence time for humans and chimpanzees of 4.9 million years. This divergence time permitted calibration of the synonymous substitution rate (3.89 x 10(-8)/site per year). To obtain the substitution rate in the displacement (D)-loop region, we compared the three human mtDNAs and measured the relative abundance of substitutions in the D-loop region and at synonymous sites. The estimated substitution rate in the D-loop region was 7.00 x 10(-8)/site per year. Using both synonymous and D-loop substitutions, we inferred the age of the last common ancestor of the human mtDNAs as 143,000 +/- 18,000 years. The shallow ancestry of human mtDNAs, together with the observation that the African sequence is the most diverged among humans, strongly supports the recent African origin of modern humans, Homo sapiens sapiens. PMID:7530363

The application of dimensional analysis to the problem of solar wind-magnetosphere energy coupling

NASA Technical Reports Server (NTRS)

Bargatze, L. F.; Mcpherron, R. L.; Baker, D. N.; Hones, E. W., Jr.

1984-01-01

The constraints imposed by dimensional analysis are used to find how the solar wind-magnetosphere energy transfer rate depends upon interplanetary parameters. The analyses assume that only magnetohydrodynamic processes are important in controlling the rate of energy transfer. The study utilizes ISEE-3 solar wind observations, the AE index, and UT from three 10-day intervals during the International Magnetospheric Study. Simple linear regression and histogram techniques are used to find the value of the magnetohydrodynamic coupling exponent, alpha, which is consistent with observations of magnetospheric response. Once alpha is estimated, the form of the solar wind energy transfer rate is obtained by substitution into an equation of the interplanetary variables whose exponents depend upon alpha.

Phylogeny, rate variation, and genome size evolution of Pelargonium (Geraniaceae).

PubMed

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

2012-09-01

The phylogeny of 58 Pelargonium species was estimated using five plastid markers (rbcL, matK, ndhF, rpoC1, trnL-F) and one mitochondrial gene (nad5). The results confirmed the monophyly of three major clades and four subclades within Pelargonium but also indicate the need to revise some sectional classifications. This phylogeny was used to examine karyotype evolution in the genus: plotting chromosome sizes, numbers and 2C-values indicates that genome size is significantly correlated with chromosome size but not number. Accelerated rates of nucleotide substitution have been previously detected in both plastid and mitochondrial genes in Pelargonium, but sparse taxon sampling did not enable identification of the phylogenetic distribution of these elevated rates. Using the multigene phylogeny as a constraint, we investigated lineage- and locus-specific heterogeneity of substitution rates in Pelargonium for an expanded number of taxa and demonstrated that both plastid and mitochondrial genes have had accelerated substitution rates but with markedly disparate patterns. In the plastid, the exons of rpoC1 have significantly accelerated substitution rates compared to its intron and the acceleration was mainly due to nonsynonymous substitutions. In contrast, the mitochondrial gene, nad5, experienced substantial acceleration of synonymous substitution rates in three internal branches of Pelargonium, but this acceleration ceased in all terminal branches. Several lineages also have dN/dS ratios significantly greater than one for rpoC1, indicating that positive selection is acting on this gene, whereas the accelerated synonymous substitutions in the mitochondrial gene are the result of elevated mutation rates. Published by Elsevier Inc.

Protein substitute dosage in PKU: how much do young patients need?

PubMed

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-07-01

The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Relaxed clocks and inferences of heterogeneous patterns of nucleotide substitution and divergence time estimates across whales and dolphins (Mammalia: Cetacea).

PubMed

Dornburg, Alex; Brandley, Matthew C; McGowen, Michael R; Near, Thomas J

2012-02-01

Various nucleotide substitution models have been developed to accommodate among lineage rate heterogeneity, thereby relaxing the assumptions of the strict molecular clock. Recently developed "uncorrelated relaxed clock" and "random local clock" (RLC) models allow decoupling of nucleotide substitution rates between descendant lineages and are thus predicted to perform better in the presence of lineage-specific rate heterogeneity. However, it is uncertain how these models perform in the presence of punctuated shifts in substitution rate, especially between closely related clades. Using cetaceans (whales and dolphins) as a case study, we test the performance of these two substitution models in estimating both molecular rates and divergence times in the presence of substantial lineage-specific rate heterogeneity. Our RLC analyses of whole mitochondrial genome alignments find evidence for up to ten clade-specific nucleotide substitution rate shifts in cetaceans. We provide evidence that in the uncorrelated relaxed clock framework, a punctuated shift in the rate of molecular evolution within a subclade results in posterior rate estimates that are either misled or intermediate between the disparate rate classes present in baleen and toothed whales. Using simulations, we demonstrate abrupt changes in rate isolated to one or a few lineages in the phylogeny can mislead rate and age estimation, even when the node of interest is calibrated. We further demonstrate how increasing prior age uncertainty can bias rate and age estimates, even while the 95% highest posterior density around age estimates decreases; in other words, increased precision for an inaccurate estimate. We interpret the use of external calibrations in divergence time studies in light of these results, suggesting that rate shifts at deep time scales may mislead inferences of absolute molecular rates and ages.

Accelerated hydrolysis of substituted cellulose for potential biofuel production: kinetic study and modeling.

PubMed

Mu, Bingnan; Xu, Helan; Yang, Yiqi

2015-11-01

In this work, kinetics of substitution accelerated cellulose hydrolysis with multiple reaction stages was investigated to lay foundation for mechanism study and molecular design of substituting compounds. High-efficiency hydrolysis of cellulose is critical for cellulose-based bioethanol production. It is known that, substitution could substantially decrease activation energy and increase reaction rate of acidic hydrolysis of glycosidic bonds in cellulose. However, reaction kinetics and mechanism of the accelerated hydrolysis were not fully revealed. In this research, it was proved that substitution therefore accelerated hydrolysis only occurred in amorphous regions of cellulose fibers, and was a process with multiple reaction stages. With molar ratio of substitution less than 1%, the overall hydrolysis rate could be increased for around 10 times. We also quantified the relationship between the hydrolysis rate of individual reaction stage and its major influences, including molar ratio of substitution, activation energy of acidic hydrolysis, pH and temperature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tobramycin exposure from active calcium sulfate bone graft substitute

PubMed Central

2014-01-01

Background Bone graft substitute such as calcium sulfate are frequently used as carrier material for local antimicrobial therapy in orthopedic surgery. This study aimed to assess the systemic absorption and disposition of tobramycin in patients treated with a tobramycin-laden bone graft substitute (Osteoset® T). Methods Nine blood samples were taken from 12 patients over 10 days after Osteoset® T surgical implantation. Tobramycin concentration was measured by fluorescence polarization. Population pharmacokinetic analysis was performed using NONMEM to assess the average value and variability (CV) of pharmacokinetic parameters. Bioavailability (F) was assessed by equating clearance (CL) with creatinine clearance (Cockcroft CLCr). Based on the final model, simulations with various doses and renal function levels were performed. (ClinicalTrials.gov number, NCT01938417). Results The patients were 52 +/− 20 years old, their mean body weight was 73 +/− 17 kg and their mean CLCr was 119 +/− 55 mL/min. Either 10 g or 20 g Osteoset® T with 4% tobramycin sulfate was implanted in various sites. Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing important variability. With CL equated to CLCr, mean absorption rate constant (ka) was 0.06 h-1, F was 63% or 32% (CV 74%) for 10 and 20 g Osteoset® T respectively, and volume of distribution (V) was 16.6 L (CV 89%). Simulations predicted sustained high, potentially toxic concentrations with 10 g, 30 g and 50 g Osteoset® T for CLCr values below 10, 20 and 30 mL/min, respectively. Conclusions Osteoset® T does not raise toxicity concerns in subjects without significant renal failure. The risk/benefit ratio might turn unfavorable in case of severe renal failure, even after standard dose implantation. PMID:24593819

Electron-ion dissociative recombination rate constants relevant to the Titan atmosphere and the Interstellar Medium

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

Osborne, David; Lawson, Patrick; Adams, Nigel, E-mail: ngadams@uga.edu

Following the arrival of Cassini at Titan in 2004, the Titan atmosphere has been shown to contain large complex polycyclic-aromatic hydrocarbons. Since Cassini has provided a great deal of data, there exists a need for kinetic rate data to help with modeling this atmosphere. One type of kinetic data needed is electron-ion dissociative recombination (e-IDR) rate constants. These data are not readily available for larger compounds, such as naphthalene, or oxygen containing compounds, such as 1,4 dioxane or furan. Here, the rate constants for naphthalene, 1,4 dioxane, and furan have been measured and their temperature dependencies are determined when possible,more » using the University of Georgia's Variable Temperature Flowing Afterglow. The rate constants are compared with those previously published for other compounds; these show trends which illustrate the effects which multi-rings and oxygen heteroatoms substitutions have upon e-IDR rate constants.« less

Electron-ion dissociative recombination rate constants relevant to the Titan atmosphere and the Interstellar Medium

NASA Astrophysics Data System (ADS)

Osborne, David; Lawson, Patrick; Adams, Nigel

2014-01-01

Following the arrival of Cassini at Titan in 2004, the Titan atmosphere has been shown to contain large complex polycyclic-aromatic hydrocarbons. Since Cassini has provided a great deal of data, there exists a need for kinetic rate data to help with modeling this atmosphere. One type of kinetic data needed is electron-ion dissociative recombination (e-IDR) rate constants. These data are not readily available for larger compounds, such as naphthalene, or oxygen containing compounds, such as 1,4 dioxane or furan. Here, the rate constants for naphthalene, 1,4 dioxane, and furan have been measured and their temperature dependencies are determined when possible, using the University of Georgia's Variable Temperature Flowing Afterglow. The rate constants are compared with those previously published for other compounds; these show trends which illustrate the effects which multi-rings and oxygen heteroatoms substitutions have upon e-IDR rate constants.

Ambient temperature effect on pulse rate variability as an alternative to heart rate variability in young adult.

PubMed

Shin, Hangsik

2016-12-01

Pulse rate variability (PRV) is a promising physiological and analytic technique used as a substitute for heart rate variability (HRV). PRV is measured by pulse wave from various devices including mobile and wearable devices but HRV is only measured by an electrocardiogram (ECG). The purpose of this study was to evaluate PRV and HRV at various ambient temperatures and elaborate on the interchangeability of PRV and HRV. Twenty-eight healthy young subjects were enrolled in the experiment. We prepared temperature-controlled rooms and recorded the ECG and photoplethysmography (PPG) under temperature-controlled, constant humidity conditions. The rooms were kept at 17, 25, and 38 °C as low, moderate, and high ambient temperature environments, respectively. HRV and PRV were derived from the synchronized ECG and PPG measures and they were studied in time and frequency domain analysis for PRV/HRV ratio and pulse transit time (PTT). Similarity and differences between HRV and PRV were determined by a statistical analysis. PRV/HRV ratio analysis revealed that there was a significant difference between HRV and PRV for a given ambient temperature; this was with short-term variability measures such as SDNN SDSD or RMSSD, and HF-based variables including HF, LF/HF and normalized HF. In our analysis the absolute value of PTT was not significantly influenced by temperature. Standard deviation of PTT, however, showed significant difference not only between low and moderate temperatures but also between low and high temperatures. Our results suggest that ambient temperature induces a significant difference in PRV compared to HRV and that the difference becomes greater at a higher ambient temperature.

ortho- and meta-substituted aromatic thiols are efficient redox buffers that increase the folding rate of a disulfide-containing protein.

PubMed

Gough, Jonathan D; Barrett, Elvis J; Silva, Yenia; Lees, Watson J

2006-08-20

Thiol based redox buffers are used to enhance the folding rates of disulfide-containing proteins in vitro. Traditionally, small molecule aliphatic thiols such as glutathione are employed. Recently, we have demonstrated that aromatic thiols can further enhance protein-folding rates. In the presence of para-substituted aromatic thiols the folding rate of a disulfide-containing protein was increased by 4-23 times over that measured for glutathione. However, several important practical issues remain to be addressed. Aromatic thiols have never been tested in the presence of denaturants such as guanidine hydrochloride. Only two of the para-substituted aromatic thiols previously examined are commercially available. To expand the number of aromatic thiols for protein folding, several commercially available meta- and ortho-substituted aromatic thiols were studied. Furthermore, an ortho-substituted aromatic thiol, easily obtained from inexpensive starting materials, was investigated. Folding rates of scrambled ribonuclease A at pH 6.0, 7.0 and 7.7, with ortho- and meta-substituted aromatic thiols, were up to 10 times greater than those with glutathione. In the presence of the common denaturant guanidine hydrochloride (0.5M) aromatic thiols provided 100% yield of active protein while maintaining equivalent folding rates.

Epistasis increases the rate of conditionally neutral substitution in an adapting population.

PubMed

Draghi, Jeremy A; Parsons, Todd L; Plotkin, Joshua B

2011-04-01

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations--i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations--substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations.

Epistasis Increases the Rate of Conditionally Neutral Substitution in an Adapting Population

PubMed Central

Draghi, Jeremy A.; Parsons, Todd L.; Plotkin, Joshua B.

2011-01-01

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations—i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations—substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations. PMID:21288876

No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation

PubMed Central

Hellberg, Michael E

2006-01-01

Background The mitochondrial DNA (mtDNA) of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin), by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans) known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea). Results The mtDNA surveyed (630 bp of cytochrome oxidase subunit I) was invariant among individuals sampled from 18 populations spanning 3000 km of the range of B. elegans, despite high levels of variation and population subdivision for allozymes over these same populations. The synonymous substitution rate between B. elegans and T. coccinea (0.05%/site/106 years) is similar to that in most plants, but 50–100 times lower than rates typical for most animals. In addition, while substitutions to mtDNA in most animals exhibit a strong bias toward transitions, mtDNA from these corals does not. Conclusion Slow rates of mitochondrial nucleotide substitution result in low levels of intraspecific mtDNA variation in corals, even when nuclear loci vary. Slow mtDNA evolution appears to be the basal condition among eukaryotes. mtDNA substitution rates switch from slow to fast abruptly and unidirectionally. This switch may stem from the loss of just one or a few mitochondrion-specific DNA repair or replication genes. PMID:16542456

Incorporating Alternative Care Site Characteristics Into Estimates of Substitutable ED Visits.

PubMed

Trueger, Nathan Seth; Chua, Kao-Ping; Hussain, Aamir; Liferidge, Aisha T; Pitts, Stephen R; Pines, Jesse M

2017-07-01

Several recent efforts to improve health care value have focused on reducing emergency department (ED) visits that potentially could be treated in alternative care sites (ie, primary care offices, retail clinics, and urgent care centers). Estimates of the number of these visits may depend on assumptions regarding the operating hours and functional capabilities of alternative care sites. However, methods to account for the variability in these characteristics have not been developed. To develop methods to incorporate the variability in alternative care site characteristics into estimates of ED visit "substitutability." Our approach uses the range of hours and capabilities among alternative care sites to estimate lower and upper bounds of ED visit substitutability. We constructed "basic" and "extended" criteria that captured the plausible degree of variation in each site's hours and capabilities. To illustrate our approach, we analyzed data from 22,697 ED visits by adults in the 2011 National Hospital Ambulatory Medical Care Survey, defining a visit as substitutable if it was treat-and-release and met both the operating hours and functional capabilities criteria. Use of the combined basic hours/basic capabilities criteria and extended hours/extended capabilities generated lower and upper bounds of estimates. Our criteria classified 5.5%-27.1%, 7.6%-20.4%, and 10.6%-46.0% of visits as substitutable in primary care offices, retail clinics, and urgent care centers, respectively. Alternative care sites vary widely in operating hours and functional capabilities. Methods such as ours may help incorporate this variability into estimates of ED visit substitutability.

Use and misuse of motor-vehicle crash death rates in assessing highway-safety performance.

PubMed

O'Neill, Brian; Kyrychenko, Sergey Y

2006-12-01

The objectives of the article are to assess the extent to which comparisons of motor-vehicle crash death rates can be used to determine the effectiveness of highway-safety policies over time in a country or to compare policy effectiveness across countries. Motor-vehicle crash death rates per mile traveled in the 50 U.S. states from 1980 to 2003 are used to show the influence on these rates of factors independent of highway-safety interventions. Multiple regression models relating state death rates to various measures related to urbanization and demographics are used. The analyses demonstrate strong relationships between state death rates and urbanization and demographics. Almost 60% of the variability among the state death rates can be explained by the independent variables in the multiple regression models. When the death rates for passenger vehicle occupants (i.e., excluding motorcycle, pedestrian, and other deaths) are used in the regression models, almost 70% of the variability in the rates can be explained by urbanization and demographics. The analyses presented in the article demonstrate that motor-vehicle crash death rates are strongly influenced by factors unrelated to highway-safety countermeasures. Overall death rates should not be used as a basis for judging the effectiveness (or ineffectiveness) of specific highway-safety countermeasures or to assess overall highway-safety policies, especially across jurisdictions. There can be no substitute for the use of carefully designed scientific evaluations of highway-safety interventions that use outcome measures directly related to the intervention; e.g., motorcyclist deaths should be used to assess the effectiveness of motorcycle helmet laws. While this may seem obvious, there are numerous examples in the literature of death rates from all crashes being used to assess the effectiveness of interventions aimed at specific subsets of crashes.

Protein substitute dosage in PKU: how much do young patients need?

PubMed Central

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-01-01

Background The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). Aim To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.1 Methods In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2–10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre‐breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8–14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5–3.1 g/kg/day). Results When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre‐breakfast by 301 μmol/l (95% CI 215 to 386) and in the evening by 337 μmol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. Conclusions A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/− fat) content of the protein substitute. PMID:16547085

The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

PubMed Central

2017-01-01

The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with S-substitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening. PMID:28910418

Behavioral economics

PubMed Central

Hursh, Steven R.

1984-01-01

Economics, like behavioral psychology, is a science of behavior, albeit highly organized human behavior. The value of economic concepts for behavioral psychology rests on (1) their empirical validity when tested in the laboratory with individual subjects and (2) their uniqueness when compared to established behavioral concepts. Several fundamental concepts are introduced and illustrated by reference to experimental data: open and closed economies, elastic and inelastic demand, and substitution versus complementarity. Changes in absolute response rate are analyzed in relation to elasticity and intensity of demand. The economic concepts of substitution and complementarity are related to traditional behavioral studies of choice and to the matching relation. The economic approach has many implications for the future of behavioral research and theory. In general, economic concepts are grounded on a dynamic view of reinforcement. The closed-economy methodology extends the generality of behavioral principles to situations in which response rate and obtained rate of reinforcement are interdependent. Analysis of results in terms of elasticity and intensity of demand promises to provide a more direct method for characterizing the effects of “motivational” variables. Future studies of choice should arrange heterogeneous reinforcers with varying elasticities, use closed economies, and modulate scarcity or income. The economic analysis can be extended to the study of performances that involve subtle discriminations or skilled movements that vary in accuracy or quality as opposed to rate or quantity, and thus permit examination of time/accuracy trade-offs. PMID:16812401

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.

Genome variability of foot-and-mouth disease virus during the short period of the 2010 epidemic in Japan.

PubMed

Nishi, Tatsuya; Yamada, Manabu; Fukai, Katsuhiko; Shimada, Nobuaki; Morioka, Kazuki; Yoshida, Kazuo; Sakamoto, Kenichi; Kanno, Toru; Yamakawa, Makoto

2017-02-01

Foot-and-mouth disease virus (FMDV) is highly contagious and has a high mutation rate, leading to extensive genetic variation. To investigate how FMDV genetically evolves over a short period of an epidemic after initial introduction into an FMD-free area, whole L-fragment sequences of 104 FMDVs isolated from the 2010 epidemic in Japan, which continued for less than three months were determined and phylogenetically and comparatively analyzed. Phylogenetic analysis of whole L-fragment sequences showed that these isolates were classified into a single group, indicating that FMDV was introduced into Japan in the epidemic via a single introduction. Nucleotide sequences of 104 virus isolates showed more than 99.56% pairwise identity rates without any genetic deletion or insertion, although no sequences were completely identical with each other. These results indicate that genetic substitutions of FMDV occurred gradually and constantly during the epidemic and generation of an extensive mutant virus could have been prevented by rapid eradication strategy. From comparative analysis of variability of each FMDV protein coding region, VP4 and 2C regions showed the highest average identity rates and invariant rates, and were confirmed as highly conserved. In contrast, the protein coding regions VP2 and VP1 were confirmed to be highly variable regions with the lowest average identity rates and invariant rates, respectively. Our data demonstrate the importance of rapid eradication strategy in an FMD epidemic and provide valuable information on the genome variability of FMDV during the short period of an epidemic. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD).

PubMed

Jung, In Young; Boettiger, David; Wong, Wing Wai; Lee, Man Po; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Avihingsanon, Anchalee; Tanuma, Junko; Kumarasamy, Nagalingeswaran; Kamarulzaman, Adeeba; Zhang, Fujie; Kantipong, Pacharee; Ng, Oon Tek; Sim, Benedict Lim Heng; Law, Matthew; Ross, Jeremy; Choi, Jun Yong

2017-12-01

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 treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Fish mislabelling in France: substitution rates and retail types.

PubMed

Bénard-Capelle, Julien; Guillonneau, Victoire; Nouvian, Claire; Fournier, Nicolas; Le Loët, Karine; Dettai, Agnès

2015-01-01

Market policies have profound implications for consumers as well as for the management of resources. One of the major concerns in fish trading is species mislabelling: the commercial name used does not correspond to the product, most often because the product is in fact a cheaper or a more easily available species. Substitution rates depend heavily on species, some often being sold mislabelled while others rarely or never mislabelled. Rates also vary largely depending on countries. In this study, we analyse the first market-wide dataset collected for France, the largest sea food market in Europe, for fish species substitution. We sequenced and analysed 371 samples bearing 55 commercial species names, collected in fishmonger shops, supermarkets and restaurants; the largest dataset assembled to date in an European country. Sampling included fish fillets, both fresh and frozen, and prepared meals. We found a total of 14 cases of mislabelling in five species: bluefin tuna, cod, yellowfin tuna, sole and seabream, setting the overall substitution rate at 3.7% CI [2.2-6.4], one of the lowest observed for comparable surveys with large sampling. We detected no case of species mislabelling among the frozen fillets or in industrially prepared meals, and all the substitutions were observed in products sold in fishmongers shops or restaurants. The rate of mislabelling does not differ between species, except for bluefin tuna. Despite a very small sample size ( n = 6), the rate observed for this species (83.3% CI [36-99]) stands in sharp contrast with the low substitution rate observed for the other substituted species. In agreement with studies from other countries, this work shows that fish mislabelling can vary greatly within a country depending on the species. It further suggests that more efforts should be directed to the control of high value species like bluefin tuna.

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.

Substitution rate and natural selection in parvovirus B19

PubMed Central

Stamenković, Gorana G.; Ćirković, Valentina S.; Šiljić, Marina M.; Blagojević, Jelena V.; Knežević, Aleksandra M.; Joksić, Ivana D.; Stanojević, Maja P.

2016-01-01

The aim of this study was to estimate substitution rate and imprints of natural selection on parvovirus B19 genotype 1. Studied datasets included 137 near complete coding B19 genomes (positions 665 to 4851) for phylogenetic and substitution rate analysis and 146 and 214 partial genomes for selection analyses in open reading frames ORF1 and ORF2, respectively, collected 1973–2012 and including 9 newly sequenced isolates from Serbia. Phylogenetic clustering assigned majority of studied isolates to G1A. Nucleotide substitution rate for total coding DNA was 1.03 (0.6–1.27) x 10−4 substitutions/site/year, with higher values for analyzed genome partitions. In spite of the highest evolutionary rate, VP2 codons were found to be under purifying selection with rare episodic positive selection, whereas codons under diversifying selection were found in the unique part of VP1, known to contain B19 immune epitopes important in persistent infection. Analyses of overlapping gene regions identified nucleotide positions under opposite selective pressure in different ORFs, suggesting complex evolutionary mechanisms of nucleotide changes in B19 viral genomes. PMID:27775080

Gender-dependence of substituted judgment on quality of life in patients with dementia

PubMed Central

2011-01-01

Background Substituted judgment asks the proxy to decide what the patient would have decided, had he or she been competent. It is unclear whether substituted judgment of the patient's quality of life can serve as a surrogate measure in patients with dementia. Methods 212 patients with dementia and their proxies were interviewed in their homes. Dementia syndrome was characterized with cognitive, non-cognitive and functional scales. Quality of life (QoL) was assessed with the QoL-AD. Results Substituted judgment of the patient's QoL was unrelated to dementia severity but also correlated with the proxie's own QoL (r = 0.356; p < 0.001). Gender-specific analysis reveals that for male proxies the most important variable is severity of patient's depression (r = -0.895; p = 0.001) while for female proxies it is the proxie's own QoL (r = 0.371; p < 0.001). Subjective burden correlates with the proxie's QoL in females (r = -0.282; p = 0.001) but not in males (r = -0.163, p = 0.161). Conclusion Substituted judgment of the patient's QoL does not correlate with dementia severity. Substituted judgment is subject to proxy-related variables in a gender-dependent fashion and therefore not suited to serve as an appropriate surrogate of the patients' quality of life. PMID:21961477

Coestimation of recombination, substitution and molecular adaptation rates by approximate Bayesian computation.

PubMed

Lopes, J S; Arenas, M; Posada, D; Beaumont, M A

2014-03-01

The estimation of parameters in molecular evolution may be biased when some processes are not considered. For example, the estimation of selection at the molecular level using codon-substitution models can have an upward bias when recombination is ignored. Here we address the joint estimation of recombination, molecular adaptation and substitution rates from coding sequences using approximate Bayesian computation (ABC). We describe the implementation of a regression-based strategy for choosing subsets of summary statistics for coding data, and show that this approach can accurately infer recombination allowing for intracodon recombination breakpoints, molecular adaptation and codon substitution rates. We demonstrate that our ABC approach can outperform other analytical methods under a variety of evolutionary scenarios. We also show that although the choice of the codon-substitution model is important, our inferences are robust to a moderate degree of model misspecification. In addition, we demonstrate that our approach can accurately choose the evolutionary model that best fits the data, providing an alternative for when the use of full-likelihood methods is impracticable. Finally, we applied our ABC method to co-estimate recombination, substitution and molecular adaptation rates from 24 published human immunodeficiency virus 1 coding data sets.

Comparison of Porcine and Bovine Collagen Dural Substitutes in Posterior Fossa Decompression for Chiari I Malformation in Adults.

PubMed

Lee, Christine K; Mokhtari, Tara; Connolly, Ian D; Li, Gordon; Shuer, Lawrence M; Chang, Steven D; Steinberg, Gary K; Hayden Gephart, Melanie

2017-12-01

Posterior fossa decompression surgeries for Chiari malformations are susceptible to postoperative complications such as pseudomeningocele, external cerebrospinal fluid (CSF) leak, and meningitis. Various dural substitutes have been used to improve surgical outcomes. This study examined whether the collagen matrix dural substitute type correlated with the incidence of postoperative complications after posterior fossa decompression in adult patients with Chiari I malformations. A retrospective cohort study was conducted of 81 adult patients who underwent an elective decompressive surgery for treatment of symptomatic Chiari I malformations, with duraplasty involving a dural substitute derived from either bovine or porcine collagen matrix. Demographics and treatment characteristics were correlated with surgical outcomes. A total of 81 patients were included in the study. Compared with bovine dural substitute, porcine dural substitute was associated with a significantly higher risk of pseudomeningocele occurrence (odds ratio, 5.78; 95% confidence interval, 1.65-27.15; P = 0.01) and a higher overall complication rate (odds ratio, 3.70; 95% confidence interval, 1.23-12.71; P = 0.03) by univariate analysis. There was no significant difference in the rate of meningitis, repeat operations, or overall complication rate between the 2 dural substitutes. In addition, estimated blood loss was a significant risk factor for meningitis (P = 0.03). Multivariate analyses again showed that porcine dural substitute was associated with pseudomeningocele occurrence, although the association with higher overall complication rate did not reach significance. Dural substitutes generated from porcine collagen, compared with those from bovine collagen, were associated with a higher likelihood of pseudomeningocele development in adult patients undergoing Chiari I malformation decompression and duraplasty. Copyright © 2017 Elsevier Inc. All rights reserved.

Substitution laws, insurance coverage, and generic drug use.

PubMed

Anis, A H

1994-03-01

This study examined the role of various policies (drug product substitution laws) that are usually motivated by cost containment objectives of insurers in facilitating entry by generic firms. Using data for six Canadian provinces over the years 1981-1988, we evaluated the impact of specific aspects of substitution laws on the level of generic use. We find that formularies and the passage of time are not significant determinants of substitution levels. Legal liability, mandatory product selection, deductible and co-payment schemes, and consumer awareness were found to be important variables. Price responsiveness of generic drugs is indicated but the evidence is not strong.

The Iodochlorination of Styrene: An Experiment that Makes a Difference

ERIC Educational Resources Information Center

Amiet, R. Gary; Urban, Sylvia

2008-01-01

The iodochlorination of styrene, involving the addition of iodine monochloride to styrene, followed by the sodium methoxide-initiated dehydrohalogenation of the product results in a variable mixture of substituted styrenes by way of various substitution and elimination reaction mechanisms. As a result individual results are obtained for each…

Fish mislabelling in France: substitution rates and retail types

PubMed Central

Bénard-Capelle, Julien; Guillonneau, Victoire; Nouvian, Claire; Fournier, Nicolas; Le Loët, Karine

2015-01-01

Market policies have profound implications for consumers as well as for the management of resources. One of the major concerns in fish trading is species mislabelling: the commercial name used does not correspond to the product, most often because the product is in fact a cheaper or a more easily available species. Substitution rates depend heavily on species, some often being sold mislabelled while others rarely or never mislabelled. Rates also vary largely depending on countries. In this study, we analyse the first market-wide dataset collected for France, the largest sea food market in Europe, for fish species substitution. We sequenced and analysed 371 samples bearing 55 commercial species names, collected in fishmonger shops, supermarkets and restaurants; the largest dataset assembled to date in an European country. Sampling included fish fillets, both fresh and frozen, and prepared meals. We found a total of 14 cases of mislabelling in five species: bluefin tuna, cod, yellowfin tuna, sole and seabream, setting the overall substitution rate at 3.7% CI [2.2–6.4], one of the lowest observed for comparable surveys with large sampling. We detected no case of species mislabelling among the frozen fillets or in industrially prepared meals, and all the substitutions were observed in products sold in fishmongers shops or restaurants. The rate of mislabelling does not differ between species, except for bluefin tuna. Despite a very small sample size (n = 6), the rate observed for this species (83.3% CI [36–99]) stands in sharp contrast with the low substitution rate observed for the other substituted species. In agreement with studies from other countries, this work shows that fish mislabelling can vary greatly within a country depending on the species. It further suggests that more efforts should be directed to the control of high value species like bluefin tuna. PMID:28462014

Density functional theory study of hydrogen atom abstraction from a series of para-substituted phenols: why is the Hammett σ(p)+ constant able to represent radical reaction rates?

PubMed

Yoshida, Tatsusada; Hirozumi, Koji; Harada, Masataka; Hitaoka, Seiji; Chuman, Hiroshi

2011-06-03

The rate of hydrogen atom abstraction from phenolic compounds by a radical is known to be often linear with the Hammett substitution constant σ(+), defined using the S(N)1 solvolysis rates of substituted cumyl chlorides. Nevertheless, a physicochemical reason for the above "empirical fact" has not been fully revealed. The transition states of complexes between the 2,2-diphenyl-1-picrylhydrazyl radical (dpph·) and a series of para-substituted phenols were determined by DFT (Density Functional Theory) calculations, and then the activation energy as well as the homolytic bond dissociation energy of the O-H bond and charge distribution in the transition state were calculated. The heterolytic bond dissociation energy of the C-Cl bond and charge distribution in the corresponding para-substituted cumyl chlorides were calculated in parallel. Excellent correlations among σ(+), charge distribution, and activation and bond dissociation energies revealed quantitatively that there is a strong similarity between the two reactions, showing that the electron-deficiency of the π-electron system conjugated with a substituent plays a crucial role in determining rates of the two reactions. The results provide a new insight into and physicochemical understanding of σ(+) in the hydrogen abstraction from substituted phenols by a radical.

Gait pattern alteration by functional sensory substitution in healthy subjects and in diabetic subjects with peripheral neuropathy.

PubMed

Walker, S C; Helm, P A; Lavery, L A

1997-08-01

To evaluate the ability of diabetic and nondiabetic individuals to learn to use a lower extremity sensory substitution device to cue gait pattern changes. Case-control study. Gait laboratory. Thirty diabetic persons and 20 age- and education-matched nondiabetic controls responded to advertisements for study participation. Participants walked on a treadmill at three speeds (1, 2, and 2.5mph) with auditory sensory feedback to cue ground contact greater than 80% duration of baseline. The variables measured included gait cycle (steps per minute) and number of times per minute that any step during a trial exceeded 80% duration of ground contacted compared with a measured baseline step length for each speed. Persons in both groups were able to rapidly and significantly alter their gait patterns in response to signals from the sensory substitution device, by changing their gait cycles (nondiabetic group, F(17,124) = 5.27, p < .001; diabetic group, F(5,172) = 3.45, p < .001). Post hoc analyses showed early gait cycle modification and error reduction among both groups. The nondiabetic group learned to use the device significantly more quickly than the diabetic group during the slow (1mph, t = 3.57, p < .001) and average (2mph, t = 2.97, p < .05) trials. By the fast (2.5mph) ambulation trial, both groups were performing equally, suggesting a rapid rate of adjustment to the device. No technical failures from gait trainer malfunction occurred during the study. Diabetic persons with neuropathy effectively used lower extremity sensory substitution, and the technology is now available to manufacture a durable, effective lower extremity sensory substitution system.

Evaluation of the risk of fungal spoilage when substituting sucrose with commercial purified Stevia glycosides in sweetened bakery products.

PubMed

Rodríguez, Alicia; Magan, Naresh; Medina, Angel

2016-08-16

The objectives of this study were to compare the effect of different Stevia-based sugar substitutes (S1-S3), sucrose alone and a mixture of sucrose+S1 on: (a) humectant properties, (b) relative colonisation rates of sponge cake slices at 0.90 aw by strains of Aspergillus flavus, Eurotium amstelodami, Fusarium graminearum and Penicillium verrucosum at 20 and 25°C and (c) shelf-life periods in days prior to visible growth. Results showed that sucrose, S1 commercial sugar substitute and the mixture of sucrose+S1 in water solutions were able to reach water activity levels similar to those of glycerol and glucose mixtures. The S2 and S3 commercial sugar substitutes were unable to reduce aw levels significantly. At 25°C, colonisation of sponge cake slices by E. amstelodami, A. flavus and P. verrucosum occurred in all the treatments. Growth of F. graminearum only occurred on sponge cake slices containing S2 and S3 Stevia-based products at both temperatures. The best control of growth (30days) was achieved in cake slices modified with sucrose or S1 Stevia treatments inoculated with A. flavus and in the sucrose treatment for E. amstelodami at 20°C. F. graminearum growth was completely inhibited when sucrose alone, S1 or sucrose+S1 treatments were used at both temperatures. This study suggests that, as part of a hurdle technology approach, replacing sucrose with low calorie sugar substitutes based on Stevia glycosides needs to be done with care. This is because different products may have variable humectant properties and bulking agents which may shorten the potential shelf-life of intermediate moisture bakery products. Copyright © 2016 Elsevier B.V. All rights reserved.

Large-Scale Comparative Analysis Reveals the Mechanisms Driving Plastomic Compaction, Reduction, and Inversions in Conifers II (Cupressophytes).

PubMed

Wu, Chung-Shien; Chaw, Shu-Miaw

2016-12-01

Conifers II (cupressophytes), comprising about 400 tree species in five families, are the most diverse group of living gymnosperms. Their plastid genomes (plastomes) are highly variable in size and organization, but such variation has never been systematically studied. In this study, we assessed the potential mechanisms underlying the evolution of cupressophyte plastomes. We analyzed the plastomes of 24 representative genera in all of the five cupressophyte families, focusing on their variation in size, noncoding DNA content, and nucleotide substitution rates. Using a tree-based method, we further inferred the ancestral plastomic organizations of internal nodes and evaluated the inversions across the evolutionary history of cupressophytes. Our data showed that variation in plastome size is statistically associated with the dynamics of noncoding DNA content, which results in different degrees of plastomic compactness among the cupressophyte families. The degrees of plastomic inversions also vary among the families, with the number of inversions per genus ranging from 0 in Araucariaceae to 1.27 in Cupressaceae. In addition, we demonstrated that synonymous substitution rates are significantly correlated with plastome size as well as degree of inversions. These data suggest that in cupressophytes, mutation rates play a critical role in driving the evolution of plastomic size while plastomic inversions evolve in a neutral manner. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Prevalence and impact of baseline resistance-associated substitutions on the efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV infection.

PubMed

Wang, Gary P; Terrault, Norah; Reeves, Jacqueline D; Liu, Lin; Li, Eric; Zhao, Lisa; Lim, Joseph K; Morelli, Giuseppe; Kuo, Alexander; Levitsky, Josh; Sherman, Kenneth E; Frazier, Lynn M; Ramani, Ananthakrishnan; Peter, Joy; Akuskevich, Lucy; Fried, Michael W; Nelson, David R

2018-02-16

Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup was associated with 2-4% lower SVR12 rates. SMV RASs was associated with lower SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19) in patients treated for longer than 98 days but was 87% (81/93) in patients treated for shorter than 98 days. These results demonstrate that RASs prevalence and their impact in real world practice are in general agreement with registration trials, and suggest that longer treatment duration may overcome the negative impact of baseline RASs on SVR12 rates in clinical practice.

Time Clustered Sampling Can Inflate the Inferred Substitution Rate in Foot-And-Mouth Disease Virus Analyses.

PubMed

Pedersen, Casper-Emil T; Frandsen, Peter; Wekesa, Sabenzia N; Heller, Rasmus; Sangula, Abraham K; Wadsworth, Jemma; Knowles, Nick J; Muwanika, Vincent B; Siegismund, Hans R

2015-01-01

With the emergence of analytical software for the inference of viral evolution, a number of studies have focused on estimating important parameters such as the substitution rate and the time to the most recent common ancestor (tMRCA) for rapidly evolving viruses. Coupled with an increasing abundance of sequence data sampled under widely different schemes, an effort to keep results consistent and comparable is needed. This study emphasizes commonly disregarded problems in the inference of evolutionary rates in viral sequence data when sampling is unevenly distributed on a temporal scale through a study of the foot-and-mouth (FMD) disease virus serotypes SAT 1 and SAT 2. Our study shows that clustered temporal sampling in phylogenetic analyses of FMD viruses will strongly bias the inferences of substitution rates and tMRCA because the inferred rates in such data sets reflect a rate closer to the mutation rate rather than the substitution rate. Estimating evolutionary parameters from viral sequences should be performed with due consideration of the differences in short-term and longer-term evolutionary processes occurring within sets of temporally sampled viruses, and studies should carefully consider how samples are combined.

Male Mutation Bias Is the Main Force Shaping Chromosomal Substitution Rates in Monotreme Mammals

PubMed Central

Link, Vivian; Aguilar-Gómez, Diana; Ramírez-Suástegui, Ciro; Hurst, Laurence D.

2017-01-01

Abstract In many species, spermatogenesis involves more cell divisions than oogenesis, and the male germline, therefore, accumulates more DNA replication errors, a phenomenon known as male mutation bias. The extent of male mutation bias (α) is estimated by comparing substitution rates of the X, Y, and autosomal chromosomes, as these chromosomes spend different proportions of their time in the germlines of the two sexes. Male mutation bias has been characterized in placental and marsupial mammals as well as birds, but analyses in monotremes failed to detect any such bias. Monotremes are an ancient lineage of egg-laying mammals with distinct biological properties, which include unique germline features. Here, we sought to assess the presence and potential characteristics of male mutation bias in platypus and the short-beaked echidna based on substitution rate analyses of X, Y, and autosomes. We established the presence of moderate male mutation bias in monotremes, corresponding to an α value of 2.12–3.69. Given that it has been unclear what proportion of the variation in substitution rates on the different chromosomal classes is really due to differential number of replications, we analyzed the influence of other confounding forces (selection, replication-timing, etc.) and found that male mutation bias is the main force explaining the between-chromosome classes differences in substitution rates. Finally, we estimated the proportion of variation at the gene level in substitution rates that is owing to replication effects and found that this phenomenon can explain >68% of these variations in monotremes, and in control species, rodents, and primates. PMID:28922870

Estimation of Free Radical Ionization Energies by the Kinetic Method and the Relationship between the Kinetic Method and the Hammett Equation.

PubMed

Chen, G; Wong, P; Cooks, R G

1997-09-01

Substituted 1,2-diphenylethanes undergo competitive dissociations upon electron ionization (EI) to generate substituted benzyl cation and benzyl radical pairs. Application of the kinetic method to the previous reported EI mass spectra of these covalently bound precursor ions (data are taken from McLafferty et al. J. Am. Chem. Soc. 1970, 92, 6867)) is used to estimate the ionization energies of substituted benzyl free radicals. A correlation is observed between the Hammett σ constant of the substituents and the kinetic method parameter, ln(k(x)/k(H)), where k(x) is the rate of fragmentation to give the substituted product ion and k(H) is the rate to give the benzyl ion itself. Systems involving weakly bound cluster ions, including proton-bound dimers of meta- and para-substituted pyridines and meta- and para-substituted anilines, and electron-bound dimers of meta- and para-substituted nitrobenzenes, also show good correlations between the kinetic method parameter and the Hammett σ constant.

76 FR 39474 - Monthly Median Cost of Funds Reporting, and Publication of Cost of Funds Indices

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... commenter noted that there are ``numerous adjustable interest rate home loans including loans sold to the... original indices; and (B) the substitution of the new indices will result in an interest rate substantially... direct substitute because of recent changes in interest rate relationships resulting from monetary policy...

Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database

PubMed Central

Cornish, Rosie; Macleod, John; Strang, John; Vickerman, Peter

2010-01-01

Objective To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment. Design Prospective cohort study. Setting UK General Practice Research Database Participants Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice. Main outcome measures Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users’ mortality with general population mortality rates. Results Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months. Conclusions Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment. Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality. PMID:20978062

Promotion and prelacteal feeding of breastmilk substitutes among mothers in Kathmandu Valley, Nepal.

PubMed

Pries, Alissa M; Huffman, Sandra L; Adhikary, Indu; Upreti, Senendra Raj; Dhungel, Shrid; Champeny, Mary; Zehner, Elizabeth

2016-04-01

In 1992, Nepal passed the Mother's Milk Substitutes (Control of Sale and Distribution) Act in order to regulate the sale, distribution and promotion of substitutes for breastmilk within Nepal, in an effort to protect and promote breastfeeding. Helen Keller International, in collaboration with Nepal's Ministry of Health and Population's Child Health Division, implemented a study to assess mothers' exposure to promotions for and utilization of breastmilk substitutes in Kathmandu Valley, Nepal. A health facility-based, cross-sectional survey was conducted among 304 mothers being discharged after delivery. Prelacteal feeding of breastmilk substitutes is prevalent (55.9% of mothers, n = 170). Reported recommendations during antenatal checks and after delivery from health professionals to use breastmilk substitutes were prevalent, occurring among 47.4% (n = 144) of mothers; rates of these recommendations were significantly higher for mothers that delivered in private health facilities, as compared with public (67.7% vs. 38.0%, P < 0.001). Mothers that received a recommendation to use a breastmilk substitute from a health worker were 16.7 times more likely to provide a prelacteal feed of a breastmilk substitute, as compared with mothers that did not receive a recommendation (P < 0.001). Few mothers reported observation of commercial advertisements for breastmilk substitutes inside a health facility (reported by 3.6% of mothers). No mothers reported receiving a sample of a breastmilk substitute, bottle or teat from a health professional. More information is needed to determine why there is such a high rate of health worker recommendations for breastmilk substitute use in the first few days after delivery. While utilization of breastmilk substitutes is low among mothers of young children in Nepal, prelacteal feeding of breastmilk substitutes is highly prevalent in Kathmandu Valley. Reported recommendations from health professionals to use breastmilk substitutes are common (over 40%) and are associated with prelacteal feeding among Nepal mothers included in this study. Provision of lactation management training to health workers and monitoring their practices regularly could strengthen breastfeeding counselling, aid in reducing high rates of prelacteal feeding and contribute to improved infant feeding practices. © 2016 The Authors. Maternal & Child Nutrition published byJohn Wiley & Sons Ltd.

Pattern of state coal taxation. [Review

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

Gulley, D.A.

1981-01-01

This paper reviews the recent history of state coal taxation and reports an empirically-based effort at defining the key determinants of state and local coal taxation. A pattern emerges but the analysis is complicated by the empirical and conceptual difficulties typical of such studies. Perhaps as important a result as the detection of a pattern is the recognition that many seemingly important variables do not appear to have consistently influenced tax levels. For policy makers and for industry, it appears that the present concern over a coal-states cartel is excessive. One can speculate that draconian tax adjustments on the basismore » of a crude-indicator-like reserve base will ultimately transfer less wealth than would skillful preemption of rent. It is also noteworthy that the sign of the tax effort variable is positive, indicating that coal tax rates are consistent with other tax efforts, not a substitute for them. Accepting impacts and general tax effort variables as the best explanations of interstate variations in tax effort is a somewhat different matter than determining what any given state's tax rate ought to be; such a question lies beyond the scope of this paper. This tax-determinant study can not define the right level of coal taxation, but it can suggest that no trend is yet evident toward entrepreneurial tax rates. 20 references, 4 figures.« less

Evolution of Dengue Virus Type 3 Genotype III in Venezuela: Diversification, Rates and Population Dynamics

PubMed Central

2010-01-01

Background Dengue virus (DENV) is a member of the genus Flavivirus of the family Flaviviridae. DENV are comprised of four distinct serotypes (DENV-1 through DENV-4) and each serotype can be divided in different genotypes. Currently, there is a dramatic emergence of DENV-3 genotype III in Latin America. Nevertheless, we still have an incomplete understanding of the evolutionary forces underlying the evolution of this genotype in this region of the world. In order to gain insight into the degree of genetic variability, rates and patterns of evolution of this genotype in Venezuela and the South American region, phylogenetic analysis, based on a large number (n = 119) of envelope gene sequences from DENV-3 genotype III strains isolated in Venezuela from 2001 to 2008, were performed. Results Phylogenetic analysis revealed an in situ evolution of DENV-3 genotype III following its introduction in the Latin American region, where three different genetic clusters (A to C) can be observed among the DENV-3 genotype III strains circulating in this region. Bayesian coalescent inference analyses revealed an evolutionary rate of 8.48 × 10-4 substitutions/site/year (s/s/y) for strains of cluster A, composed entirely of strains isolated in Venezuela. Amino acid substitution at position 329 of domain III of the E protein (A→V) was found in almost all E proteins from Cluster A strains. Conclusions A significant evolutionary change between DENV-3 genotype III strains that circulated in the initial years of the introduction in the continent and strains isolated in the Latin American region in recent years was observed. The presence of DENV-3 genotype III strains belonging to different clusters was observed in Venezuela, revealing several introduction events into this country. The evolutionary rate found for Cluster A strains circulating in Venezuela is similar to the others previously established for this genotype in other regions of the world. This suggests a lack of correlation among DENV genotype III substitution rate and ecological pattern of virus spread. PMID:21087501

Laboratory determination of the carbon kinetic isotope effects (KIEs) for reactions of methyl halides with various nucleophiles in solution

USGS Publications Warehouse

Baesman, S.M.; Miller, L.G.

2005-01-01

Large carbon kinetic isotope effects (KIEs) were measured for reactions of methyl bromide (MeBr), methyl chloride (MeCl), and methyl iodide (MeI) with various nucleophiles at 287 and 306 K in aqueous solutions. Rates of reaction of MeBr and MeI with H2O (neutral hydrolysis) or Cl- (halide substitution) were consistent with previous measurements. Hydrolysis rates increased with increasing temperature or pH (base hydrolysis). KIEs for hydrolysis were 51 ?? 6??? for MeBr and 38 ?? 8??? for MeI. Rates of halide substitution increased with increasing temperature and greater reactivity of the attacking nucleophile, with the fastest reaction being that of MeI with Br-. KIEs for halide substitution were independent of temperature but varied with the reactant methyl halide and the attacking nucleophile. KIEs were similar for MeBr substitution with Cl- and MeCl substitution with Br- (57 ?? 5 and 60 ?? 9??? respectively). The KIE for halide exchange of MeI was lower overall (33 ?? 8??? and was greater for substitution with Br- (46 ?? 6???) than with Cl- (29 ?? 6???). ?? Springer Science + Business Media, Inc. 2005.

Exponential decay of GC content detected by strand-symmetric substitution rates influences the evolution of isochore structure.

PubMed

Karro, J E; Peifer, M; Hardison, R C; Kollmann, M; von Grünberg, H H

2008-02-01

The distribution of guanine and cytosine nucleotides throughout a genome, or the GC content, is associated with numerous features in mammals; understanding the pattern and evolutionary history of GC content is crucial to our efforts to annotate the genome. The local GC content is decaying toward an equilibrium point, but the causes and rates of this decay, as well as the value of the equilibrium point, remain topics of debate. By comparing the results of 2 methods for estimating local substitution rates, we identify 620 Mb of the human genome in which the rates of the various types of nucleotide substitutions are the same on both strands. These strand-symmetric regions show an exponential decay of local GC content at a pace determined by local substitution rates. DNA segments subjected to higher rates experience disproportionately accelerated decay and are AT rich, whereas segments subjected to lower rates decay more slowly and are GC rich. Although we are unable to draw any conclusions about causal factors, the results support the hypothesis proposed by Khelifi A, Meunier J, Duret L, and Mouchiroud D (2006. GC content evolution of the human and mouse genomes: insights from the study of processed pseudogenes in regions of different recombination rates. J Mol Evol. 62:745-752.) that the isochore structure has been reshaped over time. If rate variation were a determining factor, then the current isochore structure of mammalian genomes could result from the local differences in substitution rates. We predict that under current conditions strand-symmetric portions of the human genome will stabilize at an average GC content of 30% (considerably less than the current 42%), thus confirming that the human genome has not yet reached equilibrium.

Stereotype threat and social function in opioid substitution therapy patients.

PubMed

von Hippel, Courtney; Henry, Julie D; Terrett, Gill; Mercuri, Kimberly; McAlear, Karen; Rendell, Peter G

2017-06-01

People with a history of substance abuse are subject to widespread stigmatization. It seems likely that this societal disapproval will result in feelings of stereotype threat, or the belief that one is the target of demeaning stereotypes. If so, stereotype threat has the potential to contribute to functional difficulties including poor social outcomes. Eighty drug users on opioid substitution therapy and 84 demographically matched controls completed measures of mental health and social function. The opioid substitution therapy group were additionally asked to complete a measure that focused on their feelings of stereotype threat in relation to their drug use history. Bivariate correlations and hierarchical regression analyses were conducted to establish the magnitude and specificity of the relationship between stereotype threat and social functioning. Relative to controls, the opioid substitution therapy group reported higher levels of negative affect and schizotypy, and poorer social functioning, with all three of these indices significantly correlated with their feelings of stereotype threat. The results also showed that stereotype threat contributed significant unique variance to social functioning in the opioid substitution therapy group, even after taking into account other background, clinical, and mental health variables. Social functioning is an important aspect of recovery, yet these data indicate that people with a history of drug abuse who believe they are the target of stereotypical attitudes have poorer social functioning. This relationship holds after controlling for the impact of other variables on social functioning, including mental health. The theoretical and practical implications of these findings are discussed. Concerns about being stereotyped can shape the social experiences of opioid substitution therapy patients. Opioid substitution therapy patients who feel negatively stereotyped experience greater social function deficits, and this relationship emerges after controlling for important clinical and mental health variables. Understanding the relationship between feeling stereotyped and social function may assist practitioners in their treatment. The study is cross-sectional, and thus, experimental or longitudinal research is required to determine the causal direction between stereotype threat and social function. © 2017 The British Psychological Society.

Evolution and dispersal of St. Louis encephalitis virus in the Americas.

PubMed

Auguste, Albert J; Pybus, Oliver G; Carrington, Christine V F

2009-07-01

Using a Bayesian coalescent approach on a dataset of 73 envelope gene sequences we estimated substitution rates and dates of divergence for St. Louis encephalitis virus (SLEV) in the Americas. We found significant rate heterogeneity among lineages, such that "relaxed" molecular clock models were much better supported than a strict molecular clock. The mean substitution rate estimated for all SLEV was 4.1x10(-4)substitutions/site/year (95% HPD 2.5-5.7)-higher than previous estimates that relied on the less well-suited strict clock. Mean substitution rates for individual lineages varied from 3.7x10(-4) to 7.2x10(-4)substitutions/site/year. For the first time we also assessed the magnitude and direction of viral gene flow within the Americas. The overall direction of gene flow during the period represented by the phylogeny is from South to North, and the region between 15 degrees N and 30 degrees N latitude appears to be the major source of virus for the rest of North America, which is consistent with migratory birds returning to their northern breeding grounds having acquired infection while wintering in the region of the Gulf of Mexico.

Synthesis and Hydrolytic Degradation of Substituted Poly(DL-Lactic Acid)s

PubMed Central

Tsuji, Hideto; Eto, Takehiko; Sakamoto, Yuzuru

2011-01-01

Non-substituted racemic poly(DL-lactic acid) (PLA) and substituted racemic poly(DL-lactic acid)s or poly(DL-2-hydroxyalkanoic acid)s with different side-chain lengths, i.e., poly(DL-2-hydroxybutanoic acid) (PBA), poly(DL-2-hydroxyhexanoic acid) (PHA), and poly(DL-2-hydroxydecanoic acid) (PDA) were synthesized by acid-catalyzed polycondensation of DL-lactic acid (LA), DL-2-hydroxybutanoic acid (BA), DL-2-hydroxyhexanoic acid (HA), and DL-2-hydroxydecanoic acid (DA), respectively. The hydrolytic degradation behavior was investigated in phosphate-buffered solution at 80 and 37 °C by gravimetry and gel permeation chromatography. It was found that the reactivity of monomers during polycondensation as monitored by the degree of polymerization (DP) decreased in the following order: LA > DA > BA > HA. The hydrolytic degradation rate traced by DP and weight loss at 80 °C decreased in the following order: PLA > PDA > PHA > PBA and that monitored by DP at 37 °C decreased in the following order: PLA > PDA > PBA > PHA. LA and PLA had the highest reactivity during polymerization and hydrolytic degradation rate, respectively, and were followed by DA and PDA. BA, HA, PBA, and PHA had the lowest reactivity during polymerization and hydrolytic degradation rate. The findings of the present study strongly suggest that inter-chain interactions play a major role in the reactivity of non-substituted and substituted LA monomers and degradation rate of the non-substituted and substituted PLA, along with steric hindrance of the side chains as can be expected. PMID:28824149

Male Mutation Bias Is the Main Force Shaping Chromosomal Substitution Rates in Monotreme Mammals.

PubMed

Link, Vivian; Aguilar-Gómez, Diana; Ramírez-Suástegui, Ciro; Hurst, Laurence D; Cortez, Diego

2017-09-01

In many species, spermatogenesis involves more cell divisions than oogenesis, and the male germline, therefore, accumulates more DNA replication errors, a phenomenon known as male mutation bias. The extent of male mutation bias (α) is estimated by comparing substitution rates of the X, Y, and autosomal chromosomes, as these chromosomes spend different proportions of their time in the germlines of the two sexes. Male mutation bias has been characterized in placental and marsupial mammals as well as birds, but analyses in monotremes failed to detect any such bias. Monotremes are an ancient lineage of egg-laying mammals with distinct biological properties, which include unique germline features. Here, we sought to assess the presence and potential characteristics of male mutation bias in platypus and the short-beaked echidna based on substitution rate analyses of X, Y, and autosomes. We established the presence of moderate male mutation bias in monotremes, corresponding to an α value of 2.12-3.69. Given that it has been unclear what proportion of the variation in substitution rates on the different chromosomal classes is really due to differential number of replications, we analyzed the influence of other confounding forces (selection, replication-timing, etc.) and found that male mutation bias is the main force explaining the between-chromosome classes differences in substitution rates. Finally, we estimated the proportion of variation at the gene level in substitution rates that is owing to replication effects and found that this phenomenon can explain >68% of these variations in monotremes, and in control species, rodents, and primates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Trends in electron-ion dissociative recombination of benzene analogs with functional group substitutions: Negative Hammett σpara values

NASA Astrophysics Data System (ADS)

Osborne, David; Lawson, Patrick Andrew; Adams, Nigel; Dotan, Itzhak

2014-06-01

An in-depth study of the effects of functional group substitution on benzene's electron-ion dissociative recombination (e-IDR) rate constant has been conducted. The e-IDR rate constants for benzene, biphenyl, toluene, ethylbenzene, anisole, phenol, and aniline have been measured using a Flowing Afterglow equipped with an electrostatic Langmuir probe (FALP). These measurements have been made over a series of temperatures from 300 to 550 K. A relationship between the Hammett σpara values for each compound and rate constant has indicated a trend in the e-IDR rate constants and possibly in their temperature dependence data. The Hammett σpara value is a method to describe the effect a functional group substituted to a benzene ring has upon the reaction rate constant.

Mind the gap! The mitochondrial control region and its power as a phylogenetic marker in echinoids.

PubMed

Bronstein, Omri; Kroh, Andreas; Haring, Elisabeth

2018-05-30

In Metazoa, mitochondrial markers are the most commonly used targets for inferring species-level molecular phylogenies due to their extremely low rate of recombination, maternal inheritance, ease of use and fast substitution rate in comparison to nuclear DNA. The mitochondrial control region (CR) is the main non-coding area of the mitochondrial genome and contains the mitochondrial origin of replication and transcription. While sequences of the cytochrome oxidase subunit 1 (COI) and 16S rRNA genes are the prime mitochondrial markers in phylogenetic studies, the highly variable CR is typically ignored and not targeted in such analyses. However, the higher substitution rate of the CR can be harnessed to infer the phylogeny of closely related species, and the use of a non-coding region alleviates biases resulting from both directional and purifying selection. Additionally, complete mitochondrial genome assemblies utilizing next generation sequencing (NGS) data often show exceptionally low coverage at specific regions, including the CR. This can only be resolved by targeted sequencing of this region. Here we provide novel sequence data for the echinoid mitochondrial control region in over 40 species across the echinoid phylogenetic tree. We demonstrate the advantages of directly targeting the CR and adjacent tRNAs to facilitate complementing low coverage NGS data from complete mitochondrial genome assemblies. Finally, we test the performance of this region as a phylogenetic marker both in the lab and in phylogenetic analyses, and demonstrate its superior performance over the other available mitochondrial markers in echinoids. Our target region of the mitochondrial CR (1) facilitates the first thorough investigation of this region across a wide range of echinoid taxa, (2) provides a tool for complementing missing data in NGS experiments, and (3) identifies the CR as a powerful, novel marker for phylogenetic inference in echinoids due to its high variability, lack of selection, and high compatibility across the entire class, outperforming conventional mitochondrial markers.

Heart Rate Variability Biofeedback Does Not Substitute for Asthma Steroid Controller Medication.

PubMed

Lehrer, Paul M; Irvin, Charles G; Lu, Shou-En; Scardella, Anthony; Roehmheld-Hamm, Beatrix; Aviles-Velez, Milisyaris; Graves, Jessica; Vaschillo, Evgeny G; Vaschillo, Bronya; Hoyte, Flavia; Nelson, Harold; Wamboldt, Frederick S

2018-03-01

Despite previous findings of therapeutic effects for heart rate variability biofeedback (HRVB) on asthma, it is not known whether HRVB can substitute either for controller or rescue medication, or whether it affects airway inflammation. Sixty-eight paid volunteer steroid naïve study participants with mild or moderate asthma were given 3 months of HRVB or a comparison condition consisting of EEG alpha biofeedback with relaxing music and relaxed paced breathing (EEG+), in a two-center trial. All participants received a month of intensive asthma education prior to randomization. Both treatment conditions produced similar significant improvements on the methacholine challenge test (MCT), asthma symptoms, and asthma quality of life (AQOL). MCT effects were of similar size to those of enhanced placebo procedures reported elsewhere, and were 65% of those of a course of a high-potency inhaled steroid budesonide given to a sub-group of participants following biofeedback training. Exhaled nitric oxide decreased significantly only in the HRVB group, 81% of the budesonide effect, but with no significant differences between groups. Participants reported becoming more relaxed during practice of both techniques. Administration of albuterol after biofeedback sessions produced a large improvement in pulmonary function test results, indicating that neither treatment normalized pulmonary function as a potent controller medication would have done. Impulse oscillometry showed increased upper airway (vocal cord) resistance during biofeedback periods in both groups. These data suggest that HRVB should not be considered an alternative to asthma controller medications (e.g., inhaled steroids), although both biofeedback conditions produced some beneficial effects, warranting further research, and suggesting potential complementary effects. Various hypotheses are presented to explain why HRVB effects on asthma appeared smaller in this study than in earlier studies. Clinical Trial Registration NCT02766374.

Determining factors affecting tourism demand for Malaysia using ARDL modeling: A case of Europe countries

NASA Astrophysics Data System (ADS)

Borhan, Nurbaizura; Arsad, Zainudin

2016-10-01

Tourism industry is the second largest foreign exchange earner after manufacturing in Malaysia. With regards to the importance of tourism industry in Malaysia, any factors that influence tourism demand should be considered cautiously by the government and tourism authorities in order to attract more international tourists in the near future. The purpose of this study is to investigate the dynamic long-run and short-run relationship between the number of international tourist arrivals from six European countries and four selected economic variables. The economic variables used in this study are exchange rate, gross domestic product, relative price and substitute relative price. This study also examines the impact of the European Sovereign crisis on the number of arrivals from the selected European countries to Malaysia. The data covers the period from quarter 1 (Q1) of 1999 to quarter 3 (Q3) of 2014 and employs the autoregressive distributed lag (ARDL) bounds testing approach proposed by Pesaran et al. (2001). The results of unit root test show a mixture of integrated at level and order one, I(0) and I(1). The results show that there exist long-run cointegration between the number of international tourist arrivals and exchange rate, level of income, tourism price and substitute tourism price for all countries. Generally, the results show that level of income is in line with the economic theory and Thailand is a competing destination for the tourism industry in Malaysia. Surprisingly, relative price is found to have positive impact on the number of arrivals to Malaysia and this suggests that an increase in the price level in Malaysia is unexpectedly increase the number of international tourist arrivals to Malaysia. Therefore the Malaysian government and tourism authorities should continue the efforts to withstand the growth of the tourism industry.

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.

Morphology and properties of poly vinyl alcohol (PVA) scaffolds: impact of process variables.

PubMed

Ye, Mao; Mohanty, Pravansu; Ghosh, Gargi

2014-09-01

Successful engineering of functional biological substitutes requires scaffolds with three-dimensional interconnected porous structure, controllable rate of biodegradation, and ideal mechanical strength. In this study, we report the development and characterization of micro-porous PVA scaffolds fabricated by freeze drying method. The impact of molecular weight of PVA, surfactant concentration, foaming time, and stirring speed on pore characteristics, mechanical properties, swelling ratio, and rate of degradation of the scaffolds was characterized. Results show that a foaming time of 60s, a stirring speed of 1,000 rpm, and a surfactant concentration of 5% yielded scaffolds with rigid structure but with interconnected pores. Study also demonstrated that increased foaming time increased porosity and swelling ratio and reduced the rigidity of the samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Local Variability of the Peierls Barrier of Screw Dislocations in Ta-10W.

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

Foiles, Stephen M.

2017-10-01

It is well know that the addition of substitutional elements changes the mechanical behavior of metals, a effect referred to solid solution hardening. For body-centered-cubic (BCC) metals, screw dislocation play a key role in the mechanical properties. Here the detailed modification of the Peierls barrier for screw dislocation motion in Ta with W substitutional atoms is computing using density functional theory (DFT). A reduced order model (ROM) of the influence of W substitution on the Peierls barrier is developed. The mean field change in the Peierls barrier for a Ta10W alloy is determined and shown to be larger than anticipatedmore » based on simple elasticity considerations. The ROM could be used in future calculations to determine the local variability of the Peierls barrier and the resultant influence on the motion of screw dislocation in this alloy.« less

[Development and validation of quality standards for colonoscopy].

PubMed

Sánchez Del Río, Antonio; Baudet, Juan Salvador; Naranjo Rodríguez, Antonio; Campo Fernández de Los Ríos, Rafael; Salces Franco, Inmaculada; Aparicio Tormo, Jose Ramón; Sánchez Muñoz, Diego; Llach, Joseph; Hervás Molina, Antonio; Parra-Blanco, Adolfo; Díaz Acosta, Juan Antonio

2010-01-30

Before starting programs for colorectal cancer screening it is necessary to evaluate the quality of colonoscopy. Our objectives were to develop a group of quality indicators of colonoscopy easily applicable and to determine the variability of their achievement. After reviewing the bibliography we prepared 21 potential indicators of quality that were submitted to a process of selection in which we measured their facial validity, content validity, reliability and viability of their measurement. We estimated the variability of their achievement by means of the coefficient of variability (CV) and the variability of the achievement of the standards by means of chi(2). Six indicators overcome the selection process: informed consent, medication administered, completed colonoscopy, complications, every polyp removed and recovered, and adenoma detection rate in patients older than 50 years. 1928 colonoscopies were included from eight endoscopy units. Every unit included the same number of colonoscopies selected by means of simple random sampling with substitution. There was an important variability in the achievement of some indicators and standards: medication administered (CV 43%, p<0.01), complications registered (CV 37%, p<0.01), every polyp removed and recovered (CV 12%, p<0.01) and adenoma detection rate in older than fifty years (CV 2%, p<0.01). We have validated six quality indicators for colonoscopy which are easily measurable. An important variability exists in the achievement of some indicators and standards. Our data highlight the importance of the development of continuous quality improvement programmes for colonoscopy before starting colorectal cancer screening. Copyright (c) 2009 Elsevier España, S.L. All rights reserved.

Human Germline Mutation and the Erratic Evolutionary Clock

PubMed Central

Przeworski, Molly

2016-01-01

Our understanding of the chronology of human evolution relies on the “molecular clock” provided by the steady accumulation of substitutions on an evolutionary lineage. Recent analyses of human pedigrees have called this understanding into question by revealing unexpectedly low germline mutation rates, which imply that substitutions accrue more slowly than previously believed. Translating mutation rates estimated from pedigrees into substitution rates is not as straightforward as it may seem, however. We dissect the steps involved, emphasizing that dating evolutionary events requires not “a mutation rate” but a precise characterization of how mutations accumulate in development in males and females—knowledge that remains elusive. PMID:27760127

Variable presence of the inverted repeat and plastome stability in Erodium

PubMed Central

Blazier, John C.; Jansen, Robert K.; Mower, Jeffrey P.; Govindu, Madhu; Zhang, Jin; Weng, Mao-Lun; Ruhlman, Tracey A.

2016-01-01

Background and Aims Several unrelated lineages such as plastids, viruses and plasmids, have converged on quadripartite genomes of similar size with large and small single copy regions and a large inverted repeat (IR). Except for Erodium (Geraniaceae), saguaro cactus and some legumes, the plastomes of all photosynthetic angiosperms display this structure. The functional significance of the IR is not understood and Erodium provides a system to examine the role of the IR in the long-term stability of these genomes. We compared the degree of genomic rearrangement in plastomes of Erodium that differ in the presence and absence of the IR. Methods We sequenced 17 new Erodium plastomes. Using 454, Illumina, PacBio and Sanger sequences, 16 genomes were assembled and categorized along with one incomplete and two previously published Erodium plastomes. We conducted phylogenetic analyses among these species using a dataset of 19 protein-coding genes and determined if significantly higher evolutionary rates had caused the long branch seen previously in phylogenetic reconstructions within the genus. Bioinformatic comparisons were also performed to evaluate plastome evolution across the genus. Key Results Erodium plastomes fell into four types (Type 1–4) that differ in their substitution rates, short dispersed repeat content and degree of genomic rearrangement, gene and intron content and GC content. Type 4 plastomes had significantly higher rates of synonymous substitutions (dS) for all genes and for 14 of the 19 genes non-synonymous substitutions (dN) were significantly accelerated. We evaluated the evidence for a single IR loss in Erodium and in doing so discovered that Type 4 plastomes contain a novel IR. Conclusions The presence or absence of the IR does not affect plastome stability in Erodium. Rather, the overall repeat content shows a negative correlation with genome stability, a pattern in agreement with other angiosperm groups and recent findings on genome stability in bacterial endosymbionts. PMID:27192713

Variable presence of the inverted repeat and plastome stability in Erodium.

PubMed

Blazier, John C; Jansen, Robert K; Mower, Jeffrey P; Govindu, Madhu; Zhang, Jin; Weng, Mao-Lun; Ruhlman, Tracey A

2016-06-01

Several unrelated lineages such as plastids, viruses and plasmids, have converged on quadripartite genomes of similar size with large and small single copy regions and a large inverted repeat (IR). Except for Erodium (Geraniaceae), saguaro cactus and some legumes, the plastomes of all photosynthetic angiosperms display this structure. The functional significance of the IR is not understood and Erodium provides a system to examine the role of the IR in the long-term stability of these genomes. We compared the degree of genomic rearrangement in plastomes of Erodium that differ in the presence and absence of the IR. We sequenced 17 new Erodium plastomes. Using 454, Illumina, PacBio and Sanger sequences, 16 genomes were assembled and categorized along with one incomplete and two previously published Erodium plastomes. We conducted phylogenetic analyses among these species using a dataset of 19 protein-coding genes and determined if significantly higher evolutionary rates had caused the long branch seen previously in phylogenetic reconstructions within the genus. Bioinformatic comparisons were also performed to evaluate plastome evolution across the genus. Erodium plastomes fell into four types (Type 1-4) that differ in their substitution rates, short dispersed repeat content and degree of genomic rearrangement, gene and intron content and GC content. Type 4 plastomes had significantly higher rates of synonymous substitutions (dS) for all genes and for 14 of the 19 genes non-synonymous substitutions (dN) were significantly accelerated. We evaluated the evidence for a single IR loss in Erodium and in doing so discovered that Type 4 plastomes contain a novel IR. The presence or absence of the IR does not affect plastome stability in Erodium. Rather, the overall repeat content shows a negative correlation with genome stability, a pattern in agreement with other angiosperm groups and recent findings on genome stability in bacterial endosymbionts. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparative mitogenomic analysis of mirid bugs (Hemiptera: Miridae) and evaluation of potential DNA barcoding markers.

PubMed

Wang, Juan; Zhang, Li; Zhang, Qi-Lin; Zhou, Min-Qiang; Wang, Xiao-Tong; Yang, Xing-Zhuo; Yuan, Ming-Long

2017-01-01

The family Miridae is one of the most species-rich families of insects. To better understand the diversity and evolution of mirids, we determined the mitogenome of Lygus pratenszs and re-sequenced the mitogenomes of four mirids (i.e., Apolygus lucorum , Adelphocoris suturalis , Ade. fasciaticollis and Ade. lineolatus ). We performed a comparative analysis for 15 mitogenomic sequences representing 11 species of five genera within Miridae and evaluated the potential of these mitochondrial genes as molecular markers. Our results showed that the general mitogenomic features (gene content, gene arrangement, base composition and codon usage) were well conserved among these mirids. Four protein-coding genes (PCGs) ( cox1 , cox3 , nad1 and nad3 ) had no length variability, where nad5 showed the largest size variation; no intraspecific length variation was found in PCGs. Two PCGs ( nad4 and nad5 ) showed relatively high substitution rates at the nucleotide and amino acid levels, where cox1 had the lowest substitution rate. The Ka/Ks values for all PCGs were far lower than 1 (<0.59), but the Ka/Ks values of cox1 -barcode sequences were always larger than 1 (1.34 -15.20), indicating that the 658 bp sequences of cox1 may be not the appropriate marker due to positive selection or selection relaxation. Phylogenetic analyses based on two concatenated mitogenomic datasets consistently supported the relationship of Nesidiocoris + ( Trigonotylus + ( Adelphocoris + ( Apolygus + Lygus ))), as revealed by nad4 , nad5 , rrnL and the combined 22 transfer RNA genes (tRNAs), respectively. Taken sequence length, substitution rate and phylogenetic signal together, the individual genes ( nad4 , nad5 and rrnL ) and the combined 22 tRNAs could been used as potential molecular markers for Miridae at various taxonomic levels. Our results suggest that it is essential to evaluate and select suitable markers for different taxa groups when performing phylogenetic, population genetic and species identification studies.

On the Overdispersed Molecular Clock

PubMed Central

Takahata, Naoyuki

1987-01-01

Rates of molecular evolution at some loci are more irregular than described by simple Poisson processes. Three situations under which molecular evolution would not follow simple Poisson processes are reevaluated from the viewpoint of the neutrality hypothesis: (i) concomitant or multiple substitutions in a gene, (ii) fluctuating substitution rates in time caused by coupled effects of deleterious mutations and bottlenecks, and (iii) changes in the degree of selective constraints against a gene (neutral space) caused by successive substitutions. The common underlying assumption that these causes are lineage nonspecific excludes the case where mutation rates themselves change systematically among lineages or taxonomic groups, and severely limits the extent of variation in the number of substitutions among lineages. Even under this stringent condition, however, the third hypothesis, the fluctuating neutral space model, can generate fairly large variation. This is described by a time-dependent renewal process, which does not exhibit any episodic nature of molecular evolution. It is argued that the observed elevated variances in the number of nucleotide or amino acid substitutions do not immediately call for positive Darwinian selection in molecular evolution. PMID:3596230

The tangled bank of amino acids

PubMed Central

Pollock, David D.

2016-01-01

Abstract The use of amino acid substitution matrices to model protein evolution has yielded important insights into both the evolutionary process and the properties of specific protein families. In order to make these models tractable, standard substitution matrices represent the average results of the evolutionary process rather than the underlying molecular biophysics and population genetics, treating proteins as a set of independently evolving sites rather than as an integrated biomolecular entity. With advances in computing and the increasing availability of sequence data, we now have an opportunity to move beyond current substitution matrices to more interpretable mechanistic models with greater fidelity to the evolutionary process of mutation and selection and the holistic nature of the selective constraints. As part of this endeavour, we consider how epistatic interactions induce spatial and temporal rate heterogeneity, and demonstrate how these generally ignored factors can reconcile standard substitution rate matrices and the underlying biology, allowing us to better understand the meaning of these substitution rates. Using computational simulations of protein evolution, we can demonstrate the importance of both spatial and temporal heterogeneity in modelling protein evolution. PMID:27028523

Reducing Cognitive Biases in Probabilistic Reasoning by the Use of Logarithm Formats

ERIC Educational Resources Information Center

Juslin, Peter; Nilsson, Hakan; Winman, Anders; Lindskog, Marcus

2011-01-01

Research on probability judgment has traditionally emphasized that people are susceptible to biases because they rely on "variable substitution": the assessment of normative variables is replaced by assessment of heuristic, subjective variables. A recent proposal is that many of these biases may rather derive from constraints on cognitive…

Correlations of nucleotide substitution rates and base composition of mammalian coding sequences with protein structure.

PubMed

Chiusano, M L; D'Onofrio, G; Alvarez-Valin, F; Jabbari, K; Colonna, G; Bernardi, G

1999-09-30

We investigated the relationships between the nucleotide substitution rates and the predicted secondary structures in the three states representation (alpha-helix, beta-sheet, and coil). The analysis was carried out on 34 alignments, each of which comprised sequences belonging to at least four different mammalian orders. The rates of synonymous substitution were found to be significantly different in regions predicted to be alpha-helix, beta-sheet, or coil. Likewise, the nonsynonymous rates also differ, although expectedly at a lower extent, in the three types of secondary structure, suggesting that different selective constraints associated with the different structures are affecting in a similar way the synonymous and nonsynonymous rates. Moreover, the base composition of the third codon positions is different in coding sequence regions corresponding to different secondary structures of proteins.

Shifts in the evolutionary rate and intensity of purifying selection between two Brassica genomes revealed by analyses of orthologous transposons and relics of a whole genome triplication.

PubMed

Zhao, Meixia; Du, Jianchang; Lin, Feng; Tong, Chaobo; Yu, Jingyin; Huang, Shunmou; Wang, Xiaowu; Liu, Shengyi; Ma, Jianxin

2013-10-01

Recent sequencing of the Brassica rapa and Brassica oleracea genomes revealed extremely contrasting genomic features such as the abundance and distribution of transposable elements between the two genomes. However, whether and how these structural differentiations may have influenced the evolutionary rates of the two genomes since their split from a common ancestor are unknown. Here, we investigated and compared the rates of nucleotide substitution between two long terminal repeats (LTRs) of individual orthologous LTR-retrotransposons, the rates of synonymous and non-synonymous substitution among triplicated genes retained in both genomes from a shared whole genome triplication event, and the rates of genetic recombination estimated/deduced by the comparison of physical and genetic distances along chromosomes and ratios of solo LTRs to intact elements. Overall, LTR sequences and genic sequences showed more rapid nucleotide substitution in B. rapa than in B. oleracea. Synonymous substitution of triplicated genes retained from a shared whole genome triplication was detected at higher rates in B. rapa than in B. oleracea. Interestingly, non-synonymous substitution was observed at lower rates in the former than in the latter, indicating shifted densities of purifying selection between the two genomes. In addition to evolutionary asymmetry, orthologous genes differentially regulated and/or disrupted by transposable elements between the two genomes were also characterized. Our analyses suggest that local genomic and epigenomic features, such as recombination rates and chromatin dynamics reshaped by independent proliferation of transposable elements and elimination between the two genomes, are perhaps partially the causes and partially the outcomes of the observed inter-specific asymmetric evolution. © 2013 Purdue University The Plant Journal © 2013 John Wiley & Sons Ltd.

Buffel grass (Cenchrus ciliaria L.) substitution for orange pulp on intake, digestibility, and performance of hairsheep lambs.

PubMed

Macías-Cruz, Ulises; Quintero-Elisea, Juan A; Avendaño-Reyes, Leonel; Correa-Calderón, Abelardo; Alvarez-Valenzuela, Francisco D; Soto-Navarro, S A; Lucero-Magaña, F A; González-Reyna, Arnoldo

2010-02-01

Twenty Dorper x Pelibuey male lambs were used to evaluate the effect of substitution of forage with fresh orange pulp (FOP) in diets for fattening lambs on productive behavior, nutrient intake, apparent digestibility coefficient, and feeding costs. Lambs were divided into five groups (n = 4) and then housed in individual pens during 70 d. Treatments consisted of five levels of FOP (0, 25, 50, 75 and 100%) which substituted buffel grass hay on the base diet (40:60%, forage:concentrate). Additionally, changes in chemical composition of FOP stored in stack during 8 d were evaluated (from the day 1 until day 8). Daily feed intake expressed as kg/day and % live weight, lamb growth rate, feeding cost of each lamb per day and per fattening period, hemicellulose intake, and DM, OM, CP, NDF and hemicellulose digestibility showed a quadratic effect (P < 0.05), while DM, OM and CP intake presented a cubic effect (P < 0.05) with the increasing level of FOP. The maximum estimated value for those variables was observed at 75% of hay replacement with FOP. With respect to changes in chemical composition of pulp stored, DM content increased (P = 0.0011) from 210 to 310 g/kg FOP and OM, fiber fraction, and ash content were constant (P > 0.05) among storage days. Therefore, replacing around 75% of buffel grass hay with FOP in diets for fattening lambs resulted in the best growth rate and more efficient diet utilization. Fresh orange pulp stored in a stack did not change its chemical composition, and did not affect its utilization as a sheep feedstuff.

Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans

PubMed Central

Pritchard, Jonathan K.

2016-01-01

The site frequency spectrum (SFS) has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the “phylogenetically-conditioned SFS” or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC), combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans. PMID:27977673

Artificial gravity - The evolution of variable gravity research

NASA Technical Reports Server (NTRS)

Fuller, Charles A.; Sulzman, Frank M.; Keefe, J. Richard

1987-01-01

The development of a space life science research program based on the use of rotational facilities is described. In-flight and ground centrifuges can be used as artificial gravity environments to study the following: nongravitational biological factors; the effects of 0, 1, and hyper G on man; counter measures for deconditioning astronauts in weightlessness; and the development of suitable artificial gravity for long-term residence in space. The use of inertial fields as a substitute for gravity, and the relations between the radius of the centrifuge and rotation rate and specimen height and rotation radius are examined. An example of a centrifuge study involving squirrel monkeys is presented.

The effect of canine characteristics and symmetry on perceived smile attractiveness when canine teeth are substituted for lateral incisors.

PubMed

Rayner, Wendy Jane; Barber, Sophy K; Spencer, Richard James

2015-03-01

To determine the effect of canine tooth characteristics and symmetry on perceived smile attractiveness when maxillary canine teeth are substituted for missing lateral incisors. Prospective, cross-sectional study. Non-clinical study undertaken from Leeds Dental Institute, UK. A composite full-face image of a smiling female was used to display various dentitions; a control image with an 'ideal' smile, plus six further images substituting the maxillary lateral incisors with canine teeth either unilaterally or bilaterally with varying size, shape, colour and gingival margin level. The seven images were shown to orthodontists (n = 30), dentists (n = 30) and lay people (n = 30) who were asked to rate smile attractiveness using a visual analogue scale. Dental professionals rated smiles with canine substitution for lateral incisor agenesis to be significantly less attractive than an ideal smile unless the substituted canine teeth approximated the lateral incisor in terms of size, shape, colour and gingival margin. Lay people did not find smiles where canine teeth were substituted for lateral incisors significantly more or less attractive than an ideal smile regardless of the canine tooth characteristics. Dental professionals were significantly more perceptive than lay people to the deviation from ideal smile aesthetics due to canine substitution. Smiles with unilateral canine substitution were not found to be significantly less attractive than bilateral canine substitution by all groups. Canine characteristics and observer status will affect how canine substitution for lateral incisor agenesis is viewed in terms of aesthetic outcome.

The computational analysis and modelling of substitution effects on hydrolysis of formanilides in acidic aqueous solutions

NASA Astrophysics Data System (ADS)

Lukeš, Vladimír; Škorňa, Peter; Michalík, Martin; Klein, Erik

2017-11-01

Various para, meta and ortho substituted formanilides have been theoretically studied. For trans and cis-isomers of non-substituted formanilide, the calculated B3LYP vibration normal modes were analyzed. Substituent effect on the selected normal modes was described and the comparison with the available experimental data is presented. The calculated B3LYP proton affinities were correlated with Hammett constants, Fujita-Nishioka equation and the rate constants of the hydrolysis in 1 M HCl. Found linear dependences allow predictions of dissociation constants (pKBH+) and hydrolysis rate constants. Obtained results indicate that protonation of amide group may represent the rate determining step of acid catalyzed hydrolysis.

Fat substitutes in processing of sausages using piramutaba waste.

PubMed

de Fátima Henriques Lourenço, Lúcia; Dos Santos Galvão, Giane Célia; da Conceição Amaral Ribeiro, Suezilde; de Fátima Amaral Ribeiro, Carmelita; Park, Kil Jin

2014-07-01

The aim of this study was to evaluate fat substitute in processing of sausages prepared with surimi of waste from piramutaba filleting. The formulation ingredients were mixed with the fat substitutes added according to a fractional planning 2(4-1), where the independent variables, manioc starch (Ms), hydrogenated soy fat (F), texturized soybean protein (Tsp) and carrageenan (Cg) were evaluated on the responses of pH, texture (Tx), raw batter stability (RBS) and water holding capacity (WHC) of the sausage. Fat substitutes were evaluated in 11 formulations and the results showed that the greatest effects on the responses were found to Ms, F and Cg, being eliminated from the formulation Tsp. To find the best formulation for processing piramutaba sausage was made a complete factorial planning of 2(3) to evaluate the concentrations of fat substitutes in an enlarged range. The optimum condition found for fat substitutes in the sausages formulation were carrageenan (0.51%), manioc starch (1.45%) and fat (1.2%).

Can Wearable Devices Accurately Measure Heart Rate Variability? A Systematic Review.

PubMed

Georgiou, Konstantinos; Larentzakis, Andreas V; Khamis, Nehal N; Alsuhaibani, Ghadah I; Alaska, Yasser A; Giallafos, Elias J

2018-03-01

A growing number of wearable devices claim to provide accurate, cheap and easily applicable heart rate variability (HRV) indices. This is mainly accomplished by using wearable photoplethysmography (PPG) and/or electrocardiography (ECG), through simple and non-invasive techniques, as a substitute of the gold standard RR interval estimation through electrocardiogram. Although the agreement between pulse rate variability (PRV) and HRV has been evaluated in the literature, the reported results are still inconclusive especially when using wearable devices. The purpose of this systematic review is to investigate if wearable devices provide a reliable and precise measurement of classic HRV parameters in rest as well as during exercise. A search strategy was implemented to retrieve relevant articles from MEDLINE and SCOPUS databases, as well as, through internet search. The 308 articles retrieved were reviewed for further evaluation according to the predetermined inclusion/exclusion criteria. Eighteen studies were included. Sixteen of them integrated ECG - HRV technology and two of them PPG - PRV technology. All of them examined wearable devices accuracy in RV detection during rest, while only eight of them during exercise. The correlation between classic ECG derived HRV and the wearable RV ranged from very good to excellent during rest, yet it declined progressively as exercise level increased. Wearable devices may provide a promising alternative solution for measuring RV. However, more robust studies in non-stationary conditions are needed using appropriate methodology in terms of number of subjects involved, acquisition and analysis techniques implied.

THE INTERACTION OF PHENOL AND AROMATIC AMINE INHIBITORS IN HYDROCARBON OXIDATION REACTIONS,

DTIC Science & Technology

and the structure of the phenols. This phenomenon is observed for o,o’-substituted alkylphenols and it is not observed for o,o’-nonsubstituted and...o-substituted alkylphenols . The rate of amine reduction by phenol is determined by the activity of the formed phenoxyl radical. The rate constants

Economic substitutability of electrical brain stimulation, food, and water.

PubMed Central

Green, L; Rachlin, H

1991-01-01

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other. PMID:2037823

Formal properties of the probability of fixation: identities, inequalities and approximations.

PubMed

McCandlish, David M; Epstein, Charles L; Plotkin, Joshua B

2015-02-01

The formula for the probability of fixation of a new mutation is widely used in theoretical population genetics and molecular evolution. Here we derive a series of identities, inequalities and approximations for the exact probability of fixation of a new mutation under the Moran process (equivalent results hold for the approximate probability of fixation under the Wright-Fisher process, after an appropriate change of variables). We show that the logarithm of the fixation probability has particularly simple behavior when the selection coefficient is measured as a difference of Malthusian fitnesses, and we exploit this simplicity to derive inequalities and approximations. We also present a comprehensive comparison of both existing and new approximations for the fixation probability, highlighting those approximations that induce a reversible Markov chain when used to describe the dynamics of evolution under weak mutation. To demonstrate the power of these results, we consider the classical problem of determining the total substitution rate across an ensemble of biallelic loci and prove that, at equilibrium, a strict majority of substitutions are due to drift rather than selection. Copyright © 2014 Elsevier Inc. All rights reserved.

High isolation rate and multidrug resistance tendency of penicillin-susceptible group B Streptococcus with reduced ceftibuten susceptibility in Japan.

PubMed

Banno, Hirotsugu; Kimura, Kouji; Seki, Tomomi; Jin, Wanchun; Wachino, Jun-Ichi; Yamada, Keiko; Nagano, Noriyuki; Arakawa, Yoshichika

2018-05-17

Group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) have emerged through acquisition of amino acid substitutions in penicillin-binding protein 2X (PBP2X). Moreover, we also reported the emergence of penicillin-susceptible GBS clinical isolates with reduced ceftibuten susceptibility (CTB r PSGBS) due to amino acid substitutions in PBPs. However, whether or not these amino acid substitutions are responsible for the reduced ceftibuten susceptibility (RCTBS) profile remains unclear. Furthermore, the rate of CTB r PSGBS isolation and their multidrug resistance tendency remain uncertain. Therefore, we collected 377 clinical GBS isolates from multiple regions in Japan between August 2013 and August 2015. These isolates were characterized by determining MICs and sequencing the pbp2x gene. The isolation rate of CTB r PSGBS was 7.2% (27/377). CTB r PSGBS isolate harbor two types of amino acid substitutions in PBP2X [(T394A type) and (I377V, G398A, Q412L, and H438H type)]. The relevance of the amino acid substitutions found to the RCTBS was confirmed with allelic exchange techniques. Allelic exchange recombinant clones acquired two types of amino acid substitutions in PBP2X showed RCTBS. Furthermore, total ratio of resistance and non-susceptibility to both macrolides and fluoroquinolones in CTB r PSGBS was 51.9% (14/27). The isolation rate of CTB r PSGBS is non-negligibly high and the CTB r PSGBS tends to exhibit resistance and non-susceptible profile to both macrolides and fluoroquinolones.

Leaching kinetics of bottom ash waste as a source of calcium ions.

PubMed

Koech, Lawrence; Everson, Ray; Neomagus, Hein; Rutto, Hilary

2015-02-01

Bottom ash is a waste material from coal-fired power plants, and it is known to contain elements that are potentially toxic at high concentration levels when disposed in landfills. This study investigates the use of bottom ash as a partial substitute sorbent for wet flue gas desulfurization (FGD) processes by focusing on its leaching kinetics in adipic acid. This was studied basing on the shrinking core model that was applied to the experimental data obtained by the authors presented at the International Conference on Industrial, Manufacturing, Automation and Mechanical Engineering, Johannesburg, South Africa, November 27-28, 2013) on dissolution of bottom ash. The leaching rate constant was obtained from different reaction variables, namely, temperature, pH, acid concentration, and solid-to-liquid ratio, that could affect the leaching process. The solid sample of bottom ash was characterized at different leaching periods using X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was found that solid-to-liquid ratio had a significant effect on the leaching rate constant when compared with other variables. The leaching kinetics showed that diffusion through the product layer was the rate-controlling step during leaching, and the activation energy for the process was found to be 18.92 kJ/mol.

The tangled bank of amino acids.

PubMed

Goldstein, Richard A; Pollock, David D

2016-07-01

The use of amino acid substitution matrices to model protein evolution has yielded important insights into both the evolutionary process and the properties of specific protein families. In order to make these models tractable, standard substitution matrices represent the average results of the evolutionary process rather than the underlying molecular biophysics and population genetics, treating proteins as a set of independently evolving sites rather than as an integrated biomolecular entity. With advances in computing and the increasing availability of sequence data, we now have an opportunity to move beyond current substitution matrices to more interpretable mechanistic models with greater fidelity to the evolutionary process of mutation and selection and the holistic nature of the selective constraints. As part of this endeavour, we consider how epistatic interactions induce spatial and temporal rate heterogeneity, and demonstrate how these generally ignored factors can reconcile standard substitution rate matrices and the underlying biology, allowing us to better understand the meaning of these substitution rates. Using computational simulations of protein evolution, we can demonstrate the importance of both spatial and temporal heterogeneity in modelling protein evolution. © 2016 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

How far can sodium substitute for potassium in red beet?

NASA Technical Reports Server (NTRS)

Subbarao, G. V.; Wheeler, R. M.; Stutte, G. W.; Levine, L. H.; Sager, J. C. (Principal Investigator)

1999-01-01

Sodium (Na) movement between plants and humans is one of the more critical aspects of bioregenerative systems of life support, which NASA is studying for the establishment of long-term bases on the Lunar or Martian surface. This study was conducted to determine the extent to which Na can replace potassium (K) in red beet (Beta vulgaris L. ssp vulgaris) without adversely affecting metabolic functions such as water relations, photosynthetic rates, and thus growth. Two cultivars, Ruby Queen and Klein Bol, were grown for 42 days at 1200 micromoles mol-1 CO2 in a growth chamber using a re-circulating nutrient film technique with 0%, 75%, 95%, and 98% Na substitution for K in a modified half-strength Hoagland solution. Total biomass of Ruby Queen was greatest at 95% Na substitution and equal at 0% and 98% Na substitution. For Klein Bol, there was a 75% reduction in total biomass at 98% Na substitution. Nearly 95% of the total plant K was replaced with Na at 98% Na substitution in both cultivars. Potassium concentrations in leaves decreased from 120 g kg-1 dwt in 0% Na substitution to 3.5 g kg-1 dwt at 98% Na substitution. Leaf chlorophyll concentration, photosynthetic rate, and osmotic potential were not affected in either cultivar by Na substitution for K. Leaf glycinebetaine levels were doubled at 75% Na substitution in Klein Bol, but decreased at higher levels of Na substitution. For Ruby Queen, glycinebetaine levels in leaf increased with the first increase of Na levels and were maintained at the higher Na levels. These results indicate that in some cultivars of red beet, 95% of the normal tissue K can be replaced by Na without a reduction in growth.

Measurement of a linear free energy relationship one molecule at a time

PubMed Central

Rao, B. V.; Kwon, K.-Y.; Liu, A.; Bartels, L.

2004-01-01

A systematic study of the dehydrogenation of substituted thiophenols by controlled charge injection from the tip of a scanning tunneling microscope (STM) reveals a pronounced dependence of the reaction yield on the position and the chemical nature of the substituent. We evaluate the dehydrogenation rate of para-halo-substituted species within a linear free energy relationship, namely the Hammett equation. The resultant ρ value of 1.4 can faithfully predict the reaction rates of molecules that are meta-halo-substituted or para-methyl-substituted. The positive sign of ρ suggests a negatively charged transition state at the core of the STM-induced process, and the magnitude of the ρ value indicates that the presence of the substrate does not preclude substantial substituent effects. The applicability of the Hammett equation to single-molecule chemistry offers facile prediction of the rate of STM-based single-molecule chemistry in a field, which so far has been addressed by focusing on involved quantum-mechanical modeling of its underlying processes. PMID:15601774

Measurement of a linear free energy relationship one molecule at a time.

PubMed

Rao, B V; Kwon, K-Y; Liu, A; Bartels, L

2004-12-28

A systematic study of the dehydrogenation of substituted thiophenols by controlled charge injection from the tip of a scanning tunneling microscope (STM) reveals a pronounced dependence of the reaction yield on the position and the chemical nature of the substituent. We evaluate the dehydrogenation rate of para-halo-substituted species within a linear free energy relationship, namely the Hammett equation. The resultant rho value of 1.4 can faithfully predict the reaction rates of molecules that are meta-halo-substituted or para-methyl-substituted. The positive sign of rho suggests a negatively charged transition state at the core of the STM-induced process, and the magnitude of the rho value indicates that the presence of the substrate does not preclude substantial substituent effects. The applicability of the Hammett equation to single-molecule chemistry offers facile prediction of the rate of STM-based single-molecule chemistry in a field, which so far has been addressed by focusing on involved quantum-mechanical modeling of its underlying processes.

Determinants of quality of life of patients with heart failure and iron deficiency treated with ferric carboxymaltose: FAIR-HF sub-analysis.

PubMed

Gutzwiller, Florian S; Pfeil, Alena M; Comin-Colet, Josep; Ponikowski, Piotr; Filippatos, Gerasimos; Mori, Claudio; Braunhofer, Peter G; Szucs, Thomas D; Schwenkglenks, Matthias; Anker, Stefan D

2013-10-09

Heart failure (HF) is a burden to patients and health care systems. The objectives of HF treatment are to improve health related quality of life (HRQoL) and reduce mortality and morbidity. We aimed to evaluate determinants of health-related quality of life (HRQoL) in patients with iron deficiency and HF treated with intravenous (i.v.) iron substitution or placebo. A randomised, double-blind, placebo-controlled trial (n = 459) in iron-deficient chronic heart failure (CHF) patients with or without anaemia studied clinical and HRQoL benefits of i.v. iron substitution using ferric carboxymaltose (FCM) over a 24-week trial period. Multivariate analysis was carried out with various clinical variables as independent variables and HRQoL measures as dependent variables. Mean change from baseline of European Quality of Life - 5 Dimensions (EQ-5D) (value set-based) utilities (on a 0 to 100 scale) at week 24 was 8.91 (i.v. iron) and 0.68 (placebo; p < 0.01). In a multivariate analysis excluding baseline HRQoL, a higher exercise tolerance and i.v. iron substitution positively influenced HRQoL, whereas impaired renal function and a history of stroke had a negative effect. The level of HRQoL was also influenced by country of residence. When baseline HRQoL was factored in, the multivariate model remained stable. In this study, i.v. iron substitution, exercise tolerance, stroke, country of residence and renal function influenced measures of HRQoL in patients with heart failure and iron deficiency. © 2013.

Genetic and evolutionary characterization of RABVs from China using the phosphoprotein gene.

PubMed

Wang, Lihua; Wu, Hui; Tao, Xiaoyan; Li, Hao; Rayner, Simon; Liang, Guodong; Tang, Qing

2013-01-07

While the function of the phosphoprotein (P) gene of the rabies virus (RABV) has been well studied in laboratory adapted RABVs, the genetic diversity and evolution characteristics of the P gene of street RABVs remain unclear. The objective of the present study was to investigate the mutation and evolution of P genes in Chinese street RABVs. The P gene of 77 RABVs from brain samples of dogs and wild animals collected in eight Chinese provinces through 2003 to 2008 were sequenced. The open reading frame (ORF) of the P genes was 894 nucleotides (nt) in length, with 85-99% (80-89%) amino acid (nucleotide) identity compared with the laboratory RABVs and vaccine strains. Phylogenetic analysis based on the P gene revealed that Chinese RABVs strains could be divided into two distinct clades, and several RABV variants were found to co circulating in the same province. Two conserved (CD1, 2) and two variable (VD1, 2) domains were identified by comparing the deduced primary sequences of the encoded P proteins. Two sequence motifs, one believed to confer binding to the cytoplasmic dynein light chain LC8 and a lysine-rich sequence were conserved throughout the Chinese RABVs. In contrast, the isolates exhibited lower conservation of one phosphate acceptor and one internal translation initiation site identified in the P protein of the rabies challenge virus standard (CVS) strain. Bayesian coalescent analysis showed that the P gene in Chinese RABVs have a substitution rate (3.305x10(-4) substitutions per site per year) and evolution history (592 years ago) similar to values for the glycoprotein (G) and nucleoprotein (N) reported previously. Several substitutions were found in the P gene of Chinese RABVs strains compared to the laboratory adapted and vaccine strains, whether these variations could affect the biological characteristics of Chinese RABVs need to be further investigated. The substitution rate and evolution history of P gene is similar to G and N gene, combine the topology of phylogenetic tree based on the P gene is similar to the G and N gene trees, indicate that the P, G and N genes are equally valid for examining the phylogenetics of RABVs.

Dynamic Nucleotide Mutation Gradients and Control Region Usage in Squamate Reptile Mitochondrial Genomes

PubMed Central

Castoe, T.A.; Gu, W.; de Koning, A.P.J.; Daza, J.M.; Jiang, Z.J.; Parkinson, C.L.; Pollock, D.D.

2010-01-01

Gradients of nucleotide bias and substitution rates occur in vertebrate mitochondrial genomes due to the asymmetric nature of the replication process. The evolution of these gradients has previously been studied in detail in primates, but not in other vertebrate groups. From the primate study, the strengths of these gradients are known to evolve in ways that can substantially alter the substitution process, but it is unclear how rapidly they evolve over evolutionary time or how different they may be in different lineages or groups of vertebrates. Given the importance of mitochondrial genomes in phylogenetics and molecular evolutionary research, a better understanding of how asymmetric mitochondrial substitution gradients evolve would contribute key insights into how this gradient evolution may mislead evolutionary inferences, and how it may also be incorporated into new evolutionary models. Most snake mitochondrial genomes have an additional interesting feature, 2 nearly identical control regions, which vary among different species in the extent that they are used as origins of replication. Given the expanded sampling of complete snake genomes currently available, together with 2 additional snakes sequenced in this study, we reexamined gradient strength and CR usage in alethinophidian snakes as well as several lizards that possess dual CRs. Our results suggest that nucleotide substitution gradients (and corresponding nucleotide bias) and CR usage is highly labile over the ∼200 m.y. of squamate evolution, and demonstrates greater overall variability than previously shown in primates. The evidence for the existence of such gradients, and their ability to evolve rapidly and converge among unrelated species suggests that gradient dynamics could easily mislead phylogenetic and molecular evolutionary inferences, and argues strongly that these dynamics should be incorporated into phylogenetic models. PMID:20215734

Cigarette and e-liquid demand and substitution in e-cigarette-naïve smokers.

PubMed

Stein, Jeffrey S; Koffarnus, Mikhail N; Stepanov, Irina; Hatsukami, Dorothy K; Bickel, Warren K

2018-06-01

Behavioral economic methods allow experimental manipulation of price and examination of its effects on tobacco product purchasing. These methods may be used to examine tobacco product abuse liability and to prospectively model possible effects of price regulation. In the present study, we examined multiple measures of behavioral economic demand for cigarettes and e-liquid for use in a second-generation electronic cigarette (e-cigarette) in e-cigarette-naïve cigarette smokers. Twenty-five smokers received an e-cigarette (eGo ONE CT), sampled study e-liquid (24 mg/mL nicotine), and completed recurring sessions in which they used an experimental income to purchase real-world supplies of cigarettes and/or e-liquid. Participants also completed self-report measures of drug effects/liking. When products were available alone, we observed lower demand for e-liquid than for cigarettes. This effect was magnified when cigarettes and e-liquid were available concurrently. In additional assessments, e-liquid served as a partial substitute for cigarettes, but cigarettes did not serve as a substitute for e-liquid. Finally, participants rated e-liquid more poorly than cigarettes on several dimensions of drug effects/liking (any effects, liking, desire, and probability of continued use). We conclude that e-cigarette-naïve smokers value cigarettes more highly than e-liquid across multiple contexts and measurements. Nonetheless, participants still valued e-liquid positively and purchased it frequently, both as a substitute for cigarettes and independently of cigarettes. To understand the variables that influence transitions from exclusive smoking to either dual cigarette/e-cigarette use or exclusive e-cigarette use, future work should systematically examine the role of duration of e-liquid exposure. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Fertilizer performance of liquid fraction of digestate as synthetic nitrogen substitute in silage maize cultivation for three consecutive years.

PubMed

Sigurnjak, I; Vaneeckhaute, C; Michels, E; Ryckaert, B; Ghekiere, G; Tack, F M G; Meers, E

2017-12-01

Following changes over recent years in fertilizer legislative framework throughout Europe, phosphorus (P) is taking over the role of being the limiting factor in fertilizer application rate of animal manure. This results in less placement area for spreading animal manure. As a consequence, more expensive and energy demanding synthetic fertilizers are required to meet crop nutrient requirements despite existing manure surpluses. Anaerobic digestion followed by mechanical separation of raw digestate, results in liquid fraction (LF) of digestate, a product poor in P but rich in nitrogen (N) and potassium (K). A 3-year field experiment was conducted to evaluate the impact of using the LF of digestate as a (partial) substitute for synthetic N fertilizer. Two different fertilization strategies, the LF of digestate in combination with respectively animal manure and digestate, were compared to the conventional fertilization regime of raw animal manure with synthetic fertilizers. Results from the 3-year trial indicate that the LF of digestate may substitute synthetic N fertilizers without crop yield losses. Through fertilizer use efficiency assessment it was observed that under-fertilization of soils with a high P status could reduce P availability and consequently the potential for P leaching. Under conditions of lower K application, more sodium was taken up by the crop. In arid regions, this effect might reduce the potential risk of salt accumulation that is associated with organic fertilizer application. Finally, economic and ecological benefits were found to be higher when LF of digestate was used as a synthetic N substitute. Future perspectives indicate that nutrient variability in bio-based fertilizers will be one of the greatest challenges to address in the future utilization of these products. Copyright © 2017 Elsevier B.V. All rights reserved.

A new molecular evolution model for limited insertion independent of substitution.

PubMed

Lèbre, Sophie; Michel, Christian J

2013-10-01

We recently introduced a new molecular evolution model called the IDIS model for Insertion Deletion Independent of Substitution [13,14]. In the IDIS model, the three independent processes of substitution, insertion and deletion of residues have constant rates. In order to control the genome expansion during evolution, we generalize here the IDIS model by introducing an insertion rate which decreases when the sequence grows and tends to 0 for a maximum sequence length nmax. This new model, called LIIS for Limited Insertion Independent of Substitution, defines a matrix differential equation satisfied by a vector P(t) describing the sequence content in each residue at evolution time t. An analytical solution is obtained for any diagonalizable substitution matrix M. Thus, the LIIS model gives an expression of the sequence content vector P(t) in each residue under evolution time t as a function of the eigenvalues and the eigenvectors of matrix M, the residue insertion rate vector R, the total insertion rate r, the initial and maximum sequence lengths n0 and nmax, respectively, and the sequence content vector P(t0) at initial time t0. The derivation of the analytical solution is much more technical, compared to the IDIS model, as it involves Gauss hypergeometric functions. Several propositions of the LIIS model are derived: proof that the IDIS model is a particular case of the LIIS model when the maximum sequence length nmax tends to infinity, fixed point, time scale, time step and time inversion. Using a relation between the sequence length l and the evolution time t, an expression of the LIIS model as a function of the sequence length l=n(t) is obtained. Formulas for 'insertion only', i.e. when the substitution rates are all equal to 0, are derived at evolution time t and sequence length l. Analytical solutions of the LIIS model are explicitly derived, as a function of either evolution time t or sequence length l, for two classical substitution matrices: the 3-parameter symmetric substitution matrix [12] (LIIS-SYM3) and the HKY asymmetric substitution matrix[9] (LIIS-HKY). An evaluation of the LIIS model (precisely, LIIS-HKY) based on four statistical analyses of the GC content in complete genomes of four prokaryotic taxonomic groups, namely Chlamydiae, Crenarchaeota, Spirochaetes and Thermotogae, shows the expected improvement from the theory of the LIIS model compared to the IDIS model. Copyright © 2013 Elsevier Inc. All rights reserved.

Measles virus genetic evolution throughout an imported epidemic outbreak in a highly vaccinated population.

PubMed

Muñoz-Alía, Miguel Ángel; Fernández-Muñoz, Rafael; Casasnovas, José María; Porras-Mansilla, Rebeca; Serrano-Pardo, Ángela; Pagán, Israel; Ordobás, María; Ramírez, Rosa; Celma, María Luisa

2015-01-22

Measles virus circulates endemically in African and Asian large urban populations, causing outbreaks worldwide in populations with up-to-95% immune protection. We studied the natural genetic variability of genotype B3.1 in a population with 95% vaccine coverage throughout an imported six month measles outbreak. From first pass viral isolates of 47 patients we performed direct sequencing of genomic cDNA. Whilst no variation from index case sequence occurred in the Nucleocapsid gene hyper-variable carboxy end, in the Hemagglutinin gene, main target for neutralizing antibodies, we observed gradual nucleotide divergence from index case along the outbreak (0% to 0.380%, average 0.138%) with the emergence of transient and persistent non-synonymous and synonymous mutations. Little or no variation was observed between the index and last outbreak cases in Phosphoprotein, Nucleocapsid, Matrix and Fusion genes. Most of the H non-synonymous mutations were mapped on the protein surface near antigenic and receptors binding sites. We estimated a MV-Hemagglutinin nucleotide substitution rate of 7.28 × 10-6 substitutions/site/day by a Bayesian phylogenetic analysis. The dN/dS analysis did not suggest significant immune or other selective pressures on the H gene during the outbreak. These results emphasize the usefulness of MV-H sequence analysis in measles epidemiological surveillance and elimination programs, and in detection of potentially emergence of measles virus neutralization-resistant mutants. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of detergent systems on bacterial survival on laundered fabrics.

PubMed Central

Jaska, J M; Fredell, D L

1980-01-01

The survival of Staphylococcus aureus was determined from inoculated swatches laundered in either a phosphate or a phosphate-substitute detergent. In a Plackett-Burman design study, the independent variables of detergent type, concentration, and variation, wash water temperature, soil load, cycle time, and water hardness were assigned high and low values. Wash water temperatures of 27, 38, 49, and 60 degrees C were employed. Viable bacteria were recovered from macerated swatches. Statistical analysis disclosed that there was no practical difference in the ability of phosphate or phosphate-substitute detergents to reduce the level of S. aureus on the laundered swatches in this controlled design. Analysis did reveal that water temperature was the most significant independent variables. The remaining variables did not appear to have any practical significance upon bacterial reduction. This bacteriological study did not evaluate other essential detergent properties. PMID:7377775

Detecting Adaptation in Protein-Coding Genes Using a Bayesian Site-Heterogeneous Mutation-Selection Codon Substitution Model.

PubMed

Rodrigue, Nicolas; Lartillot, Nicolas

2017-01-01

Codon substitution models have traditionally attempted to uncover signatures of adaptation within protein-coding genes by contrasting the rates of synonymous and non-synonymous substitutions. Another modeling approach, known as the mutation-selection framework, attempts to explicitly account for selective patterns at the amino acid level, with some approaches allowing for heterogeneity in these patterns across codon sites. Under such a model, substitutions at a given position occur at the neutral or nearly neutral rate when they are synonymous, or when they correspond to replacements between amino acids of similar fitness; substitutions from high to low (low to high) fitness amino acids have comparatively low (high) rates. Here, we study the use of such a mutation-selection framework as a null model for the detection of adaptation. Following previous works in this direction, we include a deviation parameter that has the effect of capturing the surplus, or deficit, in non-synonymous rates, relative to what would be expected under a mutation-selection modeling framework that includes a Dirichlet process approach to account for across-codon-site variation in amino acid fitness profiles. We use simulations, along with a few real data sets, to study the behavior of the approach, and find it to have good power with a low false-positive rate. Altogether, we emphasize the potential of recent mutation-selection models in the detection of adaptation, calling for further model refinements as well as large-scale applications. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Constructing general partial differential equations using polynomial and neural networks.

PubMed

Zjavka, Ladislav; Pedrycz, Witold

2016-01-01

Sum fraction terms can approximate multi-variable functions on the basis of discrete observations, replacing a partial differential equation definition with polynomial elementary data relation descriptions. Artificial neural networks commonly transform the weighted sum of inputs to describe overall similarity relationships of trained and new testing input patterns. Differential polynomial neural networks form a new class of neural networks, which construct and solve an unknown general partial differential equation of a function of interest with selected substitution relative terms using non-linear multi-variable composite polynomials. The layers of the network generate simple and composite relative substitution terms whose convergent series combinations can describe partial dependent derivative changes of the input variables. This regression is based on trained generalized partial derivative data relations, decomposed into a multi-layer polynomial network structure. The sigmoidal function, commonly used as a nonlinear activation of artificial neurons, may transform some polynomial items together with the parameters with the aim to improve the polynomial derivative term series ability to approximate complicated periodic functions, as simple low order polynomials are not able to fully make up for the complete cycles. The similarity analysis facilitates substitutions for differential equations or can form dimensional units from data samples to describe real-world problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

New description of gradual substitution of graft by bone tissue including biomechanical and structural effects, nutrients supply and consumption

NASA Astrophysics Data System (ADS)

Lu, Yanfei; Lekszycki, Tomasz

2018-03-01

A new description of graft substitution by bone tissue is proposed in this work. The studied domain is considered as a continuum model consisting of a mixture of the bone tissue and the graft material. Densities of both components evolve in time as a result of cellular activity and biodegradation. The proposed model focuses on the interaction between the bone cell activity, mechanical stimuli, nutrients supply and scaffold microstructure. Different combinations of degradation rate and stiffness of the graft material were examined by numerical simulation. It follows from the calculations that the degradation rate of the scaffold should be tuned to the synthesis/resorption rate of the tissue, which are dependent among the others on scaffold porosity changes. Simulation results imply potential criteria to choose proper bone substitute material in consideration of degradation rate, initial porosity and mechanical characteristics.

Driving force analysis of proton tunnelling across a reactivity series for an enzyme-substrate complex.

PubMed

Hothi, Parvinder; Hay, Sam; Roujeinikova, Anna; Sutcliffe, Michael J; Lee, Michael; Leys, David; Cullis, Paul M; Scrutton, Nigel S

2008-11-24

Quantitative structure-activity relationships are widely used to probe C-H bond breakage by quinoprotein enzymes. However, we showed recently that p-substituted benzylamines are poor reactivity probes for the quinoprotein aromatic amine dehydrogenase (AADH) because of a requirement for structural change in the enzyme-substrate complex prior to C-H bond breakage. This rearrangement is partially rate limiting, which leads to deflated kinetic isotope effects for p-substituted benzylamines. Here we report reactivity (driving force) studies of AADH with p-substituted phenylethylamines for which the kinetic isotope effect (approximately 16) accompanying C-H/C-(2)H bond breakage is elevated above the semi-classical limit. We show bond breakage occurs by quantum tunnelling and that within the context of the environmentally coupled framework for H-tunnelling the presence of the p-substituent places greater demand on the apparent need for fast promoting motions. The crystal structure of AADH soaked with phenylethylamine or methoxyphenylethylamine indicates that the structural change identified with p-substituted benzylamines should not limit the reaction with p-substituted phenylethylamines. This is consistent with the elevated kinetic isotope effects measured with p-substituted phenylethylamines. We find a good correlation in the rate constant for proton transfer with bond dissociation energy for the reactive C-H bond, consistent with a rate that is limited by a Marcus-like tunnelling mechanism. As the driving force becomes larger, the rate of proton transfer increases while the Marcus activation energy becomes smaller. This is the first experimental report of the driving force perturbation of H-tunnelling in enzymes using a series of related substrates. Our study provides further support for proton tunnelling in AADH.

Higher-level phylogeny of paraneopteran insects inferred from mitochondrial genome sequences

PubMed Central

Li, Hu; Shao, Renfu; Song, Nan; Song, Fan; Jiang, Pei; Li, Zhihong; Cai, Wanzhi

2015-01-01

Mitochondrial (mt) genome data have been proven to be informative for animal phylogenetic studies but may also suffer from systematic errors, due to the effects of accelerated substitution rate and compositional heterogeneity. We analyzed the mt genomes of 25 insect species from the four paraneopteran orders, aiming to better understand how accelerated substitution rate and compositional heterogeneity affect the inferences of the higher-level phylogeny of this diverse group of hemimetabolous insects. We found substantial heterogeneity in base composition and contrasting rates in nucleotide substitution among these paraneopteran insects, which complicate the inference of higher-level phylogeny. The phylogenies inferred with concatenated sequences of mt genes using maximum likelihood and Bayesian methods and homogeneous models failed to recover Psocodea and Hemiptera as monophyletic groups but grouped, instead, the taxa that had accelerated substitution rates together, including Sternorrhyncha (a suborder of Hemiptera), Thysanoptera, Phthiraptera and Liposcelididae (a family of Psocoptera). Bayesian inference with nucleotide sequences and heterogeneous models (CAT and CAT + GTR), however, recovered Psocodea, Thysanoptera and Hemiptera each as a monophyletic group. Within Psocodea, Liposcelididae is more closely related to Phthiraptera than to other species of Psocoptera. Furthermore, Thysanoptera was recovered as the sister group to Hemiptera. PMID:25704094

The Repeat Sequences and Elevated Substitution Rates of the Chloroplast accD Gene in Cupressophytes

PubMed Central

Li, Jia; Su, Yingjuan; Wang, Ting

2018-01-01

The plastid accD gene encodes a subunit of the acetyl-CoA carboxylase (ACCase) enzyme. The length of accD gene has been supposed to expand in Cryptomeria japonica, Taiwania cryptomerioides, Cephalotaxus, Taxus chinensis, and Podocarpus lambertii, and the main reason for this phenomenon was the existence of tandemly repeated sequences. However, it is still unknown whether the accD gene length in other cupressophytes has expanded. Here, in order to investigate how widespread this phenomenon was, 18 accD sequences and its surrounding regions of cupressophyte were sequenced and analyzed. Together with 39 GenBank sequence data, our taxon sampling covered all the extant gymnosperm orders. The repetitive elements and substitution rates of accD among 57 gymnosperm species were analyzed, the results show: (1) Reading frame length of accD gene in 18 cupressophytes species has also expanded. (2) Many repetitive elements were identified in accD gene of cupressophyte lineages. (3) The synonymous and non-synonymous substitution rates of accD were accelerated in cupressophytes. (4) accD was located in rearrangement endpoints. These results suggested that repetitive elements may mediate the chloroplast genome rearrangement and accelerated the substitution rates. PMID:29731764

Sensory evaluation ratings and melting characteristics show that okra gum is an acceptable milk-fat ingredient substitute in chocolate frozen dairy dessert.

PubMed

Romanchik-Cerpovicz, Joelle E; Costantino, Amanda C; Gunn, Laura H

2006-04-01

Reducing dietary fat intake may lower the risk of developing coronary heart disease. This study examined the feasibility of substituting okra gum for 25%, 50%, 75%, or 100% milk fat in frozen chocolate dairy dessert. Fifty-six consumers evaluated the frozen dairy desserts using a hedonic scale. Consumers rated color, smell, texture, flavor, aftertaste, and overall acceptability characteristics of all products as acceptable. All ratings were similar among the products except for the aftertaste rating, which was significantly lower for chocolate frozen dairy dessert containing 100% milk-fat replacement with okra gum compared with the control (0% milk-fat replacement) (P<0.05). Whereas melting points of all products were similar, melting rates slowed significantly as milk-fat replacement with okra gum increased, suggesting that okra gum may increase the stability of frozen dairy desserts (P<0.05). Overall, this study shows that okra gum is an acceptable milk-fat ingredient substitute in chocolate frozen dairy dessert.

Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

PubMed

O'Leary, A; Usher, C; Lynch, M; Hall, M; Hemeryk, L; Spillane, S; Gallagher, P; Barry, M

2015-12-15

The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84% of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74% of prescribers and 84% of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines.

Synthesis and Late-Stage Functionalization of Complex Molecules through C–H Fluorination and Nucleophilic Aromatic Substitution

PubMed Central

2015-01-01

We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (SNAr) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals. PMID:24918484

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.

Thermodynamics of axial substitution and kinetics of reactions with amino acids for the paddlewheel complex tetrakis(acetato)chloridodiruthenium(II,III).

PubMed

Santos, Rodrigo L S R; van Eldik, Rudi; de Oliveira Silva, Denise

2012-06-18

The known paddlewheel, tetrakis(acetato)chloridodiruthenium(II,III), offers a versatile synthetic route to a novel class of antitumor diruthenium(II,III) metallo drugs, where the equatorial ligands are nonsteroidal anti-inflammatory carboxylates. This complex was studied here as a soluble starting prototype model for antitumor analogues to elucidate the reactivity of the [Ru(2)(CH(3)COO)(4)](+) framework. Thermodynamic studies on equilibration reactions for axial substitution of water by chloride and kinetic studies on reactions of the diaqua complexes with the amino acids glycine, cysteine, histidine, and tryptophan were performed. The standard thermodynamic reaction parameters ΔH°, ΔS°, and ΔV° were determined and showed that both of the sequential axial substitution reactions are enthalpy driven. Kinetic rate laws and rate constants were determined for the axial substitution reactions of coordinated water by the amino acids that gave the corresponding aqua(amino acid)-Ru(2) substituted species. The results revealed that the [Ru(2)(CH(3)COO)(4)](+) paddlewheel framework remained stable during the axial ligand substitution reactions and was also mostly preserved in the presence of the amino acids.

Dural Repair in Cranial Surgery Is Associated with Moderate Rates of Complications with Both Autologous and Nonautologous Dural Substitutes.

PubMed

Azzam, Daniel; Romiyo, Prasanth; Nguyen, Thien; Sheppard, John P; Alkhalid, Yasmine; Lagman, Carlito; Prashant, Giyarpuram N; Yang, Isaac

2018-05-01

Duraplasty, a common neurosurgical intervention, involves synthetic or biological graft placement to ensure dural closure. The objective of this study is to advance our understanding of the use of dural substitutes in cranial surgery. The PubMed database was systematically searched to identify studies published over the past decade (2007-2017) that described duraplasty procedures. Clinical data were disaggregated and analyzed for the comparisons of biological versus synthetic grafts. A total of 462 cases were included in the quantitative synthesis. Overall, the most common indication for duraplasty was tumor resection (53%). Allografts were more frequently used in decompression for Chiari malformations compared with xenografts and synthetic grafts (P < 0.001). Xenografts were more frequently used in decompressive hemicraniectomy procedures for evacuation of acute subdural hematomas over allografts and synthetics (P < 0.001). Synthetic grafts were more frequently used in tumor cases than biological grafts (P = 0.002). The cumulative complication rate for dural substitutes of all types was 11%. There were no significant differences in complication rates among the 3 types of dural substitutes. Dural substitutes are commonly used to ensure dural closure in a variety of cranial procedures. This study provides greater insight into duraplasty practices and highlights the moderate complication rate associated with the procedure. Future studies are needed to determine the safety and efficacy of such procedures in larger prospective cohorts. Copyright © 2018. Published by Elsevier Inc.

Autonomic nervous system function in chronic exogenous subclinical thyrotoxicosis and the effect of restoring euthyroidism.

PubMed

Eustatia-Rutten, Carmen F A; Corssmit, Eleonora P M; Heemstra, Karen A; Smit, Johannes W A; Schoemaker, Rik C; Romijn, Johannes A; Burggraaf, Jacobus

2008-07-01

Knowledge on the relationship between the autonomic nervous system and subclinical hyperthyroidism is mainly based upon cross-sectional studies in heterogeneous patient populations, and the effect of restoration to euthyroidism in subclinical hyperthyroidism has not been studied. We investigated the long-term effects of exogenous subclinical hyperthyroidism on the autonomic nervous system and the potential effects of restoration of euthyroidism. This was a prospective single-blinded, placebo-controlled, randomized trial. The study was performed at a university hospital. A total of 25 patients who were on more than 10-yr TSH suppressive therapy after thyroidectomy was examined. Patients were studied at baseline and subsequently randomized to a 6-month thyroid hormone substitution regimen to obtain either euthyroidism or maintenance of the subclinical hyperthyroid state. Urinary excretion of catecholamines and heart rate variability were measured. Baseline data of the subclinical hyperthyroidism patients were compared with data obtained in patients with hyperthyroidism and controls. Urinary excretion of norepinephrine and vanillylmandelic acid was higher in the subclinical hyperthyroidism patients compared with controls and lower compared with patients with overt hyperthyroidism. Heart rate variability was lower in patients with hyperthyroidism, intermediate in subclinical hyperthyroidism patients, and highest in the healthy controls. No differences were observed after restoration of euthyroidism. Long-term exogenous subclinical hyperthyroidism has effects on the autonomic nervous system measured by heart rate variability and urinary catecholamine excretion. No differences were observed after restoration to euthyroidism. This may indicate the occurrence of irreversible changes or adaptation during long-term exposure to excess thyroid hormone that is not remedied by 6-month euthyroidism.

Space-for-Time Substitution Works in Everglades Ecological Forecasting Models

PubMed Central

Banet, Amanda I.; Trexler, Joel C.

2013-01-01

Space-for-time substitution is often used in predictive models because long-term time-series data are not available. Critics of this method suggest factors other than the target driver may affect ecosystem response and could vary spatially, producing misleading results. Monitoring data from the Florida Everglades were used to test whether spatial data can be substituted for temporal data in forecasting models. Spatial models that predicted bluefin killifish (Lucania goodei) population response to a drying event performed comparably and sometimes better than temporal models. Models worked best when results were not extrapolated beyond the range of variation encompassed by the original dataset. These results were compared to other studies to determine whether ecosystem features influence whether space-for-time substitution is feasible. Taken in the context of other studies, these results suggest space-for-time substitution may work best in ecosystems with low beta-diversity, high connectivity between sites, and small lag in organismal response to the driver variable. PMID:24278368

Anthropogenic areas as incidental substitutes for original habitat.

PubMed

Martínez-Abraín, Alejandro; Jiménez, Juan

2016-06-01

One speaks of ecological substitutes when an introduced species performs, to some extent, the ecosystem function of an extirpated native species. We suggest that a similar case exists for habitats. Species evolve within ecosystems, but habitats can be destroyed or modified by natural and human-made causes. Sometimes habitat alteration forces animals to move to or remain in a suboptimal habitat type. In that case, the habitat is considered a refuge, and the species is called a refugee. Typically refugee species have lower population growth rates than in their original habitats. Human action may lead to the unintended generation of artificial or semiartificial habitat types that functionally resemble the essential features of the original habitat and thus allow a population growth rate of the same magnitude or higher than in the original habitat. We call such areas substitution habitats and define them as human-made habitats within the focal species range that by chance are partial substitutes for the species' original habitat. We call species occupying a substitution habitat adopted species. These are 2 new terms in conservation biology. Examples of substitution habitats are dams for European otters, wheat and rice fields for many steppeland and aquatic birds, and urban areas for storks, falcons, and swifts. Although substitution habitats can bring about increased resilience against the agents of global change, the conservation of original habitat types remains a conservation priority. © 2016 Society for Conservation Biology.

Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity

PubMed Central

Zhang, Jin; Ruhlman, Tracey A.; Sabir, Jamal S. M.; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K.

2016-01-01

Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear–plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. PMID:26893456

Mechanisms of Exchange Reactions of Primary and Secondary Alkyl Iodides with Elementary Iodine

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

Bujake, John E.; Pratt, M. W. T.; Noyes, Richard M.

1961-04-01

Several primary and secondary alkyl iodides exchange thermally with I/ sup 131/ in hexachlorobutadiene between 130 and 200 deg . If the solutions are saturated with oxygen at one atmosphere, rates of exchange fit the kinetic expression k/sub b/STARI! STAl/sub 2/!1/2. Degassed solutions always exchange faster than oxygen saturated ones, but methyl, ethyl, and n-propyl iodides show the same kinetics as with oxygen. Exchange rates of degassed isopropyl and neopentyl iodides also show contributions from a k/sub a/STARI! term. Exchange in degassed ethylene dichloride is 3 to 4 times as fast as in degassed hexachlorobutadiene. Activation energies for k/sub b/more » are usually about 27 to 31 kcal/mole. Effects of substitution on alpha carbon are illustrated by the rate sequence methyl < ethyl < i-propyl = sec-butyl. Effects of substitution on beta carbon are illustrated by the rate sequence ethyl < npropyl>> neopentyl. Since the rates of exchange of methyl, ethyl, and i-propyl iodides vary in the opposite direction from the sequence for bimolecular nucleophilic substitution, the explanation proposed suggests that for nucleophilic substitution the effect of added methyl groups on an alpha carbon is a steric hindrance to solvation by solvent dipoles rather than a steric hindrance to the group attacking the carbon atom itself.« less

Algebraic solution for the forward displacement analysis of the general 6-6 stewart mechanism

NASA Astrophysics Data System (ADS)

Wei, Feng; Wei, Shimin; Zhang, Ying; Liao, Qizheng

2016-01-01

The solution for the forward displacement analysis(FDA) of the general 6-6 Stewart mechanism(i.e., the connection points of the moving and fixed platforms are not restricted to lying in a plane) has been extensively studied, but the efficiency of the solution remains to be effectively addressed. To this end, an algebraic elimination method is proposed for the FDA of the general 6-6 Stewart mechanism. The kinematic constraint equations are built using conformal geometric algebra(CGA). The kinematic constraint equations are transformed by a substitution of variables into seven equations with seven unknown variables. According to the characteristic of anti-symmetric matrices, the aforementioned seven equations can be further transformed into seven equations with four unknown variables by a substitution of variables using the Gröbner basis. Its elimination weight is increased through changing the degree of one variable, and sixteen equations with four unknown variables can be obtained using the Gröbner basis. A 40th-degree univariate polynomial equation is derived by constructing a relatively small-sized 9´9 Sylvester resultant matrix. Finally, two numerical examples are employed to verify the proposed method. The results indicate that the proposed method can effectively improve the efficiency of solution and reduce the computational burden because of the small-sized resultant matrix.

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

Evidence for adaptive evolution of low-temperature stress response genes in a Pooideae grass ancestor.

PubMed

Vigeland, Magnus D; Spannagl, Manuel; Asp, Torben; Paina, Cristiana; Rudi, Heidi; Rognli, Odd-Arne; Fjellheim, Siri; Sandve, Simen R

2013-09-01

Adaptation to temperate environments is common in the grass subfamily Pooideae, suggesting an ancestral origin of cold climate adaptation. Here, we investigated substitution rates of genes involved in low-temperature-induced (LTI) stress responses to test the hypothesis that adaptive molecular evolution of LTI pathway genes was important for Pooideae evolution. Substitution rates and signatures of positive selection were analyzed using 4330 gene trees including three warm climate-adapted species (maize (Zea mays), sorghum (Sorghum bicolor), and rice (Oryza sativa)) and five temperate Pooideae species (Brachypodium distachyon, wheat (Triticum aestivum), barley (Hordeum vulgare), Lolium perenne and Festuca pratensis). Nonsynonymous substitution rate differences between Pooideae and warm habitat-adapted species were elevated in LTI trees compared with all trees. Furthermore, signatures of positive selection were significantly stronger in LTI trees after the rice and Pooideae split but before the Brachypodium divergence (P < 0.05). Genome-wide heterogeneity in substitution rates was also observed, reflecting divergent genome evolution processes within these grasses. Our results provide evidence for a link between adaptation to cold habitats and adaptive evolution of LTI stress responses in early Pooideae evolution and shed light on a poorly understood chapter in the evolutionary history of some of the world's most important temperate crops. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Imitation of contrastive lexical stress in children with speech delay

NASA Astrophysics Data System (ADS)

Vick, Jennell C.; Moore, Christopher A.

2005-09-01

This study examined the relationship between acoustic correlates of stress in trochaic (strong-weak), spondaic (strong-strong), and iambic (weak-strong) nonword bisyllables produced by children (30-50) with normal speech acquisition and children with speech delay. Ratios comparing the acoustic measures (vowel duration, rms, and f0) of the first syllable to the second syllable were calculated to evaluate the extent to which each phonetic parameter was used to mark stress. In addition, a calculation of the variability of jaw movement in each bisyllable was made. Finally, perceptual judgments of accuracy of stress production were made. Analysis of perceptual judgments indicated a robust difference between groups: While both groups of children produced errors in imitating the contrastive lexical stress models (~40%), the children with normal speech acquisition tended to produce trochaic forms in substitution for other stress types, whereas children with speech delay showed no preference for trochees. The relationship between segmental acoustic parameters, kinematic variability, and the ratings of stress by trained listeners will be presented.

Marginal Bone Loss in Implants Placed in the Maxillary Sinus Grafted With Anorganic Bovine Bone: A Prospective Clinical and Radiographic Study.

PubMed

Dinato, Thiago R; Grossi, Márcio L; Teixeira, Eduardo R; Dinato, José C; Sczepanik, Fábio S C; Gehrke, Sergio A

2016-08-01

Sinus elevation is a reliable and often-used technique. Success of implants placed in such situations, even with bone substitutes alone, prompted the authors of this study to strive for bone loss close to zero and research variables that cause higher or lower rates of resorption. The objective of this study is to evaluate survival rates and marginal bone loss (MBL) around implants placed in sites treated with maxillary sinus augmentation using anorganic bovine bone (ABB), and identify surgical and prosthetic prognostic variables. Fifty-five implants were placed in 30 grafted maxillary sinuses in 24 patients. Periapical radiographs were evaluated immediately after implant placement (baseline), 6 months, and at the most recent follow-up. MBL was calculated from the difference between initial and final measurements, taking into account a distortion rate for each radiograph compared with original implant measurements. Survival rate was 98.2%, with only one implant lost (100% survival rate after loading) over a mean follow-up time of 2.0 ± 0.9 years. MBL ranged from 0 to 2.85 mm: 75.9% of mesial sites and 83.4% of distal sites showed <1 mm of MBL, whereas 35.2% of mesial sites and 37% of distal sites exhibited no bone loss. MBL was significantly (P <0.05) greater in open-flap compared with flapless surgery. Within the limitations of the present study, it was concluded that maxillary sinus elevation with 100% ABB gives predictable results, and that flapless surgery results in less MBL compared with traditional open-flap surgery.

State generic substitution laws can lower drug outlays under medicaid

PubMed Central

Choudhry, Niteesh K.; Agnew-Blais, Jessica; Federman, Alex D.; Liberman, Joshua N.; Liu, Jun; Kesselheim, Aaron S.; Brookhart, M. Alan; Fischer, Michael A.

2011-01-01

To stem the rising costs of medications, states have implemented varying generic substitution policies. These policies differ in the extent to which pharmacists or patients can influence medication choice. Using national Medicaid data, we evaluated the relationship between different generic substitution policies and generic simvastatin use after patent expiration of branded Zocor. States implementing policies that require patient consent prior to generic substitution experienced 25% lower rates of generic substitution. By eliminating patient consent requirements, state Medicaid programs could expect to save over $100 million dollars in coverage for 3 top-selling medications nearing patent expiration. The implications of these regulations on national medication spending should be considered. PMID:20606192

Solvolysis of para-substituted cumyl chlorides. Brown and Okamoto's electrophilic substituent constants revisited using continuum solvent models.

PubMed

DiLabio, Gino A; Ingold, K U

2004-03-05

Brown and Okamoto (J. Am. Chem. Soc. 1958, 80, 4979) derived their electrophilic substitutent constants, sigma(p)+, from the relative rates of solvolysis of ring-substituted cumyl chlorides in an acetone/water solvent mixture. Application of the Hammett equation to the rates for the meta-substituted cumyl chlorides, where there could be no resonance interaction with the developing carbocation, gave a slope, rho(+) = -4.54 ( identical with 6.2 kcal/mol free energy). Rates for the para-substituted chlorides were then used to obtain sigma(p)+ values. We have calculated gas-phase C-Cl heterolytic bond dissociation enthalpy differences, Delta BDE(het) (= BDE(het)(4-YC(6)H(4)CMe(2)Cl) - BDE(het)(C(6)H(5)CMe(2)Cl)), for 16 of the 4-Y substituents employed by Brown and Okamoto. The plot of Delta BDE(het) vs sigma(p)+ gave rho(+) (SD) = 16.3 (2.3) kcal/mol, i.e., a rho(+) value roughly 2.5 times greater than experiment. Inclusion of solvation (water) energies, calculated using three continuum solvent models, reduced rho(+) and SD. The computationally least expensive model used, SM5.42R (Li et al. Theor. Chem. Acc. 1999, 103, 9) gave the best agreement with experiment. This model yielded rho(+) (SD) = 7.7 (0.9) kcal/mol, i.e., a rho(+) value that is only 24% larger than experiment.

Effects of saliva substitutes on oral status in patients with Type 2 diabetes.

PubMed

Montaldo, L; Montaldo, P; Papa, A; Caramico, N; Toro, G

2010-11-01

To assess oral status in a sample of Type 2 diabetic patients before and after therapy with saliva substitutes and oral status in a control group of diabetic patients who were not given saliva substitutes. Salivary flow rate was determined in 134 patients (mean age 47.9 ± 2.9 years) with Type 2 diabetes. Mean salivary rate was significantly low compared with a healthy control group. The sample of 134 patients was randomly divided into two groups of 67 people each. One group was given immunologically active salivary substitutes for 6 months, the other group was given nothing. Each patient of the two groups underwent a dental and periodontal examination at the beginning of the study and 6 months later. As regards carious teeth and teeth loss, there was no statistical difference between the first group after 6 months of treatment with salivary substitutes and the control group (P>0.01). Salivary substitutes did not significantly reduce the periodontal disease (P>0.01). In the group treated with salivary substitutes, after 6 months of therapy, the average dental plaque index decreased from 2.3 ± 0.73 to 1.6 ± 0.56, patients with gingivitis decreased from 66 to 43% and patients with positive yeast counts decreased from 60 to 37%. These differences were statistically significant (P<0.01). In Type 2 diabetes, in the case of hyposalivation, a therapy with immunologically active saliva substitutes can be of help in reducing the amount of plaque, gingivitis and positive yeast counts. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.

Sequence analysis of the GP, NP, VP40 and VP24 genes of Ebola virus isolated from deceased, surviving and asymptomatically infected individuals during the 1996 outbreak in Gabon: comparative studies and phylogenetic characterization.

PubMed

Leroy, Eric M; Baize, Sylvain; Mavoungou, Elie; Apetrei, Cristian

2002-01-01

The aims of this study were to determine if the clinical outcome of Ebola virus (EBOV) infection is associated with virus genetic structure and to document the genetic changes in the Gabon strains of EBOV by sequencing the GP, NP, VP40 and VP24 genes from deceased and surviving symptomatic and asymptomatic individuals. GP and NP sequences were identical in the three groups of patients and only one silent substitution occurred in the VP40 and VP24 genes in asymptomatic individuals. A strain from an asymptomatic individual had a reverse substitution to the Gabon-94 sequence, indicating that minor virus variants may cocirculate during an outbreak. These results suggest that the different clinical outcomes of EBOV infection do not result from virus mutations. Phylogenetic analysis confirmed that Gabon-96 belonged to the Zaire subtype of EBOV and revealed that synonymous substitution rates were higher than nonsynonymous substitution rates in the GP, VP40 and VP24 genes. In contrast, nonsynonymous substitutions predominated over synonymous substitutions in the NP gene of the two Gabon strains, pointing to divergent evolution of these strains and to selective pressures on this gene.

Photoswitchable carbohydrate-based fluorosurfactants as tuneable ice recrystallization inhibitors.

PubMed

Adam, Madeleine K; Hu, Yingxue; Poisson, Jessica S; Pottage, Matthew J; Ben, Robert N; Wilkinson, Brendan L

2017-02-01

Cryopreservation is an important technique employed for the storage and preservation of biological tissues and cells. The limited effectiveness and significant toxicity of conventionally-used cryoprotectants, such as DMSO, have prompted efforts toward the rational design of less toxic alternatives, including carbohydrate-based surfactants. In this paper, we report the modular synthesis and ice recrystallization inhibition (IRI) activity of a library of variably substituted, carbohydrate-based fluorosurfactants. Carbohydrate-based fluorosurfactants possessed a variable mono- or disaccharide head group appended to a hydrophobic fluoroalkyl-substituted azobenzene tail group. Light-addressable fluorosurfactants displayed weak-to-moderate IRI activity that could be tuned through selection of carbohydrate head group, position of the trifluoroalkyl group on the azobenzene ring, and isomeric state of the azobenzene tail fragment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in Ultrasonic Velocity from Fluid Substitution, Calculated with Laboratory Methods, Digital Rock Physics, and Biot Theory

NASA Astrophysics Data System (ADS)

Goldfarb, E. J.; Ikeda, K.; Tisato, N.

2017-12-01

Seismic and ultrasonic velocities of rocks are function of several variables including fluid saturation and type. Understanding the effect of each variable on elastic waves can be valuable when using seismic methods for subsurface modeling. Fluid type and saturation are of specific interest to volcanology, water, and hydrocarbon exploration. Laboratory testing is often employed to understand the effects of fluids on elastic waves. However, laboratory testing is expensive and time consuming. It normally requires cutting rare samples into regular shapes. Fluid injection can also destroy specimens as removing the fluid after testing can prove difficult. Another option is theoretical modeling, which can be used to predict the effect of fluids on elastic properties, but it is often inaccurate. Alternatively, digital rock physics (DRP) can be used to investigate the effect of fluid substitution. DRP has the benefit of being non invasive, as it does not require regular sample shapes or fluid injection. Here, we compare the three methods for dry and saturated Berea sandstone to test the reliability of DRP. First, ultrasonic velocities were obtained from laboratory testing. Second, for comparison, we used a purely theoretical approach - i.e., Hashin-Shtrikman and Biot theory - to estimate the wave speeds at dry and wet conditions. Third, we used DRP. The dry sample was scanned with micro Computed Tomography (µCT), and a three dimensional (3D) array was recorded. We employed a segmentation-less method to convert each 3D array value to density, porosity, elastic moduli, and wave speeds. Wave propagation was simulated numerically at similar frequency as the laboratory. To simulate fluid substitution, we numerically substituted air values for water and repeated the simulation. The results from DRP yielded similar velocities to the laboratory, and accurately predicted the velocity change from fluid substitution. Theoretical modeling could not accurately predict velocity, and under-predicted the velocity change from fluid substitution. The mathematical approach proved to be a poor comparison for the laboratory measurement. DRP proved to be effective, and could be used in future with drill cuttings, perhaps to limit the use of expensive cores. DRP could also limit the requirement for physically testing fluid substitution.

Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling.

PubMed

Vrancken, Bram; Suchard, Marc A; Lemey, Philippe

2017-07-01

Analyses of virus evolution in known transmission chains have the potential to elucidate the impact of transmission dynamics on the viral evolutionary rate and its difference within and between hosts. Lin et al. (2015, Journal of Virology , 89/7: 3512-22) recently investigated the evolutionary history of hepatitis B virus in a transmission chain and postulated that the 'colonization-adaptation-transmission' model can explain the differential impact of transmission on synonymous and non-synonymous substitution rates. Here, we revisit this dataset using a full probabilistic Bayesian phylogenetic framework that adequately accounts for the non-independence of sequence data when estimating evolutionary parameters. Examination of the transmission chain data under a flexible coalescent prior reveals a general inconsistency between the estimated timings and clustering patterns and the known transmission history, highlighting the need to incorporate host transmission information in the analysis. Using an explicit genealogical transmission chain model, we find strong support for a transmission-associated decrease of the overall evolutionary rate. However, in contrast to the initially reported larger transmission effect on non-synonymous substitution rate, we find a similar decrease in both non-synonymous and synonymous substitution rates that cannot be adequately explained by the colonization-adaptation-transmission model. An alternative explanation may involve a transmission/establishment advantage of hepatitis B virus variants that have accumulated fewer within-host substitutions, perhaps by spending more time in the covalently closed circular DNA state between each round of viral replication. More generally, this study illustrates that ignoring phylogenetic relationships can lead to misleading evolutionary estimates.

First quadruple-glycine bridging mono-lanthanide-substituted borotungstate hybrids.

PubMed

Liu, Jiancai; Yu, Jing; Han, Qing; Wen, Yue; Chen, Lijuan; Zhao, Junwei

2016-10-18

A class of novel organic-inorganic hybrid lanthanide (Ln)-substituted Keggin-type borotungstates K 4 Na 4 H 4 [Ln 2 (gly) 4 (α-BW 11 O 39 ) 2 ]·23H 2 O [Ln = Ce 3+ (1), Pr 3+ (2), Nd 3+ (3), Sm 3+ (4), Eu 3+ (5), Tm 3+ (6); gly = glycine] have been synthesized from the reaction of K 8 [BW 11 O 39 H]·13H 2 O, NaAc·6H 2 O and Ln(NO 3 ) 3 ·6H 2 O by employing gly ligands as structure-stabilizing agents in the conventional aqueous solution system and structurally characterized by elemental analyses, IR spectroscopy, thermogravimetric (TG) analyses, powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction. The common prominent structural feature of isomorphic 1-6 is that all of them consist of two mono-Ln-substituted Keggin [Ln(α-BW 11 O 39 )] 6- fragments linked by four gly ligands, furnishing an intriguing dimeric assembly of the quadruple-gly-connective mono-Ln-substituted borotungstate, in which each carboxylic oxygen atom from gly ligands is bound to Ln 3+ cations in the μ 2 -O or μ 3 -O mode. To the best of our knowledge, 1-6 represent the first examples of inorganic-organic hybrid Ln-substituted borotungstates functionalized by quadruple amino acid bridges. The solid-state photoluminescence properties of 3-5 have been determined at ambient temperature and the photoluminescence emission spectra exhibit the characteristic emission bands derived from Ln 3+ centers. The thermostability of 1-6 has been studied and the thermal decomposition procedure of 3 has been comprehensively investigated with the assistance of variable-temperature PXRD patterns and variable-temperature IR spectra. Furthermore, magnetic susceptibility measurements of 1, 2 and 4 have been conducted.

Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity.

PubMed

Zhang, Jin; Ruhlman, Tracey A; Sabir, Jamal S M; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K

2016-02-17

Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear-plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Variation in the molecular clock of primates.

PubMed

Moorjani, Priya; Amorim, Carlos Eduardo G; Arndt, Peter F; Przeworski, Molly

2016-09-20

Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.

Oral substitution treatment of injecting opioid users for prevention of HIV infection.

PubMed

Gowing, Linda; Farrell, Michael F; Bornemann, Reinhard; Sullivan, Lynn E; Ali, Robert

2011-08-10

Injecting drug users are vulnerable to infection with Human Immunodeficiency Virus (HIV) and other blood borne viruses as a result of collective use of injecting equipment as well as sexual behaviour To assess the effect of oral substitution treatment for opioid dependent injecting drug users on risk behaviours and rates of HIV infections We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO to May 2011. We also searched reference lists of articles, reviews and conference abstracts Studies were required to consider the incidence of risk behaviours, or the incidence of HIV infection related to substitution treatment of opioid dependence. All types of original studies were considered. Two authors independently assessed each study for inclusion Two authors independently extracted key information from each of the included studies. Any differences were resolved by discussion or by referral to a third author. Thirty-eight studies, involving some 12,400 participants, were included. The majority were descriptive studies, or randomisation processes did not relate to the data extracted, and most studies were judged to be at high risk of bias. Studies consistently show that oral substitution treatment for opioid-dependent injecting drug users with methadone or buprenorphine is associated with statistically significant reductions in illicit opioid use, injecting use and sharing of injecting equipment. It is also associated with reductions in the proportion of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but has little effect on condom use. It appears that the reductions in risk behaviours related to drug use do translate into reductions in cases of HIV infection. However, because of the high risk of bias and variability in several aspects of the studies, combined totals were not calculated. Oral substitution treatment for injecting opioid users reduces drug-related behaviours with a high risk of HIV transmission, but has less effect on sex-related risk behaviours. The lack of data from randomised controlled studies limits the strength of the evidence presented in this review.

Slow but not low: genomic comparisons reveal slower evolutionary rate and higher dN/dS in conifers compared to angiosperms.

PubMed

Buschiazzo, Emmanuel; Ritland, Carol; Bohlmann, Jörg; Ritland, Kermit

2012-01-20

Comparative genomics can inform us about the processes of mutation and selection across diverse taxa. Among seed plants, gymnosperms have been lacking in genomic comparisons. Recent EST and full-length cDNA collections for two conifers, Sitka spruce (Picea sitchensis) and loblolly pine (Pinus taeda), together with full genome sequences for two angiosperms, Arabidopsis thaliana and poplar (Populus trichocarpa), offer an opportunity to infer the evolutionary processes underlying thousands of orthologous protein-coding genes in gymnosperms compared with an angiosperm orthologue set. Based upon pairwise comparisons of 3,723 spruce and pine orthologues, we found an average synonymous genetic distance (dS) of 0.191, and an average dN/dS ratio of 0.314. Using a fossil-established divergence time of 140 million years between spruce and pine, we extrapolated a nucleotide substitution rate of 0.68 × 10(-9) synonymous substitutions per site per year. When compared to angiosperms, this indicates a dramatically slower rate of nucleotide substitution rates in conifers: on average 15-fold. Coincidentally, we found a three-fold higher dN/dS for the spruce-pine lineage compared to the poplar-Arabidopsis lineage. This joint occurrence of a slower evolutionary rate in conifers with higher dN/dS, and possibly positive selection, showcases the uniqueness of conifer genome evolution. Our results are in line with documented reduced nucleotide diversity, conservative genome evolution and low rates of diversification in conifers on the one hand and numerous examples of local adaptation in conifers on the other hand. We propose that reduced levels of nucleotide mutation in large and long-lived conifer trees, coupled with large effective population size, were the main factors leading to slow substitution rates but retention of beneficial mutations.

Substitutions of dairy product intake and risk of stroke: a Danish cohort study.

PubMed

Laursen, Anne Sofie Dam; Dahm, Christina Catherine; Johnsen, Søren Paaske; Tjønneland, Anne; Overvad, Kim; Jakobsen, Marianne Uhre

2018-02-01

Low fat dairy products are part of dietary guidelines to prevent stroke. However, epidemiological evidence is inconclusive with regard to the association between dairy products and stroke. We therefore investigated associations for substitutions between dairy product subgroups and risk of total stroke and stroke subtypes. We included 55,211 Danish men and women aged 50-64 years without previous stroke. Baseline diet was assessed by a food frequency questionnaire. Cases were identified through a national register and subsequently verified. The associations were analyzed using Cox proportional hazard regression. During a median follow-up of 13.4 years, we identified 2272 strokes, of which 1870 were ischemic (318 large artery atherosclerotic, 839 lacunar, 102 cardioembolic, 98 other determined types, 513 of unknown type), 389 were hemorrhages (273 intracerebral, 116 subarachnoid) and 13 of unknown etiology. Substitution of semi-skimmed fermented milk or cheese for whole-fat fermented milk was associated with a higher rate of ischemic stroke [semi-skimmed fermented milk: hazard ratio (HR) = 1.20 (95% confidence interval (CI) 0.99-1.45), cheese: HR = 1.14 (95% CI 0.98-1.31) per serving/day substituted] and substitutions of whole-fat fermented milk for low-fat milk, whole-fat milk or buttermilk were associated with a lower rate [low-fat milk: HR = 0.85 (95% CI 0.74-0.99), whole-fat milk: HR = 0.84 (95% CI 0.71-0.98) and buttermilk: HR = 0.83 (95% CI 0.70-0.99)]. We observed no associations for substitutions between dairy products and hemorrhagic stroke. Our results suggest that intake of whole-fat fermented milk as a substitution for semi-skimmed fermented milk, cheese, buttermilk or milk, regardless of fat content, is associated with a lower rate of ischemic stroke.

A case study in generic drug use: should there be risk adjustment in incentive payments for the use of generic medications?

PubMed

Walton, Surrey M; Rash, Christine; Lambert, Bruce L; Galanter, William L

2014-11-01

Encouraging generic drug use has reduced health care costs for payers and consumers, but the availability of therapeutically interchangeable medications or generic medications of choice is not equal across disease states. The extent to which systems of care are able to substitute with generics is not well understood.  To (a) define and measure the maximum generic rate (MGR) of currently prescribed drugs within an academic medical group in and (b) illustrate differences across drugs associated with selected underlying diseases.   Prescription claims data were examined from an academic medical group in Chicago, Illinois. Based on pharmacologic and therapeutic criteria, drugs were classified into 2 categories-potentially substitutable and not potentially substitutable-based on whether the drugs are branded forms of the same chemical entities that are available as generics or are therapeutically interchangeable with other medications that have different chemical compositions but the same mechanisms of action and potential efficacy. A medication was considered potentially substitutable if it (a) did not have a narrow therapeutic index as defined by the FDA; (b) did not belong to 1 of 6 protected classes of drugs in the Medicare D provisions; (c) was substitutable with a generic medication containing the same chemical entity; or (d) was therapeutically interchangeable with a therapeutically equivalent medication. MGR was defined as the percentage of prescriptions that could potentially be prescribed in generic form. This rate was examined overall and across drugs known to be associated with illustrative diseases including hypertension, diabetes mellitus, and obstructive lung diseases.   The MGR ranged from 100% for drugs used in hypertension to 26.7% for drugs used in obstructive lung diseases. The MGR was 83.6%.  Payers wishing to promote generic substitution should incorporate the potential for substitution of clinically appropriate generic medications as part of incentives for generic utilization to avoid unintended consequences of using a fixed target rate. A practical methodology for determining an MGR is offered.

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.

A Chemically Defined Medium for Rabbit Embryo Cryopreservation

PubMed Central

Bruyère, Pierre; Baudot, Anne; Joly, Thierry; Commin, Loris; Pillet, Elodie; Guérin, Pierre; Louis, Gérard; Josson-Schramme, Anne; Buff, Samuel

2013-01-01

This study evaluates a new synthetic substitute (CRYO3, Ref. 5617, Stem Alpha, France) for animal-based products in rabbit embryo cryopreservation solutions. This evaluation was performed using two approaches: a thermodynamic approach using differential scanning calorimetry and a biological approach using rabbit embryo slow-freezing. During the experiment, foetal calf serum (FCS) was used as a reference. Because FCS varies widely by supplier, three different FCS were selected for the thermodynamic approach. The rabbit embryo slow-freezing solutions were made from Dulbecco's phosphate buffer saline containing 1.5 M Dimethyl Sulfoxide and 18% (v.v−1) of CRYO3 or 18% (v.v−1) of FCS. These solutions were evaluated using four characteristics: the end of melting temperature, the enthalpy of crystallisation (thermodynamic approach) and the embryo survival rates after culture and embryo transfer (biological approach). In the thermodynamic approach, the solutions containing one of the three different FCS had similar mean thermodynamic characteristics but had different variabilities in the overall data with aberrant values. The solution containing CRYO3 had similar thermodynamic properties when compared to those containing FCS. Moreover, no aberrant value was measured in the solution containing CRYO3. This solution appears to be more stable than the solutions containing a FCS. In the biological approach, the in vitro embryo survival rates obtained with the solution containing CRYO3 (73.7% and 81.3%) and with the solution containing a FCS (77.6% and 71.9%) were similar (p = 0.7). Nevertheless, during the in vivo evaluation, the implantation rate (21.8%) and the live-foetuses rate (18.8%) of the CRYO3 group were significantly higher than the implantation rate (7.1%, p = 0.0002) and the live-foetuses rate (5.3%, p = 0.0002) of the FCS group. The pregnancy rate was also higher in the CRYO3 group compared to the FCS group (81.3% and 43.8%, respectively, p = 0.066). We conclude that CRYO3 can be used as a chemically defined substitute for animal-based products in rabbit embryo cryopreservation solutions. PMID:23977074

Photocatalytic water oxidation by a pyrochlore oxide upon irradiation with visible light: rhodium substitution into yttrium titanate.

PubMed

Kiss, Borbala; Didier, Christophe; Johnson, Timothy; Manning, Troy D; Dyer, Matthew S; Cowan, Alexander J; Claridge, John B; Darwent, James R; Rosseinsky, Matthew J

2014-12-22

A stable visible-light-driven photocatalyst (λ≥450 nm) for water oxidation is reported. Rhodium substitution into the pyrochlore Y2 Ti2 O7 is demonstrated by monitoring Vegard's law evolution of the unit-cell parameters with changing rhodium content, to a maximum content of 3 % dopant. Substitution renders the solid solutions visible-light active. The overall rate of oxygen evolution is comparable to WO3 but with superior light-harvesting and surface-area-normalized turnover rates, making Y2 Ti1.94 Rh0.06 O7 an excellent candidate for use in a Z-scheme water-splitting system. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Applying a behavioral economic framework to understanding adolescent smoking.

PubMed

Audrain-McGovern, Janet; Rodriguez, Daniel; Tercyak, Kenneth P; Epstein, Leonard H; Goldman, Paula; Wileyto, E Paul

2004-03-01

Adolescents' choice to smoke may depend on substitute reinforcers for smoking, complementary activities to smoking, and individual differences in reinforcer value. The influence of these variables on smoking was determined among 983 adolescents. Substitutes were school involvement, academic performance, physical activity, and sports team participation: complements were peer smoking and substance use; delay discounting assessed individual differences in reinforcer value. Latent growth modeling indicated that substitute reinforcers reduced the odds of smoking progression almost two-fold, complementary reinforcers increased the odds by 1.14. and delay discounting indirectly influenced the odds of smoking progression through complementary reinforcers. Adolescents who smoke may have fewer reinforcers that protect against smoking and more reinforcers that promote smoking. Discounting of future rewards affects smoking through reinforcer type.

Lanthanide chelates of (bis)-hydroxymethyl-substituted DTTA with potential application as contrast agents in magnetic resonance imaging.

PubMed

Silvério, Sara; Torres, Susana; Martins, André F; Martins, José A; André, João P; Helm, Lothar; Prata, M Isabel M; Santos, Ana C; Geraldes, Carlos F G C

2009-06-28

A novel bis-hydroxymethyl-substituted DTTA chelator N'-Bz-C(4,4')-(CH(2)OH)(2)-DTTA () and its DTPA analogue C(4,4')-(CH(2)OH)(2)-DTPA () were synthesized and characterized. A variable-temperature (1)H NMR spectroscopy study of the solution dynamics of their diamagnetic (La) and paramagnetic (Sm, Eu) Ln(3+) complexes showed them to be rigid when compared with analogous Ln(3+)-DTTA and Ln(3+)-DTPA complexes, as a result of their C(4,4')-(CH(2)OH)(2) ligand backbone substitution. The parameters that govern the water (1)H relaxivity of the [Gd()(H(2)O)(2)](-) and [Gd()(H(2)O)](2-) complexes were obtained by (17)O and (1)H NMR relaxometry. While the relaxometric behaviour of the [Gd()(H(2)O)](2-) complex is very similar to the parent [Gd(DTPA)(H(2)O)](2-) system, the [Gd()(H(2)O)(2)](-) complex displays higher relaxivity, due to the presence of two inner sphere water molecules and an accelerated, near optimal water exchange rate. The [Gd()(H(2)O)(2)](-) complex interacts weakly with human serum albumin (HSA), and its fully bound relaxivity is limited by slow water exchange, as monitored by (1)H NMR relaxometry. This complex interacts weakly with phosphate, but does not form ternary complexes with bidentate bicarbonate and l-lactate anions, indicating that the two inner-sphere water molecules of the [Gd()(H(2)O)(2)](-) complex are not located in adjacent positions in the coordination sphere of the Gd(3+) ion. The transmetallation reaction rate of [Gd()(H(2)O)(2)](-) with Zn(2+) in phosphate buffer solution (pH 7.0) was measured to be similar to that of the backbone unsubstituted [Gd(DTTA-Me)(H(2)O)(2)](-), but twice faster than for [Gd(DTPA-BMA)(H(2)O)]. The in vivo biodistribution studies of the (153)Sm(3+)-labelled ligand () in Wistar rats reveal slow blood elimination and short term fixation in various organs, indicating some dissociation. The bis-hydroxymethyl-substituted DTTA skeleton can be seen as a new lead for the synthesis of high relaxivity contrast agents, although its low thermodynamic and kinetic stability will limit its use to in vitro and animal studies.

Selective modes determine evolutionary rates, gene compactness and expression patterns in Brassica.

PubMed

Guo, Yue; Liu, Jing; Zhang, Jiefu; Liu, Shengyi; Du, Jianchang

2017-07-01

It has been well documented that most nuclear protein-coding genes in organisms can be classified into two categories: positively selected genes (PSGs) and negatively selected genes (NSGs). The characteristics and evolutionary fates of different types of genes, however, have been poorly understood. In this study, the rates of nonsynonymous substitution (K a ) and the rates of synonymous substitution (K s ) were investigated by comparing the orthologs between the two sequenced Brassica species, Brassica rapa and Brassica oleracea, and the evolutionary rates, gene structures, expression patterns, and codon bias were compared between PSGs and NSGs. The resulting data show that PSGs have higher protein evolutionary rates, lower synonymous substitution rates, shorter gene length, fewer exons, higher functional specificity, lower expression level, higher tissue-specific expression and stronger codon bias than NSGs. Although the quantities and values are different, the relative features of PSGs and NSGs have been largely verified in the model species Arabidopsis. These data suggest that PSGs and NSGs differ not only under selective pressure (K a /K s ), but also in their evolutionary, structural and functional properties, indicating that selective modes may serve as a determinant factor for measuring evolutionary rates, gene compactness and expression patterns in Brassica. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

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.

Replication-associated mutational asymmetry in the human genome.

PubMed

Chen, Chun-Long; Duquenne, Lauranne; Audit, Benjamin; Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Huvet, Maxime; d'Aubenton-Carafa, Yves; Hyrien, Olivier; Arneodo, Alain; Thermes, Claude

2011-08-01

During evolution, mutations occur at rates that can differ between the two DNA strands. In the human genome, nucleotide substitutions occur at different rates on the transcribed and non-transcribed strands that may result from transcription-coupled repair. These mutational asymmetries generate transcription-associated compositional skews. To date, the existence of such asymmetries associated with replication has not yet been established. Here, we compute the nucleotide substitution matrices around replication initiation zones identified as sharp peaks in replication timing profiles and associated with abrupt jumps in the compositional skew profile. We show that the substitution matrices computed in these regions fully explain the jumps in the compositional skew profile when crossing initiation zones. In intergenic regions, we observe mutational asymmetries measured as differences between complementary substitution rates; their sign changes when crossing initiation zones. These mutational asymmetries are unlikely to result from cryptic transcription but can be explained by a model based on replication errors and strand-biased repair. In transcribed regions, mutational asymmetries associated with replication superimpose on the previously described mutational asymmetries associated with transcription. We separate the substitution asymmetries associated with both mechanisms, which allows us to determine for the first time in eukaryotes, the mutational asymmetries associated with replication and to reevaluate those associated with transcription. Replication-associated mutational asymmetry may result from unequal rates of complementary base misincorporation by the DNA polymerases coupled with DNA mismatch repair (MMR) acting with different efficiencies on the leading and lagging strands. Replication, acting in germ line cells during long evolutionary times, contributed equally with transcription to produce the present abrupt jumps in the compositional skew. These results demonstrate that DNA replication is one of the major processes that shape human genome composition.

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

Kinetics of the substitution of dehydroacetic acid in tris (dehydroacetato) Fe(III) complex by 8-hydroxyquinoline, di- and tetra-hydroxyquinone

NASA Astrophysics Data System (ADS)

Fouad, D. M.; Ismail, N. M.; El-Gahami, M. A.; Ibrahim, S. A.

2007-06-01

The ligand substitution reactions of dehydroacetic acid (Hdha) in [Fe(dha) 3] with second ligand such as 8-hydroxyquinoline (Hquin), 1,4-dihydroxyanthraquinone (H 2dhaq) and 1,4,5,8-tetra-hydroxyanthraquinone (H 4thaq) were investigated spectrophotometrically by in low polarity solvents like benzene, chloroform and dichloromethane. It is deduced that the substitution reaction takes place through one successive step. The reaction was performed at four different temperatures (5-25) °C, and it exhibits a first order dependence on the concentration of the starting complex. The observed rate constant depends on the concentration of both leaving and entering ligands. The evaluation of the kinetic data gives activation parameters which support an associative mechanism in the transition states and the higher rate of substitution of the dha in Fe(dha) 3 complex is due to entropy effect. The solid complexes were synthesized and characterized by elemental analysis, IR and UV-vis spectral techniques.

The effects of substitute multisensory feedback on task performance and the sense of presence in a virtual reality environment

PubMed Central

Milella, Ferdinando; Pinto, Carlo; Cant, Iain; White, Mark; Meyer, Georg

2018-01-01

Objective and subjective measures of performance in virtual reality environments increase as more sensory cues are delivered and as simulation fidelity increases. Some cues (colour or sound) are easier to present than others (object weight, vestibular cues) so that substitute cues can be used to enhance informational content in a simulation at the expense of simulation fidelity. This study evaluates how substituting cues in one modality by alternative cues in another modality affects subjective and objective performance measures in a highly immersive virtual reality environment. Participants performed a wheel change in a virtual reality (VR) environment. Auditory, haptic and visual cues, signalling critical events in the simulation, were manipulated in a factorial design. Subjective ratings were recorded via questionnaires. The time taken to complete the task was used as an objective performance measure. The results show that participants performed best and felt an increased sense of immersion and involvement, collectively referred to as ‘presence’, when substitute multimodal sensory feedback was provided. Significant main effects of audio and tactile cues on task performance and on participants' subjective ratings were found. A significant negative relationship was found between the objective (overall completion times) and subjective (ratings of presence) performance measures. We conclude that increasing informational content, even if it disrupts fidelity, enhances performance and user’s overall experience. On this basis we advocate the use of substitute cues in VR environments as an efficient method to enhance performance and user experience. PMID:29390023

The effects of substitute multisensory feedback on task performance and the sense of presence in a virtual reality environment.

PubMed

Cooper, Natalia; Milella, Ferdinando; Pinto, Carlo; Cant, Iain; White, Mark; Meyer, Georg

2018-01-01

Objective and subjective measures of performance in virtual reality environments increase as more sensory cues are delivered and as simulation fidelity increases. Some cues (colour or sound) are easier to present than others (object weight, vestibular cues) so that substitute cues can be used to enhance informational content in a simulation at the expense of simulation fidelity. This study evaluates how substituting cues in one modality by alternative cues in another modality affects subjective and objective performance measures in a highly immersive virtual reality environment. Participants performed a wheel change in a virtual reality (VR) environment. Auditory, haptic and visual cues, signalling critical events in the simulation, were manipulated in a factorial design. Subjective ratings were recorded via questionnaires. The time taken to complete the task was used as an objective performance measure. The results show that participants performed best and felt an increased sense of immersion and involvement, collectively referred to as 'presence', when substitute multimodal sensory feedback was provided. Significant main effects of audio and tactile cues on task performance and on participants' subjective ratings were found. A significant negative relationship was found between the objective (overall completion times) and subjective (ratings of presence) performance measures. We conclude that increasing informational content, even if it disrupts fidelity, enhances performance and user's overall experience. On this basis we advocate the use of substitute cues in VR environments as an efficient method to enhance performance and user experience.

Convergent evolution of marine mammals is associated with distinct substitutions in common genes

PubMed Central

Zhou, Xuming; Seim, Inge; Gladyshev, Vadim N.

2015-01-01

Phenotypic convergence is thought to be driven by parallel substitutions coupled with natural selection at the sequence level. Multiple independent evolutionary transitions of mammals to an aquatic environment offer an opportunity to test this thesis. Here, whole genome alignment of coding sequences identified widespread parallel amino acid substitutions in marine mammals; however, the majority of these changes were not unique to these animals. Conversely, we report that candidate aquatic adaptation genes, identified by signatures of likelihood convergence and/or elevated ratio of nonsynonymous to synonymous nucleotide substitution rate, are characterized by very few parallel substitutions and exhibit distinct sequence changes in each group. Moreover, no significant positive correlation was found between likelihood convergence and positive selection in all three marine lineages. These results suggest that convergence in protein coding genes associated with aquatic lifestyle is mainly characterized by independent substitutions and relaxed negative selection. PMID:26549748

Similar Mutation Rates but Highly Diverse Mutation Spectra in Ascomycete and Basidiomycete Yeasts.

PubMed

Long, Hongan; Behringer, Megan G; Williams, Emily; Te, Ronald; Lynch, Michael

2016-12-01

Yeast species are extremely diverse and not monophyletic. Because the majority of yeast research focuses on ascomycetes, the mutational determinants of genetic diversity across yeast species are not well understood. By combining mutation-accumulation techniques with whole-genome sequencing, we resolved the genomic mutation rate and spectrum of the oleaginous (oil-producing) ‘red yeast’ Rhodotorula toruloides, the first such study in the fungal phylum Basidiomycota. We find that the mutation spectrum is quite different from what has been observed in all other studied unicellular eukaryotes, but similar to that in most bacteria—a predominance of transitions relative to transversions. Rhodotorula toruloides has a significantly higher A:T→G:C transition rate—possibly elevated by the abundant flanking G/C nucleotides in the GC-rich genome, as well as a much lower G:C→T:A transversion rate. In spite of these striking differences, there are substantial consistencies between R. toruloides and the ascomycete model yeasts: a spontaneous base-substitution mutation rate of 1.90 × 10 −10 per site per cell division as well as an elevated mutation rate at non-methylated 5'CpG3' sites. These results imply the evolution of variable mutation spectra in the face of similar mutation rates in yeasts.

Rate of novel host invasion affects adaptability of evolving RNA virus lineages.

PubMed

Morley, Valerie J; Mendiola, Sandra Y; Turner, Paul E

2015-08-22

Although differing rates of environmental turnover should be consequential for the dynamics of adaptive change, this idea has been rarely examined outside of theory. In particular, the importance of RNA viruses in disease emergence warrants experiments testing how differing rates of novel host invasion may impact the ability of viruses to adaptively shift onto a novel host. To test whether the rate of environmental turnover influences adaptation, we experimentally evolved 144 Sindbis virus lineages in replicated tissue-culture environments, which transitioned from being dominated by a permissive host cell type to a novel host cell type. The rate at which the novel host 'invaded' the environment varied by treatment. The fitness (growth rate) of evolved virus populations was measured on each host type, and molecular substitutions were mapped via whole genome consensus sequencing. Results showed that virus populations more consistently reached high fitness levels on the novel host when the novel host 'invaded' the environment more gradually, and gradual invasion resulted in less variable genomic outcomes. Moreover, virus populations that experienced a rapid shift onto the novel host converged upon different genotypes than populations that experienced a gradual shift onto the novel host, suggesting a strong effect of historical contingency. © 2015 The Author(s).

Interplay between Chaperones and Protein Disorder Promotes the Evolution of Protein Networks

PubMed Central

Pechmann, Sebastian; Frydman, Judith

2014-01-01

Evolution is driven by mutations, which lead to new protein functions but come at a cost to protein stability. Non-conservative substitutions are of interest in this regard because they may most profoundly affect both function and stability. Accordingly, organisms must balance the benefit of accepting advantageous substitutions with the possible cost of deleterious effects on protein folding and stability. We here examine factors that systematically promote non-conservative mutations at the proteome level. Intrinsically disordered regions in proteins play pivotal roles in protein interactions, but many questions regarding their evolution remain unanswered. Similarly, whether and how molecular chaperones, which have been shown to buffer destabilizing mutations in individual proteins, generally provide robustness during proteome evolution remains unclear. To this end, we introduce an evolutionary parameter λ that directly estimates the rate of non-conservative substitutions. Our analysis of λ in Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens sequences reveals how co- and post-translationally acting chaperones differentially promote non-conservative substitutions in their substrates, likely through buffering of their destabilizing effects. We further find that λ serves well to quantify the evolution of intrinsically disordered proteins even though the unstructured, thus generally variable regions in proteins are often flanked by very conserved sequences. Crucially, we show that both intrinsically disordered proteins and highly re-wired proteins in protein interaction networks, which have evolved new interactions and functions, exhibit a higher λ at the expense of enhanced chaperone assistance. Our findings thus highlight an intricate interplay of molecular chaperones and protein disorder in the evolvability of protein networks. Our results illuminate the role of chaperones in enabling protein evolution, and underline the importance of the cellular context and integrated approaches for understanding proteome evolution. We feel that the development of λ may be a valuable addition to the toolbox applied to understand the molecular basis of evolution. PMID:24968255

Impact of elementary school-located influenza vaccinations: A stepped wedge trial across a community.

PubMed

Szilagyi, Peter G; Schaffer, Stanley; Rand, Cynthia M; Goldstein, Nicolas P N; Hightower, A Dirk; Younge, Mary; Eagan, Ashley; Blumkin, Aaron; Albertin, Christina S; DiBitetto, Kristine; Concannon, Cathleen; Vincelli, Phyllis; Yoo, Byung-Kwang; Humiston, Sharon G

2018-05-11

Influenza vaccination rates among children are low and novel strategies are needed to raise coverage. We measured the impact of school-located influenza vaccination (SLIV) on coverage, examined whether SLIV substitutes for practice-based influenza vaccination ("substitution"), and estimated whether a second year of experience with SLIV increases its impact. We implemented a stepped wedge study design with schools as clusters. In Year 1, we randomly allocated schools to SLIV or control. In Year 2, all schools performed SLIV. We used emails (suburban schools) or backpack fliers (both urban and suburban schools) to notify parents, and offered web-based (suburban) or paper-based vaccination (urban) consent forms. Local health department nurses administered SLIV vaccinations and billed insurers. We analyzed state immunization registry data to measure influenza vaccination rates. 42 schools (38,078 children) participated over 2 years. Overall vaccination rates were 5 and 7 percentage points higher among SLIV- school children versus control-school children in suburban (aOR 1.36, 95% CI 1.25-1.49 in Years 1-2 SLIV vs. Year 1 control schools) and urban schools (aOR 1.22, 95% CI 1.10-1.36), respectively, adjusting for prior year's vaccination and other covariates. While no substitution occurred among children attending suburban schools, some substitution occurred among children attending urban schools, although overall vaccination rates were still higher in urban schools due to SLIV. Compared to an initial year of SLIV, more children were vaccinated in a second year of SLIV at urban (8.3% vs. 6.8%, aOR 1.24, 95% CI 1.04-1.47) but not suburban schools (3.5% vs. 2.7%, aOR 1.24, 95% CI 0.98-1.57). In this stepped wedge trial, SLIV increased overall influenza vaccination rates in suburban and urban schools. Some substitution for primary care vaccination occurred in urban settings. A second year of SLIV expanded its reach slightly in urban schools. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 20835 - Combined Notice of Filings No. 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

... 08, 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and...: White River Hub, LLC submits Substitute First Revised Sheet 242 et al to FERC Gas Tariff, Original... Company. Description: Questar Southern Trails Pipeline Company submits Third Substitute Revised Sheet 130...

75 FR 11156 - Combined Notice of Filings No. 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

..., 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund.... Description: Gulf Crossing Pipeline Company, LLC submits Substitute Original Sheet No 1307A to FERC Gas Tariff...: Texas Gas Transmission. LLC. Description: Texas Gas Transmission, LLC submits Substitute Original Sheet...

Reinforcement value and substitutability of sucrose and wheel running: implications for activity anorexia.

PubMed

Belke, Terry W; Pierce, W David; Duncan, Ian D

2006-09-01

Choice between sucrose and wheel-running reinforcement was assessed in two experiments. In the first experiment, ten male Wistar rats were exposed to concurrent VI 30 s VI 30 s schedules of wheel-running and sucrose reinforcement. Sucrose concentration varied across concentrations of 2.5, 7.5, and 12.5%. As concentration increased, more behavior was allocated to sucrose and more reinforcements were obtained from that alternative. Allocation of behavior to wheel running decreased, but obtained wheel-running reinforcement did not change. Overall, the results suggested that food-deprived rats were sensitive to qualitative changes in food supply (sucrose concentration) while continuing to defend a level of physical activity (wheel running). In the second study, 15 female Long Evans rats were exposed to concurrent variable ratio schedules of sucrose and wheel-running, wheel-running and wheel-running, and sucrose and sucrose reinforcement. For each pair of reinforcers, substitutability was assessed by the effect of income-compensated price changes on consumption of the two reinforcers. Results showed that, as expected, sucrose substituted for sucrose and wheel running substituted for wheel running. Wheel running, however, did not substitute for sucrose; but sucrose partially substituted for wheel running. We address the implications of the interrelationships of sucrose and wheel running for an understanding of activity anorexia.

Reinforcement Value and Substitutability of Sucrose and Wheel Running: Implications for Activity Anorexia

PubMed Central

Belke, Terry W; Duncan, Ian D; David Pierce, W

2006-01-01

Choice between sucrose and wheel-running reinforcement was assessed in two experiments. In the first experiment, ten male Wistar rats were exposed to concurrent VI 30 s VI 30 s schedules of wheel-running and sucrose reinforcement. Sucrose concentration varied across concentrations of 2.5, 7.5, and 12.5%. As concentration increased, more behavior was allocated to sucrose and more reinforcements were obtained from that alternative. Allocation of behavior to wheel running decreased, but obtained wheel-running reinforcement did not change. Overall, the results suggested that food-deprived rats were sensitive to qualitative changes in food supply (sucrose concentration) while continuing to defend a level of physical activity (wheel running). In the second study, 15 female Long Evans rats were exposed to concurrent variable ratio schedules of sucrose and wheel-running, wheel-running and wheel-running, and sucrose and sucrose reinforcement. For each pair of reinforcers, substitutability was assessed by the effect of income-compensated price changes on consumption of the two reinforcers. Results showed that, as expected, sucrose substituted for sucrose and wheel running substituted for wheel running. Wheel running, however, did not substitute for sucrose; but sucrose partially substituted for wheel running. We address the implications of the interrelationships of sucrose and wheel running for an understanding of activity anorexia. PMID:17002224

Comparison of different methods to include recycling in LCAs of aluminium cans and disposable polystyrene cups.

PubMed

van der Harst, Eugenie; Potting, José; Kroeze, Carolien

2016-02-01

Many methods have been reported and used to include recycling in life cycle assessments (LCAs). This paper evaluates six widely used methods: three substitution methods (i.e. substitution based on equal quality, a correction factor, and alternative material), allocation based on the number of recycling loops, the recycled-content method, and the equal-share method. These six methods were first compared, with an assumed hypothetical 100% recycling rate, for an aluminium can and a disposable polystyrene (PS) cup. The substitution and recycled-content method were next applied with actual rates for recycling, incineration and landfilling for both product systems in selected countries. The six methods differ in their approaches to credit recycling. The three substitution methods stimulate the recyclability of the product and assign credits for the obtained recycled material. The choice to either apply a correction factor, or to account for alternative substituted material has a considerable influence on the LCA results, and is debatable. Nevertheless, we prefer incorporating quality reduction of the recycled material by either a correction factor or an alternative substituted material over simply ignoring quality loss. The allocation-on-number-of-recycling-loops method focusses on the life expectancy of material itself, rather than on a specific separate product. The recycled-content method stimulates the use of recycled material, i.e. credits the use of recycled material in products and ignores the recyclability of the products. The equal-share method is a compromise between the substitution methods and the recycled-content method. The results for the aluminium can follow the underlying philosophies of the methods. The results for the PS cup are additionally influenced by the correction factor or credits for the alternative material accounting for the drop in PS quality, the waste treatment management (recycling rate, incineration rate, landfilling rate), and the source of avoided electricity in case of waste incineration. The results for the PS cup, which are less dominated by production of virgin material than aluminium can, furthermore depend on the environmental impact categories. This stresses the importance to consider other impact categories besides the most commonly used global warming impact. The multitude of available methods complicates the choice of an appropriate method for the LCA practitioner. New guidelines keep appearing and industries also suggest their own preferred method. Unambiguous ISO guidelines, particularly related to sensitivity analysis, would be a great step forward in making more robust LCAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Enhanced magnetism of perovskite oxides, Sr(Sn,Fe)O3- δ , by substitution of nonmagnetic Ca and Ti ions

NASA Astrophysics Data System (ADS)

Nomura, Kiyoshi; Suzuki, Shigeyo; Mizunuma, Tomoya; Koike, Yuya; Okazawa, Atsushi

2017-11-01

Magnetic properties of perovskite oxides, SrSn1- x Fe x O3- δ ( x ≤ 0.15), substituted with nonmagnetic Ca and Ti ions were studied. XRD patterns showed the orthorhombic structure (close to tetragonal) of (Sr1- y Ca y )(Sn1- x Fe x )O3- δ and Sr(Sn1- x- y Fe x Ti y )O3- δ . The cell volumes decreased with the increase of Ca and Ti doping rates. Although Ti-substituted Sr(Sn, Fe)O3- δ showed small saturation magnetizations as compared with non-Ti substituted one, the magnetization increased a little with Ti doping rates up to 15%. On the other hand, all Ca-substituted Sr(Sn, Fe)O3- δ showed larger saturation magnetization than non-Ca substituted one. Two doublets of Fe3+ and a doublet of Fe4+ were observed in Mössbauer spectra of Ca-substituted Sr(Sn, Fe)O3- δ with weak ferromagnetism, and two sextets of high spin Fe3+ were additionally observed in Mössbauer spectra of Ca-doped Sr(Sn, Fe)O3- δ with relatively strong ferromagnetism. When Sr(Sn, Fe)O3- δ were further codoped with Ca and Ti ions, they showed the stable and enhanced ferromagnetic properties. It is considered that magnetic polarons among high spin Fe3+ species are overlapped by shrinking or deforming the crystal structure of perovskite oxides. That is the magnetism induced by a chemical pressure of perovskite oxides.

Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic.

PubMed

Sanger, D J; Zivkovic, B

1994-01-01

Alpidem in an imidazopyridine derivative which binds selectively to the omega 1 (BZ1) receptor subtype. It is active in some, but not all, behavioural tests sensitive to benzodiazepine anxiolytics and has clinical anti-anxiety effects. However, in a previous study, it was shown that alpidem did not substitute for chlordiazepoxide in rats trained to discriminate this benzodiazepine. The present experiments were carried out to investigate the discriminative stimulus properties of alpidem in greater detail. In the first experiment rats learned to discriminate a dose of 10 mg/kg alpidem from saline. Acquisition of the discrimination was long and performance unstable. Chlordiazepoxide, clorazepate and zolpidem substituted only partially for alpidem but the effects of the training dose of alpidem were blocked by 10 mg/kg flumazenil. The second experiment established stimulus control more rapidly to a dose of 30 mg/kg alpidem. Alpidem induced dose-related stimulus control, and dose-related and complete substitution for alpidem was produced by zolpidem, abecarnil, CL 218,872, triazolam and suriclone. Partial substitution occurred with chlordiazepoxide, clorazepate and pentobarbital. In most cases, high levels of substitution were produced only by doses which greatly reduced response rates even though the training dose of alpidem produced only modest decreases in rates. Ethanol, buspirone and bretazenil produced very little substitution for alpidem and both flumazenil and bretazenil antagonised the effects of alpidem. In two further experiments alpidem was found to substitute for the stimulus produced by zolpidem (2 mg/kg) but not for that produced by ethanol (1.5 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Dissolution kinetics of iron-, manganese-, and copper-containing synthetic hydroxyapatites

NASA Technical Reports Server (NTRS)

Sutter, B.; Hossner, L. R.; Ming, D. W.

2005-01-01

Micronutrient-substituted synthetic hydroxyapatite (SHA) is being evaluated by the National Aeronautics and Space Administration's (NASA) Advanced Life Support (ALS) Program for crop production on long-duration human missions to the International Space Station or for future Lunar or Martian outposts. The stirred-flow technique was utilized to characterize Ca, P, Fe, Mn, and Cu release characteristics from Fe-, Mn-, and Cu-containing SHA in deionized (DI) water, citric acid, and diethylene-triamine-pentaacetic acid (DTPA). Initially, Ca and P release rates decreased rapidly with time and were controlled by a non-SHA calcium phosphate phase(s) with low Ca/P solution molar ratios (0.91-1.51) relative to solid SHA ratios (1.56-1.64). At later times, Ca/P solution molar ratios (1.47-1.79) were near solid SHA ratios and release rates decreased slowly indicating that SHA controlled Ca and P release. Substituted SHA materials had faster dissolution rates relative to unsubstituted SHA. The initial metal release rate order was Mn >> Cu > Fe which followed metal-oxide/phosphate solubility suggesting that poorly crystalline metal-oxides/phosphates were dominating metal release. Similar metal release rates for all substituted SHA (approximately 0.01 cmol kg-1 min-1) at the end of the DTPA experiment indicated that SHA dissolution was supplying the metals into solution and that poorly crystalline metal-oxide/phosphates were not controlling metal release. Results indicate that non-SHA Ca-phosphate phases and poorly crystalline metal-oxide/phosphates will contribute Ca, P, and metals. After these phases have dissolved, substituted SHA will be the source of Ca, P, and metals for plants.

Analysis of evolutionary rate of HIV-1 subtype B using blood donor samples in Japan.

PubMed

Shinohara, Naoya; Matsumoto, Chieko; Matsubayashi, Keiji; Nagai, Tadashi; Satake, Masahiro

2018-06-01

There are few reports on HIV-1 intra-host evolutionary rate in asymptomatic treatment-naïve patients. Here, the HIV-1 intra-host evolutionary rate was estimated based on HIV-1 RNA sequences from plasma samples of blood donors in Japan. Blood donors were assumed to have received no treatment for and have no symptoms of HIV-1 infection because they were healthy, and declared no risky behaviors of HIV-1 infection on a self-reported questionnaire or interview followed by donation. HIV-1 RNA was obtained from 85 plasma samples from 36 blood donors who donated blood multiple times and were HIV-1-positive. The C2V3C3 region which encodes for a part of the envelope protein, and the V3 loop in the C2V3C3 region were analyzed by RT-PCR and direct sequencing, and the sequences were compared. The nucleotide substitution rate was calculated by linear regression. All HIV-1 samples analyzed were classified as subtype B. The mean nucleotide substitution rate in C2V3C3 was calculated to be 6.2 × 10 -3 -1.8 × 10 -2 /site/year (V3: 4.5 × 10 -3 -2.3 × 10 -2 /site/year). The mean non-synonymous substitution rate in C2V3C3 was calculated to be 5.2 × 10 -3 -1.7 × 10 -2 /site/year (V3: 4.5 × 10 -3 -2.1 × 10 -2 /site/year). The mean synonymous substitution rate in C2V3C3 was calculated to be 1.1 × 10 -4 -2.3 × 10 -3 /site/year (V3: 2.9 × 10 -3 /site/year). Among HIV-1 subtype B RNA-positive blood donors in Japan, the nucleotide substitution rate in C2V3C3 was estimated to be higher than that of reported cases using HIV-1 samples mainly obtained from AIDS patients. Compared to AIDS patients, immune responses against HIV-1 are probably more effective in HIV-1 RNA-positive blood donors. Consequently, immune pressure presumably promotes mutation of the virus genome.

Lives in Motion: A Review of Former Foster Youth in the Context of their Experiences in the Child Welfare System

PubMed Central

Havlicek, Judy

2011-01-01

In light of the poor prospects facing many former foster youth during the transition to adulthood, it is surprising that so little attention has been given to substitute care contexts during child welfare system involvement. A review of child welfare research finds that many former foster youth go through an alarming number of placement changes and report a high rate of placement into congregate care settings and other unplanned events. Future research should take explicit account of substitute care contexts in designing and carrying out studies examining the adult outcomes of aging out foster care populations. Interventions intended to circumvent high rates of movement in foster care should also be broadened to target multiple aspects of substitute care contexts. PMID:21643470

75 FR 10239 - Combined Notice of Filings No 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... 25, 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and...: Millennium Pipeline Company, LLC submits Substitute First Revised Sheet No 485 to FERC Gas Tariff, Original.... Description: TW Phillips Pipeline Corp submits Substitute First Revised Sheet No 86 to replace First Revised...

Endowment Spending Rates, Intergenerational Equity and the Sources of Capital Gains

ERIC Educational Resources Information Center

Woglom, Geoffrey

2003-01-01

This paper analyzes how James Tobin's widely cited concept of "intergenerational equity" for university endowments relates to the economic concepts of intertemporal substitutability and risk aversion. I show that Tobin's concept of intergenerational equity is a very special case of intertemporal substitutability; a special case that implies very…

Evolution and molecular epidemiology of classical swine fever virus during a multi-annual outbreak amongst European wild boar.

PubMed

Goller, Katja V; Gabriel, Claudia; Dimna, Mireille Le; Le Potier, Marie-Frédérique; Rossi, Sophie; Staubach, Christoph; Merboth, Matthias; Beer, Martin; Blome, Sandra

2016-03-01

Classical swine fever is a viral disease of pigs that carries tremendous socio-economic impact. In outbreak situations, genetic typing is carried out for the purpose of molecular epidemiology in both domestic pigs and wild boar. These analyses are usually based on harmonized partial sequences. However, for high-resolution analyses towards the understanding of genetic variability and virus evolution, full-genome sequences are more appropriate. In this study, a unique set of representative virus strains was investigated that was collected during an outbreak in French free-ranging wild boar in the Vosges-du-Nord mountains between 2003 and 2007. Comparative sequence and evolutionary analyses of the nearly full-length sequences showed only slow evolution of classical swine fever virus strains over the years and no impact of vaccination on mutation rates. However, substitution rates varied amongst protein genes; furthermore, a spatial and temporal pattern could be observed whereby two separate clusters were formed that coincided with physical barriers.

Autotransplantation of endodontically treated third molars.

PubMed

Sobhi, Muhammad Bakhsh; Rana, Muzammil Jamil Ahmed; Manzoor, Manzoor Ahmed; Ibrahim, Mohammad; Tasleem-ul-Hudda

2003-07-01

To determine the success rate in autotransplantation of endodontically treated third molars. A descriptive study. This study was carried out at Armed Forces Institute of Dentistry (AFID), Rawalpindi (Pakistan) from January 2002 to December 2002. A total of 50 patients meeting the inclusion criteria were selected who had their first or second molars in unrestorable condition with intact third molars. The donor teeth were extracted after the preparation of recipient site. After endodontically treated in vitro the donor teeth were carried to the recipient site and immobilized. Postoperative variables were recorded and analyzed on SPSS version 10. The overall success rate after six months of the transplantation of third molars was 88% with complete root formation after endodontic treatment. All the patients(12%) who had complaints were more than 35 years of age. Third molars are good substitute for the unrestorable first or second molars and would be as effective as endosseous implants. The procedure is likely to have complications in the advanced age group.

Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications.

PubMed

Tavtigian, Sean V; Byrnes, Graham B; Goldgar, David E; Thomas, Alun

2008-11-01

Many individually rare missense substitutions are encountered during deep resequencing of candidate susceptibility genes and clinical mutation screening of known susceptibility genes. BRCA1 and BRCA2 are among the most resequenced of all genes, and clinical mutation screening of these genes provides an extensive data set for analysis of rare missense substitutions. Align-GVGD is a mathematically simple missense substitution analysis algorithm, based on the Grantham difference, which has already contributed to classification of missense substitutions in BRCA1, BRCA2, and CHEK2. However, the distribution of genetic risk as a function of Align-GVGD's output variables Grantham variation (GV) and Grantham deviation (GD) has not been well characterized. Here, we used data from the Myriad Genetic Laboratories database of nearly 70,000 full-sequence tests plus two risk estimates, one approximating the odds ratio and the other reflecting strength of selection, to display the distribution of risk in the GV-GD plane as a series of surfaces. We abstracted contours from the surfaces and used the contours to define a sequence of missense substitution grades ordered from greatest risk to least risk. The grades were validated internally using a third, personal and family history-based, measure of risk. The Align-GVGD grades defined here are applicable to both the genetic epidemiology problem of classifying rare missense substitutions observed in known susceptibility genes and the molecular epidemiology problem of analyzing rare missense substitutions observed during case-control mutation screening studies of candidate susceptibility genes. (c) 2008 Wiley-Liss, Inc.

Runaway evolution of the male-specific exon of the doublesex gene in Diptera.

PubMed

Hughes, Austin L

2011-02-01

In Diptera (Insecta), alternatively spliced male-specific and female-specific products of the doublesex (dsx) gene play a key role in regulating development of the adult genital structures from the genital disc. Analysis of the pattern of nucleotide substitution of different domains of the dsx gene in 29 dipteran species showed that, over short evolutionary times, purifying selection predominated on the domain common to both sexes, the female-specific exons, and the and male-specific exon. However, over longer the evolutionary time frames represented by between-family comparisons, the male-specific exon accumulated nonsynonymous substitutions at a much more rapid rate than either the common domain or the female-specific exon. Overall, the accumulation of nonsynonymous substitutions in the male-specific exon occurred at a significantly greater than linear rate relative to the common domain, whereas the accumulation of nonsynonymous substitutions in the female-specific exon occurred at less than linear rate relative to the common domain. The evolution of the male-specific exon of dsx thus shows a pattern reminiscent of that seen in the "runaway" evolution of male secondary sexual characters at the morphological level, consistent with the hypothesis that female choice is an important factor in the morphological diversification of insect male genitalia. Copyright © 2010 Elsevier B.V. All rights reserved.

High temperature dissolution of chromium substituted nickel ferrite in nitrilotriacetic acid medium

NASA Astrophysics Data System (ADS)

Sathyaseelan, V. S.; Chandramohan, P.; Velmurugan, S.

2016-12-01

High temperature (HT) dissolution of chromium substituted nickel ferrite was carried out with relevance to the decontamination of nuclear reactors by way of chemical dissolution of contaminated corrosion product oxides present on stainless steel coolant circuit surfaces. Chromium substituted nickel ferrites of composition, NiFe(2-x)CrxO4 (x ≤ 1), was synthetically prepared and characterized. HT dissolution of these oxides was carried out in nitrilotriacetic acid medium at 160 °C. Dissolution was remarkably increased at 160 °C when compared to at 85 °C in a reducing decontamination formulation. Complete dissolution could be achieved for the oxides with chromium content 0 and 0.2. Increasing the chromium content brought about a marked reduction in the dissolution rate. About 40 fold decrease in rate of dissolution was observed when chromium was increased from 0 to 1. The rate of dissolution was not very significantly reduced in the presence of N2H4. Dissolution of oxide was found to be stoichiometric.

Common pitfalls in statistical analysis: Measures of agreement.

PubMed

Ranganathan, Priya; Pramesh, C S; Aggarwal, Rakesh

2017-01-01

Agreement between measurements refers to the degree of concordance between two (or more) sets of measurements. Statistical methods to test agreement are used to assess inter-rater variability or to decide whether one technique for measuring a variable can substitute another. In this article, we look at statistical measures of agreement for different types of data and discuss the differences between these and those for assessing correlation.

Hollow cathode restartable 15 cm diameter ion thruster

NASA Technical Reports Server (NTRS)

Wilbur, P. J.

1973-01-01

The effects of substituting high perveance dished grids for low perveance flat ones on performance variables and plasma properties within a 15 cm modified SERT II thruster are discussed. Results suggest good performance may be achieved as an ion thruster is throttled if the screen grid transparency is decreased with propellant flow rate. Thruster startup tests, which employ a pulsed high voltage tickler electrode between the keeper and the cathode to initiate the discharge, are described. High startup reliability at cathode tip temperatures of about 500 C without excessive component wear over 2000 startup cycles is demonstrated. Testing of a single cusp magnetic field concept of discharge plasma containment is discussed. A theory which explains the observed behavior of the device is presented and proposed thruster modifications and future testing plans are discussed.

Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

PubMed Central

Harvey, William T.; Benton, Donald J.; Gregory, Victoria; Hall, James P. J.; Daniels, Rodney S.; Bedford, Trevor; Haydon, Daniel T.; Hay, Alan J.; McCauley, John W.; Reeve, Richard

2016-01-01

Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. PMID:27057693

Calibration of Multiple In Silico Tools for Predicting Pathogenicity of Mismatch Repair Gene Missense Substitutions

PubMed Central

Thompson, Bryony A.; Greenblatt, Marc S.; Vallee, Maxime P.; Herkert, Johanna C.; Tessereau, Chloe; Young, Erin L.; Adzhubey, Ivan A.; Li, Biao; Bell, Russell; Feng, Bingjian; Mooney, Sean D.; Radivojac, Predrag; Sunyaev, Shamil R.; Frebourg, Thierry; Hofstra, Robert M.W.; Sijmons, Rolf H.; Boucher, Ken; Thomas, Alun; Goldgar, David E.; Spurdle, Amanda B.; Tavtigian, Sean V.

2015-01-01

Classification of rare missense substitutions observed during genetic testing for patient management is a considerable problem in clinical genetics. The Bayesian integrated evaluation of unclassified variants is a solution originally developed for BRCA1/2. Here, we take a step toward an analogous system for the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) that confer colon cancer susceptibility in Lynch syndrome by calibrating in silico tools to estimate prior probabilities of pathogenicity for MMR gene missense substitutions. A qualitative five-class classification system was developed and applied to 143 MMR missense variants. This identified 74 missense substitutions suitable for calibration. These substitutions were scored using six different in silico tools (Align-Grantham Variation Grantham Deviation, multivariate analysis of protein polymorphisms [MAPP], Mut-Pred, PolyPhen-2.1, Sorting Intolerant From Tolerant, and Xvar), using curated MMR multiple sequence alignments where possible. The output from each tool was calibrated by regression against the classifications of the 74 missense substitutions; these calibrated outputs are interpretable as prior probabilities of pathogenicity. MAPP was the most accurate tool and MAPP + PolyPhen-2.1 provided the best-combined model (R2 = 0.62 and area under receiver operating characteristic = 0.93). The MAPP + PolyPhen-2.1 output is sufficiently predictive to feed as a continuous variable into the quantitative Bayesian integrated evaluation for clinical classification of MMR gene missense substitutions. PMID:22949387

Effects of Combined Application of Biogas Slurry and Chemical Fertilizer on Soil Aggregation and C/N Distribution in an Ultisol.

PubMed

Zheng, Xuebo; Fan, Jianbo; Xu, Lei; Zhou, Jing

2017-01-01

Unreasonable use of chemical fertilizer (CF) on agricultural soil leads to massive losses of soil organic carbon (SOC) and total nitrogen (TN) in tropical and subtropical areas, where soil conditions are unfavorable for aggregate formation. This study evaluated the effects of combined application of biogas slurry (BS) plus CF on soil aggregation and aggregate-associated C/N concentration and storage in an Ultisol. Six treatments included: no fertilizer (T1), CF only (T2), partial (15% (T3), 30% (T4) and 45% (T5)) substitution of TN with BS and BS only (T6). Soil mechanical-stable aggregates (MSAs) formation and stability as well as MSAs-associated C/N concentration and storage were observed in different aggregate sizes (>5, 5-2, 2-1, 1.0-0.5, 0.50-0.25 and <0.25 mm). The proportion of MSAs >5 mm significantly increased with BS substitution (T5), while the proportions of MSAs 1.0-0.5 mm, MSAs 0.50-0.25 mm and MSAs <0.25 mm significantly decreased. Both mean weight diameter and geometric mean diameter were highest in T5, which improved soil aggregation stability as well as resulted in significantly higher SOC and TN concentrations and storage in MSAs >0.5 mm that constituted 72-82% of MSAs. Stepwise regression analysis showed that MSAs >5 mm, SOC in MSAs >5 mm and TN in MSAs >5 mm were the dominant variables affecting aggregate stability. Meanwhile SOC in MSAs <0.25 mm and TN in MSAs 2-1 mm were independent variables affecting SOC and TN concentrations in bulk soils. Therefore, certain rate of combined application of BS plus CF is an effective, eco-friendly way to improve soil quality in an Ultisol.

Substitute fluid examinations for liquid manure

NASA Astrophysics Data System (ADS)

Schrader, Kevin; Riedel, Marco; Eichert, Helmut

For the farming industry it is essential to use liquid manure as natural fertilizer. Through new agricultural regulation 2015 in Germany the industry must develop new liquid manure spreader systems because the ammonia and methane emission are limited. In a research project the University of Applied Sciences Zwickau and some other industry partners will develop such a new innovative liquid manure spreader. The new liquid manure spreader should use pulsating air to distribute the liquid manure exactly. The pulsating air, which flows through the pipelines, should be analysed at a test station. For examinations at this test station it is important to find another substitute fluid because liquid manure smells strong, is not transparent and is also not homogeneous enough for scientific investigations. Furthermore it is important to ensure that the substitute fluid is, like liquid manure, a non-Newtonian fluid. The substitute fluid must be a shear-thinning substance - this means the viscosity decrease at higher shear rate. Many different samples like soap-water-farragoes, jelly-water-farragoes, agar-water-farragoes, soap-ethanol-farragoes and more are, for the project, examined in regard of their physical properties to find the best substitute fluid. The samples are examined at the rotational viscometer for viscosity at various shear rates and then compared with the viscosity values of liquid manure.

Slow Strain Rate Testing for Hydrogen Embrittlement Susceptibility of Alloy 718 in Substitute Ocean Water

NASA Astrophysics Data System (ADS)

LaCoursiere, M. P.; Aidun, D. K.; Morrison, D. J.

2017-05-01

The hydrogen embrittlement susceptibility of near-peak-aged UNS N07718 (Alloy 718) was evaluated by performing slow strain rate tests at room temperature in air and substitute ocean water. Tests in substitute ocean water were accomplished in an environmental cell that enabled in situ cathodic charging under an applied potential of -1.1 V versus SCE. Some specimens were cathodically precharged for 4 or 16 weeks at the same potential in a 3.5 wt.% NaCl-distilled water solution at 50 °C. Unprecharged specimens tested in substitute ocean water exhibited only moderate embrittlement with plastic strain to failure decreasing by about 20% compared to unprecharged specimens tested in air. However, precharged specimens exhibited significant embrittlement with plastic strain to failure decreasing by about 70%. Test environment (air or substitute ocean water with in situ charging) and precharge time (4 or 16 weeks) had little effect on the results of the precharged specimens. Fracture surfaces of precharged specimens were typical of hydrogen embrittlement and consisted of an outer brittle ring related to the region in which hydrogen infused during precharging, a finely dimpled transition zone probably related to the region where hydrogen was drawn in by dislocation transport, and a central highly dimpled ductile region. Fracture surfaces of unprecharged specimens tested in substitute ocean water consisted of a finely dimpled outer ring and heavily dimpled central region typical of ductile fracture.

QSAR studies in substituted 1,2,3,4,6,7,12,12a-octa-hydropyrazino[2',1':6,1]pyrido[3,4-b]indoles--a potent class of neuroleptics.

PubMed

Saxena, Anil K; Ram, Siya; Saxena, Mridula; Singh, Nidhi; Prathipati, Philip; Jain, Padam C; Singh, H K; Anand, Nitya

2003-05-01

A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.688). The best model describes a high correlation between predicted and experimental activity data (r=0.967). Statistical analysis of the equation populations indicates that hydrophobicity (as measured by pi(R), logP(o/w) and SlogP_VSA8), dipole y and structural parameters in terms of indicator variable, (In(1)) and globularity are important variables in describing the variation in the neuroleptic activity in the series.

The NBS Reaction: A Simple Explanation for the Predominance of Allylic Substitution over Olefin Addition by Bromine at Low Concentrations.

ERIC Educational Resources Information Center

Wamser, Carl C.; Scott, Lawrence T.

1985-01-01

Examines mechanisms related to use of N-bromosuccinimide (NBS) for bromination at an allylic position. Also presents derived rate laws for three possible reactions of molecular bromine with an alkene: (1) free radical substitution; (2) free radical addition; and (3) electrophilic addition. (JN)

75 FR 22397 - Combined Notice of Filings No. 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

... 19, 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and... Substitute Second Revised Sheet 2 et al. to FERC Gas Tariff, Fourth Revised Volume 1, to be effective 4/1/10.... Description: Dauphin Island Gathering Partners submits the Substitute Ninth Revised Sheet No. 7 et al. to FERC...

75 FR 4367 - Combined Notice of Filings No. 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... 14, 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and... submits Substitute Original Sheet 739c to FERC Gas Tariff, Sixth Revised Volume 1 to be effective 1/1/10...: Texas Gas Transmission, LLC submits Substitute Second Revised Sheet 4000 to FERC Gas Tariff, Third...

Robust linear discriminant analysis with distance based estimators

NASA Astrophysics Data System (ADS)

Lim, Yai-Fung; Yahaya, Sharipah Soaad Syed; Ali, Hazlina

2017-11-01

Linear discriminant analysis (LDA) is one of the supervised classification techniques concerning relationship between a categorical variable and a set of continuous variables. The main objective of LDA is to create a function to distinguish between populations and allocating future observations to previously defined populations. Under the assumptions of normality and homoscedasticity, the LDA yields optimal linear discriminant rule (LDR) between two or more groups. However, the optimality of LDA highly relies on the sample mean and pooled sample covariance matrix which are known to be sensitive to outliers. To alleviate these conflicts, a new robust LDA using distance based estimators known as minimum variance vector (MVV) has been proposed in this study. The MVV estimators were used to substitute the classical sample mean and classical sample covariance to form a robust linear discriminant rule (RLDR). Simulation and real data study were conducted to examine on the performance of the proposed RLDR measured in terms of misclassification error rates. The computational result showed that the proposed RLDR is better than the classical LDR and was comparable with the existing robust LDR.

Birth-death prior on phylogeny and speed dating

PubMed Central

2008-01-01

Background In recent years there has been a trend of leaving the strict molecular clock in order to infer dating of speciations and other evolutionary events. Explicit modeling of substitution rates and divergence times makes formulation of informative prior distributions for branch lengths possible. Models with birth-death priors on tree branching and auto-correlated or iid substitution rates among lineages have been proposed, enabling simultaneous inference of substitution rates and divergence times. This problem has, however, mainly been analysed in the Markov chain Monte Carlo (MCMC) framework, an approach requiring computation times of hours or days when applied to large phylogenies. Results We demonstrate that a hill-climbing maximum a posteriori (MAP) adaptation of the MCMC scheme results in considerable gain in computational efficiency. We demonstrate also that a novel dynamic programming (DP) algorithm for branch length factorization, useful both in the hill-climbing and in the MCMC setting, further reduces computation time. For the problem of inferring rates and times parameters on a fixed tree, we perform simulations, comparisons between hill-climbing and MCMC on a plant rbcL gene dataset, and dating analysis on an animal mtDNA dataset, showing that our methodology enables efficient, highly accurate analysis of very large trees. Datasets requiring a computation time of several days with MCMC can with our MAP algorithm be accurately analysed in less than a minute. From the results of our example analyses, we conclude that our methodology generally avoids getting trapped early in local optima. For the cases where this nevertheless can be a problem, for instance when we in addition to the parameters also infer the tree topology, we show that the problem can be evaded by using a simulated-annealing like (SAL) method in which we favour tree swaps early in the inference while biasing our focus towards rate and time parameter changes later on. Conclusion Our contribution leaves the field open for fast and accurate dating analysis of nucleotide sequence data. Modeling branch substitutions rates and divergence times separately allows us to include birth-death priors on the times without the assumption of a molecular clock. The methodology is easily adapted to take data from fossil records into account and it can be used together with a broad range of rate and substitution models. PMID:18318893

Birth-death prior on phylogeny and speed dating.

PubMed

Akerborg, Orjan; Sennblad, Bengt; Lagergren, Jens

2008-03-04

In recent years there has been a trend of leaving the strict molecular clock in order to infer dating of speciations and other evolutionary events. Explicit modeling of substitution rates and divergence times makes formulation of informative prior distributions for branch lengths possible. Models with birth-death priors on tree branching and auto-correlated or iid substitution rates among lineages have been proposed, enabling simultaneous inference of substitution rates and divergence times. This problem has, however, mainly been analysed in the Markov chain Monte Carlo (MCMC) framework, an approach requiring computation times of hours or days when applied to large phylogenies. We demonstrate that a hill-climbing maximum a posteriori (MAP) adaptation of the MCMC scheme results in considerable gain in computational efficiency. We demonstrate also that a novel dynamic programming (DP) algorithm for branch length factorization, useful both in the hill-climbing and in the MCMC setting, further reduces computation time. For the problem of inferring rates and times parameters on a fixed tree, we perform simulations, comparisons between hill-climbing and MCMC on a plant rbcL gene dataset, and dating analysis on an animal mtDNA dataset, showing that our methodology enables efficient, highly accurate analysis of very large trees. Datasets requiring a computation time of several days with MCMC can with our MAP algorithm be accurately analysed in less than a minute. From the results of our example analyses, we conclude that our methodology generally avoids getting trapped early in local optima. For the cases where this nevertheless can be a problem, for instance when we in addition to the parameters also infer the tree topology, we show that the problem can be evaded by using a simulated-annealing like (SAL) method in which we favour tree swaps early in the inference while biasing our focus towards rate and time parameter changes later on. Our contribution leaves the field open for fast and accurate dating analysis of nucleotide sequence data. Modeling branch substitutions rates and divergence times separately allows us to include birth-death priors on the times without the assumption of a molecular clock. The methodology is easily adapted to take data from fossil records into account and it can be used together with a broad range of rate and substitution models.

Triazine-Substituted and Acyl Hydrazones: Experiment and Computation Reveal a Stability Inversion at Low pH.

PubMed

Ji, Kun; Lee, Changsuk; Janesko, Benjamin G; Simanek, Eric E

2015-08-03

Condensation of a hydrazine-substituted s-triazine with an aldehyde or ketone yields an equivalent to the widely used, acid-labile acyl hydrazone. Hydrolysis of these hydrazones using a formaldehyde trap as monitored using HPLC reveals that triazine-substituted hydrazones are more labile than acetyl hydrazones at pH>5. The reactivity trends mirror that of the corresponding acetyl hydrazones, with hydrolysis rates increasing along the series (aromatic aldehyde

Slow but not low: genomic comparisons reveal slower evolutionary rate and higher dN/dS in conifers compared to angiosperms

PubMed Central

2012-01-01

Background Comparative genomics can inform us about the processes of mutation and selection across diverse taxa. Among seed plants, gymnosperms have been lacking in genomic comparisons. Recent EST and full-length cDNA collections for two conifers, Sitka spruce (Picea sitchensis) and loblolly pine (Pinus taeda), together with full genome sequences for two angiosperms, Arabidopsis thaliana and poplar (Populus trichocarpa), offer an opportunity to infer the evolutionary processes underlying thousands of orthologous protein-coding genes in gymnosperms compared with an angiosperm orthologue set. Results Based upon pairwise comparisons of 3,723 spruce and pine orthologues, we found an average synonymous genetic distance (dS) of 0.191, and an average dN/dS ratio of 0.314. Using a fossil-established divergence time of 140 million years between spruce and pine, we extrapolated a nucleotide substitution rate of 0.68 × 10-9 synonymous substitutions per site per year. When compared to angiosperms, this indicates a dramatically slower rate of nucleotide substitution rates in conifers: on average 15-fold. Coincidentally, we found a three-fold higher dN/dS for the spruce-pine lineage compared to the poplar-Arabidopsis lineage. This joint occurrence of a slower evolutionary rate in conifers with higher dN/dS, and possibly positive selection, showcases the uniqueness of conifer genome evolution. Conclusions Our results are in line with documented reduced nucleotide diversity, conservative genome evolution and low rates of diversification in conifers on the one hand and numerous examples of local adaptation in conifers on the other hand. We propose that reduced levels of nucleotide mutation in large and long-lived conifer trees, coupled with large effective population size, were the main factors leading to slow substitution rates but retention of beneficial mutations. PMID:22264329

Solute-solvent complex switching dynamics of chloroform between acetone and dimethylsulfoxide-two-dimensional IR chemical exchange spectroscopy.

PubMed

Kwak, Kyungwon; Rosenfeld, Daniel E; Chung, Jean K; Fayer, Michael D

2008-11-06

Hydrogen bonds formed between C-H and various hydrogen bond acceptors play important roles in the structure of proteins and organic crystals, and the mechanisms of C-H bond cleavage reactions. Chloroform, a C-H hydrogen bond donor, can form weak hydrogen-bonded complexes with acetone and with dimethylsulfoxide (DMSO). When chloroform is dissolved in a mixed solvent consisting of acetone and DMSO, both types of hydrogen-bonded complexes exist. The two complexes, chloroform-acetone and chloroform-DMSO, are in equilibrium, and they rapidly interconvert by chloroform exchanging hydrogen bond acceptors. This fast hydrogen bond acceptor substitution reaction is probed using ultrafast two-dimensional infrared (2D-IR) vibrational echo chemical exchange spectroscopy. Deuterated chloroform is used in the experiments, and the 2D-IR spectrum of the C-D stretching mode is measured. The chemical exchange of the chloroform hydrogen bonding partners is tracked by observing the time-dependent growth of off-diagonal peaks in the 2D-IR spectra. The measured substitution rate is 1/30 ps for an acetone molecule to replace a DMSO molecule in a chloroform-DMSO complex and 1/45 ps for a DMSO molecule to replace an acetone molecule in a chloroform-acetone complex. Free chloroform exists in the mixed solvent, and it acts as a reactive intermediate in the substitution reaction, analogous to a SN1 type reaction. From the measured rates and the equilibrium concentrations of acetone and DMSO, the dissociation rates for the chloroform-DMSO and chloroform-acetone complexes are found to be 1/24 ps and 1/5.5 ps, respectively. The difference between the measured rate for the complete substitution reaction and the rate for complex dissociation corresponds to the diffusion limited rate. The estimated diffusion limited rate agrees well with the result from a Smoluchowski treatment of diffusive reactions.

Parameters of proteome evolution from histograms of amino-acid sequence identities of paralogous proteins

PubMed Central

Axelsen, Jacob Bock; Yan, Koon-Kiu; Maslov, Sergei

2007-01-01

Background The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic parameters of these three basic processes is contained in the proteome-wide distribution of sequence identities of pairs of paralogous proteins. Results We introduce a simple mathematical framework based on a stochastic birth-and-death model that allows one to extract some of this information and apply it to the set of all pairs of paralogous proteins in H. pylori, E. coli, S. cerevisiae, C. elegans, D. melanogaster, and H. sapiens. It was found that the histogram of sequence identities p generated by an all-to-all alignment of all protein sequences encoded in a genome is well fitted with a power-law form ~ p-γ with the value of the exponent γ around 4 for the majority of organisms used in this study. This implies that the intra-protein variability of substitution rates is best described by the Gamma-distribution with the exponent α ≈ 0.33. Different features of the shape of such histograms allow us to quantify the ratio between the genome-wide average deletion/duplication rates and the amino-acid substitution rate. Conclusion We separately measure the short-term ("raw") duplication and deletion rates rdup∗, rdel∗ which include gene copies that will be removed soon after the duplication event and their dramatically reduced long-term counterparts rdup, rdel. High deletion rate among recently duplicated proteins is consistent with a scenario in which they didn't have enough time to significantly change their functional roles and thus are to a large degree disposable. Systematic trends of each of the four duplication/deletion rates with the total number of genes in the genome were analyzed. All but the deletion rate of recent duplicates rdel∗ were shown to systematically increase with Ngenes. Abnormally flat shapes of sequence identity histograms observed for yeast and human are consistent with lineages leading to these organisms undergoing one or more whole-genome duplications. This interpretation is corroborated by our analysis of the genome of Paramecium tetraurelia where the p-4 profile of the histogram is gradually restored by the successive removal of paralogs generated in its four known whole-genome duplication events. PMID:18039386

Codon adaptation and synonymous substitution rate in diatom plastid genes.

PubMed

Morton, Brian R; Sorhannus, Ulf; Fox, Martin

2002-07-01

Diatom plastid genes are examined with respect to codon adaptation and rates of silent substitution (Ks). It is shown that diatom genes follow the same pattern of codon usage as other plastid genes studied previously. Highly expressed diatom genes display codon adaptation, or a bias toward specific major codons, and these major codons are the same as those in red algae, green algae, and land plants. It is also found that there is a strong correlation between Ks and variation in codon adaptation across diatom genes, providing the first evidence for such a relationship in the algae. It is argued that this finding supports the notion that the correlation arises from selective constraints, not from variation in mutation rate among genes. Finally, the diatom genes are examined with respect to variation in Ks among different synonymous groups. Diatom genes with strong codon adaptation do not show the same variation in synonymous substitution rate among codon groups as the flowering plant psbA gene which, previous studies have shown, has strong codon adaptation but unusually high rates of silent change in certain synonymous groups. The lack of a similar finding in diatoms supports the suggestion that the feature is unique to the flowering plant psbA due to recent relaxations in selective pressure in that lineage.

High-energy lithium-ion battery using substituted LiCoPO4: From coin type to 1 Ah cell

NASA Astrophysics Data System (ADS)

Liu, D.; Zhu, W.; Kim, C.; Cho, M.; Guerfi, A.; Delp, S. A.; Allen, J. L.; Jow, T. R.; Zaghib, K.

2018-06-01

Cr, Fe and Si were added to improve the performance of olivine LiCoPO4 in cathodes for lithium-ion batteries. A substituted-LiCoPO4 in a half cell delivered a reversible capacity of 125 mAh/g at C/3 rate, with no capacity loss after over 100 cycles at 25 °C. The well-known capacity fade of LiCoPO4-based cathodes was almost completely eliminated by substituting Cr, Fe and Si.

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.

[Guidelines for substitution treatments in prison populations].

PubMed

Michel, L; Maguet, O

2005-01-01

Care access for the drug addict patients in prison (in particular for the treatments of substitution) in France is very unequal from one establishment to another. This reflects the great variability of the practices of substitution and especially the absence of consensus on the methods of adaptation of these practices to the prison environment. Because of difficulties expressed by prisoners and medical staff on this subject and of stakes (let us recall that approximately 30% of the prisoners are dependent or abusers of one or more psychoactive substances), the formulation of recommendations or of a good practices guide of substitution in prison appeared necessary. Work that we detail here answers a ordering of the Advisory Commission of the Treatments of Substitution (September 2001) whose authors are members. It was presented at the session April 2003. It results from the confrontation of a review of the literature (including legal texts and official reports concerning substitution, the organization of the care in prison environment and the lawful framework), with a vast investigation. The latter was carried out near medical staff (22 prisons), penitentiary staff (3 prisons, 27 people met including directors of these establishments) and prisoners (7 establishments, 28 prisoners met) in the form of individual talks (semi-directing interviews with evaluation of the type of existing device and its knowledge by the penitentiary staff and the prisoners; statement of the suggestions, needs and requests of the medical, penitentiary staffs and of the prisoners). In the whole visited prisons, 7.8% (870) of the prisoners received substitution treatments (6.35% by buprenorphine, 1.44% by methadone), representing a proportion of substituted drug addicts (870 substituted for an evaluation of 3,350 prisoners drug addicts among the 11,168 prisoners of the 22 visited prisons) notably lower than that in free environment (56%, ie 96,000 substituted for an evaluated population of drug addicts for heroin of 160,000). There are however considerable variations (from 0 to 16.2%) of the proportion of substituted of one establishment for the other according to the type of prison, of its size, its localization and the type of medical device present. If a consensus exists for methadone (daily delivery with sanitary control), the organization of the care relating to the buprenorphine is extremely variable from one establishment to another, often putting in difficulty as well the medical teams as the prisoners. One recommendation is essential: the formulation of an individualized therapeutic project. Thirteen other recommendations are made in the following fields: renewal of substitution treatments, initiation of substitution treatments, urinary controls, methods of prescription, methods of delivery, co-prescriptions, global care, confidentiality, files, exits and transfers, extractions, formation, accompaniment of the teams. These recommendations being formulated, many medical concerns remain present and several questions open. The report of joint mission IGAS/IGSJ of June 2001 on the health of the prisoners underlines the principal persistent gaps: hygiene and public health, treatment of the mental disorders, the follow-up of the sexual delinquents, handling ageing, handicap and the end of lifetime. In the same way, the difficulties listed in prison environment concerning substitution are only the exacerbation of those existing outside: the misuses and traffics are common in free environment, risk reduction in prison, as outside, handle with obstacles related to the penalization of the drug use and can hardly evolve except questioning the law of 1970. The prison practice opens also questions: that of the "duration" of the substitution, frequently posed by the prisoners; concern to see the prison becoming a privileged place of access to the care, combining sanction and care whereas the law of 1970 allows the alternative (care or sanction); that of the clinic of the misuse, particularly "readable" in prison environment; and finally the question of the shared secrecy, extremely delicate in prison context although clarified by the law of March 04, 2002.

Virtual libraries of tetrapyrrole macrocycles. Combinatorics, isomers, product distributions, and data mining.

PubMed

Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S

2011-09-26

A software program (PorphyrinViLiGe) has been developed to enumerate the type and relative amounts of substituted tetrapyrrole macrocycles in a virtual library formed by one of four different classes of reactions. The classes include (1) 4-fold reaction of n disubstituted heterocycles (e.g., pyrroles or diiminoisoindolines) to form β-substituted porphyrins, β-substituted tetraazaporphyrins, or α- or β-substituted phthalocyanines; (2) combination of m aminoketones and n diones to form m × n pyrroles, which upon 4-fold reaction give β-substituted porphyrins; (3) derivatization of an 8-point tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and pyrrole to form meso-substituted porphyrins. The program accommodates variable ratios of reactants, reversible or irreversible reaction (reaction classes 1 and 2), and degenerate modes of formation. Pólya's theorem (for enumeration of cyclic entities) has also been implemented and provides validation for reaction classes 3 and 4. The output includes the number and identity of distinct reaction-accessible substituent combinations, the number and identity of isomers thereof, and the theoretical mass spectrum. Provisions for data mining enable assessment of the number of products having a chosen pattern of substituents. Examples include derivatization of an octa-substituted phthalocyanine with eight reagents to afford a library of 2,099,728 members (yet only 6435 distinct substituent combinations) and reversible reaction of six distinct disubstituted pyrroles to afford 2649 members (yet only 126 distinct substituent combinations). In general, libraries of substituted tetrapyrrole macrocycles occupy a synthetically accessible region of chemical space that is rich in isomers (>99% or 95% for the two examples, respectively).

Folding and conformational consequences of glycine to alanine replacements at different positions in a collagen model peptide.

PubMed

Bhate, Manjiri; Wang, Xin; Baum, Jean; Brodsky, Barbara

2002-05-21

The collagen model peptide T1-892 includes a C-terminal nucleation domain, (Gly-Pro-Hyp)(4), and an N-terminal (Gly-X-Y)(6) sequence taken from type I collagen. In osteogenesis imperfecta (OI) and other collagen diseases, single base mutations often convert one Gly to a larger residue, and T1-892 homologues modeling such mutations were synthesized with Gly to Ala substitutions in either the (Gly-Pro-Hyp)(4) domain, Gly25Ala, or the (Gly-X-Y)(6) domain, Gly10Ala. CD and NMR studies show the Gly10Ala peptide forms a normal triple-helix at the C-terminal end and propagates from the C- to the N-terminus until the Gly --> Ala substitution is encountered. At this point, triple-helix folding is terminated and cannot be reinitiated, leaving a nonhelical N-terminus. A decreased thermal stability is observed as a result of the shorter length of the triple-helix. In contrast, introduction of the Gly to Ala replacement at position 25, in the nucleation domain, shifts the monomer/trimer equilibrium toward the monomer form. The increased monomer and lower trimer populations are reflected in the dramatic decrease in triple-helix content and stability. Unlike the Ala replacement at position 10, the Ala substitution in the (Gly-Pro-Hyp)(4) region can still be incorporated into a triple-helix, but at a greatly decreased rate of folding, since the original efficient nucleation site is no longer operative. The specific consequences of Gly to Ala replacements in two distinctive sequences in this triple-helical peptide may help clarify the variability in OI clinical severity resulting from mutations at different sites along type I collagen chains.

Large-scale analyses of synonymous substitution rates can be sensitive to assumptions about the process of mutation.

PubMed

Aris-Brosou, Stéphane; Bielawski, Joseph P

2006-08-15

A popular approach to examine the roles of mutation and selection in the evolution of genomes has been to consider the relationship between codon bias and synonymous rates of molecular evolution. A significant relationship between these two quantities is taken to indicate the action of weak selection on substitutions among synonymous codons. The neutral theory predicts that the rate of evolution is inversely related to the level of functional constraint. Therefore, selection against the use of non-preferred codons among those coding for the same amino acid should result in lower rates of synonymous substitution as compared with sites not subject to such selection pressures. However, reliably measuring the extent of such a relationship is problematic, as estimates of synonymous rates are sensitive to our assumptions about the process of molecular evolution. Previous studies showed the importance of accounting for unequal codon frequencies, in particular when synonymous codon usage is highly biased. Yet, unequal codon frequencies can be modeled in different ways, making different assumptions about the mutation process. Here we conduct a simulation study to evaluate two different ways of modeling uneven codon frequencies and show that both model parameterizations can have a dramatic impact on rate estimates and affect biological conclusions about genome evolution. We reanalyze three large data sets to demonstrate the relevance of our results to empirical data analysis.

State generic substitution laws can lower drug outlays under Medicaid.

PubMed

Shrank, William H; Choudhry, Niteesh K; Agnew-Blais, Jessica; Federman, Alex D; Liberman, Joshua N; Liu, Jun; Kesselheim, Aaron S; Brookhart, M Alan; Fischer, Michael A

2010-07-01

To stem the rising costs of medications provided to patients enrolled in Medicaid, states have implemented varying policies about generic substitution. These policies differ in the extent to which pharmacists or patients can influence which medications they choose. Using national Medicaid data, we evaluated the relationship between different generic substitution policies and the use of generic simvastatin, a cholesterol-lowering drug, after the patent for the brand-name equivalent, Zocor, expired. States that implemented policies requiring patients' consent prior to generic substitution experienced rates of substitution that were 25 percent lower than those of states that did not require patient consent. By eliminating patient consent requirements, state Medicaid programs could expect to save more than $100 million in coverage for three top-selling medications that are nearing patent expiration. Although these consent requirements are probably intended to increase patient autonomy, policy makers should consider the sizable opportunity costs.

Research of Energy Substitution Strategy of China

NASA Astrophysics Data System (ADS)

Zhang, Lifeng; kai, Chen

For a long time, China's energy endowment structure determines the production structure and consumption structure of energy are coal-based.This situation is difficult to change for quite a long time. With the rapid economic growth, industrialization and urbanization, the demand for energy, especially for oil, natural gas will continue to increase. But the oil and gas supply can not meet the needs of rapid growth. The most direct way is to import, and imports will be charged by the international energy situation, and will affect energy and economic security. In view of our country abundant coal resources, we can consider to use coal substituting oil and natural gas to reduce dependence on foreign energy, to strengthen energy and economic security. Therefore, using translog production function, the text forecasts substitution elasticity and the marginal substitution rate between the capital, coal, oil and natural gas, and puts forward substitution program.

Improvement in low-temperature and instantaneous high-rate output performance of Al-free AB5-type hydrogen storage alloy for negative electrode in Ni/MH battery: Effect of thermodynamic and kinetic regulation via partial Mn substituting

NASA Astrophysics Data System (ADS)

Zhou, Wanhai; Zhu, Ding; Tang, Zhengyao; Wu, Chaoling; Huang, Liwu; Ma, Zhewen; Chen, Yungui

2017-03-01

A series of Al-free Mn-modified AB5-type hydrogen storage alloys have been designed and the effects of thermodynamic stability and electrochemical kinetics on electrochemical performance via Mn substituting have been investigated. Compared with high-Al alloys, the Al-free alloys in this study have better low-temperature performance and instantaneous high-rate output because of the higher surface catalytic ability. After partial substitution of Ni by Mn, both the hydrogen desorption capacity and plateau pressure decrease, and correspondingly results in an improved thermodynamic stability which is adverse to low-temperature delivery. Additionally, with the improvement of charge acceptance ability and anti-corrosion property via Mn substitution, the room-temperature discharge capacity and cycling stability increase slightly. However, Mn adversely affects the electrochemical kinetics and deteriorates both the surface catalytic ability and the bulk hydrogen diffusion ability, leading to the drop of low-temperature dischargeability, high-rate dischargeability and peak power (Ppeak). Based on the thermodynamic and kinetic regulation and overall electrochemical properties, the optimal composition is obtained when x = 0.2, the discharge capacity is 243.6 mAh g-1 at -40 °C with 60 mA g-1, and the Ppeak attains to 969.6 W kg-1 at -40 °C.

Photobiomodulation of a flowable matrix in a human skin ex vivo model demonstrates energy-based enhancement of engraftment integration and remodeling.

PubMed

Neves, Lia M G; Parizotto, Nivaldo A; Cominetti, Marcia R; Bayat, Ardeshir

2018-04-24

The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transcriptome sequencing reveals genome-wide variation in molecular evolutionary rate among ferns.

PubMed

Grusz, Amanda L; Rothfels, Carl J; Schuettpelz, Eric

2016-08-30

Transcriptomics in non-model plant systems has recently reached a point where the examination of nuclear genome-wide patterns in understudied groups is an achievable reality. This progress is especially notable in evolutionary studies of ferns, for which molecular resources to date have been derived primarily from the plastid genome. Here, we utilize transcriptome data in the first genome-wide comparative study of molecular evolutionary rate in ferns. We focus on the ecologically diverse family Pteridaceae, which comprises about 10 % of fern diversity and includes the enigmatic vittarioid ferns-an epiphytic, tropical lineage known for dramatically reduced morphologies and radically elongated phylogenetic branch lengths. Using expressed sequence data for 2091 loci, we perform pairwise comparisons of molecular evolutionary rate among 12 species spanning the three largest clades in the family and ask whether previously documented heterogeneity in plastid substitution rates is reflected in their nuclear genomes. We then inquire whether variation in evolutionary rate is being shaped by genes belonging to specific functional categories and test for differential patterns of selection. We find significant, genome-wide differences in evolutionary rate for vittarioid ferns relative to all other lineages within the Pteridaceae, but we recover few significant correlations between faster/slower vittarioid loci and known functional gene categories. We demonstrate that the faster rates characteristic of the vittarioid ferns are likely not driven by positive selection, nor are they unique to any particular type of nucleotide substitution. Our results reinforce recently reviewed mechanisms hypothesized to shape molecular evolutionary rates in vittarioid ferns and provide novel insight into substitution rate variation both within and among fern nuclear genomes.

The reluctance to burden others as a value in end-of-life decision making: a source of inaccuracy in substituted judgment.

PubMed

Winter, Laraine; Parks, Susan M

2012-03-01

Most patients are decisionally incapacitated at the end of life, leaving final treatment decisions to proxies, whose substituted judgment is often inaccurate. We investigated the reluctance to burden others (RBO), a commonly cited patient value, as a possible source of proxy inaccuracy. In a sample of 202 elders and their proxies, elders responded to three burden-related questions and the Life-prolonging Treatment Preferences Questionnaire. Proxies used substituted judgment to respond to the same questions. Although RBO predicted treatment preferences for both elders and proxies, elders rated RBO significantly more important than did proxies. In addition, larger elder-proxy differences in RBO were associated with more inaccurate substituted judgment.

Comparisons of pollen substitute diets for honey bees: consumption rates by colonies and effects on brood and adult populations.

USDA-ARS?s Scientific Manuscript database

Commercially available pollen substitute diets for honey bees (Apis mellifera L.) were evaluated for consumption and colony growth (brood and adult populations) and compared with pollen cake and high fructose corn syrup (HFCS). Two trials were conducted; the first for 3 months during the fall and w...

Plastid–Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae

PubMed Central

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

2016-01-01

Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid–nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (ω) were accelerated in both plastid- (CpRP) and nuclear-encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased ω in CpRP was mainly due to intensified positive selection whereas increased ω in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. PMID:27190001

Evolutionary Stasis in Cycad Plastomes and the First Case of Plastome GC-Biased Gene Conversion

PubMed Central

Wu, Chung-Shien; Chaw, Shu-Miaw

2015-01-01

In angiosperms, gene conversion has been known to reduce the mutational load of plastid genomes (the plastomes). Particularly, more frequent gene conversions in inverted repeat (IR) than in single copy (SC) regions result in contrasting substitution rates between these two regions. However, little has been known about the effect of gene conversion in the evolution of gymnosperm plastomes. Cycads (Cycadophyta) are the second largest gymnosperm group. Evolutionary study of their plastomes is limited to the basal cycad genus, Cycas. In this study, we addressed three questions. 1) Do the plastomes of other cycad genera evolve slowly as previously observed in the plastome of Cycas taitungensis? 2) Do substitution rates differ between their SC and IR regions? And 3) Does gene conversion occur in the cycad plastomes? If yes, is it AT-biased or GC-biased? Plastomes of eight species from other eight genera of cycads were sequenced. These plastomes are highly conserved in genome organization. Excluding ginkgo, cycad plastomes have significantly lower synonymous and nonsynonymous substitution rates than other gymnosperms, reflecting their evolutionary stasis in nucleotide mutations. In the IRs of cycad plastomes, the reduced substitution rates and GC-biased mutations are associated with a GC-biased gene conversion (gBGC) mechanism. Further investigations suggest that in cycads, gBGC is able to rectify plastome-wide mutations. Therefore, this study is the first to uncover the plastomic gBGC in seed plants. We also propose a gBGC model to interpret the dissimilar evolutionary patterns as well as the compositionally biased mutations in the SC and IR regions of cycad plastomes. PMID:26116919

Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32.

PubMed

Brennan, Matthew J; Karcz, Jennifer; Vaughn, Nicholas R; Woolwine-Cunningham, Yvonne; DePriest, Adam D; Escalona, Yerko; Perez-Acle, Tomas; Skerrett, I Martha

2015-07-10

Tryptophan was substituted for residues in all four transmembrane domains of connexin32. Function was assayed using dual cell two-electrode voltage clamp after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15 substitutions were made, six abolished coupling and five others significantly reduced function. Only TM2 and TM3 included a distinct helical face that lacked sensitivity to tryptophan substitution. Results were visualized on a comparative model of Cx32 hemichannel. In this model, a region midway through the membrane appears highly sensitive to tryptophan substitution and includes residues Arg-32, Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1 and TM2 were highly sensitive to tryptophan substitution, whereas the lipid-facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also highly sensitive to tryptophan substitution. Although future studies will be required to separate trafficking-defective mutants from those that alter channel function, a subset of interactions important for voltage gating was identified. Interactions important for voltage gating occurred mainly in the mid-region of the channel and focused on TM1. To determine whether results could be extrapolated to other connexins, TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of Cx32. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Body weight manipulation, reinforcement value and choice between sucrose and wheel running: a behavioral economic analysis.

PubMed

Belke, Terry W; Pierce, W David

2009-02-01

Twelve female Long-Evans rats were exposed to concurrent variable (VR) ratio schedules of sucrose and wheel-running reinforcement (Sucrose VR 10 Wheel VR 10; Sucrose VR 5 Wheel VR 20; Sucrose VR 20 Wheel VR 5) with predetermined budgets (number of responses). The allocation of lever pressing to the sucrose and wheel-running alternatives was assessed at high and low body weights. Results showed that wheel-running rate and lever-pressing rates for sucrose and wheel running increased, but the choice of wheel running decreased at the low body weight. A regression analysis of relative consumption as a function of relative price showed that consumption shifted toward sucrose and interacted with price differences in a manner consistent with increased substitutability. Demand curves showed that demand for sucrose became less elastic while demand for wheel running became more elastic at the low body weight. These findings reflect an increase in the difference in relative value of sucrose and wheel running as body weight decreased. Discussion focuses on the limitations of response rates as measures of reinforcement value. In addition, we address the commonalities between matching and demand curve equations for the analysis of changes in relative reinforcement value.

Impact of marital status on health

NASA Astrophysics Data System (ADS)

Richmond, Peter; Roehner, Bertrand M.

2017-11-01

The Farr-Bertillon law states that the mortality rate of single and widowed persons is about three times the rate of married people of same age. This excess mortality can be measured with good accuracy for all ages except for young widowers. The reason is that, at least nowadays, very few people become widowed under the age of 30. Here we show that disability data from census records can also be used as a reliable substitute for mortality rates. In fact excess-disability and excess-mortality go hand in hand. Moreover, as there are about ten times more cases of disability than deaths, the disability variable is able to offer more accurate measurements in all cases where the number of deaths is small. This allows a more accurate investigation of the young widower effect; it confirms that, as already suspected from death rate data, there is a huge spike between the ages of 20 and 30. By using disability rates we can also study additional features not accessible using death rate data. For example we can examine the health impact of a change in living place. The observed temporary inflated disability rate confirms what could be expected by invoking the ;Transient Shock; conjecture formuladted by the authors in a previous paper. Finally, in another observation it is shown that the disability rate of newly married persons is higher than for those who have been married for more than one year, a result which comes in confirmation of the ;newly married couple; effect reported in an earlier paper.

How to calculate the non-synonymous to synonymous rate ratio of protein-coding genes under the Fisher-Wright mutation-selection framework.

PubMed

Dos Reis, Mario

2015-04-01

First principles of population genetics are used to obtain formulae relating the non-synonymous to synonymous substitution rate ratio to the selection coefficients acting at codon sites in protein-coding genes. Two theoretical cases are discussed and two examples from real data (a chloroplast gene and a virus polymerase) are given. The formulae give much insight into the dynamics of non-synonymous substitutions and may inform the development of methods to detect adaptive evolution. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Combustion Properties of Amino-Substituted Guanidinium 4,4',5,5'-Tetranitro-2,2'-biimidazolate(N4BIM) Salts

DOE PAGES

Tappan, Bryce C.; Chavez, David E.

2014-12-02

This paper describes the combustion properties of the amino-substituted guanidinium 4,4’,5,5’-tetranitro-2,2’-biimidazolate (N4BIM) series, including the bis-mono, di and triaminoguanidinium salts. These salts are of interest as propellant ingredient additives, and in particular, the bis-triaminoguanidinium salt of N4BIM displays excellent burn rate and combustion behavior. Our combustion studies have shown that TAGN4-BIM displays a fast burning rate and has the lowest pressure dependence exponent yet measured for a triaminoguanidinium salt.

Clinical and genetic characterization of a founder PKHD1 mutation in Afrikaners with ARPKD.

PubMed

Lambie, Lindsay; Amin, Rasheda; Essop, Fahmida; Cnaan, Avital; Krause, Amanda; Guay-Woodford, Lisa M

2015-02-01

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) occurs in 1:20,000 live births. Disease expression is widely variable, with approximately 30 % of affected neonates dying perinatally, while others survive to adulthood. Mutations at the PKHD1 locus are responsible for all typical presentations. The objectives of this study were to define the clinical and genetic characteristics in a cohort of South African patients of Afrikaner origin, a population with a high prevalence of ARPKD. DNA from the cohort was analyzed for background haplotypes and the p.M627K mutation previously identified in two unrelated Afrikaner patients. The clinical phenotype of the homozygous group was characterized. Analysis of 36 Afrikaner families revealed that 27 patients, from 24 (67 %) families, were homozygous for the p.M627K substitution, occurring on a common haplotype. The clinical phenotype of the homozygous individuals was variable. Our data provide strong evidence that the p.M627K substitution is a founder mutation in the Afrikaner population and can be used for streamlined diagnostic testing for at-risk pregnancies. The observed clinical variability suggests that disease expression is modulated by other genetic loci or by gene-environment interactions.

Autism and Diagnostic Substitution: Evidence from a Study of Adults with a History of Developmental Language Disorder

ERIC Educational Resources Information Center

Bishop, Dorothy V. M.; Whitehouse, Andrew J. O.; Watt, Helen J.; Line, Elizabeth A.

2008-01-01

Rates of diagnosis of autism have risen since 1980, raising the question of whether some children who previously had other diagnoses are now being diagnosed with autism. We applied contemporary diagnostic criteria for autism to adults with a history of developmental language disorder, to discover whether diagnostic substitution has taken place. A…

Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies

PubMed Central

Millhouse, Paul W; Kepler, Christopher K; Radcliff, Kris E.; Fehlings, Michael G.; Janssen, Michael E.; Sasso, Rick C.; Benedict, James J.; Vaccaro, Alexander R

2016-01-01

Study Design A narrative review of literature. Objective This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature. Summary of Background Data Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results. Methods A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes. Results A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes. Conclusions There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall. PMID:27909654

Predictors of generic substitution: The role of psychological, sociodemographic, and contextual factors.

PubMed

Drozdowska, Aleksandra; Hermanowski, Tomasz

2016-01-01

Escalating pharmaceutical costs have become a global challenge for both governments and patients. Generic substitution is one way of decreasing these costs. The aim of this study was to investigate factors associated with patients' choice between generic drugs and innovator drugs. The survey was conducted in June 2013, 1000 people from across Poland were chosen as a representative population sample. The outcome (a preference for generics/a preference for innovator pharmaceuticals/no preference) was modeled by multinomial logistic regression, adjusted for several variables describing patients' sensitivity to selected generic features (price, brand, and country of origin), to third-party opinions about generics (information on generics in the mass media, opinions of health professionals (i.e. physicians, pharmacists), relatives/friends), as well as patients' personal experiences and income per household. The results supported the predictive capacity of most independent variables (except for patient sensitivity to the country of origin and to the information on generics in the mass media), denoting patients' preferences toward generic substitution. Patient sensitivity to recommendations by physicians, generic brand, and household income were the strongest predictors of the choice between generic and innovator pharmaceuticals (P < 0.001). The probability of choosing generics over innovator drugs was significantly higher among respondents with the lowest income levels, in those who were indifferent to generic brand or their physician's opinion, as well as in respondents who were sensitive to recommendations by pharmacists or attached a greater value to a past experience with generics (their own experience or that of relatives/friends). In consideration of the foregoing, awareness-raising campaigns may be recommended, supported by a variety of systemic solutions and tools to encourage generic substitution. Copyright © 2016 Elsevier Inc. All rights reserved.

The Relationship between the Structure of the Tick-Borne Encephalitis Virus Strains and Their Pathogenic Properties

PubMed Central

Belikov, Sergei I.; Kondratov, Ilya G.; Potapova, Ulyana V.; Leonova, Galina N.

2014-01-01

Tick-borne encephalitis virus (TBEV) is transmitted to vertebrates by taiga or forest ticks through bites, inducing disease of variable severity. The reasons underlying these differences in the severity of the disease are unknown. In order to identify genetic factors affecting the pathogenicity of virus strains, we have sequenced and compared the complete genomes of 34 Far-Eastern subtype (FE) TBEV strains isolated from patients with different disease severity (Primorye, the Russian Far East). We analyzed the complete genomes of 11 human pathogenic strains isolated from the brains of dead patients with the encephalitic form of the disease (Efd), 4 strains from the blood of patients with the febrile form of TBE (Ffd), and 19 strains from patients with the subclinical form of TBE (Sfd). On the phylogenetic tree, pathogenic Efd strains formed two clusters containing the prototype strains, Senzhang and Sofjin, respectively. Sfd strains formed a third separate cluster, including the Oshima strain. The strains that caused the febrile form of the disease did not form a separate cluster. In the viral proteins, we found 198 positions with at least one amino acid residue substitution, of which only 17 amino acid residue substitutions were correlated with the variable pathogenicity of these strains in humans and they authentically differed between the groups. We considered the role of each amino acid substitution and assumed that the deletion of 111 amino acids in the capsid protein in combination with the amino acid substitutions R16K and S45F in the NS3 protease may affect the budding process of viral particles. These changes may be the major reason for the diminished pathogenicity of TBEV strains. We recommend Sfd strains for testing as attenuation vaccine candidates. PMID:24740396

The degree of attenuation of tick-borne encephalitis virus depends on the cumulative effects of point mutations.

PubMed

Gritsun, T S; Desai, A; Gould, E A

2001-07-01

An infectious clone (pGGVs) of the tick-borne encephalitis complex virus Vasilchenko (Vs) was constructed previously. Virus recovered from pGGVs produced slightly smaller plaques than the Vs parental virus. Sequence analysis demonstrated five nucleotide differences between the original Vs virus and pGGVs; four of these mutations resulted in amino acid substitutions, while the fifth mutation was located in the 3' untranslated region (3'UTR). Two mutations were located in conserved regions and three mutations were located in variable regions of the virus genome. Reverse substitutions from the conserved regions of the genome, R(496)-->H in the envelope (E) gene and C(10884)-->T in the 3'UTR, were introduced both separately and together into the infectious clone and their biological effect on virus phenotype was evaluated. The engineered viruses with R(496) in the E protein produced plaques of smaller size than viruses with H(496) at this position. This mutation also affected the growth and neuroinvasiveness of the virus. In contrast, the consequence of a T(10884)-->C substitution within the 3'UTR was noticeable only in cytotoxicity and neuroinvasiveness tests. However, all virus mutants engineered by modification of the infectious clone, including one with two wild-type mutations, H(496) and T(10884), showed reduced neuroinvasiveness in comparison with the Vs parental virus. Therefore, although the H(496)-->R and T(10884)-->C substitutions clearly reduce virus virulence, the other mutations within the variable regions of the capsid (I(45)-->F) and the NS5 (T(2688)-->A and M(3385)-->I) genes also contribute to the process of attenuation. In terms of developing flavivirus vaccines, the impact of accumulating apparently minor mutations should be assessed in detail.

Effect of rare-earth substitution at La-site on structural, electrical and thermoelectric properties of La0.7-xRExSr0.3MnO3 compounds (x = 0, 0.2, 0.3; RE = Eu, Gd, Y)

NASA Astrophysics Data System (ADS)

Choudhary, Y. R. S.; Mangavati, Suraj; Patil, Siddanagouda; Rao, Ashok; Nagaraja, B. S.; Thomas, Riya; Okram, G. S.; Kini, Savitha G.

2018-04-01

In the present communication, we present results on the effect of rare-earth (RE) substitution at La-site on the structural, electrical and thermoelectric properties of La0.7-xRExSr0.3MnO3 compounds. The lattice parameters are observed to decrease with RE-doping which is attributed to the fact that the substituted RE ions (RE = Eu, Gd and Y) are smaller than that of La ion. In high temperature semiconducting regime, small polaron hopping (SPH) model is valid, whereas, variable hopping model is valid in low temperature metallic region. The resistivity in the entire temperature range follows percolation model. All the samples exhibit sign reversal in thermopower, S. From temperature dependent S data, it is seen that SPH model is applicable in high temperature regime.

The initial impact of Medicare's new prospective payment system for kidney dialysis.

PubMed

Hirth, Richard A; Turenne, Marc N; Wheeler, John R C; Nahra, Tammie A; Sleeman, Kathryn K; Zhang, Wei; Messana, Joseph A

2013-10-01

Medicare implemented a new prospective payment system (PPS) on January 1, 2011. This PPS covers an expanded bundle of services, including services previously paid on a fee-for-service basis. The objectives of the new PPS include more efficient decisions about treatment service combinations and modality choice. Primary data for this study are Medicare claims files for all dialysis patients for whom Medicare is the primary payer. We compare use of key injectable medications under the bundled PPS to use when those drugs were separately billable and examine variability across providers. We also compare each patient's dialysis modality before and after the PPS. Use of relatively expensive drugs, including erythropoiesis-stimulating agents, declined substantially after institution of the new PPS, whereas use of iron products, often therapeutic substitutes for erythropoiesis-stimulating agents, increased. Less expensive vitamin D products were substituted for more expensive types. Drug spending overall decreased by ∼$25 per session, or about 5 times the mandated reduction in the base payment rate of ∼$5. Use of peritoneal dialysis increased in 2011 after being nearly flat in the years prior to the PPS, with the increase concentrated in patients in their first or second year of dialysis. Home hemodialysis continued to increase as a percentage of total dialysis services, but at a rate similar to the pre-PPS trend. The expanded bundle dialysis PPS provided incentives for the use of lower cost therapies. These incentives seem to have motivated dialysis providers to move toward lower cost methods of care in both their use of drugs and choice of modalities. Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.

Double-strand break repair processes drive evolution of the mitochondrial genome in Arabidopsis.

PubMed

Davila, Jaime I; Arrieta-Montiel, Maria P; Wamboldt, Yashitola; Cao, Jun; Hagmann, Joerg; Shedge, Vikas; Xu, Ying-Zhi; Weigel, Detlef; Mackenzie, Sally A

2011-09-27

The mitochondrial genome of higher plants is unusually dynamic, with recombination and nonhomologous end-joining (NHEJ) activities producing variability in size and organization. Plant mitochondrial DNA also generally displays much lower nucleotide substitution rates than mammalian or yeast systems. Arabidopsis displays these features and expedites characterization of the mitochondrial recombination surveillance gene MSH1 (MutS 1 homolog), lending itself to detailed study of de novo mitochondrial genome activity. In the present study, we investigated the underlying basis for unusual plant features as they contribute to rapid mitochondrial genome evolution. We obtained evidence of double-strand break (DSB) repair, including NHEJ, sequence deletions and mitochondrial asymmetric recombination activity in Arabidopsis wild-type and msh1 mutants on the basis of data generated by Illumina deep sequencing and confirmed by DNA gel blot analysis. On a larger scale, with mitochondrial comparisons across 72 Arabidopsis ecotypes, similar evidence of DSB repair activity differentiated ecotypes. Forty-seven repeat pairs were active in DNA exchange in the msh1 mutant. Recombination sites showed asymmetrical DNA exchange within lengths of 50- to 556-bp sharing sequence identity as low as 85%. De novo asymmetrical recombination involved heteroduplex formation, gene conversion and mismatch repair activities. Substoichiometric shifting by asymmetrical exchange created the appearance of rapid sequence gain and loss in association with particular repeat classes. Extensive mitochondrial genomic variation within a single plant species derives largely from DSB activity and its repair. Observed gene conversion and mismatch repair activity contribute to the low nucleotide substitution rates seen in these genomes. On a phenotypic level, these patterns of rearrangement likely contribute to the reproductive versatility of higher plants.

Analysis of Evolutionary Processes of Species Jump in Waterfowl Parvovirus

PubMed Central

Fan, Wentao; Sun, Zhaoyu; Shen, Tongtong; Xu, Danning; Huang, Kehe; Zhou, Jiyong; Song, Suquan; Yan, Liping

2017-01-01

Waterfowl parvoviruses are classified into goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV) according to their antigenic features and host preferences. A novel duck parvovirus (NDPV), identified as a new variant of GPV, is currently infecting ducks, thus causing considerable economic loss. This study analyzed the molecular evolution and population dynamics of the emerging parvovirus capsid gene to investigate the evolutionary processes concerning the host shift of NDPV. Two important amino acids changes (Asn-489 and Asn-650) were identified in NDPV, which may be responsible for host shift of NDPV. Phylogenetic analysis indicated that the currently circulating NDPV originated from the GPV lineage. The Bayesian Markov chain Monte Carlo tree indicated that the NDPV diverged from GPV approximately 20 years ago. Evolutionary rate analyses demonstrated that GPV evolved with 7.674 × 10-4 substitutions/site/year, and the data for MDPV was 5.237 × 10-4 substitutions/site/year, whereas the substitution rate in NDPV branch was 2.25 × 10-3 substitutions/site/year. Meanwhile, viral population dynamics analysis revealed that the GPV major clade, including NDPV, grew exponentially at a rate of 1.717 year-1. Selection pressure analysis showed that most sites are subject to strong purifying selection and no positively selected sites were found in NDPV. The unique immune-epitopes in waterfowl parvovirus were also estimated, which may be helpful for the prediction of antibody binding sites against NDPV in ducks. PMID:28352261

Evolutionary Stasis in Cycad Plastomes and the First Case of Plastome GC-Biased Gene Conversion.

PubMed

Wu, Chung-Shien; Chaw, Shu-Miaw

2015-06-27

In angiosperms, gene conversion has been known to reduce the mutational load of plastid genomes (the plastomes). Particularly, more frequent gene conversions in inverted repeat (IR) than in single copy (SC) regions result in contrasting substitution rates between these two regions. However, little has been known about the effect of gene conversion in the evolution of gymnosperm plastomes. Cycads (Cycadophyta) are the second largest gymnosperm group. Evolutionary study of their plastomes is limited to the basal cycad genus, Cycas. In this study, we addressed three questions. 1) Do the plastomes of other cycad genera evolve slowly as previously observed in the plastome of Cycas taitungensis? 2) Do substitution rates differ between their SC and IR regions? And 3) Does gene conversion occur in the cycad plastomes? If yes, is it AT-biased or GC-biased? Plastomes of eight species from other eight genera of cycads were sequenced. These plastomes are highly conserved in genome organization. Excluding ginkgo, cycad plastomes have significantly lower synonymous and nonsynonymous substitution rates than other gymnosperms, reflecting their evolutionary stasis in nucleotide mutations. In the IRs of cycad plastomes, the reduced substitution rates and GC-biased mutations are associated with a GC-biased gene conversion (gBGC) mechanism. Further investigations suggest that in cycads, gBGC is able to rectify plastome-wide mutations. Therefore, this study is the first to uncover the plastomic gBGC in seed plants. We also propose a gBGC model to interpret the dissimilar evolutionary patterns as well as the compositionally biased mutations in the SC and IR regions of cycad plastomes. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Plastid-Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae.

PubMed

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

2016-06-27

Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid-nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (ω) were accelerated in both plastid- (CpRP) and nuclear-encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased ω in CpRP was mainly due to intensified positive selection whereas increased ω in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Influence of Al substitution on magnetism and adsorption properties of hematite

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

Cao, Shanshan; Kang, Feifei; Yang, Xin

2015-08-15

A series of Al-substituted hematite was prepared. The structures and properties of as-prepared samples were characterized by various techniques. The magnetic property of the samples was determined and the adsorption of three dyes Acid Blue 74, Methylene Blue and Phenol Red onto the samples was investigated. The results showed that Al incorporation into the crystal structure of hematite occurs via isomorphous ionic substitution of Al for Fe. With increasing Al content, the particle size of samples decreases, the magnetization increases and the remanent magnetization remains unchanged. The coercivity of the samples increases with Al substitution up to n{sub Al}/n{sub Fe}more » 0.03, and then decreases as Al content further increases. Compared with Al-free hematite, Al-substituted samples exhibit better adsorption ability to all of the three dyes. The adsorption rates of the three dyes on the surface of Al substituted samples depend on the structure of dye, pH and Al content in hematite. - Graphical abstract: Effect of Al on the structure, magnetic properties and adsorption performance of hematite was investigated. - Highlights: • A series of Al-substituted α-Fe{sub 2}O{sub 3} was prepared. • Effect of Al content on the crystal structure and magnetic property of hematite was investigated. • Al-substituted hematite exhibits better adsorption ability than hematite.« less

Eco-friendly porous concrete using bottom ash aggregate for marine ranch application.

PubMed

Lee, Byung Jae; Prabhu, G Ganesh; Lee, Bong Chun; Kim, Yun Yong

2016-03-01

This article presents the test results of an investigation carried out on the reuse of coal bottom ash aggregate as a substitute material for coarse aggregate in porous concrete production for marine ranch applications. The experimental parameters were the rate of bottom ash aggregate substitution (30%, 50% and 100%) and the target void ratio (15%, 20% and 25%). The cement-coated granular fertiliser was substituted into a bottom ash aggregate concrete mixture to improve marine ranch applications. The results of leaching tests revealed that the bottom ash aggregate has only a negligible amount of the ten deleterious substances specified in the Ministry of Environment - Enforcement Regulation of the Waste Management Act of Republic Korea. The large amount of bubbles/air gaps in the bottom ash aggregate increased the voids of the concrete mixtures in all target void ratios, and decreased the compressive strength of the porous concrete mixture; however, the mixture substituted with 30% and 10% of bottom ash aggregate and granular fertiliser, respectively, showed an equal strength to the control mixture. The sea water resistibility of the bottom ash aggregate substituted mixture was relatively equal to that of the control mixture, and also showed a great deal of improvement in the degree of marine organism adhesion compared with the control mixture. No fatality of fish was observed in the fish toxicity test, which suggested that bottom ash aggregate was a harmless material and that the combination of bottom ash aggregate and granular fertiliser with substitution rates of 30% and 10%, respectively, can be effectively used in porous concrete production for marine ranch application. © The Author(s) 2015.

Some new results on stability and synchronization for delayed inertial neural networks based on non-reduced order method.

PubMed

Li, Xuanying; Li, Xiaotong; Hu, Cheng

2017-12-01

In this paper, without transforming the second order inertial neural networks into the first order differential systems by some variable substitutions, asymptotic stability and synchronization for a class of delayed inertial neural networks are investigated. Firstly, a new Lyapunov functional is constructed to directly propose the asymptotic stability of the inertial neural networks, and some new stability criteria are derived by means of Barbalat Lemma. Additionally, by designing a new feedback control strategy, the asymptotic synchronization of the addressed inertial networks is studied and some effective conditions are obtained. To reduce the control cost, an adaptive control scheme is designed to realize the asymptotic synchronization. It is noted that the dynamical behaviors of inertial neural networks are directly analyzed in this paper by constructing some new Lyapunov functionals, this is totally different from the traditional reduced-order variable substitution method. Finally, some numerical simulations are given to demonstrate the effectiveness of the derived theoretical results. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

X-Ray Absorption Spectroscopy of Fe-Substituted Allophane and Imogolite

NASA Astrophysics Data System (ADS)

Baker, L. L.; Strawn, D. G.; Nickerson, R. D.; McDaniel, P.

2011-12-01

Martian rocks and sediments contain weathering products including clay minerals formed as a result of interaction between rocks and water, and these materials can act as important indicators of past surface conditions on Mars. Weathering of terrestrial volcanic rocks similar to those on Mars produces nano-sized, variably hydrated aluminosilicate and iron oxide minerals, including allophane, imogolite, halloysite, hisingerite, and ferrihydrite. The nanoaluminosilicates can contain isomorphically substituted Fe, which may affect their spectral and physical properties as well as their eventual recrystallization products. Detection and quantification of such minerals in natural environments on Earth is difficult due to their variable chemical composition and lack of long-range crystalline order. Their accurate detection and quantification on Mars requires a better understanding of how composition affects their spectral properties and evolution to more crystalline phases. Aluminosilicate nanoparticles of varying composition were synthesized with isomorphically substituted Fe at Fe:Al ratios of 1:100. Allophanes were synthesized with Al:Si ratios of 2:1, 1:1, and 1:3. The substituted Fe was probed using Fe K-edge X-ray absorption fine structure spectroscopy (XAFS). The XAFS spectrum contains information about the molecular environment surrounding the target atom, and is an ideal technique for studying poorly crystalline materials that are difficult to characterize using bulk methods such as XRD. The near-edge (XANES) and extended (EXAFS) portions of the XAFS spectrum were examined, and allophane backscattering paths were fit using coordinates for a modified nanoball model (1). XANES spectra rule out ferrihydrite in the synthetic samples, suggesting all Fe was incorporated into the aluminosilicate structure. The XAFS results suggest that Fe substituted into the allophane structure is present as Fe(III) in octahedral coordination in a well-ordered sheet. Some Fe substitution in tetrahedral sites occurs in allophane with Al:Si = 2:1, but not in higher-Si compositions. These results support the nanoball model for allophane (1) based on a rolled octahedral sheet and indicate that sheet is well ordered. They do not support proposed models of an incomplete octahedral sheet in high-Si allophanes. Analysis of Fe distribution suggests considerable Fe clustering in the octahedral sheet which increases with sample aging. This clustering could lead to eventual nucleation of a separate Fe (oxyhydr)oxide phase. (1) Creton et al. (2008) J Phys Chem C 112, 358.

Oil-based compositions as saliva substitutes: A pilot study to investigate in-mouth retention.

PubMed

Hanning, Sara M; Medlicott, Natalie J

2016-03-30

This pilot study aimed to compare the in-mouth retention of an oil-based saliva substitute (emulsion, consisting of rice bran oil, soy lecithin and water) with water and a 1% w/v methylcellulose suspension (polymer) in healthy volunteers. Each formulation was tagged with 1 mmol/L lithium and participants (n=30) rinsed their mouth with one randomly assigned formulation (emulsion, polymer or water) for 30s, before expectorating into a cup. Concentration of lithium expectorated was measured and amount of each formulation remaining in the mouth was estimated. Patient acceptability was investigated using questionnaires, and Fourier-Transform Infrared spectroscopy (FTIR) was used to determine the presence of oil in expectorated samples. Immediately after rinsing, taste was rated lower in the emulsion group compared to the polymer or water groups (p>0.05), although variability was high. Mean retention was highest in the emulsion group, with a difference of 8.34 ± 2.71% (p=0.003) and 4.57 ± 2.71% (p=0.06) compared with the water and polymer groups, respectively. FTIR confirmed the presence of oil in all expectorated emulsion samples. The emulsion was not inferior to the polymer in terms of retention immediately after rinsing. The next step is to conduct larger clinical studies over longer time periods in participants with salivary hypofunction. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Numerical investigation of exhaust gas emissions for a dual fuel engine configuration using diesel and pongamia oil.

PubMed

Mohamed Ibrahim, N H; Udayakumar, M

2016-12-01

The investigation presented in this paper focuses on determination of gaseous exhaust emissions by computational simulation during combustion in compression ignition engine with pongamia oil substitution. Combustion is modeled using Equilibrium Constants Method (ECM) with MATLAB program to calculate the mole fraction of 10 combustion products when pongamia oil is burnt along with diesel at variable equivalence ratio and blend ratio. It had been observed that pongamia oil substitution causes decrease in the CO emission and increase in the NO x emission as the blend ratio as well as equivalence ratio increases. Copyright © 2015 Elsevier Inc. All rights reserved.

Suicide by Jumping and Accessibility of Bridges: Results from a National Survey in Switzerland

ERIC Educational Resources Information Center

Reisch, Thomas; Schuster, Ursula; Michel, Konrad

2007-01-01

Rates of suicide by jumping show large regional differences. Barriers on bridges may prevent suicides but also may lead to a substitution of jumping site or method. The aim of our study was to compare suicide data from regions with and without suicide bridges and to estimate the effects on method and site substitution if bridges were to be…

Positive selection in the N-terminal extramembrane domain of lung surfactant protein C (SP-C) in marine mammals.

PubMed

Foot, Natalie J; Orgeig, Sandra; Donnellan, Stephen; Bertozzi, Terry; Daniels, Christopher B

2007-07-01

Maximum-likelihood models of codon and amino acid substitution were used to analyze the lung-specific surfactant protein C (SP-C) from terrestrial, semi-aquatic, and diving mammals to identify lineages and amino acid sites under positive selection. Site models used the nonsynonymous/synonymous rate ratio (omega) as an indicator of selection pressure. Mechanistic models used physicochemical distances between amino acid substitutions to specify nonsynonymous substitution rates. Site models strongly identified positive selection at different sites in the polar N-terminal extramembrane domain of SP-C in the three diving lineages: site 2 in the cetaceans (whales and dolphins), sites 7, 9, and 10 in the pinnipeds (seals and sea lions), and sites 2, 9, and 10 in the sirenians (dugongs and manatees). The only semi-aquatic contrast to indicate positive selection at site 10 was that including the polar bear, which had the largest body mass of the semi-aquatic species. Analysis of the biophysical properties that were influential in determining the amino acid substitutions showed that isoelectric point, chemical composition of the side chain, polarity, and hydrophobicity were the crucial determinants. Amino acid substitutions at these sites may lead to stronger binding of the N-terminal domain to the surfactant phospholipid film and to increased adsorption of the protein to the air-liquid interface. Both properties are advantageous for the repeated collapse and reinflation of the lung upon diving and resurfacing and may reflect adaptations to the high hydrostatic pressures experienced during diving.

Monte Carlo algorithms for Brownian phylogenetic models.

PubMed

Horvilleur, Benjamin; Lartillot, Nicolas

2014-11-01

Brownian models have been introduced in phylogenetics for describing variation in substitution rates through time, with applications to molecular dating or to the comparative analysis of variation in substitution patterns among lineages. Thus far, however, the Monte Carlo implementations of these models have relied on crude approximations, in which the Brownian process is sampled only at the internal nodes of the phylogeny or at the midpoints along each branch, and the unknown trajectory between these sampled points is summarized by simple branchwise average substitution rates. A more accurate Monte Carlo approach is introduced, explicitly sampling a fine-grained discretization of the trajectory of the (potentially multivariate) Brownian process along the phylogeny. Generic Monte Carlo resampling algorithms are proposed for updating the Brownian paths along and across branches. Specific computational strategies are developed for efficient integration of the finite-time substitution probabilities across branches induced by the Brownian trajectory. The mixing properties and the computational complexity of the resulting Markov chain Monte Carlo sampler scale reasonably with the discretization level, allowing practical applications with up to a few hundred discretization points along the entire depth of the tree. The method can be generalized to other Markovian stochastic processes, making it possible to implement a wide range of time-dependent substitution models with well-controlled computational precision. The program is freely available at www.phylobayes.org. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A reassessment of the emergence time of European bat lyssavirus type 1.

PubMed

Hughes, Gareth J

2008-12-01

The previous study of the evolutionary rates of European bat lyssavirus type 1 (EBLV-1) used a strict molecular clock to estimate substitution rates of the nucleoprotein gene and in turn times of the most recent common ancestor (tMRCA) of the entire genotype and the two major EBLV-1 lineages (EBLV-1A and EBLV-1B). The results of that study suggested that the evolutionary rate of EBLV-1 was one of the lowest recorded for RNA viruses and that genetic diversity of EBLV-1 arose 500-750 years ago. Here I have shown that the use of a relaxed molecular clock (allowing branch rates to vary within a phylogeny) shows that these previous estimates should be revised. The relaxed clock provides a significantly better fit to all datasets. The substitution rate of EBLV-1B is compatible to that expected given previous estimates for the N gene of rabies virus whilst rate estimations for EBLV-1A appear to be confounded by substantial rate variation within the phylogeny. The relaxed clock substitution rate for EBLV-1 (1.1 x 10(-4)) is higher than had been estimated previously, and closer to that expected for the N gene. Moreover, tMRCA estimates for EBLV-1 are substantially reduced using the relaxed molecular clock (70-300 years) although the differing dynamics of EBLV-1A and EBLV-1B confound the confidence in this estimate. Current diversity of both EBLV-1A and EBLV-1B appears to have emerged within the last 100 years. Reconstruction of the population histories suggests that EBLV-1B may be emerging whilst the signal derived from the EBLV-1A phylogeny may be dampened by clade-specific dynamics.

Treatment of unicameral bone cyst: surgical technique.

PubMed

Hou, Hsien-Yang; Wu, Karl; Wang, Chen-Ti; Chang, Shun-Min; Lin, Wei-Hsin; Yang, Rong-Sen

2011-03-01

There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 ± 2.3 months compared with 23.4 ± 14.9, 12.2 ± 8.5, and 6.6 ± 4.3 months in Groups 1, 2, and 3, respectively. This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

Treatment of unicameral bone cyst: a comparative study of selected techniques.

PubMed

Hou, Hsien-Yang; Wu, Karl; Wang, Chen-Ti; Chang, Shun-Min; Lin, Wei-Hsin; Yang, Rong-Sen

2010-04-01

There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 +/- 2.3 months compared with 23.4 +/- 14.9, 12.2 +/- 8.5, and 6.6 +/- 4.3 months in Groups 1, 2, and 3, respectively. This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

Rates of evolution in stress-related genes are associated with habitat preference in two Cardamine lineages

PubMed Central

2012-01-01

Background Elucidating the selective and neutral forces underlying molecular evolution is fundamental to understanding the genetic basis of adaptation. Plants have evolved a suite of adaptive responses to cope with variable environmental conditions, but relatively little is known about which genes are involved in such responses. Here we studied molecular evolution on a genome-wide scale in two species of Cardamine with distinct habitat preferences: C. resedifolia, found at high altitudes, and C. impatiens, found at low altitudes. Our analyses focussed on genes that are involved in stress responses to two factors that differentiate the high- and low-altitude habitats, namely temperature and irradiation. Results High-throughput sequencing was used to obtain gene sequences from C. resedifolia and C. impatiens. Using the available A. thaliana gene sequences and annotation, we identified nearly 3,000 triplets of putative orthologues, including genes involved in cold response, photosynthesis or in general stress responses. By comparing estimated rates of molecular substitution, codon usage, and gene expression in these species with those of Arabidopsis, we were able to evaluate the role of positive and relaxed selection in driving the evolution of Cardamine genes. Our analyses revealed a statistically significant higher rate of molecular substitution in C. resedifolia than in C. impatiens, compatible with more efficient positive selection in the former. Conversely, the genome-wide level of selective pressure is compatible with more relaxed selection in C. impatiens. Moreover, levels of selective pressure were heterogeneous between functional classes and between species, with cold responsive genes evolving particularly fast in C. resedifolia, but not in C. impatiens. Conclusions Overall, our comparative genomic analyses revealed that differences in effective population size might contribute to the differences in the rate of protein evolution and in the levels of selective pressure between the C. impatiens and C. resedifolia lineages. The within-species analyses also revealed evolutionary patterns associated with habitat preference of two Cardamine species. We conclude that the selective pressures associated with the habitats typical of C. resedifolia may have caused the rapid evolution of genes involved in cold response. PMID:22257588

10 CFR 903.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

.... (h) Power Marketing Administration or PMA means the Alaska Power Administration, Southeastern Power... been confirmed, approved, and placed in effect on an interim basis by the Deputy Secretary. (l) Rate... means sales that last for no longer than one year. (p) Substitute Rate means a rate which has been...

10 CFR 903.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... (h) Power Marketing Administration or PMA means the Alaska Power Administration, Southeastern Power... been confirmed, approved, and placed in effect on an interim basis by the Deputy Secretary. (l) Rate... means sales that last for no longer than one year. (p) Substitute Rate means a rate which has been...

Influence of provider and urgent care density across different socioeconomic strata on outpatient antibiotic prescribing in the USA

PubMed Central

Klein, Eili Y.; Makowsky, Michael; Orlando, Megan; Hatna, Erez; Braykov, Nikolay P.; Laxminarayan, Ramanan

2015-01-01

Objectives Despite a strong link between antibiotic use and resistance, and highly variable antibiotic consumption rates across the USA, drivers of differences in consumption rates are not fully understood. The objective of this study was to examine how provider density affects antibiotic prescribing rates across socioeconomic groups in the USA. Methods We aggregated data on all outpatient antibiotic prescriptions filled in retail pharmacies in the USA in 2000 and 2010 from IMS Health into 3436 geographically distinct hospital service areas and combined this with socioeconomic and structural factors that affect antibiotic prescribing from the US Census. We then used fixed-effect models to estimate the interaction between poverty and the number of physician offices per capita (i.e. physician density) and the presence of urgent care and retail clinics on antibiotic prescribing rates. Results We found large geographical variation in prescribing, driven in part by the number of physician offices per capita. For an increase of one standard deviation in the number of physician offices per capita there was a 25.9% increase in prescriptions per capita. However, the determinants of the prescription rate were dependent on socioeconomic conditions. In poorer areas, clinics substitute for traditional physician offices, reducing the impact of physician density. In wealthier areas, clinics increase the effect of physician density on the prescribing rate. Conclusions In areas with higher poverty rates, access to providers drives the prescribing rate. However, in wealthier areas, where access is less of a problem, a higher density of providers and clinics increases the prescribing rate, potentially due to competition. PMID:25604743

The effects of trace element content on pyrite oxidation rates

NASA Astrophysics Data System (ADS)

Gregory, D. D.; Lyons, T.; Cliff, J. B.; Perea, D. E.; Johnson, A.; Romaniello, S. J.; Large, R. R.

2017-12-01

Pyrite acts as both an important source and sink for many different metals and metalloids in the environment, including many that are toxic. Oxidation of pyrite can release these elements while at the same time producing significant amounts of sulfuric acid. Such issues are common in the vicinity of abandoned mines and smelters, but, as pyrite is a common accessory mineral in many different lithologies, significant pyrite oxidation can occur whenever pyritic rocks are exposed to oxygenated water or the atmosphere. Accelerated exposure to oxygen can occur during deforestation, fracking for petroleum, and construction projects. Geochemical models for pyrite oxidation can help us develop strategies to mitigate these deleterious effects. An important component of these models is an accurate pyrite oxidation rate; however, current pyrite oxidation rates have been determined using relatively pure pyrite. Natural pyrite is rarely pure and has a wide range of trace element concentrations that may affect the oxidation rate. Furthermore, the position of trace elements within the mineral lattice can also affect the oxidation rate. For example, elements such as Ni and Co, which substitute into the pyrite lattice, are thought to stabilize the lattice and thus prevent pyrite oxidation. Alternatively, trace elements that are held within inclusions of other minerals could form a galvanic cell with the surrounding pyrite, thus enhancing pyrite oxidation rates. In this study, we present preliminary analyses from three different pyrite oxidation experiments each using natural pyrite with different trace element compositions. These results show that the pyrite with the highest trace element concentration has approximately an order of magnitude higher oxidation rate compared to the lowest trace element sample. To further elucidate the mechanisms, we employed microanalytical techniques to investigate how the trace elements are held within the pyrite. LA-ICPMS was used to determine the variability of trace element content from the pyrite samples. These data were then used to select areas of interest for NanoSIMS analyses, which in turn was used to select areas for TEM and APT. These analyses show that the trace element content of pyrite can be highly variable, which may significantly affect the rate of pyrite oxidation.

A density functional theory study of the structure of pure-silica and aluminium-substituted MFI nanosheets

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

Hernandez-Tamargo, Carlos E.; Roldan, Alberto; School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT

The layered MFI zeolite allows a straightforward hierarchization of the pore system which accelerates mass transfer and increases its lifetime as a catalyst. Here, we present a theoretical study of the structural features of the pure-silica and aluminium-substituted MFI nanosheets. We have analysed the effects of aluminium substitution on the vibrational properties of silanols as well as the features of protons as counter-ions. The formation of the two-dimensional system did not lead to appreciable distortions within the framework. Moreover, the effects on the structure due to the aluminium dopants were the same in both the bulk and the slab. Themore » principal differences were related to the silanol groups that form hydrogen-bonds with neighbouring aluminium-substituted silanols, whereas intra-framework hydrogen-bonds increase the stability of aluminium-substituted silanols toward dehydration. Thus, we have complemented previous experimental and theoretical studies, showing the lamellar MFI zeolite to be a very stable material of high crystallinity regardless of its very thin structure. - Graphical abstract: The structure of MFI zeolite nanosheet was investigated using Density Functional Theory. The results showed no differences against the bulk-type material upon aluminium doping. The aluminium-substituted silanol dehydrates toward a more stable configuration composed by a water molecule adsorbed on a Lewis centre. - Highlights: • MFI nanosheets with variable thicknesses were characterised using DFT calculations. • The distortions in the nanosheets after Al substitution reproduced those of the bulk. • H-bonds were only observed between silanol groups when the Al substitution took place. • The kinetic of the Al-silanol dehydration is dependent on intra-framework H-bonds. • Lewis acids with adsorbed water are more stable than Al-silanols. • The proton accessibility was related to the framework O atom binding the proton.« less

The Effect of Inappropriate Calibration: Three Case Studies in Molecular Ecology

PubMed Central

Ho, Simon Y. W.; Saarma, Urmas; Barnett, Ross; Haile, James; Shapiro, Beth

2008-01-01

Time-scales estimated from sequence data play an important role in molecular ecology. They can be used to draw correlations between evolutionary and palaeoclimatic events, to measure the tempo of speciation, and to study the demographic history of an endangered species. In all of these studies, it is paramount to have accurate estimates of time-scales and substitution rates. Molecular ecological studies typically focus on intraspecific data that have evolved on genealogical scales, but often these studies inappropriately employ deep fossil calibrations or canonical substitution rates (e.g., 1% per million years for birds and mammals) for calibrating estimates of divergence times. These approaches can yield misleading estimates of molecular time-scales, with significant impacts on subsequent evolutionary and ecological inferences. We illustrate this calibration problem using three case studies: avian speciation in the late Pleistocene, the demographic history of bowhead whales, and the Pleistocene biogeography of brown bears. For each data set, we compare the date estimates that are obtained using internal and external calibration points. In all three cases, the conclusions are significantly altered by the application of revised, internally-calibrated substitution rates. Collectively, the results emphasise the importance of judicious selection of calibrations for analyses of recent evolutionary events. PMID:18286172

The effect of inappropriate calibration: three case studies in molecular ecology.

PubMed

Ho, Simon Y W; Saarma, Urmas; Barnett, Ross; Haile, James; Shapiro, Beth

2008-02-20

Time-scales estimated from sequence data play an important role in molecular ecology. They can be used to draw correlations between evolutionary and palaeoclimatic events, to measure the tempo of speciation, and to study the demographic history of an endangered species. In all of these studies, it is paramount to have accurate estimates of time-scales and substitution rates. Molecular ecological studies typically focus on intraspecific data that have evolved on genealogical scales, but often these studies inappropriately employ deep fossil calibrations or canonical substitution rates (e.g., 1% per million years for birds and mammals) for calibrating estimates of divergence times. These approaches can yield misleading estimates of molecular time-scales, with significant impacts on subsequent evolutionary and ecological inferences. We illustrate this calibration problem using three case studies: avian speciation in the late Pleistocene, the demographic history of bowhead whales, and the Pleistocene biogeography of brown bears. For each data set, we compare the date estimates that are obtained using internal and external calibration points. In all three cases, the conclusions are significantly altered by the application of revised, internally-calibrated substitution rates. Collectively, the results emphasise the importance of judicious selection of calibrations for analyses of recent evolutionary events.

Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction.

PubMed

Virych, P A; Shelyuk, O V; Kabanova, T A; Khalimova, E I; Martynyuk, V S; Pavlovsky, V I; Andronati, S A

2017-01-01

Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors. MX-1626 demonstrated unidirectional changes of maximal normalized rate and force of smooth muscle that proportionally depended on bradykinin concentration in the range 10-10-10-6 M. MX-1828 has statistically significant decrease of normalized rate of smooth muscle contraction for bradykinin concentrations 10-10 and 10-9 M by 20.7 and 8.6%, respectively, but for agonist concentration 10-6 M, this parameter increased by 10.7% and amplitude was reduced by 29.5%. Compounds MX-2011, MX-1785 and MX-2004 showed no natural effect on bradykinin-induced smooth muscle contraction. Compounds MX-1775, MX-1828, MX-1626 were selected for further research of their influence on kinin-kallikrein system and pain perception.

The role of marine reserves in achieving sustainable fisheries

PubMed Central

Roberts, Callum M.; Hawkins, Julie P.; Gell, Fiona R.

2005-01-01

Many fishery management tools currently in use have conservation value. They are designed to maintain stocks of commercially important species above target levels. However, their limitations are evident from continuing declines in fish stocks throughout the world. We make the case that to reverse fishery declines, safeguard marine life and sustain ecosystem processes, extensive marine reserves that are off limits to fishing must become part of the management strategy. Marine reserves should be incorporated into modern fishery management because they can achieve many things that conventional tools cannot. Only complete and permanent protection from fishing can protect the most sensitive habitats and vulnerable species. Only reserves will allow the development of natural, extended age structures of target species, maintain their genetic variability and prevent deleterious evolutionary change from the effects of fishing. Species with natural age structures will sustain higher rates of reproduction and will be more resilient to environmental variability. Higher stock levels maintained by reserves will provide insurance against management failure, including risk-prone quota setting, provided the broader conservation role of reserves is firmly established and legislatively protected. Fishery management measures outside protected areas are necessary to complement the protection offered by marine reserves, but cannot substitute for it. PMID:15713592

Mutations in the nucleotide binding pocket of MreB can alter cell curvature and polar morphology in Caulobacter.

PubMed

Dye, Natalie A; Pincus, Zachary; Fisher, Isabelle C; Shapiro, Lucy; Theriot, Julie A

2011-07-01

The maintenance of cell shape in Caulobacter crescentus requires the essential gene mreB, which encodes a member of the actin superfamily and the target of the antibiotic, A22. We isolated 35 unique A22-resistant Caulobacter strains with single amino acid substitutions near the nucleotide binding site of MreB. Mutations that alter cell curvature and mislocalize the intermediate filament crescentin cluster on the back surface of MreB's structure. Another subset have variable cell widths, with wide cell bodies and actively growing thin extensions of the cell poles that concentrate fluorescent MreB. We found that the extent to which MreB localization is perturbed is linearly correlated with the development of pointed cell poles and variable cell widths. Further, we find that a mutation to glycine of two conserved aspartic acid residues that are important for nucleotide hydrolysis in other members of the actin superfamily abolishes robust midcell recruitment of MreB but supports a normal rate of growth. These mutant strains provide novel insight into how MreB's protein structure, subcellular localization, and activity contribute to its function in bacterial cell shape. © 2011 Blackwell Publishing Ltd.

Mutations in the nucleotide binding pocket of MreB can alter cell curvature and polar morphology in Caulobacter

PubMed Central

Dye, Natalie A; Pincus, Zachary; Fisher, Isabelle C; Shapiro, Lucy; Theriot, Julie A

2011-01-01

Summary The maintenance of cell shape in Caulobacter crescentus requires the essential gene mreB, which encodes a member of the actin superfamily and the target of the antibiotic, A22. We isolated 35 unique A22-resistant Caulobacter strains with single amino acid substitutions near the nucleotide binding site of MreB. Mutations that alter cell curvature and mislocalize the intermediate filament crescentin cluster on the back surface of MreB's structure. Another subset have variable cell widths, with wide cell bodies and actively growing thin extensions of the cell poles that concentrate fluorescent MreB. We found that the extent to which MreB localization is perturbed is linearly correlated with the development of pointed cell poles and variable cell widths. Further, we find that a mutation to glycine of two conserved aspartic acid residues that are important for nucleotide hydrolysis in other members of the actin superfamily abolishes robust midcell recruitment of MreB but supports a normal rate of growth. These mutant strains provide novel insight into how MreB's protein structure, subcellular localization, and activity contribute to its function in bacterial cell shape. PMID:21564339

Combining censored and uncensored data in a U-statistic: design and sample size implications for cell therapy research.

PubMed

Moyé, Lemuel A; Lai, Dejian; Jing, Kaiyan; Baraniuk, Mary Sarah; Kwak, Minjung; Penn, Marc S; Wu, Colon O

2011-01-01

The assumptions that anchor large clinical trials are rooted in smaller, Phase II studies. In addition to specifying the target population, intervention delivery, and patient follow-up duration, physician-scientists who design these Phase II studies must select the appropriate response variables (endpoints). However, endpoint measures can be problematic. If the endpoint assesses the change in a continuous measure over time, then the occurrence of an intervening significant clinical event (SCE), such as death, can preclude the follow-up measurement. Finally, the ideal continuous endpoint measurement may be contraindicated in a fraction of the study patients, a change that requires a less precise substitution in this subset of participants.A score function that is based on the U-statistic can address these issues of 1) intercurrent SCE's and 2) response variable ascertainments that use different measurements of different precision. The scoring statistic is easy to apply, clinically relevant, and provides flexibility for the investigators' prospective design decisions. Sample size and power formulations for this statistic are provided as functions of clinical event rates and effect size estimates that are easy for investigators to identify and discuss. Examples are provided from current cardiovascular cell therapy research.

Hydrogen-assisted post-growth substitution of tellurium into molybdenum disulfide monolayers with tunable compositions

NASA Astrophysics Data System (ADS)

Yin, Guoli; Zhu, Dancheng; Lv, Danhui; Hashemi, Arsalan; Fei, Zhen; Lin, Fang; Krasheninnikov, Arkady V.; Zhang, Ze; Komsa, Hannu-Pekka; Jin, Chuanhong

2018-04-01

Herein we report the successful doping of tellurium (Te) into molybdenum disulfide (MoS2) monolayers to form MoS2x Te2(1-x) alloy with variable compositions via a hydrogen-assisted post-growth chemical vapor deposition process. It is confirmed that H2 plays an indispensable role in the Te substitution into as-grown MoS2 monolayers. Atomic-resolution transmission electron microscopy allows us to determine the lattice sites and the concentration of introduced Te atoms. At a relatively low concentration, tellurium is only substituted in the sulfur sublattice to form monolayer MoS2(1-x)Te2x alloy, while with increasing Te concentration (up to ˜27.6% achieved in this study), local regions with enriched tellurium, large structural distortions, and obvious sulfur deficiency are observed. Statistical analysis of the Te distribution indicates the random substitution. Density functional theory calculations are used to investigate the stability of the alloy structures and their electronic properties. Comparison with experimental results indicate that the samples are unstrained and the Te atoms are predominantly substituted in the top S sublattice. Importantly, such ultimately thin Janus structure of MoS2(1-x)Te2x exhibits properties that are distinct from their constituents. We believe our results will inspire further exploration of the versatile properties of asymmetric 2D TMD alloys.

Localization, structure and polymorphism of two paralogous Xenopus laevis mitochondrial malate dehydrogenase genes.

PubMed

Tlapakova, Tereza; Krylov, Vladimir; Macha, Jaroslav

2005-01-01

Two paralogous mitochondrial malate dehydrogenase 2 (Mdh2) genes of Xenopus laevis have been cloned and sequenced, revealing 95% identity. Fluorescence in-situ hybridization (FISH) combined with tyramide amplification discriminates both genes; Mdh2a was localized into chromosome q3 and Mdh2b into chromosome q8. One kb cDNA probes detect both genes with 85% accuracy. The remaining signals were on the paralogous counterpart. Introns interrupt coding sequences at the same nucleotide as defined for mouse. Restriction polymorphism has been detected in the first intron of Mdh2a, while the individual variability in intron 6 of Mdh2b gene is represented by an insertion of incomplete retrotransposon L1Xl. Rates of nucleotide substitutions indicate that both genes are under similar evolutionary constraints. X. laevis Mdh2 genes can be used as markers for physical mapping and linkage analysis.

Atropisomerization of di-para-substituted propyl-bridged biphenyl cyclophanes.

PubMed

Rotzler, Jürgen; Gsellinger, Heiko; Bihlmeier, Angela; Gantenbein, Markus; Vonlanthen, David; Häussinger, Daniel; Klopper, Wim; Mayor, Marcel

2013-01-07

The influence of electron donors and electron acceptors of variable strength in the 4 and 4' position of 2 and 2' propyl-bridged axial chiral biphenyl cyclophanes on their atropisomerization process was studied. Estimated free energies ΔG(‡)(T) of the rotation around the central biphenyl bond which were obtained from (1)H-NMR coalescence measurements were correlated to the Hammett parameters σ(p) as a measure for electron donor and acceptor strength. It is demonstrated that the resulting nice linear correlation is mainly based on the influence of the different substituents on the π-system of the biphenyl cyclophanes. By lineshape analysis the rate constants were calculated and by the use of the Eyring equation the enthalpic and entropic contributions were evaluated. Density functional theory calculations show a planar transition state of the isomerization process and the calculated energy barriers based on this reaction mechanism are in good agreement with the experimentally obtained free energies.

Heterogeneous Nucleation of Protein Crystals on Fluorinated Layered Silicate

PubMed Central

Ino, Keita; Udagawa, Itsumi; Iwabata, Kazuki; Takakusagi, Yoichi; Kubota, Munehiro; Kurosaka, Keiichi; Arai, Kazuhito; Seki, Yasutaka; Nogawa, Masaya; Tsunoda, Tatsuo; Mizukami, Fujio; Taguchi, Hayao; Sakaguchi, Kengo

2011-01-01

Here, we describe an improved system for protein crystallization based on heterogeneous nucleation using fluorinated layered silicate. In addition, we also investigated the mechanism of nucleation on the silicate surface. Crystallization of lysozyme using silicates with different chemical compositions indicated that fluorosilicates promoted nucleation whereas the silicates without fluorine did not. The use of synthesized saponites for lysozyme crystallization confirmed that the substitution of hydroxyl groups contained in the lamellae structure for fluorine atoms is responsible for the nucleation-inducing property of the nucleant. Crystallization of twelve proteins with a wide range of pI values revealed that the nucleation promoting effect of the saponites tended to increase with increased substitution rate. Furthermore, the saponite with the highest fluorine content promoted nucleation in all the test proteins regardless of their overall net charge. Adsorption experiments of proteins on the saponites confirmed that the density of adsorbed molecules increased according to the substitution rate, thereby explaining the heterogeneous nucleation on the silicate surface. PMID:21818343

Life cycle assessment of flexibly fed biogas processes for an improved demand-oriented biogas supply.

PubMed

Ertem, Funda Cansu; Martínez-Blanco, Julia; Finkbeiner, Matthias; Neubauer, Peter; Junne, Stefan

2016-11-01

This paper analyses concepts to facilitate a demand oriented biogas supply at an agricultural biogas plant of a capacity of 500kWhel, operated with the co-digestion of maize, grass, rye silage and chicken manure. In contrast to previous studies, environmental impacts of flexible and the traditional baseload operation are compared. Life Cycle Assessment (LCA) was performed to detect the environmental impacts of: (i) variety of feedstock co-digestion scenarios by substitution of maize and (ii) loading rate scenarios with a focus on flexible feedstock utilization. Demand-driven biogas production is critical for an overall balanced power supply to the electrical grid. It results in lower amounts of emissions; feedstock loading rate scenarios resulted in 48%, 20%, 11% lower global warming (GWP), acidification (AP) and eutrophication potentials, and a 16% higher cumulative energy demand. Substitution of maize with biogenic-waste regarding to feedstock substitution scenarios could create 10% lower GWP and AP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential Predictability of U.S. Summer Climate with "Perfect" Soil Moisture

NASA Technical Reports Server (NTRS)

Yang, Fanglin; Kumar, Arun; Lau, K.-M.

2004-01-01

The potential predictability of surface-air temperature and precipitation over the United States continent was assessed for a GCM forced by observed sea surface temperatures and an estimate of observed ground soil moisture contents. The latter was obtained by substituting the GCM simulated precipitation, which is used to drive the GCM's land-surface component, with observed pentad-mean precipitation at each time step of the model's integration. With this substitution, the simulated soil moisture correlates well with an independent estimate of observed soil moisture in all seasons over the entire US continent. Significant enhancements on the predictability of surface-air temperature and precipitation were found in boreal late spring and summer over the US continent. Anomalous pattern correlations of precipitation and surface-air temperature over the US continent in the June-July-August season averaged for the 1979-2000 period increased from 0.01 and 0.06 for the GCM simulations without precipitation substitution to 0.23 and 0.3 1, respectively, for the simulations with precipitation substitution. Results provide an estimate for the limits of potential predictability if soil moisture variability is to be perfectly predicted. However, this estimate may be model dependent, and needs to be substantiated by other modeling groups.

Evolutionary rates of mitochondrial genomes correspond to diversification rates and to contemporary species richness in birds and reptiles

PubMed Central

Eo, Soo Hyung; DeWoody, J. Andrew

2010-01-01

Rates of biological diversification should ultimately correspond to rates of genome evolution. Recent studies have compared diversification rates with phylogenetic branch lengths, but incomplete phylogenies hamper such analyses for many taxa. Herein, we use pairwise comparisons of confamilial sauropsid (bird and reptile) mitochondrial DNA (mtDNA) genome sequences to estimate substitution rates. These molecular evolutionary rates are considered in light of the age and species richness of each taxonomic family, using a random-walk speciation–extinction process to estimate rates of diversification. We find the molecular clock ticks at disparate rates in different families and at different genes. For example, evolutionary rates are relatively fast in snakes and lizards, intermediate in crocodilians and slow in turtles and birds. There was also rate variation across genes, where non-synonymous substitution rates were fastest at ATP8 and slowest at CO3. Family-by-gene interactions were significant, indicating that local clocks vary substantially among sauropsids. Most importantly, we find evidence that mitochondrial genome evolutionary rates are positively correlated with speciation rates and with contemporary species richness. Nuclear sequences are poorly represented among reptiles, but the correlation between rates of molecular evolution and species diversification also extends to 18 avian nuclear genes we tested. Thus, the nuclear data buttress our mtDNA findings. PMID:20610427

40 CFR 75.36 - Missing data procedures for heat input rate determinations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Missing data procedures for heat input... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.36 Missing data procedures for heat input rate determinations. (a) When hourly heat input rate is...

40 CFR 75.36 - Missing data procedures for heat input rate determinations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Missing data procedures for heat input... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.36 Missing data procedures for heat input rate determinations. (a) When hourly heat input rate is...

40 CFR 75.36 - Missing data procedures for heat input rate determinations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Missing data procedures for heat input... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.36 Missing data procedures for heat input rate determinations. (a) When hourly heat input rate is...

40 CFR 75.36 - Missing data procedures for heat input rate determinations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Missing data procedures for heat input... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.36 Missing data procedures for heat input rate determinations. (a) When hourly heat input rate is...

40 CFR 75.36 - Missing data procedures for heat input rate determinations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Missing data procedures for heat input... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.36 Missing data procedures for heat input rate determinations. (a) When hourly heat input rate is...

Chemoselective ratiometric imaging of protein S-sulfenylation.

PubMed

Tom, Christopher T M B; Crellin, John E; Motiwala, Hashim F; Stone, Matthew B; Davda, Dahvid; Walker, William; Kuo, Yu-Hsuan; Hernandez, Jeannie L; Labby, Kristin J; Gomez-Rodriguez, Lyanne; Jenkins, Paul M; Veatch, Sarah L; Martin, Brent R

2017-06-29

Here we report a ratiometric fluorescent probe for chemoselective conjugation to sulfenic acids in living cells. Our approach couples an α-fluoro-substituted dimedone to an aminonaphthalene fluorophore (F-DiNap), which upon sulfenic acid conjugation is locked as the 1,3-diketone, changing the fluorophore excitation. F-DiNap reacts with S-sulfenylated proteins at equivalent rates to current probes, but the α-fluorine substitution blocks side-reactions with biological aldehydes.

The impact of generic substitution on the turnover and gross margin of pharmaceutical companies a survey 1 year and 5 years after the introduction of generic substitution in Finland.

PubMed

Timonen, Johanna; Karttunen, Pekka; Bengtström, Marina; Ahonen, Riitta

2009-10-01

To explore and compare the impact of generic substitution (GS) on the turnover and gross margin per cent of pharmaceutical companies representing mainly original or generic products in Finland. A mail survey to pharmaceutical companies with an office in Finland and substitutable medicines in the Finnish pharmaceutical market 1 year (2004) and nearly 5 years (2008) after GS. The questionnaire were answered by 16 original and 7 generic product companies in 2004 (response rate 56%, n=41) and by 16 original and 6 generic product companies in 2008 (response rate 56%, n=39). Turnover had decreased in the original product companies and increased in the generic product companies. The gross margin per cent had decreased in the original and generic product companies, and the companies had also compensated for it in many ways. The study suggests that GS has promoted the sales of generic product companies in Finland. However, price competition caused by GS has generally decreased the proportion of profit from turnover in the original and generic product companies. The companies have also compensated for their decreased gross margin, which suggests that the profit in euros has not been sufficient to cover fixed costs in the companies.

Quality-by-design case study: investigation of the role of poloxamer in immediate-release tablets by experimental design and multivariate data analysis.

PubMed

Kaul, Goldi; Huang, Jun; Chatlapalli, Ramarao; Ghosh, Krishnendu; Nagi, Arwinder

2011-12-01

The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed. Poloxamer was found to increase dissolution rates in granules as expected of surfactants in general but retard dissolution in tablets. The unexpected effect of poloxamer in tablets was accompanied by an increase in tablet-disintegration-time-mediated slowdown of tablet dissolution and by a surrogate binding effect of poloxamer at higher concentrations. It was additionally realized through MVDA that poloxamer in tablets either acts as a binder by itself or promotes binder action of the binder povidone resulting in increased intragranular cohesion. Additionally, poloxamer was found to mediate tablet dissolution on stability as well. In contrast to tablet dissolution at release (time zero), poloxamer appeared to increase tablet dissolution in a concentration-dependent manner on accelerated open-dish stability. Substituting polysorbate 80 as an alternate surfactant in place of poloxamer in the formulation was found to stabilize tablet dissolution.

Tri- and tetra-substituted cyclen based lanthanide(III) ion complexes as ribonuclease mimics: a study into the effect of log Ka, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP).

PubMed

Fanning, Ann-Marie; Plush, Sally E; Gunnlaugsson, Thorfinnur

2015-05-28

A series of tetra-substituted 'pseudo' dipeptide ligands of cyclen (1,4,7,10,-tetraazacyclododecane) and a tri-substituted 3'-pyridine ligand of cyclen, and the corresponding lanthanide(III) complexes were synthesised and characterised as metallo-ribonuclease mimics. All complexes were shown to promote hydrolysis of the phosphodiester bond of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP, τ1/2 = 5.87 × 10(3) h), a well known RNA mimic. The La(III) and Eu(III) tri-substituted 3'-pyridine lanthanide(III) complexes being the most efficient in promoting such hydrolysis at pH 7.4 and at 37 °C; with τ1/2 = 1.67 h for La(III) and 1.74 h for Eu(III). The series was developed to provide the opportunity to investigate the consequences of altering the lanthanide(III) ion, coordination ability and hydrophobicity of a metallo-cavity on the rate of hydrolysis using the model phosphodiester, HPNP, at 37 °C. To further provide information on the role that the log Ka of the metal bound water plays in phosphodiester hydrolysis the protonation constants and the metal ion stability constants of both a tri and tetra-substituted 3'pyridine complex were determined. Our results highlighted several key features for the design of lanthanide(III) ribonucelase mimics; the presence of two metal bound water molecules are vital for pH dependent rate constants for Eu(III) complexes, optimal pH activity approximating physiological pH (∼7.4) may be achieved if the log Ka values for both MLOH and ML(OH)2 species occur in this region, small changes to hydrophobicity within the metallo cavity influence the rate of hydrolysis greatly and an amide adjacent to the metal ion capable of forming hydrogen bonds with the substrate is required for achieving fast hydrolysis.

A Pilot Study of Perceived Mouth Dryness, Perceived Swallowing Effort, and Saliva Substitute Effects in Healthy Adults Across the Age Range.

PubMed

Rogus-Pulia, Nicole M; Gangnon, Ronald; Kind, Amy; Connor, Nadine P; Asthana, Sanjay

2018-04-01

Xerostomia, or perceived mouth dryness, increases with advancing age, but its influence on swallowing effort is unknown. This study: (1) quantified relationships among age, perceived sense of swallowing effort, and ratings of perceived mouth dryness, and (2) examined changes in swallowing effort following application of a gel-based saliva substitute in healthy participants. This was a cross-sectional observational study and data were collected from attendees of a community healthy aging fair. Forty-two healthy participants (mean age = 65 years; 20 female) were enrolled. Each participant rated perceived effort with swallowing and perceived mouth dryness on a 10-cm horizontal, undifferentiated line. After participants applied a gel-based saliva substitute (Biotene ® Oral Balance) to their tongue and oral mucosa, they rated perceived effort with swallowing again. Age was associated with greater perceived mouth dryness (r = 0.37, p < 0.03) but not with perceived swallowing effort (r = 0.16, p = 0.32). Perceived mouth dryness was associated with greater perceived swallowing effort (r = 0.62, p < 0.001). Perceived swallowing effort declined following application of the salivary substitute (mean difference = 9.39 mm, p < 0.002). Age was found to be a significant predictor of perceived mouth dryness (p < .02); and perceived mouth dryness was found to significantly predict perceived swallow effort (p < .001). Perceived mouth dryness increased with advancing age, but perceived swallowing effort did not. Regardless of age, participants with higher levels of perceived mouth dryness also reported more perceived effort with swallowing suggesting a role for adequate oral lubrication in this perception. Even in healthy participants, use of a gel-based saliva substitute lowered perceived swallowing effort.

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.

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach.

PubMed

Pahwa, Mrinal; Gupta, Sanjeev; Pahwa, Mayank; Jain, Brig D K; Gupta, Manu

2013-01-01

Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6-24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique.

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach

PubMed Central

Pahwa, Mrinal; Gupta, Sanjeev; Pahwa, Mayank; Jain, Brig D. K.; Gupta, Manu

2013-01-01

Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6–24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique. PMID:24194754

In vitro Starch Hydrolysis Rate, Physico-chemical Properties and Sensory Evaluation of Butter Cake Prepared Using Resistant Starch Type III Substituted for Wheat Flour.

PubMed

Pongjanta, J; Utaipattanaceep, A; Naivikul, O; Piyachomkwan, K

2008-09-01

Resistant starch type III (RS III) derived from enzymatically debranched high amylose rice starch was prepared and used to make butter cake at different levels (0, 5, 10, 15 and 20%) in place of wheat flour. Physico-chemical properties, sensory evaluation, and in vitro starch hydrolysis rate of the developed butter cake were investigated. This study showed that the content of resistant starch in butter cake increased significantly (P<0.05) as the level of substitution with RS III increased from 2.1 to 4.4% of resistant starch content. The butter cake with RS III replacement had a significantly lower in vitro starch hydrolysis rate compared to the control cake (0% RS III). The rates of starch hydrolysis from 0 to 180 min digestion time for 0, 5, 10 15, and 20% RS III in place of wheat flour in butter cakes were 3.70 to 67.65%, 2.97 to 64.86%, 2.86 to 59.99%, 2.79 to 55.96 and 2.78 to 53.04% respectively. The physico-chemical properties of 5 to 10% RS III substituted with wheat flour in the butter cake were not significantly different from the control cake and were moderately accepted by panellists in the sensory evaluation test.

Organization and Finance of China's Health Sector: Historical Antecedents for Macroeconomic Structural Adjustment.

PubMed

Li, Hui; Hilsenrath, Peter

2016-01-01

China has exploded onto the world economy over the past few decades and is undergoing rapid transformation toward relatively more services. The health sector is an important part of this transition. This article provides a historical account of the development of health care in China since 1949. It also focuses on health insurance and macroeconomic structural adjustment to less saving and more consumption. In particular, the question of how health insurance impacts precautionary savings is considered. Multivariate analysis using data from 1990 to 2012 is employed. The household savings rate is the dependent variable in 3 models segmented for rural and urban populations. Independent variables include out-of-pocket health expenditures, health insurance payouts, housing expenditure, education expenditure, and consumption as a share of gross domestic product (GDP). Out-of-pocket health expenditures were positively correlated with household savings rates. But health insurance remains weak, and increased payouts by health insurers have not been associated with lower levels of household savings so far. Housing was positively correlated, whereas education had a negative association with savings rates. This latter finding was unexpected. Perhaps education is perceived as investment and a substitute for savings. China's shift toward a more service-oriented economy includes growing dependence on the health sector. Better health insurance is an important part of this evolution. The organization and finance of health care is integrally linked with macroeconomic policy in an environment constrained by prevailing institutional convention. Problems of agency relationships, professional hegemony, and special interest politics feature prominently, as they do elsewhere. China also has a dual approach to medicine relying heavily on providers of traditional Chinese medicine. Both of these segments will take part in China's evolution, adding another layer of complexity to policy. © The Author(s) 2016.

Organization and Finance of China’s Health Sector

PubMed Central

Li, Hui; Hilsenrath, Peter

2016-01-01

China has exploded onto the world economy over the past few decades and is undergoing rapid transformation toward relatively more services. The health sector is an important part of this transition. This article provides a historical account of the development of health care in China since 1949. It also focuses on health insurance and macroeconomic structural adjustment to less saving and more consumption. In particular, the question of how health insurance impacts precautionary savings is considered. Multivariate analysis using data from 1990 to 2012 is employed. The household savings rate is the dependent variable in 3 models segmented for rural and urban populations. Independent variables include out-of-pocket health expenditures, health insurance payouts, housing expenditure, education expenditure, and consumption as a share of gross domestic product (GDP). Out-of-pocket health expenditures were positively correlated with household savings rates. But health insurance remains weak, and increased payouts by health insurers have not been associated with lower levels of household savings so far. Housing was positively correlated, whereas education had a negative association with savings rates. This latter finding was unexpected. Perhaps education is perceived as investment and a substitute for savings. China’s shift toward a more service-oriented economy includes growing dependence on the health sector. Better health insurance is an important part of this evolution. The organization and finance of health care is integrally linked with macroeconomic policy in an environment constrained by prevailing institutional convention. Problems of agency relationships, professional hegemony, and special interest politics feature prominently, as they do elsewhere. China also has a dual approach to medicine relying heavily on providers of traditional Chinese medicine. Both of these segments will take part in China’s evolution, adding another layer of complexity to policy. PMID:26831625

Contribution of variable-speed pump hydro storage for power system dynamic performance

NASA Astrophysics Data System (ADS)

Silva, B.; Moreira, C.

2017-04-01

This paper presents the study of variable-speed Pump Storage Powerplant (PSP) in the Portuguese power system. It evaluates the progressive integration in three major locations and compares the power system performance following a severe fault event with consequent disconnection of non-Fault Ride-through (FRT) compliant Wind Farms (WF). To achieve such objective, a frequency responsive model was developed in PSS/E and was further used to substitute existing fixed-speed PSP. The results allow identifying a clear enhancement on the power system performance by the presence of frequency responsive variable-speed PSP, especially for the scenario presented, with high level of renewables integration.

ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

PubMed

Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

2006-12-01

The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

Synthesis and antifungal activities of 3-alkyl substituted thieno[2,3-d]pyrimidinones

NASA Astrophysics Data System (ADS)

Wang, H. M.; Deng, S. H.; Zheng, A. H.; Zhang, Q. Y.; Chen, X. B.; Zeng, X. H.; Hu, Y. G.

2016-08-01

The 3-aryl substituted thieno[2,3-d]pyrimidinones 3 by sequential reaction of iminophosphorane 1, aromatic isocyanates and various nucleophiles (HY), found some compounds showed good antitumor and antibacterial activities. Meanwhile, aliphatic isocyanates were applied in the reaction to prepare 3-alkyl substituted thieno[2,3- d]pyrimidinones, but there are no reports of their antifungal activities. As a continuation of our research for new biologically active heterocycles, we herein wish to report a facile synthesis and antifungal activities of 3-alkyl substituted thieno[2,3-d]pyrimidinones 6 via easily accessible iminophosphorane 1. The growth inhibitory effect of one concentration (50mg/L) of compounds 6 against five fungus(Fusarium oxysporium, Rhizoctonia solani, Colletotrichum gossypii, Gibberella zeae and Dothiorella gregaria) in vitro was tested by the method of toxic medium. Compound 6d showed the best inhibition rate against Gibberella zeae with 85.68%.

Breast milk substitutes in Hong Kong.

PubMed

Nelson, E A S; Chan, C W; Yu, C M

2004-07-01

In 1981 the World Health Assembly (WHA) adopted the International Code of Marketing of Breast Milk Substitutes (the Code) to support breastfeeding. Despite improving trends, Hong Kong has low rates of breastfeeding compared to other developed countries. We surveyed companies marketing breast milk substitutes in Hong Kong to determine self-reported adherence to the Code. Companies were informed that individual responses would not be published and seven of nine companies responded to the questionnaire. The majority of respondents promoted infant and follow-on formula in hospitals and provided free supplies of infant formula to hospitals. Follow-on formula and weaning foods were promoted in shops and to the general public and free samples were given to mothers reflecting a belief that, despite WHA resolutions, follow-on formula is not a breast milk substitute. Transnational companies should follow the Code and subsequent WHA resolutions equally in all countries.

Effects of Combined Application of Biogas Slurry and Chemical Fertilizer on Soil Aggregation and C/N Distribution in an Ultisol

PubMed Central

Zheng, Xuebo; Fan, Jianbo; Xu, Lei; Zhou, Jing

2017-01-01

Unreasonable use of chemical fertilizer (CF) on agricultural soil leads to massive losses of soil organic carbon (SOC) and total nitrogen (TN) in tropical and subtropical areas, where soil conditions are unfavorable for aggregate formation. This study evaluated the effects of combined application of biogas slurry (BS) plus CF on soil aggregation and aggregate—associated C/N concentration and storage in an Ultisol. Six treatments included: no fertilizer (T1), CF only (T2), partial (15% (T3), 30% (T4) and 45% (T5)) substitution of TN with BS and BS only (T6). Soil mechanical—stable aggregates (MSAs) formation and stability as well as MSAs—associated C/N concentration and storage were observed in different aggregate sizes (>5, 5–2, 2–1, 1.0–0.5, 0.50–0.25 and <0.25 mm). The proportion of MSAs >5 mm significantly increased with BS substitution (T5), while the proportions of MSAs 1.0–0.5 mm, MSAs 0.50–0.25 mm and MSAs <0.25 mm significantly decreased. Both mean weight diameter and geometric mean diameter were highest in T5, which improved soil aggregation stability as well as resulted in significantly higher SOC and TN concentrations and storage in MSAs >0.5 mm that constituted 72–82% of MSAs. Stepwise regression analysis showed that MSAs >5 mm, SOC in MSAs >5 mm and TN in MSAs >5 mm were the dominant variables affecting aggregate stability. Meanwhile SOC in MSAs <0.25 mm and TN in MSAs 2–1 mm were independent variables affecting SOC and TN concentrations in bulk soils. Therefore, certain rate of combined application of BS plus CF is an effective, eco—friendly way to improve soil quality in an Ultisol. PMID:28125647

On the materials basis of modern society

PubMed Central

Graedel, T. E.; Nassar, N. T.; Reck, Barbara K.

2015-01-01

It is indisputable that modern life is enabled by the use of materials in its technologies. Those technologies do many things very well, largely because each material is used for purposes to which it is exquisitely fitted. The result over time has been a steady increase in product performance. We show that this materials complexity has markedly increased in the past half-century and that elemental life cycle analyses characterize rates of recycling and loss. A further concern is that of possible scarcity of some of the elements as their use increases. Should materials availability constraints occur, the use of substitute materials comes to mind. We studied substitution potential by generating a comprehensive summary of potential substitutes for 62 different metals in all their major uses and of the performance of the substitutes in those applications. As we show herein, for a dozen different metals, the potential substitutes for their major uses are either inadequate or appear not to exist at all. Further, for not 1 of the 62 metals are exemplary substitutes available for all major uses. This situation largely decouples materials substitution from price, thereby forcing material design changes to be primarily transformative rather than incremental. As wealth and population increase worldwide in the next few decades, scientists will be increasingly challenged to maintain and improve product utility by designing new and better materials, but doing so under potential constraints in resource availability. PMID:24297915

Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

PubMed

Labhardt, Niklaus D; Sello, Motlalepula; Lejone, Thabo; Ehmer, Jochen; Mokhantso, Mohlaba; Lynen, Lutgarde; Pfeiffer, Karolin

2012-10-01

In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32-1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83-3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83-2.84). Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them. © 2012 Blackwell Publishing Ltd.

Determinants of Base-Pair Substitution Patterns Revealed by Whole-Genome Sequencing of DNA Mismatch Repair Defective Escherichia coli.

PubMed

Foster, Patricia L; Niccum, Brittany A; Popodi, Ellen; Townes, Jesse P; Lee, Heewook; MohammedIsmail, Wazim; Tang, Haixu

2018-06-15

Mismatch repair (MMR) is a major contributor to replication fidelity, but its impact varies with sequence context and the nature of the mismatch. Mutation accumulation experiments followed by whole-genome sequencing of MMR-defective E. coli strains yielded ≈30,000 base-pair substitutions, revealing mutational patterns across the entire chromosome. The base-pair substitution spectrum was dominated by A:T > G:C transitions, which occurred predominantly at the center base of 5'N A C3'+5'G T N3' triplets. Surprisingly, growth on minimal medium or at low temperature attenuated these mutations. Mononucleotide runs were also hotspots for base-pair substitutions, and the rate at which these occurred increased with run length. Comparison with ≈2000 base-pair substitutions accumulated in MMR-proficient strains revealed that both kinds of hotspots appeared in the wild-type spectrum and so are likely to be sites of frequent replication errors. In MMR-defective strains transitions were strand biased, occurring twice as often when A and C rather than T and G were on the lagging-strand template. Loss of nucleotide diphosphate kinase increases the cellular concentration of dCTP, which resulted in increased rates of mutations due to misinsertion of C opposite A and T. In an mmr ndk double mutant strain, these mutations were more frequent when the template A and T were on the leading strand, suggesting that lagging-strand synthesis was more error-prone or less well corrected by proofreading than was leading strand synthesis. Copyright © 2018, Genetics.

ABTS as an Electron Shuttle to Enhance the Oxidation Kinetics of Substituted Phenols by Aqueous Permanganate.

PubMed

Song, Yang; Jiang, Jin; Ma, Jun; Pang, Su-Yan; Liu, Yong-Ze; Yang, Yi; Luo, Cong-Wei; Zhang, Jian-Qiao; Gu, Jia; Qin, Wen

2015-10-06

In this study, it was, interestingly, found that 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate (ABTS), a widely used electron shuttle, could greatly accelerate the oxidation of substituted phenols by potassium permanganate (Mn(VII)) in aqueous solutions at pH 5-9. This was attributed to the fact that these substituted phenols could be readily oxidized by the stable radical cation (ABTS(•+)), which was quickly produced from the oxidation of ABTS by Mn(VII). The reaction of Mn(VII) with ABTS exhibited second-order kinetics, with stoichiometries of ∼5:1 at pH 5-6 and ∼3:1 at pH 7-9, and the rate constants varied negligibly from pH 5 to 9 (k = (9.44 ± 0.21) × 10(4) M(-1) s(-1)). Comparatively, the reaction of ABTS(•+) with phenol showed biphasic kinetics. The second-order rate constants for the reactions of ABTS(•+) with substituted phenols obtained in the initial phase were strongly affected by pH, and they were several orders of magnitude higher than those for the reactions of Mn(VII) with substituted phenols at each pH. Good Hammett-type correlations were found for the reactions of ABTS(•+) with undissociated (log(k) = 2.82-4.31σ) and dissociated phenols (log(k) = 7.29-5.90σ). The stoichiometries of (2.2 ± 0.06):1 (ABTS(•+) in excess) and (1.38 ± 0.18):1 (phenol in excess) were achieved in the reaction of ABTS(•+) with phenol, but they exhibited no pH dependency.

Chewing gum and a saliva substitute alleviate thirst and xerostomia in patients on haemodialysis.

PubMed

Bots, Casper P; Brand, Henk S; Veerman, Enno C I; Korevaar, Johanna C; Valentijn-Benz, Marianne; Bezemer, Pieter D; Valentijn, Robert M; Vos, Pieter F; Bijlsma, Joost A; ter Wee, Piet M; Van Amerongen, Barbara M; Nieuw Amerongen, Arie V

2005-03-01

Most patients on haemodialysis (HD) have to maintain a fluid-restricted diet to prevent a high interdialytic weight gain (IWG). The prevalence of xerostomia (the feeling of a dry mouth) is higher in HD patients than in controls. Recently, we demonstrated that xerostomia and thirst were positively correlated with IWG in HD patients. Thus, this may play a role as a stimulus for fluid intake between dialysis sessions. The aim of the present study was to investigate the effect of chewing gum or a saliva substitute on xerostomia, thirst and IWG. This study was a randomized two-treatment crossover design with repeated measures. After the use of chewing gum or saliva substitute for 2 weeks, a wash-out period of 2 weeks was introduced and hereafter the other regimen was carried out. Xerostomia and thirst were assessed by validated questionnaires as xerostomia inventory (XI) and dialysis thirst inventory (DTI), at baseline and after each treatment period, as were IWG and salivary flow rates. Sixty-five HD patients (42 men, 54.6+/-14.1 years; 23 women, 54.7+/-16.3 years) participated in this study. Chewing gum decreased XI from 29.9+/-9.5 to 28.1+/-9.1 (P<0.05). Chewing gum as well as a saliva substitute reduced DTI significantly (P<0.05), but no differences occurred for the average IWG or salivary flow rates. The use of chewing gum and, to a lesser extent, a saliva substitute may alleviate thirst and xerostomia in some HD patients.

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.

Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench.

PubMed

Talk, Ruaa A; Duperray, Alexia; Li, Xiabing; Coldham, Iain

2016-06-07

Substituted N-tert-butoxycarbonyl (Boc)-1,2,3,4-tetrahydroisoquinolines were prepared and treated with n-butyllithium in THF at -50 °C to test the scope of the metallation and electrophilic quench. The lithiation was optimised by using in situ ReactIR spectroscopy and the rate of rotation of the carbamate was determined. The 1-lithiated intermediates could be trapped with a variety of electrophiles to give good yields of 1-substituted tetrahydroisoquinoline products. Treatment with acid or reduction with LiAlH4 allows conversion to the N-H or N-Me compound. The chemistry was applied to the efficient total syntheses of the alkaloids (±)-crispine A and (±)-dysoxyline.

Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy

PubMed Central

Adnan, Liyana Hazwani Mohd; Bakar, Nor Hidayah Abu; Mohamad, Nasir

2014-01-01

Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ) as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency. PMID:25859295

Synthesis and characterization of polyphosphazene copolymers using phosphorus-31 NMR spectroscopy

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

Stewart, F.F.; Peterson, E.S.; Stone, M.L.

It was observed that competitive nucleophilic addition processes may be observed by {sup 31}P NMR spectroscopy. Methoxyethoxyethanol (MEE) and p-methoxyphenol readily substitute for chlorineonto phosphorus and the relative rates are generally comparable to each other. Sterically, the phenol presents is slightly larger than MEE but this does not appear to effect substitution judging by the observed PN(OAr){sub 2} NMR signal. These processes are still being studied.

30 CFR 203.49 - May I substitute the deep gas drilling provisions in § 203.0 and §§ 203.40 through 203.47 for the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false May I substitute the deep gas drilling... MINERALS REVENUE MANAGEMENT RELIEF OR REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General Royalty Relief for Drilling Deep Gas Wells on Leases Not Subject to Deep Water Royalty Relief § 203.49 May I...

Inversion of substrate stereoselectivity of horse liver alcohol dehydrogenase by substitutions of Ser-48 and Phe-93

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

Kim, Keehyuk; Plapp, Bryce V.

The substrate specificities of alcohol dehydrogenases (ADH) are of continuing interest for understanding the physiological functions of these enzymes. Ser-48 and Phe-93 have been identified as important residues in the substrate binding sites of ADHs, but more comprehensive structural and kinetic studies are required. The S48T substitution in horse ADH1E has small effects on kinetic constants and catalytic efficiency (V/Km) with ethanol, but decreases activity with benzyl alcohol and affinity for 2,2,2-trifluoroethanol (TFE) and 2,3,4,5,6-pentafluorobenzyl alcohol (PFB). Nevertheless, atomic resolution crystal structures of the S48T enzyme complexed with NAD+ and TFE or PFB are very similar to the structures formore » the wild-type enzyme. (The S48A substitution greatly diminishes catalytic activity.) The F93A substitution significantly decreases catalytic efficiency (V/Km) for ethanol and acetaldehyde while increasing activity for larger secondary alcohols and the enantioselectivity for the R-isomer relative to the S-isomer of 2-alcohols. The doubly substituted S48T/F93A enzyme has kinetic constants for primary and secondary alcohols similar to those for the F93A enzyme, but the effect of the S48T substitution is to decrease V/Km for (S)-2-alcohols without changing V/Km for (R)-2-alcohols. Thus, the S48T/F93A substitutions invert the enantioselectivity for alcohol oxidation, increasing the R/S ratio by 10, 590, and 200-fold for 2-butanol, 2-octanol, and sec-phenethyl alcohol, respectively. Transient kinetic studies and simulations of the ordered bi bi mechanism for the oxidation of the 2-butanols by the S48T/F93A ADH show that the rate of hydride transfer is increased about 7-fold for both isomers (relative to wild-type enzyme) and that the inversion of enantioselectivity is due to more productive binding for (R)-2-butanol than for (S)-2-butanol in the ternary complex. Molecular modeling suggests that both of the sec-phenethyl alcohols could bind to the enzyme and that dynamics must affect the rates of catalysis.« less

Lithium in Jack Hills zircons: Evidence for extensive weathering of Earth's earliest crust

NASA Astrophysics Data System (ADS)

Ushikubo, Takayuki; Kita, Noriko T.; Cavosie, Aaron J.; Wilde, Simon A.; Rudnick, Roberta L.; Valley, John W.

2008-08-01

In situ Li analyses of 4348 to 3362 Ma detrital zircons from the Jack Hills, Western Australia by SIMS reveal that the Li abundances (typically 10 to 60 ppm) are commonly over 10,000 times higher than in zircons crystallized from mantle-derived magmas and in mantle-derived zircon megacrysts (typically < 2 ppb). High Li concentrations in zircons (10 to 250 ppm) have also been found in igneous zircons from three continental parent rocks: granites, Li-rich pegmatites, and migmatites in pelitic metasediment. The substitution of trivalent cations (REEs and Y) in zircon correlates with Li + 1 and P + 5 , suggesting that an interstitial site for Li, as well as the xenotime substitution for P, provides charge balance for REEs. Li is thus fixed in the zircon structure by coupled substitutions, and diffusive changes in [Li] composition are rate-limited by slow diffusion of REEs. The Jack Hills zircons also have fractionated lithium isotope ratios ( δ7Li = - 19 to + 13‰) about five times more variable than those recorded in primitive ocean floor basalts (2 to 8‰), but similar to continental crust and its weathering products. Values of δ7Li below - 10‰ are found in zircons that formed as early as 4300 Ma. The high Li compositions indicate that primitive magmas were not the source of Jack Hills zircons and the fractionated values of δ7Li suggest that highly weathered regolith was sampled by these early Archean magmas. These new Li data provide evidence that the parent magmas of ancient zircons from Jack Hills incorporated materials from the surface of the Earth that interacted at low temperature with liquid water. These data support the hypothesis that continental-type crust and oceans existed by 4300 Ma, within 250 million years of the formation of Earth and the low values of δ7Li suggest that weathering was extensive in the early Archean.

Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease.

PubMed Central

Salvatori, F; Masiero, S; Giaquinto, C; Wade, C M; Brown, A J; Chieco-Bianchi, L; De Rossi, A

1997-01-01

We addressed the relationship between the origin and evolution of human immunodeficiency virus type 1 (HIV-1) variants and disease outcome in perinatally infected infants by studying the V3 regions of viral variants in samples obtained from five transmitting mothers at delivery and obtained sequentially over the first year of life from their infected infants, two of whom (rapid progressors) rapidly progressed to having AIDS. Phylogenetic analyses disclosed that the V3 sequences from each mother-infant pair clustered together and were clearly distinct from those of the other pairs. Within each pair, the child's sequences formed a monophyletic group, indicating that a single variant initiated the infection in both rapid and slow progressors. Plasma HIV-1 RNA levels increased in all five infants during their first months of life and then declined within the first semester of life only in the three slow progressors. V3 variability increased over time in all infants, but no differences in the pattern of V3 evolution in terms of potential viral phenotype were observed. The numbers of synonymous and nonsynonymous substitutions varied during the first semester of life regardless of viral load, CD4+-cell count, and disease progression. Conversely, during the second semester of life the rate of nonsynonymous substitutions was higher than that of synonymous substitutions in the slow progressors but not in the rapid progressors, thus suggesting a stronger host selective pressure in the former. In view of the proposal that V3 genetic evolution is driven mainly by host immune constraints, these findings suggest that while the immune response to V3 might contribute to regulating viral levels after the first semester of life, it is unlikely to play a determinant role in the initial viral decline soon after birth. PMID:9151863

Substituting values for censored data from Texas, USA, reservoirs inflated and obscured trends in analyses commonly used for water quality target development.

PubMed

Grantz, Erin; Haggard, Brian; Scott, J Thad

2018-06-12

We calculated four median datasets (chlorophyll a, Chl a; total phosphorus, TP; and transparency) using multiple approaches to handling censored observations, including substituting fractions of the quantification limit (QL; dataset 1 = 1QL, dataset 2 = 0.5QL) and statistical methods for censored datasets (datasets 3-4) for approximately 100 Texas, USA reservoirs. Trend analyses of differences between dataset 1 and 3 medians indicated percent difference increased linearly above thresholds in percent censored data (%Cen). This relationship was extrapolated to estimate medians for site-parameter combinations with %Cen > 80%, which were combined with dataset 3 as dataset 4. Changepoint analysis of Chl a- and transparency-TP relationships indicated threshold differences up to 50% between datasets. Recursive analysis identified secondary thresholds in dataset 4. Threshold differences show that information introduced via substitution or missing due to limitations of statistical methods biased values, underestimated error, and inflated the strength of TP thresholds identified in datasets 1-3. Analysis of covariance identified differences in linear regression models relating transparency-TP between datasets 1, 2, and the more statistically robust datasets 3-4. Study findings identify high-risk scenarios for biased analytical outcomes when using substitution. These include high probability of median overestimation when %Cen > 50-60% for a single QL, or when %Cen is as low 16% for multiple QL's. Changepoint analysis was uniquely vulnerable to substitution effects when using medians from sites with %Cen > 50%. Linear regression analysis was less sensitive to substitution and missing data effects, but differences in model parameters for transparency cannot be discounted and could be magnified by log-transformation of the variables.

Frequency of Interferon-Resistance Conferring Substitutions in Amino Acid Positions 70 and 91 of Core Protein of the Russian HCV 1b Isolates Analyzed in the T-Cell Epitopic Context

PubMed Central

Soboleva, N. V.; Karlsen, A. A.; Isaeva, O. V.; Isaguliants, M. G.; Mikhailov, M. I.

2018-01-01

Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can affect the response to interferon and are associated with the development of hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in the European (18.0%, p = 0.0010), but lower than that in the US HCV 1b strains (62.8%, p < 0.0001). Substitution L91M was found in 80.4% of the Russian HCV 1b isolates, higher than in Asian isolates (43.8%, p < 0.0001). Thus, a significant proportion of Russian HCV 1b isolates carry the unfavorable R70Q/H and/or L91M substitution. In silico analysis of the epitopic structure of the regions of substitutions revealed that both harbor clusters of T-cell epitopes. Peptides encompassing these regions were predicted to bind to a panel of HLA class I molecules, with substitutions impairing peptide recognition by HLA I molecules of the alleles prevalent in Russia. This indicates that HCV 1b with R70Q/H and L91M substitutions may have evolved as the immune escape variants. Impairment of T-cell recognition may play a part in the negative effect of these substitutions on the response to IFN treatment. PMID:29577052

Epistatic interactions influence terrestrial–marine functional shifts in cetacean rhodopsin

PubMed Central

2017-01-01

Like many aquatic vertebrates, whales have blue-shifting spectral tuning substitutions in the dim-light visual pigment, rhodopsin, that are thought to increase photosensitivity in underwater environments. We have discovered that known spectral tuning substitutions also have surprising epistatic effects on another function of rhodopsin, the kinetic rates associated with light-activated intermediates. By using absorbance spectroscopy and fluorescence-based retinal release assays on heterologously expressed rhodopsin, we assessed both spectral and kinetic differences between cetaceans (killer whale) and terrestrial outgroups (hippo, bovine). Mutation experiments revealed that killer whale rhodopsin is unusually resilient to pleiotropic effects on retinal release from key blue-shifting substitutions (D83N and A292S), largely due to a surprisingly specific epistatic interaction between D83N and the background residue, S299. Ancestral sequence reconstruction indicated that S299 is an ancestral residue that predates the evolution of blue-shifting substitutions at the origins of Cetacea. Based on these results, we hypothesize that intramolecular epistasis helped to conserve rhodopsin's kinetic properties while enabling blue-shifting spectral tuning substitutions as cetaceans adapted to aquatic environments. Trade-offs between different aspects of molecular function are rarely considered in protein evolution, but in cetacean and other vertebrate rhodopsins, may underlie multiple evolutionary scenarios for the selection of specific amino acid substitutions. PMID:28250185

Array-Based Rational Design of Short Peptide Probe-Derived from an Anti-TNT Monoclonal Antibody.

PubMed

Okochi, Mina; Muto, Masaki; Yanai, Kentaro; Tanaka, Masayoshi; Onodera, Takeshi; Wang, Jin; Ueda, Hiroshi; Toko, Kiyoshi

2017-10-09

Complementarity-determining regions (CDRs) are sites on the variable chains of antibodies responsible for binding to specific antigens. In this study, a short peptide probe for recognition of 2,4,6-trinitrotoluene (TNT), was identified by testing sequences derived from the CDRs of an anti-TNT monoclonal antibody. The major TNT-binding site in this antibody was identified in the heavy chain CDR3 by antigen docking simulation and confirmed by an immunoassay using a spot-synthesis based peptide array comprising amino acid sequences of six CDRs in the variable region. A peptide derived from heavy chain CDR3 (RGYSSFIYWF) bound to TNT with a dissociation constant of 1.3 μM measured by surface plasmon resonance. Substitution of selected amino acids with basic residues increased TNT binding while substitution with acidic amino acids decreased affinity, an isoleucine to arginine change showed the greatest improvement of 1.8-fold. The ability to create simple peptide binders of volatile organic compounds from sequence information provided by the immune system in the creation of an immune response will be beneficial for sensor developments in the future.

One device, one equation: the simplest way to objectively evaluate psoriasis severity.

PubMed

Choi, Jae Woo; Kim, Bo Ri; Choi, Chong Won; Youn, Sang Woong

2015-02-01

The erythema, scale and thickness of psoriasis lesions could be converted to bioengineering parameters. An objective psoriasis severity assessment is advantageous in terms of accuracy and reproducibility over conventional severity assessment. We aimed to formulate an objective psoriasis severity index with a single bioengineering device that can possibly substitute the conventional subjective Psoriasis Severity Index. A linear regression analysis was performed to derive the formula with the subjective Psoriasis Severity Index as the dependent variable and various bioengineering parameters determined from 157 psoriasis lesions as independent variables. The construct validity of the objective Psoriasis Severity Index was evaluated with an additional 30 psoriasis lesions through a Pearson correlation analysis. The formula is composed of hue and brightness, which are sufficiently obtainable with a Colorimeter alone. A very strong positive correlation was found between the objective and subjective psoriasis severity indexes. The objective Psoriasis Severity Index is a novel, practical and valid assessment method that can substitute the conventional one. Combined with subjective area assessment, it could further replace the Psoriasis Area and Severity Index which is currently most popular. © 2014 Japanese Dermatological Association.

Contrasting Patterns of Nucleotide Substitution Rates Provide Insight into Dynamic Evolution of Plastid and Mitochondrial Genomes of Geranium.

PubMed

Park, Seongjun; Ruhlman, Tracey A; Weng, Mao-Lun; Hajrah, Nahid H; Sabir, Jamal S M; Jansen, Robert K

2017-06-01

Geraniaceae have emerged as a model system for investigating the causes and consequences of variation in plastid and mitochondrial genomes. Incredible structural variation in plastid genomes (plastomes) and highly accelerated evolutionary rates have been reported in selected lineages and functional groups of genes in both plastomes and mitochondrial genomes (mitogenomes), and these phenomena have been implicated in cytonuclear incompatibility. Previous organelle genome studies have included limited sampling of Geranium, the largest genus in the family with over 400 species. This study reports on rates and patterns of nucleotide substitutions in plastomes and mitogenomes of 17 species of Geranium and representatives of other Geraniaceae. As detected across other angiosperms, substitution rates in the plastome are 3.5 times higher than the mitogenome in most Geranium. However, in the branch leading to Geranium brycei/Geranium incanum mitochondrial genes experienced significantly higher dN and dS than plastid genes, a pattern that has only been detected in one other angiosperm. Furthermore, rate accelerations differ in the two organelle genomes with plastomes having increased dN and mitogenomes with increased dS. In the Geranium phaeum/Geranium reflexum clade, duplicate copies of clpP and rpoA genes that experienced asymmetric rate divergence were detected in the single copy region of the plastome. In the case of rpoA, the branch leading to G. phaeum/G. reflexum experienced positive selection or relaxation of purifying selection. Finally, the evolution of acetyl-CoA carboxylase is unusual in Geraniaceae because it is only the second angiosperm family where both prokaryotic and eukaryotic ACCases functionally coexist in the plastid. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Contrasting Patterns of Nucleotide Substitution Rates Provide Insight into Dynamic Evolution of Plastid and Mitochondrial Genomes of Geranium

PubMed Central

Park, Seongjun; Ruhlman, Tracey A.; Weng, Mao-Lun; Hajrah, Nahid H.; Sabir, Jamal S.M.

2017-01-01

Abstract Geraniaceae have emerged as a model system for investigating the causes and consequences of variation in plastid and mitochondrial genomes. Incredible structural variation in plastid genomes (plastomes) and highly accelerated evolutionary rates have been reported in selected lineages and functional groups of genes in both plastomes and mitochondrial genomes (mitogenomes), and these phenomena have been implicated in cytonuclear incompatibility. Previous organelle genome studies have included limited sampling of Geranium, the largest genus in the family with over 400 species. This study reports on rates and patterns of nucleotide substitutions in plastomes and mitogenomes of 17 species of Geranium and representatives of other Geraniaceae. As detected across other angiosperms, substitution rates in the plastome are 3.5 times higher than the mitogenome in most Geranium. However, in the branch leading to Geranium brycei/Geranium incanum mitochondrial genes experienced significantly higher dN and dS than plastid genes, a pattern that has only been detected in one other angiosperm. Furthermore, rate accelerations differ in the two organelle genomes with plastomes having increased dN and mitogenomes with increased dS. In the Geranium phaeum/Geranium reflexum clade, duplicate copies of clpP and rpoA genes that experienced asymmetric rate divergence were detected in the single copy region of the plastome. In the case of rpoA, the branch leading to G. phaeum/G. reflexum experienced positive selection or relaxation of purifying selection. Finally, the evolution of acetyl-CoA carboxylase is unusual in Geraniaceae because it is only the second angiosperm family where both prokaryotic and eukaryotic ACCases functionally coexist in the plastid. PMID:28854633

Pleistocene evolutionary history of the Clouded Apollo (Parnassius mnemosyne): genetic signatures of climate cycles and a 'time-dependent' mitochondrial substitution rate.

PubMed

Gratton, P; Konopiński, M K; Sbordoni, V

2008-10-01

Genetic data are currently providing a large amount of new information on past distribution of species and are contributing to a new vision of Pleistocene ice ages. Nonetheless, an increasing number of studies on the 'time dependency' of mutation rates suggest that date assessments for evolutionary events of the Pleistocene might be overestimated. We analysed mitochondrial (mt) DNA (COI) sequence variation in 225 Parnassius mnemosyne individuals sampled across central and eastern Europe in order to assess (i) the existence of genetic signatures of Pleistocene climate shifts; and (ii) the timescale of demographic and evolutionary events. Our analyses reveal a phylogeographical pattern markedly influenced by the Pleistocene/Holocene climate shifts. Eastern Alpine and Balkan populations display comparatively high mtDNA diversity, suggesting multiple glacial refugia. On the other hand, three widely distributed and spatially segregated lineages occupy most of northern and eastern Europe, indicating postglacial recolonization from different refugial areas. We show that a conventional 'phylogenetic' substitution rate cannot account for the present distribution of genetic variation in this species, and we combine phylogeographical pattern and palaeoecological information in order to determine a suitable intraspecific rate through a Bayesian coalescent approach. We argue that our calibrated 'time-dependent' rate (0.096 substitutions/ million years), offers the most convincing time frame for the evolutionary events inferred from sequence data. When scaled by the new rate, estimates of divergence between Balkan and Alpine lineages point to c. 19 000 years before present (last glacial maximum), and parameters of demographic expansion for northern lineages are consistent with postglacial warming (5-11 000 years before present).

Predominance of influenza A(H3N2) viruses during the 2016/2017 season in Bulgaria.

PubMed

Korsun, Neli; Angelova, Svetla; Trifonova, Ivelina; Tzotcheva, Iren; Mileva, Sirma; Voleva, Silvia; Georgieva, Irina; Perenovska, Penka

2018-02-01

Influenza viruses are characterised by high variability, which makes them able to cause annual epidemics. The aim of this study is to determine the antigenic and genetic characteristics of influenza viruses circulating in Bulgaria during the 2016/2017 season. The detection and typing/subtyping of influenza viruses were performed using real time RT-PCR. Results of antigenic characterisation, phylogenetic and amino acid sequence analyses of representative influenza strains are presented herein. The 2016/2017 season was characterised by an early start, an exclusive dominance of A(H3N2) viruses accounting for 93 % of total influenza virus detections, and a low circulation of A(H1N1)pdm09 (4.2 %) and type B (2.5 %) viruses. The analysed A(H3N2) viruses belonged to subclades 3C.2a (52 %) and 3C.2a1 (48 %); all studied A(H1N1)pdm09 and B/Victoria-lineage viruses belonged to subclades 6B.1 and 1A, respectively. The amino acid sequence analysis of 56 A(H3N2) isolates revealed the presence of substitutions in 18 positions in haemagglutinin (HA) as compared to the A/Hong Kong/4801/2014 vaccine virus, seven of which occurred in four antigenic sites, together with changes in 23 positions in neuraminidase (NA), and a number of substitutions in internal proteins PB2, PB1, PB1-F2, PA, NP and NS1. Despite the many amino acid substitutions, A(H3N2) viruses remained antigenically similar to the vaccine strain. Substitutions in HA and NA sequences of A(H1N1)pdm09 and B/Victoria-lineage strains were also identified, including in antigenic sites. The results of this study confirm the genetic variability of circulating influenza viruses, particularly A(H3N2), and the need for continued antigenic and molecular surveillance.

Divergence Times and the Evolutionary Radiation of New World Monkeys (Platyrrhini, Primates): An Analysis of Fossil and Molecular Data.

PubMed

Perez, S Ivan; Tejedor, Marcelo F; Novo, Nelson M; Aristide, Leandro

2013-01-01

The estimation of phylogenetic relationships and divergence times among a group of organisms is a fundamental first step toward understanding its biological diversification. The time of the most recent or last common ancestor (LCA) of extant platyrrhines is one of the most controversial among scholars of primate evolution. Here we use two molecular based approaches to date the initial divergence of the platyrrhine clade, Bayesian estimations under a relaxed-clock model and substitution rate plus generation time and body size, employing the fossil record and genome datasets. We also explore the robustness of our estimations with respect to changes in topology, fossil constraints and substitution rate, and discuss the implications of our findings for understanding the platyrrhine radiation. Our results suggest that fossil constraints, topology and substitution rate have an important influence on our divergence time estimates. Bayesian estimates using conservative but realistic fossil constraints suggest that the LCA of extant platyrrhines existed at ca. 29 Ma, with the 95% confidence limit for the node ranging from 27-31 Ma. The LCA of extant platyrrhine monkeys based on substitution rate corrected by generation time and body size was established between 21-29 Ma. The estimates based on the two approaches used in this study recalibrate the ages of the major platyrrhine clades and corroborate the hypothesis that they constitute very old lineages. These results can help reconcile several controversial points concerning the affinities of key early Miocene fossils that have arisen among paleontologists and molecular systematists. However, they cannot resolve the controversy of whether these fossil species truly belong to the extant lineages or to a stem platyrrhine clade. That question can only be resolved by morphology. Finally, we show that the use of different approaches and well supported fossil information gives a more robust divergence time estimate of a clade.

Divergence Times and the Evolutionary Radiation of New World Monkeys (Platyrrhini, Primates): An Analysis of Fossil and Molecular Data

PubMed Central

Perez, S. Ivan; Tejedor, Marcelo F.; Novo, Nelson M.; Aristide, Leandro

2013-01-01

The estimation of phylogenetic relationships and divergence times among a group of organisms is a fundamental first step toward understanding its biological diversification. The time of the most recent or last common ancestor (LCA) of extant platyrrhines is one of the most controversial among scholars of primate evolution. Here we use two molecular based approaches to date the initial divergence of the platyrrhine clade, Bayesian estimations under a relaxed-clock model and substitution rate plus generation time and body size, employing the fossil record and genome datasets. We also explore the robustness of our estimations with respect to changes in topology, fossil constraints and substitution rate, and discuss the implications of our findings for understanding the platyrrhine radiation. Our results suggest that fossil constraints, topology and substitution rate have an important influence on our divergence time estimates. Bayesian estimates using conservative but realistic fossil constraints suggest that the LCA of extant platyrrhines existed at ca. 29 Ma, with the 95% confidence limit for the node ranging from 27–31 Ma. The LCA of extant platyrrhine monkeys based on substitution rate corrected by generation time and body size was established between 21–29 Ma. The estimates based on the two approaches used in this study recalibrate the ages of the major platyrrhine clades and corroborate the hypothesis that they constitute very old lineages. These results can help reconcile several controversial points concerning the affinities of key early Miocene fossils that have arisen among paleontologists and molecular systematists. However, they cannot resolve the controversy of whether these fossil species truly belong to the extant lineages or to a stem platyrrhine clade. That question can only be resolved by morphology. Finally, we show that the use of different approaches and well supported fossil information gives a more robust divergence time estimate of a clade. PMID:23826358

Extreme primary and secondary protein structure variability in the chimeric male-transmitted cytochrome c oxidase subunit II protein in freshwater mussels: Evidence for an elevated amino acid substitution rate in the face of domain-specific purifying selection

PubMed Central

2008-01-01

Background Freshwater unionoidean bivalves, and species representing two marine bivalve orders (Mytiloida and Veneroida), exhibit a mode of mtDNA inheritance involving distinct maternal (F) and paternal (M) transmission routes concomitant with highly divergent gender-associated mtDNA genomes. Additionally, male unionoidean bivalves have a ~550 bp 3' coding extension to the cox2 gene (Mcox2e), that is apparently absent from all other metazoan taxa. Results Our molecular sequence analyses of MCOX2e indicate that both the primary and secondary structures of the MCOX2e region are evolving much faster than other regions of the F and M COX2-COX1 gene junction. The near N-terminus ~2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices (TMH) and interhelical loops (IHL) whereas the C-terminus ~1/3 is relatively conserved and hydrophilic while containing conserved functional motifs. MCOX2e displays an overall pattern of purifying selection that leads to the preservation of TMH/IHL and C-terminus tail sub-regions. However, 14 amino acid positions in the MCOX2e TMH/IHL sub-region might be targeted by diversifying selection, each representing a site where there exists interspecific variation for the constituent amino acids residing in a TMH or IHL. Conclusion Our results indicate that Mcox2e is unique to unionoidean bivalves, likely the result of a single insertion event that took place over 65 MYA and that MCOX2e is functional. The predicted TMH number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of primary and secondary structure evolution, with some amino acid residues potentially subjected to site-specific positive selection, yet an overall pattern of purifying selection leading to the preservation of the TMH/IHL and hydrophilic C-terminus tail subregions. The more conserved C-terminus tail (relative to the TMH/IHL sub-region of MCOX2e) is likely biologically active because it contains functional motifs. The rapid evolution of primary and secondary structure in MCOX2e, combined with the action of both positive and purifying selection, provide supporting evidence for the hypothesis that MCOX2e has a novel reproductive function within unionoidean bivalves. All tolled, our data indicate that unionoidean bivalve MCOX2 is the first reported chimeric animal mtDNA-encoded protein. PMID:18513440

What does the Sr-substituted 2.1 Å resolution crystal structure of photosystem II reveal about the water oxidation mechanism?

PubMed

Terrett, Richard; Petrie, Simon; Pace, Ron J; Stranger, Robert

2014-03-25

A density functional study of the Sr-substituted photosystem II water oxidising complex demonstrates that its recent X-ray crystal structure is consistent with a (Mn(III))4 oxidation state pattern, and with a Sr-bound hydroxide ion. The Sr-water-hydroxide interactions rationalize differences in the exchange rates of substrate water and kinetics of dioxygen bond formation relative to the Ca-containing structure.

Performance of Clarias gariepinus Fed Dried Brewer's Yeast (Saccharomyces cerevisiae) Slurry in Replacement for Soybean Meal.

PubMed

Solomon, Shola Gabriel; Ataguba, Gabriel Arome; Itodo, Gabriel Enemona

2017-01-01

Following disparity of earlier results, this study tested the performance of African catfish Clarias gariepinus fed dried brewer's yeast slurry meal (DBYM) based diets. Fingerlings of C. gariepinus with pooled mean initial weight of 1.58 ± 0.01 g were stocked in hapas (1 m × 1 m × 1 m) immersed in an earthen pond at a density of 15 fish per cage. Five diets with increasing substitution of soybean meal with 25%, 50%, 75%, and 100% of dried brewer's yeast and a control without dried brewer's yeast (0% substitution) were evaluated for 8 weeks. Palatability of diets reduced with increasing levels of DBYM. Growth and utilization parameters such as weight gain, feed conversion ratio, protein efficiency ratio, and specific growth rate differed significantly ( p < 0.05) among treated groups. Specific growth rate decreased with increasing substitution while the best feed conversion ratio was obtained in the diet devoid of DBYM. Protein efficiency and utilization decreased with increasing levels of DBYM. Body composition was also affected by inclusion of DBYM with significant differences ( p < 0.05) being observed across the diets. The trend in body composition follows the utilization of the diets. We conclude that the optimal range of inclusion and substitution of soybean meal with DBYM in C. gariepinus feed is between 1% and 14% of dry matter.

Performance of Clarias gariepinus Fed Dried Brewer's Yeast (Saccharomyces cerevisiae) Slurry in Replacement for Soybean Meal

PubMed Central

Solomon, Shola Gabriel; Itodo, Gabriel Enemona

2017-01-01

Following disparity of earlier results, this study tested the performance of African catfish Clarias gariepinus fed dried brewer's yeast slurry meal (DBYM) based diets. Fingerlings of C. gariepinus with pooled mean initial weight of 1.58 ± 0.01 g were stocked in hapas (1 m × 1 m × 1 m) immersed in an earthen pond at a density of 15 fish per cage. Five diets with increasing substitution of soybean meal with 25%, 50%, 75%, and 100% of dried brewer's yeast and a control without dried brewer's yeast (0% substitution) were evaluated for 8 weeks. Palatability of diets reduced with increasing levels of DBYM. Growth and utilization parameters such as weight gain, feed conversion ratio, protein efficiency ratio, and specific growth rate differed significantly (p < 0.05) among treated groups. Specific growth rate decreased with increasing substitution while the best feed conversion ratio was obtained in the diet devoid of DBYM. Protein efficiency and utilization decreased with increasing levels of DBYM. Body composition was also affected by inclusion of DBYM with significant differences (p < 0.05) being observed across the diets. The trend in body composition follows the utilization of the diets. We conclude that the optimal range of inclusion and substitution of soybean meal with DBYM in C. gariepinus feed is between 1% and 14% of dry matter. PMID:28239492

Identifying improvement potentials in cement production with life cycle assessment.

PubMed

Boesch, Michael Elias; Hellweg, Stefanie

2010-12-01

Cement production is an environmentally relevant process responsible for 5% of total anthropogenic carbon dioxide emissions and 7% of industrial fuel use. In this study, life cycle assessment is used to evaluate improvement potentials in the cement production process in Europe and the USA. With a current fuel substitution rate of 18% in Europe and 11% in the USA, both regions have a substantial potential to reduce greenhouse gas emissions and save virgin resources by further increasing the coprocessing of waste fuels. Upgrading production technology would be particularly effective in the USA where many kiln systems with very low energy efficiency are still in operation. Using best available technology and a thermal substitution rate of 50% for fuels, greenhouse gas emissions could be reduced by 9% for Europe and 18% for the USA per tonne of cement. Since clinker production is the dominant pollution producing step in cement production, the substitution of clinker with mineral components such as ground granulated blast furnace slag or fly ash is an efficient measure to reduce the environmental impact. Blended cements exhibit substantially lower environmental footprints than Portland cement, even if the substitutes feature lower grindability and require additional drying and large transport distances. The highest savings in CO(2) emissions and resource consumption are achieved with a combination of measures in clinker production and cement blending.

No influence of simultaneous bone-substitute application on the success of immediately loaded dental implants: a retrospective cohort study.

PubMed

Kopp, Sigmar; Behrend, Detlef; Kundt, Günther; Ottl, Peter; Frerich, Bernhard; Warkentin, Mareike

2013-06-01

To examine the influence of bone-substitute application during implantation on the success of immediately placed and loaded dental implants. A total of 147 consecutive patients (age, 16.5-80.4 years) were provided with 696 immediately loaded implants. The mean follow-up time was 34.1 months. Of these implants, 50.4% (n=351) were immediately placed into extraction sockets. A total of 119 implants were added by simultaneous bone-substitute application (NanoBone, Artoss GmbH, Rostock Germany), whereas the other implants were placed in healed bone. Univariate and multivariate analysis was performed using IBM SPSS V.20. The overall implant success rate was 96.1%. Implants with simultaneous bone replacement had a hazard ratio of 0.877 (p=0.837); 95% CI, 0.253-3.04). Factors found to be statistically significant modifiers of success on multivariate analysis (p<0.05) included type of superstructure (p<0.001), implant-abutment connection (p<0.001), membrane use (p=0.010), and jaw (p=0.026). None of the other factors investigated were significant modifiers. The present study demonstrates high success rates for immediately loaded implants and their superstructures independent of the simultaneous application of bone substitute. The declared aim of socket preservation, the prevention avoiding bone loss, is achieved in the immediate implant placement scenario under immediate-loading conditions.

Optimization of Microencapsulation of Human Milk Fat Substitute by Response Surface Methodology.

PubMed

Li, Xue; Cao, Jun; Bai, Xinpeng; Jiang, Zefang; Shen, Xuanri

2018-04-01

Human milk fat substitutes (HMFS) are rich in polyunsaturated fatty acids which upon microencapsulation, can be used as a source of high quality lipids in infant formula. The response surface methodology (RSM) was employed to optimize the microencapsulation condition of HMFS as a functional product. The microencapsulation efficiency (MEE) of microencapsulated HMFS was investigated with respect to four variables including concentration of soy lecithin (A), ratio of demineralized whey powder to malt dextrin (B), HFMS concentration (C), and homogenizing pressure (D). The optimum conditions for efficient microencapsulation of HMFS by the spray drying technique were determined as follows: the amount of soybean lecithin-0.96%, ratio of desalted whey powder to malt dextrin-2.04:1, oil content-17.37% and homogeneous pressure-0.46MPa. Under these conditions, the MEE was 84.72%, and the basic indices of the microcapsules were good. The structure of the microcapsules, as observed by scanning electron microscopy (SEM), revealed spherical, smooth-surfaced capsules with diameters ranging between 10-50 μm. Compared with HFMS, the peroxide value (POV) and acid value (AV) of the microcapsule were significantly lower during storage indicating that the microencapsulation process increases stability and shelf life. Infrared spectroscopic analyses indicated that HFMS had the same characteristic functional groups as the oil extracted from microcapsules. Simulated in vitro digestion revealed that the microcapsules were digested completely within 2h with maximum lipid absorption rate of 64%. Furthermore, these results advocate the embedding process of HFMS by RSM due to its efficacy.

First-Person Perspective Virtual Body Posture Influences Stress: A Virtual Reality Body Ownership Study

PubMed Central

Bergström, Ilias; Kilteni, Konstantina; Slater, Mel

2016-01-01

In immersive virtual reality (IVR) it is possible to replace a person’s real body by a life-sized virtual body that is seen from first person perspective to visually substitute their own. Multisensory feedback from the virtual to the real body (such as the correspondence of touch and also movement) can also be present. Under these conditions participants typically experience a subjective body ownership illusion (BOI) over the virtual body, even though they know that it is not their real one. In most studies and applications the posture of the real and virtual bodies are as similar as possible. Here we were interested in whether the BOI is diminished when there are gross discrepancies between the real and virtual body postures. We also explored whether a comfortable or uncomfortable virtual body posture would induce feelings and physiological responses commensurate with the posture. We carried out an experiment with 31 participants in IVR realized with a wide field-of-view head-mounted display. All participants were comfortably seated. Sixteen of them were embodied in a virtual body designed to be in a comfortable posture, and the remainder in an uncomfortable posture. The results suggest that the uncomfortable body posture led to lesser subjective BOI than the comfortable one, but that participants in the uncomfortable posture experienced greater awareness of their autonomic physiological responses. Moreover their heart rate, heart rate variability, and the number of mistakes in a cognitive task were associated with the strength of their BOI in the uncomfortable posture: greater heart rate, lower heart rate variability and more mistakes were associated with higher levels of the BOI. These findings point in a consistent direction—that the BOI over a body that is in an uncomfortable posture can lead to subjective, physiological and cognitive effects consistent with discomfort that do not occur with the BOI over a body in a comfortable posture. PMID:26828365

Impact of generic substitution decision support on electronic prescribing behavior.

PubMed

Stenner, Shane P; Chen, Qingxia; Johnson, Kevin B

2010-01-01

To evaluate the impact of generic substitution decision support on electronic (e-) prescribing of generic medications. The authors analyzed retrospective outpatient e-prescribing data from an academic medical center and affiliated network for July 1, 2005-September 30, 2008 using an interrupted time-series design to assess the rate of generic prescribing before and after implementing generic substitution decision support. To assess background secular trends, e-prescribing was compared with a concurrent random sample of hand-generated prescriptions. Proportion of generic medications prescribed before and after the intervention, evaluated over time, and compared with a sample of prescriptions generated without e-prescribing. The proportion of generic medication prescriptions increased from 32.1% to 54.2% after the intervention (22.1% increase, 95% CI 21.9% to 22.3%), with no diminution in magnitude of improvement post-intervention. In the concurrent control group, increases in proportion of generic prescriptions (29.3% to 31.4% to 37.4% in the pre-intervention, post-intervention, and end-of-study periods, respectively) were not commensurate with the intervention. There was a larger change in generic prescribing rates among authorized prescribers (24.6%) than nurses (18.5%; adjusted OR 1.38, 95% CI 1.17 to 1.63). Two years after the intervention, the proportion of generic prescribing remained significantly higher for e-prescriptions (58.1%; 95% CI 57.5% to 58.7%) than for hand-generated prescriptions ordered at the same time (37.4%; 95% CI 34.9% to 39.9%) (p<0.0001). Generic prescribing increased significantly in every specialty. Implementation of generic substitution decision support was associated with dramatic and sustained improvements in the rate of outpatient generic e-prescribing across all specialties.

Impact of generic substitution decision support on electronic prescribing behavior

PubMed Central

Chen, Qingxia; Johnson, Kevin B

2010-01-01

Objective To evaluate the impact of generic substitution decision support on electronic (e-) prescribing of generic medications. Design The authors analyzed retrospective outpatient e-prescribing data from an academic medical center and affiliated network for July 1, 2005–September 30, 2008 using an interrupted time-series design to assess the rate of generic prescribing before and after implementing generic substitution decision support. To assess background secular trends, e-prescribing was compared with a concurrent random sample of hand-generated prescriptions. Measurements Proportion of generic medications prescribed before and after the intervention, evaluated over time, and compared with a sample of prescriptions generated without e-prescribing. Results The proportion of generic medication prescriptions increased from 32.1% to 54.2% after the intervention (22.1% increase, 95% CI 21.9% to 22.3%), with no diminution in magnitude of improvement post-intervention. In the concurrent control group, increases in proportion of generic prescriptions (29.3% to 31.4% to 37.4% in the pre-intervention, post-intervention, and end-of-study periods, respectively) were not commensurate with the intervention. There was a larger change in generic prescribing rates among authorized prescribers (24.6%) than nurses (18.5%; adjusted OR 1.38, 95% CI 1.17 to 1.63). Two years after the intervention, the proportion of generic prescribing remained significantly higher for e-prescriptions (58.1%; 95% CI 57.5% to 58.7%) than for hand-generated prescriptions ordered at the same time (37.4%; 95% CI 34.9% to 39.9%) (p<0.0001). Generic prescribing increased significantly in every specialty. Conclusion Implementation of generic substitution decision support was associated with dramatic and sustained improvements in the rate of outpatient generic e-prescribing across all specialties. PMID:20962131

Role of platelet-rich plasma in combination with alloplastic bone substitute in regeneration of osseous defects

PubMed Central

Singh, Indrajeet; Gupta, Hemant; Pradhan, R; Sinha, VP; Gupta, Sumit

2012-01-01

Introduction Bone grafts are frequently used for the treatment of bone defects, but can cause postoperative complications, and sometimes a sufficient quantity of bone is not available. Hence, synthetic biomaterials have been used as an alternative to autogenous bone grafts. Recent clinical reports suggest that application of autologous blood plasma enriched with platelets can enhance the formation of new bone. There are very few in vitro or in vivo studies published on the efficiency of platelet-rich plasma (PRP). The objective of this study was to evaluate the alloplastic bone substitute for its osteogenic potential with or without PRP. Materials and Methods Twenty-three patients with periapical bony defects were selected for this study. Clinical parameters such as pain visual analog scale (VAS), swelling, infection, graft migration, rejection, radiographical interpretations at regular interval and scintigraphic evaluation were done to evaluate osteogenic potential of alloplastic bone substitute with or without PRP. Results The highest acceleration in bone formation was observed in groups where alloplastic bone substitute was used with PRP. There were no statistically significant differences between the two groups regarding other outcome variables throughout the postoperative period. Conclusion Addition of PRP significantly accelerates vascularization of the graft, improves soft tissue healing, reduces postoperative morbidity and enhances bone regeneration. PMID:25756013

Effect of glycerol concentrations on the mechanical properties of additive manufactured porous calcium polyphosphate structures for bone substitute applications.

PubMed

Sheydaeian, Esmat; Vlasea, Mihaela; Woo, Ami; Pilliar, Robert; Hu, Eugene; Toyserkani, Ehsan

2017-05-01

This article addresses the effects of glycerol (GLY) concentrations on the mechanical properties of calcium polyphosphate (CPP) bone substitute structures manufactured using binder jetting additive manufacturing. To achieve this goal, nine types of water-based binder solutions were prepared with 10, 12.5, and 15 wt % GLY liquid-binding agent, mixed, respectively, with 0, 0.75, and 1.5 wt % ethylene glycol diacetate (EGD) flow enhancer. The print quality of each of the solutions was established quantitatively using an image processing algorithm. The print quality analysis narrowed down the solutions to three batches containing 1.5 wt % EGD and variable amount of GLY. These solutions were used to manufacture porous CPP bone substitute samples, which were characterized physically to determine shrinkage, porosity, microstructure, and compression strength. The 12.5 wt % GLY, 1.5 wt % EGD solution resulted in the highest mechanical strength after sintering (34.6 ± 5.8 MPa), illustrating similar mechanical properties when compared to previous studies (33.9 ± 6.3 MPa) of additively manufactured CPP bone substitutes using a commercially available binder. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 828-835, 2017. © 2016 Wiley Periodicals, Inc.

Effect of uniaxial stress on the electrochemical properties of graphene with point defects

NASA Astrophysics Data System (ADS)

Szroeder, Paweł; Sagalianov, Igor Yu.; Radchenko, Taras M.; Tatarenko, Valentyn A.; Prylutskyy, Yuriy I.; Strupiński, Włodzimierz

2018-06-01

We report a calculational study of electron states and the resulting electrochemical properties of uniaxially strained graphene with point defects. For this study the reduction of ferricyanide to ferrocyanide serves as a benchmark electrochemical reaction. We find that the heterogeneous electron transfer activity of the perfect graphene electrode rises under uniaxial strain. However, evolution of the cathodic reaction rate depends on the direction of strain. For moderate lattice deformations, the zigzag strain improves electrochemical performance better than the armchair strain. Standard rate constant increases by 50% at the zigzag strain of 10%. Vacancies, covalently bonded moieties, charged adatoms and substitutional impurities in the zigzag strained graphene induce changes in the shape of the curve of the cathodic reaction rate. However, this changes do not translate into the electrocatalytic activity. Vacancies and covalently bonded moieties at concentration of 0.1% do not affect the electrochemical performance. Charged adatoms and substitutional impurities give a slight increase in the standard rate constant by, respectively, 2.2% and 3.4%.

Attitudes towards informed consent, confidentiality, and substitute treatment decisions in southern African medical students: a case study from Zimbabwe.

PubMed

Hipshman, L

1999-08-01

This study explored the attitudes of biomedical science students (medical students) in a non-Western setting towards three medical ethics concepts that are based on fundamental Western culture ethical principles. A dichotomous (agree/disagree) response questionnaire was constructed using Western ethnocentric culture (WEC) based perspectives of informed consent, confidentiality, and substitute decision-making. Hypothesized WEC-Biased responses were assigned to the questionnaire's questions or propositions. A number of useful responses (169) were obtained from a large, cross-sectional, convenience sample of the MBChB students at the University of Zimbabwe Medical School. Statistical analysis described the differences in response patterns between the student's responses compared to the hypothesized WEC-Biased response. The effect of the nine independent variables on selected dependent variables (responses to certain questionnaire questions) was analyzed by stepwise logistic regression. Students concurred with the hypothesized WEC-Biased responses for two-thirds of the questionnaire items. This agreement included support for the role of legal advocacy in the substitute decision-making process. The students disagreed with the hypothesized WEC-Biased responses in several important medical ethics aspects. Most notably, the students indicated that persons with mental dysfunctions, as a class, were properly considered incompetent to make treatment decisions. None of the studied independent variables was often associated with students' responses, but training year was more frequently implicated than either ethnicity or gender. In order to develop internationally and culturally relevant medical ethics standards, non-Western perspectives ought to be acknowledged and incorporated. Two main areas for further efforts include: curriculum development in ethics reasoning and related clinical (medico-legal) decision-making processes that would be relevant to medical students from various cultures, and; the testing of models that could increase legal system input in the clinical process in societies with limited jurisprudence resources.

Self-Substitution and the Temperature Effects on the Electrochemical Performance in the High Voltage Cathode System LiMn 1.5+xNi 0.5-xO 4 (x = 0.1)

DOE PAGES

Xu, Yun; Zhao, Mingyang; Khalid, Syed; ...

2017-05-09

The high voltage cathode material, LiMn 1.6Ni 0.4O 4, was prepared by a polymer-assisted method. The novelty of this paper is the substitution of Ni with Mn, which already exists in the crystal structure instead of other isovalent metal ion dopants which would result in capacity loss. The electrochemical performance testing including stability and rate capability was evaluated. The temperature was found to impose a change on the valence and structure of the cathode materials. Specifically, manganese tends to be reduced at a high temperature of 800 °C and leads to structural changes. The manganese substituted LiMn 1.5Ni 0.5O 4more » (LMN) has proved to be a good candidate material for Li-ion battery cathodes displaying good rate capability and capacity retention. Finally, the cathode materials processed at 550 °C showed a stable performance with negligible capacity loss for 400 cycles.« less

[Xerostomia, hyposialia, sicca syndrome--quantitative disturbances of the salivary flow rate].

PubMed

Slezák, R; Berglová, I; Krejsek, J

2011-04-01

Diseases of salivary glands may be associated with salivary flow rate disturbances. Production of the saliva is evaluated by sialometric tests. The stress is putted on salivary flow rate disturbances in Sjögren's syndrome, drug-induced and postirradiative sialopathy, and diabetes mellitus. The possibility of the stimulation and substitution of the saliva is discussed.

Reproducible Crystallite Size of Mono-Dispersed and Scalable Biologically Produced Metal-Substituted Nanometer-Sized Magnetites

NASA Astrophysics Data System (ADS)

Moon, J.; Rawn, C.; Rondinone, A.; Love, L.; Roh, Y.; Lauf, R.; Phelps, T.

2008-12-01

Our previous research demonstrated that biosynthesized magnetite (biomagnetite) exhibited similar properties as chemically synthesized magnetite. To complement uses of the traditional chemically synthesized magnetite (chem-magnetite) biomagnetite must be exhibit highly reproducible sizes and be available in scalable qualities. Here we emphasize potentially advantageous properties of biomagnetite regarding size, reproducibility and scaling availability. Average crystallite size (ACS) of biomagnetites ranging from 10-100 nm was determined after varied 1) incubation times, 2) substitution of metal and lanthanide species, 3) degrees of congruent incorporation or retardation of substitution elements, 4) bacterial species with their varied ability to substitute elemental species, and 6) incubation temperature that can influence coalescence. The microbial production of biomagnetite has demonstrated capacity to make highly crystalline nanoscale particles of metal-substituted ferrites including compounds of Co, Ni, Cr, Mn, Zn and the rare earths in large quantity. Selected Zn-substituted magnetite (nominal composition of Zn0.6Fe2.4O4) has been recovered at over 1 kg (wet weight) in batches from 30 L fermentations. The massively produced extracellular magnetites were confirmed to exhibit good mono- dispersity via transmission electron microscopy (TEM). TEM also validated highly reproducible ACS of 13.1±0.8 nm size as determined through X-ray diffraction (N=7) at a 99 % confidence level. Based on the scale-up experiments performed using the 35 L reactor, the reduction in ACS variability and shorted incubation times of several days may be attributed to increases of electron donor input, and availability of divalent ions of the substitution metal with less ferrous ions in the case of doped magnetite, or a combination of the above. While costs of commercial nanometer sized magnetite (25-50 nm) may vary from 500/kg to > 1,000/kg, microbial mass production is likely capable of producing 13-90 nm magnetite or doped magnetites at a fraction of the cost of traditional chemical synthesis. While there are numerous approaches for the synthesis of nanoparticles, bacterial fermentation of magnetite or metal-substituted magnetite may represent a disruptive manufacturing technology with respect to yield, reproducibility and scalability.

BDNF polymorphism predicts the rate of decline in skilled task performance and hippocampal volume in healthy individuals

PubMed Central

Sanchez, M Millan; Das, D; Taylor, J L; Noda, A; Yesavage, J A; Salehi, A

2011-01-01

Numerous studies have indicated a link between the presence of polymorphism in brain-derived neurotrophic factor (BDNF) and cognitive and affective disorders. However, only a few have studied these effects longitudinally along with structural changes in the brain. This study was carried out to investigate whether valine-to-methionine substitution at position 66 (val66met) of pro-BDNF could be linked to alterations in the rate of decline in skilled task performance and structural changes in hippocampal volume. Participants consisted of 144 healthy Caucasian pilots (aged 40–69 years) who completed a minimum of 3 consecutive annual visits. Standardized flight simulator score (SFSS) was measured as a reliable and quantifiable indicator for skilled task performance. In addition, a subset of these individuals was assessed for hippocampal volume alterations using magnetic resonance imaging. We found that val66met substitution in BDNF correlated longitudinally with the rate of decline in SFSS. Structurally, age-dependent hippocampal volume changes were also significantly altered by this substitution. Our study suggests that val66met polymorphism in BDNF can be linked to the rate of decline in skilled task performance. Furthermore, this polymorphism could be used as a predictor of the effects of age on the structure of the hippocampus in healthy individuals. Such results have implications for understanding possible disabilities in older adults performing skilled tasks who are at a higher risk for cognitive and affective disorders. PMID:22833197

Effect of Abrupt Substitution of Gadobenate Dimeglumine for Gadopentetate Dimeglumine on Rate of Allergic-like Reactions

PubMed Central

Dillman, Jonathan R.; Cohan, Richard H.; Hussain, Hero K.; Khalatbari, Shokoufeh; McHugh, Jonathan B.; Ellis, James H.

2013-01-01

Purpose: To evaluate the effect of abruptly substituting gadobenate dimeglumine for gadopentetate dimeglumine on allergic-like reactions. Materials and Methods: The institutional review board approved and waived patient consent for this HIPAA-compliant retrospective study. Allergic-like reactions related to gadolinium-based contrast media were assessed 2 years before and 3.5 years after gadobenate dimeglumine was substituted for gadopentetate dimeglumine. Reaction rates and severity were compared by using χ2 tests, Fisher exact tests, odds ratios (ORs), and confidence intervals (CIs). Results: Allergic-like reactions (137 mild, 19 moderate, and six severe) occurred in 162 (0.15%) of 105 607 injections of gadolinium-based contrast media (gadopentetate dimeglumine, 31 540; gadobenate dimeglumine, 66 152; other, 7915). Gadobenate dimeglumine was associated with significantly more overall (0.19% [123 of 66 152] vs 0.08% [24 of 31 540]; OR, 2.4; 95% CI: 1.6, 3.8; P < .0001) and mild (0.16% [107 of 66 152] vs 0.06% [18 of 31 540]; OR, 2.8; 95% CI: 1.7, 4.7; P < .0001) allergic-like reactions than was gadopentetate dimeglumine. The reaction rate for gadobenate dimeglumine peaked (maximum per quarter, 0.38% [16 of 4262]; minimum per quarter, 0.07% [three of 4237]) in the 2nd year after it replaced gadopentetate dimeglumine (maximum per quarter, 0.10% [four of 4122]; minimum per quarter, 0.05% [two of 4222]) and then declined in the 3rd year. The final gadobenate dimeglumine reaction rate (last 3 quarters, 0.12% [17 of 14 387]) did not significantly differ from the original baseline reaction rate with gadopentetate dimeglumine. Conclusion: After gadobenate dimeglumine was substituted for gadopentetate dimeglumine, a significant transient increase occurred in the frequency of reported allergic-like reactions that demonstrated a temporal pattern suggestive of the Weber effect (a transient increase in adverse event reporting that tends to peak in the 2nd year after a new agent or indication is introduced). © RSNA, 2012 PMID:23238152

Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world.

PubMed

Robertson, M P; Miller, S L

1995-05-05

Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world

NASA Technical Reports Server (NTRS)

Robertson, M. P.; Miller, S. L.

1995-01-01

Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

Estimating Divergence Dates and Substitution Rates in the Drosophila Phylogeny

PubMed Central

Obbard, Darren J.; Maclennan, John; Kim, Kang-Wook; Rambaut, Andrew; O’Grady, Patrick M.; Jiggins, Francis M.

2012-01-01

An absolute timescale for evolution is essential if we are to associate evolutionary phenomena, such as adaptation or speciation, with potential causes, such as geological activity or climatic change. Timescales in most phylogenetic studies use geologically dated fossils or phylogeographic events as calibration points, but more recently, it has also become possible to use experimentally derived estimates of the mutation rate as a proxy for substitution rates. The large radiation of drosophilid taxa endemic to the Hawaiian islands has provided multiple calibration points for the Drosophila phylogeny, thanks to the "conveyor belt" process by which this archipelago forms and is colonized by species. However, published date estimates for key nodes in the Drosophila phylogeny vary widely, and many are based on simplistic models of colonization and coalescence or on estimates of island age that are not current. In this study, we use new sequence data from seven species of Hawaiian Drosophila to examine a range of explicit coalescent models and estimate substitution rates. We use these rates, along with a published experimentally determined mutation rate, to date key events in drosophilid evolution. Surprisingly, our estimate for the date for the most recent common ancestor of the genus Drosophila based on mutation rate (25–40 Ma) is closer to being compatible with independent fossil-derived dates (20–50 Ma) than are most of the Hawaiian-calibration models and also has smaller uncertainty. We find that Hawaiian-calibrated dates are extremely sensitive to model choice and give rise to point estimates that range between 26 and 192 Ma, depending on the details of the model. Potential problems with the Hawaiian calibration may arise from systematic variation in the molecular clock due to the long generation time of Hawaiian Drosophila compared with other Drosophila and/or uncertainty in linking island formation dates with colonization dates. As either source of error will bias estimates of divergence time, we suggest mutation rate estimates be used until better models are available. PMID:22683811

Assessing the role of aromatic residues in the amyloid aggregation of human muscle acylphosphatase

PubMed Central

Bemporad, Francesco; Taddei, Niccolò; Stefani, Massimo; Chiti, Fabrizio

2006-01-01

Among the many parameters that have been proposed to promote amyloid fibril formation is the π-stacking of aromatic residues. We have studied the amyloid aggregation of several mutants of human muscle acylphosphatase in which an aromatic residue was substituted with a non-aromatic one. The aggregation rate was determined using the Thioflavin T test under conditions in which the variants populated initially an ensemble of partially unfolded conformations. Substitutions in aggregation-promoting fragments of the sequence result in a dramatically decreased aggregation rate of the protein, confirming the propensity of aromatic residues to promote this process. Nevertheless, a statistical analysis shows that the measured decrease of aggregation rate following mutation arises predominantly from a reduction of hydrophobicity and intrinsic β-sheet propensity. This suggests that aromatic residues favor aggregation because of these factors rather than for their aromaticity. PMID:16600970

[Performance based regulation: a strategy to increase breastfeeding rates].

PubMed

Cobo-Armijo, Fernanda; Charvel, Sofía; Hernández-Ávila, Mauricio

2017-01-01

The decreasing breastfeeding rate in México is of public health concern. In this paper we discus an innovative regulatory approach -Performance Based Regulation- and its application to improve breastfeeding rates. This approach, forces industry to take responsibility for the lack of breastfeeding and its consequences. Failure to comply with this targets results in financial penalties. Applying performance based regulation as a strategy to improve breastfeeding is feasible because: the breastmilk substitutes market is an oligopoly, hence it is easy to identify the contribution of each market participant; the regulation's target population is clearly defined; it has a clear regulatory standard which can be easily evaluated, and sanctions to infringement can be defined under objective parameters. modify public policy, celebrate concertation agreements with the industry, create persuasive sanctions, strengthen enforcement activities and coordinate every action with the International Code of Marketing of Breast-milk Substitutes.

Energy Storage on the Grid and the Short-term Variability of Wind

NASA Astrophysics Data System (ADS)

Hittinger, Eric Stephen

Wind generation presents variability on every time scale, which must be accommodated by the electric grid. Limited quantities of wind power can be successfully integrated by the current generation and demand-side response mix but, as deployment of variable resources increases, the resulting variability becomes increasingly difficult and costly to mitigate. In Chapter 2, we model a co-located power generation/energy storage block composed of wind generation, a gas turbine, and fast-ramping energy storage. A scenario analysis identifies system configurations that can generate power with 30% of energy from wind, a variability of less than 0.5% of the desired power level, and an average cost around $70/MWh. While energy storage technologies have existed for decades, fast-ramping grid-level storage is still an immature industry and is experiencing relatively rapid improvements in performance and cost across a variety of technologies. Decreased capital cost, increased power capability, and increased efficiency all would improve the value of an energy storage technology and each has cost implications that vary by application, but there has not yet been an investigation of the marginal rate of technical substitution between storage properties. The analysis in chapter 3 uses engineering-economic models of four emerging fast-ramping energy storage technologies to determine which storage properties have the greatest effect on cost-of-service. We find that capital cost of storage is consistently important, and identify applications for which power/energy limitations are important. In some systems with a large amount of wind power, the costs of wind integration have become significant and market rules have been slowly changing in order to internalize or control the variability of wind generation. Chapter 4 examines several potential market strategies for mitigating the effects of wind variability and estimate the effect that each strategy would have on the operation and profitability of wind farms. We find that market scenarios using existing price signals to motivate wind to reduce variability allow wind generators to participate in variability reduction when the market conditions are favorable, and can reduce short-term (30-minute) fluctuations while having little effect on wind farm revenue.

Direct comparison of oligochaete erythrocruorins as potential blood substitutes

PubMed Central

Zimmerman, Devon; DiIusto, Matthew; Dienes, Jack; Abdulmalik, Osheiza

2017-01-01

Abstract While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s). Several metrics were used to compare the Ecs, including their oxidation rates, dissociation at physiological pH, thermal stability, and oxygen transport characteristics. Overall, the Ecs of Lumbricus terrestris (LtEc) and Eisenia fetida (EfEc) were identified as promising candidates, since they demonstrated high thermal and oligomeric stability, while also exhibiting relatively low oxidation rates. Interestingly, the O2 affinity of LtEc (P 50 = 26.25 mmHg at 37 °C) was also observed to be uniquely lower than EfEc and all of the other Ecs (P 50 = 9.29–13.62 mmHg). Subsequent alignment of the primary sequences of LtEc and EfEc revealed several significant amino acid substitutions within the D subunit interfaces that may be responsible for this significant change in O2 affinity. Nonetheless, these results show that LtEc and EfEc are promising potential blood substitutes that are resistant to oxidation and denaturation, but additional experiments will need to be conducted to determine their safety, efficacy, and the effects of their disparate oxygen affinities in vivo. PMID:29313031

A plasmid borne, functionally novel glycoside hydrolase family 30 subfamily 8 endoxylanase from solventogenic Clostridium

PubMed Central

Dietrich, Diane; Crooks, Casey; Balogun, Peter; deSerrano, Vesna; Pozharski, Edwin; Smith, James Kennon; Bales, Elizabeth; Hurlbert, Jason

2018-01-01

Glycoside hydrolase family 30 subfamily 8 (GH30-8) β-1,4-endoxylanases are known for their appendage-dependent function requiring recognition of an α-1,2-linked glucuronic acid (GlcA) common to glucuronoxylans for hydrolysis. Structural studies have indicated that the GlcA moiety of glucuronoxylans is coordinated through six hydrogen bonds and a salt bridge. These GlcA-dependent endoxylanases do not have significant activity on xylans that do not bear GlcA substitutions such as unsubstituted linear xylooligosaccharides or cereal bran arabinoxylans. In the present study, we present the structural and biochemical characteristics of xylanase 30A from Clostridium acetobutylicum (CaXyn30A) which was originally selected for study due to predicted structural differences within the GlcA coordination loops. Amino acid sequence comparisons indicated that this Gram-positive-derived GH30-8 more closely resembles Gram-negative derived forms of these endoxylanases: a hypothesis borne out in the developed crystallographic structure model of the CaXyn30A catalytic domain (CaXyn30A-CD). CaXyn30A-CD hydrolyzes xylans to linear and substituted oligoxylosides showing the greatest rate with the highly arabinofuranose (Araf)-substituted cereal arabinoxylans. CaXyn30A-CD hydrolyzes xylooligosaccharides larger than xylotriose and shows an increased relative rate of hydrolysis for xylooligosaccharides containing α-1,2-linked arabinofuranose substitutions. Biochemical analysis confirms that CaXyn30A benefits from five xylose-binding subsites which extend from the −3 subsite to the +2 subsite of the binding cleft. These studies indicate that CaXyn30A is a GlcA-independent endoxylanase that may have evolved for the preferential recognition of α-1,2-Araf substitutions on xylan chains. PMID:29626157

Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach

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

Navarro, Amparo, E-mail: anavarro@ujaen.es; Fernández-Liencres, M. Paz; Peña-Ruiz, Tomás

2016-08-07

Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ∼0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier comparedmore » to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ∼0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials.« less

Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach.

PubMed

Navarro, Amparo; Fernández-Liencres, M Paz; Peña-Ruiz, Tomás; García, Gregorio; Granadino-Roldán, José M; Fernández-Gómez, Manuel

2016-08-07

Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ∼0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier compared to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ∼0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials.

Theoretical Study of near Neutrality. II. Effect of Subdivided Population Structure with Local Extinction and Recolonization

PubMed Central

Ohta, T.

1992-01-01

There are several unsolved problems concerning the model of nearly neutral mutations. One is the interaction of subdivided population structure and weak selection that spatially fluctuates. The model of nearly neutral mutations whose selection coefficient spatially fluctuates has been studied by adopting the island model with periodic extinction-recolonization. Both the number of colonies and the migration rate play significant roles in determining mutants' behavior, and selection is ineffective when the extinction-recolonization is frequent with low migration rate. In summary, the number of mutant substitutions decreases and the polymorphism increases by increasing the total population size, and/or decreasing the extinction-recolonization rate. However, by increasing the total size of the population, the mutant substitution rate does not become as low when compared with that in panmictic populations, because of the extinction-recolonization, especially when the migration rate is limited. It is also found that the model satisfactorily explains the contrasting patterns of molecular polymorphisms observed in sibling species of Drosophila, including heterozygosity, proportion of polymorphism and fixation index. PMID:1582566

Phenolic content variability and its chromosome location in tritordeum

PubMed Central

Navas-Lopez, José F.; Ostos-Garrido, Francisco J.; Castillo, Almudena; Martín, Antonio; Gimenez, Maria J.; Pistón, Fernando

2014-01-01

For humans, wheat is the most important source of calories, but it is also a source of antioxidant compounds that are involved in the prevention of chronic disease. Among the antioxidant compounds, phenolic acids have great potential to improve human health. In this paper we evaluate the effect of environmental and genetic factors on the phenolics content in the grain of a collection of tritordeums with different cytoplasm and chromosome substitutions. To this purpose, tritordeum flour was used for extraction of the free, conjugates and bound phenolic compounds. These phenolic compounds were identified and quantified by RP-HPLC and the results were analyzed by univariate and multivariate methods. This is the first study that describes the composition of phenolic acids of the amphiploid tritordeum. As in wheat, the predominant phenolic compound is ferulic acid. In tritordeum there is great variability for the content of phenolic compounds and the main factor which determines its content is the genotype followed by the environment, in this case included in the year factor. Phenolic acid content is associated with the substitution of chromosome DS1D(1Hch) and DS2D(2Hch), and the translocation 1RS/1BL in tritordeum. The results show that there is high potential for further improving the quality and quantity of phenolics in tritordeum because this amphiploid shows high variability for the content of phenolic compounds. PMID:24523725

Electronic and Photoelectron Spectroscopy of Toluene

NASA Astrophysics Data System (ADS)

Gardner, Adrian M.; Green, Alistair M.; Tame-Reyes, Victor; Wright, Timothy G.

2012-06-01

Electronic and photoelectron spectra of toluene are presented and discussed. The utilization of a recently reported scheme for assigning the normal vibrations of substituted benzenes allows these spectra to be compared to those of other molecules with unprecedented clarity. Changes in vibrational activity within a series of substituted benzene molecules will be discussed, specifically the increased rate of intramolecular vibrational energy redistribution observed in molecules where the substituent is a methyl group. A. M. Gardner and T. G. Wright, J. Chem. Phys., 135, 114305 (2011)

A comparative study of rhodopsin function in the great bowerbird (P tilonorhynchus nuchalis): Spectral tuning and light‐activated kinetics

PubMed Central

van Hazel, Ilke; Dungan, Sarah Z.; Hauser, Frances E.; Morrow, James M.; Endler, John A.

2016-01-01

Abstract Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well‐characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein‐coupled receptors. While this substitution is present in some dim‐light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site‐directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue‐shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light‐activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure‐function as well as their evolutionary significance for dim‐light vision across vertebrates. PMID:26889650

A comparative study of rhodopsin function in the great bowerbird (Ptilonorhynchus nuchalis): Spectral tuning and light-activated kinetics.

PubMed

van Hazel, Ilke; Dungan, Sarah Z; Hauser, Frances E; Morrow, James M; Endler, John A; Chang, Belinda S W

2016-07-01

Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well-characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein-coupled receptors. While this substitution is present in some dim-light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site-directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue-shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light-activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure-function as well as their evolutionary significance for dim-light vision across vertebrates. © 2016 The Protein Society.

The substitution reaction of (CNC)Fe-2N₂ with CO.

PubMed

Liu, Hongyan; Liu, Shuangshuang; Zhang, Xiang

2013-06-01

The substitution mechanism of two N₂ ligands in (CNC)Fe-2N₂ replaced by CO was studied theoretically at the B3LYP/LACVP* level. Both SN1 and SN₂ mechanisms were considered. The calculated results for the gas phase suggested that: 1) in SN1 mechanism, N₂ elimination, which involves S₀-T₁ PESs crossing, is the rate control step for both substitution stages. The barrier heights are 9.7 kcal mol(-1) and 13.05 kcal mol(-1), respectively. 2) In SN2 mechanism, the calculated barrier heights on LS PES are respectively 13.7 and 19.83 kcal mol(-1) for the two substitution steps, but S₀-T₁ PESs crossing lowers the two barriers to 10.7 and 15.7 kcal mol(-1), respectively. 3) Inclusion of solvation effect of THF by PCM model, the relative energies of all the key species (including minima, transition states and S₀-T₁ crossing points) do not have great difference from their gas phase relative energies. Considering that for each substitution step, SN1 barrier heights is slightly smaller than SN2 barrier, SN1 mechanism seems to be slightly preferable to SN2 mechanism.

Substitutional Doping for Aluminosilicate Mineral and Superior Water Splitting Performance.

PubMed

Zhang, Yi; Fu, Liangjie; Shu, Zhan; Yang, Huaming; Tang, Aidong; Jiang, Tao

2017-12-01

Substitutional doping is a strategy in which atomic impurities are optionally added to a host material to promote its properties, while the geometric and electronic structure evolution of natural nanoclay mineral upon substitutional metal doping is still ambiguous. This paper first designed an efficient lanthanum (La) doping strategy for nanotubular clay (halloysite nanotube, HNT) through the dynamic equilibrium of a substitutional atom in the presence of saturated AlCl 3 solution, and systematic characterization of the samples was performed. Further density functional theory (DFT) calculations were carried out to reveal the geometric and electronic structure evolution upon metal doping, as well as to verify the atom-level effect of the La doping. The CdS loading and its corresponding water splitting performance could demonstrate the effect of La doping. CdS nanoparticles (11 wt.%) were uniformly deposited on the surface of La-doped halloysite nanotube (La-HNT) with the average size of 5 nm, and the notable photocatalytic hydrogen evolution rate of CdS/La-HNT reached up to 47.5 μmol/h. The results could provide a new strategy for metal ion doping and constructive insight into the substitutional doping mechanism.

Substitutional Doping for Aluminosilicate Mineral and Superior Water Splitting Performance

NASA Astrophysics Data System (ADS)

Zhang, Yi; Fu, Liangjie; Shu, Zhan; Yang, Huaming; Tang, Aidong; Jiang, Tao

2017-07-01

Substitutional doping is a strategy in which atomic impurities are optionally added to a host material to promote its properties, while the geometric and electronic structure evolution of natural nanoclay mineral upon substitutional metal doping is still ambiguous. This paper first designed an efficient lanthanum (La) doping strategy for nanotubular clay (halloysite nanotube, HNT) through the dynamic equilibrium of a substitutional atom in the presence of saturated AlCl3 solution, and systematic characterization of the samples was performed. Further density functional theory (DFT) calculations were carried out to reveal the geometric and electronic structure evolution upon metal doping, as well as to verify the atom-level effect of the La doping. The CdS loading and its corresponding water splitting performance could demonstrate the effect of La doping. CdS nanoparticles (11 wt.%) were uniformly deposited on the surface of La-doped halloysite nanotube (La-HNT) with the average size of 5 nm, and the notable photocatalytic hydrogen evolution rate of CdS/La-HNT reached up to 47.5 μmol/h. The results could provide a new strategy for metal ion doping and constructive insight into the substitutional doping mechanism.

FoxP2 in song-learning birds and vocal-learning mammals.

PubMed

Webb, D M; Zhang, J

2005-01-01

FoxP2 is the first identified gene that is specifically involved in speech and language development in humans. Population genetic studies of FoxP2 revealed a selective sweep in recent human history associated with two amino acid substitutions in exon 7. Avian song learning and human language acquisition share many behavioral and neurological similarities. To determine whether FoxP2 plays a similar role in song-learning birds, we sequenced exon 7 of FoxP2 in multiple song-learning and nonlearning birds. We show extreme conservation of FoxP2 sequences in birds, including unusually low rates of synonymous substitutions. However, no amino acid substitutions are shared between the song-learning birds and humans. Furthermore, sequences from vocal-learning whales, dolphins, and bats do not share the human-unique substitutions. While FoxP2 appears to be under strong functional constraints in mammals and birds, we find no evidence for its role during the evolution of vocal learning in nonhuman animals as in humans.

Paracrystalline Disorder from Phosphate Ion Orientation and Substitution in Synthetic Bone Mineral.

PubMed

Marisa, Mary E; Zhou, Shiliang; Melot, Brent C; Peaslee, Graham F; Neilson, James R

2016-12-05

Hydroxyapatite is an inorganic mineral closely resembling the mineral phase in bone. However, as a biological mineral, it is highly disordered, and its composition and atomistic structure remain poorly understood. Here, synchrotron X-ray total scattering and pair distribution function analysis methods provide insight into the nature of atomistic disorder in a synthetic bone mineral analogue, chemically substituted hydroxyapatite. By varying the effective hydrolysis rate and/or carbonate concentration during growth of the mineral, compounds with varied degrees of paracrystallinity are prepared. From advanced simulations constrained by the experimental pair distribution function and density functional theory, the paracrystalline disorder prevalent in these materials appears to result from accommodation of carbonate in the lattice through random displacement of the phosphate groups. Though many substitution modalities are likely to occur in concert, the most predominant substitution places carbonate into the mirror plane of an ideal phosphate site. Understanding the mineralogical imperfections of a biologically analogous hydroxyapatite is important not only to potential bone grafting applications but also to biological mineralization processes themselves.

Toluene nitration in irradiated nitric acid and nitrite solutions

NASA Astrophysics Data System (ADS)

Elias, Gracy; Mincher, Bruce J.; Mezyk, Stephen P.; Muller, Jim; Martin, Leigh R.

2011-04-01

The kinetics, mechanisms, and stable products produced for the nitration of aryl alkyl mild ortho-para director toluene in irradiated nitric acid and neutral nitrite solutions were investigated using γ and pulse radiolysis. Electron pulse radiolysis was used to determine the bimolecular rate constants for the reaction of toluene with different transient species produced by irradiation. HPLC with UV detection, GC-MS and LC-MS, were used to assess the stable reaction products. Free-radical based nitration reaction products were found in irradiated acidic and neutral media. In 6.0 M HNO3, ring substitution, side chain substitution, and oxidation, produced different nitrated toluene products. For ring substitution, nitrogen oxide radicals were added mainly to cyclohexadienyl radicals, whereas for side chain substitution, these radicals were added to the carbon-centered benzyl radical produced by H-atom abstraction. In neutral nitrite solutions, radiolytically-induced ring nitration products approached a statistically random distribution, suggesting a direct free-radical reaction involving addition of the rad NO2 radical.

Federal fire managers' perceptions of the importance, scarcity and substitutability of suppression resources

Treesearch

Crystal S. Stonesifer; David E. Calkin; Michael S. Hand

2017-01-01

Wildland firefighting in the United States is a complex and costly enterprise. While there are strong seasonal signatures for fire occurrence in specific regions of the United States, spatiotemporal occurrence of wildfire activity can have high inter-annual variability. Suppression resources come from a variety of jurisdictions and provide a wide range of skills,...

Synthesis and Characterization of a New Class of Thermosetting Resins: Allyl and Propargyl Substituted Cyclopentadiene Derivatives

DTIC Science & Technology

1994-07-15

from Fisher or Aldrich. AS-4 unsized carbon fibers were donated by Hercules Chemical Company and vinyl silane treated glass fibers were donated by Owens ... Corning Fiberglass Company. Composites were made using a mold that gave samples 60 mm long and 12.7 mm wide with variable thickness. Cure analysis

The Acquisition of Verbal Inflection in Child Grammars in a Variability Model of Early Morphosyntactic Development: A Biolinguistic Perspective

ERIC Educational Resources Information Center

Rus, Dominik

2010-01-01

This dissertation investigates the acquisition of early verb inflection in child Slovenian from morphosyntactic and morphophonological perspectives. It centers on the phenomenon of root nonfinites, particularly the patterns of omission and substitution errors in verb inflection marking. It argues that every acquisition model needs to account…

Enantioselective Rhodium Enolate Protonations. A New Methodology for the Synthesis of β2-Amino Acids

PubMed Central

Sibi, Mukund P.; Tatamidani, Hiroto; Patil, Kalyani

2008-01-01

Rhodium catalyzed conjugate addition of an aryl boronic acid to α-methylamino acrylates followed by enantioselective protonation of the oxa-π-allylrhodium intermediate provides access to aryl substituted β2-amino acids. The impact of the different variables of the reaction on the levels of enantioselectivity has been assessed. PMID:15957893

Estimating Demand and Cross-Price Elasticity for Very Low Nicotine Content (VLNC) Cigarettes Using a Simulated Demand Task.

PubMed

Tucker, Megan R; Laugesen, Murray; Grace, Randolph C

2017-03-03

Very Low Nicotine Content (VLNC) cigarettes might be useful as part of a tobacco control strategy, but relatively little is known about their acceptability as substitutes for regular cigarettes. We compared subjective effects and demand for regular cigarettes and Very Low Nicotine Content (VLNC) cigarettes, and estimated cross-price elasticity for VLNC cigarettes, using simulated demand tasks. 40 New Zealand smokers sampled a VLNC cigarette and completed Cigarette Purchase Tasks to indicate their demand for regular cigarettes and VLNC cigarettes at a range of prices, and a cross-price task indicating how many regular cigarettes and VLNC cigarettes they would purchase at 0.5x, 1x, and 2x the current market price for regular cigarettes, assuming the price of VLNC cigarettes remained constant. They also rated the subjective effects of the VLNC cigarette and their usual-brand regular cigarettes. Cross-price elasticity for VLNC cigarettes was estimated as 0.24 and was significantly positive, indicating that VLNC cigarettes are partially substitutable for regular cigarettes. VLNC cigarettes were rated as less satisfying and psychologically rewarding than regular cigarettes, but this was unrelated to demand or substitutability. VLNC cigarettes are potentially substitutable for regular cigarettes. Their availability may reduce tobacco consumption, nicotine intake and addiction; making it easier for smokers to quit. VLNC cigarettes share the behavioural and sensory components of smoking whilst delivering negligible levels of nicotine. Although smokers rated VLNCs as less satisfying than regular cigarettes, smokers said they would increase their consumption of VLNCs as the price of regular cigarettes increased, if VLNCs were available at a lower price. This suggests that VLNCs are partially substitutable for regular cigarettes. VLNCs can be part of an effective tobacco control strategy, by reducing nicotine dependence and improving health and financial outcomes for smokers. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dynamics and spatio-temporal variability of environmental factors in Eastern Australia using functional principal component analysis

USGS Publications Warehouse

Szabo, J.K.; Fedriani, E.M.; Segovia-Gonzalez, M. M.; Astheimer, L.B.; Hooper, M.J.

2010-01-01

This paper introduces a new technique in ecology to analyze spatial and temporal variability in environmental variables. By using simple statistics, we explore the relations between abiotic and biotic variables that influence animal distributions. However, spatial and temporal variability in rainfall, a key variable in ecological studies, can cause difficulties to any basic model including time evolution. The study was of a landscape scale (three million square kilometers in eastern Australia), mainly over the period of 19982004. We simultaneously considered qualitative spatial (soil and habitat types) and quantitative temporal (rainfall) variables in a Geographical Information System environment. In addition to some techniques commonly used in ecology, we applied a new method, Functional Principal Component Analysis, which proved to be very suitable for this case, as it explained more than 97% of the total variance of the rainfall data, providing us with substitute variables that are easier to manage and are even able to explain rainfall patterns. The main variable came from a habitat classification that showed strong correlations with rainfall values and soil types. ?? 2010 World Scientific Publishing Company.

Attitude dynamics and control of spacecraft with a partially filled liquid tank and flexible panels

NASA Astrophysics Data System (ADS)

Liu, Feng; Yue, Baozeng; Zhao, Liangyu

2018-02-01

A liquid-filled flexible spacecraft is essentially a time-variant fully-coupled system, whose dynamics characteristics are closely associated with its motion features. This paper focuses on the mathematical modelling and attitude control of the spacecraft coupled with fuel sloshing dynamics and flexible solar panels vibration. The slosh motion is represented by a spherical pendulum, whose motion description method is improved by using split variable operation. Benefiting from this improvement, the nonlinear lateral sloshing and the rotary sloshing as well as the rigid motion of a liquid respect to the spacecraft can be approximately described. The assumed modes discretization method has been adopted to approximate the elastic displacements of the attached panels, and the coupled dynamics is derived by using the Lagrangian formulation. A variable substitution method is proposed to obtain the apparently-uncoupled mathematical model of the rigid-flexible-liquid spacecraft. After linearization, this model can be directly used for designing Lyapunov output-feedback attitude controller (OFAC). With only torque actuators, and attitude and rate sensors installed, this kind of attitude controller, as simulation results show, is capable of not only bringing the spacecraft to the desired orientation, but also suppressing the effect of flex and slosh on the attitude motion of the spacecraft.

Kinetic Analysis for the Multistep Profiles of Organic Reactions: Significance of the Conformational Entropy on the Rate Constants of the Claisen Rearrangement.

PubMed

Sumiya, Yosuke; Nagahata, Yutaka; Komatsuzaki, Tamiki; Taketsugu, Tetsuya; Maeda, Satoshi

2015-12-03

The significance of kinetic analysis as a tool for understanding the reactivity and selectivity of organic reactions has recently been recognized. However, conventional simulation approaches that solve rate equations numerically are not amenable to multistep reaction profiles consisting of fast and slow elementary steps. Herein, we present an efficient and robust approach for evaluating the overall rate constants of multistep reactions via the recursive contraction of the rate equations to give the overall rate constants for the products and byproducts. This new method was applied to the Claisen rearrangement of allyl vinyl ether, as well as a substituted allyl vinyl ether. Notably, the profiles of these reactions contained 23 and 84 local minima, and 66 and 278 transition states, respectively. The overall rate constant for the Claisen rearrangement of allyl vinyl ether was consistent with the experimental value. The selectivity of the Claisen rearrangement reaction has also been assessed using a substituted allyl vinyl ether. The results of this study showed that the conformational entropy in these flexible chain molecules had a substantial impact on the overall rate constants. This new method could therefore be used to estimate the overall rate constants of various other organic reactions involving flexible molecules.

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.

Spectroscopic and DFT Study of RhIII Chloro Complex Transformation in Alkaline Solutions.

PubMed

Vasilchenko, Danila B; Berdyugin, Semen N; Korenev, Sergey V; O'Kennedy, Sean; Gerber, Wilhelmus J

2017-09-05

The hydrolysis of [RhCl 6 ] 3- in NaOH-water solutions was studied by spectrophotometric methods. The reaction proceeds via successive substitution of chloride with hydroxide to quantitatively form [Rh(OH) 6 ] 3- . Ligand substitution kinetics was studied in an aqueous 0.434-1.085 M NaOH matrix in the temperature range 5.5-15.3 °C. Transformation of [RhCl 6 ] 3- into [RhCl 5 (OH)] 3- was found to be the rate-determining step with activation parameters of ΔH † = 105 ± 4 kJ mol -1 and ΔS † = 59 ± 10 J K -1 mol -1 . The coordinated hydroxo ligand(s) induces rapid ligand substitution to form [Rh(OH) 6 ] 3- . By simulating ligand substitution as a dissociative mechanism, using density functional theory (DFT), we can now explain the relatively fast and slow kinetics of chloride substitution in basic and acidic matrices, respectively. Moreover, the DFT calculated activation energies corroborated experimental data that the kinetic stereochemical sequence of [RhCl 6 ] 3- hydrolysis in an acidic solution proceeds as [RhCl 6 ] 3- → [RhCl 5 (H 2 O)] 2- → cis-[RhCl 4 (H 2 O) 2 ] - . However, DFT calculations predict in a basic solution the trans route of substitution [RhCl 6 ] 3- → [RhCl 5 (OH)] 3- → trans-[RhCl 4 (OH) 2 ] 3- is kinetically favored.

Investigation of Cr substitution in Co ferrite (CoCrxFe2-xO4) using Mossbauer spectroscopy

NASA Astrophysics Data System (ADS)

Krieble, K.; Lo, C. C. H.; Melikhov, Y.; Snyder, J. E.

2006-04-01

Substitution of other metals for Fe in cobalt ferrite has been proposed as a method to tailor the magnetic and magnetoelastic properties for sensor and actuator applications [H. Zheng et al., Science 303, 661 (2004)]. However, to understand the effect of Cr substitution, one needs atomic-level information on the local environments and interactions of the transition-metal ions. In this study, Mossbauer spectroscopy was used to investigate the local environments of the Fe atoms in these materials. A series of five powder samples with compositions CoCrxFe2-xO4 (x=0.0 to 0.8) was investigated using transmission geometry. Results show two distinct six-line hyperfine patterns, indicating Fe in A and B spinel sites. Increasing Cr concentration is seen to decrease the hyperfine field strength for both A and B sites, as well as increasing the width of those distributions. Results for Cr substitution show generally similar behavior to a prior study using Mn; however, Cr substitution has more pronounced effects: the hyperfine fields decrease and distribution widths increase at greater rates for Cr substitution, and the differences between A and B site behavior are more pronounced. Results are consistent with a model in which Cr has an even stronger B-site preference than Mn, and displaces more of the Co from the B to the A sites.

Influence of SrO substitution for CaO on the properties of bioactive glass S53P4.

PubMed

Massera, Jonathan; Hupa, Leena

2014-03-01

Commercial melt-quenched bioactive glasses consist of the oxides of silicon, phosphorus, calcium and sodium. Doping of the glasses with oxides of some other elements is known to affect their capability to support hydroxyapatite formation and thus bone tissue healing but also to modify their high temperature processing parameters. In the present study, the influence of gradual substitution of SrO for CaO on the properties of the bioactive glass S53P4 was studied. Thermal analysis and hot stage microscopy were utilized to measure the thermal properties of the glasses. The in vitro bioactivity and solubility was measured by immersing the glasses in simulated body fluid for 6 h to 1 week. The formation of silica rich and hydroxyapatite layers was assessed from FTIR spectra analysis and SEM images of the glass surface. Increasing substitution of SrO for CaO decreased all characteristic temperatures and led to a slightly stronger glass network. The initial glass dissolution rate increased with SrO content. Hydroxyapatite layer was formed on all glasses but on the SrO containing glasses the layer was thinner and contained also strontium. The results suggest that substituting SrO for CaO in S53P4 glass retards the bioactivity. However, substitution greater than 10 mol% allow for precipitation of a strontium substituted hydroxyapatite layer.

The substitutability of cigarettes and food: A behavioral economic comparison in normal weight and overweight or obese smokers.

PubMed

Murphy, Cara M; Owens, Max M; Sweet, Lawrence H; MacKillop, James

2016-12-01

Obesity and cigarette smoking contribute to a multitude of preventable deaths in the United States and eating and smoking behavior may influence each other. The field of behavioral economics integrates principles from psychology and economics and permits systematic examination of how commodities interrelate with one another. Using this framework, the current study evaluated the effects of rising food and cigarette prices on consumption to investigate their substitutability and their relationship to BMI and associated variables. Behavioral economics categorizes commodities as substitutable when the consumption of one increases as a function of a price increase in the other. Smokers (N = 86) completed a 2-part hypothetical task in which money was allocated to purchase cigarettes and fast-food-style reinforcers (e.g., hamburgers, ice cream) at various prices. Results indicated that food and cigarettes were not substitutes for one another (cross-price elasticity coefficients < .20). Food purchases were independent of cigarette price, whereas cigarette purchases decreased as food price rose. Cross-price elasticity coefficients were significantly associated with confidence in one's ability to control weight without smoking (rs = -.23 and .29), but not BMI (rs = .04 and .04) or postcessation weight concerns (rs = -.05 and .12). Perceived ability to manage weight without cigarettes may influence who substitutes food for cigarettes when quitting. In addition, given observed decreases in purchases of both commodities as food prices increased, these findings imply that greater taxation of fast-food-style reinforcers could potentially reduce consumption of these foods and also cigarettes among smokers. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Substitutability of Cigarettes and Food: A Behavioral Economic Comparison in Normal Weight and Overweight or Obese Smokers

PubMed Central

Murphy, Cara M.; Owens, Max M.; Sweet, Lawrence H.; MacKillop, James

2017-01-01

Obesity and cigarette smoking contribute to a multitude of preventable deaths in the US and eating and smoking behavior may influence each other. The field of behavioral economics integrates principles from psychology and economics and permits systematic examination of how commodities interrelate with one another. Using this framework, the current study evaluated the effects of rising food and cigarette prices on consumption to investigate their substitutability and their relationship to BMI and associated variables. Behavioral economics categorizes commodities as substitutable when the consumption of one increases as a function of a price increase in the other. Smokers (N = 86) completed a two-part hypothetical task in which money was allocated to purchase cigarettes and fast food-style reinforcers (e.g., hamburgers, ice cream) at various prices. Results indicated that food and cigarettes were not substitutes for one another (cross-price elasticity coefficients > .20). Food purchases were independent of cigarette price, whereas cigarette purchases decreased as food price rose. Cross-price elasticity coefficients were significantly associated with confidence in one’s ability to control weight without smoking (rs = −.23 and .29), but not BMI (rs = .04 and .04) or post-cessation weight concerns (rs = −.05 and .12). Perceived ability to manage weight without cigarettes may influence who substitutes food for cigarettes when quitting. In addition, given observed decreases in purchases of both commodities as food prices increased, these findings imply that greater taxation of fast food-style reinforcers could potentially reduce consumption of these foods and also cigarettes among smokers. PMID:27736143

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.

Effects of compositional defects on small polaron hopping in micas.

PubMed

Rosso, Kevin M; Ilton, Eugene S

2005-06-22

Hartree-Fock calculations and electron transfer (ET) theory were used to model the effects of compositional defects on ET in the brucite-like octahedral sheet of mica. ET was modeled as an Fe(IIIII) valence interchange reaction across shared octahedral edges of the M2-M2 iron sublattice. The model entails the hopping of localized electrons and small polaron behavior. Hartree-Fock calculations indicate that substitution of F for structural OH bridges increases the reorganization energy lambda, decreases the electronic coupling matrix element V(AB), and thereby substantially decreases the hopping rate. The lambda increase arises from modification of the metal-ligand bond force constants, and the V(AB) decrease arises from reduction of superexchange interaction through anion bridges. Deprotonation of an OH bridge, consistent with a possible mechanism of maintaining charge neutrality during net oxidation, yields a net increase in the ET rate. Although substitution of Al or Mg for Fe in M1 sites distorts the structure of adjacent Fe-occupied M2 sites, the distortion has little net impact on ET rates through these M2 sites. Hence the main effect of Al or Mg substitution for Fe, should it occur in the M2 sublattice, is to block ET pathways. Collectively, these findings pave the way for larger-scale oxidation/reduction models to be constructed for realistic, compositionally diverse micas.

Reconstruction of the ancestral plastid genome in Geraniaceae reveals a correlation between genome rearrangements, repeats, and nucleotide substitution rates.

PubMed

Weng, Mao-Lun; Blazier, John C; Govindu, Madhumita; Jansen, Robert K

2014-03-01

Geraniaceae plastid genomes are highly rearranged, and each of the four genera already sequenced in the family has a distinct genome organization. This study reports plastid genome sequences of six additional species, Francoa sonchifolia, Melianthus villosus, and Viviania marifolia from Geraniales, and Pelargonium alternans, California macrophylla, and Hypseocharis bilobata from Geraniaceae. These genome sequences, combined with previously published species, provide sufficient taxon sampling to reconstruct the ancestral plastid genome organization of Geraniaceae and the rearrangements unique to each genus. The ancestral plastid genome of Geraniaceae has a 4 kb inversion and a reduced, Pelargonium-like small single copy region. Our ancestral genome reconstruction suggests that a few minor rearrangements occurred in the stem branch of Geraniaceae followed by independent rearrangements in each genus. The genomic comparison demonstrates that a series of inverted repeat boundary shifts and inversions played a major role in shaping genome organization in the family. The distribution of repeats is strongly associated with breakpoints in the rearranged genomes, and the proportion and the number of large repeats (>20 bp and >60 bp) are significantly correlated with the degree of genome rearrangements. Increases in the degree of plastid genome rearrangements are correlated with the acceleration in nonsynonymous substitution rates (dN) but not with synonymous substitution rates (dS). Possible mechanisms that might contribute to this correlation, including DNA repair system and selection, are discussed.

Time-lagged effects of weather on plant demography: drought and Astragalus scaphoides.

PubMed

Tenhumberg, Brigitte; Crone, Elizabeth E; Ramula, Satu; Tyre, Andrew J

2018-04-01

Temperature and precipitation determine the conditions where plant species can occur. Despite their significance, to date, surprisingly few demographic field studies have considered the effects of abiotic drivers. This is problematic because anticipating the effect of global climate change on plant population viability requires understanding how weather variables affect population dynamics. One possible reason for omitting the effect of weather variables in demographic studies is the difficulty in detecting tight associations between vital rates and environmental drivers. In this paper, we applied Functional Linear Models (FLMs) to long-term demographic data of the perennial wildflower, Astragalus scaphoides, and explored sensitivity of the results to reduced amounts of data. We compared models of the effect of average temperature, total precipitation, or an integrated measure of drought intensity (standardized precipitation evapotranspiration index, SPEI), on plant vital rates. We found that transitions to flowering and recruitment in year t were highest if winter/spring of year t was wet (positive effect of SPEI). Counterintuitively, if the preceding spring of year t - 1 was wet, flowering probabilities were decreased (negative effect of SPEI). Survival of vegetative plants from t - 1 to t was also negatively affected by wet weather in the spring of year t - 1 and, for large plants, even wet weather in the spring of t - 2 had a negative effect. We assessed the integrated effect of all vital rates on life history performance by fitting FLMs to the asymptotic growth rate, log(λt). Log(λt) was highest if dry conditions in year t - 1 were followed by wet conditions in the year t. Overall, the positive effects of wet years exceeded their negative effects, suggesting that increasing frequency of drought conditions would reduce population viability of A. scaphoides. The drought signal weakened when reducing the number of monitoring years. Substituting space for time did not recover the weather signal, probably because the weather variables varied little between sites. We detected the SPEI signal when the analysis included data from two sites monitored over 20 yr (2 × 20 observations), but not when analyzing data from four sites monitored over 10 yr (4 × 10 observations). © 2018 by the Ecological Society of America.

Synthesis of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}-N-substituted acetamides as potential antimicrobial and hemolytic agents.

PubMed

Rehman, Aziz-ur; Abbasi, Muhammad Athar; Siddiqui, Sabahat Zahra; Ahmad, Irshad; Shahid, Muhammad; Subhani, Zinayyera

2016-05-01

A new series of N-substituted derivatives of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}acetamides was synthesized. The synthesis was carried out by converting benzoic acid (1) into ethyl benzoate (2), benzohydrazide (3) and then 5-pheny-1,3,4-Oxadiazol-2-thiol (4) step by st0ep. The target compounds 6a-p were synthesized by reaction of compound 4 with equimolar ratios of different N-alkyl/aryl substituted 2-bromoacetamide (5a-p) in the presence of DMF and sodium hydride (NaH). The spectral (EI-MS, IR, (1)H-NMR) characterization of all the synthesized compounds reveal their successful synthesis. The compounds were also screened for antimicrobial & hemolytic activity and most of them were found to be active against the selected microbial species at variable extent relative to reference standards. But 6h was the most active against the selected panel of microbes. This series showed less toxicity and may be considered for further biological screening and application trial except 6m, possessing higher cytotoxicity.

Stacking interactions between nitrogen-containing six-membered heterocyclic aromatic rings and substituted benzene: studies in solution and in the solid state.

PubMed

Gung, Benjamin W; Wekesa, Francis; Barnes, Charles L

2008-03-07

The stacking interactions between an aromatic ring and a pyridine or a pyrimidine ring are studied by using a series of triptycene-derived scaffolds. The indicative ratios of the syn and anti conformers were determined by variable-temperature NMR spectroscopy. The syn conformer aligns the attached aromatic ring and the heterocycle in a parallel-displaced orientation while the anti conformer sets the two rings apart from each other. Comparing to the corresponding control compounds where a benzene ring is in the position of the heterocycle, higher attractive interactions are observed as indicated by the higher syn/anti ratios. In general, the attractive interactions are much less sensitive to the substituent effects than the corresponding nonheterocycles. The greatest attractive interactions were observed between a pyrimidine ring and a N,N-dimethylaminobenzene, consistent with a predominant donor-acceptor interaction. The interactions between a pyridine ring and a substituted benzene ring show that the pyridine is comparable to that of a NO2- or a CN-substituted benzene ring except for the unpredictable substituent effects.

Factor demand in Swedish manufacturing industry with special reference to the demand for energy. Instantaneous adjustment models; some results

NASA Astrophysics Data System (ADS)

Sjoeholm, K. R.

1981-02-01

The dual approach to the theory of production is used to estimate factor demand functions of the Swedish manufacturing industry. Two approximations of the cost function, the translog and the generalized Leontief models, are used. The price elasticities of the factor demand do not seem to depend on the choice of model. This is at least true as to the sign pattern and as to the inputs capital, labor, total energy and other materials. Total energy is separated into solid fuels, gasoline, fuel oil, electricity and a residual. Fuel oil and electricity are found to be substitutes by both models. Capital and energy are shown to be substitutes. This implies that Swedish industry will save more energy if the capital cost can be reduced. Both models are, in the best versions, able to detect an inappropriate variable. The assumption of perfect competition on the product market, is shown to be inadequate by both models. When this assumption is relaxed, the normal substitution pattern among the inputs is resumed.

Peculiar properties of photoinduced hydroxylaminolysis in different bacteriorhodopsin-based media using O-substituted hydroxylamines.

PubMed

Dyukova, Tatyana V; Druzhko, Anna B

2010-01-01

The process of photoinduced hydroxylaminolysis has been re-examined in different bacteriorhodopsin (BR)-based media using O-substituted hydroxylamines, in particular, O-(4-nitrobenzyl) hydroxylamine hydrochloride (NBHA), O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride (FBHA) and O-(t-butyl) hydroxylamine hydrochloride (BHA). Both wild type (WT) and D96N BR-based gelatine films and gels were studied. The expected increase in the bleaching rate of BR in gelatin films by using O-substituted hydroxylamines in place of HA was not achieved. On the other hand, it was shown that in gels HA derivatives NBHA and FBHA (as against HA itself) do provide about three- to four-fold higher bleaching rate. By contrast to that in films, D96N BR in gels demonstrates more effective bleaching as compared to WT BR. The plausible interpretation for the results is discussed in frames of reduced mobilities of large-sized molecules of O-substituted hydroxylamines in dehydrated media. FBHA- or NBHA-modified gels possess higher photosensitivity both with D96N and WT BR (as compared with that for HA-modified gels) and offer a potentiality for application as an irreversible-recording medium. As anticipated, it is specifically D96N BR gel modified with FBHA that may present a promising medium suitable for write-once recording thus extending the range of recording materials in the optical processing field. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Inversion of substrate stereoselectivity of horse liver alcohol dehydrogenase by substitutions of Ser-48 and Phe-93.

PubMed

Kim, Keehyuk; Plapp, Bryce V

2017-10-01

The substrate specificities of alcohol dehydrogenases (ADH) are of continuing interest for understanding the physiological functions of these enzymes. Ser-48 and Phe-93 have been identified as important residues in the substrate binding sites of ADHs, but more comprehensive structural and kinetic studies are required. The S48T substitution in horse ADH1E has small effects on kinetic constants and catalytic efficiency (V/K m ) with ethanol, but decreases activity with benzyl alcohol and affinity for 2,2,2-trifluoroethanol (TFE) and 2,3,4,5,6-pentafluorobenzyl alcohol (PFB). Nevertheless, atomic resolution crystal structures of the S48T enzyme complexed with NAD + and TFE or PFB are very similar to the structures for the wild-type enzyme. (The S48A substitution greatly diminishes catalytic activity.) The F93A substitution significantly decreases catalytic efficiency (V/K m ) for ethanol and acetaldehyde while increasing activity for larger secondary alcohols and the enantioselectivity for the R-isomer relative to the S-isomer of 2-alcohols. The doubly substituted S48T/F93A enzyme has kinetic constants for primary and secondary alcohols similar to those for the F93A enzyme, but the effect of the S48T substitution is to decrease V/K m for (S)-2-alcohols without changing V/K m for (R)-2-alcohols. Thus, the S48T/F93A substitutions invert the enantioselectivity for alcohol oxidation, increasing the R/S ratio by 10, 590, and 200-fold for 2-butanol, 2-octanol, and sec-phenethyl alcohol, respectively. Transient kinetic studies and simulations of the ordered bi bi mechanism for the oxidation of the 2-butanols by the S48T/F93A ADH show that the rate of hydride transfer is increased about 7-fold for both isomers (relative to wild-type enzyme) and that the inversion of enantioselectivity is due to more productive binding for (R)-2-butanol than for (S)-2-butanol in the ternary complex. Molecular modeling suggests that both of the sec-phenethyl alcohols could bind to the enzyme and that dynamics must affect the rates of catalysis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Growth Modeling of Aspergillus niger Strains Isolated from Citrus Fruit as a Function of Temperature on a Synthetic Medium from Lime (Citrus latifolia T.) Pericarp.

PubMed

Sandoval-Contreras, T; Marín, S; Villarruel-López, A; Gschaedler, A; Garrido-Sánchez, L; Ascencio, F

2017-07-01

Molds are responsible for postharvest spoilage of citrus fruits. The objective of this study was to evaluate the effect of temperature on growth rate and the time to visible growth of Aspergillus niger strains isolated from citrus fruits. The growth of these strains was studied on agar lime medium (AL) at different temperatures, and growth rate was estimated using the Baranyi and Roberts model (Int. J. Food Microbiol. 23:277-294, 1994). The Rosso et al. cardinal model with inflexion (L. Rosso, J. R. Lobry, S. Bajard, and J. P. Flandrois, J. Theor. Biol. 162:447-463, 1993) was used as a secondary model to describe the effect of temperature on growth rate and the lag phase. We hypothesized that the same model could be used to calculate the time for the mycelium to become visible (t v ) by substituting the lag phase (1/λ and 1/λ opt ) with the time to visible colony (1/t v -opt and 1/t v ), respectively, in the Rosso et al. High variability was observed at suboptimal conditions. Extremes of temperature of growth for A. niger seem to have a normal variability. For the growth rate and time t v , the model was satisfactorily compared with results of previous studies. An external validation was performed in lime fruits; the bias and accuracy factors were 1.3 and 1.5, respectively, for growth rate and 0.24 and 3.72, respectively, for the appearance time. The discrepancy may be due to the influence of external factors. A. niger grows significantly more slowly on lime fruit than in culture medium, probably because the nutrients are more easily available in medium than in fruits, where the peel consistency may be a physical barrier. These findings will help researchers understand the postharvest behavior of mold on lime fruits, host-pathogen interactions, and environmental conditions infecting fruit and also help them develop guidelines for future work in the field of predictive mycology to improve models for control of postharvest fungi.

Solar Radiation during Rewarming from Torpor in Elephant Shrews: Supplementation or Substitution of Endogenous Heat Production?

PubMed Central

Thompson, Michelle L.; Mzilikazi, Nomakwezi; Bennett, Nigel C.; McKechnie, Andrew E.

2015-01-01

Many small mammals bask in the sun during rewarming from heterothermy, but the implications of this behaviour for their energy balance remain little understood. Specifically, it remains unclear whether solar radiation supplements endogenous metabolic thermogenesis (i.e., rewarming occurs through the additive effects of internally-produced and external heat), or whether solar radiation reduces the energy required to rewarm by substituting (i.e, replacing) metabolic heat production. To address this question, we examined patterns of torpor and rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in outdoor cages with access to either natural levels of solar radiation or levels that were experimentally reduced by means of shade cloth. We also tested whether acclimation to solar radiation availability was manifested via phenotypic flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST) capacity and/or summit metabolism (Msum). Rewarming rates varied significantly among treatments, with elephant shrews experiencing natural solar radiation levels rewarming faster than conspecifics experiencing solar radiation levels equivalent to approximately 20% or 40% of natural levels. BMR differed significantly between individuals experiencing natural levels of solar radiation and conspecifics experiencing approximately 20% of natural levels, but no between-treatment difference was evident for NST capacity or Msum. The positive relationship between solar radiation availability and rewarming rate, together with the absence of acclimation in maximum non-shivering and total heat production capacities, suggests that under the conditions of this study solar radiation supplemented rather than substituted metabolic thermogenesis as a source of heat during rewarming from heterothermy. PMID:25853244

Solar radiation during rewarming from torpor in elephant shrews: supplementation or substitution of endogenous heat production?

PubMed

Thompson, Michelle L; Mzilikazi, Nomakwezi; Bennett, Nigel C; McKechnie, Andrew E

2015-01-01

Many small mammals bask in the sun during rewarming from heterothermy, but the implications of this behaviour for their energy balance remain little understood. Specifically, it remains unclear whether solar radiation supplements endogenous metabolic thermogenesis (i.e., rewarming occurs through the additive effects of internally-produced and external heat), or whether solar radiation reduces the energy required to rewarm by substituting (i.e, replacing) metabolic heat production. To address this question, we examined patterns of torpor and rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in outdoor cages with access to either natural levels of solar radiation or levels that were experimentally reduced by means of shade cloth. We also tested whether acclimation to solar radiation availability was manifested via phenotypic flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST) capacity and/or summit metabolism (Msum). Rewarming rates varied significantly among treatments, with elephant shrews experiencing natural solar radiation levels rewarming faster than conspecifics experiencing solar radiation levels equivalent to approximately 20% or 40% of natural levels. BMR differed significantly between individuals experiencing natural levels of solar radiation and conspecifics experiencing approximately 20% of natural levels, but no between-treatment difference was evident for NST capacity or Msum. The positive relationship between solar radiation availability and rewarming rate, together with the absence of acclimation in maximum non-shivering and total heat production capacities, suggests that under the conditions of this study solar radiation supplemented rather than substituted metabolic thermogenesis as a source of heat during rewarming from heterothermy.

Greenhouse gas impacts of natural gas: Influence of deployment choice, methane leak rate, and methane GWP

NASA Astrophysics Data System (ADS)

Cohan, D. S.

2015-12-01

Growing supplies of natural gas have heightened interest in the net impacts of natural gas on climate. Although its production and consumption result in greenhouse gas emissions, natural gas most often substitutes for other fossil fuels whose emission rates may be higher. Because natural gas can be used throughout the sectors of the energy economy, its net impacts on greenhouse gas emissions will depend not only on the leak rates of production and distribution, but also on the use for which natural gas is substituted. Here, we present our estimates of the net greenhouse gas emissions impacts of substituting natural gas for other fossil fuels for five purposes: light-duty vehicles, transit buses, residential heating, electricity generation, and export for electricity generation overseas. Emissions are evaluated on a fuel cycle basis, from production and transport of each fuel through end use combustion, based on recent conditions in the United States. We show that displacement of existing coal-fired electricity and heating oil furnaces yield the largest reductions in emissions. The impact of compressed natural gas replacing petroleum-based vehicles is highly uncertain, with the sign of impact depending on multiple assumptions. Export of liquefied natural gas for electricity yields a moderate amount of emissions reductions. We further show how uncertainties in upstream emission rates for natural gas and in the global warming potential of methane influence the net greenhouse gas impacts. Our presentation will make the case that how natural gas is deployed is crucial to determining how it will impact climate.

Optimization of GM(1,1) power model

NASA Astrophysics Data System (ADS)

Luo, Dang; Sun, Yu-ling; Song, Bo

2013-10-01

GM (1,1) power model is the expansion of traditional GM (1,1) model and Grey Verhulst model. Compared with the traditional models, GM (1,1) power model has the following advantage: The power exponent in the model which best matches the actual data values can be found by certain technology. So, GM (1,1) power model can reflect nonlinear features of the data, simulate and forecast with high accuracy. It's very important to determine the best power exponent during the modeling process. In this paper, according to the GM(1,1) power model of albino equation is Bernoulli equation, through variable substitution, turning it into the GM(1,1) model of the linear albino equation form, and then through the grey differential equation properly built, established GM(1,1) power model, and parameters with pattern search method solution. Finally, we illustrate the effectiveness of the new methods with the example of simulating and forecasting the promotion rates from senior secondary schools to higher education in China.

Predicting rates of inbreeding in populations undergoing selection.

PubMed Central

Woolliams, J A; Bijma, P

2000-01-01

Tractable forms of predicting rates of inbreeding (DeltaF) in selected populations with general indices, nonrandom mating, and overlapping generations were developed, with the principal results assuming a period of equilibrium in the selection process. An existing theorem concerning the relationship between squared long-term genetic contributions and rates of inbreeding was extended to nonrandom mating and to overlapping generations. DeltaF was shown to be approximately (1)/(4)(1 - omega) times the expected sum of squared lifetime contributions, where omega is the deviation from Hardy-Weinberg proportions. This relationship cannot be used for prediction since it is based upon observed quantities. Therefore, the relationship was further developed to express DeltaF in terms of expected long-term contributions that are conditional on a set of selective advantages that relate the selection processes in two consecutive generations and are predictable quantities. With random mating, if selected family sizes are assumed to be independent Poisson variables then the expected long-term contribution could be substituted for the observed, providing (1)/(4) (since omega = 0) was increased to (1)/(2). Established theory was used to provide a correction term to account for deviations from the Poisson assumptions. The equations were successfully applied, using simple linear models, to the problem of predicting DeltaF with sib indices in discrete generations since previously published solutions had proved complex. PMID:10747074

Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes

PubMed Central

Proulx, Maryse; Aubin, Kim; Lagueux, Jean; Audet, Pierre; Auger, Michèle

2015-01-01

Adipose tissue (AT) substitutes are being developed to answer the strong demand in reconstructive surgery. To facilitate the validation of their functional performance in vivo, and to avoid resorting to excessive number of animals, it is crucial at this stage to develop biomedical imaging methodologies, enabling the follow-up of reconstructed AT substitutes. Until now, biomedical imaging of AT substitutes has scarcely been reported in the literature. Therefore, the optimal parameters enabling good resolution, appropriate contrast, and graft delineation, as well as blood perfusion validation, must be studied and reported. In this study, human adipose substitutes produced from adipose-derived stem/stromal cells using the self-assembly approach of tissue engineering were implanted into athymic mice. The fate of the reconstructed AT substitutes implanted in vivo was successfully followed by magnetic resonance imaging (MRI), which is the imaging modality of choice for visualizing soft ATs. T1-weighted images allowed clear delineation of the grafts, followed by volume integration. The magnetic resonance (MR) signal of reconstructed AT was studied in vitro by proton nuclear magnetic resonance (1H-NMR). This confirmed the presence of a strong triglyceride peak of short longitudinal proton relaxation time (T1) values (200±53 ms) in reconstructed AT substitutes (total T1=813±76 ms), which establishes a clear signal difference between adjacent muscle, connective tissue, and native fat (total T1 ∼300 ms). Graft volume retention was followed up to 6 weeks after implantation, revealing a gradual resorption rate averaging at 44% of initial substitute's volume. In addition, vascular perfusion measured by dynamic contrast-enhanced-MRI confirmed the graft's vascularization postimplantation (14 and 21 days after grafting). Histological analysis of the grafted tissues revealed the persistence of numerous adipocytes without evidence of cysts or tissue necrosis. This study describes the in vivo grafting of human adipose substitutes devoid of exogenous matrix components, and for the first time, the optimal parameters necessary to achieve efficient MRI visualization of grafted tissue-engineered adipose substitutes. PMID:25549069

Self-Calibrating, Variable-Flow Pumping System

NASA Technical Reports Server (NTRS)

Walls, Joe T.

1994-01-01

Pumping system provides accurate, controlled flows of two chemical liquids mixed in spray head and react to form rigid or flexible polyurethane or polyisocyanurate foam. Compatible with currently used polyurethane-based coating materials and gas-bubble-forming agents (called "blowing agents" in industry) and expected to be compatible with materials that used in near future. Handles environmentally acceptable substitutes for chlorofluorocarbon foaming agents.

Research on potential user identification model for electric energy substitution

NASA Astrophysics Data System (ADS)

Xia, Huaijian; Chen, Meiling; Lin, Haiying; Yang, Shuo; Miao, Bo; Zhu, Xinzhi

2018-01-01

The implementation of energy substitution plays an important role in promoting the development of energy conservation and emission reduction in china. Energy service management platform of alternative energy users based on the data in the enterprise production value, product output, coal and other energy consumption as a potential evaluation index, using principal component analysis model to simplify the formation of characteristic index, comprehensive index contains the original variables, and using fuzzy clustering model for the same industry user’s flexible classification. The comprehensive index number and user clustering classification based on constructed particle optimization neural network classification model based on the user, user can replace electric potential prediction. The results of an example show that the model can effectively predict the potential of users’ energy potential.

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

Recommendations for Adopting the International Code of Marketing of Breast-milk Substitutes Into U.S. Policy.

PubMed

Soldavini, Jessica; Taillie, Lindsey Smith

2017-08-01

In 1981, the World Health Organization adopted the International Code of Marketing of Breast-milk Substitutes ( International Code), with subsequent resolutions adopted since then. The International Code contributes to the safe and adequate provision of nutrition for infants by protecting and promoting breastfeeding and ensuring that human milk substitutes, when necessary, are used properly through adequate information and appropriate marketing and distribution. Despite the World Health Organization recommendations for all member nations to implement the International Code in its entirety, the United States has yet to take action to translate it into any national measures. In 2012, only 22.3% of infants in the United States met the American Academy of Pediatrics recommendation of at least 6 months of exclusive breastfeeding. Countries adopting legislation reflecting the provisions of the International Code have seen increases in breastfeeding rates. This article discusses recommendations for translating the International Code into U.S. policy. Adopting legislation that implements, monitors, and enforces the International Code in its entirety has the potential to contribute to increased rates of breastfeeding in the United States, which can lead to improved health outcomes in both infants and breastfeeding mothers.

Comparison of in Situ and in Vitro Regulation of Soybean Seed Growth and Development

PubMed Central

Dyer, Daniel J.; Cotterman, C. Daniel; Cotterman, Josephine C.

1987-01-01

The growth characteristics of soybean (Glycine max [L.] Merr.) embryos in culture and seeds in situ were found to be similar, but developmental differences were observed. Embryos placed in culture when very small (<2 milligrams dry weight) failed to attain the maximal growth rates attained by embryos which were more mature when placed in culture. When nutrient levels were maintained in the culture medium, embryos continued to grow indefinitely, reaching dry weights far in excess of seeds matured in situ. Apparently, maternal factors were important in early and late development during the determination of maximum growth rate and the cessation of growth. Embryo growth rate was not affected by substituting glucose plus fructose for sucrose in the medium, nor by hormone treatments, including abscisic acid. Glutamine was found to give substantially better growth than glutamate, however. Contrary to prior reports, the response of soybean embryo growth rate to irradiance was found to be primarily an artifact of the effect of irradiance on media temperature. Across seven genotypes the correlation coefficient between seed growth rate in situ and embryo growth rate in vitro was 0.94, indicating essentially all of the variability of in situ seed growth rate between cultivars could be attributed to inherent growth rate differences associated with the embryos. The response to temperature was very similar for both embryos in culture and seeds in situ at temperatures below 30°C. Beyond that temperature, embryo growth rate continued to increase, while seed growth rate did not. The implication is that in situ seed growth rate is determined by the inherent growth potential of the embryo at low to moderate temperatures; however, at higher temperatures, the maternal plant is unable to support the rapid growth rates that the embryo is capable of attaining under conditions of unlimited assimilate supply. PMID:16665434

26 CFR 1.401(a)(4)-8 - Cross-testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... under § 1.401(a)(4)-1(b)(2). Paragraphs (b)(1) and (c)(1) of this section provide general tests for... design basis. (b) Nondiscrimination in amount of benefits provided under a defined contribution plan—(1... this section, were substituted for each employee's allocation rate in the determination of rate groups...

40 CFR 75.33 - Standard missing data procedures for SO2, NOX, Hg, and flow rate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Standard missing data procedures for... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.33 Standard missing data procedures for SO2, NOX, Hg, and flow rate. (a) Following initial...

40 CFR 75.33 - Standard missing data procedures for SO2, NOX, and flow rate.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Standard missing data procedures for... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.33 Standard missing data procedures for SO2, NOX, and flow rate. (a) Following initial certification...

40 CFR 75.33 - Standard missing data procedures for SO2, NOX, and flow rate.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Standard missing data procedures for... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.33 Standard missing data procedures for SO2, NOX, and flow rate. (a) Following initial certification...

40 CFR 75.33 - Standard missing data procedures for SO2, NOX, and flow rate.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Standard missing data procedures for... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.33 Standard missing data procedures for SO2, NOX, and flow rate. (a) Following initial certification...

40 CFR 75.33 - Standard missing data procedures for SO2, NOX, and flow rate.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Standard missing data procedures for... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Missing Data Substitution Procedures § 75.33 Standard missing data procedures for SO2, NOX, and flow rate. (a) Following initial certification...

An Examination of the Changing Rates of Autism in Special Education

ERIC Educational Resources Information Center

Brock, Stephen E.

2006-01-01

Using U.S. Department of Education data, the current study examined changes in the rates of special education eligibility classifications. This was done to determine if classification substitution might be an explanation for increases in the number of students being found eligible for special education using the Autism criteria. Results reveal…

Mechanical characterization of alloys in extreme conditions of high strain rates and high temperature

NASA Astrophysics Data System (ADS)

Cadoni, Ezio

2018-03-01

The aim of this paper is the description of the mechanical characterization of alloys under extreme conditions of temperature and loading. In fact, in the frame of the Cost Action CA15102 “Solutions for Critical Raw Materials Under Extreme Conditions (CRM-EXTREME)” this aspect is crucial and many industrial applications have to consider the dynamic response of materials. Indeed, for a reduction and substitution of CRMs in alloys is necessary to design the materials and understand if the new materials behave better or if the substitution or reduction badly affect their performance. For this reason, a deep knowledge of the mechanical behaviour at high strain-rates of considered materials is required. In general, machinery manufacturing industry or transport industry as well as energy industry have important dynamic phenomena that are simultaneously affected by extended strain, high strain-rate, damage and pressure, as well as conspicuous temperature gradients. The experimental results in extreme conditions of high strain rate and high temperature of an austenitic stainless steel as well as a high-chromium tempered martensitic reduced activation steel Eurofer97 are presented.

Structural features of soluble cereal arabinoxylan fibers associated with a slow rate of in vitro fermentation by human fecal microbiota.

PubMed

Rumpagaporn, Pinthip; Reuhs, Brad L; Kaur, Amandeep; Patterson, John A; Keshavarzian, Ali; Hamaker, Bruce R

2015-10-05

Most soluble dietary fibers ferment rapidly in the proximal colon, potentially causing discomfort and poor tolerability. Alkali-extracted arabinoxylan isolates from corn, wheat, rice and sorghum brans were prepared, through hydrolysis (except sorghum) and ethanol fractionation, to have a broad range of initial fermentation rates, and their linkage patterns were determined to understand structural aspects related to slow fermentation rate. They were all highly branched polymers with degree of substitution greater than 64%. There was no relationship of molecular mass, arabinose:xylose ratio, or degree of substitution to fermentation rate patterns. Slow fermenting wheat and corn arabinoxylans had much higher amount of terminal xylose in branches than fast fermenting rice and sorghum arabinoxylans. The slowest fermenting wheat arabinoxylan additionally contained a complex trisaccharide side chain with two arabinoses linked at the O-2 and O-3 positions of an arabinose that is O-2 linked to the xylan backbone. Structural features were proposed for tolerable slowly fermentable arabinoxylan with possible beneficial fermentation function into the distal colon. Copyright © 2015 Elsevier Ltd. All rights reserved.

When time is more than money: the allocation of time between work and leisure in HIV-infected patients.

PubMed

Sendi, Pedram; Brouwer, Werner B F; Bucher, Heiner C; Weber, Rainer; Battegay, Manuel

2007-06-01

Time is a limited resource and individuals have to decide how many hours they should allocate to work and to leisure activities. Differences in wage rate or availability of non-labour income (financial support from families and savings) may influence how individuals allocate their time between work and leisure. An increase in wage rate may induce income effects (leisure time demanded increases) and substitution effects (leisure time demanded decreases) whereas an increase in non-labour income only induces income effects. We explored the effects of differences in wage rate and non-labour income on the allocation of time in HIV-infected patients. Patients enrolled in the Swiss HIV Cohort Study (SHCS) provided information on their time allocation, i.e. number of hours worked in 1998. A multinomial logistic regression model was used to test for income and substitution effects. Our results indicate that (i) the allocation of time in HIV-infected patients does not differ with level of education (i.e., wage rate), and that (ii) availability of non-labour income induces income effects, i.e. individuals demand more leisure time.

Risk management with substitution options: Valuing flexibility in small-scale energy systems

NASA Astrophysics Data System (ADS)

Knapp, Karl Eric

Several features of small-scale energy systems make them more easily adapted to a changing operating environment than large centralized designs. This flexibility is often manifested as the ability to substitute inputs. This research explores the value of this substitution flexibility and the marginal value of becoming a "little more flexible" in the context of real project investment in developing countries. The elasticity of substitution is proposed as a stylized measure of flexibility and a choice variable. A flexible alternative (elasticity > 0) can be thought of as holding a fixed-proportions "nflexible" asset plus a sequence of exchange options---the option to move to another feasible "recipe" each period. Substitutability derives value from following a contour of anticipated variations and from responding to new information. Substitutability value, a "cost savings option", increases with elasticity and price risk. However, the required premium to incrementally increase flexibility can in some cases decrease with an increase in risk. Variance is not always a measure of risk. Tools from stochastic dominance are newly applied to real options with convex payoffs to correct some misperceptions and clarify many common modeling situations that meet the criteria for increased variance to imply increased risk. The behavior of the cost savings option is explored subject to a stochastic input price process. At the point where costs are identical for all alternatives, the stochastic process for cost savings becomes deterministic, with savings directly proportional to elasticity of substitution and price variance. The option is also formulated as a derivative security via dynamic programming. The partial differential equation is solved for the special case of Cobb-Douglas (elasticity = 1) (also shown are linear (infinite elasticity), Leontief (elasticity = 0)). Risk aversion is insufficient to prefer a more flexible alternative with the same expected value. Intertemporal links convert the sequence of independent options to a single compound option and require an expansion of the flexibility concept. Additional options increase the value of the project but generally decrease flexibility value. The framework is applied to case study in India: an urban industry electricity strategy decision with reliability risk.

Effects of DNA Methylation and Chromatin State on Rates of Molecular Evolution in Insects.

PubMed

Glastad, Karl M; Goodisman, Michael A D; Yi, Soojin V; Hunt, Brendan G

2015-12-04

Epigenetic information is widely appreciated for its role in gene regulation in eukaryotic organisms. However, epigenetic information can also influence genome evolution. Here, we investigate the effects of epigenetic information on gene sequence evolution in two disparate insects: the fly Drosophila melanogaster, which lacks substantial DNA methylation, and the ant Camponotus floridanus, which possesses a functional DNA methylation system. We found that DNA methylation was positively correlated with the synonymous substitution rate in C. floridanus, suggesting a key effect of DNA methylation on patterns of gene evolution. However, our data suggest the link between DNA methylation and elevated rates of synonymous substitution was explained, in large part, by the targeting of DNA methylation to genes with signatures of transcriptionally active chromatin, rather than the mutational effect of DNA methylation itself. This phenomenon may be explained by an elevated mutation rate for genes residing in transcriptionally active chromatin, or by increased structural constraints on genes in inactive chromatin. This result highlights the importance of chromatin structure as the primary epigenetic driver of genome evolution in insects. Overall, our study demonstrates how different epigenetic systems contribute to variation in the rates of coding sequence evolution. Copyright © 2016 Glastad et al.

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

PubMed

Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

2018-02-01

Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Hydro and geothermal electricity as an alternative for industrial petroleum consumption in Costa Rica

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

Mendis, M.; Park, W.; Sabadell, A.

This report assesses the potential for substitution of electricity for petroleum in the industrial/agro-industrial sector of Costa Rica. The study includes a preliminary estimate of the process energy needs in this sector, a survey of the principal petroleum consuming industries in Costa Rica, an assessment of the electrical technologies appropriate for substitution, and an analysis of the cost trade offs of alternative fuels and technologies. The report summarizes the total substitution potential both by technical feasibility and by cost effectiveness under varying fuel price scenarios and identifies major institutional constraints to the introduction of electric based technologies. Recommendations to themore » Government of Costa Rica are presented. The key to the success of a Costa Rican program for substitution of electricity for petroleum in industry rests in energy pricing policy. The report shows that if Costa Rica Bunker C prices are increased to compare equitably with Caribbean Bunker C prices, and increase at 3 percent per annum relative to a special industrial electricity rate structure, the entire substitution program, including both industrial and national electric investment, would be cost effective. The definition of these pricing structures and their potential impacts need to be assessed in depth.« less

Can we cut out the meat of the dish? Constructing consumer-oriented pathways towards meat substitution.

PubMed

Schösler, Hanna; de Boer, Joop; Boersema, Jan J

2012-02-01

The shift towards a more sustainable diet necessitates less reliance on foods of animal origin. This study presents data from a representative survey of Dutch consumers on their practices related to meat, meat substitution and meat reduction. The practices reflected a cultural gradient of meat substitution options running from other products of animal origin and conventional meat free meals to real vegetarian meals. To investigate feasible substitution options, a variety of meals without meat were presented using photos, which were rated by the participants in terms of attractiveness and chances that they would prepare a similar meal at home. The results demonstrated the influence of meal formats, product familiarity, cooking skills, preferences for plant-based foods and motivational orientations towards food. In particular, a lack of familiarity and skill hampered the preparation of real vegetarian meals. Based on the findings we propose a diversified understanding of meat substitution and we specify four policy-relevant pathways for a transition towards a more plant-based diet, including an incremental change towards more health-conscious vegetarian meals, a pathway that utilizes the trend towards convenience, a pathway of reduced portion size, and practice-oriented change towards vegetarian meals. Copyright © 2011 Elsevier Ltd. All rights reserved.

The potential of avocado paste (Persea americana) as fat substitute in non-dairy ice cream

NASA Astrophysics Data System (ADS)

Ervina; Surjawan, I.; Abdillah, E.

2018-01-01

Consumer preferences towards plant-based food have shifted significantly due to sustainable and healthy reasons. Dairy products consist of high Saturated Fatty Acid (SFA) and overconsumption of SFA could lead to cardiovascular diseases. Avocado contains high levels of fat dominated by Monounsaturated Fatty Acid (MUFA) and phytosterol that have the potential as a plant-based fat source to substitute dairy-fat in ice cream. The objective of this study was to analyze the physicochemical, rheological and sensorial properties of ice cream substituted with different concentrations of avocado paste ranging from 0%, 25%, 50%, 75% and 100% respectively against dairy fat to produce non-dairy fat ice cream. The psychochemical properties and total fat were determined. Sensorial quality and hedonic attributes of ice cream were investigated using 60 semi-trained panelists. There were significant differences (p<0.05) for overrun, melting rate, and viscosity of the ice cream substituted with avocado paste. The addition of avocado paste lead to the increase in viscosity and hardness of the ice cream significantly (p<0.05) while the sensorial properties for airiness and creaminess were perceived the same (p>0.05). The addition of 50% avocado paste was the most preferred among the panelists. Avocado could provide a potential substitution for dairy-fat in ice cream.

The estimation of genetic divergence

NASA Technical Reports Server (NTRS)

Holmquist, R.; Conroy, T.

1981-01-01

Consideration is given to the criticism of Nei and Tateno (1978) of the REH (random evolutionary hits) theory of genetic divergence in nucleic acids and proteins, and to their proposed alternative estimator of total fixed mutations designated X2. It is argued that the assumption of nonuniform amino acid or nucleotide substitution will necessarily increase REH estimates relative to those made for a model where each locus has an equal likelihood of fixing mutations, thus the resulting value will not be an overestimation. The relative values of X2 and measures calculated on the basis of the PAM and REH theories for the number of nucleotide substitutions necessary to explain a given number of observed amino acid differences between two homologous proteins are compared, and the smaller values of X2 are attributed to (1) a mathematical model based on the incorrect assumption that an entire structural gene is free to fix mutations and (2) the assumptions of different numbers of variable codons for the X2 and REH calculations. Results of a repeat of the computer simulations of Nei and Tateno are presented which, in contrast to the original results, confirm the REH theory. It is pointed out that while a negative correlation is observed between estimations of the fixation intensity per varion and the number of varions for a given pair of sequences, the correlation between the two fixation intensities and varion numbers of two different pairs of sequences need not be negative. Finally, REH theory is used to resolve a paradox concerning the high rate of covarion turnover and the nature of general function sites as permanent covarions.

The Effects of Breakfast Consumption and Composition on Metabolic Wellness with a Focus on Carbohydrate Metabolism.

PubMed

Maki, Kevin C; Phillips-Eakley, Alyssa K; Smith, Kristen N

2016-05-01

Findings from epidemiologic studies indicate that there are associations between breakfast consumption and a lower risk of type 2 diabetes mellitus (T2DM) and metabolic syndrome, prompting interest in the influence of breakfast on carbohydrate metabolism and indicators of T2DM risk. The objective of this review was to summarize the available evidence from randomized controlled trials assessing the impact of breakfast on variables related to carbohydrate metabolism and metabolic wellness. Consuming compared with skipping breakfast appeared to improve glucose and insulin responses throughout the day. Breakfast composition may also be important. Dietary patterns high in rapidly available carbohydrate were associated with elevated T2DM risk. Therefore, partial replacement of rapidly available carbohydrate with other dietary components, such as whole grains and cereal fibers, proteins, and unsaturated fatty acids (UFAs), at breakfast may be a useful strategy for producing favorable metabolic outcomes. Consumption of fermentable and viscous dietary fibers at breakfast lowers glycemia and insulinemia. Fermentable fibers likely act through enhancing insulin sensitivity later in the day, and viscous fibers have an acute effect to slow the rate of carbohydrate absorption. Partially substituting protein for rapidly available carbohydrate enhances satiety and diet-induced thermogenesis, and also favorably affects lipoprotein lipids and blood pressure. Partially substituting UFA for carbohydrate has been associated with improved insulin sensitivity, lipoprotein lipids, and blood pressure. Overall, the available evidence suggests that consuming breakfast foods high in whole grains and cereal fiber, while limiting rapidly available carbohydrate, is a promising strategy for metabolic health promotion. © 2016 American Society for Nutrition.

Pharmacists' views and reported practices in relation to a new generic drug substitution policy in Lebanon: a mixed methods study.

PubMed

El-Jardali, Fadi; Fadlallah, Racha; Morsi, Rami Z; Hemadi, Nour; Al-Gibbawi, Mounir; Haj, Magda; Khalil, Suzan; Saklawi, Youssef; Jamal, Diana; Akl, Elie A

2017-02-17

Governments in both developed and developing countries have adopted generic drug substitution policies to decrease pharmaceutical expenditures and improve access to medicine. In August 2015, the Ministry of Public Health (MOPH) in Lebanon introduced generic drug substitution and a unified medical prescription form as policy instruments to promote generic drug use. The objective of this exploratory study was to examine the attitudes of community pharmacists and the reported practices in relation to the implementation of the new generic drug substitution policy. We used a cross-sectional mixed methods approach composed of self-administered questionnaires and semi-structured interviews. The study population consisted of community pharmacists in Lebanon. We randomly approached one pharmacy personnel from each selected community pharmacy. We conducted descriptive analyses to assess responses to questionnaire and regression analyses to understand associations between responses and respondent demographics. We analyzed qualitative data thematically. Out of 204 invited community pharmacies, 153 pharmacies participated (75% response rate). The majority of respondents (64%) were in favor of generic drug substitution; however, less than half (40%) indicated they have substituted brand drugs for generic equivalents. Moreover, 57% indicated that the existing pricing system discourages them from performing generic drug substitution. Most respondents indicated that physicians are overusing the "non-substitutable" option (84%) and that there are technical problems with processing the new prescription form (78%). Less than half (47%) reported that the MOPH is performing regular audits on the forms collected by the pharmacy. While 45% of the respondents indicated that consumers have accepted most of the generic substitutions, 21% perceived the increase in generic drug dispensing to be significant. Findings suggested a potentially significant association between being informed about generic drugs and respondents' support of the policy. Suggested strategies to address implementation challenges included strengthening stewardship function of MOPH, securing full commitment of health care providers, conducting educational and awareness campaigns about generic drugs and generic drug substitution, and aligning incentive systems of the key stakeholders. The majority of community pharmacists were supportive of generic drug substitution in general but not of the current implementation of the policy in Lebanon. Findings revealed implementation challenges at the provider, patient, and system level which are hindering attainment of the policy objectives. The key lessons derived from this study can be used for continuous improvement of the policy and its implementation.

Big and slow: phylogenetic estimates of molecular evolution in baleen whales (suborder mysticeti).

PubMed

Jackson, J A; Baker, C S; Vant, M; Steel, D J; Medrano-González, L; Palumbi, S R

2009-11-01

Baleen whales are the largest animals that have ever lived. To develop an improved estimation of substitution rate for nuclear and mitochondrial DNA for this taxon, we implemented a relaxed-clock phylogenetic approach using three fossil calibration dates: the divergence between odontocetes and mysticetes approximately 34 million years ago (Ma), between the balaenids and balaenopterids approximately 28 Ma, and the time to most recent common ancestor within the Balaenopteridae approximately 12 Ma. We examined seven mitochondrial genomes, a large number of mitochondrial control region sequences (219 haplotypes for 465 bp) and nine nuclear introns representing five species of whales, within which multiple species-specific alleles were sequenced to account for within-species diversity (1-15 for each locus). The total data set represents >1.65 Mbp of mitogenome and nuclear genomic sequence. The estimated substitution rate for the humpback whale control region (3.9%/million years, My) was higher than previous estimates for baleen whales but slow relative to other mammal species with similar generation times (e.g., human-chimp mean rate > 20%/My). The mitogenomic third codon position rate was also slow relative to other mammals (mean estimate 1%/My compared with a mammalian average of 9.8%/My for the cytochrome b gene). The mean nuclear genomic substitution rate (0.05%/My) was substantially slower than average synonymous estimates for other mammals (0.21-0.37%/My across a range of studies). The nuclear and mitogenome rate estimates for baleen whales were thus roughly consistent with an 8- to 10-fold slowing due to a combination of large body size and long generation times. Surprisingly, despite the large data set of nuclear intron sequences, there was only weak and conflicting support for alternate hypotheses about the phylogeny of balaenopterid whales, suggesting that interspecies introgressions or a rapid radiation has obscured species relationships in the nuclear genome.

Rising longitudinal trajectories in suicide rates: The role of firearm suicide rates and firearm legislation.

PubMed

Anestis, Michael D; Selby, Edward A; Butterworth, Sarah E

2017-07-01

Firearms account for approximately half of all US suicide deaths each year despite being utilized in only a small minority of suicide attempts. We examined the extent to which overall suicide rates fluctuated relative to firearm and non-firearm suicide rates across a period of 16years (1999-2015). We further tested the notion of means substitution by examining the association between firearm suicide rates and non-firearm suicide rates. Lastly, we examined the extent to which the presence of specific laws related to handgun ownership previously shown cross-sectionally to be associated with lower suicide rates (universal background checks, mandatory waiting periods) were associated with an attenuated trajectory in suicide rates across the study period. As anticipated, whereas decreases in firearm suicide rates were associated with decreases in overall suicide rates (b=0.46, SE=0.07, p<0.001), decreases in firearm suicides were not associated with off-setting increases in suicides by other methods (b=-0.04, SE=0.05, p=0.36). Furthermore, the absence of universal background check (b=0.12, SE=0.05, p=0.028) and mandatory waiting period (b=0.16, SE=0.06, p=0.008) laws was associated with a more steeply rising trajectory of statewide suicide rates. These results mitigate concerns regarding means substitution and speak to the potential high yield impact of systematically implemented means safety prevention efforts focused on firearms. Copyright © 2017 Elsevier Inc. All rights reserved.

Pervasive promotion of breastmilk substitutes in Phnom Penh, Cambodia, and high usage by mothers for infant and young child feeding

PubMed Central

Huffman, Sandra L.; Mengkheang, Khin; Kroeun, Hou; Champeny, Mary; Roberts, Margarette; Zehner, Elizabeth

2016-01-01

Abstract In 2005, Cambodia passed the Sub‐Decree on Marketing of Products for Infant and Young Child Feeding (no. 133) to regulate promotion of commercial infant and young child food products, including breastmilk substitutes. Helen Keller International assessed mothers' exposure to commercial promotions for breastmilk substitutes and use of these products through a cross‐sectional survey among 294 mothers of children less than 24 months of age. Eighty‐six per cent of mothers reported observing commercial promotions for breastmilk substitutes, 19.0% reported observing infant and young child food product brands/logos on health facility equipment and 18.4% reported receiving a recommendation from a health professional to use a breastmilk substitute. Consumption of breastmilk substitutes was high, occurring among 43.1% of children 0–5 months and 29.3% of children 6–23 months of age. Findings also indicated a need to improve breastfeeding practices among Phnom Penh mothers. Only 36.1% of infants 0–5 months of age were exclusively breastfed, and 12.5% of children 20–23 months of age were still breastfed. Children that received a breastmilk substitute as a prelacteal feed were 3.9 times more likely to be currently consuming a breastmilk substitute than those who did not. Despite restriction of commercial promotions for breastmilk substitutes without government approval, occurrence of promotions is high and use is common among Phnom Penh mothers. In a country with high rates of child malnutrition and pervasive promotions in spite of restrictive national law, full implementation of Cambodia's Sub‐Decree 133 is necessary, as are policies and interventions to support exclusive and continued breastfeeding. Key messages Despite prohibition without specific approval by the national government, companies are pervasively promoting breast‐milk substitutes in Phnom Penh, particularly on television and at points of sale.Strengthened implementation and enforcement of Cambodia's subdecree 133 are needed to better regulate promotion in order to protect breastfeeding for the nutrition and health of infants and young children in Cambodia.Mothers who used a breast‐milk substitute as a prelacteal feed were 3.9 times more likely to currently feed this same child a breast‐milk substitute, as compared with mothers who did not provide breast‐milk substitute as a prelacteal feed. Supporting breastfeeding among mothers after delivery is critical to establish and sustain optimal breastfeeding practices.Use of breast‐milk substitutes is also very common among mothers of children under 2 years of age in Phnom Penh. We recommend promoting exclusive and continued breastfeeding as beneficial to children's health and development, and supporting policy and workplace environments that enable breastfeeding up to and beyond 24 months of age. PMID:27061955

Pervasive promotion of breastmilk substitutes in Phnom Penh, Cambodia, and high usage by mothers for infant and young child feeding.

PubMed

Pries, Alissa M; Huffman, Sandra L; Mengkheang, Khin; Kroeun, Hou; Champeny, Mary; Roberts, Margarette; Zehner, Elizabeth

2016-04-01

In 2005, Cambodia passed the Sub-Decree on Marketing of Products for Infant and Young Child Feeding (no. 133) to regulate promotion of commercial infant and young child food products, including breastmilk substitutes. Helen Keller International assessed mothers' exposure to commercial promotions for breastmilk substitutes and use of these products through a cross-sectional survey among 294 mothers of children less than 24 months of age. Eighty-six per cent of mothers reported observing commercial promotions for breastmilk substitutes, 19.0% reported observing infant and young child food product brands/logos on health facility equipment and 18.4% reported receiving a recommendation from a health professional to use a breastmilk substitute. Consumption of breastmilk substitutes was high, occurring among 43.1% of children 0-5 months and 29.3% of children 6-23 months of age. Findings also indicated a need to improve breastfeeding practices among Phnom Penh mothers. Only 36.1% of infants 0-5 months of age were exclusively breastfed, and 12.5% of children 20-23 months of age were still breastfed. Children that received a breastmilk substitute as a prelacteal feed were 3.9 times more likely to be currently consuming a breastmilk substitute than those who did not. Despite restriction of commercial promotions for breastmilk substitutes without government approval, occurrence of promotions is high and use is common among Phnom Penh mothers. In a country with high rates of child malnutrition and pervasive promotions in spite of restrictive national law, full implementation of Cambodia's Sub-Decree 133 is necessary, as are policies and interventions to support exclusive and continued breastfeeding. Despite prohibition without specific approval by the national government, companies are pervasively promoting breast-milk substitutes in Phnom Penh, particularly on television and at points of sale. Strengthened implementation and enforcement of Cambodia's subdecree 133 are needed to better regulate promotion in order to protect breastfeeding for the nutrition and health of infants and young children in Cambodia. Mothers who used a breast-milk substitute as a prelacteal feed were 3.9 times more likely to currently feed this same child a breast-milk substitute, as compared with mothers who did not provide breast-milk substitute as a prelacteal feed. Supporting breastfeeding among mothers after delivery is critical to establish and sustain optimal breastfeeding practices. Use of breast-milk substitutes is also very common among mothers of children under 2 years of age in Phnom Penh. We recommend promoting exclusive and continued breastfeeding as beneficial to children's health and development, and supporting policy and workplace environments that enable breastfeeding up to and beyond 24 months of age. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons, Ltd.

Data mining identifies Digit Symbol Substitution Test score and serum cystatin C as dominant predictors of mortality in older men and women.

PubMed

Swindell, William R; Cummings, Steven R; Sanders, Jason L; Caserotti, Paolo; Rosano, Caterina; Satterfield, Suzanne; Strotmeyer, Elsa S; Harris, Tamara B; Simonsick, Eleanor M; Cawthon, Peggy M

2012-08-01

Characterization of long-term health trajectory in older individuals is important for proactive health management. However, the relative prognostic value of information contained in clinical profiles of nonfrail older adults is often unclear. We screened 825 phenotypic and genetic measures evaluated during the Health, Aging, and Body Composition Study (Health ABC) baseline visit (3,067 men and women aged 70-79). Variables that best predicted mortality over 13 years of follow-up were identified using 10-fold cross-validation. Mortality was most strongly associated with low Digit Symbol Substitution Test (DSST) score (DSST<25; 21.9% of cohort; hazard ratio [HR]=1.87±0.06) and elevated serum cystatin C (≥1.30 mg/mL; 12.1% of cohort; HR=2.25±0.07). These variables predicted mortality better than 823 other measures, including baseline age and a 45-variable health deficit index. Given elevated cystatin C (≥1.30 mg/mL), mortality risk was further increased by high serum creatinine, high abdominal visceral fat density, and smoking history (2.52≤HR ≤3.73). Given a low DSST score (<25) combined with low-to-moderate cystatin C (<1.30 mg/mL), mortality risk was highest among those with elevated plasma resistin and smoking history (1.90≤HR≤2.02). DSST score and serum cystatin C warrant priority consideration for the evaluation of mortality risk in older individuals. Both variables, taken individually, predict mortality better than chronological age or a health deficit index in well-functioning older adults (ages 70-79). DSST score and serum cystatin C can thus provide evidence-based tools for geriatric assessment.

The hospital nursing shortage. A paradox of increasing supply and increasing vacancy rates.

PubMed Central

Aiken, L H

1989-01-01

A serious shortage of nurses has developed since 1984 despite a growing number of employed nurses and a substantial decline in the number of hospital inpatient days. The evidence suggests that the shortage is the result of an increased demand for nurses, not a decline in supply. The increased demand in large part has resulted from the substitution of registered nurses for licensed practical nurses, aides, and other patient services personnel. The substitution was feasible because nurses' wages have been depressed compared with those of other hospital employees. The shortage is likely to abate if nurses' wages increase, making substitution more costly. Even in the absence of continuing wage increases, hospitals could ease the shortage by restructuring patient services and enabling nurses to spend a greater portion of their time in direct patient care. PMID:2669349

Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.

PubMed

Gronert, Scott; Garver, John M; Nichols, Charles M; Worker, Benjamin B; Bierbaum, Veronica M

2014-11-21

The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group). With nitrogen nucleophiles, the SN2 at bromine channel is suppressed. In the SNAr channels, the "element effect" is observed, and fluoride loss competes with bromide loss. The computational modeling indicates that all the substitution barriers are well below the entrance channel and that entropy and dynamics effects control the product distributions.

Kinetics of gibbsite dissolution under low ionic strength conditions

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

Ganor, J.; Mogollon, J.L.; Lasaga, A.C.

1999-06-01

Experiments measuring synthetic gibbsite dissolution rates were carried out using both a stirred-flow-through reactor and a column reactor at 25 C, and pH range of 2.5--4.1. All experiments were conducted under far from equilibrium conditions ({Delta}G < {minus}1.1 kcal/mole). The experiments were performed with perchloric acid under relatively low (and variable) ionic strength conditions. An excellent agreement was found between the results of the well-mixed flow-through experiments and those of the (nonmixed) column experiments. This agreement shows that the gibbsite dissolution rate is independent of the stirring rate and therefore supports the conclusion of Bloom and Erich (1987) that gibbsitemore » dissolution reaction is surface controlled and not diffusion controlled. The Brunauer-Emmett-Teller (BET) surface area of the gibbsite increased during the flow-through experiments, while in the column experiments no significant change in surface area was observed. The significant differences in the BET surface area between the column experiments and the flow-through experiments, and the excellent agreement between the rates obtained by both methods, enable the authors to justify the substitution of the BET surface area for the reactive surface area. The dissolution rate of gibbsite varied as a function of the perchloric acid concentration. The authors interpret the gibbsite dissolution rate as a result of a combined effect of proton catalysis and perchlorate inhibition. Following the theoretical study of Ganor and Lasaga (1998) they propose specific reaction mechanisms for the gibbsite dissolution in the presence of perchloric acid. The mathematical predictions of two of these reaction mechanisms adequately describe the experimental data.« less

Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans.

PubMed

Sattath, Shmuel; Elyashiv, Eyal; Kolodny, Oren; Rinott, Yosef; Sella, Guy

2011-02-10

In Drosophila, multiple lines of evidence converge in suggesting that beneficial substitutions to the genome may be common. All suffer from confounding factors, however, such that the interpretation of the evidence-in particular, conclusions about the rate and strength of beneficial substitutions-remains tentative. Here, we use genome-wide polymorphism data in D. simulans and sequenced genomes of its close relatives to construct a readily interpretable characterization of the effects of positive selection: the shape of average neutral diversity around amino acid substitutions. As expected under recurrent selective sweeps, we find a trough in diversity levels around amino acid but not around synonymous substitutions, a distinctive pattern that is not expected under alternative models. This characterization is richer than previous approaches, which relied on limited summaries of the data (e.g., the slope of a scatter plot), and relates to underlying selection parameters in a straightforward way, allowing us to make more reliable inferences about the prevalence and strength of adaptation. Specifically, we develop a coalescent-based model for the shape of the entire curve and use it to infer adaptive parameters by maximum likelihood. Our inference suggests that ∼13% of amino acid substitutions cause selective sweeps. Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3%) that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects. These estimates therefore help to reconcile the apparent conflict among previously published estimates of the strength of selection. More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis of adaptation.

Influence of ECG sampling rate in fetal heart rate variability analysis.

PubMed

De Jonckheere, J; Garabedian, C; Charlier, P; Champion, C; Servan-Schreiber, E; Storme, L; Debarge, V; Jeanne, M; Logier, R

2017-07-01

Fetal hypoxia results in a fetal blood acidosis (pH<;7.10). In such a situation, the fetus develops several adaptation mechanisms regulated by the autonomic nervous system. Many studies demonstrated significant changes in heart rate variability in hypoxic fetuses. So, fetal heart rate variability analysis could be of precious help for fetal hypoxia prediction. Commonly used fetal heart rate variability analysis methods have been shown to be sensitive to the ECG signal sampling rate. Indeed, a low sampling rate could induce variability in the heart beat detection which will alter the heart rate variability estimation. In this paper, we introduce an original fetal heart rate variability analysis method. We hypothesize that this method will be less sensitive to ECG sampling frequency changes than common heart rate variability analysis methods. We then compared the results of this new heart rate variability analysis method with two different sampling frequencies (250-1000 Hz).

Paracrystalline Disorder from Phosphate Ion Orientation and Substitution in Synthetic Bone Mineral

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

Marisa, Mary E.; Zhou, Shiliang; Melot, Brent C.

Hydroxyapatite is an inorganic mineral closely resembling the mineral phase in bone. However, as a biological mineral, it is highly disordered, and its composition and atomistic structure remain poorly understood. Here, synchrotron X-ray total scattering and pair distribution function analysis methods provide insight into the nature of atomistic disorder in a synthetic bone mineral analogue, chemically substituted hydroxyapatite. By varying the effective hydrolysis rate and/or carbonate concentration during growth of the mineral, compounds with varied degrees of paracrystallinity are prepared. From advanced simulations constrained by the experimental pair distribution function and density functional theory, the paracrystalline disorder prevalent in thesemore » materials appears to result from accommodation of carbonate in the lattice through random displacement of the phosphate groups. Though many substitution modalities are likely to occur in concert, the most predominant substitution places carbonate into the mirror plane of an ideal phosphate site. Understanding the mineralogical imperfections of a biologically analogous hydroxyapatite is important not only to potential bone grafting applications but also to biological mineralization processes themselves.« less

On the conservative nature of intragenic recombination

PubMed Central

Drummond, D. Allan; Silberg, Jonathan J.; Meyer, Michelle M.; Wilke, Claus O.; Arnold, Frances H.

2005-01-01

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function. Here, we compare recombination of the distantly related β-lactamases PSE-4 and TEM-1 to mutation of PSE-4. We show that, among β-lactamase variants containing the same number of amino acid substitutions, variants created by recombination retain function with a significantly higher probability than those generated by random mutagenesis. We present a simple model that accurately captures the differing effects of mutation and recombination in real and simulated proteins with only four parameters: (i) the amino acid sequence distance between parents, (ii) the number of substitutions, (iii) the average probability that random substitutions will preserve function, and (iv) the average probability that substitutions generated by recombination will preserve function. Our results expose a fundamental functional enrichment in regions of protein sequence space accessible by recombination and provide a framework for evaluating whether the relative rates of mutation and recombination observed in nature reflect the underlying imbalance in their effects on protein function. PMID:15809422

On the conservative nature of intragenic recombination.

PubMed

Drummond, D Allan; Silberg, Jonathan J; Meyer, Michelle M; Wilke, Claus O; Arnold, Frances H

2005-04-12

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function. Here, we compare recombination of the distantly related beta-lactamases PSE-4 and TEM-1 to mutation of PSE-4. We show that, among beta-lactamase variants containing the same number of amino acid substitutions, variants created by recombination retain function with a significantly higher probability than those generated by random mutagenesis. We present a simple model that accurately captures the differing effects of mutation and recombination in real and simulated proteins with only four parameters: (i) the amino acid sequence distance between parents, (ii) the number of substitutions, (iii) the average probability that random substitutions will preserve function, and (iv) the average probability that substitutions generated by recombination will preserve function. Our results expose a fundamental functional enrichment in regions of protein sequence space accessible by recombination and provide a framework for evaluating whether the relative rates of mutation and recombination observed in nature reflect the underlying imbalance in their effects on protein function.

Modeling and molecular dynamics simulations of the V33 variant of the integrin subunit β3: Structural comparison with the L33 (HPA-1a) and P33 (HPA-1b) variants.

PubMed

Jallu, Vincent; Poulain, Pierre; Fuchs, Patrick F J; Kaplan, Cecile; de Brevern, Alexandre G

2014-10-01

The human platelet alloantigen (HPA)-1 system, the first cause of alloimmune thrombocytopenia in Caucasians, results from leucine-to-proline substitution (alleles 1a and 1b) of residue 33 in β3 subunit of the integrin αIIbβ3. A third variant with a valine (V33) has been described. Although leucine and valine share similar physicochemical properties, sera containing alloantibodies to the HPA-1a antigen variably reacted with V33-β3, suggesting structural alterations of β3. To analyze the effect of the L33V transition, molecular dynamics simulations were performed on a 3D structural model of the V33 form of the whole β3 extracellular domain (690 residues). Dynamics of the PSI (carrying residue 33), I-EGF-1, and I-EGF-2 domains of β3 were compared to previously obtained dynamics of HPA-1a structure and HPA-1b structural model using classical and innovative developments (a structural alphabet). Clustering approach and local structure analysis showed that L33-β3 and V33-β3 mostly share common structures co-existing in different dynamic equilibria. The L33V substitution mainly displaces the equilibrium between common structures. These observations can explain the variable reactivity of anti-HPA-1a alloantibodies suggesting that molecular dynamic plays a key role in the binding of these alloantibodies. Unlike the L33P substitution, the L33V transition would not affect the structure flexibility of the β3 knee, and consequently the functions of αIIbβ3. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A Large-Radius High-Mass-Resolution Multiple-Collector Isotope Ratio Mass Spectrometer for Analysis of Rare Isotopologues of CH4 and Other Gases

NASA Astrophysics Data System (ADS)

Young, E. D.; Rumble, D.; Freedman, P.; Mills, M.

2016-12-01

We describe a unique and novel isotope ratio mass spectrometer (IRMS), the Panorama, developed explicitly for high-mass-resolution analysis of isotopologue ratios of gas samples. The double-focussing instrument routinely operates at a mass resolving power of 40,000 with a maximum useful MRP of 80,000. The instrument achieves this exceptional MRP for a multi-collector using a Matsuda ion optical design with an ESA radius of 1018 mm and a magnetic sector radius of 800 mm. Collectors comprise 9 Faraday cups and a single channel of ion counting each with continuously variable collector slits. The continously variable collector slits are key for making meausrements of rare doubly-substituted species free of corrections that would otherwise be necessitated by intefereing ion beams. First results demonstrate both accuracy and precision for singly and doubly-substituted molecular species. Our first applications have focussed on resolving the mass-18 rare isotopologues of methane, 12CH2D2 and 13CH3D. By measuring a wide variety of natural methane sources, we find that the ability to separate these two species allows one to substantiate temperatures of methane bond formation where temperatures from the two species are concordant, representing thermodynamic equilibrium. Conversely, where the species are in disequilibrium, the data provide evidence for the reaction pathways for methane formation or subsequent processing, including mixing with other reservoirs. Concordant temperatures are sometimes inconsistent with previous estimates from indirect methods. These sometimes surprising results are fortified by the concordancy of two doubly-substituted isotopologues. Similarly, there are instances in which the temperatures derived from the relative concentrations of 13CH3D seem plausible, yet substantial kinetically-induced deficits in 12CH2D2show that these temperatures are in fact suspect. The ability to measure more than one doubly-substituted istopologue in the same gas, now demonstrated for both O2 and CH4, gives us tools beyond thermometry for constraining the sources of these gases. High mass resolution gas-source mass spectrometry makes it possible to distinguish thermodynamic equiibrium from irreversible intra-species isotope exchange.

Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein.

PubMed

Ryan, J G; Masters, S L; Booty, M G; Habal, N; Alexander, J D; Barham, B K; Remmers, E F; Barron, K S; Kastner, D L; Aksentijevich, I

2010-07-01

Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin's B-box domain is necessary for interactions with proline serine threonine phosphatase interacting protein 1 (PSTPIP1). The aim was to characterise the phenotype of patients with these substitutions and to determine their functional significance. A database of genetic tests undertaken at the US National Institutes of Health was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Coimmunoprecipitation techniques were employed to determine the variants' effects on pyrin/PSTPIP1 interactions. A total of 40 symptomatic and 4 asymptomatic family members with these substitutions were identified. P369S and R408Q were found in cis, and cosegregated in all patients sequenced. Clinical details were available on 22 patients. In all, 5 patients had symptoms and signs fulfilling a clinical diagnosis of FMF, and 15 received colchicine. In patients not achieving the criteria, trials of anti-tumour necrosis factor (TNF) agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Coimmunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modelling studies suggest that these substitutions do not significantly affect pyrin's interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms.

Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein

PubMed Central

Ryan, JG; Masters, SL; Booty, MG; Habal, N; Alexander, JD; Barham, BK; Remmers, EF; Barron, KS; Kastner, DL; Aksentijevich, I

2013-01-01

Objectives Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin’s B-box domain is necessary for interactions with PSTPIP1. We aimed to characterize the phenotype of patients with these substitutions and to determine their functional significance. Methods A database of genetic tests undertaken in our institution was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Co-immunoprecipation techniques were employed to determine the variants’ effects on pyrin/PSTPIP1 interactions. Results We identified 40 symptomatic and 4 asymptomatic family members with these substitutions. P369S and R408Q were found in cis, and co-segregated in all patients sequenced. Clinical details were available on 22 patients. Five patients had symptoms and signs fulfilling a clinical diagnosis of FMF. Fourteen received colchicine. In patients not reaching the criteria, trials of anti-TNF agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Co-immunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. Conclusions P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modeling studies suggest that these substitutions do not significantly affect pyrin’s interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms. PMID:19934105

The oxidation of alkylaryl sulfides and benzo[b]thiophenes by Escherichia coli cells expressing wild-type and engineered styrene monooxygenase from Pseudomonas putida CA-3.

PubMed

Nikodinovic-Runic, Jasmina; Coulombel, Lydie; Francuski, Djordje; Sharma, Narain D; Boyd, Derek R; Ferrall, Rory Moore O; O'Connor, Kevin E

2013-06-01

Nine different sulfur-containing compounds were biotransformed to the corresponding sulfoxides by Escherichia coli Bl21(DE3) cells expressing styrene monooxygenase (SMO) from Pseudomonas putida CA-3. Thioanisole was consumed at 83.3 μmoles min(-1) g cell dry weight(-1) resulting mainly in the formation of R-thioanisole sulfoxide with an enantiomeric excess (ee) value of 45 %. The rate of 2-methyl-, 2-chloro- and 2-bromo-thioanisole consumption was 2-fold lower than that of thioanisole. Surprisingly, the 2-methylthioanisole sulfoxide product had the opposite (S) configuration to that of the other 2-substituted thioanisole derivatives and had a higher ee value (84 %). The rate of oxidation of 4-substituted thioanisoles was higher than the corresponding 2-substituted substrates but the ee values of the products were consistently lower (10-23 %). The rate of benzo[b]thiophene and 2-methylbenzo[b]thiophene sulfoxidation was approximately 10-fold lower than that of thioanisole. The ee value of the benzo[b]thiophene sulfoxide could not be determined as the product racemized rapidly. E. coli cells expressing an engineered SMO (SMOeng R3-11) oxidised 2-substituted thioanisoles between 1.8- and 2.8-fold faster compared to cells expressing the wild-type enzyme. SMOeng R3-11 oxidised benzo[b]thiophene and 2-methylbenzo[b]thiophene 10.1 and 5.6 times faster that the wild-type enzyme. The stereospecificity of the reaction catalysed by SMOeng was unchanged from that of the wild type. Using the X-ray crystal structure of the P. putida S12 SMO, it was evident that the entrance of substrates into the SMO active site is limited by the binding pocket bottleneck formed by the side chains of Val-211 and Asn-46 carboxyamide group.

Food security for infants and young children: an opportunity for breastfeeding policy?

PubMed

Salmon, Libby

2015-01-01

Increased global demand for imported breast milk substitutes (infant formula, follow-on formula and toddler milks) in Asia, particularly China, and food safety recalls have led to shortages of these products in high income countries. At the same time, commodification and trade of expressed breast milk have fuelled debate about its regulation, cost and distribution. In many economies suboptimal rates of breastfeeding continue to be perpetuated, at least partially, because of a failure to recognise the time, labour and opportunity costs of breast milk production. To date, these issues have not figured prominently in discussions of food security. Policy responses have been piecemeal and reveal conflicts between promotion and protection of breastfeeding and a deregulated trade environment that facilitates the marketing and consumption of breast milk substitutes. The elements of food security are the availability, accessibility, utilization and stability of supply of nutritionally appropriate and acceptable quantities of food. These concepts have been applied to food sources for infants and young children: breastfeeding, shared breast milk and breast milk substitutes, in accordance with World Health Organization (WHO)/United Nations Children's Fund (UNICEF) guidelines on infant feeding. A preliminary analysis indicates that a food security framework may be used to respond appropriately to the human rights, ethical, economic and environmental sustainability issues that affect the supply and affordability of different infant foods. Food security for infants and young children is not possible without high rates of breastfeeding. Existing international and national instruments to protect, promote and support breastfeeding have not been implemented on a wide scale globally. These instruments need review to take into account the emerging trade environment that includes use of the internet, breast milk markets and globalised supply chains for breast milk substitutes. New approaches are required to handle the long-standing policy conflicts that surround infant and young child feeding. Placing breastfeeding in a food security framework may achieve the political attention and policy co-ordination required to accelerate breastfeeding rates in a range of economies.

[Detection of underlying causes of death among the deceased of Yusho patients by linkage to the national vital statistics data].

PubMed

Kaneko, S; Yoshimura, T; Ikeda, M; Nishisaka, K

2001-05-01

As of January 31, 1996, 292 deaths among registered patients of Yusho were identified by three follow-up studies conducted in 1986, 1990, and 1996. In this study, we attempted to identify underlying causes of death by linkage of the registered data to the National Vital Statistics Data provided by the Management and Coordination Agency of Japan, which included 15 million deaths between 1978 and 1996. The two datasets were linked by matching for six variables; birth year/month/day, death year/month, and sex, along with a variable of death day or death place, or both. The matched cases were 203 among 235 deaths between 1978 and 1996 (matching rate was 86%). Among the 203 deaths, 58 underlying causes of death were newly identified, 146 causes of death were already grasped by the follow-up studies, and 31 deaths did not have matching pair in the National Vital Statistics data. Among the 146 deaths, 110 causes of death were concordant with each other, however, 35 causes of death were completely discord. The reason of the discordance and the unmatched deaths might be due to difference in information of the matching variables in the two datasets. In order to conduct an efficient follow-up study of Yusho patients, identification of underlying causes of death by linkage to the National Vital Statistics Date is evitable. For that, we need to substitute basic information in the Yusho database to those compatible to the National civil registration system.

78 FR 77094 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... dairy products subject to tariff-rate quotas (TRQs). The importation of most cheese made from cow's milk and certain non-cheese dairy articles (butter, dried milks, and butter substitutes) are subject to...

Evolution of foot-and-mouth disease virus serotype A capsid coding (P1) region on a timescale of three decades in an endemic context.

PubMed

Das, Biswajit; Mohapatra, Jajati K; Pande, Veena; Subramaniam, Saravanan; Sanyal, Aniket

2016-07-01

Three decades-long (1977-2013) evolutionary trend of the capsid coding (P1) region of foot-and-mouth disease virus (FMDV) serotype A isolated in India was analysed. The exclusive presence of genotype 18 since 2001 and the dominance of the VP3(59)-deletion group of genotype 18 was evident in the recent years. Clade 18c was found to be currently the only active one among the three clades (18a, 18b and 18c) identified in the deletion group. The rate of evolution of the Indian isolates at the capsid region was found to be 4.96×10(-3)substitutions/site/year. The timescale analysis predicted the most recent common ancestor to have existed during 1962 for Indian FMDV serotype A and around 1998 for the deletion group. The evolutionary pattern of serotype A in India appears to be homogeneous as no spatial or temporal structure was observed. Bayesian skyline plots indicate a sharp decline in the effective number of infections after 2008, which might be a result of mass vaccination or inherent loss of virus fitness. Analyses of variability at 38 known antigenically critical positions in a countrywide longitudinal data set suggested that the substitutions neither followed any specific trend nor remained fixed for a long period since frequent reversions and convergence was noticed. A maximum of 6 different amino acid residues was seen in the gene pool at any antigenically critical site over the decades, suggesting a limited combination of residues being responsible for the observed antigenic variation. Evidence of positive selection at some of the antigenically critical residues and the structurally proximal positions suggest a possible role of pre-existing immunity in the host population in driving evolution. The VP1 C-terminus neither revealed variability nor positive selection, suggesting the possibility that this stretch does not contribute to the antigenic variation and adaptation under immune selection. Copyright © 2016 Elsevier B.V. All rights reserved.

ETA-MACRO: A user's guide

NASA Astrophysics Data System (ADS)

Manne, A. S.

1981-02-01

The ETA-MACRO model is designed to estimate the extent of two way linkage between the energy sector and the balance of the economy. It represents a merger between ETA (a process analysis for energy technology assessment) together with a macroeconomic growth model providing for substitution between capital, labor, and energy inputs. The ETA-MACRO allows explicitly for: (1) energy economy interactions; (2) cost effective conservation; (3) interfuel substitution, and (4) new supply technologies, each with its own difficulties and uncertainties on dates and rates of introduction. This user's guide includes an overview of the model, an illustrative application to long term US energy projections, and technical descriptions of the macro and ETA submodels. It also includes an analysis of how market penetration rates may be related to the profitability of new technologies. Finally, the appendices provide a detailed guide to the computer implementation.

Mechanistic Studies of para-Substituted N,N'-Dibenzyl-1,4-diaminobutanes as Substrates for a Mammalian Polyamine Oxidase

PubMed Central

Pozzi, Michelle Henderson; Gawandi, Vijay; Fitzpatrick, Paul F.

2009-01-01

The kinetics of oxidation of a series of para-substituted N, N'-dibenzyl-1,4-diaminobutanes by the flavoprotein polyamine oxidase from mouse have been determined to gain insight into the mechanism of amine oxidation by this member of the monoamine oxidase structural family. The kcat/Km values are maximal at pH 9, consistent with the singly charged substrate being the active form. The rate constant for flavin reduction, kred, by N,N'-dibenzyl-1,4-diaminobutane decreases about 5-fold below a pKa of ~8; this is attributed to the need for a neutral nitrogen at the site of oxidation. The kred and kcat values are comparable for each of the N, N'-dibenzyl-1,4-diaminobutanes, consistent with rate-limiting reduction. The deuterium kinetic isotope effects on kred and kcat are identical for each of the N, N'-dibenzyl-1,4-diaminobutanes, consistent with rate-limiting cleavage of the substrate CH bond. The kred values for seven different para-substituted N, N'-dibenzyl-1,4-diaminobutanes correlate with a combination of the van der Waals volume and σ value of the substrates, with ρ values of −0.59 at pH 8.6 and −0.09 at pH 6.6. These results are consistent with direct transfer of a hydride from the neutral CN bond of the substrate to the flavin as the mechanism of polyamine oxidase. PMID:19911805

A Model of Substitution Trajectories in Sequence Space and Long-Term Protein Evolution

PubMed Central

Usmanova, Dinara R.; Ferretti, Luca; Povolotskaya, Inna S.; Vlasov, Peter K.; Kondrashov, Fyodor A.

2015-01-01

The nature of factors governing the tempo and mode of protein evolution is a fundamental issue in evolutionary biology. Specifically, whether or not interactions between different sites, or epistasis, are important in directing the course of evolution became one of the central questions. Several recent reports have scrutinized patterns of long-term protein evolution claiming them to be compatible only with an epistatic fitness landscape. However, these claims have not yet been substantiated with a formal model of protein evolution. Here, we formulate a simple covarion-like model of protein evolution focusing on the rate at which the fitness impact of amino acids at a site changes with time. We then apply the model to the data on convergent and divergent protein evolution to test whether or not the incorporation of epistatic interactions is necessary to explain the data. We find that convergent evolution cannot be explained without the incorporation of epistasis and the rate at which an amino acid state switches from being acceptable at a site to being deleterious is faster than the rate of amino acid substitution. Specifically, for proteins that have persisted in modern prokaryotic organisms since the last universal common ancestor for one amino acid substitution approximately ten amino acid states switch from being accessible to being deleterious, or vice versa. Thus, molecular evolution can only be perceived in the context of rapid turnover of which amino acids are available for evolution. PMID:25415964

A review of negative-pressure wound therapy in the management of burn wounds.

PubMed

Kantak, Neelesh A; Mistry, Riyam; Halvorson, Eric G

2016-12-01

Negative pressure has been employed in various aspects of burn care and the aim of this study was to evaluate the evidence for each of those uses. The PubMed and Cochrane CENTRAL databases were queried for articles in the following areas: negative pressure as a dressing for acute burns, intermediate treatment prior to skin grafting, bolster for skin autografts, dressing for integration of dermal substitutes, dressing for skin graft donor sites, and integrated dressing in large burns. Fifteen studies met our inclusion criteria. One study showed negative pressure wound therapy improved perfusion in acute partial-thickness burns, 8 out of 9 studies showed benefits when used as a skin graft bolster dressing, 1 out of 2 studies showed improved rate of revascularization when used over dermal substitutes, and 1 study showed increased rate of re-epithelialization when used over skin graft donor sites. Negative pressure can improve autograft take when used as a bolster dressing. There is limited data to suggest that it may also improve the rate of revascularization of dermal substitutes and promote re-epithelialization of skin graft donor sites. Other uses suggested by studies that did not meet our inclusion criteria include improving vascularity in acute partial-thickness burns and as an integrated dressing for the management of large burns. Further studies are warranted for most clinical applications to establish negative pressure as an effective adjunct in burn wound care. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.

PubMed

Lalli, M J; Yong, J; Prasad, V; Hashimoto, K; Plank, D; Babu, G J; Kirkpatrick, D; Walsh, R A; Sussman, M; Yatani, A; Marbán, E; Periasamy, M

2001-07-20

Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.

Medication-related clinical decision support alert overrides in inpatients.

PubMed

Nanji, Karen C; Seger, Diane L; Slight, Sarah P; Amato, Mary G; Beeler, Patrick E; Her, Qoua L; Dalleur, Olivia; Eguale, Tewodros; Wong, Adrian; Silvers, Elizabeth R; Swerdloff, Michael; Hussain, Salman T; Maniam, Nivethietha; Fiskio, Julie M; Dykes, Patricia C; Bates, David W

2018-05-01

To define the types and numbers of inpatient clinical decision support alerts, measure the frequency with which they are overridden, and describe providers' reasons for overriding them and the appropriateness of those reasons. We conducted a cross-sectional study of medication-related clinical decision support alerts over a 3-year period at a 793-bed tertiary-care teaching institution. We measured the rate of alert overrides, the rate of overrides by alert type, the reasons cited for overrides, and the appropriateness of those reasons. Overall, 73.3% of patient allergy, drug-drug interaction, and duplicate drug alerts were overridden, though the rate of overrides varied by alert type (P < .0001). About 60% of overrides were appropriate, and that proportion also varied by alert type (P < .0001). Few overrides of renal- (2.2%) or age-based (26.4%) medication substitutions were appropriate, while most duplicate drug (98%), patient allergy (96.5%), and formulary substitution (82.5%) alerts were appropriate. Despite warnings of potential significant harm, certain categories of alert overrides were inappropriate >75% of the time. The vast majority of duplicate drug, patient allergy, and formulary substitution alerts were appropriate, suggesting that these categories of alerts might be good targets for refinement to reduce alert fatigue. Almost three-quarters of alerts were overridden, and 40% of the overrides were not appropriate. Future research should optimize alert types and frequencies to increase their clinical relevance, reducing alert fatigue so that important alerts are not inappropriately overridden.

Dual fuel diesel engine operation using LPG

NASA Astrophysics Data System (ADS)

Mirica, I.; Pana, C.; Negurescu, N.; Cernat, Al; Nutu, N. C.

2016-08-01

Diesel engine fuelling with LPG represents a good solution to reduce the pollutant emissions and to improve its energetic performances. The high autoignition endurance of LPG requires specialized fuelling methods. From all possible LPG fuelling methods the authors chose the diesel-gas method because of the following reasons: is easy to be implemented even at already in use engines; the engine does not need important modifications; the LPG-air mixture has a high homogeneity with favorable influences over the combustion efficiency and over the level of the pollutant emissions, especially on the nitrogen oxides emissions. This paper presents results of the theoretical and experimental investigations on operation of a LPG fuelled heavy duty diesel engine at two operating regimens, 40% and 55%. For 55% engine load is also presented the exhaust gas recirculation influence on the pollutant emission level. Was determined the influence of the diesel fuel with LPG substitution ratio on the combustion parameters (rate of heat released, combustion duration, maximum pressure, maximum pressure rise rate), on the energetic parameters (indicate mean effective pressure, effective efficiency, energetic specific fuel consumption) and on the pollutant emissions level. Therefore with increasing substitute ratio of the diesel fuel with LPG are obtained the following results: the increase of the engine efficiency, the decrease of the specific energetic consumption, the increase of the maximum pressure and of the maximum pressure rise rate (considered as criteria to establish the optimum substitute ratio), the accentuated reduction of the nitrogen oxides emissions level.

A study of the relationships of cultivated peanut (Arachis hypogaea) and its most closely related wild species using intron sequences and microsatellite markers

PubMed Central

Moretzsohn, Márcio C.; Gouvea, Ediene G.; Inglis, Peter W.; Leal-Bertioli, Soraya C. M.; Valls, José F. M.; Bertioli, David J.

2013-01-01

Background and Aims The genus Arachis contains 80 described species. Section Arachis is of particular interest because it includes cultivated peanut, an allotetraploid, and closely related wild species, most of which are diploids. This study aimed to analyse the genetic relationships of multiple accessions of section Arachis species using two complementary methods. Microsatellites allowed the analysis of inter- and intraspecific variability. Intron sequences from single-copy genes allowed phylogenetic analysis including the separation of the allotetraploid genome components. Methods Intron sequences and microsatellite markers were used to reconstruct phylogenetic relationships in section Arachis through maximum parsimony and genetic distance analyses. Key Results Although high intraspecific variability was evident, there was good support for most species. However, some problems were revealed, notably a probable polyphyletic origin for A. kuhlmannii. The validity of the genome groups was well supported. The F, K and D genomes grouped close to the A genome group. The 2n = 18 species grouped closer to the B genome group. The phylogenetic tree based on the intron data strongly indicated that A. duranensis and A. ipaënsis are the ancestors of A. hypogaea and A. monticola. Intron nucleotide substitutions allowed the ages of divergences of the main genome groups to be estimated at a relatively recent 2·3–2·9 million years ago. This age and the number of species described indicate a much higher speciation rate for section Arachis than for legumes in general. Conclusions The analyses revealed relationships between the species and genome groups and showed a generally high level of intraspecific genetic diversity. The improved knowledge of species relationships should facilitate the utilization of wild species for peanut improvement. The estimates of speciation rates in section Arachis are high, but not unprecedented. We suggest these high rates may be linked to the peculiar reproductive biology of Arachis. PMID:23131301

Growth Speed and Substitution Effects on Alignment and Thermal Transport Properties of Bi-2212 Textured Superconductors

NASA Astrophysics Data System (ADS)

Ozabaci, M.; Rasekh, Sh.; Kizilaslan, O.; Madre, M. A.; Sotelo, A.; Yakinci, M. E.

2015-01-01

Fe-substituted superconducting thin BiSrCaCuO rods with nominal compositions of Bi2Sr2Ca1Cu2- x Fe x O8+ δ ( x = 0, 0.01, 0.03, 0.05, and 0.1) were fabricated using the laser floating zone technique at two different growth speeds, 15 mm h-1 and 30 mm h-1. The influences of growth speed and Fe substitution on the grain alignment in the rods were evaluated by means of x-ray pole figure studies. The obtained results showed that both applied growth speed and Fe substitution play a crucial role on grain alignment, which is strongly connected with the current-carrying capacity of the rods. It was found that the rods grown at 15 mm h-1 (G15) have stronger orientation than the rods grown at 30 mm h-1 (G30). However, in contrast to the G15 rods, an increased substitution rate improved the orientation of the G30 rods. Another important observation is that the increase on the substitution caused a decrease on the grain size of all the rods. The decrease of critical temperature values of the rods upon substitution was ascribed to both grain size effect and formation of a nonsuperconducting Fe-rich phase detected in scanning electron microscope/energy-dispersive x-ray analyses. The thermal conductivity values of the G15 and G30 rods were found to be in the range of 0.9-1.9 and 1.1-1.18 W m-1 K-1 at 150 K, respectively. The higher values of figure of merit ( ZT), at all temperature ranges, were obtained from the highest substituted rods ( x = 0.1) for both of the applied growth speeds. In addition, it was observed that the ZT of G30 rods are up to three times higher than that of G15 ones.

The Oxidation of Ascorbic Acid by Hexacyanoferrate(III) Ion in Acidic Aqueous Media.

ERIC Educational Resources Information Center

Martins, Luis J. A.; da Costa, J. Barbosa

1988-01-01

Describes a kinetic and mechanistic investigation of ascorbic acid by a substitution-inert complex in acidic medium suitable for the undergraduate level. Discusses obtaining the second order rate constant for the rate determining step at a given temperature and comparison with the value predicted on the basis of the Marcus cross-relation. (CW)

"Anything "You" Can Do, "Tu" Can Do Better": "Tu" and "Vous" as Substitutes for Indefinite "On" in French.

ERIC Educational Resources Information Center

Coveney, Aidan

2003-01-01

Presents a survey of the French indefinite "tu/vous" in in earlier periods and in a range of varieties. Draws on a corpus of French spoken in Picardy in Northern France to investigate the extent to which this use of second person pronouns helps to avoid ambiguity and co-occurs with another grammatical variable. (Author/VWL)

Variations in the Solution of Linear First-Order Differential Equations. Classroom Notes

ERIC Educational Resources Information Center

Seaman, Brian; Osler, Thomas J.

2004-01-01

A special project which can be given to students of ordinary differential equations is described in detail. Students create new differential equations by changing the dependent variable in the familiar linear first-order equation (dv/dx)+p(x)v=q(x) by means of a substitution v=f(y). The student then creates a table of the new equations and…

Speech in Adults Treated for Unilateral Cleft Lip and Palate: Long-Term Follow-Up After One- or Two-Stage Palate Repair.

PubMed

Morén, Staffan; Mani, Maria; Lilian, Stålhammar; Lindestad, Per Åke; Holmström, Mats

2017-11-01

  To evaluate speech in adults treated for unilateral cleft lip and palate with one-stage or two-stage palate closure and compare the speech of the patients with that of a noncleft control group.   Cross-sectional study with long-term follow-up.   All unilateral cleft lip and palate patients born from 1960 to 1987 and treated at Uppsala University Hospital, Sweden, were invited (n = 109). Participation rate was 67% (n = 73) at a mean of 35 years after primary surgery. Forty-seven had been treated according to one-stage palate closure and 26 according to two-stage palate closure. Pharyngeal flap surgery had been performed in 11 of the 73 patients (15%). The noncleft control group consisted of 63 age-matched volunteers.   Speech-language pathologists rated perceptual speech characteristics from blinded audio recordings.   Among patients, seven (10%) presented with hypernasality, 12 (16%) had audible nasal emission and/or nasal turbulence, five (7%) had consonant production errors, one (2%) had glottal reinforcements/substitutions, and one (2%) had reduced intelligibility. Controls had no audible signs of velopharyngeal insufficiency and no quantifiable problems with the other speech production variables. No significant differences were identified between patients treated with one-stage and two-stage palate closure for any of the variables.   The prevalence of speech outcome indicative of velopharyngeal insufficiency among adult patients treated for unilateral cleft lip and palate was low but higher compared with individuals without cleft. Whether palatal closure is performed in one or two stages does not seem to affect the speech outcome at a mean age of 35 years.

Design principles and theory of paramagnetic fluorine-labelled lanthanide complexes as probes for (19)F magnetic resonance: a proof-of-concept study.

PubMed

Chalmers, Kirsten H; De Luca, Elena; Hogg, Naomi H M; Kenwright, Alan M; Kuprov, Ilya; Parker, David; Botta, Mauro; Wilson, J Ian; Blamire, Andrew M

2010-01-04

The synthesis and spectroscopic properties of a series of CF(3)-labelled lanthanide(III) complexes (Ln=Gd, Tb, Dy, Ho, Er, Tm) with amide-substituted ligands based on 1,4,7,10-tetraazacyclododecane are described. The theoretical contributions of the (19)F magnetic relaxation processes in these systems are critically assessed and selected volumetric plots are presented. These plots allow an accurate estimation of the increase in the rates of longitudinal and transverse relaxation as a function of the distance between the Ln(III) ion and the fluorine nucleus, the applied magnetic field, and the re-rotational correlation time of the complex, for a given Ln(III) ion. Selected complexes exhibit pH-dependent chemical shift behaviour, and a pK(a) of 7.0 was determined in one example based on the holmium complex of an ortho-cyano DO3A-monoamide ligand, which allowed the pH to be assessed by measuring the difference in chemical shift (varying by over 14 ppm) between two (19)F resonances. Relaxation analyses of variable-temperature and variable-field (19)F, (17)O and (1)H NMR spectroscopy experiments are reported, aided by identification of salient low-energy conformers by using density functional theory. The study of fluorine relaxation rates, over a field range of 4.7 to 16.5 T allowed precise computation of the distance between the Ln(III) ion and the CF(3) reporter group by using global fitting methods. The sensitivity benefits of using such paramagnetic fluorinated probes in (19)F NMR spectroscopic studies are quantified in preliminary spectroscopic and imaging experiments with respect to a diamagnetic yttrium(III) analogue.

Effectiveness of different music-playing devices for reducing preoperative anxiety: a clinical control study.

PubMed

Lee, Kwo-Chen; Chao, Yuh-Huey; Yiin, Jia-Jean; Chiang, Pei-Yi; Chao, Yann-Fen

2011-10-01

While waiting for surgery, patients often exhibit fear and anxiety. Music is thought to be an alternative to medication to relieve anxiety. However, due to concerns about infection control, devices other than headphones may be considered for this purpose. The purpose of this study was to determine the anxiety-relieving effect of broadcast versus headphone music playing for patients awaiting surgery. A randomized controlled clinical study. The waiting area of an operating theater of a metropolitan teach hospital in Taiwan. Alert adult with age between 20 and 65 years old waiting for surgery without premedications. A total of 167 patients were randomly assigned to the headphone, broadcast and control groups. Both the headphone and the broadcast groups were provided with the same instrumental music, while the control group did not listen to any music. The tools for measuring anxiety were visual analogue scale (VAS) ranging from "not anxious at all" to "extremely anxious" and heart rate variability (HRV). The VAS score exhibited a significant decrease for both the headphone and broadcast groups. The low frequency and low-to-high frequency LF/HF ratio of the broadcast and headphone groups were significantly lower than those of the control group. None of the heart rate variables showed significant differences between the broadcast group and the headphone group. Both headphone and broadcast music are effective for reducing the preoperative patient's anxiety in the waiting room. In order to take infection control into account, broadcast speakers can substitute for headphones for playing music to lower the anxiety level of patients waiting for surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of dolutegravir functional monotherapy on HIV-1 virological response in integrase strand transfer inhibitor resistant patients.

PubMed

Naeger, Lisa K; Harrington, Patrick; Komatsu, Takashi; Deming, Damon

2016-01-01

VIKING-4 assessed the safety and efficacy of dolutegravir in heavily antiretroviral treatment-experienced patients who had documented integrase strand transfer inhibitor (INSTI) resistance-associated substitutions in their HIV. VIKING-4 had a placebo-controlled 7-day dolutegravir functional monotherapy phase followed by dolutegravir plus an optimized background regimen for 48 weeks. Independent resistance analyses evaluated week 48 virological responses in the VIKING-4 trial based on the presence of baseline INSTI resistance-associated substitutions and baseline dolutegravir phenotypic susceptibility. Response rates at week 48 based on baseline dolutegravir resistance subgroups were compared for the 7-day dolutegravir functional monotherapy arm and placebo-control arm. Additionally, genotypic and phenotypic resistance at day 8 and time of failure was analysed for the virological failures from both arms. Week 48 response rates for VIKING-4 were 23% (3/13) in the 7-day dolutegravir functional monotherapy arm compared with 60% (9/15) in the 7-day placebo arm. Response rates were consistently lower in the dolutegravir functional monotherapy arm across baseline INSTI genotypic and phenotypic subgroups. There was a higher proportion of virological failures in the 7-day dolutegravir functional monotherapy arm (n=6/13; 46%) compared with the 7-day placebo arm (n=3/15; 20%). Additionally, five virological failures in the dolutegravir arm had virus expressing emergent INSTI resistance-associated substitutions compared with two in the placebo arm. Analysis of response rates and resistance emergence in VIKING-4 suggests careful consideration should be given to the duration of functional monotherapy in future studies of highly treatment-experienced patients to reduce the risk of resistance and virological failure.

Effects of incorporating agro-industrial by-products into diet of New Zealand rabbits: Case of rebus of date and apricot kernel meal.

PubMed

Mennani, Achour; Arbouche, Rafik; Arbouche, Yasmine; Montaigne, Etienne; Arbouche, Fodil; Arbouche, Halima Saâdia

2017-12-01

The aim of this study was to determine the effects of incorporating the by-products complex of date and apricot on the fattening performance of the New Zealand breed of rabbits, to reduce the economic costs of the food formula. A total of 288 young New Zealand rabbits aged 35 days were divided into four equal groups each containing 72 animals and into sub-groups of 6 rabbits per cage, depending on the rate of substitution of corn by date rebus and of soybean meal by apricot kernel meal (0%, 10%, 20%, and 30%). The change in weight from day 35 to 77 and the average daily gain are not significantly different, regardless of the diet. The pH and water content are proportional to the substitution rates (6.4-6.6% and 66.5-68.8%). Meat protein levels increased significantly, in particular for the 10% and 30% groups (+8.1% and 6%) while the fat and mineral content levels decreased significantly, in particular for the 30% group displaying -16% and -17%, respectively. Incorporation of dates and apricot kernel meal into the ration of rabbits reduces the cost of the kilogram of food produced of -9%, with an opportunity cost of 165 Algerian dinars (DZD). The date rebus/apricot kernel meal complex can be used as an alternative to the corn/soybean meal complex at substitution rates of up to 30% without adverse effects on growth rates, feed contribution, or slaughter yield. It improves the chemical composition of the meat and reduces the cost price of the quintal of feed produced.

Effects of incorporating agro-industrial by-products into diet of New Zealand rabbits: Case of rebus of date and apricot kernel meal

PubMed Central

Mennani, Achour; Arbouche, Rafik; Arbouche, Yasmine; Montaigne, Etienne; Arbouche, Fodil; Arbouche, Halima Saâdia

2017-01-01

Aim: The aim of this study was to determine the effects of incorporating the by-products complex of date and apricot on the fattening performance of the New Zealand breed of rabbits, to reduce the economic costs of the food formula. Materials and Methods: A total of 288 young New Zealand rabbits aged 35 days were divided into four equal groups each containing 72 animals and into sub-groups of 6 rabbits per cage, depending on the rate of substitution of corn by date rebus and of soybean meal by apricot kernel meal (0%, 10%, 20%, and 30%). Results: The change in weight from day 35 to 77 and the average daily gain are not significantly different, regardless of the diet. The pH and water content are proportional to the substitution rates (6.4-6.6% and 66.5-68.8%). Meat protein levels increased significantly, in particular for the 10% and 30% groups (+8.1% and 6%) while the fat and mineral content levels decreased significantly, in particular for the 30% group displaying −16% and −17%, respectively. Incorporation of dates and apricot kernel meal into the ration of rabbits reduces the cost of the kilogram of food produced of −9%, with an opportunity cost of 165 Algerian dinars (DZD). Conclusion: The date rebus/apricot kernel meal complex can be used as an alternative to the corn/soybean meal complex at substitution rates of up to 30% without adverse effects on growth rates, feed contribution, or slaughter yield. It improves the chemical composition of the meat and reduces the cost price of the quintal of feed produced. PMID:29391686

Genomic gigantism: DNA loss is slow in mountain grasshoppers.

PubMed

Bensasson, D; Petrov, D A; Zhang, D X; Hartl, D L; Hewitt, G M

2001-02-01

Several studies have shown DNA loss to be inversely correlated with genome size in animals. These studies include a comparison between Drosophila and the cricket, Laupala, but there has been no assessment of DNA loss in insects with very large genomes. Podisma pedestris, the brown mountain grasshopper, has a genome over 100 times as large as that of Drosophila and 10 times as large as that of Laupala. We used 58 paralogous nuclear pseudogenes of mitochondrial origin to study the characteristics of insertion, deletion, and point substitution in P. pedestris and Italopodisma. In animals, these pseudogenes are "dead on arrival"; they are abundant in many different eukaryotes, and their mitochondrial origin simplifies the identification of point substitutions accumulated in nuclear pseudogene lineages. There appears to be a mononucleotide repeat within the 643-bp pseudogene sequence studied that acts as a strong hot spot for insertions or deletions (indels). Because the data for other insect species did not contain such an unusual region, hot spots were excluded from species comparisons. The rate of DNA loss relative to point substitution appears to be considerably and significantly lower in the grasshoppers studied than in Drosophila or Laupala. This suggests that the inverse correlation between genome size and the rate of DNA loss can be extended to comparisons between insects with large or gigantic genomes (i.e., Laupala and Podisma). The low rate of DNA loss implies that in grasshoppers, the accumulation of point mutations is a more potent force for obscuring ancient pseudogenes than their loss through indel accumulation, whereas the reverse is true for Drosophila. The main factor contributing to the difference in the rates of DNA loss estimated for grasshoppers, crickets, and Drosophila appears to be deletion size. Large deletions are relatively rare in Podisma and Italopodisma.

Growth of mixed cultures on mixtures of substitutable substrates: the operating diagram for a structured model.

PubMed

Reeves, Gregory T; Narang, Atul; Pilyugin, Sergei S

2004-01-21

The growth of mixed microbial cultures on mixtures of substrates is a problem of fundamental biological interest. In the last two decades, several unstructured models of mixed-substrate growth have been studied. It is well known, however, that the growth patterns in mixed-substrate environments are dictated by the enzymes that catalyse the transport of substrates into the cell. We have shown previously that a model taking due account of transport enzymes captures and explains all the observed patterns of growth of a single species on two substitutable substrates (J. Theor. Biol. 190 (1998) 241). Here, we extend the model to study the steady states of growth of two species on two substitutable substrates. The model is analysed to determine the conditions for existence and stability of the various steady states. Simulations are performed to determine the flow rates and feed concentrations at which both species coexist. We show that if the interaction between the two species is purely competitive, then at any given flow rate, coexistence is possible only if the ratio of the two feed concentrations lies within a certain interval; excessive supply of either one of the two substrates leads to annihilation of one of the species. This result simplifies the construction of the operating diagram for purely competing species. This is because the two-dimensional surface that bounds the flow rates and feed concentrations at which both species coexist has a particularly simple geometry: It is completely determined by only two coordinates, the flow rate and the ratio of the two feed concentrations. We also study commensalistic interactions between the two species by assuming that one of the species excretes a product that can support the growth of the other species. We show that such interactions enhance the coexistence region.

Service-oriented workflow to efficiently and automatically fulfill products in a highly individualized web and mobile environment

NASA Astrophysics Data System (ADS)

Qiao, Mu

2015-03-01

Service Oriented Architecture1 (SOA) is widely used in building flexible and scalable web sites and services. In most of the web or mobile photo book and gifting business space, the products ordered are highly variable without a standard template that one can substitute texts or images from similar to that of commercial variable data printing. In this paper, the author describes a SOA workflow in a multi-sites, multi-product lines fulfillment system where three major challenges are addressed: utilization of hardware and equipment, highly automation with fault recovery, and highly scalable and flexible with order volume fluctuation.

Latin American Clinical Epidemiology Network Series - Paper 8: Ticagrelor was cost-effective vs. clopidogrel in acute coronary syndrome in Chile.

PubMed

De la Puente, Catherine; Vallejos, Carlos; Bustos, Luis; Zaror, Carlos; Velasquez, Monica; Lanas, Fernando

2017-06-01

To evaluate the incremental cost-effectiveness ratio (ICER) of the use of ticagrelor as a substitute for clopidogrel for secondary prevention of acute coronary syndrome in Chile. Cost-effectiveness analysis based on a Markov model: Safety and effectiveness data of ticagrelor were obtained from a systematic review of the literature. Costs are expressed in Chilean pesos (CLP) as of 2013. The evaluation was conducted from the payer standpoint. A probabilistic sensitivity analysis comprising discount rates and national cost variability was done. A budget impact analysis estimated for 2015 was conducted to calculate the total cost for both treatments. The ICER with a discount rate of 6% for ticagrelor vs. clopidogrel was CLP 4,893,126 per quality-adjusted life-year (QALY) gained (=9,689 US$). In the budget impact analysis for the baseline scenario, considering 100% of treatment, coverage, and adherence, ticagrelor represented an additional cost of CLP 5,233,854,272, for 979 QALYs gained compared with clopidogrel. Ticagrelor is cost-effective in comparison with clopidogrel for the secondary prevention of acute coronary syndrome. These findings are similar to those reported in other international cost-effectiveness studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Multilocus resolution of phylogeny and timescale in the extant adaptive radiation of Hawaiian honeycreepers.

PubMed

Lerner, Heather R L; Meyer, Matthias; James, Helen F; Hofreiter, Michael; Fleischer, Robert C

2011-11-08

Evolutionary theory has gained tremendous insight from studies of adaptive radiations. High rates of speciation, morphological divergence, and hybridization, combined with low sequence variability, however, have prevented phylogenetic reconstruction for many radiations. The Hawaiian honeycreepers are an exceptional adaptive radiation, with high phenotypic diversity and speciation that occurred within the geologically constrained setting of the Hawaiian Islands. Here we analyze a new data set of 13 nuclear loci and pyrosequencing of mitochondrial genomes that resolves the Hawaiian honeycreeper phylogeny. We show that they are a sister taxon to Eurasian rosefinches (Carpodacus) and probably came to Hawaii from Asia. We use island ages to calibrate DNA substitution rates, which vary substantially among gene regions, and calculate divergence times, showing that the radiation began roughly when the oldest of the current large Hawaiian Islands (Kauai and Niihau) formed, ~5.7 million years ago (mya). We show that most of the lineages that gave rise to distinctive morphologies diverged after Oahu emerged (4.0-3.7 mya) but before the formation of Maui and adjacent islands (2.4-1.9 mya). Thus, the formation of Oahu, and subsequent cycles of colonization and speciation between Kauai and Oahu, played key roles in generating the morphological diversity of the extant honeycreepers. Copyright © 2011 Elsevier Ltd. All rights reserved.

The mitochondrial genome of the ascalaphid owlfly Libelloides macaronius and comparative evolutionary mitochondriomics of neuropterid insects

PubMed Central

2011-01-01

Background The insect order Neuroptera encompasses more than 5,700 described species. To date, only three neuropteran mitochondrial genomes have been fully and one partly sequenced. Current knowledge on neuropteran mitochondrial genomes is limited, and new data are strongly required. In the present work, the mitochondrial genome of the ascalaphid owlfly Libelloides macaronius is described and compared with the known neuropterid mitochondrial genomes: Megaloptera, Neuroptera and Raphidioptera. These analyses are further extended to other endopterygotan orders. Results The mitochondrial genome of L. macaronius is a circular molecule 15,890 bp long. It includes the entire set of 37 genes usually present in animal mitochondrial genomes. The gene order of this newly sequenced genome is unique among Neuroptera and differs from the ancestral type of insects in the translocation of trnC. The L. macaronius genome shows the lowest A+T content (74.50%) among known neuropterid genomes. Protein-coding genes possess the typical mitochondrial start codons, except for cox1, which has an unusual ACG. Comparisons among endopterygotan mitochondrial genomes showed that A+T content and AT/GC-skews exhibit a broad range of variation among 84 analyzed taxa. Comparative analyses showed that neuropterid mitochondrial protein-coding genes experienced complex evolutionary histories, involving features ranging from codon usage to rate of substitution, that make them potential markers for population genetics/phylogenetics studies at different taxonomic ranks. The 22 tRNAs show variable substitution patterns in Neuropterida, with higher sequence conservation in genes located on the α strand. Inferred secondary structures for neuropterid rrnS and rrnL genes largely agree with those known for other insects. For the first time, a model is provided for domain I of an insect rrnL. The control region in Neuropterida, as in other insects, is fast-evolving genomic region, characterized by AT-rich motifs. Conclusions The new genome shares many features with known neuropteran genomes but differs in its low A+T content. Comparative analysis of neuropterid mitochondrial genes showed that they experienced distinct evolutionary patterns. Both tRNA families and ribosomal RNAs show composite substitution pathways. The neuropterid mitochondrial genome is characterized by a complex evolutionary history. PMID:21569260

Paraquat prohibition and change in the suicide rate and methods in South Korea.

PubMed

Myung, Woojae; Lee, Geung-Hee; Won, Hong-Hee; Fava, Maurizio; Mischoulon, David; Nyer, Maren; Kim, Doh Kwan; Heo, Jung-Yoon; Jeon, Hong Jin

2015-01-01

The annual suicide rate in South Korea is the highest among the developed countries. Paraquat is a highly lethal herbicide, commonly used in South Korea as a means for suicide. We have studied the effect of the 2011 paraquat prohibition on the national suicide rate and method of suicide in South Korea. We obtained the monthly suicide rate from 2005 to 2013 in South Korea. In our analyses, we adjusted for the effects of celebrity suicides, and economic, meteorological, and seasonal factors on suicide rate. We employed change point analysis to determine the effect of paraquat prohibition on suicide rate over time, and the results were verified by structural change analysis, an alternative statistical method. After the paraquat prohibition period in South Korea, there was a significant reduction in the total suicide rate and suicide rate by poisoning with herbicides or fungicides in all age groups and in both genders. The estimated suicide rates during this period decreased by 10.0% and 46.1% for total suicides and suicides by poisoning of herbicides or fungicides, respectively. In addition, method substitution effect of paraquat prohibition was found in suicide by poisoning by carbon monoxide, which did not exceed the reduction in the suicide rate of poisoning with herbicides or fungicides. In South Korea, paraquat prohibition led to a lower rate of suicide by paraquat poisoning, as well as a reduction in the overall suicide rate. Paraquat prohibition should be considered as a national suicide prevention strategy in developing and developed countries alongside careful observation for method substitution effects.

SU-G-201-06: Directional Low-Dose Rate Brachytherapy: Determination of the TG-43 Dose-Rate Constant Analog for a New Pd-103 Source

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

Aima, M; Culberson, W; Hammer, C

Purpose: The aim of this work is to determine the TG-43 dose-rate constant analog for a new directional low-dose rate brachytherapy source based on experimental methods and comparison to Monte Carlo simulations. The CivaSheet™ is a new commercially available planar source array comprised of a variable number of discrete directional source elements called “CivaDots”. Given the directional nature and non-conventional design of the source, modifications to the AAPM TG-43 protocol for dosimetry are required. As a result, various parameters of the TG-43 dosimetric formalism have to be adapted to accommodate this source. This work focuses on the dose-rate constant analogmore » determination for a CivaDot. Methods: Dose to water measurements of the CivaDot were performed in a polymethyl methacrylate phantom (20×20×12 cm{sup 3}) using thermoluminescent dosimeters (TLDs) and Gafchromic EBT3 film. The source was placed in the center of the phantom, and nine TLD micro-cubes were irradiated along its central axis at a distance of 1 cm. For the film measurements, the TLDs were substituted by a (3×3) cm{sup 2} EBT3 film. Primary air-kerma strength measurements of the source were performed using a variable-aperture free-air chamber. Finally, the source was modeled using the Monte Carlo N-Particle Transport Code 6. Results: Dose-rate constant analog observed for a total of eight CivaDots using TLDs and five CivaDots using EBT3 film was within ±7.0% and ±2.9% of the Monte Carlo predicted value respectively. The average difference observed was −4.8% and −0.1% with a standard deviation of 1.7% and 2.1% for the TLD and the film measurements respectively, which are both within the comparison uncertainty. Conclusion: A preliminary investigation to determine the doserate constant analog for a CivaDot was conducted successfully with good agreement between experimental and Monte Carlo based methods. This work will aid in the eventual realization of a clinically-viable dosimetric framework for the CivaSheet. This work was partially supported by NCI contract (HHSN261201200052C) through CivaTech Oncology Inc.« less

Does Conceptual Understanding of Limit Partially Lead Students to Misconceptions?

NASA Astrophysics Data System (ADS)

Mulyono, B.; Hapizah

2017-09-01

This article talks about the result of preliminary research of my dissertation, which will investigate student’s retention of conceptual understanding. In my preliminary research, I surveyed 73 students of mathematics education program by giving some questions to test their retention of conceptual understanding of limits. Based on the results of analyzing of students’ answers I conclude that most of the students have problems with their retention of conceptual understanding and they also have misconception of limits. The first misconception I identified is that students always used the substitution method to determine a limit of a function at a point, but they did not check whether the function is continue or not at the point. It means that they only use the substitution theorem partially, because they do not consider that the substitution theorem \\mathop{{lim}}\\limits\\text{x\\to \\text{c}}f(x)=f(c) works only if f(x) is defined at χ = c. The other misconception identified is that some students always think there must be available of variables χ in a function to determine the limit of the function. I conjecture that conceptual understanding of limit partially leads students to misconceptions.

Synthesis of fluorine substituted hydroxyapatite nanopowders and application of the central composite design for determination of its antimicrobial effects

NASA Astrophysics Data System (ADS)

Stanić, Vojislav; Dimitrijević, Suzana; Antonović, Dušan G.; Jokić, Bojan M.; Zec, Slavica P.; Tanasković, Sladjana T.; Raičević, Slavica

2014-01-01

Synthetic biomaterials based on fluorine substituted hydroxyapatite are potentially attractive for orthopedic and dental implant applications. The new synthesis of fluorine substituted hydroxyapatite samples were done by neutralization, which consists of adding the solution of HF and H3PO4 in suspension of Ca(OH)2. Characterization studies from XRD, SEM and FTIR spectra showed that crystals are obtained with apatite structure and those particles of all samples are nano size, with an average length of 80 nm and about 15-25 nm in diameter. The central composite design was used in order to determine the optimal conditions for the antimicrobial activity of the synthesized samples. In order to evaluate the influence of operating parameters on the percent of viable cell reduction of Streptococcus mutans, three independent variables were chosen: exposure time, pH of saline and floride concentration in apatite samples. The experimental and predicted antimicrobial activities were in close agreement. Antimicrobial activity of the samples increases with the increase of fluoride concentration and the decreased pH of saline. The maximum antimicrobial activity was achieved at the initial pH of 4.

New fluorescent perylene bisimide indicators--a platform for broadband pH optodes.

PubMed

Aigner, Daniel; Borisov, Sergey M; Klimant, Ingo

2011-06-01

Asymmetric perylene bisimide (PBI) dyes are prepared and are shown to be suitable for the preparation of fluorescence chemosensors for pH. They carry one amino-functional substituent which introduces pH sensitivity via photoinduced electron transfer (PET) while the other one increases solubility. The luminescence quantum yields for the new indicators exceed 75% in the protonated form. The new indicators are non-covalently entrapped in polyurethane hydrogel D4 and poly(hydroxyalkylmethacrylates). Several PET functions including aliphatic and aromatic amino groups were successfully used to tune the dynamic range of the sensor. Because of their virtually identical spectral properties, various PBIs with selected PET functions can easily be integrated into a single sensor with enlarged dynamic range (over 4 pH units). PBIs with two different substitution patterns in the bay position are investigated and possess variable spectral properties. Compared with their tetrachloro analogues, tetra-tert-butyl-substituted PBIs yield more long-wave excitable sensors which feature excellent photostability. Cross-sensitivity to ionic strength was found to be negligible. The practical applicability of the sensors may be compromised by the long response times (especially in case of tetra-tert-butyl-substituted PBIs).

Climate Change Mitigation Challenge for Wood Utilization-The Case of Finland.

PubMed

Soimakallio, Sampo; Saikku, Laura; Valsta, Lauri; Pingoud, Kim

2016-05-17

The urgent need to mitigate climate change invokes both opportunities and challenges for forest biomass utilization. Fossil fuels can be substituted by using wood products in place of alternative materials and energy, but wood harvesting reduces forest carbon sink and processing of wood products requires material and energy inputs. We assessed the extended life cycle carbon emissions considering substitution impacts for various wood utilization scenarios over 100 years from 2010 onward for Finland. The scenarios were based on various but constant wood utilization structures reflecting current and anticipated mix of wood utilization activities. We applied stochastic simulation to deal with the uncertainty in a number of input variables required. According to our analysis, the wood utilization decrease net carbon emissions with a probability lower than 40% for each of the studied scenarios. Furthermore, large emission reductions were exceptionally unlikely. The uncertainty of the results were influenced clearly the most by the reduction in the forest carbon sink. There is a significant trade-off between avoiding emissions through fossil fuel substitution and reduction in forest carbon sink due to wood harvesting. This creates a major challenge for forest management practices and wood utilization activities in responding to ambitious climate change mitigation targets.

Human genetics: measuring the raw material of evolution.

PubMed

Armour, John A L

2009-09-15

By direct sequencing of two Y chromosomes inherited from the same paternal ancestor, a landmark study has derived a good direct estimate for the rate of base substitution mutations on the human Y chromosome.

Uncertainty Quantification in CO 2 Sequestration Using Surrogate Models from Polynomial Chaos Expansion

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

Zhang, Yan; Sahinidis, Nikolaos V.

2013-03-06

In this paper, surrogate models are iteratively built using polynomial chaos expansion (PCE) and detailed numerical simulations of a carbon sequestration system. Output variables from a numerical simulator are approximated as polynomial functions of uncertain parameters. Once generated, PCE representations can be used in place of the numerical simulator and often decrease simulation times by several orders of magnitude. However, PCE models are expensive to derive unless the number of terms in the expansion is moderate, which requires a relatively small number of uncertain variables and a low degree of expansion. To cope with this limitation, instead of using amore » classical full expansion at each step of an iterative PCE construction method, we introduce a mixed-integer programming (MIP) formulation to identify the best subset of basis terms in the expansion. This approach makes it possible to keep the number of terms small in the expansion. Monte Carlo (MC) simulation is then performed by substituting the values of the uncertain parameters into the closed-form polynomial functions. Based on the results of MC simulation, the uncertainties of injecting CO{sub 2} underground are quantified for a saline aquifer. Moreover, based on the PCE model, we formulate an optimization problem to determine the optimal CO{sub 2} injection rate so as to maximize the gas saturation (residual trapping) during injection, and thereby minimize the chance of leakage.« less

Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients.

PubMed

Peters, A L; Davidson, M B; Eisenberg, K

1990-08-01

Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia.

Aging, health, and the "electronic church".

PubMed

Hays, J C; Landerman, L R; Blazer, D G; Koenig, H G; Carroll, J W; Musick, M A

1998-11-01

We tested whether elders substitute religious media use for church attendance when health declines (using multidimensional disengagement theory) with data from a multiracial, population-based sample in the Bible Belt (N = 2,971). In adjusted models, 3-year declines in functional status were significantly associated with concurrent reduction in frequency of church attendance but not with any change in rates of religious media (TV/radio) use. Age-related declines in church attendance were substantively explained by declining functional ability. Changes in religious media use were independent of age and less sensitive to declining functional status or service attendance than to cultural heritage such as race, socioeconomic status, and rural upbringing. Our data do not support the hypothesis that elders with deteriorating health substitute increased engagement with religious media as their participation in organizational religious activities is reduced. However, applicability of the substitution hypothesis to other dimensions of nonorganizational religiousness (e.g., prayer) awaits similar scrutiny.

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

Socket preservation.

PubMed

Fee, L

2017-04-21

Socket preservation maintains bone volume post-extraction in anticipation of an implant placement or fixed partial denture pontic site. This procedure helps compensate for the resorption of the facial bone wall. Socket preservation should be considered when implant placement needs to be delayed for patient or site-related reasons. The ideal healing time before implant placement is six months. Socket preservation can reduce the need for later bone augmentation. By reducing bone resorption and accelerating bone formation it increases implant success and survival. Biomaterials for socket grafting including autograft, allograft, xenograft and alloplast. A bone substitute with a low substitution rate is recommended.

Kinetic Studies on the Reaction of Chlorosulfonyl Isocyanate with Monofluoralkenes: Experimental Evidence for Both Stepwise and Concerted Mechanisms, and a Pre-equilibrium Complex on the Reaction Pathway

DTIC Science & Technology

2012-12-14

lactams that are readily reduced to β-lactams. Substitution of a vinyl hydrogen for a vinyl fluorine changes the dynamics for reaction with CSI so...hydrogen for a vinyl fluorine changes the dynamics for reaction with CSI so that a concerted pathway is favored. Rate constants were measured for...step pathway has not been demonstrated experimentally.3c In a recent paper, we found that substituting a hydrogen for a fluorine on the π-bond of an

Variability among the Most Rapidly Evolving Plastid Genomic Regions is Lineage-Specific: Implications of Pairwise Genome Comparisons in Pyrus (Rosaceae) and Other Angiosperms for Marker Choice

PubMed Central

Ter-Voskanyan, Hasmik; Allgaier, Martin; Borsch, Thomas

2014-01-01

Plastid genomes exhibit different levels of variability in their sequences, depending on the respective kinds of genomic regions. Genes are usually more conserved while noncoding introns and spacers evolve at a faster pace. While a set of about thirty maximum variable noncoding genomic regions has been suggested to provide universally promising phylogenetic markers throughout angiosperms, applications often require several regions to be sequenced for many individuals. Our project aims to illuminate evolutionary relationships and species-limits in the genus Pyrus (Rosaceae)—a typical case with very low genetic distances between taxa. In this study, we have sequenced the plastid genome of Pyrus spinosa and aligned it to the already available P. pyrifolia sequence. The overall p-distance of the two Pyrus genomes was 0.00145. The intergenic spacers between ndhC–trnV, trnR–atpA, ndhF–rpl32, psbM–trnD, and trnQ–rps16 were the most variable regions, also comprising the highest total numbers of substitutions, indels and inversions (potentially informative characters). Our comparative analysis of further plastid genome pairs with similar low p-distances from Oenothera (representing another rosid), Olea (asterids) and Cymbidium (monocots) showed in each case a different ranking of genomic regions in terms of variability and potentially informative characters. Only two intergenic spacers (ndhF–rpl32 and trnK–rps16) were consistently found among the 30 top-ranked regions. We have mapped the occurrence of substitutions and microstructural mutations in the four genome pairs. High AT content in specific sequence elements seems to foster frequent mutations. We conclude that the variability among the fastest evolving plastid genomic regions is lineage-specific and thus cannot be precisely predicted across angiosperms. The often lineage-specific occurrence of stem-loop elements in the sequences of introns and spacers also governs lineage-specific mutations. Sequencing whole plastid genomes to find markers for evolutionary analyses is therefore particularly useful when overall genetic distances are low. PMID:25405773

Inhibition and interference in the think/no-think task.

PubMed

Racsmány, Mihály; Conway, Martin A; Keresztes, Attila; Krajcsi, Attila

2012-02-01

Five experiments using the think/no-think (TNT) procedure investigated the effect of the no-think and substitute instructions on cued recall. In Experiment 1, when unrelated A-B paired associates were studied and cued for recall with A items, recall rates were reliably enhanced in the think condition and reliably impaired below baseline in the no-think condition. In Experiments 2 and 5, final recall was cued with B items, leading to reliably higher recall rates, as compared with baseline, in both the think and no-think conditions. This pattern indicates backward priming of no-think items. In Experiments 3 and 4, the no-think instruction was replaced with a thought substitution instruction, and participants were asked to think of another word instead of the studied one when they saw the no-think cued items. As in Experiments 1 and 2, the same amount of forgetting of B items was observed when A items were the cues, but in contrast to Experiment 2, there was no increase in the recall performance of A items when B items were the cues. These results suggest that not thinking of studied items or, alternatively, thinking of a substitute item to avoid a target item may involve different processes: the former featuring inhibition and the latter interference.

Molecular evolution of emerging Banna virus.

PubMed

Liu, Hong; Gao, Xiao-Yan; Fu, Shi-Hong; Li, Ming-Hua; Zhai, You-Gang; Meng, Wei-Shan; Sun, Xiao-Hong; Lv, Zhi; Wang, Huan-Yu; Shen, Xin-Xin; Cao, Yu-Xi; He, Ying; Liang, Guo-Dong

2016-11-01

Banna virus (BAV) is an emerging pathogen that causes human viral encephalitis and has been isolated from types of blood-sucking insects and mammals in Asia. However, there are no reported systematic studies that describe the origin and evolution of BAV. Here, a phylogenetic analysis of BAVs isolated from a variety of potential vectors and vertebrate hosts worldwide revealed that BAVs emerged in the beginning of the 20th century and do not exhibit a species barrier. The mean substitution rate of BAVs was 2.467×10 -2 substitution/site/year (95% HPD, 1.093×10 -3 to 5.628×10 -2 ). The lineage is mainly composed of BAVs from high-latitude regions, which are the most recently emerged viruses with significantly higher substitution rates compared with the lineage comprised of the isolates from middle or low-latitude regions. The genetic differences between BAV strains are positively correlated with the geographic distribution. Strains from the same latitude regions are almost 100% identical, whereas the differences between strains from long distance regions with different latitudes could be >60%. Our results demonstrate that BAV is an emerging virus at a stage that involves rapid evolution and has great potential for introduction into non-endemic areas. Thus, enhanced surveillance of BAV is highly recommended worldwide. Copyright © 2016 Elsevier B.V. All rights reserved.

Tuning Li2MO3 phase abundance and suppressing migration of transition metal ions to improve the overall performance of Li- and Mn-rich layered oxide cathode

NASA Astrophysics Data System (ADS)

Zhang, Shiming; Tang, Tian; Ma, Zhihua; Gu, Haitao; Du, Wubing; Gao, Mingxia; Liu, Yongfeng; Jian, Dechao; Pan, Hongge

2018-03-01

The poor cycling stability of Li- and Mn-rich layered oxide cathodes used in lithium-ion batteries (LIBs) has severely limited their practical application. Unfortunately, current strategies to improve their lifecycle sacrifice initial capacity. In this paper, we firstly report the synergistic improvement of the electrochemical performance of a Li1.2Ni0.13Co0.13Mn0.54O2 (LNCMO) cathode material, including gains for capacity, cycling stability, and rate capability, by the partial substitution of Li+ ions by Mg2+ ions. Electrochemical performance is evaluated by a galvanostatic charge and discharge test and electrochemical impedance spectroscopy (EIS). Structure and morphology are characterized by X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Compared with the substitution of transition metal (TM) ions with Mg2+ ions reported previously, the substitution of Li+ ions by Mg2+ ions not only drastically ameliorates the capacity retention and rate performance challenges of LNCMO cathodes but also markedly suppresses their voltage fading, due to the inhibition of the migration of TM ions during cycling, while also increasing the capacity of the cathode due to an increased abundance of the Li2MO3 phase.

Long-range dispersal moved Francisella tularensis into Western Europe from the East.

PubMed

Dwibedi, Chinmay; Birdsell, Dawn; Lärkeryd, Adrian; Myrtennäs, Kerstin; Öhrman, Caroline; Nilsson, Elin; Karlsson, Edvin; Hochhalter, Christian; Rivera, Andrew; Maltinsky, Sara; Bayer, Brittany; Keim, Paul; Scholz, Holger C; Tomaso, Herbert; Wittwer, Matthias; Beuret, Christian; Schuerch, Nadia; Pilo, Paola; Hernández Pérez, Marta; Rodriguez-Lazaro, David; Escudero, Raquel; Anda, Pedro; Forsman, Mats; Wagner, David M; Larsson, Pär; Johansson, Anders

2016-12-01

For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis , the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains ( n =205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains ( n =195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.

Calculating Higher-Order Moments of Phylogenetic Stochastic Mapping Summaries in Linear Time.

PubMed

Dhar, Amrit; Minin, Vladimir N

2017-05-01

Stochastic mapping is a simulation-based method for probabilistically mapping substitution histories onto phylogenies according to continuous-time Markov models of evolution. This technique can be used to infer properties of the evolutionary process on the phylogeny and, unlike parsimony-based mapping, conditions on the observed data to randomly draw substitution mappings that do not necessarily require the minimum number of events on a tree. Most stochastic mapping applications simulate substitution mappings only to estimate the mean and/or variance of two commonly used mapping summaries: the number of particular types of substitutions (labeled substitution counts) and the time spent in a particular group of states (labeled dwelling times) on the tree. Fast, simulation-free algorithms for calculating the mean of stochastic mapping summaries exist. Importantly, these algorithms scale linearly in the number of tips/leaves of the phylogenetic tree. However, to our knowledge, no such algorithm exists for calculating higher-order moments of stochastic mapping summaries. We present one such simulation-free dynamic programming algorithm that calculates prior and posterior mapping variances and scales linearly in the number of phylogeny tips. Our procedure suggests a general framework that can be used to efficiently compute higher-order moments of stochastic mapping summaries without simulations. We demonstrate the usefulness of our algorithm by extending previously developed statistical tests for rate variation across sites and for detecting evolutionarily conserved regions in genomic sequences.

A pilot iron substitution programme in female blood donors with iron deficiency without anaemia.

PubMed

Pittori, C; Buser, A; Gasser, U E; Sigle, J; Job, S; Rüesch, M; Tichelli, A; Infanti, L

2011-04-01

Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non-anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain. Women aged≤50 with haemoglobin levels adequate for donation and serum ferritin≤10 ng/ml were offered iron supplementation. Substitution lasted 16 weeks and the donation interval was extended. History collection including iron deficiency-related symptoms, whole blood count and serum ferritin determination was performed at baseline and after 2 and 6 months. Data were recorded prospectively and compared with those of 108 female controls with iron deficiency not receiving iron substitution (retrospective data). Of the 116 participating subjects, 60% completed the programme. Significant results were serum ferritin increase (from a mean value of 7.12 to 25.2 ng/ml), resolution of prostration, fatigue, sleep disturbances, tension in the neck, hair loss and nail breakage. No case of anaemia occurred. Sixty per cent of the women completed the programme and donated blood again. Targeted iron substitution prevents the development of anaemia and enhances donation return in premenopausal female blood donors with iron deficiency. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Calculating Higher-Order Moments of Phylogenetic Stochastic Mapping Summaries in Linear Time

PubMed Central

Dhar, Amrit

2017-01-01

Abstract Stochastic mapping is a simulation-based method for probabilistically mapping substitution histories onto phylogenies according to continuous-time Markov models of evolution. This technique can be used to infer properties of the evolutionary process on the phylogeny and, unlike parsimony-based mapping, conditions on the observed data to randomly draw substitution mappings that do not necessarily require the minimum number of events on a tree. Most stochastic mapping applications simulate substitution mappings only to estimate the mean and/or variance of two commonly used mapping summaries: the number of particular types of substitutions (labeled substitution counts) and the time spent in a particular group of states (labeled dwelling times) on the tree. Fast, simulation-free algorithms for calculating the mean of stochastic mapping summaries exist. Importantly, these algorithms scale linearly in the number of tips/leaves of the phylogenetic tree. However, to our knowledge, no such algorithm exists for calculating higher-order moments of stochastic mapping summaries. We present one such simulation-free dynamic programming algorithm that calculates prior and posterior mapping variances and scales linearly in the number of phylogeny tips. Our procedure suggests a general framework that can be used to efficiently compute higher-order moments of stochastic mapping summaries without simulations. We demonstrate the usefulness of our algorithm by extending previously developed statistical tests for rate variation across sites and for detecting evolutionarily conserved regions in genomic sequences. PMID:28177780

The influence of aliovalent impurities on the oxidation kinetics of nickel at high temperatures

NASA Astrophysics Data System (ADS)

Mrowec, S.; Grzesik, Z.; Rajchel, B.; Gil, A.; Dabek, J.

2005-01-01

The influence of chromium and sodium on the nickel oxidation kinetics has been studied as a function of temperature (1373-1673 K) and oxygen activity (10-105 Pa O2), using microthermogravimetric techniques. It has been shown that the oxidation of Ni-Cr and Ni-Na alloys, like that of pure nickel, follows strictly the parabolic rate law being thus diffusion controlled. In agreement with the defect model of Ni1-yO, it has been found that the oxidation rate of the Ni-Cr alloy is higher than that of pure nickel, the reaction rate is pressure independent and the activation energy of this process is lower. This implies that the concentration of double ionized cation vacancies in a Ni1-yO-Cr2O3 solid solution is fixed on a constant level by trivalent chromium ions, substitutionally incorporated into the cation sublattice of this oxide. In the case of the Ni-Na alloy, on the other hand, the oxidation rate is lower than that of pure nickel, the activation energy is higher and the oxidation rate increases more rapidly with oxygen pressure. These results can again be explained in terms of the doping effect, by assuming that univalent sodium ions dissolve substitutionally in the cation sublattice of nickel oxide.