Fidelity of DNA Replication in Normal and Malignant Human Breast Cells

DTIC Science & Technology

1998-07-01

synthesome has been extensively demonstrated to carry out full length DNA replication in vitro, and to accurately depict the DNA replication process as it...occurs in the intact cell. By examining the fidelity of the DNA replication process carried out by the DNA synthesome from a number of breast cell types...we have demonstrated for the first time, that the cellular DNA replication machinery of malignant human breast cells is significantly more error-prone than that of non- malignant human breast cells.

Accuracy and Precision of Silicon Based Impression Media for Quantitative Areal Texture Analysis

PubMed Central

Goodall, Robert H.; Darras, Laurent P.; Purnell, Mark A.

2015-01-01

Areal surface texture analysis is becoming widespread across a diverse range of applications, from engineering to ecology. In many studies silicon based impression media are used to replicate surfaces, and the fidelity of replication defines the quality of data collected. However, while different investigators have used different impression media, the fidelity of surface replication has not been subjected to quantitative analysis based on areal texture data. Here we present the results of an analysis of the accuracy and precision with which different silicon based impression media of varying composition and viscosity replicate rough and smooth surfaces. Both accuracy and precision vary greatly between different media. High viscosity media tested show very low accuracy and precision, and most other compounds showed either the same pattern, or low accuracy and high precision, or low precision and high accuracy. Of the media tested, mid viscosity President Jet Regular Body and low viscosity President Jet Light Body (Coltène Whaledent) are the only compounds to show high levels of accuracy and precision on both surface types. Our results show that data acquired from different impression media are not comparable, supporting calls for greater standardisation of methods in areal texture analysis. PMID:25991505

Biochemical analysis of DNA polymerase η fidelity in the presence of replication protein A.

PubMed

Suarez, Samuel C; Toffton, Shannon M; McCulloch, Scott D

2014-01-01

DNA polymerase η (pol η) synthesizes across from damaged DNA templates in order to prevent deleterious consequences like replication fork collapse and double-strand breaks. This process, termed translesion synthesis (TLS), is an overall positive for the cell, as cells deficient in pol η display higher mutation rates. This outcome occurs despite the fact that the in vitro fidelity of bypass by pol η alone is moderate to low, depending on the lesion being copied. One possible means of increasing the fidelity of pol η is interaction with replication accessory proteins present at the replication fork. We have previously utilized a bacteriophage based screening system to measure the fidelity of bypass using purified proteins. Here we report on the fidelity effects of a single stranded binding protein, replication protein A (RPA), when copying the oxidative lesion 7,8-dihydro-8-oxo-guanine(8-oxoG) and the UV-induced cis-syn thymine-thymine cyclobutane pyrimidine dimer (T-T CPD). We observed no change in fidelity dependent on RPA when copying these damaged templates. This result is consistent in multiple position contexts. We previously identified single amino acid substitution mutants of pol η that have specific effects on fidelity when copying both damaged and undamaged templates. In order to confirm our results, we examined the Q38A and Y52E mutants in the same full-length construct. We again observed no difference when RPA was added to the bypass reaction, with the mutant forms of pol η displaying similar fidelity regardless of RPA status. We do, however, observe some slight effects when copying undamaged DNA, similar to those we have described previously. Our results indicate that RPA by itself does not affect pol η dependent lesion bypass fidelity when copying either 8-oxoG or T-T CPD lesions.

Sequential structures provide insights into the fidelity of RNA replication.

PubMed

Ferrer-Orta, Cristina; Arias, Armando; Pérez-Luque, Rosa; Escarmís, Cristina; Domingo, Esteban; Verdaguer, Nuria

2007-05-29

RNA virus replication is an error-prone event caused by the low fidelity of viral RNA-dependent RNA polymerases. Replication fidelity can be decreased further by the use of mutagenic ribonucleoside analogs to a point where viral genetic information can no longer be maintained. For foot-and-mouth disease virus, the antiviral analogs ribavirin and 5-fluorouracil have been shown to be mutagenic, contributing to virus extinction through lethal mutagenesis. Here, we report the x-ray structure of four elongation complexes of foot-and-mouth disease virus polymerase 3D obtained in presence of natural substrates, ATP and UTP, or mutagenic nucleotides, ribavirin triphosphate and 5-fluorouridine triphosphate with different RNAs as template-primer molecules. The ability of these complexes to synthesize RNA in crystals allowed us to capture different successive replication events and to define the critical amino acids involved in (i) the recognition and positioning of the incoming nucleotide or analog; (ii) the positioning of the acceptor base of the template strand; and (iii) the positioning of the 3'-OH group of the primer nucleotide during RNA replication. The structures identify key interactions involved in viral RNA replication and provide insights into the molecular basis of the low fidelity of viral RNA polymerases.

Influence of DNA Lesions on Polymerase-Mediated DNA Replication at Single-Molecule Resolution.

PubMed

Gahlon, Hailey L; Romano, Louis J; Rueda, David

2017-11-20

Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidelity of a DNA polymerase. In this instance, DNA polymerases are confronted with an obstacle that can result in genomic instability during replication, for example, by nucleotide misinsertion or replication fork collapse. It is important to know how DNA polymerases respond to damaged DNA substrates to understand the mechanism of mutagenesis and chemical carcinogenesis. Single-molecule techniques have helped to improve our current understanding of DNA polymerase-mediated DNA replication, as they enable the dissection of mechanistic details that can otherwise be lost in ensemble-averaged experiments. These techniques have also been used to gain a deeper understanding of how single DNA polymerases behave at the site of the damage in a DNA substrate. In this review, we evaluate single-molecule studies that have examined the interaction between DNA polymerases and damaged sites on a DNA template.

Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation.

PubMed

Li, Chen; Wang, Haiwei; Yuan, Tiangang; Woodman, Andrew; Yang, Decheng; Zhou, Guohui; Cameron, Craig E; Yu, Li

2018-05-01

Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D pol fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3D pol in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV. Copyright © 2018 Elsevier Inc. All rights reserved.

Precise replication of antireflective nanostructures from biotemplates

NASA Astrophysics Data System (ADS)

Gao, Hongjun; Liu, Zhongfan; Zhang, Jin; Zhang, Guoming; Xie, Guoyong

2007-03-01

The authors report herein a new type of nanonipple structures on the cicada's eye and the direct structural replication of the complex micro- and nanostructures for potential functional emulation. A two-step direct molding process is developed to replicate these natural micro- and nanostructures using epoxy resin with high fidelity, which demonstrates a general way of fabricating functional nanostructures by direct replication of natural biotemplates via a suitable physicochemical process. Measurements of spectral reflectance showed that this kind of replicated nanostructure has remarkable antireflective property, suggestive of its potential applications to optical devices.

Replicating an Intervention: The Tension between Fidelity and Adaptation

ERIC Educational Resources Information Center

Morrison, Diane M.; Hoppe, Marilyn J.; Gillmore, Mary Rogers; Kluver, Carisa; Higa, Darrel; Wells, Elizabeth A.

2009-01-01

Increased awareness of the importance of tailoring interventions to participants' cultures has focused attention on the limited generalizability of a single test of an intervention to determine efficacy. Adaptation is often necessary to replicate interventions across cultures. This produces a tension between fidelity to the original intervention…

Changes in protein domains outside the catalytic site of the bacteriophage Qβ replicase reduce the mutagenic effect of 5-azacytidine.

PubMed

Cabanillas, Laura; Sanjuán, Rafael; Lázaro, Ester

2014-09-01

The high genetic heterogeneity and great adaptability of RNA viruses are ultimately caused by the low replication fidelity of their polymerases. However, single amino acid substitutions that modify replication fidelity can evolve in response to mutagenic treatments with nucleoside analogues. Here, we investigated how two independent mutants of the bacteriophage Qβ replicase (Thr210Ala and Tyr410His) reduce sensitivity to the nucleoside analogue 5-azacytidine (AZC). Despite being located outside the catalytic site, both mutants reduced the mutation frequency in the presence of the drug. However, they did not modify the type of AZC-induced substitutions, which was mediated mainly by ambiguous base pairing of the analogue with purines. Furthermore, the Thr210Ala and Tyr410His substitutions had little or no effect on replication fidelity in untreated viruses. Also, both substitutions were costly in the absence of AZC or when the action of the drug was suppressed by adding an excess of natural pyrimidines (uridine or cytosine). Overall, the phenotypic properties of these two mutants were highly convergent, despite the mutations being located in different domains of the Qβ replicase. This suggests that treatment with a given nucleoside analogue tends to select for a unique functional response in the viral replicase. In the last years, artificial increase of the replication error rate has been proposed as an antiviral therapy. In this study, we investigated the mechanisms by which two substitutions in the Qβ replicase confer partial resistance to the mutagenic nucleoside analogue AZC. As opposed to previous work with animal viruses, where different mutations selected sequentially conferred nucleoside analogue resistance through different mechanisms, our results suggest that there are few or no alternative AZC resistance phenotypes in Qβ. Also, despite resistance mutations being highly costly in the absence of the drug, there was no sequential fixation of secondary mutations. Bacteriophage Qβ is the virus with the highest reported mutation rate, which should make it particularly sensitive to nucleoside analogue treatments, probably favoring resistance mutations even if they incur high costs. The results are also relevant for understanding the possible pathways by which fidelity of the replication machinery can be modified. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Thermodynamic Basis for the Emergence of Genomes during Prebiotic Evolution

PubMed Central

Woo, Hyung-June; Vijaya Satya, Ravi; Reifman, Jaques

2012-01-01

The RNA world hypothesis views modern organisms as descendants of RNA molecules. The earliest RNA molecules must have been random sequences, from which the first genomes that coded for polymerase ribozymes emerged. The quasispecies theory by Eigen predicts the existence of an error threshold limiting genomic stability during such transitions, but does not address the spontaneity of changes. Following a recent theoretical approach, we applied the quasispecies theory combined with kinetic/thermodynamic descriptions of RNA replication to analyze the collective behavior of RNA replicators based on known experimental kinetics data. We find that, with increasing fidelity (relative rate of base-extension for Watson-Crick versus mismatched base pairs), replications without enzymes, with ribozymes, and with protein-based polymerases are above, near, and below a critical point, respectively. The prebiotic evolution therefore must have crossed this critical region. Over large regions of the phase diagram, fitness increases with increasing fidelity, biasing random drifts in sequence space toward ‘crystallization.’ This region encloses the experimental nonenzymatic fidelity value, favoring evolutions toward polymerase sequences with ever higher fidelity, despite error rates above the error catastrophe threshold. Our work shows that experimentally characterized kinetics and thermodynamics of RNA replication allow us to determine the physicochemical conditions required for the spontaneous crystallization of biological information. Our findings also suggest that among many potential oligomers capable of templated replication, RNAs may have evolved to form prebiotic genomes due to the value of their nonenzymatic fidelity. PMID:22693440

Molecular replication

NASA Technical Reports Server (NTRS)

Orgel, Leslie E.

1992-01-01

Recent experiments demonstrating nonenzymatic replication in molecular systems are reviewed. The difficulties facing nonenzymatic replication are discussed along with specificity, fidelity, and mutation in nonenzymatic replication. The prospects for research in this area are considered.

Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy

PubMed Central

Kautz, Tiffany F; Guerbois, Mathilde; Khanipov, Kamil; Yun, Ruimei; Warmbrod, Kelsey L; Fofanov, Yuriy; Weaver, Scott C; Forrester, Naomi L

2018-01-01

Abstract During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For live-attenuated vaccines, this has implications for stability, as replication may result in mutations that either restore the wild-type phenotype via reversion or compensate for the attenuating mutations by increasing virulence (pseudoreversion). Recent studies have demonstrated that altering the mutation rate of an RNA virus is an effective attenuation tool. To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Next generation sequencing after passage in the presence of mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to have decreased replication fidelity, while a second mutant, TC-83 4x displayed no change in fidelity, but shared many phenotypic characteristics with TC-83 3x. Both mutants exhibited increased, albeit inconsistent attenuation in an infant mouse model, as well as increased immunogenicity and complete protection against lethal challenge of an adult murine model compared with the parent TC-83. During serial passaging in a highly permissive model, the mutants increased in virulence but remained less virulent than the parent TC-83. These results suggest that the incorporation of low-fidelity mutations into the RdRp of live-attenuated vaccines for RNA viruses can confer increased immunogenicity whilst showing some evidence of increased attenuation. However, while in theory such constructs may result in more effective vaccines, the instability of the vaccine phenotype decreases the likelihood of this being an effective vaccine strategy. PMID:29593882

Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer

DTIC Science & Technology

2015-12-01

normal DNA synthesis. In contrast, pol eta shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties...are consistent with a pro- mutagenic role for pol eta when replicating this DNA lesion under cellular conditions. Studies with modified nucleotide...analogs indicate that pol eta relies heavily on hydrogen-bonding interactions during normal and translesion synthesis. However, some nucleobase

Sustaining Fidelity Following the Nationwide PMTO™ Implementation in Norway

PubMed Central

Forgatch, Marion S.; DeGarmo, David S.

2011-01-01

This report describes three studies from the nationwide Norwegian implementation of Parent Management Training – Oregon Model (PMTO™), an empirically supported treatment for families of children with behavior problems (Forgatch and Patterson 2010). Separate stages of the implementation were evaluated using a fidelity measure based on direct observation of intervention sessions. Study 1 assessed growth in fidelity observed early, mid, and late in the training of a group of practitioners. We hypothesized increased fidelity and decreased variability in practice. Study 2 evaluated method fidelity over the course of three generations of practitioners trained in PMTO. Generation 1 (G1) was trained by the PMTO developer/purveyors; Generation 2 (G2) was trained by selected G1 Norwegian trainers; and Generation 3 (G3) was trained by G1 and G2 trainers. We hypothesized decrease in fidelity with each generation. Study 3 tested the predictive validity of fidelity in a cross-cultural replication, hypothesizing that higher fidelity scores would correlate with improved parenting practices observed in parent-child interactions before and after treatment. In Study 1, trainees' performance improved and became more homogeneous as predicted. In Study 2, a small decline in fidelity followed the transfer from the purveyor trainers to Norwegian trainers in G2, but G3 scores were equivalent to those attained by G1. Thus, the hypothesis was not fully supported. Finally, the FIMP validity model replicated; PMTO fidelity significantly contributed to improvements in parenting practices from pre- to post-treatment. The data indicate that PMTO was transferred successfully to Norwegian implementation with sustained fidelity and cross-cultural generalization. PMID:21671090

The putative hydrolase YycJ (WalJ) affects the coordination of cell division with DNA replication in Bacillus subtilis and may play a conserved role in cell wall metabolism.

PubMed

Biller, Steven J; Wayne, Kyle J; Winkler, Malcolm E; Burkholder, William F

2011-02-01

Bacteria must accurately replicate and segregate their genetic information to ensure the production of viable daughter cells. The high fidelity of chromosome partitioning is achieved through mechanisms that coordinate cell division with DNA replication. We report that YycJ (WalJ), a predicted member of the metallo-β-lactamase superfamily found in most low-G+C Gram-positive bacteria, contributes to the fidelity of cell division in Bacillus subtilis. B. subtilis ΔwalJ (ΔwalJ(Bsu)) mutants divide over unsegregated chromosomes more frequently than wild-type cells, and this phenotype is exacerbated when DNA replication is inhibited. Two lines of evidence suggest that WalJ(Bsu) and its ortholog in the Gram-positive pathogen Streptococcus pneumoniae, WalJ(Spn) (VicX), play a role in cell wall metabolism: (i) strains of B. subtilis and S. pneumoniae lacking walJ exhibit increased sensitivity to a narrow spectrum of cephalosporin antibiotics, and (ii) reducing the expression of a two-component system that regulates genes involved in cell wall metabolism, WalRK (YycFG), renders walJ essential for growth in B. subtilis, as observed previously with S. pneumoniae. Together, these results suggest that the enzymatic activity of WalJ directly or indirectly affects cell wall metabolism and is required for accurate coordination of cell division with DNA replication.

Chromium reduces the in vitro activity and fidelity of DNA replication mediated by the human cell DNA synthesome

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

Dai Heqiao; Liu Jianying; Malkas, Linda H.

2009-04-15

Hexavalent chromium Cr(VI) is known to be a carcinogenic metal ion, with a complicated mechanism of action. It can be found within our environment in soil and water contaminated by manufacturing processes. Cr(VI) ion is readily taken up by cells, and is recognized to be both genotoxic and cytotoxic; following its reduction to the stable trivalent form of the ion, chromium(Cr(III)), within cells. This form of the ion is known to impede the activity of cellular DNA polymerase and polymerase-mediated DNA replication. Here, we report the effects of chromium on the activity and fidelity of the DNA replication process mediatedmore » by the human cell DNA synthesome. The DNA synthesome is a functional multiprotein complex that is fully competent to carry-out each phase of the DNA replication process. The IC{sub 50} of Cr(III) toward the activity of DNA synthesome-associated DNA polymerases {alpha}, {delta} and {epsilon} is 15, 45 and 125 {mu}M, respectively. Cr(III) inhibits synthesome-mediated DNA synthesis (IC{sub 50} = 88 {mu}M), and significantly reduces the fidelity of synthesome-mediated DNA replication. The mutation frequency induced by the different concentrations of Cr(III) ion used in our assays ranges from 2-13 fold higher than that which occurs spontaneously, and the types of mutations include single nucleotide substitutions, insertions, and deletions. Single nucleotide substitutions are the predominant type of mutation, and they occur primarily at GC base-pairs. Cr(III) ion produces a lower number of transition and a higher number of transversion mutations than occur spontaneously. Unlike Cr(III), Cr(VI) ion has little effect on the in vitro DNA synthetic activity and fidelity of the DNA synthesome, but does significantly inhibit DNA synthesis in intact cells. Cell growth and proliferation is also arrested by increasing concentrations of Cr(VI) ion. Our studies provide evidence indicating that the chromium ion induced decrease in the fidelity and activity of synthesome mediated DNA replication correlates with the genotoxic and cytotoxic effects of this metal ion; and promotes cell killing via inhibition of the DNA polymerase activity mediating the DNA replication and repair processes utilized by human cells.« less

Chromium reduces the in vitro activity and fidelity of DNA replication mediated by the human cell DNA synthesome

PubMed Central

Dai, Heqiao; Liu, Jianying; Malkas, Linda H.; Catalano, Jennifer; Alagharu, Srilakshmi; Hickey, Robert J.

2009-01-01

Hexavalent chromium Cr(VI) is known to be a carcinogenic metal ion, with a complicated mechanism of action. It can be found within our environment in soil and water contaminated by manufacturing processes. Cr(VI) ion is readily taken up by cells, and is recognized to be both genotoxic and cytotoxic; following its reduction to the stable trivalent form of the ion, chromium(Cr(III)), within cells. This form of the ion is known to impede the activity of cellular DNA polymerase and polymerase-mediated DNA replication. Here, we report the effects of chromium on the activity and fidelity of the DNA replication process mediated by the human cell DNA synthesome. The DNA synthesome is a functional multiprotein complex that is fully competent to carry-out each phase of the DNA replication process. The IC50 of Cr(III) toward the activity of DNA synthesome-associated DNA polymerases α, δ and ε is 15, 45 and 125 μM, respectively. Cr(III) inhibits synthesome-mediated DNA synthesis (IC50 =88 μM), and significantly reduces the fidelity of synthesome-mediated DNA replication. The mutation frequency induced by the different concentrations of Cr(III) ion used in our assays ranges from 2–13 fold higher than that which occurs spontaneously, and the types of mutations include single nucleotide substitutions, insertions, and deletions. Single nucleotide substitutions are the predominant type of mutation, and they occur primarily at GC base-pairs. Cr(III) ion produces a lower number of transition and a higher number of transversion mutations than occur spontaneously. Unlike Cr (III), Cr(VI) ion has little effect on the in vitro DNA synthetic activity and fidelity of the DNA synthesome, but does significantly inhibit DNA synthesis in intact cells. Cell growth and proliferation is also arrested by increasing concentrations of Cr(VI) ion. Our studies provide evidence indicating that the chromium ion induced decrease in the fidelity and activity of synthesome mediated DNA replication correlates with the genotoxic and cytotoxic effects of this metal ion; and promotes cell killing via inhibition of the DNA polymerase activity mediating the DNA replication and repair processes utilized by human cells. PMID:19371627

Enquire within: cultural evolution and cognitive science.

PubMed

Heyes, Cecilia

2018-04-05

Cultural evolution and cognitive science need each other. Cultural evolution needs cognitive science to find out whether the conditions necessary for Darwinian evolution are met in the cultural domain. Cognitive science needs cultural evolution to explain the origins of distinctively human cognitive processes. Focusing on the first question, I argue that cultural evolutionists can get empirical traction on third-way cultural selection by rooting the distinction between replication and reconstruction, two modes of cultural inheritance, in the distinction between System 1 and System 2 cognitive processes. This move suggests that cultural epidemiologists are right in thinking that replication has higher fidelity than reconstruction, and replication processes are not genetic adaptations for culture, but wrong to assume that replication is rare. If replication is not rare, an important requirement for third-way cultural selection, one-shot fidelity , is likely to be met. However, there are other requirements, overlooked by dual-inheritance theorists when they conflate strong (Darwinian) and weak (choice) senses of 'cultural selection', including dumb choices and recurrent fidelity In a second excursion into cognitive science, I argue that these requirements can be met by metacognitive social learning strategies , and trace the origins of these distinctively human cognitive processes to cultural evolution. Like other forms of cultural learning, they are not cognitive instincts but cognitive gadgets.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'. © 2018 The Author(s).

DNA-directed mutations. Leading and lagging strand specificity

NASA Technical Reports Server (NTRS)

Sinden, R. R.; Hashem, V. I.; Rosche, W. A.

1999-01-01

The fidelity of replication has evolved to reproduce B-form DNA accurately, while allowing a low frequency of mutation. The fidelity of replication can be compromised, however, by defined order sequence DNA (dosDNA) that can adopt unusual or non B-DNA conformations. These alternative DNA conformations, including hairpins, cruciforms, triplex DNAs, and slipped-strand structures, may affect enzyme-template interactions that potentially lead to mutations. To analyze the effect of dosDNA elements on spontaneous mutagenesis, various mutational inserts containing inverted repeats or direct repeats were cloned in a plasmid containing a unidirectional origin of replication and a selectable marker for the mutation. This system allows for analysis of mutational events that are specific for the leading or lagging strands during DNA replication in Escherichia coli. Deletions between direct repeats, involving misalignment stabilized by DNA secondary structure, occurred preferentially on the lagging strand. Intermolecular strand switch events, correcting quasipalindromes to perfect inverted repeats, occurred preferentially during replication of the leading strand.

The fidelity of replication of the three-base-pair set adenine/thymine, hypoxanthine/cytosine and 6-thiopurine/5-methyl-2-pyrimidinone with T7 DNA polymerase

PubMed Central

2004-01-01

With the goal of constructing a genetic alphabet consisting of a set of three base pairs, the fidelity of replication of the three base pairs TH (5-methyl-2-pyrimidinone)/HS (6-thiopurine; thiohypoxanthine), C/H (hypoxanthine) and T/A was evaluated using T7 DNA polymerase, a polymerase with a strong 3′→5′ exonuclease activity. An evaluation of the suitability of a new base pair for replication should include both the contribution of the fidelity of a polymerase activity and the contribution of proofreading by a 3′→5′ exonuclease activity. Using a steady-state kinetics method that included the contribution of the 3′→5′ exonuclease activity, the fidelity of replication was determined. The method determined the ratio of the apparent rate constant for the addition of a deoxynucleotide to the primer across from a template base by the polymerase activity and the rate constant for removal of the added deoxynucleotide from the primer by the 3′→5′ exonuclease activity. This ratio was designated the eni (efficiency of net incorporation). The eni of the base pair C/H was equal to or greater than the eni of T/A. The eni of the base pair TH/HS was 0.1 times that of A/T for TH in the template and 0.01 times that of A/T for HS in the template. The ratio of the eni of a mismatched deoxynucleotide to the eni of a matched deoxynucleotide was a measure of the error frequency. The error frequencies were as follows: thymine or TH opposite a template hypoxanthine, 2×10−6; HS opposite a template cytosine, <3×10−4. The remaining 24 mismatched combinations of bases gave no detectable net incorporation. Two mismatches, hypoxanthine opposite a template thymine or a template TH, showed trace incorporation in the presence of a standard dNTP complementary to the next template base. T7 DNA polymerase extended the primer beyond each of the matched base pairs of the set. The level of fidelity of replication of the three base pairs with T7 DNA polymerase suggests that they are adequate for a three-base-pair alphabet for DNA replication. PMID:15078225

DNA Replication Fidelity in the Mycobacterium tuberculosis Complex.

PubMed

Warner, Digby F; Rock, Jeremy M; Fortune, Sarah M; Mizrahi, Valerie

2017-01-01

Mycobacterium tuberculosis is genetically isolated, with no evidence for horizontal gene transfer or the acquisition of episomal genetic information in the modern evolution of strains of the Mycobacterium tuberculosis complex. When considered in the context of the specific features of the disease M. tuberculosis causes (e.g., transmission via cough aerosol, replication within professional phagocytes, subclinical persistence, and stimulation of a destructive immune pathology), this implies that to understand the mechanisms ensuring preservation of genomic integrity in infecting mycobacterial populations is to understand the source of genetic variation, including the emergence of microdiverse sub-populations that may be linked to the acquisition of drug resistance. In this chapter, we focus on mechanisms involved in maintaining DNA replication fidelity in M. tuberculosis, and consider the potential to target components of the DNA replication machinery as part of novel therapeutic regimens designed to curb the emerging threat of drug-resistance.

Fidelity of DNA Replication in Normal and Malignant Human Brest Cells.

DTIC Science & Technology

1995-08-31

cellular DNA replication machinery, we have initiated experiments that utilize a multiprotein DNA replication complex (MRC) isolated from breast cancer...gene in an in vitro DNA replication assay. By utilizing the target gene in a bacterial mutant selection assay we have begun to determine the...frequency with which mutational sequence errors occur as a result of the in vitro DNA replication mediated by the breast cancer cell MRC and the normal breast

Time to unravel the conceptual confusion of authenticity and fidelity and their contribution to learning within simulation-based nurse education. A discussion paper.

PubMed

Bland, Andrew J; Topping, Annie; Tobbell, Jane

2014-07-01

High-fidelity patient simulation is a method of education increasingly utilised by educators of nursing to provide authentic learning experiences. Fidelity and authenticity, however, are not conceptually equivalent. Whilst fidelity is important when striving to replicate a life experience such as clinical practice, authenticity can be produced with low fidelity. A challenge for educators of undergraduate nursing is to ensure authentic representation of the clinical situation which is a core component for potential success. What is less clear is the relationship between fidelity and authenticity in the context of simulation based learning. Authenticity does not automatically follow fidelity and as a result, educators of nursing cannot assume that embracing the latest technology-based educational tools will in isolation provide a learning environment perceived authentic by the learner. As nursing education programmes increasingly adopt simulators that offer the possibility of representing authentic real world situations, there is an urgency to better articulate and understand the terms fidelity and authenticity. Without such understanding there is a real danger that simulation as a teaching and learning resource in nurse education will never reach its potential and be misunderstood, creating a potential barrier to learning. This paper examines current literature to promote discussion within nurse education, concluding that authenticity in the context of simulation-based learning is complex, relying on far more than engineered fidelity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fast and cheap fabrication of molding tools for polymer replication

NASA Astrophysics Data System (ADS)

Richter, Christiane; Kirschner, Nadine; Worgull, Matthias; Rapp, Bastian E.

2017-02-01

Polymer replication is a prerequisite for low-cost microstructure components for consumer and end user market. The production of cost-effective microstructure in polymers requires metal molding tools which are often fabricated by direct structuring methods like milling or laser machining both of which are time-consuming and cost-intensive. We present an alternative fabrication method based on replication processes which allows the cheap ( 50 €) and fast ( 12 h) replication of complex microstructures into metal. The process comprises three steps: 1. Generation of the microstructure in a photoresist via lithography. 2. Casting of the structure into a high-temperature silicone which serves as original mold for creation of the metal molding tool. 3. Melting of an eutectic alloy of Sn, Ag and Cu under light pressure directly inside of the silicone within an oven. After cooling to room temperature the metal molding tool can be used for polymer replication into conventional thermoplastic polymers. As a first example we structured polymethylmethacrylate (PMMA) foils with a thickness of 1 mm via hot embossing and feature sizes of 100 μm could be replicated with high fidelity.

Insect Cell-Derived Cofactors Become Fully Functional after Proteinase K and Heat Treatment for High-Fidelity Amplification of Glycosylphosphatidylinositol-Anchored Recombinant Scrapie and BSE Prion Proteins

PubMed Central

Imamura, Morikazu; Kato, Nobuko; Okada, Hiroyuki; Yoshioka, Miyako; Iwamaru, Yoshifumi; Shimizu, Yoshihisa; Mohri, Shirou; Yokoyama, Takashi; Murayama, Yuichi

2013-01-01

The central event in prion infection is the conformational conversion of host-encoded cellular prion protein (PrPC) into the pathogenic isoform (PrPSc). Diverse mammalian species possess the cofactors required for in vitro replication of PrPSc by protein-misfolding cyclic amplification (PMCA), but lower organisms, such as bacteria, yeasts, and insects, reportedly lack the essential cofactors. Various cellular components, such as RNA, lipids, and other identified cofactor molecules, are commonly distributed in both eukaryotes and prokaryotes, but the reasons for the absence of cofactor activity in lower organisms remain to be elucidated. Previously, we reported that brain-derived factors were necessary for the in vitro replication of glycosylphosphatidylinositol-anchored baculovirus-derived recombinant PrP (Bac-PrP). Here, we demonstrate that following protease digestion and heat treatment, insect cell lysates had the functional cofactor activity required for Bac-PrP replication by PMCA. Mammalian PrPSc seeds and Bac-PrPSc generated by PMCA using Bac-PrP and insect cell-derived cofactors showed similar pathogenicity and produced very similar lesions in the brains of inoculated mice. These results suggested that the essential cofactors required for the high-fidelity replication of mammalian PrPSc were present in the insect cells but that the cofactor activity was masked or inhibited in the native state. We suggest that not only RNA, but also DNA, are the key components of PMCA, although other cellular factors were necessary for the expression of the cofactor activity of nucleic acids. PMCA using only insect cell-derived substances (iPMCA) was highly useful for the ultrasensitive detection of PrPSc of some prion strains. PMID:24367521

Epistatic Interactions within the Influenza A Virus Polymerase Complex Mediate Mutagen Resistance and Replication Fidelity

PubMed Central

Pauly, Matthew D.; Lyons, Daniel M.; Fitzsimmons, William J.

2017-01-01

ABSTRACT Lethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal mutagenesis of influenza A virus using three nucleoside analogs as well as the virus’s high genetic barrier to mutagen resistance. Here, we investigate the mutagen-resistant phenotypes of mutations that were enriched in drug-treated populations. We find that PB1 T123A has higher replicative fitness than the wild type, PR8, and maintains its level of genome production during 5-fluorouracil (2,4-dihydroxy-5-fluoropyrimidine) treatment. Surprisingly, this mutagen-resistant variant also has an increased baseline rate of C-to-U and G-to-A mutations. A second drug-selected mutation, PA T97I, interacts epistatically with PB1 T123A to mediate high-level mutagen resistance, predominantly by limiting the inhibitory effect of nucleosides on polymerase activity. Consistent with the importance of epistatic interactions in the influenza virus polymerase, our data suggest that nucleoside analog resistance and replication fidelity are strain dependent. Two previously identified ribavirin {1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide} resistance mutations, PB1 V43I and PB1 D27N, do not confer drug resistance in the PR8 background, and the PR8-PB1 V43I polymerase exhibits a normal baseline mutation rate. Our results highlight the genetic complexity of the influenza A virus polymerase and demonstrate that increased replicative capacity is a mechanism by which an RNA virus can counter the negative effects of elevated mutation rates. IMPORTANCE RNA viruses exist as genetically diverse populations. This standing genetic diversity gives them the potential to adapt rapidly, evolve resistance to antiviral therapeutics, and evade immune responses. Viral mutants with altered mutation rates or mutational tolerance have provided insights into how genetic diversity arises and how it affects the behavior of RNA viruses. To this end, we identified variants within the polymerase complex of influenza virus that are able to tolerate drug-mediated increases in viral mutation rates. We find that drug resistance is highly dependent on interactions among mutations in the polymerase complex. In contrast to other viruses, influenza virus counters the effect of higher mutation rates primarily by maintaining high levels of genome replication. These findings suggest the importance of maintaining large population sizes for viruses with high mutation rates and show that multiple proteins can affect both mutation rate and genome synthesis. PMID:28815216

Organic preservation of fossil musculature with ultracellular detail

PubMed Central

McNamara, Maria; Orr, Patrick J.; Kearns, Stuart L.; Alcalá, Luis; Anadón, Pere; Peñalver-Mollá, Enrique

2010-01-01

The very labile (decay-prone), non-biomineralized, tissues of organisms are rarely fossilized. Occurrences thereof are invaluable supplements to a body fossil record dominated by biomineralized tissues, which alone are extremely unrepresentative of diversity in modern and ancient ecosystems. Fossil examples of extremely labile tissues (e.g. muscle) that exhibit a high degree of morphological fidelity are almost invariably replicated by inorganic compounds such as calcium phosphate. There is no consensus as to whether such tissues can be preserved with similar morphological fidelity as organic remains, except when enclosed inside amber. Here, we report fossilized musculature from an approximately 18 Myr old salamander from lacustrine sediments of Ribesalbes, Spain. The muscle is preserved organically, in three dimensions, and with the highest fidelity of morphological preservation yet documented from the fossil record. Preserved ultrastructural details include myofilaments, endomysium, layering within the sarcolemma, and endomysial circulatory vessels infilled with blood. Slight differences between the fossil tissues and their counterparts in extant amphibians reflect limited degradation during fossilization. Our results provide unequivocal evidence that high-fidelity organic preservation of extremely labile tissues is not only feasible, but likely to be common. This is supported by the discovery of similarly preserved tissues in the Eocene Grube Messel biota. PMID:19828545

Influence of oxidized purine processing on strand directionality of mismatch repair.

PubMed

Repmann, Simone; Olivera-Harris, Maite; Jiricny, Josef

2015-04-17

Replicative DNA polymerases are high fidelity enzymes that misincorporate nucleotides into nascent DNA with a frequency lower than [1/10(5)], and this precision is improved to about [1/10(7)] by their proofreading activity. Because this fidelity is insufficient to replicate most genomes without error, nature evolved postreplicative mismatch repair (MMR), which improves the fidelity of DNA replication by up to 3 orders of magnitude through correcting biosynthetic errors that escaped proofreading. MMR must be able to recognize non-Watson-Crick base pairs and excise the misincorporated nucleotides from the nascent DNA strand, which carries by definition the erroneous genetic information. In eukaryotes, MMR is believed to be directed to the nascent strand by preexisting discontinuities such as gaps between Okazaki fragments in the lagging strand or breaks in the leading strand generated by the mismatch-activated endonuclease of the MutL homologs PMS1 in yeast and PMS2 in vertebrates. We recently demonstrated that the eukaryotic MMR machinery can make use also of strand breaks arising during excision of uracils or ribonucleotides from DNA. We now show that intermediates of MutY homolog-dependent excision of adenines mispaired with 8-oxoguanine (G(O)) also act as MMR initiation sites in extracts of human cells or Xenopus laevis eggs. Unexpectedly, G(O)/C pairs were not processed in these extracts and failed to affect MMR directionality, but extracts supplemented with exogenous 8-oxoguanine DNA glycosylase (OGG1) did so. Because OGG1-mediated excision of G(O) might misdirect MMR to the template strand, our findings suggest that OGG1 activity might be inhibited during MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural Mechanism of Replication Stalling on a Bulky Amino-Polycyclic Aromatic Hydrocarbon DNA Adduct by a Y Family DNA Polymerase

PubMed Central

Kirouac, Kevin N.; Basu, Ashis K.; Ling, Hong

2013-01-01

Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the detrimental health effects of environmental pollution. These hydrophobic compounds metabolize to reactive species and attach to DNA producing bulky lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The bulky adducts block DNA replication by high-fidelity polymerases and compromise replication fidelities and efficiencies by specialized lesion bypass polymerases. Here we present three crystal structures of the DNA polymerase Dpo4, a model translesion DNA polymerase of the Y family, in complex with APG-lesion-containing DNA in pre-insertion and extension stages. APG is captured in two conformations in the pre-insertion complex; one is highly exposed to the solvent, whereas the other is harbored in a shallow cleft between the finger and unique Y family little finger domain. In contrast, APG is in a single conformation at the extension stage, in which the pyrene ring is sandwiched between the little finger domain and a base from the turning back single-stranded template strand. Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA structure at the extension stage. The unique APG DNA conformations in Dpo4 inhibit DNA translocation through the polymerase active site for APG bypass. We also modeled an insertion complex that illustrates a solvent-exposed pyrene ring contributing to an unstable insertion state. The structural work combined with our lesion replication assays provides a novel structural mechanism on bypass of DNA adducts containing polycyclic aromatic hydrocarbon moieties. PMID:23876706

Structural mechanism of replication stalling on a bulky amino-polycyclic aromatic hydrocarbon DNA adduct by a y family DNA polymerase.

PubMed

Kirouac, Kevin N; Basu, Ashis K; Ling, Hong

2013-11-15

Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the detrimental health effects of environmental pollution. These hydrophobic compounds metabolize to reactive species and attach to DNA producing bulky lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The bulky adducts block DNA replication by high-fidelity polymerases and compromise replication fidelities and efficiencies by specialized lesion bypass polymerases. Here we present three crystal structures of the DNA polymerase Dpo4, a model translesion DNA polymerase of the Y family, in complex with APG-lesion-containing DNA in pre-insertion and extension stages. APG is captured in two conformations in the pre-insertion complex; one is highly exposed to the solvent, whereas the other is harbored in a shallow cleft between the finger and unique Y family little finger domain. In contrast, APG is in a single conformation at the extension stage, in which the pyrene ring is sandwiched between the little finger domain and a base from the turning back single-stranded template strand. Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA structure at the extension stage. The unique APG DNA conformations in Dpo4 inhibit DNA translocation through the polymerase active site for APG bypass. We also modeled an insertion complex that illustrates a solvent-exposed pyrene ring contributing to an unstable insertion state. The structural work combined with our lesion replication assays provides a novel structural mechanism on bypass of DNA adducts containing polycyclic aromatic hydrocarbon moieties. © 2013.

Proofreading of DNA polymerase: a new kinetic model with higher-order terminal effects

NASA Astrophysics Data System (ADS)

Song, Yong-Shun; Shu, Yao-Gen; Zhou, Xin; Ou-Yang, Zhong-Can; Li, Ming

2017-01-01

The fidelity of DNA replication by DNA polymerase (DNAP) has long been an important issue in biology. While numerous experiments have revealed details of the molecular structure and working mechanism of DNAP which consists of both a polymerase site and an exonuclease (proofreading) site, there were quite a few theoretical studies on the fidelity issue. The first model which explicitly considered both sites was proposed in the 1970s and the basic idea was widely accepted by later models. However, all these models did not systematically investigate the dominant factor on DNAP fidelity, i.e. the higher-order terminal effects through which the polymerization pathway and the proofreading pathway coordinate to achieve high fidelity. In this paper, we propose a new and comprehensive kinetic model of DNAP based on some recent experimental observations, which includes previous models as special cases. We present a rigorous and unified treatment of the corresponding steady-state kinetic equations of any-order terminal effects, and derive analytical expressions for fidelity in terms of kinetic parameters under bio-relevant conditions. These expressions offer new insights on how the higher-order terminal effects contribute substantially to the fidelity in an order-by-order way, and also show that the polymerization-and-proofreading mechanism is dominated only by very few key parameters. We then apply these results to calculate the fidelity of some real DNAPs, which are in good agreements with previous intuitive estimates given by experimentalists.

Extraordinary genome stability in the ciliate Paramecium tetraurelia

PubMed Central

Sung, Way; Tucker, Abraham E.; Doak, Thomas G.; Choi, Eunjin; Thomas, W. Kelley; Lynch, Michael

2012-01-01

Mutation plays a central role in all evolutionary processes and is also the basis of genetic disorders. Established base-substitution mutation rates in eukaryotes range between ∼5 × 10−10 and 5 × 10−8 per site per generation, but here we report a genome-wide estimate for Paramecium tetraurelia that is more than an order of magnitude lower than any previous eukaryotic estimate. Nevertheless, when the mutation rate per cell division is extrapolated to the length of the sexual cycle for this protist, the measure obtained is comparable to that for multicellular species with similar genome sizes. Because Paramecium has a transcriptionally silent germ-line nucleus, these results are consistent with the hypothesis that natural selection operates on the cumulative germ-line replication fidelity per episode of somatic gene expression, with the germ-line mutation rate per cell division evolving downward to the lower barrier imposed by random genetic drift. We observe ciliate-specific modifications of widely conserved amino acid sites in DNA polymerases as one potential explanation for unusually high levels of replication fidelity. PMID:23129619

A New Real - Time Fault Detection Methodology for Systems Under Test. Phase 1

NASA Technical Reports Server (NTRS)

Johnson, Roger W.; Jayaram, Sanjay; Hull, Richard A.

1998-01-01

The purpose of this research is focussed on the identification/demonstration of critical technology innovations that will be applied to various applications viz. Detection of automated machine Health Monitoring (BM, real-time data analysis and control of Systems Under Test (SUT). This new innovation using a High Fidelity Dynamic Model-based Simulation (BFDMS) approach will be used to implement a real-time monitoring, Test and Evaluation (T&E) methodology including the transient behavior of the system under test. The unique element of this process control technique is the use of high fidelity, computer generated dynamic models to replicate the behavior of actual Systems Under Test (SUT). It will provide a dynamic simulation capability that becomes the reference truth model, from which comparisons are made with the actual raw/conditioned data from the test elements.

Factors contributing to intervention fidelity in a multi-site chronic disease self-management program.

PubMed

Perrin, Karen M; Burke, Somer Goad; O'Connor, Danielle; Walby, Gary; Shippey, Claire; Pitt, Seraphine; McDermott, Robert J; Forthofer, Melinda S

2006-10-26

Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity.

Collaborative Strategic Reading: Replications with Consideration of the Role of Fidelity

ERIC Educational Resources Information Center

Vaughn, Sharon; Roberts, Greg; Reutebuch, Colleen

2013-01-01

Collaborative Strategic Reading (CSR) is a multicomponent reading intervention aimed at improving students' text comprehension. Two 1-year randomized controlled trials were conducted to determine the efficacy of CSR with seventh and eighth grade students. The Year 2 replication study was identical to the original Year 1 study except that the…

Nonequilibrium Phase Transitions Associated with DNA Replication

DTIC Science & Technology

2011-02-11

bioanalysis.org [1] R. Dawkins , The Selfish Gene (Oxford, New York, 1989). [2] F. Jülicher, A. Ajdari, and J. Prost, Rev. Mod. Phys. 69, 1269 (1997). [3...fidelity above a threshold. DOI: 10.1103/PhysRevLett.106.060601 PACS numbers: 05.70.Ln, 87.10.Mn, 87.14.gk The replication of genes by biological

Fidelity of DNA Replication in Normal and Malignant Human Breast Cells.

DTIC Science & Technology

1997-08-01

enzyme) into the multiple cloning site (MCS). This template will not only replicate inside a mammalian cell (utilizing the E-B virus origin), and...Maniatis, T. Commonly used techniques in molecular cloning . In: Molecular cloning : REFERENCES a laboratory manual, 2nd edition. Cold Spring Harbor...A vatit"Y Of DNA synthesis and the typt of DNA replica~tion Products " celular prca including DNA rsplicatlon. DNA repsair. R~NA formed in experiments

[Development of Nanotechnology for X-Ray Astronomy Instrumentation

NASA Technical Reports Server (NTRS)

Schattenburg, Mark L.

2004-01-01

This Research Grant provides support for development of nanotechnology for x-ray astronomy instrumentation. MIT has made significant progress in several development areas. In the last year we have made considerable progress in demonstrating the high-fidelity patterning and replication of x-ray reflection gratings. We developed a process for fabricating blazed gratings in silicon with extremely smooth and sharp sawtooth profiles, and developed a nanoimprint process for replication. We also developed sophisticated new fixturing for holding thin optics during metrology without causing distortion. We developed a new image processing algorithm for our Shack-Hartmann tool that uses Zernike polynomials. This has resulted in much more accurate and repeatable measurements on thin optics.

FANCJ suppresses microsatellite instability and lymphomagenesis independent of the Fanconi anemia pathway.

PubMed

Matsuzaki, Kenichiro; Borel, Valerie; Adelman, Carrie A; Schindler, Detlev; Boulton, Simon J

2015-12-15

Microsatellites are short tandem repeat sequences that are highly prone to expansion/contraction due to their propensity to form non-B-form DNA structures, which hinder DNA polymerases and provoke template slippage. Although error correction by mismatch repair plays a key role in preventing microsatellite instability (MSI), which is a hallmark of Lynch syndrome, activities must also exist that unwind secondary structures to facilitate replication fidelity. Here, we report that Fancj helicase-deficient mice, while phenotypically resembling Fanconi anemia (FA), are also hypersensitive to replication inhibitors and predisposed to lymphoma. Whereas metabolism of G4-DNA structures is largely unaffected in Fancj(-/-) mice, high levels of spontaneous MSI occur, which is exacerbated by replication inhibition. In contrast, MSI is not observed in Fancd2(-/-) mice but is prevalent in human FA-J patients. Together, these data implicate FANCJ as a key factor required to counteract MSI, which is functionally distinct from its role in the FA pathway. © 2015 Matsuzaki et al.; Published by Cold Spring Harbor Laboratory Press.

Single-molecule visualization of fast polymerase turnover in the bacterial replisome

PubMed Central

Lewis, Jacob S; Spenkelink, Lisanne M; Jergic, Slobodan; Wood, Elizabeth A; Monachino, Enrico; Horan, Nicholas P; Duderstadt, Karl E; Cox, Michael M; Robinson, Andrew; Dixon, Nicholas E; van Oijen, Antoine M

2017-01-01

The Escherichia coli DNA replication machinery has been used as a road map to uncover design rules that enable DNA duplication with high efficiency and fidelity. Although the enzymatic activities of the replicative DNA Pol III are well understood, its dynamics within the replisome are not. Here, we test the accepted view that the Pol III holoenzyme remains stably associated within the replisome. We use in vitro single-molecule assays with fluorescently labeled polymerases to demonstrate that the Pol III* complex (holoenzyme lacking the β2 sliding clamp), is rapidly exchanged during processive DNA replication. Nevertheless, the replisome is highly resistant to dilution in the absence of Pol III* in solution. We further show similar exchange in live cells containing labeled clamp loader and polymerase. These observations suggest a concentration-dependent exchange mechanism providing a balance between stability and plasticity, facilitating replacement of replisomal components dependent on their availability in the environment. DOI: http://dx.doi.org/10.7554/eLife.23932.001 PMID:28432790

Replicative DNA polymerase mutations in cancer☆

PubMed Central

Heitzer, Ellen; Tomlinson, Ian

2014-01-01

Three DNA polymerases — Pol α, Pol δ and Pol ɛ — are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson–Crick base pairing and 3′exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to ‘polymerase proofreading associated polyposis’ (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an ‘ultramutator’ phenotype, with a dramatic increase in base substitutions. PMID:24583393

Factors contributing to intervention fidelity in a multi-site chronic disease self-management program

PubMed Central

Perrin, Karen M; Burke, Somer Goad; O'Connor, Danielle; Walby, Gary; Shippey, Claire; Pitt, Seraphine; McDermott, Robert J; Forthofer, Melinda S

2006-01-01

Background and objectives Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. Methods The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. Results This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Conclusion Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity. PMID:17067388

Digital replication of chest radiographs without altering diagnostic observer performance

NASA Astrophysics Data System (ADS)

Flynn, Michael J.; Davies, Eric; Spizarny, David; Beute, Gordon H.; Peterson, Edward; Eyler, William R.; Gross, Barry; Chen, Ji

1991-05-01

A study to test the ability of a high-fidelity system to digitize chest radiographs, store the data in a computer, and reprint the film without altering diagnostic observer performance is reported. Two hundred and fifty-two (252) chest films with subtle image features indicative of interstitial disease, pulmonary nodule, or pneumothorax, along with 36 normal chest films were used in the study. Films were selected from a key word search on a computerized report archive and were graded by two experienced radiologists. Each film was digitized with 86 micron pixels and stored in 4000 X 5000 arrays using a research instrument. Replicates were printed using a commercial laser film printer (Eastman Kodak Company) having 80 micron pixels. Originals and replicates were observed separately by two different experienced radiologists. Each indicated a graded response for the three possible pathologies. The agreement of observers between responses for replicates and originals was described by the kappa statistic and compared to the agreement when rereading the original film. The final result of this study supports a hypothesis that the replicate is indistinguishable from the original.

DNA Repair and Genome Maintenance in Bacillus subtilis

PubMed Central

Lenhart, Justin S.; Schroeder, Jeremy W.; Walsh, Brian W.

2012-01-01

Summary: From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis. PMID:22933559

Minichromosome maintenance helicase paralog MCM9 is dispensible for DNA replication but functions in germ-line stem cells and tumor suppression.

PubMed

Hartford, Suzanne A; Luo, Yunhai; Southard, Teresa L; Min, Irene M; Lis, John T; Schimenti, John C

2011-10-25

Effective DNA replication is critical to the health and reproductive success of organisms. The six MCM2-7 proteins, which form the replicative helicase, are essential for high-fidelity replication of the genome. Many eukaryotes have a divergent paralog, MCM9, that was reported to be essential for loading MCM2-7 onto replication origins in the Xenopus oocyte extract system. To address the in vivo role of mammalian MCM9, we created and analyzed the phenotypes of mice with various mutations in Mcm9 and an intronic DNA replication-related gene Asf1a. Ablation of Mcm9 was compatible with cell proliferation and mouse viability, showing that it is nonessential for MCM2-7 loading or DNA replication. Mcm9 mutants underwent p53-independent embryonic germ-cell depletion in both sexes, with males also exhibiting defective spermatogonial stem-cell renewal. MCM9-deficient cells had elevated genomic instability and defective cell cycle reentry following replication stress, and mutant animals were prone to sex-specific cancers, most notably hepatocellular carcinoma in males. The phenotypes of mutant mice and cells suggest that MCM9 evolved a specialized but nonessential role in DNA replication or replication-linked quality-control mechanisms that are especially important for germ-line stem cells, and also for tumor suppression and genome maintenance in the soma.

Picornaviral Polymerase Structure, Function, and Fidelity Modulation

PubMed Central

Peersen, Olve B.

2017-01-01

Like all positive strand RNA viruses, the picornaviruses replicate their genomes using a virally encoded RNA-dependent RNA polymerase enzyme known as 3Dpol. Over the past decade we have made tremendous advances in our understanding of 3Dpol structure and function, including the discovery of a novel mechanism for closing the active site that allows these viruses to easily fine tune replication fidelity and quasispecies distributions. This review summarizes current knowledge of picornaviral polymerase structure and how the enzyme interacts with RNA and other viral proteins to form stable and processive elongation complexes. The picornaviral RdRPs are among the smallest viral polymerases, but their fundamental molecular mechanism for catalysis appears to be generally applicable as a common feature of all positive strand RNA virus polymerases. PMID:28163093

PTEN in the maintenance of genome integrity: From DNA replication to chromosome segregation.

PubMed

Hou, Sheng-Qi; Ouyang, Meng; Brandmaier, Andrew; Hao, Hongbo; Shen, Wen H

2017-10-01

Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. © 2017 WILEY Periodicals, Inc.

Alteration of the carbohydrate for deoxyguanosine analogs markedly changes DNA replication fidelity, cell cycle progression and cytotoxicity

PubMed Central

O’Konek, Jessica J.; Ladd, Brendon; Flanagan, Sheryl A.; Im, Mike M.; Boucher, Paul D.; Thepsourinthone, Tico S.; Secrist, John A.; Shewach, Donna S.

2011-01-01

Nucleoside analogs are efficacious cancer chemotherapeutics due to their incorporation into tumor cell DNA. However, they exhibit vastly different antitumor efficacies, suggesting that incorporation produces divergent effects on DNA replication. Here we have evaluated the consequences of incorporation on DNA replication and its fidelity for three structurally related deoxyguanosine analogs: ganciclovir (GCV), currently in clinical trials in a suicide gene therapy approach for cancer, D-carbocyclic 2′-deoxyguanosine (CdG) and penciclovir (PCV). GCV and CdG elicited similar cytotoxicity at low concentrations, whereas PCV was 10–100-fold less cytotoxic in human tumor cells. DNA replication fidelity was evaluated using a supF plasmid-based mutation assay. Only GCV induced a dose-dependent increase in mutation frequency, predominantly GC→TA transversions, which contributed to cytotoxicity and implicated the ether oxygen in mutagenicity. Activation of mismatch repair with hydroxyurea decreased mutations but failed to repair the GC→TA transversions. GCV slowed S-phase progression and CdG also induced a G2/M block, but both drugs allowed completion of one cell cycle after drug treatment followed by cell death in the second cell cycle. In contrast, PCV induced a lengthy early S-phase block due to profound suppression of DNA synthesis, with cell death in the first cell cycle after drug treatment. These data suggest that GCV and CdG elicit superior cytotoxicity due to their effects in template DNA, whereas strong inhibition of nascent strand synthesis by PCV may protect against cytotoxicity. Nucleoside analogs based on the carbohydrate structures of GCV and CdG is a promising area for antitumor drug development. PMID:20004674

Implementing the LifeSkills Training drug prevention program: factors related to implementation fidelity.

PubMed

Mihalic, Sharon F; Fagan, Abigail A; Argamaso, Susanne

2008-01-18

Widespread replication of effective prevention programs is unlikely to affect the incidence of adolescent delinquency, violent crime, and substance use until the quality of implementation of these programs by community-based organizations can be assured. This paper presents the results of a process evaluation employing qualitative and quantitative methods to assess the extent to which 432 schools in 105 sites implemented the LifeSkills Training (LST) drug prevention program with fidelity. Regression analysis was used to examine factors influencing four dimensions of fidelity: adherence, dosage, quality of delivery, and student responsiveness. Although most sites faced common barriers, such as finding room in the school schedule for the program, gaining full support from key participants (i.e., site coordinators, principals, and LST teachers), ensuring teacher participation in training workshops, and classroom management difficulties, most schools involved in the project implemented LST with very high levels of fidelity. Across sites, 86% of program objectives and activities required in the three-year curriculum were delivered to students. Moreover, teachers were observed using all four recommended teaching practices, and 71% of instructors taught all the required LST lessons. Multivariate analyses found that highly rated LST program characteristics and better student behavior were significantly related to a greater proportion of material taught by teachers (adherence). Instructors who rated the LST program characteristics as ideal were more likely to teach all lessons (dosage). Student behavior and use of interactive teaching techniques (quality of delivery) were positively related. No variables were related to student participation (student responsiveness). Although difficult, high implementation fidelity by community-based organizations can be achieved. This study suggests some important factors that organizations should consider to ensure fidelity, such as selecting programs with features that minimize complexity while maximizing flexibility. Time constraints in the classroom should be considered when choosing a program. Student behavior also influences program delivery, so schools should train teachers in the use of classroom management skills. This project involved comprehensive program monitoring and technical assistance that likely facilitated the identification and resolution of problems and contributed to the overall high quality of implementation. Schools should recognize the importance of training and technical assistance to ensure quality program delivery.

Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

PubMed

Rai, Devendra K; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A; Kloc, Anna; de Los Santos, Teresa; Peersen, Olve; Rieder, Elizabeth

2017-08-01

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D pol ) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D pol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A 24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F HF ) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I LF ) and W237L LF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D pol mutations that affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3D pol tryptophan residue 237 were genetically stable and displayed plaque phenotypes and growth kinetics similar to those of the wild-type virus in cell culture. We further demonstrate that viruses harboring either a W237F HF substitution or W237I LF and W237L LF mutations were highly attenuated in animals. Our study shows that obtaining 3D pol fidelity variants by protein engineering based on polymerase structure and function could be exploited for the development of attenuated FMDV vaccine candidates that are safer and more stable than strains obtained by selective pressure via mutagenic nucleotides or adaptation approaches. Copyright © 2017 American Society for Microbiology.

Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity

PubMed Central

Rai, Devendra K.; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A.; Kloc, Anna; de los Santos, Teresa; Peersen, Olve

2017-01-01

ABSTRACT Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3Dpol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237ILF) and W237LLF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3Dpol mutations that affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3Dpol tryptophan residue 237 were genetically stable and displayed plaque phenotypes and growth kinetics similar to those of the wild-type virus in cell culture. We further demonstrate that viruses harboring either a W237FHF substitution or W237ILF and W237LLF mutations were highly attenuated in animals. Our study shows that obtaining 3Dpol fidelity variants by protein engineering based on polymerase structure and function could be exploited for the development of attenuated FMDV vaccine candidates that are safer and more stable than strains obtained by selective pressure via mutagenic nucleotides or adaptation approaches. PMID:28515297

Recognition of Watson-Crick base pairs: constraints and limits due to geometric selection and tautomerism

PubMed Central

Yusupov, Marat; Yusupova, Gulnara

2014-01-01

The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential. However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries. These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes. PMID:24765524

Pilot-Induced Oscillation Prediction With Three Levels of Simulation Motion Displacement

NASA Technical Reports Server (NTRS)

Schroeder, Jeffery A.; Chung, William W. Y.; Tran, Duc T.; Laforce, Soren; Bengford, Norman J.

2001-01-01

Simulator motion platform characteristics were examined to determine if the amount of motion affects pilot-induced oscillation (PIO) prediction. Five test pilots evaluated how susceptible 18 different sets of pitch dynamics were to PIOs with three different levels of simulation motion platform displacement: large, small, and none. The pitch dynamics were those of a previous in-flight experiment, some of which elicited PIOs These in-flight results served as truth data for the simulation. As such, the in-flight experiment was replicated as much as possible. Objective and subjective data were collected and analyzed With large motion, PIO and handling qualities ratings matched the flight data more closely than did small motion or no motion. Also, regardless of the aircraft dynamics, large motion increased pilot confidence in assigning handling qualifies ratings, reduced safety pilot trips, and lowered touchdown velocities. While both large and small motion provided a pitch rate cue of high fidelity, only large motion presented the pilot with a high fidelity vertical acceleration cue.

Epigenetic memory via concordant DNA methylation is inversely correlated to developmental potential of mammalian cells

PubMed Central

Goodson, Jamie; Al-Azzawi, Haneen; Allain, Shannon Q.; Simon, Noah; Palasek, Stan; Miller, Daniel G.; Johnson, Winslow C.; Laird, Charles D.

2017-01-01

In storing and transmitting epigenetic information, organisms must balance the need to maintain information about past conditions with the capacity to respond to information in their current and future environments. Some of this information is encoded by DNA methylation, which can be transmitted with variable fidelity from parent to daughter strand. High fidelity confers strong pattern matching between the strands of individual DNA molecules and thus pattern stability over rounds of DNA replication; lower fidelity confers reduced pattern matching, and thus greater flexibility. Here, we present a new conceptual framework, Ratio of Concordance Preference (RCP), that uses double-stranded methylation data to quantify the flexibility and stability of the system that gave rise to a given set of patterns. We find that differentiated mammalian cells operate with high DNA methylation stability, consistent with earlier reports. Stem cells in culture and in embryos, in contrast, operate with reduced, albeit significant, methylation stability. We conclude that preference for concordant DNA methylation is a consistent mode of information transfer, and thus provides epigenetic stability across cell divisions, even in stem cells and those undergoing developmental transitions. Broader application of our RCP framework will permit comparison of epigenetic-information systems across cells, developmental stages, and organisms whose methylation machineries differ substantially or are not yet well understood. PMID:29107996

A ``Cyber Wind Facility'' for HPC Wind Turbine Field Experiments

NASA Astrophysics Data System (ADS)

Brasseur, James; Paterson, Eric; Schmitz, Sven; Campbell, Robert; Vijayakumar, Ganesh; Lavely, Adam; Jayaraman, Balaji; Nandi, Tarak; Jha, Pankaj; Dunbar, Alex; Motta-Mena, Javier; Craven, Brent; Haupt, Sue

2013-03-01

The Penn State ``Cyber Wind Facility'' (CWF) is a high-fidelity multi-scale high performance computing (HPC) environment in which ``cyber field experiments'' are designed and ``cyber data'' collected from wind turbines operating within the atmospheric boundary layer (ABL) environment. Conceptually the ``facility'' is akin to a high-tech wind tunnel with controlled physical environment, but unlike a wind tunnel it replicates commercial-scale wind turbines operating in the field and forced by true atmospheric turbulence with controlled stability state. The CWF is created from state-of-the-art high-accuracy technology geometry and grid design and numerical methods, and with high-resolution simulation strategies that blend unsteady RANS near the surface with high fidelity large-eddy simulation (LES) in separated boundary layer, blade and rotor wake regions, embedded within high-resolution LES of the ABL. CWF experiments complement physical field facility experiments that can capture wider ranges of meteorological events, but with minimal control over the environment and with very small numbers of sensors at low spatial resolution. I shall report on the first CWF experiments aimed at dynamical interactions between ABL turbulence and space-time wind turbine loadings. Supported by DOE and NSF.

Properties of an unusual DNA primase from an archaeal plasmid

PubMed Central

Beck, Kirsten; Lipps, Georg

2007-01-01

Primases are specialized DNA-dependent RNA polymerases that synthesize a short oligoribonucleotide complementary to single-stranded template DNA. In the context of cellular DNA replication, primases are indispensable since DNA polymerases are not able to start DNA polymerization de novo. The primase activity of the replication protein from the archaeal plasmid pRN1 synthesizes a rather unusual mixed primer consisting of a single ribonucleotide at the 5′ end followed by seven deoxynucleotides. Ribonucleotides and deoxynucleotides are strictly required at the respective positions within the primer. Furthermore, in contrast to other archaeo-eukaryotic primases, the primase activity is highly sequence-specific and requires the trinucleotide motif GTG in the template. Primer synthesis starts outside of the recognition motif, immediately 5′ to the recognition motif. The fidelity of the primase synthesis is high, as non-complementary bases are not incorporated into the primer. PMID:17709343

DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity

PubMed Central

Diamant, Noam; Hendel, Ayal; Vered, Ilan; Carell, Thomas; Reißner, Thomas; de Wind, Niels; Geacinov, Nicholas; Livneh, Zvi

2012-01-01

Translesion DNA synthesis (TLS) employs low-fidelity DNA polymerases to bypass replication-blocking lesions, and being associated with chromosomal replication was presumed to occur in the S phase of the cell cycle. Using immunostaining with anti-replication protein A antibodies, we show that in UV-irradiated mammalian cells, chromosomal single-stranded gaps formed in S phase during replication persist into the G2 phase of the cell cycle, where their repair is completed depending on DNA polymerase ζ and Rev1. Analysis of TLS using a high-resolution gapped-plasmid assay system in cell populations enriched by centrifugal elutriation for specific cell cycle phases showed that TLS operates both in S and G2. Moreover, the mutagenic specificity of TLS in G2 was different from S, and in some cases overall mutation frequency was higher. These results suggest that TLS repair of single-stranded gaps caused by DNA lesions can lag behind chromosomal replication, is separable from it, and occurs both in the S and G2 phases of the cell cycle. Such a mechanism may function to maintain efficient replication, which can progress despite the presence of DNA lesions, with TLS lagging behind and patching regions of discontinuity. PMID:21908406

Biological species is the only possible form of existence for higher organisms: the evolutionary meaning of sexual reproduction

PubMed Central

2010-01-01

Consistent holistic view of sexual species as the highest form of biological existence is presented. The Weismann's idea that sex and recombination provide the variation for the natural selection to act upon is dominated in most discussions of the biological meaning of the sexual reproduction. Here, the idea is substantiated that the main advantage of sex is the opposite: the ability to counteract not only extinction but further evolution as well. Living systems live long owing to their ability to reproduce themselves with a high fidelity. Simple organisms (like bacteria) reach the continued existence due to the high fidelity of individual genome replication. In organisms with a large genome and complex development, the achievable fidelity of DNA replication is not enough for the precise reproduction of the genome. Such species must be capable of surviving and must remain unchanged in spite of the continuous changes of their genes. This problem has no solution in the frame of asexual ("homeogenomic") lineages. They would rapidly degrade and become extinct or blurred out in the course of the reckless evolution. The core outcome of the transition to sexual reproduction was the creation of multiorganismic entity - biological species. Individual organisms forfeited their ability to reproduce autonomously. It implies that individual organisms forfeited their ability to substantive evolution. They evolve as a part of the biological species. In case of obligatory sexuality, there is no such a thing as synchronic multi-level selection. Natural selection cannot select anything that is not a unit of reproduction. Hierarchy in biology implies the functional predestination of the parts for the sake of the whole. A crucial feature of the sexual reproduction is the formation of genomes of individual organisms by random picking them over from the continuously shuffled gene pool instead of the direct replication of the ancestor's genome. A clear anti-evolutionary consequence of the sexuality is evident from the fact that the genotypes of the individuals with an enhanced competitiveness are not transmitted to the next generation. Instead, after mating with "ordinary" individuals, these genotypes scatter and rearrange in new gene combinations, thus preventing the winner from exploiting the success. Reviewers This article was reviewed by Pierre Antoine Pontarotti, Michael T. Ghiselin (nominated by Dr. Juergen Brosius) and Emanuel Tannenboum (nominated by Dr. Doron Lancet) PMID:20307287

Information in the Biosphere: Biological and Digital Worlds.

PubMed

Gillings, Michael R; Hilbert, Martin; Kemp, Darrell J

2016-03-01

Evolution has transformed life through key innovations in information storage and replication, including RNA, DNA, multicellularity, and culture and language. We argue that the carbon-based biosphere has generated a cognitive system (humans) capable of creating technology that will result in a comparable evolutionary transition. Digital information has reached a similar magnitude to information in the biosphere. It increases exponentially, exhibits high-fidelity replication, evolves through differential fitness, is expressed through artificial intelligence (AI), and has facility for virtually limitless recombination. Like previous evolutionary transitions, the potential symbiosis between biological and digital information will reach a critical point where these codes could compete via natural selection. Alternatively, this fusion could create a higher-level superorganism employing a low-conflict division of labor in performing informational tasks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination.

PubMed

Woodman, Andrew; Arnold, Jamie J; Cameron, Craig E; Evans, David J

2016-08-19

Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3' non-coding region we have further developed a cell-based assay (the 3'CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies

PubMed Central

Bratic, Ana; Kauppila, Timo E. S.; Macao, Bertil; Grönke, Sebastian; Siibak, Triinu; Stewart, James B.; Baggio, Francesca; Dols, Jacqueline; Partridge, Linda; Falkenberg, Maria; Wredenberg, Anna; Larsson, Nils-Göran

2015-01-01

Replication errors are the main cause of mitochondrial DNA (mtDNA) mutations and a compelling approach to decrease mutation levels would therefore be to increase the fidelity of the catalytic subunit (POLγA) of the mtDNA polymerase. Here we genomically engineer the tamas locus, encoding fly POLγA, and introduce alleles expressing exonuclease- (exo−) and polymerase-deficient (pol−) POLγA versions. The exo− mutant leads to accumulation of point mutations and linear deletions of mtDNA, whereas pol− mutants cause mtDNA depletion. The mutant tamas alleles are developmentally lethal but can complement each other in trans resulting in viable flies with clonally expanded mtDNA mutations. Reconstitution of human mtDNA replication in vitro confirms that replication is a highly dynamic process where POLγA goes on and off the template to allow complementation during proofreading and elongation. The created fly models are valuable tools to study germ line transmission of mtDNA and the pathophysiology of POLγA mutation disease. PMID:26554610

Mapping DNA polymerase errors by single-molecule sequencing

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

Lee, David F.; Lu, Jenny; Chang, Seungwoo

Genomic integrity is compromised by DNA polymerase replication errors, which occur in a sequence-dependent manner across the genome. Accurate and complete quantification of a DNA polymerase's error spectrum is challenging because errors are rare and difficult to detect. We report a high-throughput sequencing assay to map in vitro DNA replication errors at the single-molecule level. Unlike previous methods, our assay is able to rapidly detect a large number of polymerase errors at base resolution over any template substrate without quantification bias. To overcome the high error rate of high-throughput sequencing, our assay uses a barcoding strategy in which each replicationmore » product is tagged with a unique nucleotide sequence before amplification. Here, this allows multiple sequencing reads of the same product to be compared so that sequencing errors can be found and removed. We demonstrate the ability of our assay to characterize the average error rate, error hotspots and lesion bypass fidelity of several DNA polymerases.« less

Mapping DNA polymerase errors by single-molecule sequencing

DOE PAGES

Lee, David F.; Lu, Jenny; Chang, Seungwoo; ...

2016-05-16

Genomic integrity is compromised by DNA polymerase replication errors, which occur in a sequence-dependent manner across the genome. Accurate and complete quantification of a DNA polymerase's error spectrum is challenging because errors are rare and difficult to detect. We report a high-throughput sequencing assay to map in vitro DNA replication errors at the single-molecule level. Unlike previous methods, our assay is able to rapidly detect a large number of polymerase errors at base resolution over any template substrate without quantification bias. To overcome the high error rate of high-throughput sequencing, our assay uses a barcoding strategy in which each replicationmore » product is tagged with a unique nucleotide sequence before amplification. Here, this allows multiple sequencing reads of the same product to be compared so that sequencing errors can be found and removed. We demonstrate the ability of our assay to characterize the average error rate, error hotspots and lesion bypass fidelity of several DNA polymerases.« less

Rates of Spontaneous Mutation in Bacteriophage T4 Are Independent of Host Fidelity Determinants

PubMed Central

Santos, M. E.; Drake, J. W.

1994-01-01

Bacteriophage T4 encodes most of the genes whose products are required for its DNA metabolism, and host (Escherichia coli) genes can only infrequently complement mutationally inactivated T4 genes. We screened the following host mutator mutations for effects on spontaneous mutation rates in T4: mutT (destruction of aberrant dGTPs), polA, polB and polC (DNA polymerases), dnaQ (exonucleolytic proofreading), mutH, mutS, mutL and uvrD (methyl-directed DNA mismatch repair), mutM and mutY (excision repair of oxygen-damaged DNA), mutA (function unknown), and topB and osmZ (affecting DNA topology). None increased T4 spontaneous mutation rates within a resolving power of about twofold (nor did optA, which is not a mutator but overexpresses a host dGTPase). Previous screens in T4 have revealed strong mutator mutations only in the gene encoding the viral DNA polymerase and proofreading 3'-exonuclease, plus weak mutators in several polymerase accessory proteins or determinants of dNTP pool sizes. T4 maintains a spontaneous mutation rate per base pair about 30-fold greater than that of its host. Thus, the joint high fidelity of insertion by T4 DNA polymerase and proofreading by its associated 3'-exonuclease appear to determine the T4 spontaneous mutation rate, whereas the host requires numerous additional systems to achieve high replication fidelity. PMID:7851754

The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β

PubMed Central

Koag, Myong-Chul; Nam, Kwangho; Lee, Seongmin

2014-01-01

To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an ‘intermediate’ protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound ‘pre-chemistry-state’ structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson–Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson–Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson–Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ. PMID:25200079

Assessment of Fidelity in Interventions to Improve Hand Hygiene of Healthcare Workers: A Systematic Review

PubMed Central

Musuuza, Jackson S.; Barker, Anna; Ngam, Caitlyn; Vellardita, Lia; Safdar, Nasia

2016-01-01

OBJECTIVE Compliance with hand hygiene in healthcare workers is fundamental to infection prevention yet remains a challenge to sustain. We examined fidelity reporting in interventions to improve hand hygiene compliance, and we assessed 5 measures of intervention fidelity: (1) adherence, (2) exposure or dose, (3) quality of intervention delivery, (4) participant responsiveness, and (5) program differentiation. DESIGN Systematic review METHODS A librarian performed searches of the literature in PubMed, Cumulative Index to Nursing and Allied Health (CINAHL), Cochrane Library, and Web of Science of material published prior to June 19, 2015. The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews, and assessment of study quality was conducted for each study reviewed. RESULTS A total of 100 studies met the inclusion criteria. Only 8 of these 100 studies reported all 5 measures of intervention fidelity. In addition, 39 of 100 (39%) failed to include at least 3 fidelity measures; 20 of 100 (20%) failed to include 4 measures; 17 of 100 (17%) failed to include 2 measures, while 16 of 100 (16%) of the studies failed to include at least 1 measure of fidelity. Participant responsiveness and adherence to the intervention were the most frequently unreported fidelity measures, while quality of the delivery was the most frequently reported measure. CONCLUSIONS Almost all hand hygiene intervention studies failed to report at least 1 fidelity measurement. To facilitate replication and effective implementation, reporting fidelity should be standard practice when describing results of complex behavioral interventions such as hand hygiene. PMID:26861117

Exploring the use of high-fidelity simulation training to enhance clinical skills.

PubMed

Ann Kirkham, Lucy

2018-02-07

The use of interprofessional simulation training to enhance nursing students' performance of technical and non-technical clinical skills is becoming increasingly common. Simulation training can involve the use of role play, virtual reality or patient simulator manikins to replicate clinical scenarios and assess the nursing student's ability to, for example, undertake clinical observations or work as part of a team. Simulation training enables nursing students to practise clinical skills in a safe environment. Effective simulation training requires extensive preparation, and debriefing is necessary following a simulated training session to review any positive or negative aspects of the learning experience. This article discusses a high-fidelity simulated training session that was used to assess a group of third-year nursing students and foundation level 1 medical students. This involved the use of a patient simulator manikin in a scenario that required the collaborative management of a deteriorating patient. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

β-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity

PubMed Central

Gutierrez, A.; Laureti, L.; Crussard, S.; Abida, H.; Rodríguez-Rojas, A.; Blázquez, J.; Baharoglu, Z.; Mazel, D.; Darfeuille, F.; Vogel, J.; Matic, I.

2013-01-01

Regardless of their targets and modes of action, subinhibitory concentrations of antibiotics can have an impact on cell physiology and trigger a large variety of cellular responses in different bacterial species. Subinhibitory concentrations of β-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli. Here we show that subinhibitory concentrations of β-lactam antibiotics induce the RpoS regulon. RpoS-regulon induction is required for PolIV-dependent mutagenesis because it diminishes the control of DNA-replication fidelity by depleting MutS in E. coli, Vibrio cholerae and Pseudomonas aeruginosa. We also show that in E. coli, the reduction in mismatch-repair activity is mediated by SdsR, the RpoS-controlled small RNA. In summary, we show that mutagenesis induced by subinhibitory concentrations of antibiotics is a genetically controlled process. Because this mutagenesis can generate mutations conferring antibiotic resistance, it should be taken into consideration for the development of more efficient antimicrobial therapeutic strategies. PMID:23511474

The mechanism of untargeted mutagenesis in UV-irradiated yeast.

PubMed

Lawrence, C W; Christensen, R B

1982-01-01

The SOS error-prone repair hypothesis proposes that untargeted and targeted mutations in E. coli both result from the inhibition of polymerase functions that normally maintain fidelity, and that this is a necessary precondition for translesion synthesis. Using mating experiments with excision deficient strains of Bakers' yeast, Saccharomyces cerevisiae, we find that up to 40% of cycl-91 revertants induced by UV are untargeted, showing that a reduction in fidelity is also found in irradiated cells of this organism. We are, however, unable to detect the induction or activation of any diffusible factor capable of inhibiting fidelity, and therefore suggest that untargeted and targeted mutations are the consequence of largely different processes. We propose that these observations are best explained in terms of a limited fidelity model. Untargeted mutations are thought to result from the limited capacity of processes which normally maintain fidelity, which are active during replication on both irradiated and unirradiated templates. Even moderate UV fluences saturate this capacity, leading to competition for the limited resource. Targeted mutations are believed to result from the limited, though far from negligible, capacity of lesions like pyrimidine dimers to form Watson-Crick base pairs.

Kinetics of Mismatch Formation opposite Lesions by the Replicative DNA Polymerase from Bacteriophage RB69

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

Hogg, Matthew; Rudnicki, Jean; Midkiff, John

2010-04-12

The fidelity of DNA replication is under constant threat from the formation of lesions within the genome. Oxidation of DNA bases leads to the formation of altered DNA bases such as 8-oxo-7,8-dihydroguanine, commonly called 8-oxoG, and 2-hydroxyadenenine, or 2-OHA. In this work we have examined the incorporation kinetics opposite these two oxidatively derived lesions as well as an abasic site analogue by the replicative DNA polymerase from bacteriophage RB69. We compared the kinetic parameters for both wild type and the low fidelity L561A variant. While nucleotide incorporation rates (k{sub pol}) were generally higher for the variant, the presence of amore » lesion in the templating position reduced the ability of both the wild-type and variant DNA polymerases to form ternary enzyme-DNA-dNTP complexes. Thus, the L561A substitution does not significantly affect the ability of the RB69 DNA polymerase to recognize damaged DNA; instead, the mutation increases the probability that nucleotide incorporation will occur. We have also solved the crystal structure of the L561A variant forming an 8-oxoG {center_dot} dATP mispair and show that the propensity for forming this mispair depends on an enlarged polymerase active site.« less

[Technology Development for X-Ray Reflection for the Constellation-X Reflection Grating Spectrometer (RGS)

NASA Technical Reports Server (NTRS)

Schattenburg, Mark L.

2003-01-01

This Grant covers MIT support for the technology development of x-ray reflection gratings for the Constellation-X Reflection Grating Spectrometer (RGS). Since the start of the Grant MIT has extended its previously-developed patterning and super-smooth, blazed grating fabrication technology to ten-times smaller grating periods and ten-times larger blaze angles to demonstrate feasibility and performance in the off-plane grating geometry. In the past year we successfully developed several nanoimprint grating replication methods that achieved very high fidelity replication of master silicon gratings. Grating geometry on the nano and macro scales were faithfully replicated, demonstrating the viability of the process for manufacturing the thousands of gratings required for the RGS. We also successfully developed an improved metrology truss for holding test grating substrates during metrology. The flatness goal of grating substrates is under 500 nm. In the past, grating holders would cause non-repeatable distortion of >> 500 nm to the substrates due to friction and gravity sag. The new holder has a repeatability of under 50 nm which is adequate for the proposed RGS grating substrates.

Conceptual design and analysis of a dynamic scale model of the Space Station Freedom

NASA Technical Reports Server (NTRS)

Davis, D. A.; Gronet, M. J.; Tan, M. K.; Thorne, J.

1994-01-01

This report documents the conceptual design study performed to evaluate design options for a subscale dynamic test model which could be used to investigate the expected on-orbit structural dynamic characteristics of the Space Station Freedom early build configurations. The baseline option was a 'near-replica' model of the SSF SC-7 pre-integrated truss configuration. The approach used to develop conceptual design options involved three sets of studies: evaluation of the full-scale design and analysis databases, conducting scale factor trade studies, and performing design sensitivity studies. The scale factor trade study was conducted to develop a fundamental understanding of the key scaling parameters that drive design, performance and cost of a SSF dynamic scale model. Four scale model options were estimated: 1/4, 1/5, 1/7, and 1/10 scale. Prototype hardware was fabricated to assess producibility issues. Based on the results of the study, a 1/4-scale size is recommended based on the increased model fidelity associated with a larger scale factor. A design sensitivity study was performed to identify critical hardware component properties that drive dynamic performance. A total of 118 component properties were identified which require high-fidelity replication. Lower fidelity dynamic similarity scaling can be used for non-critical components.

Randomized Control Trial of COMPASS for Improving Transition Outcomes of Students with Autism Spectrum Disorder.

PubMed

Ruble, Lisa A; McGrew, John H; Toland, Michael; Dalrymple, Nancy; Adams, Medina; Snell-Rood, Claire

2018-06-01

The postsecondary outcomes of individuals with autism spectrum disorder (ASD) are significantly worse than peers with other disabilities. One problem is the lack of empirically-supported transition planning interventions to guide services and help produce better outcomes. We applied an implementation science approach to adapt and modify an evidence-based consultation intervention originally tested with young children called the Collaborative Model for Promoting Competence and Success (COMPASS; Ruble et al., The collaborative model for promoting competence and success for students with ASD. Springer, New York, 2012a) and evaluate it for efficacy in a randomized controlled trial for transition-age youth. Results replicated findings with younger students with ASD that IEP outcomes were higher for COMPASS compared to the placebo control group (d = 2.1). Consultant fidelity was high and teacher adherence improved over time, replicating the importance of ongoing teacher coaching.

Mechanisms of viral mutation.

PubMed

Sanjuán, Rafael; Domingo-Calap, Pilar

2016-12-01

The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage

PubMed Central

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F. Peter; Zhang, Huidong

2017-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, E. coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. PMID:27234563

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.

PubMed

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F Peter; Zhang, Huidong

2016-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint.

PubMed

Luciani, M Gloria; Campregher, Christoph; Fortune, John M; Kunkel, Thomas A; Gasche, Christoph

2007-01-01

Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis.

A review of micro-powder injection moulding as a microfabrication technique

NASA Astrophysics Data System (ADS)

Attia, Usama M.; Alcock, Jeffrey R.

2011-04-01

Micro-powder injection moulding (µPIM) is a fast-developing micro-manufacturing technique for the production of metal and ceramic components. Shape complexity, dimensional accuracy, replication fidelity, material variety combined with high-volume capabilities are some of the key advantages of the technology. This review assesses the capabilities and limitations of µPIM as a micro-manufacturing technique by reviewing the latest developments in the area and by considering potential improvements. The basic elements of the process chain, variant processes and simulation attempts are discussed and evaluated. Challenges and research gaps are highlighted, and potential areas for improvement are presented.

What Tension between Fidelity and Cultural Adaptation? A Reaction to Marsiglia and Booth

ERIC Educational Resources Information Center

Sampson, McClain; Torres, Luis R.

2015-01-01

This paper is a reaction to Marsiglia and Booths' paper, "Cultural Adaptation of Interventions in Real Practice Settings." In their paper, Marsiglia and Booth present the difficulty of implementing and replicating evidence-supported treatments, such as randomized clinical trials, among culturally diverse clients. Practitioners working in…

Regulatory Control of Breast Tumor Cell Poly (ADP-Ribose) Polymerase

DTIC Science & Technology

2002-08-01

DNA replication complex (designated the DNA synthesome) from a variety of non-malignant and malignant tumor cells including breast cancer cells. We have shown that poly(ADP-ribose) polymerase PARP is among the components of the DNA synthesome. The transformation of a non-malignant human breast cell to a malignant state was accompanied by a significant alteration in the 2-D PAGE profile of specific protein components of the DNA synthesome (such as PCNA) together with a 6-8 decrease in the replication fidelity of the DNA

Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing.

PubMed

López-Carrasco, Amparo; Ballesteros, Cristina; Sentandreu, Vicente; Delgado, Sonia; Gago-Zachert, Selma; Flores, Ricardo; Sanjuán, Rafael

2017-09-01

Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplast-replicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear potato spindle tuber viroid (PSTVd, Pospiviroidae). This revealed higher mutation frequencies in ELVd than in PSTVd, as well as marked differences in the types of mutations produced. Rates of spontaneous mutation, quantified in vivo using the lethal mutation method, ranged from 1/1000 to 1/800 for ELVd and from 1/7000 to 1/3800 for PSTVd depending on sequencing run. These results suggest that extremely high mutability is a common feature of chloroplastic viroids, whereas the mutation rates of PSTVd and potentially other nuclear viroids appear significantly lower and closer to those of some RNA viruses.

Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing

PubMed Central

Ballesteros, Cristina; Sentandreu, Vicente; Gago-Zachert, Selma

2017-01-01

Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplast-replicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear potato spindle tuber viroid (PSTVd, Pospiviroidae). This revealed higher mutation frequencies in ELVd than in PSTVd, as well as marked differences in the types of mutations produced. Rates of spontaneous mutation, quantified in vivo using the lethal mutation method, ranged from 1/1000 to 1/800 for ELVd and from 1/7000 to 1/3800 for PSTVd depending on sequencing run. These results suggest that extremely high mutability is a common feature of chloroplastic viroids, whereas the mutation rates of PSTVd and potentially other nuclear viroids appear significantly lower and closer to those of some RNA viruses. PMID:28910391

An application of synchrotron based x-ray tomography in palaeontology: Investigating small, three-dimensional, exceptionally preserved fossil arthropods

NASA Astrophysics Data System (ADS)

Braiden, A. K.; Orr, P. J.; Tafforeau, P.; Kearns, S. L.

2009-04-01

The fossil record is biased towards biomineralised elements (for example bones, shells and teeth) that usually retain their original three-dimensional shape. Non-biomineralised arthropods, often comprising only exoskeletal tissues such as cuticle, are comparatively rare and are usually preserved in two-dimensions (including examples inside early diagenetic concretions). Rarer still are exceptionally preserved fossils that contain replicated soft tissues; although tissues that are replicated during the initial stages of decay are usually three- dimensional and often preserved in detail, the fossil as a whole is almost invariably two dimensional. Fossil shrimp recovered from Upper Triassic (Rhaetian) unconsolidated clays at Frome, Somerset, England represent a low diversity, three-dimensionally preserved fauna, in which certain labile tissues and organs are routinely preserved in three dimensions in life position. Initial SEM analysis of exposed, internal structures in unprepared specimens confirmed the presence of musculature (replicated in calcium phosphate) and a clay infilled gut. Due to the rarity of the material, and small size of the specimens (maximum length 12mm), non-destructive synchrotron radiation, x-ray microtomography was used to determine the extent, and fidelity, of preservation of the internal anatomy. Medium resolution (voxel size of 5.3μm) and high resolution (voxel size 0.7μm) imaging was carried out on selected specimens. This confirmed high fidelity replication of the following: limited volumes of abdominal, and more rarely, cephalothoracic musculature; the hepatopancreas; gonads and, in rare cases, blood vessels and antennal glands. Notably, these are all preserved in situ enveloped by structureless, fine-grained, authigenic carbonate. This carbonate precipitated inside the cuticle, but only at the periphery of the carcass and after, or during, the initial stages of decay; it infills voids created by the initial shrinkage of abdominal musculature (possibly due to dehydration) but not those created by its subsequent decay. The digestive tract is infilled with ingested clay material. X-ray microtomographic imaging also revealed the presence of pyrite as framboids and polyhedra. The spatial distribution of framboidal pyrite, and tissue replicating calcium phosphate, indicates their precipitation is likely to be related to the original composition of the biological tissues. For example, although the pyrite framboids do not replicate tissues, they are found in association with the hepatopancreas. It is probably not coincidental that iron is especially abundant in this area in vivo. Notably, subtle differences in greyscale tone in the x-ray images are shown to correspond to authigenic phases of different composition. When calibrated against phases for which accurate compositions can be determined using other criteria (e.g. SEM-EDX), it is possible to identify the presence of particular authigenic mineral phases in such fossils.

General misincorporation frequency: Re-evaluation of the fidelity of DNA polymerases.

PubMed

Yang, Jie; Li, Bianbian; Liu, Xiaoying; Tang, Hong; Zhuang, Xiyao; Yang, Mingqi; Xu, Ying; Zhang, Huidong; Yang, Chun

2018-02-19

DNA replication in cells is performed in the presence of four dNTPs and four rNTPs. In this study, we re-evaluated the fidelity of DNA polymerases using the general misincorporation frequency consisting of three incorrect dNTPs and four rNTPs but not using the traditional special misincorporation frequency with only the three incorrect dNTPs. We analyzed both the general and special misincorporation frequencies of nucleotide incorporation opposite dG, rG, or 8-oxoG by Pseudomonas aeruginosa phage 1 (PaP1) DNA polymerase Gp90 or Sulfolobus solfataricus DNA polymerase Dpo4. Both misincorporation frequencies of other DNA polymerases published were also summarized and analyzed. The general misincorporation frequency is obviously higher than the special misincorporation frequency for many DNA polymerases, indicating the real fidelity of a DNA polymerase should be evaluated using the general misincorporation frequency. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural Dynamics as a Contributor to Error-prone Replication by an RNA-dependent RNA Polymerase*

PubMed Central

Moustafa, Ibrahim M.; Korboukh, Victoria K.; Arnold, Jamie J.; Smidansky, Eric D.; Marcotte, Laura L.; Gohara, David W.; Yang, Xiaorong; Sánchez-Farrán, María Antonieta; Filman, David; Maranas, Janna K.; Boehr, David D.; Hogle, James M.; Colina, Coray M.; Cameron, Craig E.

2014-01-01

RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity. PMID:25378410

First-Order Model Management With Variable-Fidelity Physics Applied to Multi-Element Airfoil Optimization

NASA Technical Reports Server (NTRS)

Alexandrov, N. M.; Nielsen, E. J.; Lewis, R. M.; Anderson, W. K.

2000-01-01

First-order approximation and model management is a methodology for a systematic use of variable-fidelity models or approximations in optimization. The intent of model management is to attain convergence to high-fidelity solutions with minimal expense in high-fidelity computations. The savings in terms of computationally intensive evaluations depends on the ability of the available lower-fidelity model or a suite of models to predict the improvement trends for the high-fidelity problem, Variable-fidelity models can be represented by data-fitting approximations, variable-resolution models. variable-convergence models. or variable physical fidelity models. The present work considers the use of variable-fidelity physics models. We demonstrate the performance of model management on an aerodynamic optimization of a multi-element airfoil designed to operate in the transonic regime. Reynolds-averaged Navier-Stokes equations represent the high-fidelity model, while the Euler equations represent the low-fidelity model. An unstructured mesh-based analysis code FUN2D evaluates functions and sensitivity derivatives for both models. Model management for the present demonstration problem yields fivefold savings in terms of high-fidelity evaluations compared to optimization done with high-fidelity computations alone.

Injection and injection-compression moulding replication capability for the production of polymer lab-on-a-chip with nano structures

NASA Astrophysics Data System (ADS)

Calaon, M.; Tosello, G.; Garnaes, J.; Hansen, H. N.

2017-10-01

The manufacturing precision and accuracy in the production of polymer lab-on-a-chip components with 100-130 nm deep nanochannels are evaluated using a metrological approach. Replication fidelity on corresponding process fingerprint test nanostructures over different substrates (nickel tool and polymer part) is quantified through traceable atomic force microscope measurements. Dimensions of injection moulded (IM) and injection-compression moulded (ICM) thermoplastic cyclic olefin copolymer nanofeatures are characterized depending on process parameters and four different features positions on a 30  ×  80 mm2 area. Replication capability of IM and ICM technologies are quantified and the products tolerance at the nanometre dimensional scale verified.

Tales of Refusal, Adoption, and Maintenance: Evidence-Based Substance Abuse Prevention via School-Extension Collaborations

ERIC Educational Resources Information Center

St. Pierre, Tena L.; Kaltreider, D. Lynne

2004-01-01

Despite availability of empirically supported school-based substance abuse prevention programs, adoption and implementation fidelity of such programs appear to be low. A replicated case study was conducted to investigate school adoption and implementation processes of the EXSELS model (Project ALERT delivered by program leaders through Cooperative…

Training Paraprofessionals to Target Socialization in Students with ASD: Fidelity of Implementation and Social Validity

ERIC Educational Resources Information Center

Kim, Sunny; Koegel, Robert L.; Koegel, Lynn K.

2017-01-01

Although the literature suggests that it is feasible to train paraprofessionals to effectively implement social interventions for students with Autism Spectrum Disorders (ASD), there is a paucity of research that addresses the social validity of these programs. The present study replicated and extended previous research on paraprofessional…

Mismatch Repair Balances Leading and Lagging Strand DNA Replication Fidelity

DTIC Science & Technology

2012-10-11

mismatched base stacks with a conserved phenylalanine in Msh6, and/or (iii) DNA flexibility, since MutSa-bound mismatched DNA is kinked, and a...AB, Watt DL , Watts BE, et al. (2010) Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol 6: 774–781. 24. Poloumienko A

Hysteresis Control of Parallel-Connected Hybrid Inverters

DTIC Science & Technology

2005-09-01

92 C. MILITARY APPLICATIONS .....................................................................92 D...unbalanced to replicate the “real-world” application of the controller. Other areas of the controller could be changed to improve the fidelity of the load...a chip to perform the complex mathematics to transform from one reference frame to another while automatically adjusting the filter parameters. The

Comparison of fresh-frozen cadaver and high-fidelity virtual reality simulator as methods of laparoscopic training.

PubMed

Sharma, Mitesh; Horgan, Alan

2012-08-01

The aim of this study was to compare fresh-frozen cadavers (FFC) with a high-fidelity virtual reality simulator (VRS) as training tools in minimal access surgery for complex and relatively simple procedures. A prospective comparative face validity study between FFC and VRS (LAP Mentor(™)) was performed. Surgeons were recruited to perform tasks on both FFC and VRS appropriately paired to their experience level. Group A (senior) performed a laparoscopic sigmoid colectomy, Group B (intermediate) performed a laparoscopic incisional hernia repair, and Group C (junior) performed basic laparoscopic tasks (BLT) (camera manipulation, hand-eye coordination, tissue dissection and hand-transferring skills). Each subject completed a 5-point Likert-type questionnaire rating the training modalities in nine domains. Data were analysed using nonparametric tests. Forty-five surgeons were recruited to participate (15 per skill group). Median scores for subjects in Group A were significantly higher for evaluation of FFC in all nine domains compared to VRS (p < 0.01). Group B scored FFC significantly better (p < 0.05) in all domains except task replication (p = 0.06). Group C scored FFC significantly better (p < 0.01) in eight domains but not on performance feedback (p = 0.09). When compared across groups, juniors accepted VRS as a training model more than did intermediate and senior groups on most domains (p < 0.01) except team work. Fresh-frozen cadaver is perceived as a significantly overall better model for laparoscopic training than the high-fidelity VRS by all training grades, irrespective of the complexity of the operative procedure performed. VRS is still useful when training junior trainees in BLT.

The role of technical assistance in the replication of effective HIV interventions.

PubMed

O'Donnell, L; Scattergood, P; Adler, M; Doval, A S; Barker, M; Kelly, J A; Kegeles, S M; Rebchook, G M; Adams, J; Terry, M A; Neumann, M S

2000-01-01

This article examines the role of technical assistance (TA) in supporting the replication of proven HIV interventions. A case study of the replication of the VOICES/VOCES intervention elucidates the level and types of TA provided to support new users through the adoption process. TA included help in garnering administrative support, identifying target audiences, recruiting groups for sessions, maintaining fidelity to the intervention's core elements, tailoring the intervention to meet clients' needs, strengthening staff members' facilitation skills, troubleshooting challenges, and devising strategies to sustain the intervention. Two to four hours per month of TA were provided to each agency adopting the intervention, at an estimated monthly cost of $206 to $412. Findings illustrate how TA supports replication by establishing a conversation between the researcher TA providers experienced with the intervention and new users. This communication helps preserve key program elements and contributes to ongoing refinement of the intervention.

The trouble with memes : Inference versus imitation in cultural creation.

PubMed

Atran, S

2001-12-01

Memes are hypothetical cultural units passed on by imitation; although nonbiological, they undergo Darwinian selection like genes. Cognitive study of multimodular human minds undermines memetics: unlike in genetic replication, high-fidelity transmission of cultural information is the exception, not the rule. Constant, rapid "mutation" of information during communication generates endlessly varied creations that nevertheless adhere to modular input conditions. The sort of cultural information most susceptible to modular processing is that most readily acquired by children, most easily transmitted across individuals, most apt to survive within a culture, most likely to recur in different cultures, and most disposed to cultural variation and elaboration.

A Novel Model System to Examine Agents Used in Breast Cancer Therapy.

DTIC Science & Technology

1996-07-01

DNA replication (DNA synthesome) isolated from MDA MB 468 human breast cancer cells, human breast tumor tissue and human breast tumor cell xenografts In the presence of the viral large T-antigen and simian virus 40 (SV40) origin sequences, the DNA synthesome executes all of the steps required for the in vitro replication of the SV40 genome. Furthermore, the DNA synthesome isolated from human breast cancer cells possesses a lower fidelity for DNA synthesis in vitro than the synthesome purified from a non-malignant breast cell line. Our studies indicate that the following

Learning nursing procedures: the influence of simulator fidelity and student gender on teaching effectiveness.

PubMed

Grady, Janet L; Kehrer, Rosemary G; Trusty, Carole E; Entin, Eileen B; Entin, Elliot E; Brunye, Tad T

2008-09-01

Simulation technologies are gaining widespread acceptance across a variety of educational domains and applications. The current research examines whether basic nursing procedure training with high-fidelity versus low-fidelity mannequins results in differential skill acquisition and perceptions of simulator utility. Fifty-two first-year students were taught nasogastric tube and indwelling urinary catheter insertion in one of two ways. The first group learned nasogastric tube and urinary catheter insertion using high-fidelity and low-fidelity mannequins, respectively, and the second group learned nasogastric tube and urinary catheter insertion using low-fidelity and high-fidelity mannequins, respectively. The dependent measures included student performance on nasogastric tube and urinary catheter insertion testing, as measured by observer-based instruments, and self-report questionnaires probing student attitudes about the use of simulation in nursing education. Results demonstrated higher performance with high-fidelity than with low-fidelity mannequin training. In response to a self-report posttraining questionnaire, participants expressed a more positive attitude toward the high-fidelity mannequin, especially regarding its responsiveness and realism.

Evaluating display fidelity and interaction fidelity in a virtual reality game.

PubMed

McMahan, Ryan P; Bowman, Doug A; Zielinski, David J; Brady, Rachael B

2012-04-01

In recent years, consumers have witnessed a technological revolution that has delivered more-realistic experiences in their own homes through high-definition, stereoscopic televisions and natural, gesture-based video game consoles. Although these experiences are more realistic, offering higher levels of fidelity, it is not clear how the increased display and interaction aspects of fidelity impact the user experience. Since immersive virtual reality (VR) allows us to achieve very high levels of fidelity, we designed and conducted a study that used a six-sided CAVE to evaluate display fidelity and interaction fidelity independently, at extremely high and low levels, for a VR first-person shooter (FPS) game. Our goal was to gain a better understanding of the effects of fidelity on the user in a complex, performance-intensive context. The results of our study indicate that both display and interaction fidelity significantly affect strategy and performance, as well as subjective judgments of presence, engagement, and usability. In particular, performance results were strongly in favor of two conditions: low-display, low-interaction fidelity (representative of traditional FPS games) and high-display, high-interaction fidelity (similar to the real world).

Fabrication of cylindrical superhydrophobic microchannels by replicating lotus leaf structures on internal walls

NASA Astrophysics Data System (ADS)

Das, Ajit; Bhaumik, Soubhik Kumar

2018-04-01

Cylindrical superhydrophobic microchannels are fabricated by replicating lotus leaf structures on internal walls. The fabrication process comprises of three steps: the creation of a cylindrical mold of a glass rod (125 µm) with polystyrene films bearing negative imprints of lotus leaf (superhydrophobic) structures; casting polydimethylsiloxane (PDMS, Sylgard 184) over the mold; and solvent-assisted pulling off of the glass rod to leave a positive replica on the inner wall of the PDMS cast. The last crucial step is achieved through selective dissolution of the intermediate negative replica layer in the cylindrical mold without any swelling effect. The high fidelity of the replication process is confirmed through scanning electron microscope (SEM) imaging. The attained superhydrophobicity is assessed by comparing the dynamics of the advancing meniscus in the fabricated microchannels with that over a similarly fabricated smooth microchannel. Contact angle studies of the meniscus reveal a lower capillary effect and drag force experienced by the superhydrophobic microchannel compared to smooth ones. Studies based on velocity lead to a prediction of a drag reduction of 35%. A new avenue is thus opened up for microfabrication and flow analysis of closed superhydrophobic (SH) conduits in lab on chip and microfluidic applications.

Engineering of DNA polymerase I from Thermus thermophilus using compartmentalized self-replication.

PubMed

Aye, Seaim Lwin; Fujiwara, Kei; Ueki, Asuka; Doi, Nobuhide

2018-05-05

Although compartmentalized self-replication (CSR) and compartmentalized partnered replication (CPR) are powerful tools for directed evolution of proteins and gene circuits, limitations remain in the emulsion PCR process with the wild-type Taq DNA polymerase used so far, including long run times, low amounts of product, and false negative results due to inhibitors. In this study, we developed a high-efficiency mutant of DNA polymerase I from Thermus thermophilus HB27 (Tth pol) suited for CSR and CPR. We modified the wild-type Tth pol by (i) deletion of the N-terminal 5' to 3' exonuclease domain, (ii) fusion with the DNA-binding protein Sso7d, (iii) introduction of four known effective point mutations from other DNA polymerase mutants, and (iv) codon optimization to reduce the GC content. Consequently, we obtained a mutant that provides higher product yields than the conventional Taq pol without decreased fidelity. Next, we performed four rounds of CSR selection with a randomly mutated library of this modified Tth pol and obtained mutants that provide higher product yields in fewer cycles of emulsion PCR than the parent Tth pol as well as the conventional Taq pol. Copyright © 2018 Elsevier Inc. All rights reserved.

Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion

PubMed Central

Hanna, Joseph S.; Kroll, Evgueny S.; Lundblad, Victoria; Spencer, Forrest A.

2001-01-01

CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion. We find that Ctf18p, an RFC1-like protein, directly interacts with Rfc2p, Rfc3p, Rfc4p, and Rfc5p. However, Ctf18p is not a component of biochemically purified proliferating cell nuclear antigen loading RF-C, suggesting the presence of a discrete complex containing Ctf18p, Rfc2p, Rfc3p, Rfc4p, and Rfc5p. Recent identification and characterization of the budding yeast polymerase κ, encoded by TRF4, strongly supports a hypothesis that the DNA replication machinery is required for proper sister chromatid cohesion. Analogous to the polymerase switching role of the bacterial and human RF-C complexes, we propose that budding yeast RF-CCTF18 may be involved in a polymerase switch event that facilities sister chromatid cohesion. The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process. PMID:11287619

Monitoring intervention fidelity of a lifestyle behavioral intervention delivered through telehealth

PubMed Central

Sineath, Ashley; Lambert, Lauren; Verga, Catherine; Wagstaff, Miranda

2017-01-01

Background Technology-based lifestyle behavioral interventions (i.e., telehealth, mHealth, eHealth, and/or digital health) are becoming an alternative standard of care and possess several advantages over traditional clinical settings such as convenience, cost, and the ability to tailor plans and feedback to a participant’s individual needs. These technology-based interventions also present unique challenges to intervention fidelity due to extra elements involved in executing the intervention. Intervention fidelity monitoring is essential to ensure internal and external validity, yet the development and utilization of fidelity protocols is under-reported in the literature. The purpose of this paper is to describe the intervention fidelity protocol for the 24-START study, a behavior change intervention delivered through telephone and internet. This paper also discusses the results of a pilot audit conducted to determine the feasibility of monitoring adherence to the fidelity protocol. Methods The 24-START fidelity protocol was developed in accordance with the five fidelity areas outlined by the NIH Behavior Change Consortium (NIH BCC) including: design of study, provider training, delivery of treatment, receipt of treatment, and enactment of treatment. The fidelity strategies provided by the NIH BCC in each area were tailored to fit the specific design of the 24-START study. Twenty-six total fidelity strategies were developed in accordance with the five areas and a corresponding fidelity monitoring plan was created. Because these strategies are only beneficial if implemented, the fidelity monitoring plan was developed to ensure the fidelity strategies are consistently implemented over the course of the intervention. Results A pilot audit of nine participant files was conducted to test the feasibility of the fidelity protocol developed. Out of the nine participant files reviewed, 89% of scheduled phone calls between a telehealth coach and participant were successfully completed. Of the completed calls, telehealth coaches delivered the intervention as intended 85.3% of the time, and 74% of planned secondary contacts made through the internet were delivered successfully. Additionally, between treatment group dosing was found to be equal. Several weak areas in the fidelity protocol were identified for improvement. The results were satisfactory and the audit was deemed feasible for ongoing use. Conclusions The NIH BCC provides a valuable framework for telehealth interventions to develop fidelity protocols ultimately contributing to improved internal and external validity, better translation of results, increased transparency, and increased opportunities for replication within the field. The 24-START pilot audit found the fidelity protocol efficacious and feasible while also identifying areas of weakness in need of revision. The refined protocol will continue to be utilized throughout the data collection phase. Future telehealth interventions should develop and disclose fidelity protocols to improve the overall quality and standard of telehealth interventions. PMID:28894745

Monitoring intervention fidelity of a lifestyle behavioral intervention delivered through telehealth.

PubMed

Sineath, Ashley; Lambert, Lauren; Verga, Catherine; Wagstaff, Miranda; Wingo, Brooks C

2017-01-01

Technology-based lifestyle behavioral interventions (i.e., telehealth, mHealth, eHealth, and/or digital health) are becoming an alternative standard of care and possess several advantages over traditional clinical settings such as convenience, cost, and the ability to tailor plans and feedback to a participant's individual needs. These technology-based interventions also present unique challenges to intervention fidelity due to extra elements involved in executing the intervention. Intervention fidelity monitoring is essential to ensure internal and external validity, yet the development and utilization of fidelity protocols is under-reported in the literature. The purpose of this paper is to describe the intervention fidelity protocol for the 24-START study, a behavior change intervention delivered through telephone and internet. This paper also discusses the results of a pilot audit conducted to determine the feasibility of monitoring adherence to the fidelity protocol. The 24-START fidelity protocol was developed in accordance with the five fidelity areas outlined by the NIH Behavior Change Consortium (NIH BCC) including: design of study, provider training, delivery of treatment, receipt of treatment, and enactment of treatment. The fidelity strategies provided by the NIH BCC in each area were tailored to fit the specific design of the 24-START study. Twenty-six total fidelity strategies were developed in accordance with the five areas and a corresponding fidelity monitoring plan was created. Because these strategies are only beneficial if implemented, the fidelity monitoring plan was developed to ensure the fidelity strategies are consistently implemented over the course of the intervention. A pilot audit of nine participant files was conducted to test the feasibility of the fidelity protocol developed. Out of the nine participant files reviewed, 89% of scheduled phone calls between a telehealth coach and participant were successfully completed. Of the completed calls, telehealth coaches delivered the intervention as intended 85.3% of the time, and 74% of planned secondary contacts made through the internet were delivered successfully. Additionally, between treatment group dosing was found to be equal. Several weak areas in the fidelity protocol were identified for improvement. The results were satisfactory and the audit was deemed feasible for ongoing use. The NIH BCC provides a valuable framework for telehealth interventions to develop fidelity protocols ultimately contributing to improved internal and external validity, better translation of results, increased transparency, and increased opportunities for replication within the field. The 24-START pilot audit found the fidelity protocol efficacious and feasible while also identifying areas of weakness in need of revision. The refined protocol will continue to be utilized throughout the data collection phase. Future telehealth interventions should develop and disclose fidelity protocols to improve the overall quality and standard of telehealth interventions.

Nanoimprinting on optical fiber end faces for chemical sensing

NASA Astrophysics Data System (ADS)

Kostovski, G.; White, D. J.; Mitchell, A.; Austin, M. W.; Stoddart, P. R.

2008-04-01

Optical fiber surface-enhanced Raman scattering (SERS) sensors offer a potential solution to monitoring low chemical concentrations in-situ or in remote sensing scenarios. We demonstrate the use of nanoimprint lithography to fabricate SERS-compatible nanoarrays on the end faces of standard silica optical fibers. The antireflective nanostructure found on cicada wings was used as a convenient template for the nanoarray, as high sensitivity SERS substrates have previously been demonstrated on these surfaces. Coating the high fidelity replicas with silver creates a dense array of regular nanoscale plasmonic resonators. A monolayer of thiophenol was used as a low concentration analyte, from which strong Raman spectra were collected using both direct endface illumination and through-fiber interrogation. This unique combination of nanoscale replication with optical fibers demonstrates a high-resolution, low-cost approach to fabricating high-performance optical fiber chemical sensors.

Evaluating Multiple Levels of an Interaction Fidelity Continuum on Performance and Learning in Near-Field Training Simulations.

PubMed

Bhargava, Ayush; Bertrand, Jeffrey W; Gramopadhye, Anand K; Madathil, Kapil C; Babu, Sabarish V

2018-04-01

With costs of head-mounted displays (HMDs) and tracking technology decreasing rapidly, various virtual reality applications are being widely adopted for education and training. Hardware advancements have enabled replication of real-world interactions in virtual environments to a large extent, paving the way for commercial grade applications that provide a safe and risk-free training environment at a fraction of the cost. But this also mandates the need to develop more intrinsic interaction techniques and to empirically evaluate them in a more comprehensive manner. Although there exists a body of previous research that examines the benefits of selected levels of interaction fidelity on performance, few studies have investigated the constituent components of fidelity in a Interaction Fidelity Continuum (IFC) with several system instances and their respective effects on performance and learning in the context of a real-world skills training application. Our work describes a large between-subjects investigation conducted over several years that utilizes bimanual interaction metaphors at six discrete levels of interaction fidelity to teach basic precision metrology concepts in a near-field spatial interaction task in VR. A combined analysis performed on the data compares and contrasts the six different conditions and their overall effects on performance and learning outcomes, eliciting patterns in the results between the discrete application points on the IFC. With respect to some performance variables, results indicate that simpler restrictive interaction metaphors and highest fidelity metaphors perform better than medium fidelity interaction metaphors. In light of these results, a set of general guidelines are created for developers of spatial interaction metaphors in immersive virtual environments for precise fine-motor skills training simulations.

Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools

PubMed Central

Waisertreiger, Irina S.-R.; Liston, Victoria G.; Menezes, Miriam R.; Kim, Hyun-Min; Lobachev, Kirill S.; Stepchenkova, Elena I.; Tahirov, Tahir H.; Rogozin, Igor B.; Pavlov, Youri. I.

2014-01-01

The rate of mutations in eukaryotes depends on a plethora of factors and is not immediately derived from the fidelity of DNA polymerases (Pols). Replication of chromosomes containing the anti-parallel strands of duplex DNA occurs through the copying of leading and lagging strand templates by a trio of Pols α, δ and ε, with the assistance of Pol ζ and Y-family Pols at difficult DNA template structures or sites of DNA damage. The parameters of the synthesis at a given location are dictated by the quality and quantity of nucleotides in the pools, replication fork architecture, transcription status, regulation of Pol switches, and structure of chromatin. The result of these transactions is a subject of survey and editing by DNA repair. PMID:23055184

Structural Dynamics of Picornaviral RdRP Complexes. Implications for the Design of Antivirals

NASA Astrophysics Data System (ADS)

Verdaguer, Núria; Ferrer-Orta, Cristina; Domingo, Esteban

Genome replication in picornavirus is catalyzed by a virally encoded RNA dependent RNA polymerase, termed 3D. These viruses also use a small protein primer, named VPg to initiate RNA replication. Polymerase 3D also catalyzes the covalent linkage of UMP to a N-terminal tyrosine on VPg. Seven different crystal structures of foot-and-mouth disease virus (FMDV) 3D catalytic complexes have enhanced our understanding of template and primer recognition, VPg uridylylation and rNTP binding and catalysis. In addition, the biochemical and structural analyses of six different FMDV 3D ribavirin resistant mutants provided evidences of three different mechanisms of resistance to this mutagenic nucleoside analogue. Such structural information is providing new insights into the fidelity of RNA replication, and for the design of antiviral compounds.

Transient dominant host-range selection using Chinese hamster ovary cells to generate marker-free recombinant viral vectors from vaccinia virus.

PubMed

Liu, Liang; Cooper, Tamara; Eldi, Preethi; Garcia-Valtanen, Pablo; Diener, Kerrilyn R; Howley, Paul M; Hayball, John D

2017-04-01

Recombinant vaccinia viruses (rVACVs) are promising antigen-delivery systems for vaccine development that are also useful as research tools. Two common methods for selection during construction of rVACV clones are (i) co-insertion of drug resistance or reporter protein genes, which requires the use of additional selection drugs or detection methods, and (ii) dominant host-range selection. The latter uses VACV variants rendered replication-incompetent in host cell lines by the deletion of host-range genes. Replicative ability is restored by co-insertion of the host-range genes, providing for dominant selection of the recombinant viruses. Here, we describe a new method for the construction of rVACVs using the cowpox CP77 protein and unmodified VACV as the starting material. Our selection system will expand the range of tools available for positive selection of rVACV during vector construction, and it is substantially more high-fidelity than approaches based on selection for drug resistance.

Poliovirus RNA polymerase: in vitro enzymatic activities, fidelity of replication, and characterization of a temperature-sensitive RNA-negative mutant

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

Stokes, M.A.M.

1985-01-01

The in vitro activities of the purified poliovirus RNA polymerase were investigated in this study. The polymerase was shown to be a strict RNA dependent RNA polymerase. It only copied RNA templates but used either a DNA or RNA primer to initiate RNA synthesis. Partially purified polymerase has some DNA polymerase activities. Additional purification of the enzyme and studies with a mutant poliovirus RNA polymerase indicated that the DNA polymerase activities were due to a cellular polymerase. The fidelity of RNA replication in vitro by the purified poliovirus RNA polymerase was studied by measuring the rate of misincorporation of noncomplementarymore » ribonucleotide monophosphates on synthetic homopolymeric RNA templates. The results showed that the ratio of noncomplementary to complementary ribonucleotides incorporated was 1-5 x 10/sup -3/. The viral polymerase of a poliovirus temperature sensitive RNA-negative mutant, Ts 10, was isolated. This study confirmed that the mutant was viable 33/sup 0/, but was RNA negative at 39/sup 0/. Characterization of the Ts 10 polymerase showed it was significantly more sensitive to heat inactivation than was the old-type polymerase. Highly purified poliovirions were found to contain several noncapsid proteins. At least two of these proteins were labeled by (/sup 35/S)methionine infected cells and appeared to be virally encoded proteins. One of these proteins was immunoprecipitated by anti-3B/sup vpg/ antiserum. This protein had the approximate Mr = 50,000 and appeared to be one of the previously identified 3B/sup vpg/ precursor proteins.« less

In Vitro Lesion Bypass Studies of O(4)-Alkylthymidines with Human DNA Polymerase η.

PubMed

Williams, Nicole L; Wang, Pengcheng; Wu, Jiabin; Wang, Yinsheng

2016-04-18

Environmental exposure and endogenous metabolism can give rise to DNA alkylation. Among alkylated nucleosides, O(4)-alkylthymidine (O(4)-alkyldT) lesions are poorly repaired in mammalian systems and may compromise the efficiency and fidelity of cellular DNA replication. To cope with replication-stalling DNA lesions, cells are equipped with translesion synthesis DNA polymerases that are capable of bypassing various DNA lesions. In this study, we assessed human DNA polymerase η (Pol η)-mediated bypass of various O(4)-alkyldT lesions, with the alkyl group being Me, Et, nPr, iPr, nBu, iBu, (R)-sBu, or (S)-sBu, in template DNA by conducting primer extension and steady-state kinetic assays. Our primer extension assay results revealed that human Pol η, but not human polymerases κ and ι or yeast polymerase ζ, was capable of bypassing all O(4)-alkyldT lesions and extending the primer to generate full-length replication products. Data from steady-state kinetic measurements showed that Pol η preferentially misincorporated dGMP opposite O(4)-alkyldT lesions with a straight-chain alkyl group. The nucleotide misincorporation opposite most lesions with a branched-chain alkyl group was, however, not selective, where dCMP, dGMP, and dTMP were inserted at similar efficiencies opposite O(4)-iPrdT, O(4)-iBudT, and O(4)-(R)-sBudT. These results provide important knowledge about the effects of the length and structure of the alkyl group in O(4)-alkyldT lesions on the fidelity and efficiency of DNA replication mediated by human Pol η.

The effect of bench model fidelity on fluoroscopy-guided transforaminal epidural injection training: a randomized control study.

PubMed

Gonzalez-Cota, Alan; Chiravuri, Srinivas; Stansfield, R Brent; Brummett, Chad M; Hamstra, Stanley J

2013-01-01

The purpose of this study was to determine whether high-fidelity simulators provide greater benefit than low-fidelity models in training fluoroscopy-guided transforaminal epidural injection. This educational study was a single-center, prospective, randomized 3-arm pretest-posttest design with a control arm. Eighteen anesthesia and physical medicine and rehabilitation residents were instructed how to perform a fluoroscopy-guided transforaminal epidural injection and assessed by experts on a reusable injectable phantom cadaver. The high- and low-fidelity groups received 30 minutes of supervised hands-on practice according to group assignment, and the control group received 30 minutes of didactic instruction from an expert. We found no differences at posttest between the high- and low-fidelity groups on global ratings of performance (P = 0.17) or checklist scores (P = 0.81). Participants who received either form of hands-on training significantly outperformed the control group on both the global rating of performance (control vs low-fidelity, P = 0.0048; control vs high-fidelity, P = 0.0047) and the checklist (control vs low-fidelity, P = 0.0047; control vs high-fidelity, P = 0.0047). Training an epidural procedure using a low-fidelity model may be equally effective as training on a high-fidelity model. These results are consistent with previous research on a variety of interventional procedures and further demonstrate the potential impact of simple, low-fidelity training models.

5-ASA Affects Cell Cycle Progression in Colorectal Cells by Reversibly Activating a Replication Checkpoint

PubMed Central

LUCIANI, M. GLORIA; CAMPREGHER, CHRISTOPH; FORTUNE, JOHN M.; KUNKEL, THOMAS A.; GASCHE, CHRISTOPH

2007-01-01

Background & Aims Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. Methods CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116p53−/−, HCT116+chr3, and LoVo were treated with 5-ASA for 2–96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. Results We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. Conclusions Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis. PMID:17241873

Complete tomography of a high-fidelity solid-state entangled spin-photon qubit pair.

PubMed

De Greve, Kristiaan; McMahon, Peter L; Yu, Leo; Pelc, Jason S; Jones, Cody; Natarajan, Chandra M; Kim, Na Young; Abe, Eisuke; Maier, Sebastian; Schneider, Christian; Kamp, Martin; Höfling, Sven; Hadfield, Robert H; Forchel, Alfred; Fejer, M M; Yamamoto, Yoshihisa

2013-01-01

Entanglement between stationary quantum memories and photonic qubits is crucial for future quantum communication networks. Although high-fidelity spin-photon entanglement was demonstrated in well-isolated atomic and ionic systems, in the solid-state, where massively parallel, scalable networks are most realistically conceivable, entanglement fidelities are typically limited due to intrinsic environmental interactions. Distilling high-fidelity entangled pairs from lower-fidelity precursors can act as a remedy, but the required overhead scales unfavourably with the initial entanglement fidelity. With spin-photon entanglement as a crucial building block for entangling quantum network nodes, obtaining high-fidelity entangled pairs becomes imperative for practical realization of such networks. Here we report the first results of complete state tomography of a solid-state spin-photon-polarization-entangled qubit pair, using a single electron-charged indium arsenide quantum dot. We demonstrate record-high fidelity in the solid-state of well over 90%, and the first (99.9%-confidence) achievement of a fidelity that will unambiguously allow for entanglement distribution in solid-state quantum repeater networks.

Gaussian functional regression for output prediction: Model assimilation and experimental design

NASA Astrophysics Data System (ADS)

Nguyen, N. C.; Peraire, J.

2016-03-01

In this paper, we introduce a Gaussian functional regression (GFR) technique that integrates multi-fidelity models with model reduction to efficiently predict the input-output relationship of a high-fidelity model. The GFR method combines the high-fidelity model with a low-fidelity model to provide an estimate of the output of the high-fidelity model in the form of a posterior distribution that can characterize uncertainty in the prediction. A reduced basis approximation is constructed upon the low-fidelity model and incorporated into the GFR method to yield an inexpensive posterior distribution of the output estimate. As this posterior distribution depends crucially on a set of training inputs at which the high-fidelity models are simulated, we develop a greedy sampling algorithm to select the training inputs. Our approach results in an output prediction model that inherits the fidelity of the high-fidelity model and has the computational complexity of the reduced basis approximation. Numerical results are presented to demonstrate the proposed approach.

Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases

PubMed Central

Canard, Bruno

2018-01-01

Viral RNA-dependent RNA polymerases (RdRps) play a central role not only in viral replication, but also in the genetic evolution of viral RNAs. After binding to an RNA template and selecting 5′-triphosphate ribonucleosides, viral RdRps synthesize an RNA copy according to Watson-Crick base-pairing rules. The copy process sometimes deviates from both the base-pairing rules specified by the template and the natural ribose selectivity and, thus, the process is error-prone due to the intrinsic (in)fidelity of viral RdRps. These enzymes share a number of conserved amino-acid sequence strings, called motifs A–G, which can be defined from a structural and functional point-of-view. A co-relation is gradually emerging between mutations in these motifs and viral genome evolution or observed mutation rates. Here, we review our current knowledge on these motifs and their role on the structural and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps. PMID:29385764

Nonlinear information fusion algorithms for data-efficient multi-fidelity modelling.

PubMed

Perdikaris, P; Raissi, M; Damianou, A; Lawrence, N D; Karniadakis, G E

2017-02-01

Multi-fidelity modelling enables accurate inference of quantities of interest by synergistically combining realizations of low-cost/low-fidelity models with a small set of high-fidelity observations. This is particularly effective when the low- and high-fidelity models exhibit strong correlations, and can lead to significant computational gains over approaches that solely rely on high-fidelity models. However, in many cases of practical interest, low-fidelity models can only be well correlated to their high-fidelity counterparts for a specific range of input parameters, and potentially return wrong trends and erroneous predictions if probed outside of their validity regime. Here we put forth a probabilistic framework based on Gaussian process regression and nonlinear autoregressive schemes that is capable of learning complex nonlinear and space-dependent cross-correlations between models of variable fidelity, and can effectively safeguard against low-fidelity models that provide wrong trends. This introduces a new class of multi-fidelity information fusion algorithms that provide a fundamental extension to the existing linear autoregressive methodologies, while still maintaining the same algorithmic complexity and overall computational cost. The performance of the proposed methods is tested in several benchmark problems involving both synthetic and real multi-fidelity datasets from computational fluid dynamics simulations.

Translesion synthesis DNA polymerases promote error-free replication through the minor-groove DNA adduct 3-deaza-3-methyladenine.

PubMed

Yoon, Jung-Hoon; Roy Choudhury, Jayati; Park, Jeseong; Prakash, Satya; Prakash, Louise

2017-11-10

N3-Methyladenine (3-MeA) is formed in DNA by reaction with S -adenosylmethionine, the reactive methyl donor, and by reaction with alkylating agents. 3-MeA protrudes into the DNA minor groove and strongly blocks synthesis by replicative DNA polymerases (Pols). However, the mechanisms for replicating through this lesion in human cells remain unidentified. Here we analyzed the roles of translesion synthesis (TLS) Pols in the replication of 3-MeA-damaged DNA in human cells. Because 3-MeA has a short half-life in vitro , we used the stable 3-deaza analog, 3-deaza-3-methyladenine (3-dMeA), which blocks the DNA minor groove similarly to 3-MeA. We found that replication through the 3-dMeA adduct is mediated via three different pathways, dependent upon Polι/Polκ, Polθ, and Polζ. As inferred from biochemical studies, in the Polι/Polκ pathway, Polι inserts a nucleotide (nt) opposite 3-dMeA and Polκ extends synthesis from the inserted nt. In the Polθ pathway, Polθ carries out both the insertion and extension steps of TLS opposite 3-dMeA, and in the Polζ pathway, Polζ extends synthesis following nt insertion by an as yet unidentified Pol. Steady-state kinetic analyses indicated that Polι and Polθ insert the correct nt T opposite 3-dMeA with a much reduced catalytic efficiency and that both Pols exhibit a high propensity for inserting a wrong nt opposite this adduct. However, despite their low fidelity of synthesis opposite 3-dMeA, TLS opposite this lesion replicates DNA in a highly error-free manner in human cells. We discuss the implications of these observations for TLS mechanisms in human cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Biochemical analysis of active site mutations of human polymerase η.

PubMed

Suarez, Samuel C; Beardslee, Renee A; Toffton, Shannon M; McCulloch, Scott D

2013-01-01

DNA polymerase η (pol η) plays a critical role in suppressing mutations caused by the bypass of cis-syn cyclobutane pyrimidine dimers (CPD) that escape repair. There is evidence this is also the case for the oxidative lesion 7,8-dihydro-8-oxo-guanine (8-oxoG). Both of these lesions cause moderate to severe blockage of synthesis when encountered by replicative polymerases, while pol η displays little no to pausing during translesion synthesis. However, since lesion bypass does not remove damaged DNA from the genome and can possibly be accompanied by errors in synthesis during bypass, the process is often called 'damage tolerance' to delineate it from classical DNA repair pathways. The fidelity of lesion bypass is therefore of importance when determining how pol η suppresses mutations after DNA damage. As pol η has been implicated in numerous in vivo pathways other than lesion bypass, we wanted to better understand the molecular mechanisms involved in the relatively low-fidelity synthesis displayed by pol η. To that end, we have created a set of mutant pol η proteins each containing a single amino acid substitution in the active site and closely surrounding regions. We determined overall DNA synthesis ability as well as the efficiency and fidelity of bypass of thymine-thymine CPD (T-T CPD) and 8-oxoG containing DNA templates. Our results show that several amino acids are critical for normal polymerase function, with changes in overall activity and fidelity being observed. Of the mutants that retain polymerase activity, we demonstrate that amino acids Q38, Y52, and R61 play key roles in determining polymerase fidelity, with substation of alanine causing both increases and decreases in fidelity. Remarkably, the Q38A mutant displays increased fidelity during synthesis opposite 8-oxoG but decreased fidelity during synthesis opposite a T-T CPD. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-fidelity stochastic collocation method for computation of statistical moments

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

Zhu, Xueyu, E-mail: xueyu-zhu@uiowa.edu; Linebarger, Erin M., E-mail: aerinline@sci.utah.edu; Xiu, Dongbin, E-mail: xiu.16@osu.edu

We present an efficient numerical algorithm to approximate the statistical moments of stochastic problems, in the presence of models with different fidelities. The method extends the multi-fidelity approximation method developed in . By combining the efficiency of low-fidelity models and the accuracy of high-fidelity models, our method exhibits fast convergence with a limited number of high-fidelity simulations. We establish an error bound of the method and present several numerical examples to demonstrate the efficiency and applicability of the multi-fidelity algorithm.

High Versus Low Theoretical Fidelity Pedometer Intervention Using Social-Cognitive Theory on Steps and Self-Efficacy.

PubMed

Raedeke, Thomas D; Dlugonski, Deirdre

2017-12-01

This study was designed to compare a low versus high theoretical fidelity pedometer intervention applying social-cognitive theory on step counts and self-efficacy. Fifty-six public university employees participated in a 10-week randomized controlled trial with 2 conditions that varied in theoretical fidelity. Participants in the high theoretical fidelity condition wore a pedometer and participated in a weekly group walk followed by a meeting to discuss cognitive-behavioral strategies targeting self-efficacy. Participants in the low theoretical fidelity condition met for a group walk and also used a pedometer as a motivational tool and to monitor steps. Step counts were assessed throughout the 10-week intervention and after a no-treatment follow-up (20 weeks and 30 weeks). Self-efficacy was measured preintervention and postintervention. Participants in the high theoretical fidelity condition increased daily steps by 2,283 from preintervention to postintervention, whereas participants in the low fidelity condition demonstrated minimal change during the same time period (p = .002). Individuals attending at least 80% of the sessions in the high theoretical fidelity condition showed an increase of 3,217 daily steps (d = 1.03), whereas low attenders increased by 925 (d = 0.40). Attendance had minimal impact in the low theoretical fidelity condition. Follow-up data revealed that step counts were at least somewhat maintained. For self-efficacy, participants in the high, compared with those in the low, theoretical fidelity condition showed greater improvements. Findings highlight the importance of basing activity promotion efforts on theory. The high theoretical fidelity intervention that included cognitive-behavioral strategies targeting self-efficacy was more effective than the low theoretical fidelity intervention, especially for those with high attendance.

An information theoretic approach to use high-fidelity codes to calibrate low-fidelity codes

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

Lewis, Allison, E-mail: lewis.allison10@gmail.com; Smith, Ralph; Williams, Brian

For many simulation models, it can be prohibitively expensive or physically infeasible to obtain a complete set of experimental data to calibrate model parameters. In such cases, one can alternatively employ validated higher-fidelity codes to generate simulated data, which can be used to calibrate the lower-fidelity code. In this paper, we employ an information-theoretic framework to determine the reduction in parameter uncertainty that is obtained by evaluating the high-fidelity code at a specific set of design conditions. These conditions are chosen sequentially, based on the amount of information that they contribute to the low-fidelity model parameters. The goal is tomore » employ Bayesian experimental design techniques to minimize the number of high-fidelity code evaluations required to accurately calibrate the low-fidelity model. We illustrate the performance of this framework using heat and diffusion examples, a 1-D kinetic neutron diffusion equation, and a particle transport model, and include initial results from the integration of the high-fidelity thermal-hydraulics code Hydra-TH with a low-fidelity exponential model for the friction correlation factor.« less

Transfer the multiscale texture of crystalline Si onto thin-film micromorph cell by UV nanoimprint for light trapping

NASA Astrophysics Data System (ADS)

Liu, Daiming; Wang, Qingkang; Wang, Qing

2018-05-01

Surface texturing is of great significance in light trapping for solar cells. Herein, the multiscale texture, consisting of microscale pyramids and nanoscale porous arrangement, was fabricated on crystalline Si by KOH etching and Ag-assisted HF etching processes and subsequently replicated onto glass with high fidelity by UV nanoimprint method. Light trapping of the multiscale texture was studied by spectral (reflectance, haze ratio) characterizations. Results reveal the multiscale texture provides the broadband reflection reducing, the highlighted light scattering and the additional self-cleaning behaviors. Compared with bare cell, the multiscale textured micromorph cell achieves a 4% relative increase in power conversion efficiency. This surface texturing route paves a promising way for developing low-cost, large-scale and high-efficiency solar applications.

Synthesis and Evolution of a Threose Nucleic Acid Aptamer Bearing 7-Deaza-7-Substituted Guanosine Residues.

PubMed

Mei, Hui; Liao, Jen-Yu; Jimenez, Randi M; Wang, Yajun; Bala, Saikat; McCloskey, Cailen; Switzer, Christopher; Chaput, John C

2018-05-02

In vitro selection experiments carried out on artificial genetic polymers require robust and faithful methods for copying genetic information back and forth between DNA and xeno-nucleic acids (XNA). Previously, we have shown that Kod-RI, an engineered polymerase developed to transcribe DNA templates into threose nucleic acid (TNA), can function with high fidelity in the absence of manganese ions. However, the transcriptional efficiency of this enzyme diminishes greatly when individual templates are replaced with libraries of DNA sequences, indicating that manganese ions are still required for in vitro selection. Unfortunately, the presence of manganese ions in the transcription mixture leads to the misincorporation of tGTP nucleotides opposite dG residues in the templating strand, which are detected as G-to-C transversions when the TNA is reverse transcribed back into DNA. Here we report the synthesis and fidelity of TNA replication using 7-deaza-7-modified guanosine base analogues in the DNA template and incoming TNA nucleoside triphosphate. Our findings reveal that tGTP misincorporation occurs via a Hoogsteen base pair in which the incoming tGTP residue adopts a syn conformation with respect to the sugar. Substitution of tGTP for 7-deaza-7-phenyl tGTP enabled the synthesis of TNA polymers with >99% overall fidelity. A TNA library containing the 7-deaza-7-phenyl guanine analogue was used to evolve a biologically stable TNA aptamer that binds to HIV reverse transcriptase with low nanomolar affinity.

The steric gate of DNA polymerase ι regulates ribonucleotide incorporation and deoxyribonucleotide fidelity.

PubMed

Donigan, Katherine A; McLenigan, Mary P; Yang, Wei; Goodman, Myron F; Woodgate, Roger

2014-03-28

Accurate DNA synthesis in vivo depends on the ability of DNA polymerases to select dNTPs from a nucleotide pool dominated by NTPs. High fidelity replicative polymerases have evolved to efficiently exclude NTPs while copying long stretches of undamaged DNA. However, to bypass DNA damage, cells utilize specialized low fidelity polymerases to perform translesion DNA synthesis (TLS). Of interest is human DNA polymerase ι (pol ι), which has been implicated in TLS of oxidative and UV-induced lesions. Here, we evaluate the ability of pol ι to incorporate NTPs during DNA synthesis. pol ι incorporates and extends NTPs opposite damaged and undamaged template bases in a template-specific manner. The Y39A "steric gate" pol ι mutant is considerably more active in the presence of Mn(2+) compared with Mg(2+) and exhibits a marked increase in NTP incorporation and extension, and surprisingly, it also exhibits increased dNTP base selectivity. Our results indicate that a single residue in pol ι is able to discriminate between NTPs and dNTPs during DNA synthesis. Because wild-type pol ι incorporates NTPs in a template-specific manner, certain DNA sequences may be "at risk" for elevated mutagenesis during pol ι-dependent TLS. Molecular modeling indicates that the constricted active site of wild-type pol ι becomes more spacious in the Y39A variant. Therefore, the Y39A substitution not only permits incorporation of ribonucleotides but also causes the enzyme to favor faithful Watson-Crick base pairing over mutagenic configurations.

Fidelity to the housing first model and effectiveness of permanent supported housing programs in California.

PubMed

Gilmer, Todd P; Stefancic, Ana; Katz, Marian L; Sklar, Marisa; Tsemberis, Sam; Palinkas, Lawrence A

2014-11-01

Permanent supported housing programs are being implemented throughout the United States. This study examined the relationship between fidelity to the Housing First model and residential outcomes among clients of full service partnerships (FSPs) in California. This study had a mixed-methods design. Quantitative administrative and survey data were used to describe FSP practices and to examine the association between fidelity to Housing First and residential outcomes in the year before and after enrollment of 6,584 FSP clients in 86 programs. Focus groups at 20 FSPs provided qualitative data to enhance the understanding of these findings with actual accounts of housing-related experiences in high- and low-fidelity programs. Prior to enrollment, the mean days of homelessness were greater at high- versus low-fidelity (101 versus 46 days) FSPs. After adjustment for individual characteristics, the analysis found that days spent homeless after enrollment declined by 87 at high-fidelity programs and by 34 at low-fidelity programs. After adjustment for days spent homeless before enrollment, days spent homeless after enrollment declined by 63 at high-fidelity programs and by 53 at low-fidelity programs. After enrollment, clients at high-fidelity programs spent more than 60 additional days in apartments than clients at low-facility programs. Differences were found between high- and low-fidelity FSPs in client choice in housing and how much clients' goals were considered in housing placement. Programs with greater fidelity to the Housing First model enrolled clients with longer histories of homelessness and placed most of them in apartments.

Transcriptional fidelities of human mitochondrial POLRMT, yeast mitochondrial Rpo41, and phage T7 single-subunit RNA polymerases.

PubMed

Sultana, Shemaila; Solotchi, Mihai; Ramachandran, Aparna; Patel, Smita S

2017-11-03

Single-subunit RNA polymerases (RNAPs) are present in phage T7 and in mitochondria of all eukaryotes. This RNAP class plays important roles in biotechnology and cellular energy production, but we know little about its fidelity and error rates. Herein, we report the error rates of three single-subunit RNAPs measured from the catalytic efficiencies of correct and all possible incorrect nucleotides. The average error rates of T7 RNAP (2 × 10 -6 ), yeast mitochondrial Rpo41 (6 × 10 -6 ), and human mitochondrial POLRMT (RNA polymerase mitochondrial) (2 × 10 -5 ) indicate high accuracy/fidelity of RNA synthesis resembling those of replicative DNA polymerases. All three RNAPs exhibit a distinctly high propensity for GTP misincorporation opposite dT, predicting frequent A→G errors in RNA with rates of ∼10 -4 The A→C, G→A, A→U, C→U, G→U, U→C, and U→G errors mostly due to pyrimidine-purine mismatches were relatively frequent (10 -5 -10 -6 ), whereas C→G, U→A, G→C, and C→A errors from purine-purine and pyrimidine-pyrimidine mismatches were rare (10 -7 -10 -10 ). POLRMT also shows a high C→A error rate on 8-oxo-dG templates (∼10 -4 ). Strikingly, POLRMT shows a high mutagenic bypass rate, which is exacerbated by TEFM (transcription elongation factor mitochondrial). The lifetime of POLRMT on terminally mismatched elongation substrate is increased in the presence of TEFM, which allows POLRMT to efficiently bypass the error and continue with transcription. This investigation of nucleotide selectivity on normal and oxidatively damaged DNA by three single-subunit RNAPs provides the basic information to understand the error rates in mitochondria and, in the case of T7 RNAP, to assess the quality of in vitro transcribed RNAs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The Validity and Incremental Validity of Knowledge Tests, Low-Fidelity Simulations, and High-Fidelity Simulations for Predicting Job Performance in Advanced-Level High-Stakes Selection

ERIC Educational Resources Information Center

Lievens, Filip; Patterson, Fiona

2011-01-01

In high-stakes selection among candidates with considerable domain-specific knowledge and experience, investigations of whether high-fidelity simulations (assessment centers; ACs) have incremental validity over low-fidelity simulations (situational judgment tests; SJTs) are lacking. Therefore, this article integrates research on the validity of…

A multi-fidelity framework for physics based rotor blade simulation and optimization

NASA Astrophysics Data System (ADS)

Collins, Kyle Brian

New helicopter rotor designs are desired that offer increased efficiency, reduced vibration, and reduced noise. Rotor Designers in industry need methods that allow them to use the most accurate simulation tools available to search for these optimal designs. Computer based rotor analysis and optimization have been advanced by the development of industry standard codes known as "comprehensive" rotorcraft analysis tools. These tools typically use table look-up aerodynamics, simplified inflow models and perform aeroelastic analysis using Computational Structural Dynamics (CSD). Due to the simplified aerodynamics, most design studies are performed varying structural related design variables like sectional mass and stiffness. The optimization of shape related variables in forward flight using these tools is complicated and results are viewed with skepticism because rotor blade loads are not accurately predicted. The most accurate methods of rotor simulation utilize Computational Fluid Dynamics (CFD) but have historically been considered too computationally intensive to be used in computer based optimization, where numerous simulations are required. An approach is needed where high fidelity CFD rotor analysis can be utilized in a shape variable optimization problem with multiple objectives. Any approach should be capable of working in forward flight in addition to hover. An alternative is proposed and founded on the idea that efficient hybrid CFD methods of rotor analysis are ready to be used in preliminary design. In addition, the proposed approach recognizes the usefulness of lower fidelity physics based analysis and surrogate modeling. Together, they are used with high fidelity analysis in an intelligent process of surrogate model building of parameters in the high fidelity domain. Closing the loop between high and low fidelity analysis is a key aspect of the proposed approach. This is done by using information from higher fidelity analysis to improve predictions made with lower fidelity models. This thesis documents the development of automated low and high fidelity physics based rotor simulation frameworks. The low fidelity framework uses a comprehensive code with simplified aerodynamics. The high fidelity model uses a parallel processor capable CFD/CSD methodology. Both low and high fidelity frameworks include an aeroacoustic simulation for prediction of noise. A synergistic process is developed that uses both the low and high fidelity frameworks together to build approximate models of important high fidelity metrics as functions of certain design variables. To test the process, a 4-bladed hingeless rotor model is used as a baseline. The design variables investigated include tip geometry and spanwise twist distribution. Approximation models are built for metrics related to rotor efficiency and vibration using the results from 60+ high fidelity (CFD/CSD) experiments and 400+ low fidelity experiments. Optimization using the approximation models found the Pareto Frontier anchor points, or the design having maximum rotor efficiency and the design having minimum vibration. Various Pareto generation methods are used to find designs on the frontier between these two anchor designs. When tested in the high fidelity framework, the Pareto anchor designs are shown to be very good designs when compared with other designs from the high fidelity database. This provides evidence that the process proposed has merit. Ultimately, this process can be utilized by industry rotor designers with their existing tools to bring high fidelity analysis into the preliminary design stage of rotors. In conclusion, the methods developed and documented in this thesis have made several novel contributions. First, an automated high fidelity CFD based forward flight simulation framework has been built for use in preliminary design optimization. The framework was built around an integrated, parallel processor capable CFD/CSD/AA process. Second, a novel method of building approximate models of high fidelity parameters has been developed. The method uses a combination of low and high fidelity results and combines Design of Experiments, statistical effects analysis, and aspects of approximation model management. And third, the determination of rotor blade shape variables through optimization using CFD based analysis in forward flight has been performed. This was done using the high fidelity CFD/CSD/AA framework and method mentioned above. While the low and high fidelity predictions methods used in the work still have inaccuracies that can affect the absolute levels of the results, a framework has been successfully developed and demonstrated that allows for an efficient process to improve rotor blade designs in terms of a selected choice of objective function(s). Using engineering judgment, this methodology could be applied today to investigate opportunities to improve existing designs. With improvements in the low and high fidelity prediction components that will certainly occur, this framework could become a powerful tool for future rotorcraft design work. (Abstract shortened by UMI.)

Multilength Scale Patterning of Functional Layers by Roll-to-Roll Ultraviolet-Light-Assisted Nanoimprint Lithography.

PubMed

Leitgeb, Markus; Nees, Dieter; Ruttloff, Stephan; Palfinger, Ursula; Götz, Johannes; Liska, Robert; Belegratis, Maria R; Stadlober, Barbara

2016-05-24

Top-down fabrication of nanostructures with high throughput is still a challenge. We demonstrate the fast (>10 m/min) and continuous fabrication of multilength scale structures by roll-to-roll UV-nanoimprint lithography on a 250 mm wide web. The large-area nanopatterning is enabled by a multicomponent UV-curable resist system (JRcure) with viscous, mechanical, and surface properties that are tunable over a wide range to either allow for usage as polymer stamp material or as imprint resist. The adjustable elasticity and surface chemistry of the resist system enable multistep self-replication of structured resist layers. Decisive for defect-free UV-nanoimprinting in roll-to-roll is the minimization of the surface energies of stamp and resist, and the stepwise reduction of the stiffness from one layer to the next is essential for optimizing the reproduction fidelity especially for nanoscale features. Accordingly, we demonstrate the continuous replication of 3D nanostructures and the high-throughput fabrication of multilength scale resist structures resulting in flexible polyethylenetherephtalate film rolls with superhydrophobic properties. Moreover, a water-soluble UV-imprint resist (JRlift) is introduced that enables residue-free nanoimprinting in roll-to-roll. Thereby we could demonstrate high-throughput fabrication of metallic patterns with only 200 nm line width.

High-Fidelity Simulations of Electromagnetic Propagation and RF Communication Systems

DTIC Science & Technology

2017-05-01

addition to high -fidelity RF propagation modeling, lower-fidelity mod- els, which are less computationally burdensome, are available via a C++ API...expensive to perform, requiring roughly one hour of computer time with 36 available cores and ray tracing per- formed by a single high -end GPU...ER D C TR -1 7- 2 Military Engineering Applied Research High -Fidelity Simulations of Electromagnetic Propagation and RF Communication

Mechanical-Kinetic Modeling of a Molecular Walker from a Modular Design Principle

NASA Astrophysics Data System (ADS)

Hou, Ruizheng; Loh, Iong Ying; Li, Hongrong; Wang, Zhisong

2017-02-01

Artificial molecular walkers beyond burnt-bridge designs are complex nanomachines that potentially replicate biological walkers in mechanisms and functionalities. Improving the man-made walkers up to performance for widespread applications remains difficult, largely because their biomimetic design principles involve entangled kinetic and mechanical effects to complicate the link between a walker's construction and ultimate performance. Here, a synergic mechanical-kinetic model is developed for a recently reported DNA bipedal walker, which is based on a modular design principle, potentially enabling many directional walkers driven by a length-switching engine. The model reproduces the experimental data of the walker, and identifies its performance-limiting factors. The model also captures features common to the underlying design principle, including counterintuitive performance-construction relations that are explained by detailed balance, entropy production, and bias cancellation. While indicating a low directional fidelity for the present walker, the model suggests the possibility of improving the fidelity above 90% by a more powerful engine, which may be an improved version of the present engine or an entirely new engine motif, thanks to the flexible design principle. The model is readily adaptable to aid these experimental developments towards high-performance molecular walkers.

Implementation fidelity trajectories of a health promotion program in multidisciplinary settings: managing tensions in rehabilitation care.

PubMed

Hoekstra, Femke; van Offenbeek, Marjolein A G; Dekker, Rienk; Hettinga, Florentina J; Hoekstra, Trynke; van der Woude, Lucas H V; van der Schans, Cees P

2017-12-01

Although the importance of evaluating implementation fidelity is acknowledged, little is known about heterogeneity in fidelity over time. This study aims to generate insight into the heterogeneity in implementation fidelity trajectories of a health promotion program in multidisciplinary settings and the relationship with changes in patients' health behavior. This study used longitudinal data from the nationwide implementation of an evidence-informed physical activity promotion program in Dutch rehabilitation care. Fidelity scores were calculated based on annual surveys filled in by involved professionals (n = ± 70). Higher fidelity scores indicate a more complete implementation of the program's core components. A hierarchical cluster analysis was conducted on the implementation fidelity scores of 17 organizations at three different time points. Quantitative and qualitative data were used to explore organizational and professional differences between identified trajectories. Regression analyses were conducted to determine differences in patient outcomes. Three trajectories were identified as the following: 'stable high fidelity' (n = 9), 'moderate and improving fidelity' (n = 6), and 'unstable fidelity' (n = 2). The stable high fidelity organizations were generally smaller, started earlier, and implemented the program in a more structured way compared to moderate and improving fidelity organizations. At the implementation period's start and end, support from physicians and physiotherapists, professionals' appreciation, and program compatibility were rated more positively by professionals working in stable high fidelity organizations as compared to the moderate and improving fidelity organizations (p < .05). Qualitative data showed that the stable high fidelity organizations had often an explicit vision and strategy about the implementation of the program. Intriguingly, the trajectories were not associated with patients' self-reported physical activity outcomes (adjusted model β = - 651.6, t(613) = - 1032, p = .303). Differences in organizational-level implementation fidelity trajectories did not result in outcome differences at patient-level. This suggests that an effective implementation fidelity trajectory is contingent on the local organization's conditions. More specifically, achieving stable high implementation fidelity required the management of tensions: realizing a localized change vision, while safeguarding the program's standardized core components and engaging the scarce physicians throughout the process. When scaling up evidence-informed health promotion programs, we propose to tailor the management of implementation tensions to local organizations' starting position, size, and circumstances. The Netherlands National Trial Register NTR3961 . Registered 18 April 2013.

The Need for High Fidelity Lunar Regolith Simulants

NASA Technical Reports Server (NTRS)

Gaier, James R.

2007-01-01

The case is made for the need to have high fidelity lunar regolith simulants to verify the performance of structures and mechanisms to be used on the lunar surface. Minor constituents will in some cases have major consequences. Small amounts of sulfur in the regolith can poison catalysts, and metallic iron on the surface of nano-sized dust particles may cause a dramatic increase in its toxicity. So the definition of a high fidelity simulant is application dependent. For example, in situ resource utilization will require high fidelity in chemistry, meaning careful attention to the minor components and phases; but some other applications, such as the abrasive effects on suit fabrics, might be relatively insensitive to minor component chemistry. The lunar environment itself will change the surface chemistry of the simulant, so to have a high fidelity simulant at must be used in a high fidelity simulated environment to get a high fidelity simulation. Research must be conducted to determine how sensitive technologies will be to minor components and environmental factors before they can be dismissed as unimportant.

Replicating Evidence-Based Practices with Flexibility for Perinatal Home Visiting by Paraprofessionals.

PubMed

Rotheram-Fuller, Erin J; Swendeman, Dallas; Becker, Kimberly D; Daleiden, Eric; Chorpita, Bruce; Harris, Danielle M; Mercer, Neil T; Rotheram-Borus, Mary Jane

2017-12-01

Introduction Strategies are needed to improve the efficacy of paraprofessional home visitors for pregnant women in the United States. This study evaluates the maternal and child outcomes when evidence-based practices (EBP) are replicated with flexibility, rather than fidelity to a manualized intervention. Methods Pregnant mothers (N = 203) in five clinics were recruited in the waiting rooms and randomized to standard clinic care as the control condition (n = 104) or standard care plus home visiting (n = 99). Home visitors (n = 9) were selected, trained in foundational skills common to EBP and four problem domains (weight control, breastfeeding, daily habits, and depression). Independent interviewers assessed targeted outcomes at birth (82%) and 6 months later (83%). Home visitors, called Mentor Mothers [MM], made an average of 14.9 home visits or telephone contacts (SD = 9; total contacts = 1491) addressing maternal daily habits, breastfeeding, and depression. Intervention and control mothers were similar in weight, Body Mass Index (BMI), depression and social support at baseline and 6 months later. The percentage of low birth weight babies was similar; intervention infants' growth (weight/height Z score) tended to be significantly better compared to the control condition. There are many explanations for the failure to find significant benefits: insufficient statistical power; the benefits of repeated assessments by warm, supportive peers to improve outcomes; or the failure of EBP and the need to maintain replication with fidelity. All study mothers had better outcomes than documented among comparable published samples of low-income, Latina and Korean-American mothers in Los Angeles, CA. ClinicalTrials.gov registration NCT01687634.

Perspective: fostering biomedical literacy among America's youth: how medical simulation reshapes the strategy.

PubMed

Gordon, James A; Oriol, Nancy E

2008-05-01

Medicine is a uniquely powerful platform for teaching science and ethics, technology and humanity, life and death. Yet, society has historically limited medical education to a select few, and only after an advanced course of premedical studies. In an era when biomedical literacy is increasingly viewed as a national imperative, the authors hypothesized that advanced instruction in medicine could be intellectually transformative among a broad range of young people. Using high-fidelity patient simulators, a group of college and high school students was immersed in a weeklong course designed to replicate the practice of modern medicine. On the basis of the students' reported experiences, the authors feel that patient simulation can foster forceful interest in the life sciences at an early age. Such efforts could catalyze a significant expansion of interest in biomedical science among students nationwide.

The Application of High Energy Resolution Green's Functions to Threat Scenario Simulation

NASA Astrophysics Data System (ADS)

Thoreson, Gregory G.; Schneider, Erich A.

2012-04-01

Radiation detectors installed at key interdiction points provide defense against nuclear smuggling attempts by scanning vehicles and traffic for illicit nuclear material. These hypothetical threat scenarios may be modeled using radiation transport simulations. However, high-fidelity models are computationally intensive. Furthermore, the range of smuggler attributes and detector technologies create a large problem space not easily overcome by brute-force methods. Previous research has demonstrated that decomposing the scenario into independently simulated components using Green's functions can simulate photon detector signals with coarse energy resolution. This paper extends this methodology by presenting physics enhancements and numerical treatments which allow for an arbitrary level of energy resolution for photon transport. As a result, spectroscopic detector signals produced from full forward transport simulations can be replicated while requiring multiple orders of magnitude less computation time.

Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration

PubMed Central

Fasullo, Michael; Endres, Lauren

2015-01-01

Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated DNA damage because nucleotide imbalance can lead to mitochondrial depletion due to low replication fidelity. Failure to maintain nucleotide balance due to genetic defects can result in infantile death; however there is great variability in clinical presentation for particular diseases. This review compares genetic diseases that result from defects in specific nucleotide salvage enzymes and a signaling kinase that activates nucleotide salvage after DNA damage exposure. These diseases include Lesch-Nyhan syndrome, mitochondrial depletion syndromes, and ataxia telangiectasia. Although treatment options are available to palliate symptoms of these diseases, there is no cure. The conclusions drawn from this review include the critical role of guanine nucleotides in preventing neurodegeneration, the limitations of animals as disease models, and the need to further understand nucleotide imbalances in treatment regimens. Such knowledge will hopefully guide future studies into clinical therapies for genetic diseases. PMID:25923076

MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants

PubMed Central

Stumpf, Jeffrey D.; Copeland, William C.

2014-01-01

Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but suppresses MMS-induced mutagenesis. These results suggest a novel mechanism wherein mutations that lead to hypermutation by DNA base-damaging agents and associate with mitochondrial disease may contribute to previously unexplained phenomena, such as the wide variation of age of disease onset and acquired mitochondrial toxicities. PMID:25340760

MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

PubMed

Stumpf, Jeffrey D; Copeland, William C

2014-10-01

Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but suppresses MMS-induced mutagenesis. These results suggest a novel mechanism wherein mutations that lead to hypermutation by DNA base-damaging agents and associate with mitochondrial disease may contribute to previously unexplained phenomena, such as the wide variation of age of disease onset and acquired mitochondrial toxicities.

Insights to primitive replication derived from structures of small oligonucleotides

NASA Technical Reports Server (NTRS)

Smith, G. K.; Fox, G. E.

1995-01-01

Available information on the structure of small oligonucleotides is surveyed. It is observed that even small oligomers typically exhibit defined structures over a wide range of pH and temperature. These structures rely on a plethora of non-standard base-base interactions in addition to the traditional Watson-Crick pairings. Stable duplexes, though typically antiparallel, can be parallel or staggered and perfect complementarity is not essential. These results imply that primitive template directed reactions do not require high fidelity. Hence, the extensive use of Watson-Crick complementarity in genes rather than being a direct consequence of the primitive condensation process, may instead reflect subsequent selection based on the advantage of accuracy in maintaining the primitive genetic machinery once it arose.

The Steric Gate of DNA Polymerase ι Regulates Ribonucleotide Incorporation and Deoxyribonucleotide Fidelity*

PubMed Central

Donigan, Katherine A.; McLenigan, Mary P.; Yang, Wei; Goodman, Myron F.; Woodgate, Roger

2014-01-01

Accurate DNA synthesis in vivo depends on the ability of DNA polymerases to select dNTPs from a nucleotide pool dominated by NTPs. High fidelity replicative polymerases have evolved to efficiently exclude NTPs while copying long stretches of undamaged DNA. However, to bypass DNA damage, cells utilize specialized low fidelity polymerases to perform translesion DNA synthesis (TLS). Of interest is human DNA polymerase ι (pol ι), which has been implicated in TLS of oxidative and UV-induced lesions. Here, we evaluate the ability of pol ι to incorporate NTPs during DNA synthesis. pol ι incorporates and extends NTPs opposite damaged and undamaged template bases in a template-specific manner. The Y39A “steric gate” pol ι mutant is considerably more active in the presence of Mn2+ compared with Mg2+ and exhibits a marked increase in NTP incorporation and extension, and surprisingly, it also exhibits increased dNTP base selectivity. Our results indicate that a single residue in pol ι is able to discriminate between NTPs and dNTPs during DNA synthesis. Because wild-type pol ι incorporates NTPs in a template-specific manner, certain DNA sequences may be “at risk” for elevated mutagenesis during pol ι-dependent TLS. Molecular modeling indicates that the constricted active site of wild-type pol ι becomes more spacious in the Y39A variant. Therefore, the Y39A substitution not only permits incorporation of ribonucleotides but also causes the enzyme to favor faithful Watson-Crick base pairing over mutagenic configurations. PMID:24532793

A unified, multifidelity quasi-newton optimization method with application to aero-structural designa

NASA Astrophysics Data System (ADS)

Bryson, Dean Edward

A model's level of fidelity may be defined as its accuracy in faithfully reproducing a quantity or behavior of interest of a real system. Increasing the fidelity of a model often goes hand in hand with increasing its cost in terms of time, money, or computing resources. The traditional aircraft design process relies upon low-fidelity models for expedience and resource savings. However, the reduced accuracy and reliability of low-fidelity tools often lead to the discovery of design defects or inadequacies late in the design process. These deficiencies result either in costly changes or the acceptance of a configuration that does not meet expectations. The unknown opportunity cost is the discovery of superior vehicles that leverage phenomena unknown to the designer and not illuminated by low-fidelity tools. Multifidelity methods attempt to blend the increased accuracy and reliability of high-fidelity models with the reduced cost of low-fidelity models. In building surrogate models, where mathematical expressions are used to cheaply approximate the behavior of costly data, low-fidelity models may be sampled extensively to resolve the underlying trend, while high-fidelity data are reserved to correct inaccuracies at key locations. Similarly, in design optimization a low-fidelity model may be queried many times in the search for new, better designs, with a high-fidelity model being exercised only once per iteration to evaluate the candidate design. In this dissertation, a new multifidelity, gradient-based optimization algorithm is proposed. It differs from the standard trust region approach in several ways, stemming from the new method maintaining an approximation of the inverse Hessian, that is the underlying curvature of the design problem. Whereas the typical trust region approach performs a full sub-optimization using the low-fidelity model at every iteration, the new technique finds a suitable descent direction and focuses the search along it, reducing the number of low-fidelity evaluations required. This narrowing of the search domain also alleviates the burden on the surrogate model corrections between the low- and high-fidelity data. Rather than requiring the surrogate to be accurate in a hyper-volume bounded by the trust region, the model needs only to be accurate along the forward-looking search direction. Maintaining the approximate inverse Hessian also allows the multifidelity algorithm to revert to high-fidelity optimization at any time. In contrast, the standard approach has no memory of the previously-computed high-fidelity data. The primary disadvantage of the proposed algorithm is that it may require modifications to the optimization software, whereas standard optimizers may be used as black-box drivers in the typical trust region method. A multifidelity, multidisciplinary simulation of aeroelastic vehicle performance is developed to demonstrate the optimization method. The numerical physics models include body-fitted Euler computational fluid dynamics; linear, panel aerodynamics; linear, finite-element computational structural mechanics; and reduced, modal structural bases. A central element of the multifidelity, multidisciplinary framework is a shared parametric, attributed geometric representation that ensures the analysis inputs are consistent between disciplines and fidelities. The attributed geometry also enables the transfer of data between disciplines. The new optimization algorithm, a standard trust region approach, and a single-fidelity quasi-Newton method are compared for a series of analytic test functions, using both polynomial chaos expansions and kriging to correct discrepancies between fidelity levels of data. In the aggregate, the new method requires fewer high-fidelity evaluations than the trust region approach in 51% of cases, and the same number of evaluations in 18%. The new approach also requires fewer low-fidelity evaluations, by up to an order of magnitude, in almost all cases. The efficacy of both multifidelity methods compared to single-fidelity optimization depends significantly on the behavior of the high-fidelity model and the quality of the low-fidelity approximation, though savings are realized in a large number of cases. The multifidelity algorithm is also compared to the single-fidelity quasi-Newton method for complex aeroelastic simulations. The vehicle design problem includes variables for planform shape, structural sizing, and cruise condition with constraints on trim and structural stresses. Considering the objective function reduction versus computational expenditure, the multifidelity process performs better in three of four cases in early iterations. However, the enforcement of a contracting trust region slows the multifidelity progress. Even so, leveraging the approximate inverse Hessian, the optimization can be seamlessly continued using high-fidelity data alone. Ultimately, the proposed new algorithm produced better designs in all four cases. Investigating the return on investment in terms of design improvement per computational hour confirms that the multifidelity advantage is greatest in early iterations, and managing the transition to high-fidelity optimization is critical.

Development and testing of a multimedia internet-based system for fidelity and monitoring of multidimensional treatment foster care.

PubMed

Feil, Edward G; Sprengelmeyer, Peter G; Davis, Betsy; Chamberlain, Patricia

2012-10-16

The fields of mental health, child welfare, and juvenile justice are jointly faced with the challenge of reducing the prevalence of antisocial behavior among adolescents. In the last 20 years, conduct disorders have moved from being considered intractable difficulties to having complex but available solutions. The treatments for even long-standing offending behavior among adolescents are now well documented and supported by a growing and compelling body of evidence. These empirically validated interventions are being widely disseminated, but the replication of the results from clinical trials in community settings has yet to be documented. The treatments, which produced impressive effects in a research context, are difficult to replicate without intensive monitoring of fidelity by the developers. Such monitoring is a barrier toward adoption; as the distance between the adopter and developer increases, so does cost. At the same time, states, communities, and agencies are under increasing pressure to implement those intervention services that have been shown to be most effective. The use of the Internet offers a potential solution in that existing reporting and data collection by clinicians can be subject to remote supervision. Such a system would have the potential to provide dissemination teams with more direct access to higher-quality data and would make adopters more likely to be able to implement services at the highest possible conformity to research protocols. To create and test such an innovative system for use with the Multidimensional Treatment Foster Care (MTFC) program, which is an in-home treatment (alternative to a residential- or group-home setting) for antisocial youths. This research could advance the knowledge base about developing innovative infrastructures in community settings to disseminate empirically validated treatments. The fidelity system was used and reviewed by parent and professional users: 20 foster parent users of the Parent Daily Report function, 9 professional MTFC program supervisors, and 4 MTFC consultants. All participants rated the system's ease of use, quality of the website, and observational videos recorded at agency meetings. In addition, foster parents entered data on child behavior. All professionals and foster parents rated the system as very easy to use. We found particularly high levels of use by parents. Professionals rated the computer-collected videos of clinical meetings as being of high quality and easily codeable. The project developed a user-friendly and secure Web-based system using state-of-the-art computer-based protocols for recording questionnaire and observational data generated by community-based MTFC staff and foster parents, with positive satisfaction and utilization results.

Development of nanoimprint lithography templates for the contact hole layer application (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ichimura, Koji; Hikichi, Ryugo; Harada, Saburo; Kanno, Koichi; Kurihara, Masaaki; Hayashi, Naoya

2017-04-01

Nanoimprint lithography, NIL, is gathering much attention as one of the most potential candidates for the next generation lithography for semiconductor. This technology needs no pattern data modification for exposure, simpler exposure system, and single step patterning process without any coat/develop truck, and has potential of cost effective patterning rather than very complex optical lithography and/or EUV lithography. NIL working templates are made by the replication of the EB written high quality master templates. Fabrication of high resolution master templates is one of the most important issues. Since NIL is 1:1 pattern transfer process, master templates have 4 times higher resolution compared with photomasks. Another key is to maintain the quality of the master templates in replication process. NIL process is applied for the template replication and this imprint process determines most of the performance of the replicated templates. Expectations to the NIL are not only high resolution line and spaces but also the contact hole layer application. Conventional ArF-i lithography has a certain limit in size and pitch for contact hole fabrication. On the other hand, NIL has good pattern fidelity for contact hole fabrication at smaller sizes and pitches compared with conventional optical lithography. Regarding the tone of the templates for contact hole, there are the possibilities of both tone, the hole template and the pillar template, depending on the processes of the wafer side. We have succeeded to fabricate both types of templates at 2xnm in size. In this presentation, we will be discussing fabrication or our replica template for the contact hole layer application. Both tone of the template fabrication will be presented as well as the performance of the replica templates. We will also discuss the resolution improvement of the hole master templates by using various e-beam exposure technologies.

A randomized controlled study of manikin simulator fidelity on neonatal resuscitation program learning outcomes.

PubMed

Curran, Vernon; Fleet, Lisa; White, Susan; Bessell, Clare; Deshpandey, Akhil; Drover, Anne; Hayward, Mark; Valcour, James

2015-03-01

The neonatal resuscitation program (NRP) has been developed to educate physicians and other health care providers about newborn resuscitation and has been shown to improve neonatal resuscitation skills. Simulation-based training is recommended as an effective modality for instructing neonatal resuscitation and both low and high-fidelity manikin simulators are used. There is limited research that has compared the effect of low and high-fidelity manikin simulators for NRP learning outcomes, and more specifically on teamwork performance and confidence. The purpose of this study was to examine the effect of using low versus high-fidelity manikin simulators in NRP instruction. A randomized posttest-only control group study design was conducted. Third year undergraduate medical students participated in NRP instruction and were assigned to an experimental group (high-fidelity manikin simulator) or control group (low-fidelity manikin simulator). Integrated skills station (megacode) performance, participant satisfaction, confidence and teamwork behaviour scores were compared between the study groups. Participants in the high-fidelity manikin simulator instructional group reported significantly higher total scores in overall satisfaction (p = 0.001) and confidence (p = 0.001). There were no significant differences in teamwork behaviour scores, as observed by two independent raters, nor differences on mandatory integrated skills station performance items at the p < 0.05 level. Medical students' reported greater satisfaction and confidence with high-fidelity manikin simulators, but did not demonstrate overall significantly improved teamwork or integrated skills station performance. Low and high-fidelity manikin simulators facilitate similar levels of objectively measured NRP outcomes for integrated skills station and teamwork performance.

High Fidelity System Simulation of Multiple Components in Support of the UEET Program

NASA Technical Reports Server (NTRS)

Plybon, Ronald C.; VanDeWall, Allan; Sampath, Rajiv; Balasubramaniam, Mahadevan; Mallina, Ramakrishna; Irani, Rohinton

2006-01-01

The High Fidelity System Simulation effort has addressed various important objectives to enable additional capability within the NPSS framework. The scope emphasized High Pressure Turbine and High Pressure Compressor components. Initial effort was directed at developing and validating intermediate fidelity NPSS model using PD geometry and extended to high-fidelity NPSS model by overlaying detailed geometry to validate CFD against rig data. Both "feedforward" and feedback" approaches of analysis zooming was employed to enable system simulation capability in NPSS. These approaches have certain benefits and applicability in terms of specific applications "feedback" zooming allows the flow-up of information from high-fidelity analysis to be used to update the NPSS model results by forcing the NPSS solver to converge to high-fidelity analysis predictions. This apporach is effective in improving the accuracy of the NPSS model; however, it can only be used in circumstances where there is a clear physics-based strategy to flow up the high-fidelity analysis results to update the NPSS system model. "Feed-forward" zooming approach is more broadly useful in terms of enabling detailed analysis at early stages of design for a specified set of critical operating points and using these analysis results to drive design decisions early in the development process.

Abnormal, Error-Prone Bypass of Photoproducts by Xeroderma Pigmentosum Variant Cell Extracts Results in Extreme Strand Bias for the Kinds of Mutations Induced by UV Light

PubMed Central

McGregor, W. Glenn; Wei, Dong; Maher, Veronica M.; McCormick, J. Justin

1999-01-01

Xeroderma pigmentosum (XP) is a rare genetic disease characterized by a greatly increased susceptibility to sunlight-induced skin cancer. Cells from the majority of patients are defective in nucleotide excision repair. However, cells from one set of patients, XP variants, exhibit normal repair but are abnormally slow in replicating DNA containing UV photoproducts. The frequency of UV radiation-induced mutations in the XP variant cells is significantly higher than that in normal human cells. Furthermore, the kinds of UV-induced mutations differ very significantly from normal. Instead of transitions, mainly C→T, 30% of the base substitutions consist of C→A transversions, all arising from photoproducts located in one strand. Mutations involving cytosine in the other strand are almost all C→T transitions. Forty-five percent of the substitutions involve thymine, and the majority are transversions. To test the hypothesis that the UV hypermutability and the abnormal spectrum of mutations result from abnormal bypass of photoproducts in DNA, we compared extracts from XP variant cells with those from HeLa cells and a fibroblast cell strain, MSU-1.2, for the ability to replicate a UV-irradiated form I M13 phage. The M13 template contains a simian virus 40 origin of replication located directly to the left or to the right of the target gene, lacZα, so that the template for the leading and lagging strands of DNA replication is defined. Reduction of replication to ∼37% of the control value required only 1 photoproduct per template for XP variant cell extracts, but ∼2.2 photoproducts for HeLa or MSU-1.2 cell extracts. The frequency of mutants induced was four times higher with XP variant cell extracts than with HeLa or MSU-1.2 cell extracts. With XP variant cell extracts, the proportion of C→A transversions reached as high as 43% with either M13 template and arose from photoproducts located in the template for leading-strand synthesis; with HeLa or MSU-1.2 cell extracts, this value was only 5%, and these arose from photoproducts in either strand. With the XP variant extracts, 26% of the substitutions involved thymine, and virtually all were T→A transversions. Sequence analysis of the coding region of the catalytic subunit of DNA polymerase delta in XP variant cell lines revealed two polymorphisms, but these do not account for the reduced bypass fidelity. Our data indicate that the UV hypermutability of XP variant cells results from reduced bypass fidelity and that unlike for normal cells, bypass of photoproducts involving cytosine in the template for the leading strand differs significantly from that of photoproducts in the lagging strand. PMID:9858539

The Need for High Fidelity Lunar Regolith Simulants

NASA Technical Reports Server (NTRS)

Gaier, James R.

2008-01-01

The case is made for the need to have high fidelity lunar regolith simulants to verify the performance of structures, mechanisms, and processes to be used on the lunar surface. Minor constituents will in some cases have major consequences. Small amounts of sulfur in the regolith can poison catalysts, and metallic iron on the surface of nano-sized dust particles may cause a dramatic increase in its toxicity. So the definition of a high fidelity simulant is application-dependent. For example, in situ resource utilization will require high fidelity in chemistry, meaning careful attention to the minor components and phases; but some other applications, such as the abrasive effects on suit fabrics, might be relatively insensitive to minor component chemistry while abrasion of some metal components may be highly dependent on trace components. The lunar environment itself will change the surface chemistry of the simulant, so to have a high fidelity simulant it must be used in a high fidelity simulated environment to get an accurate simulation. Research must be conducted to determine how sensitive technologies will be to minor components and environmental factors before they can be dismissed as unimportant.

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

Wang, Weina; Hellinga, Homme W.; Beese, Lorena S.

Even though high-fidelity polymerases copy DNA with remarkable accuracy, some base-pair mismatches are incorporated at low frequency, leading to spontaneous mutagenesis. Using high-resolution X-ray crystallographic analysis of a DNA polymerase that catalyzes replication in crystals, we observe that a C {center_dot} A mismatch can mimic the shape of cognate base pairs at the site of incorporation. This shape mimicry enables the mismatch to evade the error detection mechanisms of the polymerase, which would normally either prevent mismatch incorporation or promote its nucleolytic excision. Movement of a single proton on one of the mismatched bases alters the hydrogen-bonding pattern such thatmore » a base pair forms with an overall shape that is virtually indistinguishable from a canonical, Watson-Crick base pair in double-stranded DNA. These observations provide structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis, a long-standing concept that has been difficult to demonstrate directly.« less

Economical Unsteady High-Fidelity Aerodynamics for Structural Optimization with a Flutter Constraint

NASA Technical Reports Server (NTRS)

Bartels, Robert E.; Stanford, Bret K.

2017-01-01

Structural optimization with a flutter constraint for a vehicle designed to fly in the transonic regime is a particularly difficult task. In this speed range, the flutter boundary is very sensitive to aerodynamic nonlinearities, typically requiring high-fidelity Navier-Stokes simulations. However, the repeated application of unsteady computational fluid dynamics to guide an aeroelastic optimization process is very computationally expensive. This expense has motivated the development of methods that incorporate aspects of the aerodynamic nonlinearity, classical tools of flutter analysis, and more recent methods of optimization. While it is possible to use doublet lattice method aerodynamics, this paper focuses on the use of an unsteady high-fidelity aerodynamic reduced order model combined with successive transformations that allows for an economical way of utilizing high-fidelity aerodynamics in the optimization process. This approach is applied to the common research model wing structural design. As might be expected, the high-fidelity aerodynamics produces a heavier wing than that optimized with doublet lattice aerodynamics. It is found that the optimized lower skin of the wing using high-fidelity aerodynamics differs significantly from that using doublet lattice aerodynamics.

Hepatitis B virus genetic diversity and its impact on diagnostic assays.

PubMed

Hollinger, F B

2007-11-01

Hepatitis B virus (HBV) circulates in blood as closely related, but genetically diverse molecules called quasispecies. During replication, HBV production may approach 10(11) molecules/day, although during peak activity this rate may increase 100-1000 times. Generally, DNA polymerases have excellent fidelity in reading DNA templates because they are associated with an exonuclease which removes incorrectly added nucleotides. However, the HBV-DNA polymerase lacks fidelity and proofreading function partly because exonuclease activity is either absent or deficient. Thus, the HBV genome and especially the envelope gene, is mutated with unusually high frequency. These mutations can affect more than one open reading frame because of overlapping genes. The S gene contains an exposed major hydrophilic region (residues 110-155), which encompasses the 'a' determinant that is important for inducing immunity. Nucleotide substitutions in this region are common and result in reduced binding or failure to detect hepatitis B surface antigen (HBsAg) in diagnostic assays. Adaptive immunity also depends on the recognition of HBsAg by specific antibody and variants pose a threat if they interfere with binding to antibody. Finally, genomic hypervariability allows HBV to escape selection pressures imposed by antiviral therapies, vaccines and the host immune system, and is responsible for creating genotypes, subgenotypes and subtypes.

Depth perception based 3D holograms enabled with polarization-independent metasurfaces.

PubMed

Deng, Juan; Li, Zile; Zheng, Guoxing; Tao, Jin; Dai, Qi; Deng, Liangui; He, Ping'an; Deng, Qiling; Mao, Qingzhou

2018-04-30

Metasurfaces consist of dielectric nanobrick arrays with different dimensions in the long and short axes can be used to generate different phase delays, predicting a new way to manipulate an incident beam in the two orthogonal directions separately. Here we demonstrate the concept of depth perception based three-dimensional (3D) holograms with polarization-independent metasurfaces. 4-step dielectric metasurfaces-based fan-out optical elements and holograms operating at 658 nm were designed and simulated. Two different holographic images with high fidelity were generated at the same plane in the far field for different polarization states. One can observe the 3D effect of target objects with polarized glasses. With the advantages of ultracompactness, flexibility and replicability, the polarization-independent metasurfaces open up depth perception based stereoscopic imaging in a holographic way.

Replica amplification of nucleic acid arrays

DOEpatents

Church, George M.; Mitra, Robi D.

2010-08-31

Disclosed are improved methods of making and using immobilized arrays of nucleic acids, particularly methods for producing replicas of such arrays. Included are methods for producing high density arrays of nucleic acids and replicas of such arrays, as well as methods for preserving the resolution of arrays through rounds of replication. Also included are methods which take advantage of the availability of replicas of arrays for increased sensitivity in detection of sequences on arrays. Improved methods of sequencing nucleic acids immobilized on arrays utilizing single copies of arrays and methods taking further advantage of the availability of replicas of arrays are disclosed. The improvements lead to higher fidelity and longer read lengths of sequences immobilized on arrays. Methods are also disclosed which improve the efficiency of multiplex PCR using arrays of immobilized nucleic acids.

Human-Centered Design of Human-Computer-Human Dialogs in Aerospace Systems

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1998-01-01

A series of ongoing research programs at Georgia Tech established a need for a simulation support tool for aircraft computer-based aids. This led to the design and development of the Georgia Tech Electronic Flight Instrument Research Tool (GT-EFIRT). GT-EFIRT is a part-task flight simulator specifically designed to study aircraft display design and single pilot interaction. ne simulator, using commercially available graphics and Unix workstations, replicates to a high level of fidelity the Electronic Flight Instrument Systems (EFIS), Flight Management Computer (FMC) and Auto Flight Director System (AFDS) of the Boeing 757/767 aircraft. The simulator can be configured to present information using conventional looking B757n67 displays or next generation Primary Flight Displays (PFD) such as found on the Beech Starship and MD-11.

Concept Maps: A Tool to Prepare for High Fidelity Simulation in Nursing

ERIC Educational Resources Information Center

Daley, Barbara J.; Beman, Sarah Black; Morgan, Sarah; Kennedy, Linda; Sheriff, Mandy

2017-01-01

In this study, the use of concept mapping as a method to prepare for high fidelity simulated learning experiences was investigated. Fourth year baccalaureate nursing students were taught how to use concept maps as a way to prepare for high fidelity simulated nursing experiences. Students prepared concept maps for two simulated experiences…

Information management in DNA replication modeled by directional, stochastic chains with memory

NASA Astrophysics Data System (ADS)

Arias-Gonzalez, J. Ricardo

2016-11-01

Stochastic chains represent a key variety of phenomena in many branches of science within the context of information theory and thermodynamics. They are typically approached by a sequence of independent events or by a memoryless Markov process. Stochastic chains are of special significance to molecular biology, where genes are conveyed by linear polymers made up of molecular subunits and transferred from DNA to proteins by specialized molecular motors in the presence of errors. Here, we demonstrate that when memory is introduced, the statistics of the chain depends on the mechanism by which objects or symbols are assembled, even in the slow dynamics limit wherein friction can be neglected. To analyze these systems, we introduce a sequence-dependent partition function, investigate its properties, and compare it to the standard normalization defined by the statistical physics of ensembles. We then apply this theory to characterize the enzyme-mediated information transfer involved in DNA replication under the real, non-equilibrium conditions, reproducing measured error rates and explaining the typical 100-fold increase in fidelity that is experimentally found when proofreading and edition take place. Our model further predicts that approximately 1 kT has to be consumed to elevate fidelity in one order of magnitude. We anticipate that our results are necessary to interpret configurational order and information management in many molecular systems within biophysics, materials science, communication, and engineering.

The effect of high-fidelity patient simulation on the critical thinking and clinical decision-making skills of new graduate nurses.

PubMed

Maneval, Rhonda; Fowler, Kimberly A; Kays, John A; Boyd, Tiffany M; Shuey, Jennifer; Harne-Britner, Sarah; Mastrine, Cynthia

2012-03-01

This study was conducted to determine whether the addition of high-fidelity patient simulation to new nurse orientation enhanced critical thinking and clinical decision-making skills. A pretest-posttest design was used to assess critical thinking and clinical decision-making skills in two groups of graduate nurses. Compared with the control group, the high-fidelity patient simulation group did not show significant improvement in mean critical thinking or clinical decision-making scores. When mean scores were analyzed, both groups showed an increase in critical thinking scores from pretest to posttest, with the high-fidelity patient simulation group showing greater gains in overall scores. However, neither group showed a statistically significant increase in mean test scores. The effect of high-fidelity patient simulation on critical thinking and clinical decision-making skills remains unclear. Copyright 2012, SLACK Incorporated.

High-Fidelity Simulation for Neonatal Nursing Education: An Integrative Review of the Literature.

PubMed

Cooper, Allyson

2015-01-01

The lack of safe avenues to develop neonatal nursing competencies using human subjects leads to the notion that simulation education for neonatal nurses might be an ideal form of education. This integrative literature review compares traditional, teacher-centered education with high-fidelity simulation education for neonatal nurses. It examines the theoretical frameworks used in neonatal nursing education and outlines the advantages of this type of training, including improving communication and teamwork; providing an innovative pedagogical approach; and aiding in skill acquisition, confidence, and participant satisfaction. The importance of debriefing is also examined. High-fidelity simulation is not without disadvantages, including its significant cost, the time associated with training, the need for very complex technical equipment, and increased faculty resource requirements. Innovative uses of high-fidelity simulation in neonatal nursing education are suggested. High-fidelity simulation has great potential but requires additional research to fully prove its efficacy.

Structure of human DNA polymerase iota and the mechanism of DNA synthesis.

PubMed

Makarova, A V; Kulbachinskiy, A V

2012-06-01

Cellular DNA polymerases belong to several families and carry out different functions. Highly accurate replicative DNA polymerases play the major role in cell genome replication. A number of new specialized DNA polymerases were discovered at the turn of XX-XXI centuries and have been intensively studied during the last decade. Due to the special structure of the active site, these enzymes efficiently perform synthesis on damaged DNA but are characterized by low fidelity. Human DNA polymerase iota (Pol ι) belongs to the Y-family of specialized DNA polymerases and is one of the most error-prone enzymes involved in DNA synthesis. In contrast to other DNA polymerases, Pol ι is able to use noncanonical Hoogsteen interactions for nucleotide base pairing. This allows it to incorporate nucleotides opposite various lesions in the DNA template that impair Watson-Crick interactions. Based on the data of X-ray structural analysis of Pol ι in complexes with various DNA templates and dNTP substrates, we consider the structural peculiarities of the Pol ι active site and discuss possible mechanisms that ensure the unique behavior of the enzyme on damaged and undamaged DNA.

Cultured High-Fidelity Three-Dimensional Human Urogenital Tract Carcinomas and Process

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Spaulding, Glenn F. (Inventor); Wolf, David A. (Inventor)

1998-01-01

Artificial high-fidelity three-dimensional human urogenital tract carcinomas are propagated under in vitro-microgravity conditions from carcinoma cells. Artificial high-fidelity three-dimensional human urogenital tract carcinomas are also propagated from a coculture of normal urogenital tract cells inoculated with carcinoma cells. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

An Automatic Medium to High Fidelity Low-Thrust Global Trajectory Toolchain; EMTG-GMAT

NASA Technical Reports Server (NTRS)

Beeson, Ryne T.; Englander, Jacob A.; Hughes, Steven P.; Schadegg, Maximillian

2015-01-01

Solving the global optimization, low-thrust, multiple-flyby interplanetary trajectory problem with high-fidelity dynamical models requires an unreasonable amount of computational resources. A better approach, and one that is demonstrated in this paper, is a multi-step process whereby the solution of the aforementioned problem is solved at a lower-fidelity and this solution is used as an initial guess for a higher-fidelity solver. The framework presented in this work uses two tools developed by NASA Goddard Space Flight Center: the Evolutionary Mission Trajectory Generator (EMTG) and the General Mission Analysis Tool (GMAT). EMTG is a medium to medium-high fidelity low-thrust interplanetary global optimization solver, which now has the capability to automatically generate GMAT script files for seeding a high-fidelity solution using GMAT's local optimization capabilities. A discussion of the dynamical models as well as thruster and power modeling for both EMTG and GMAT are given in this paper. Current capabilities are demonstrated with examples that highlight the toolchains ability to efficiently solve the difficult low-thrust global optimization problem with little human intervention.

Genetic Control of Replication through N1-methyladenine in Human Cells*

PubMed Central

Conde, Juan; Yoon, Jung-Hoon; Roy Choudhury, Jayati; Prakash, Louise; Prakash, Satya

2015-01-01

N1-methyl adenine (1-MeA) is formed in DNA by reaction with alkylating agents and naturally occurring methyl halides. The 1-MeA lesion impairs Watson-Crick base pairing and blocks normal DNA replication. Here we identify the translesion synthesis (TLS) DNA polymerases (Pols) required for replicating through 1-MeA in human cells and show that TLS through this lesion is mediated via three different pathways in which Pols ι and θ function in one pathway and Pols η and ζ, respectively, function in the other two pathways. Our biochemical studies indicate that in the Polι/Polθ pathway, Polι would carry out nucleotide insertion opposite 1-MeA from which Polθ would extend synthesis. In the Polη pathway, this Pol alone would function at both the nucleotide insertion and extension steps of TLS, and in the third pathway, Polζ would extend from the nucleotide inserted opposite 1-MeA by an as yet unidentified Pol. Whereas by pushing 1-MeA into the syn conformation and by forming Hoogsteen base pair with the T residue, Polι would carry out TLS opposite 1-MeA, the ability of Polη to replicate through 1-MeA suggests that despite its need for Watson-Crick hydrogen bonding, Polη can stabilize the adduct in its active site. Remarkably, even though Pols η and ι are quite error-prone at inserting nucleotides opposite 1-MeA, TLS opposite this lesion in human cells occurs in a highly error-free fashion. This suggests that the in vivo fidelity of TLS Pols is regulated by factors such as post-translational modifications, protein-protein interactions, and possibly others. PMID:26491020

Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota

PubMed Central

Kirouac, Kevin N.; Ling, Hong

2011-01-01

The 8-oxo-guanine (8-oxo-G) lesion is the most abundant and mutagenic oxidative DNA damage existing in the genome. Due to its dual coding nature, 8-oxo-G causes most DNA polymerases to misincorporate adenine. Human Y-family DNA polymerase iota (polι) preferentially incorporates the correct cytosine nucleotide opposite 8-oxo-G. This unique specificity may contribute to polι’s biological role in cellular protection against oxidative stress. However, the structural basis of this preferential cytosine incorporation is currently unknown. Here we present four crystal structures of polι in complex with DNA containing an 8-oxo-G lesion, paired with correct dCTP or incorrect dATP, dGTP, and dTTP nucleotides. An exceptionally narrow polι active site restricts the purine bases in a syn conformation, which prevents the dual coding properties of 8-oxo-G by inhibiting syn/anti conformational equilibrium. More importantly, the 8-oxo-G base in a syn conformation is not mutagenic in polι because its Hoogsteen edge does not form a stable base pair with dATP in the narrow active site. Instead, the syn 8-oxo-G template base forms the most stable replicating base pair with correct dCTP due to its small pyrimidine base size and enhanced hydrogen bonding with the Hoogsteen edge of 8-oxo-G. In combination with site directed mutagenesis, we show that Gln59 in the finger domain specifically interacts with the additional O8 atom of the lesion base, which influences nucleotide selection, enzymatic efficiency, and replication stalling at the lesion site. Our work provides the structural mechanism of high-fidelity 8-oxo-G replication by a human DNA polymerase. PMID:21300901

Kinetics and thermodynamics of DNA polymerases with exonuclease proofreading

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-04-01

Kinetic theory and thermodynamics are applied to DNA polymerases with exonuclease activity, taking into account the dependence of the rates on the previously incorporated nucleotide. The replication fidelity is shown to increase significantly thanks to this dependence at the basis of the mechanism of exonuclease proofreading. In particular, this dependence can provide up to a 100-fold lowering of the error probability under physiological conditions. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

Finite element analysis of constrained total Condylar Knee Prosthesis

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

NONE

1998-07-13

Exactech, Inc., is a prosthetic joint manufacturer based in Gainesville, FL. The company set the goal of developing a highly effective prosthetic articulation, based on scientific principles, not trial and error. They developed an evolutionary design for a total knee arthroplasty system that promised improved performance. They performed static load tests in the laboratory with similar previous designs, but dynamic laboratory testing was both difficult to perform and prohibitively expensive for a small business to undertake. Laboratory testing also cannot measure stress levels in the interior of the prosthesis where failures are known to initiate. To fully optimize their designsmore » for knee arthroplasty revisions, they needed range-of-motion stress/strain data at interior as well as exterior locations within the prosthesis. LLNL developed computer software (especially NIKE3D) specifically designed to perform stress/strain computations (finite element analysis) for complex geometries in large displacement/large deformation conditions. Additionally, LLNL had developed a high fidelity knee model for other analytical purposes. The analysis desired by Exactech could readily be performed using NIKE3D and a modified version of the high fidelity knee that contained the geometry of the condylar knee components. The LLNL high fidelity knee model was a finite element computer model which would not be transferred to Exactech during the course of this CRADA effort. The previously performed laboratory studies by Exactech were beneficial to LLNL in verifying the analytical capabilities of NIKE3D for human anatomical modeling. This, in turn, gave LLNL further entree to perform work-for-others in the prosthetics field. There were two purposes to the CRADA (1) To modify the LLNL High Fidelity Knee Model to accept the geometry of the Exactech Total Knee; and (2) To perform parametric studies of the possible design options in appropriate ranges of motion so that an optimum design could be selected for production. Because of unanticipated delays in the CRADA funding, the knee design had to be finalized before the analysis could be accomplished. Thus, the scope of work was modified by the industrial partner. It was decided that it would be most beneficial to perform FEA that would closely replicate the lab tests that had been done as the basis of the design. Exactech was responsible for transmitting the component geometries to Livermore, as well as providing complete data from the quasi-static laboratory loading tests that were performed on various designs. LLNL was responsible for defining the basic finite element mesh and carrying out the analysis. We performed the initial computer simulation and verified model integrity, using the laboratory data. After performing the parametric studies, the results were reviewed with Exactech. Also, the results were presented at the Orthopedic Research Society meeting in a poster session.« less

Development and Testing of a Multimedia Internet-Based System for Fidelity and Monitoring of Multidimensional Treatment Foster Care

PubMed Central

Sprengelmeyer, Peter G; Davis, Betsy; Chamberlain, Patricia

2012-01-01

Background The fields of mental health, child welfare, and juvenile justice are jointly faced with the challenge of reducing the prevalence of antisocial behavior among adolescents. In the last 20 years, conduct disorders have moved from being considered intractable difficulties to having complex but available solutions. The treatments for even long-standing offending behavior among adolescents are now well documented and supported by a growing and compelling body of evidence. These empirically validated interventions are being widely disseminated, but the replication of the results from clinical trials in community settings has yet to be documented. The treatments, which produced impressive effects in a research context, are difficult to replicate without intensive monitoring of fidelity by the developers. Such monitoring is a barrier toward adoption; as the distance between the adopter and developer increases, so does cost. At the same time, states, communities, and agencies are under increasing pressure to implement those intervention services that have been shown to be most effective. The use of the Internet offers a potential solution in that existing reporting and data collection by clinicians can be subject to remote supervision. Such a system would have the potential to provide dissemination teams with more direct access to higher-quality data and would make adopters more likely to be able to implement services at the highest possible conformity to research protocols. Objective To create and test such an innovative system for use with the Multidimensional Treatment Foster Care (MTFC) program, which is an in-home treatment (alternative to a residential- or group-home setting) for antisocial youths. This research could advance the knowledge base about developing innovative infrastructures in community settings to disseminate empirically validated treatments. Methods The fidelity system was used and reviewed by parent and professional users: 20 foster parent users of the Parent Daily Report function, 9 professional MTFC program supervisors, and 4 MTFC consultants. All participants rated the system’s ease of use, quality of the website, and observational videos recorded at agency meetings. In addition, foster parents entered data on child behavior. Results All professionals and foster parents rated the system as very easy to use. We found particularly high levels of use by parents. Professionals rated the computer-collected videos of clinical meetings as being of high quality and easily codeable. Conclusions The project developed a user-friendly and secure Web-based system using state-of-the-art computer-based protocols for recording questionnaire and observational data generated by community-based MTFC staff and foster parents, with positive satisfaction and utilization results. PMID:23073495

Electroforming of optical tooling in high-strength Ni-Co alloy

NASA Astrophysics Data System (ADS)

Stein, Berl

2003-05-01

Plastic optics are often mass produced by injection, compression or injection-compression molding. Optical quality molds can be directly machined in appropriate materials (tool steels, electroless nickel, aluminum, etc.), but much greater cost efficiency can be achieved with electroformed modl inserts. Traditionally, electroforming of optical quality mold inserts has been carried out in nickel, a material much softer than tool steels which, when hardened to 45 - 50 HRc usually exhibit high wear resistance and long service life (hundreds of thousands of impressions per mold). Because of their low hardness (< 20 HRc), nickel molds can produce only tens of thousands of parts before they are scrapped due to wear or accidental damage. This drawback prevented their wider usage in general plastic and optical mold making. Recently, NiCoForm has developed a proprietary Ni-CO electroforming bath combining the high strength and wear resistance of the alloy with the low stress and high replication fidelity typical of pure nickel electroforming. This paper will outline the approach to electroforming of optical quality tooling in low stress, high strength Ni-Co alloy and present several examples of electroformed NiColoy mold inserts.

Multi-fidelity methods for uncertainty quantification in transport problems

NASA Astrophysics Data System (ADS)

Tartakovsky, G.; Yang, X.; Tartakovsky, A. M.; Barajas-Solano, D. A.; Scheibe, T. D.; Dai, H.; Chen, X.

2016-12-01

We compare several multi-fidelity approaches for uncertainty quantification in flow and transport simulations that have a lower computational cost than the standard Monte Carlo method. The cost reduction is achieved by combining a small number of high-resolution (high-fidelity) simulations with a large number of low-resolution (low-fidelity) simulations. We propose a new method, a re-scaled Multi Level Monte Carlo (rMLMC) method. The rMLMC is based on the idea that the statistics of quantities of interest depends on scale/resolution. We compare rMLMC with existing multi-fidelity methods such as Multi Level Monte Carlo (MLMC) and reduced basis methods and discuss advantages of each approach.

High versus Low Theoretical Fidelity Pedometer Intervention Using Social-Cognitive Theory on Steps and Self-Efficacy

ERIC Educational Resources Information Center

Raedeke, Thomas D.; Dlugonski, Deirdre

2017-01-01

Purpose: This study was designed to compare a low versus high theoretical fidelity pedometer intervention applying social-cognitive theory on step counts and self-efficacy. Method: Fifty-six public university employees participated in a 10-week randomized controlled trial with 2 conditions that varied in theoretical fidelity. Participants in the…

Rapid localized heating of graphene coating on a silicon mold by induction for precision molding of polymer optics.

PubMed

Zhang, Lin; Zhou, Wenchen; Yi, Allen Y

2017-04-01

In compression molding of polymer optical components with micro/nanoscale surface features, rapid heating of the mold surface is critical for the implementation of this technology for large-scale applications. In this Letter, a novel method of a localized rapid heating process is reported. This process is based on induction heating of a thin conductive coating deposited on a silicon mold. Since the graphene coating is very thin (∼45  nm), a high heating rate of 10∼20°C/s can be achieved by employing a 1200 W 30 kHz electrical power unit. Under this condition, the graphene-coated surface and the polymer substrate can be heated above the polymer's glass transition temperature within 30 s and subsequently cooled down to room temperature within several tens of seconds after molding, resulting in an overall thermal cycle of about 3 min or shorter. The feasibility of this process was validated by fabrication of optical gratings, micropillar matrices, and microlens arrays on polymethylmethacrylate (PMMA) substrates with very high precision. The uniformity and surface geometries of the replicated optical elements are evaluated using an optical profilometer, a diffraction test setup, and a Shack-Hartmann wavefront sensor built with a molded PMMA microlens array. Compared with the conventional bulk heating molding process, this novel rapid localized induction heating process could improve replication efficiency with better geometrical fidelity.

Muver, a computational framework for accurately calling accumulated mutations.

PubMed

Burkholder, Adam B; Lujan, Scott A; Lavender, Christopher A; Grimm, Sara A; Kunkel, Thomas A; Fargo, David C

2018-05-09

Identification of mutations from next-generation sequencing data typically requires a balance between sensitivity and accuracy. This is particularly true of DNA insertions and deletions (indels), that can impart significant phenotypic consequences on cells but are harder to call than substitution mutations from whole genome mutation accumulation experiments. To overcome these difficulties, we present muver, a computational framework that integrates established bioinformatics tools with novel analytical methods to generate mutation calls with the extremely low false positive rates and high sensitivity required for accurate mutation rate determination and comparison. Muver uses statistical comparison of ancestral and descendant allelic frequencies to identify variant loci and assigns genotypes with models that include per-sample assessments of sequencing errors by mutation type and repeat context. Muver identifies maximally parsimonious mutation pathways that connect these genotypes, differentiating potential allelic conversion events and delineating ambiguities in mutation location, type, and size. Benchmarking with a human gold standard father-son pair demonstrates muver's sensitivity and low false positive rates. In DNA mismatch repair (MMR) deficient Saccharomyces cerevisiae, muver detects multi-base deletions in homopolymers longer than the replicative polymerase footprint at rates greater than predicted for sequential single-base deletions, implying a novel multi-repeat-unit slippage mechanism. Benchmarking results demonstrate the high accuracy and sensitivity achieved with muver, particularly for indels, relative to available tools. Applied to an MMR-deficient Saccharomyces cerevisiae system, muver mutation calls facilitate mechanistic insights into DNA replication fidelity.

Creation of a Rapid High-Fidelity Aerodynamics Module for a Multidisciplinary Design Environment

NASA Technical Reports Server (NTRS)

Srinivasan, Muktha; Whittecar, William; Edwards, Stephen; Mavris, Dimitri N.

2012-01-01

In the traditional aerospace vehicle design process, each successive design phase is accompanied by an increment in the modeling fidelity of the disciplinary analyses being performed. This trend follows a corresponding shrinking of the design space as more and more design decisions are locked in. The correlated increase in knowledge about the design and decrease in design freedom occurs partly because increases in modeling fidelity are usually accompanied by significant increases in the computational expense of performing the analyses. When running high fidelity analyses, it is not usually feasible to explore a large number of variations, and so design space exploration is reserved for conceptual design, and higher fidelity analyses are run only once a specific point design has been selected to carry forward. The designs produced by this traditional process have been recognized as being limited by the uncertainty that is present early on due to the use of lower fidelity analyses. For example, uncertainty in aerodynamics predictions produces uncertainty in trajectory optimization, which can impact overall vehicle sizing. This effect can become more significant when trajectories are being shaped by active constraints. For example, if an optimal trajectory is running up against a normal load factor constraint, inaccuracies in the aerodynamic coefficient predictions can cause a feasible trajectory to be considered infeasible, or vice versa. For this reason, a trade must always be performed between the desired fidelity and the resources available. Apart from this trade between fidelity and computational expense, it is very desirable to use higher fidelity analyses earlier in the design process. A large body of work has been performed to this end, led by efforts in the area of surrogate modeling. In surrogate modeling, an up-front investment is made by running a high fidelity code over a Design of Experiments (DOE); once completed, the DOE data is used to create a surrogate model, which captures the relationships between input variables and responses into regression equations. Depending on the dimensionality of the problem and the fidelity of the code for which a surrogate model is being created, the initial DOE can itself be computationally prohibitive to run. Cokriging, a modeling approach from the field of geostatistics, provides a desirable compromise between computational expense and fidelity. To do this, cokriging leverages a large body of data generated by a low fidelity analysis, combines it with a smaller set of data from a higher fidelity analysis, and creates a kriging surrogate model with prediction fidelity approaching that of the higher fidelity analysis. When integrated into a multidisciplinary environment, a disciplinary analysis module employing cokriging can raise the analysis fidelity without drastically impacting the expense of design iterations. This is demonstrated through the creation of an aerodynamics analysis module in NASA s OpenMDAO framework. Aerodynamic analyses including Missile DATCOM, APAS, and USM3D are leveraged to create high fidelity aerodynamics decks for parametric vehicle geometries, which are created in NASA s Vehicle Sketch Pad (VSP). Several trade studies are performed to examine the achieved level of model fidelity, and the overall impact to vehicle design is quantified.

Dissociable effects of surprising rewards on learning and memory.

PubMed

Rouhani, Nina; Norman, Kenneth A; Niv, Yael

2018-03-19

Reward-prediction errors track the extent to which rewards deviate from expectations, and aid in learning. How do such errors in prediction interact with memory for the rewarding episode? Existing findings point to both cooperative and competitive interactions between learning and memory mechanisms. Here, we investigated whether learning about rewards in a high-risk context, with frequent, large prediction errors, would give rise to higher fidelity memory traces for rewarding events than learning in a low-risk context. Experiment 1 showed that recognition was better for items associated with larger absolute prediction errors during reward learning. Larger prediction errors also led to higher rates of learning about rewards. Interestingly we did not find a relationship between learning rate for reward and recognition-memory accuracy for items, suggesting that these two effects of prediction errors were caused by separate underlying mechanisms. In Experiment 2, we replicated these results with a longer task that posed stronger memory demands and allowed for more learning. We also showed improved source and sequence memory for items within the high-risk context. In Experiment 3, we controlled for the difficulty of reward learning in the risk environments, again replicating the previous results. Moreover, this control revealed that the high-risk context enhanced item-recognition memory beyond the effect of prediction errors. In summary, our results show that prediction errors boost both episodic item memory and incremental reward learning, but the two effects are likely mediated by distinct underlying systems. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Understanding the Mechanism of the Broad-Spectrum Antiviral Activity of Favipiravir (T-705): Key Role of the F1 Motif of the Viral Polymerase.

PubMed

Abdelnabi, Rana; Morais, Ana Theresa Silveira de; Leyssen, Pieter; Imbert, Isabelle; Beaucourt, Stéphanie; Blanc, Hervé; Froeyen, Mathy; Vignuzzi, Marco; Canard, Bruno; Neyts, Johan; Delang, Leen

2017-06-15

Favipiravir (T-705) is a broad-spectrum antiviral agent that has been approved in Japan for the treatment of influenza virus infections. T-705 also inhibits the replication of various RNA viruses, including chikungunya virus (CHIKV). We demonstrated earlier that the K291R mutation in the F1 motif of the RNA-dependent RNA polymerase (RdRp) of CHIKV is responsible for low-level resistance to T-705. Interestingly, this lysine is highly conserved in the RdRp of positive-sense single-stranded RNA (+ssRNA) viruses. To obtain insights into the unique broad-spectrum antiviral activity of T-705, we explored the role of this lysine using another +ssRNA virus, namely, coxsackievirus B3 (CVB3). Introduction of the corresponding K-to-R substitution in the CVB3 RdRp (K159R) resulted in a nonviable virus. Replication competence of the K159R variant was restored by spontaneous acquisition of an A239G substitution in the RdRp. A mutagenesis analysis at position K159 identified the K159M variant as the only other viable variant which had also acquired the A239G substitution. The K159 substitutions markedly decreased the processivity of the purified viral RdRp, which was restored by the introduction of the A239G mutation. The K159R A239G and K159M A239G variants proved, surprisingly, more susceptible than the wild-type virus to T-705 and exhibited lower fidelity in polymerase assays. Furthermore, the K159R A239G variant was found to be highly attenuated in mice. We thus demonstrate that the conserved lysine in the F1 motif of the RdRp of +ssRNA viruses is involved in the broad-spectrum antiviral activity of T-705 and that it is a key amino acid for the proper functioning of the enzyme. IMPORTANCE In this study, we report the key role of a highly conserved lysine residue of the viral polymerase in the broad-spectrum antiviral activity of favipiravir (T-705) against positive-sense single-stranded RNA viruses. Substitutions of this conserved lysine have a major negative impact on the functionality of the RdRp. Furthermore, we show that this lysine is involved in the fidelity of the RdRp and that the RdRp fidelity influences the sensitivity of the virus for the antiviral efficacy of T-705. Consequently, these results provide insights into the mechanism of the antiviral activity of T-705 and may lay the basis for the design of novel chemical scaffolds that may be endowed with a more potent broad-spectrum antiviral activity than that of T-705. Copyright © 2017 American Society for Microbiology.

Kinetic measurement of 2-aminopurine X cytosine and 2-aminopurine X thymine base pairs as a test of DNA polymerase fidelity mechanisms.

PubMed Central

Watanabe, S M; Goodman, M F

1982-01-01

Enzyme kinetic measurements are presented showing that Km rather than maximum velocity (Vmax) discrimination governs the frequency of forming 2-aminopurine X cytosine base mispairs by DNA polymerase alpha. An in vitro system is used in which incorporation of dTMP or dCMP occurs opposite a template 2-aminopurine, and values for Km and Vmax are obtained. Results from a previous study in which dTTP and dCTP were competing simultaneously for insertion opposite 2-aminopurine indicated that dTMP is inserted 22 times more frequently than dCMP. We now report that the ratio of Km values KCm/KTm = 25 +/- 6, which agrees quantitatively with the dTMP/dCMP incorporation ratio obtained previously. We also report that VCmax is indistinguishable from VTmax. These Km and Vmax data are consistent with predictions from a model, the Km discrimination model, in which replication fidelity is determined by free energy differences between matched and mismatched base pairs. Central to this model is the prediction that the ratio of Km values for insertion of correct and incorrect nucleotides specifies the insertion fidelity, and the maximum velocities of insertion are the same for both nucleotides. PMID:6959128

Assessing the fidelity of the Kin KeeperSM prevention intervention in African American, Latina and Arab women.

PubMed

Ford, Sabrina; Meghea, Cristian; Estes, Tamika; Hamade, Hiam; Lockett, Murlisa; Williams, Karen Patricia

2014-02-01

We evaluated a randomized controlled treatment, utilizing Community Health Workers (CHW) to deliver breast and cervical cancer education intervention to African American, Latina, and Arab women in Detroit and Dearborn, Michigan. The main objectives of the study are to: (1) examine fidelity and consistency of treatment delivery and (2) assess qualitative elements of the intervention. We surveyed 305 women who received the intervention and 16 CHWs Survey included questions regarding the treatment integrity, treatment received, and training provided. Surveys included both quantitative and questions. The intervention group (n = 305) was made up of 48% Black, 11% Latina, and 41% Arab women. Almost all (≥ 90%) women agreed that they received the treatment in the way that it was intended. Sixteen CHWs responded affirmatively as well. Both participants and CHWs indicated that the program was mutually rewarding, indicating that there was "cross fertilization and cross benefit" of working with each other. These benefits served to endorse and confirm that CHWs are a very important mechanism in increasing health literacy in the community and referring underserved individuals to health providers. Second, with strong treatment fidelity the Kin Keeper(SM) program and has the potential to be replicated for a number of diseases in a variety of venues especially for those facing health disparities.

Evaluation of a Person-Centered, Theory-Based Intervention to Promote Health Behaviors.

PubMed

Worawong, Chiraporn; Borden, Mary Jo; Cooper, Karen M; Pérez, Oscar A; Lauver, Diane

Effective promotion of health behaviors requires strong interventions. Applying person-centered approaches and concepts synthesized from two motivational theories could strengthen the effects of such interventions. The aim of the study was to report the effect sizes, fidelity, and acceptability of a person-centered, health behavior intervention based on self-regulation and self-determination theories. Using a pre- and postintervention design, with a 4-week follow-up, advanced practice registered nurses made six weekly contacts with 52 volunteer participants. Most participants were educated White women. Advanced practice registered nurses elicited participant motives and particular goals for either healthy diet or physical activity behaviors. Minutes and type of activity and servings of fat and fruit/vegetables were assessed. Effect sizes for engaging in moderate aerobic activity and in fruit/vegetable and fat intake were 0.53, 0.82, and -0.57, respectively. The fidelity of delivery was 80-97% across contacts, and fidelity of participants' receipt of intervention components was supported. Participant acceptance of the intervention was supported by positive ratings on aspects of relevance and usefulness. To advance the science of health behavior change and improve client health status, person-centered approaches and concepts synthesized from motivational theories can be applied and tested with a randomized, controlled design and diverse samples to replicate and extend this promising behavioral intervention.

High Fidelity Simulation of Atomization in Diesel Engine Sprays

DTIC Science & Technology

2015-09-01

ARL-RP-0555 ● SEP 2015 US Army Research Laboratory High Fidelity Simulation of Atomization in Diesel Engine Sprays by L Bravo...ARL-RP-0555 ● SEP 2015 US Army Research Laboratory High Fidelity Simulation of Atomization in Diesel Engine Sprays by L...Simulation of Atomization in Diesel Engine Sprays 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) L Bravo, CB Ivey, D

Implementation Fidelity in Community-Based Interventions

PubMed Central

Breitenstein, Susan M.; Gross, Deborah; Garvey, Christine; Hill, Carri; Fogg, Louis; Resnick, Barbara

2012-01-01

Implementation fidelity is the degree to which an intervention is delivered as intended and is critical to successful translation of evidence-based interventions into practice. Diminished fidelity may be why interventions that work well in highly controlled trials may fail to yield the same outcomes when applied in real life contexts. The purpose of this paper is to define implementation fidelity and describe its importance for the larger science of implementation, discuss data collection methods and current efforts in measuring implementation fidelity in community-based prevention interventions, and present future research directions for measuring implementation fidelity that will advance implementation science. PMID:20198637

NPSS Multidisciplinary Integration and Analysis

NASA Technical Reports Server (NTRS)

Hall, Edward J.; Rasche, Joseph; Simons, Todd A.; Hoyniak, Daniel

2006-01-01

The objective of this task was to enhance the capability of the Numerical Propulsion System Simulation (NPSS) by expanding its reach into the high-fidelity multidisciplinary analysis area. This task investigated numerical techniques to convert between cold static to hot running geometry of compressor blades. Numerical calculations of blade deformations were iteratively done with high fidelity flow simulations together with high fidelity structural analysis of the compressor blade. The flow simulations were performed with the Advanced Ducted Propfan Analysis (ADPAC) code, while structural analyses were performed with the ANSYS code. High fidelity analyses were used to evaluate the effects on performance of: variations in tip clearance, uncertainty in manufacturing tolerance, variable inlet guide vane scheduling, and the effects of rotational speed on the hot running geometry of the compressor blades.

Generation and applications of an ultrahigh-fidelity four-photon Greenberger-Horne-Zeilinger state.

PubMed

Zhang, Chao; Huang, Yun-Feng; Zhang, Cheng-Jie; Wang, Jian; Liu, Bi-Heng; Li, Chuan-Feng; Guo, Guang-Can

2016-11-28

High-quality entangled photon pairs generated via spontaneous parametric down-conversion have made great contributions to the modern quantum information science and the fundamental tests of quantum mechanics. However, the quality of the entangled states decreases sharply when moving from biphoton to multiphoton experiments, mainly due to the lack of interactions between photons. Here, for the first time, we generate a four-photon Greenberger-Horne-Zeilinger state with a fidelity of 98%, which is even comparable to the best fidelity of biphoton entangled states. Thus, it enables us to demonstrate an ultrahigh-fidelity entanglement swapping-the key ingredient in various quantum information tasks. Our results push the fidelity of multiphoton entanglement generation to a new level and would be useful in some demanding tasks, e.g., we successfully demonstrate the genuine multipartite nonlocality of the observed state in the nonsignaling scenario by violating a novel Hardy-like inequality, which requires very high state-fidelity.

Implementing a high-fidelity simulation program in a community college setting.

PubMed

Tuoriniemi, Pamela; Schott-Baer, Darlene

2008-01-01

Despite their relatively high cost, there is heightened interest by faculty in undergraduate nursing programs to implement high-fidelity simulation (HFS) programs. High-fidelity simulators are appealing because they allow students to experience high-risk, low-volume patient problems in a realistic setting. The decision to purchase a simulator is the first step in the process of implementing and maintaining an HFS lab. Knowledge, technical skill, commitment, and considerable time are needed to develop a successful program. The process, as experienced by one community college nursing program, is described.

Teaching elliptical excision skills to novice medical students: a randomized controlled study comparing low- and high-fidelity bench models.

PubMed

Denadai, Rafael; Oshiiwa, Marie; Saad-Hossne, Rogério

2014-03-01

The search for alternative and effective forms of training simulation is needed due to ethical and medico-legal aspects involved in training surgical skills on living patients, human cadavers and living animals. To evaluate if the bench model fidelity interferes in the acquisition of elliptical excision skills by novice medical students. Forty novice medical students were randomly assigned to 5 practice conditions with instructor-directed elliptical excision skills' training (n = 8): didactic materials (control); organic bench model (low-fidelity); ethylene-vinyl acetate bench model (low-fidelity); chicken legs' skin bench model (high-fidelity); or pig foot skin bench model (high-fidelity). Pre- and post-tests were applied. Global rating scale, effect size, and self-perceived confidence based on Likert scale were used to evaluate all elliptical excision performances. The analysis showed that after training, the students practicing on bench models had better performance based on Global rating scale (all P < 0.0000) and felt more confident to perform elliptical excision skills (all P < 0.0000) when compared to the control. There was no significant difference (all P > 0.05) between the groups that trained on bench models. The magnitude of the effect (basic cutaneous surgery skills' training) was considered large (>0.80) in all measurements. The acquisition of elliptical excision skills after instructor-directed training on low-fidelity bench models was similar to the training on high-fidelity bench models; and there was a more substantial increase in elliptical excision performances of students that trained on all simulators compared to the learning on didactic materials.

Crystal Structure of Poliovirus 3CD Protein: Virally Encoded Protease and Precursor to the RNA-Dependent RNA Polymerase

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

Marcotte,L.; Wass, A.; Gohara, D.

2007-01-01

Poliovirus 3CD is a multifunctional protein that serves as a precursor to the protease 3Cpro and the viral polymerase 3Dpol and also plays a role in the control of viral replication. Although 3CD is a fully functional protease, it lacks polymerase activity. We have solved the crystal structures of 3CD at a 3.4- Angstroms resolution and the G64S fidelity mutant of 3Dpol at a 3.0- Angstroms resolution. In the 3CD structure, the 3C and 3D domains are joined by a poorly ordered polypeptide linker, possibly to facilitate its cleavage, in an arrangement that precludes intramolecular proteolysis. The polymerase active sitemore » is intact in both the 3CD and the 3Dpol G64S structures, despite the disruption of a network proposed to position key residues in the active site. Therefore, changes in molecular flexibility may be responsible for the differences in fidelity and polymerase activities. Extensive packing contacts between symmetry-related 3CD molecules and the approach of the 3C domain's N terminus to the VPg binding site suggest how 3Dpol makes biologically relevant interactions with the 3C, 3CD, and 3BCD proteins that control the uridylylation of VPg during the initiation of viral replication. Indeed, mutations designed to disrupt these interfaces have pronounced effects on the uridylylation reaction in vitro.« less

Electro-Optic Frequency Beam Splitters and Tritters for High-Fidelity Photonic Quantum Information Processing

DOE PAGES

Lu, Hsuan-Hao; Lukens, Joseph M.; Peters, Nicholas A.; ...

2018-01-18

In this paper, we report the experimental realization of high-fidelity photonic quantum gates for frequency-encoded qubits and qutrits based on electro-optic modulation and Fourier-transform pulse shaping. Our frequency version of the Hadamard gate offers near-unity fidelity (0.99998±0.00003), requires only a single microwave drive tone for near-ideal performance, functions across the entire C band (1530–1570 nm), and can operate concurrently on multiple qubits spaced as tightly as four frequency modes apart, with no observable degradation in the fidelity. For qutrits, we implement a 3×3 extension of the Hadamard gate: the balanced tritter. This tritter—the first ever demonstrated for frequency modes—attains fidelitymore » 0.9989±0.0004. Finally, these gates represent important building blocks toward scalable, high-fidelity quantum information processing based on frequency encoding.« less

Electro-Optic Frequency Beam Splitters and Tritters for High-Fidelity Photonic Quantum Information Processing

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

Lu, Hsuan-Hao; Lukens, Joseph M.; Peters, Nicholas A.

In this paper, we report the experimental realization of high-fidelity photonic quantum gates for frequency-encoded qubits and qutrits based on electro-optic modulation and Fourier-transform pulse shaping. Our frequency version of the Hadamard gate offers near-unity fidelity (0.99998±0.00003), requires only a single microwave drive tone for near-ideal performance, functions across the entire C band (1530–1570 nm), and can operate concurrently on multiple qubits spaced as tightly as four frequency modes apart, with no observable degradation in the fidelity. For qutrits, we implement a 3×3 extension of the Hadamard gate: the balanced tritter. This tritter—the first ever demonstrated for frequency modes—attains fidelitymore » 0.9989±0.0004. Finally, these gates represent important building blocks toward scalable, high-fidelity quantum information processing based on frequency encoding.« less

Rotorcraft Research at the NASA Vertical Motion Simulator

NASA Technical Reports Server (NTRS)

Aponso, Bimal Lalith; Tran, Duc T.; Schroeder, Jeffrey A.

2009-01-01

In the 1970 s the role of the military helicopter evolved to encompass more demanding missions including low-level nap-of-the-earth flight and operation in severely degraded visual environments. The Vertical Motion Simulator (VMS) at the NASA Ames Research Center was built to provide a high-fidelity simulation capability to research new rotorcraft concepts and technologies that could satisfy these mission requirements. The VMS combines a high-fidelity large amplitude motion system with an adaptable simulation environment including interchangeable and configurable cockpits. In almost 30 years of operation, rotorcraft research on the VMS has contributed significantly to the knowledge-base on rotorcraft performance, handling qualities, flight control, and guidance and displays. These contributions have directly benefited current rotorcraft programs and flight safety. The high fidelity motion system in the VMS was also used to research simulation fidelity. This research provided a fundamental understanding of pilot cueing modalities and their effect on simulation fidelity.

Keeping mammalian mutation load in check: regulation of the activity of error-prone DNA polymerases by p53 and p21.

PubMed

Livneh, Zvi

2006-09-01

To overcome DNA lesions that block replication the cell employs translesion DNA synthesis (TLS) polymerases, a group of low fidelity DNA polymerases that have the capacity to bypass a wide range of DNA lesions. This TLS process is also termed error-prone repair, due to its inherent mutagenic nature. We have recently shown that the tumor suppressor p53 and the cell cycle inhibitor p21 are global regulators of TLS. When these proteins are missing or nonfunctional, TLS gets out of control: its extent increases to very high levels, and its fidelity decreases, causing an overall increase in mutation load. This may be explained by the loss of selectivity in the bypass of specific DNA lesions by their cognate specialized polymerases, such that lesion bypass continues to a maximum, regardless of the price paid in increased mutations. The p53 and p21 proteins are also required for efficient UV light-induced monoubiquitination of PCNA, which is consistent with a model in which this modification of PCNA is necessary but not sufficient for the normal activity of TLS. This regulation suggests that TLS evolved in mammals as a system that balances gain in survival with a tolerable mutational cost, and that disturbing this balance causes a potentially harmful increase in mutations, which might play a role in carcinogenesis.

First-Order Frameworks for Managing Models in Engineering Optimization

NASA Technical Reports Server (NTRS)

Alexandrov, Natlia M.; Lewis, Robert Michael

2000-01-01

Approximation/model management optimization (AMMO) is a rigorous methodology for attaining solutions of high-fidelity optimization problems with minimal expense in high- fidelity function and derivative evaluation. First-order AMMO frameworks allow for a wide variety of models and underlying optimization algorithms. Recent demonstrations with aerodynamic optimization achieved three-fold savings in terms of high- fidelity function and derivative evaluation in the case of variable-resolution models and five-fold savings in the case of variable-fidelity physics models. The savings are problem dependent but certain trends are beginning to emerge. We give an overview of the first-order frameworks, current computational results, and an idea of the scope of the first-order framework applicability.

The experiences of last-year student midwives with High-Fidelity Perinatal Simulation training: A qualitative descriptive study.

PubMed

Vermeulen, Joeri; Beeckman, Katrien; Turcksin, Rivka; Van Winkel, Lies; Gucciardo, Léonardo; Laubach, Monika; Peersman, Wim; Swinnen, Eva

2017-06-01

Simulation training is a powerful and evidence-based teaching method in healthcare. It allows students to develop essential competences that are often difficult to achieve during internships. High-Fidelity Perinatal Simulation exposes them to real-life scenarios in a safe environment. Although student midwives' experiences need to be considered to make the simulation training work, these have been overlooked so far. To explore the experiences of last-year student midwives with High-Fidelity Perinatal Simulation training. A qualitative descriptive study, using three focus group conversations with last-year student midwives (n=24). Audio tapes were transcribed and a thematic content analysis was performed. The entire data set was coded according to recurrent or common themes. To achieve investigator triangulation and confirm themes, discussions among the researchers was incorporated in the analysis. Students found High-Fidelity Perinatal Simulation training to be a positive learning method that increased both their competence and confidence. Their experiences varied over the different phases of the High-Fidelity Perinatal Simulation training. Although uncertainty, tension, confusion and disappointment were experienced throughout the simulation trajectory, they reported that this did not affect their learning and confidence-building. As High-Fidelity Perinatal Simulation training constitutes a helpful learning experience in midwifery education, it could have a positive influence on maternal and neonatal outcomes. In the long term, it could therefore enhance the midwifery profession in several ways. The present study is an important first step in opening up the debate about the pedagogical use of High-Fidelity Perinatal Simulation training within midwifery education. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

[Acquiring skills in malignant hyperthermia crisis management: comparison of high-fidelity simulation versus computer-based case study].

PubMed

Mejía, Vilma; Gonzalez, Carlos; Delfino, Alejandro E; Altermatt, Fernando R; Corvetto, Marcia A

The primary purpose of this study was to compare the effect of high fidelity simulation versus a computer-based case solving self-study, in skills acquisition about malignant hyperthermia on first year anesthesiology residents. After institutional ethical committee approval, 31 first year anesthesiology residents were enrolled in this prospective randomized single-blinded study. Participants were randomized to either a High Fidelity Simulation Scenario or a computer-based Case Study about malignant hyperthermia. After the intervention, all subjects' performance in was assessed through a high fidelity simulation scenario using a previously validated assessment rubric. Additionally, knowledge tests and a satisfaction survey were applied. Finally, a semi-structured interview was done to assess self-perception of reasoning process and decision-making. 28 first year residents finished successfully the study. Resident's management skill scores were globally higher in High Fidelity Simulation versus Case Study, however they were significant in 4 of the 8 performance rubric elements: recognize signs and symptoms (p = 0.025), prioritization of initial actions of management (p = 0.003), recognize complications (p = 0.025) and communication (p = 0.025). Average scores from pre- and post-test knowledge questionnaires improved from 74% to 85% in the High Fidelity Simulation group, and decreased from 78% to 75% in the Case Study group (p = 0.032). Regarding the qualitative analysis, there was no difference in factors influencing the student's process of reasoning and decision-making with both teaching strategies. Simulation-based training with a malignant hyperthermia high-fidelity scenario was superior to computer-based case study, improving knowledge and skills in malignant hyperthermia crisis management, with a very good satisfaction level in anesthesia residents. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Higher order genomic organization and regulatory compartmentalization for cell cycle control at the G1/S-phase transition.

PubMed

Ghule, Prachi N; Seward, David J; Fritz, Andrew J; Boyd, Joseph R; van Wijnen, Andre J; Lian, Jane B; Stein, Janet L; Stein, Gary S

2018-05-10

Fidelity of histone gene regulation, and ultimately of histone protein biosynthesis, is obligatory for packaging of newly replicated DNA into chromatin. Control of histone gene expression within the 3-dimensional context of nuclear organization is reflected by two well documented observations. DNA replication-dependent histone mRNAs are synthesized at specialized subnuclear domains designated histone locus bodies (HLBs), in response to activation of the growth factor dependent Cyclin E/CDK2/HINFP/NPAT pathway at the G1/S transition in mammalian cells. Complete loss of the histone gene regulatory factors HINFP or NPAT disrupts HLB integrity that is necessary for coordinate control of DNA replication and histone gene transcription. Here we review the molecular histone-related requirements for G1/S-phase progression during the cell cycle. Recently developed experimental strategies, now enable us to explore mechanisms involved in dynamic control of histone gene expression in the context of the temporal (cell cycle) and spatial (HLBs) remodeling of the histone gene loci. © 2018 Wiley Periodicals, Inc.

Applications of fidelity measures to complex quantum systems

PubMed Central

2016-01-01

We revisit fidelity as a measure for the stability and the complexity of the quantum motion of single-and many-body systems. Within the context of cold atoms, we present an overview of applications of two fidelities, which we call static and dynamical fidelity, respectively. The static fidelity applies to quantum problems which can be diagonalized since it is defined via the eigenfunctions. In particular, we show that the static fidelity is a highly effective practical detector of avoided crossings characterizing the complexity of the systems and their evolutions. The dynamical fidelity is defined via the time-dependent wave functions. Focusing on the quantum kicked rotor system, we highlight a few practical applications of fidelity measurements in order to better understand the large variety of dynamical regimes of this paradigm of a low-dimensional system with mixed regular–chaotic phase space. PMID:27140967

Generation of high-fidelity four-photon cluster state and quantum-domain demonstration of one-way quantum computing.

PubMed

Tokunaga, Yuuki; Kuwashiro, Shin; Yamamoto, Takashi; Koashi, Masato; Imoto, Nobuyuki

2008-05-30

We experimentally demonstrate a simple scheme for generating a four-photon entangled cluster state with fidelity over 0.860+/-0.015. We show that the fidelity is high enough to guarantee that the produced state is distinguished from Greenberger-Horne-Zeilinger, W, and Dicke types of genuine four-qubit entanglement. We also demonstrate basic operations of one-way quantum computing using the produced state and show that the output state fidelities surpass classical bounds, which indicates that the entanglement in the produced state essentially contributes to the quantum operation.

Bridging burn care education with modern technology, an integration with high fidelity human patient simulation.

PubMed

Reeves, Patrick T; Borgman, Matthew A; Caldwell, Nicole W; Patel, Leela; Aden, James; Duggan, John P; Serio-Melvin, Maria L; Mann-Salinas, Elizabeth A

2018-08-01

The Advanced Burn Life Support (ABLS) program is a burn-education curriculum nearly 30 years in the making, focusing on the unique challenges of the first 24h of care after burn injury. Our team applied high fidelity human patient simulation (HFHPS) to the established ABLS curriculum. Our hypothesis was that HFHPS would be a feasible, easily replicable, and valuable adjunct to the current curriculum that would enhance learner experience. This prospective, evidenced-based practice project was conducted in a single simulation center employing the American Burn Association's ABLS curriculum using HFHPS. Participants managed 7 separate simulated polytrauma and burn scenarios with resultant clinical complications. After training, participants completed written and practical examinations as well as satisfaction surveys. From 2012 to 2013, 71 students participated in this training. Simulation (ABLS-Sim) participants demonstrated a 2.5% increase in written post-test scores compared to traditional ABLS Provider Course (ABLS Live) (p=0.0016). There was no difference in the practical examination when comparing ABLS-Sim versus ABLS Live. Subjectively, 60 (85%) participants completed surveys. The Educational Practice Questionnaire showed best practices rating of 4.5±0.7; with importance of learning rated at 4.4±0.8. The Simulation Design Scale rating for design was 4.6±0.6 with an importance rating of 4.4±0.8. Overall Satisfaction and Self-Confidence with Learning were 4.4±0.7 and 4.5±0.7, respectfully. Integrating HFHPS with the current ABLS curriculum led to higher written exam scores, high levels of confidence, satisfaction, and active learning, and presented an evidenced-based model for education that is easily employable for other facilities nationwide. Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.

Implementation of a Text-Based Content Intervention in Secondary Social Studies Classes.

PubMed

Wanzek, Jeanne; Vaughn, Sharon

2016-12-01

We describe teacher fidelity (adherence to the components of the treatment as specified by the research team) based on a series of studies of a multicomponent intervention, Promoting Acceleration of Comprehension and Content Through Text (PACT), with middle and high school social studies teachers and their students. Findings reveal that even with highly specified materials and implementing practices that are aligned with effective reading comprehension and content instruction, teachers' fidelity was consistently low for some components and high for others. Teachers demonstrated consistently high implementation fidelity and quality for the instructional components of building background knowledge (comprehension canopy) and teaching key content vocabulary (essential words), whereas we recorded consistently lower fidelity and quality of implementation for the instructional components of critical reading and knowledge application. © 2016 Wiley Periodicals, Inc.

A comparison of select image-compression algorithms for an electronic still camera

NASA Technical Reports Server (NTRS)

Nerheim, Rosalee

1989-01-01

This effort is a study of image-compression algorithms for an electronic still camera. An electronic still camera can record and transmit high-quality images without the use of film, because images are stored digitally in computer memory. However, high-resolution images contain an enormous amount of information, and will strain the camera's data-storage system. Image compression will allow more images to be stored in the camera's memory. For the electronic still camera, a compression algorithm that produces a reconstructed image of high fidelity is most important. Efficiency of the algorithm is the second priority. High fidelity and efficiency are more important than a high compression ratio. Several algorithms were chosen for this study and judged on fidelity, efficiency and compression ratio. The transform method appears to be the best choice. At present, the method is compressing images to a ratio of 5.3:1 and producing high-fidelity reconstructed images.

Scaling up the evaluation of psychotherapy: evaluating motivational interviewing fidelity via statistical text classification

PubMed Central

2014-01-01

Background Behavioral interventions such as psychotherapy are leading, evidence-based practices for a variety of problems (e.g., substance abuse), but the evaluation of provider fidelity to behavioral interventions is limited by the need for human judgment. The current study evaluated the accuracy of statistical text classification in replicating human-based judgments of provider fidelity in one specific psychotherapy—motivational interviewing (MI). Method Participants (n = 148) came from five previously conducted randomized trials and were either primary care patients at a safety-net hospital or university students. To be eligible for the original studies, participants met criteria for either problematic drug or alcohol use. All participants received a type of brief motivational interview, an evidence-based intervention for alcohol and substance use disorders. The Motivational Interviewing Skills Code is a standard measure of MI provider fidelity based on human ratings that was used to evaluate all therapy sessions. A text classification approach called a labeled topic model was used to learn associations between human-based fidelity ratings and MI session transcripts. It was then used to generate codes for new sessions. The primary comparison was the accuracy of model-based codes with human-based codes. Results Receiver operating characteristic (ROC) analyses of model-based codes showed reasonably strong sensitivity and specificity with those from human raters (range of area under ROC curve (AUC) scores: 0.62 – 0.81; average AUC: 0.72). Agreement with human raters was evaluated based on talk turns as well as code tallies for an entire session. Generated codes had higher reliability with human codes for session tallies and also varied strongly by individual code. Conclusion To scale up the evaluation of behavioral interventions, technological solutions will be required. The current study demonstrated preliminary, encouraging findings regarding the utility of statistical text classification in bridging this methodological gap. PMID:24758152

Stimulated Brillouin scattering continuous wave phase conjugation in step-index fiber optics.

PubMed

Massey, Steven M; Spring, Justin B; Russell, Timothy H

2008-07-21

Continuous wave (CW) stimulated Brillouin scattering (SBS) phase conjugation in step-index optical fibers was studied experimentally and modeled as a function of fiber length. A phase conjugate fidelity over 80% was measured from SBS in a 40 m fiber using a pinhole technique. Fidelity decreases with fiber length, and a fiber with a numerical aperture (NA) of 0.06 was found to generate good phase conjugation fidelity over longer lengths than a fiber with 0.13 NA. Modeling and experiment support previous work showing the maximum interaction length which yields a high fidelity phase conjugate beam is inversely proportional to the fiber NA(2), but find that fidelity remains high over much longer fiber lengths than previous models calculated. Conditions for SBS beam cleanup in step-index fibers are discussed.

Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production

PubMed Central

Kandasamy, Suresh K.

2016-01-01

The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22–24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report that recognition of the 5′-monophosphate of a long dsRNA substrate by a phosphate-binding pocket in the Dicer-2 PAZ (Piwi, Argonaute, and Zwille/Pinhead) domain is crucial for the length fidelity, but not the efficiency, in 21-nt siRNA production. Loss of the length fidelity, meaning increased length heterogeneity of siRNAs, caused by point mutations in the phosphate-binding pocket of the Dicer-2 PAZ domain decreased RNA silencing activity in vivo, showing the importance of the high fidelity to make 21-nt siRNAs. We propose that the 5′-monophosphate of a long dsRNA substrate is anchored by the phosphate-binding pocket in the Dicer-2 PAZ domain and the distance between the pocket and the RNA cleavage active site in the RNaseIII domain corresponds to the 21-nt pitch in the A-form duplex of a long dsRNA substrate, resulting in high-fidelity 21-nt siRNA production. This study sheds light on the molecular mechanism by which Dicer-2 produces 21-nt siRNAs with a remarkably high fidelity for efficient RNA silencing. PMID:27872309

Recombination in Enteroviruses Is a Biphasic Replicative Process Involving the Generation of Greater-than Genome Length ‘Imprecise’ Intermediates

PubMed Central

Lowry, Kym; Woodman, Andrew; Cook, Jonathan; Evans, David J.

2014-01-01

Recombination in enteroviruses provides an evolutionary mechanism for acquiring extensive regions of novel sequence, is suggested to have a role in genotype diversity and is known to have been key to the emergence of novel neuropathogenic variants of poliovirus. Despite the importance of this evolutionary mechanism, the recombination process remains relatively poorly understood. We investigated heterologous recombination using a novel reverse genetic approach that resulted in the isolation of intermediate chimeric intertypic polioviruses bearing genomes with extensive duplicated sequences at the recombination junction. Serial passage of viruses exhibiting such imprecise junctions yielded progeny with increased fitness which had lost the duplicated sequences. Mutations or inhibitors that changed polymerase fidelity or the coalescence of replication complexes markedly altered the yield of recombinants (but did not influence non-replicative recombination) indicating both that the process is replicative and that it may be possible to enhance or reduce recombination-mediated viral evolution if required. We propose that extant recombinants result from a biphasic process in which an initial recombination event is followed by a process of resolution, deleting extraneous sequences and optimizing viral fitness. This process has implications for our wider understanding of ‘evolution by duplication’ in the positive-strand RNA viruses. PMID:24945141

Recent Insight into the Kinetic Mechanisms and Conformational Dynamics of Y-Family DNA Polymerases

PubMed Central

2015-01-01

The kinetic mechanisms by which DNA polymerases catalyze DNA replication and repair have long been areas of active research. Recently discovered Y-family DNA polymerases catalyze the bypass of damaged DNA bases that would otherwise block replicative DNA polymerases and stall replication forks. Unlike DNA polymerases from the five other families, the Y-family DNA polymerases have flexible, solvent-accessible active sites that are able to tolerate various types of damaged template bases and allow for efficient lesion bypass. Their promiscuous active sites, however, also lead to fidelities that are much lower than those observed for other DNA polymerases and give rise to interesting mechanistic properties. Additionally, the Y-family DNA polymerases have several other unique structural features and undergo a set of conformational changes during substrate binding and catalysis different from those observed for replicative DNA polymerases. In recent years, pre-steady-state kinetic methods have been extensively employed to reveal a wealth of information about the catalytic properties of these fascinating noncanonical DNA polymerases. Here, we review many of the recent findings on the kinetic mechanisms of DNA polymerization with undamaged and damaged DNA substrates by the Y-family DNA polymerases, and the conformational dynamics employed by these error-prone enzymes during catalysis. PMID:24716482

High Fidelity Virtual Environments: Does Shader Quality or Higher Polygon Count Models Increase Presence and Learning

NASA Astrophysics Data System (ADS)

Horton, Scott

This research study investigated the effects of high fidelity graphics on both learning and presence, or the "sense of being there," inside a Virtual Learning Environment (VLE). Four versions of a VLE on the subject of the element mercury were created, each with a different combination of high and low fidelity polygon models and high and low fidelity shaders. A total of 76 college age (18+ years of age) participants were randomly assigned to one of the four conditions. The participants interacted with the VLE and then completed several posttest measures on learning, presence, and attitudes towards the VLE experience. Demographic information was also collected, including age, computer gameplay experience, number of virtual environments interacted with, gender and time spent in this virtual environment. The data was analyzed as a 2 x 2 between subjects ANOVA. The main effects of shader fidelity and polygon fidelity were both non-significant for both learning and all presence subscales inside the VLE. In addition, there was no significant interaction between shader fidelity and model fidelity. However, there were two significant results on the supplementary variables. First, gender was found to have a significant main effect on all the presence subscales. Females reported higher average levels of presence than their male counterparts. Second, gameplay hours, or the number of hours a participant played computer games per week, also had a significant main effect on participant score on the learning measure. The participants who reported playing 15+ hours of computer games per week, the highest amount of time in the variable, had the highest score as a group on the mercury learning measure while those participants that played 1-5 hours per week had the lowest scores.

Teaching Elliptical Excision Skills to Novice Medical Students: A Randomized Controlled Study Comparing Low- and High-Fidelity Bench Models

PubMed Central

Denadai, Rafael; Oshiiwa, Marie; Saad-Hossne, Rogério

2014-01-01

Background: The search for alternative and effective forms of training simulation is needed due to ethical and medico-legal aspects involved in training surgical skills on living patients, human cadavers and living animals. Aims: To evaluate if the bench model fidelity interferes in the acquisition of elliptical excision skills by novice medical students. Materials and Methods: Forty novice medical students were randomly assigned to 5 practice conditions with instructor-directed elliptical excision skills’ training (n = 8): didactic materials (control); organic bench model (low-fidelity); ethylene-vinyl acetate bench model (low-fidelity); chicken legs’ skin bench model (high-fidelity); or pig foot skin bench model (high-fidelity). Pre- and post-tests were applied. Global rating scale, effect size, and self-perceived confidence based on Likert scale were used to evaluate all elliptical excision performances. Results: The analysis showed that after training, the students practicing on bench models had better performance based on Global rating scale (all P < 0.0000) and felt more confident to perform elliptical excision skills (all P < 0.0000) when compared to the control. There was no significant difference (all P > 0.05) between the groups that trained on bench models. The magnitude of the effect (basic cutaneous surgery skills’ training) was considered large (>0.80) in all measurements. Conclusion: The acquisition of elliptical excision skills after instructor-directed training on low-fidelity bench models was similar to the training on high-fidelity bench models; and there was a more substantial increase in elliptical excision performances of students that trained on all simulators compared to the learning on didactic materials. PMID:24700937

Skin inspired fractal strain sensors using a copper nanowire and graphite microflake hybrid conductive network.

PubMed

Jason, Naveen N; Wang, Stephen J; Bhanushali, Sushrut; Cheng, Wenlong

2016-09-22

This work demonstrates a facile "paint-on" approach to fabricate highly stretchable and highly sensitive strain sensors by combining one-dimensional copper nanowire networks with two-dimensional graphite microflakes. This paint-on approach allows for the fabrication of electronic skin (e-skin) patches which can directly replicate with high fidelity the human skin surface they are on, regardless of the topological complexity. This leads to high accuracy for detecting biometric signals for applications in personalised wearable sensors. The copper nanowires contribute to high stretchability and the graphite flakes offer high sensitivity, and their hybrid coating offers the advantages of both. To understand the topological effects on the sensing performance, we utilized fractal shaped elastomeric substrates and systematically compared their stretchability and sensitivity. We could achieve a high stretchability of up to 600% and a maximum gauge factor of 3000. Our simple yet efficient paint-on approach enabled facile fine-tuning of sensitivity/stretchability simply by adjusting ratios of 1D vs. 2D materials in the hybrid coating, and the topological structural designs. This capability leads to a wide range of biomedical sensors demonstrated here, including pulse sensors, prosthetic hands, and a wireless ankle motion sensor.

Use of High Fidelity Methods in Multidisciplinary Optimization-A Preliminary Survey

NASA Technical Reports Server (NTRS)

Guruswamy, Guru P.; Kwak, Dochan (Technical Monitor)

2002-01-01

Multidisciplinary optimization is a key element of design process. To date multidiscipline optimization methods that use low fidelity methods are well advanced. Optimization methods based on simple linear aerodynamic equations and plate structural equations have been applied to complex aerospace configurations. However, use of high fidelity methods such as the Euler/ Navier-Stokes for fluids and 3-D (three dimensional) finite elements for structures has begun recently. As an activity of Multidiscipline Design Optimization Technical Committee (MDO TC) of AIAA (American Institute of Aeronautics and Astronautics), an effort was initiated to assess the status of the use of high fidelity methods in multidisciplinary optimization. Contributions were solicited through the members MDO TC committee. This paper provides a summary of that survey.

Measuring trainer fidelity in the transfer of suicide prevention training

PubMed Central

Cross, Wendi F.; Pisani, Anthony R.; Schmeelk-Cone, Karen; Xia, Yinglin; Tu, Xin; McMahon, Marcie; Munfakh, Jimmie Lou; Gould, Madelyn S.

2014-01-01

Background Finding effective and efficient models to train large numbers of suicide prevention interventionists, including ‘hotline’ crisis counselors, is a high priority. Train-the-trainer (TTT) models are widely used but understudied. Aims To assess the extent to which trainers following TTT delivered the Applied Suicide Intervention Skills Training (ASIST) program with fidelity, and to examine fidelity across two trainings and seven training segments. Methods We recorded and reliably rated trainer fidelity, defined as adherence to program content and competence of program delivery, for 34 newly trained ASIST trainers delivering the program to crisis center staff on two separate occasions. A total of 324 observations were coded. Trainer demographics were also collected. Results On average, trainers delivered two-thirds of the program. Previous training was associated with lower levels of trainer adherence to the program. 18% of trainers' observations were rated as solidly competent. Trainers did not improve fidelity from their first to second training. Significantly higher fidelity was found for lectures and lower fidelity was found for interactive training activities including asking about suicide and creating a safe plan. Conclusions We found wide variability in trainer fidelity to the ASIST program following TTT and few trainers had high levels of both adherence and competence. More research is needed to examine the cost-effectiveness of TTT models. PMID:24901061

Development of an in vivo Assay for Mistranslation: Inducing Activity of Pollutants and Characterization of Amino Acid Substitutions.

DTIC Science & Technology

1983-11-23

during their replication in B. subtilis cells. IV. CLONING THE 0.3 GENE OF COLIPHAGE T7 IN SPP1v We are currently investigating the fidelity of synthesis...of the product of the 0.3 gene of coliphage T7 in infected cells of E.. g by determining the frequency of misincorporation of S-cysteine into this...using a sealed hydrolysis chamber. BC1 was evaporated under vacuum and the hydrolysate resuspended in water . Unlabeled cysteine (12 ug) and methionine

Midlatitude Storm Potential in a Changing Climate

NASA Astrophysics Data System (ADS)

Seeley, J.; Romps, D. M.

2013-12-01

The effect of climate change on severe weather over the continental U.S. is calculated using CMIP5 output from ten GCMs. The potential for severe weather is evaluated in these models using an operational proxy of CAPE times shear; the calculation of CAPE is made possible by the presence of high-frequency data in the CMIP5 archive that was not available in CMIP3. First, the ability of each GCM to replicate modern-day distributions of CAPE and shear is assessed. It is found that the GCMs replicate the observed seasonal cycle of CAPE with reasonable fidelity, but a majority of the GCMs show an erroneous summertime CAPE maximum on the East Coast. The source of this persistent bias is explored. Second, the predicted changes in future severe-storm potential over the continental U.S. are evaluated using the RCP4.5 emissions scenario. The seasonal cycle of domain-averaged undilute CAPE over CONUS for 10 GCMs and radiosonde measurements. Data is averaged over the recent past ("RP") period of 1999-2008. Summertime (JJA) climatologies of CAPE over CONUS for 10 GCMs and radiosonde observations. Data is averaged over the recent past ("RP") period of 1999-2008. Six of the models show an erroneous CAPE maximum on the East Coast.

Imprint Characteristics by Photo-Induced Solidification of Liquid Polymer

NASA Astrophysics Data System (ADS)

Komuro, Masanori; Taniguchi, Jun; Inoue, Seiji; Kimura, Naoya; Tokano, Yuji; Hiroshima, Hiroshi; Matsui, Shinji

2000-12-01

Nanoimprint lithography is an attractive technology for LSIs era below 40-nm critical dimension from the viewpoints of high-throughput and low-cost equipment. In order to avoid a pattern placement error due to thermal expansion in the conventional thermal imprint process, we attempted to replicate the mold pattern onto a liquid polymer, which was solidified using ultra-violet (UV) light irradiation at room temperature. The liquid polymer used here was supplied by TEIJIN SEIKI Co., and termed TSR-820. It was spin coated on slide glass to produce approximately 1.5-μm-thick polymer film. The thickness remained after UV exposure and rinsing in acetone was observed at the dose of 10 J/cm2 and it saturated about a UV exposure dose of 100 J/cm2 with an increase in the exposure dose. The mold fabricated of quartz plate was first pressed onto the polymer film at about 100 kg/cm2 and then the UV light was irradiated using an imprint apparatus developed for this work. After releasing the mold from the film, the substrate was rinsed in acetone to remove the residual liquid polymer. Eventually the minimum feature size of 100-nm line and 300-nm space pattern was successfully replicated in the polymer with good fidelity.

Layered Double Hydroxide Minerals as Possible Prebiotic Information Storage and Transfer Compounds

NASA Astrophysics Data System (ADS)

Greenwell, H. Chris; Coveney, Peter V.

2006-02-01

One of the fundamental difficulties when considering the origin of life on Earth is the identification of an emergent system that not only replicated, but also had the capacity to undergo discrete mutation in such a way that following generations might inherit and pass on the mutation. We speculate that the layered double hydroxide (LDH) minerals are plausible candidates for a proto-RNA molecule. We describe a hypothetical LDH-like system which, when intercalated with certain anions, forms crystals with a high degree of internal order giving rise to novel information storage structures in which replication fidelity is maintained, a concept we use to propose an explanation for interstratification in terephthalate LDHs. The external surfaces of these hypothetical crystals provide active sites whose structure and chemistry is dictated by the internal information content of the LDH. Depending on the LDH polytype, the opposing external surfaces of a crystal may give rise to reactive sites that are either complementary or mirror images of each other, and so may be chiral. We also examine similarities between these proposed “proto-RNA” structures and the DNA that encodes the hereditary information in life today, concluding with a hypothetical scenario wherein these proto-RNA molecules predated the putative RNA-world.

Preschool children's development in classic Montessori, supplemented Montessori, and conventional programs.

PubMed

Lillard, Angeline S

2012-06-01

Research on the outcomes of Montessori education is scarce and results are inconsistent. One possible reason for the inconsistency is variations in Montessori implementation fidelity. To test whether outcomes vary according to implementation fidelity, we examined preschool children enrolled in high fidelity classic Montessori programs, lower fidelity Montessori programs that supplemented the program with conventional school activities, and, for comparison, conventional programs. Children were tested at the start and end of the school year on a range of social and academic skills. Although they performed no better in the fall, children in Classic Montessori programs, as compared with children in Supplemented Montessori and Conventional programs, showed significantly greater school-year gains on outcome measures of executive function, reading, math, vocabulary, and social problem-solving, suggesting that high fidelity Montessori implementation is associated with better outcomes than lower fidelity Montessori programs or conventional programs. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

An Investigation of the Impact of Aerodynamic Model Fidelity on Close-In Combat Effectiveness Prediction in Piloted Simulation

NASA Technical Reports Server (NTRS)

Persing, T. Ray; Bellish, Christine A.; Brandon, Jay; Kenney, P. Sean; Carzoo, Susan; Buttrill, Catherine; Guenther, Arlene

2005-01-01

Several aircraft airframe modeling approaches are currently being used in the DoD community for acquisition, threat evaluation, training, and other purposes. To date there has been no clear empirical study of the impact of airframe simulation fidelity on piloted real-time aircraft simulation study results, or when use of a particular level of fidelity is indicated. This paper documents a series of piloted simulation studies using three different levels of airframe model fidelity. This study was conducted using the NASA Langley Differential Maneuvering Simulator. Evaluations were conducted with three pilots for scenarios requiring extensive maneuvering of the airplanes during air combat. In many cases, a low-fidelity modified point-mass model may be sufficient to evaluate the combat effectiveness of the aircraft. However, in cases where high angle-of-attack flying qualities and aerodynamic performance are a factor or when precision tracking ability of the aircraft must be represented, use of high-fidelity models is indicated.

EAT-UP™ Family-Centered Feeding Intervention to Promote Food Acceptance and Decrease Challenging Behaviors: A Single-Case Experimental Design Replicated Across Three Families of Children with Autism Spectrum Disorder.

PubMed

Cosbey, Joanna; Muldoon, Deirdre

2017-03-01

This study evaluated the effectiveness of a family-centered feeding intervention, Easing Anxiety Together with Understanding and Perseverance (EAT-UP™), for promoting food acceptance of children with autism spectrum disorder at home. A concurrent multiple-baseline design was used with systematic replication across three families. Baseline was followed by an 'Intervention-Coaching' phase and then an 'Intervention-Independent' phase. Using direct observation and pre- and post-intervention questionnaires, data on acceptance of less preferred foods and challenging mealtime behaviors were collected. Procedural fidelity was monitored throughout all study phases. Data were analyzed using visual analysis and measures of effect size. All children demonstrated increases in food acceptance (effect size >0.90) and dietary diversity and decreased challenging behaviors. Implications for practice and research are discussed.

Comparison of Performance Predictions for New Low-Thrust Trajectory Tools

NASA Technical Reports Server (NTRS)

Polsgrove, Tara; Kos, Larry; Hopkins, Randall; Crane, Tracie

2006-01-01

Several low thrust trajectory optimization tools have been developed over the last 3% years by the Low Thrust Trajectory Tools development team. This toolset includes both low-medium fidelity and high fidelity tools which allow the analyst to quickly research a wide mission trade space and perform advanced mission design. These tools were tested using a set of reference trajectories that exercised each tool s unique capabilities. This paper compares the performance predictions of the various tools against several of the reference trajectories. The intent is to verify agreement between the high fidelity tools and to quantify the performance prediction differences between tools of different fidelity levels.

A Transfer of Training Study of Control Loader Dynamics

NASA Technical Reports Server (NTRS)

Cardullo, Frank M.; Stanco, Anthony A.; Kelly, Lon C.; Houck, Jacob A.; Grube, Richard C.

2011-01-01

The control inceptor used in a simulated vehicle is an important part in maintaining the fidelity of a simulation. The force feedback provided by the control inceptor gives the operator important cues to maintain adequate performance. The dynamics of a control inceptor are typically based on a second order spring mass damper system with damping, force gradient, breakout force, and natural frequency parameters. Changing these parameters can have a great effect on pilot or driver control of the vehicle. The neuromuscular system has a very important role in manipulating the control inceptor within a vehicle. Many studies by McRuer, Aponso, and Hess have dealt with modeling the neuromuscular system and quantifying the effects of a high fidelity control loader as compared to a low fidelity control loader. Humans are adaptive in nature and their control behavior changes based on different control loader dynamics. Humans will change their control behavior to maintain tracking bandwidth and minimize tracking error. This paper reports on a quasi-transfer of training experiment which was performed at the NASA Langley Research Center. The quasi transfer of training study used a high fidelity control loader and a low fidelity control loader. Subjects trained in both simulations and then were transferred to the high fidelity control loader simulation. The parameters for the high fidelity control loader were determined from the literature. The low fidelity control loader parameters were found through testing of a simple computer joystick. A disturbance compensatory task is employed. The compensatory task involves implementing a simple horizon out the window display. A disturbance consisting of a sum of sines is used. The task consists of the subject compensating for the disturbance on the roll angle of the aircraft. The vehicle dynamics are represented as 1/s and 1/s2. The subject will try to maintain level flight throughout the experiment. The subjects consist of non-pilots to remove any effects of pilot experience. First, this paper discusses the implementation of the disturbance compensation task. Second, the high and low fidelity parameters used within the experiment are presented. Finally, an explanation of results from the experiments is presented.

The effect of simulator fidelity on acquiring non-technical skills: a randomized non-inferiority trial.

PubMed

Gu, Yuqi; Witter, Tobias; Livingston, Patty; Rao, Purnima; Varshney, Terry; Kuca, Tom; Dylan Bould, M

2017-12-01

As simulator fidelity (i.e., realism) increases from low to high, the simulator more closely resembles the real environment, but it also becomes more expensive. It is generally assumed that the use of high-fidelity simulators results in better learning; however, the effect of fidelity on learning non-technical skills (NTS) is unknown. This was a non-inferiority trial comparing the efficacy of high- vs low-fidelity simulators on learning NTS. Thirty-six postgraduate medical trainees were recruited for the trial. During the pre-test phase, the trainees were randomly assigned to manage a scenario using either a high-fidelity simulator (HFS) or a low-fidelity simulator (LFS), followed by expert debriefing. All trainees then underwent a video recorded post-test scenario on a HFS, and the NTS were assessed between the two groups. The primary outcome was the overall post-test Ottawa Global Rating Scale (OGRS), while controlling for overall pre-test OGRS scores. Non-inferiority between the LFS and HFS was based on a non-inferiority margin of greater than 1. For our primary outcome, the mean (SD) post-test overall OGRS score was not significantly different between the HFS and LFS groups after controlling for pre-test overall OGRS scores [3.8 (0.9) vs 4.0 (0.9), respectively; mean difference, 0.2; 95% confidence interval, -0.4 to 0.8; P = 0.48]. For our secondary outcomes, the post-test total OGRS score was not significantly different between the HFS and LFS groups after controlling for pre-test total OGRS scores (P = 0.33). There were significant improvements in mean overall (P = 0.01) and total (P = 0.003) OGRS scores from pre-test to post-test. There were no significant associations between postgraduate year (P = 0.82) and specialty (P = 0.67) on overall OGRS performance. This study suggests that low-fidelity simulators are non-inferior to the more costly high-fidelity simulators for teaching NTS to postgraduate medical trainees.

Using mixed methods to assess fidelity of delivery and its influencing factors in a complex self-management intervention for people with osteoarthritis and low back pain.

PubMed

Toomey, Elaine; Matthews, James; Hurley, Deirdre A

2017-08-04

Despite an increasing awareness of the importance of fidelity of delivery within complex behaviour change interventions, it is often poorly assessed. This mixed methods study aimed to establish the fidelity of delivery of a complex self-management intervention and explore the reasons for these findings using a convergent/triangulation design. Feasibility trial of the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention (ISRCTN49875385), delivered in primary care physiotherapy. 60 SOLAS sessions were delivered across seven sites by nine physiotherapists. Fidelity of delivery of prespecified intervention components was evaluated using (1) audio-recordings (n=60), direct observations (n=24) and self-report checklists (n=60) and (2) individual interviews with physiotherapists (n=9). Quantitatively, fidelity scores were calculated using percentage means and SD of components delivered. Associations between fidelity scores and physiotherapist variables were analysed using Spearman's correlations. Interviews were analysed using thematic analysis to explore potential reasons for fidelity scores. Integration of quantitative and qualitative data occurred at an interpretation level using triangulation. Quantitatively, fidelity scores were high for all assessment methods; with self-report (92.7%) consistently higher than direct observations (82.7%) or audio-recordings (81.7%). There was significant variation between physiotherapists' individual scores (69.8% - 100%). Both qualitative and quantitative data (from physiotherapist variables) found that physiotherapists' knowledge (Spearman's association at p=0.003) and previous experience (p=0.008) were factors that influenced their fidelity. The qualitative data also postulated participant-level (eg, individual needs) and programme-level factors (eg, resources) as additional elements that influenced fidelity. The intervention was delivered with high fidelity. This study contributes to the limited evidence regarding fidelity assessment methods within complex behaviour change interventions. The findings suggest a combination of quantitative methods is suitable for the assessment of fidelity of delivery. A mixed methods approach provided a more insightful understanding of fidelity and its influencing factors. ISRCTN49875385; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Using mixed methods to assess fidelity of delivery and its influencing factors in a complex self-management intervention for people with osteoarthritis and low back pain

PubMed Central

Toomey, Elaine; Matthews, James; Hurley, Deirdre A

2017-01-01

Objectives and design Despite an increasing awareness of the importance of fidelity of delivery within complex behaviour change interventions, it is often poorly assessed. This mixed methods study aimed to establish the fidelity of delivery of a complex self-management intervention and explore the reasons for these findings using a convergent/triangulation design. Setting Feasibility trial of the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention (ISRCTN49875385), delivered in primary care physiotherapy. Methods and outcomes 60 SOLAS sessions were delivered across seven sites by nine physiotherapists. Fidelity of delivery of prespecified intervention components was evaluated using (1) audio-recordings (n=60), direct observations (n=24) and self-report checklists (n=60) and (2) individual interviews with physiotherapists (n=9). Quantitatively, fidelity scores were calculated using percentage means and SD of components delivered. Associations between fidelity scores and physiotherapist variables were analysed using Spearman’s correlations. Interviews were analysed using thematic analysis to explore potential reasons for fidelity scores. Integration of quantitative and qualitative data occurred at an interpretation level using triangulation. Results Quantitatively, fidelity scores were high for all assessment methods; with self-report (92.7%) consistently higher than direct observations (82.7%) or audio-recordings (81.7%). There was significant variation between physiotherapists’ individual scores (69.8% - 100%). Both qualitative and quantitative data (from physiotherapist variables) found that physiotherapists’ knowledge (Spearman’s association at p=0.003) and previous experience (p=0.008) were factors that influenced their fidelity. The qualitative data also postulated participant-level (eg, individual needs) and programme-level factors (eg, resources) as additional elements that influenced fidelity. Conclusion The intervention was delivered with high fidelity. This study contributes to the limited evidence regarding fidelity assessment methods within complex behaviour change interventions. The findings suggest a combination of quantitative methods is suitable for the assessment of fidelity of delivery. A mixed methods approach provided a more insightful understanding of fidelity and its influencing factors. Trial registration number ISRCTN49875385; Pre-results. PMID:28780544

High-fidelity gates towards a scalable superconducting quantum processor

NASA Astrophysics Data System (ADS)

Chow, Jerry M.; Corcoles, Antonio D.; Gambetta, Jay M.; Rigetti, Chad; Johnson, Blake R.; Smolin, John A.; Merkel, Seth; Poletto, Stefano; Rozen, Jim; Rothwell, Mary Beth; Keefe, George A.; Ketchen, Mark B.; Steffen, Matthias

2012-02-01

We experimentally explore the implementation of high-fidelity gates on multiple superconducting qubits coupled to multiple resonators. Having demonstrated all-microwave single and two qubit gates with fidelities > 90% on multi-qubit single-resonator systems, we expand the application to qubits across two resonators and investigate qubit coupling in this circuit. The coupled qubit-resonators are building blocks towards two-dimensional lattice networks for the application of surface code quantum error correction algorithms.

The efficacy of high-fidelity simulation on psychomotor clinical performance improvement of undergraduate nursing students.

PubMed

Vincent, Mary Anne; Sheriff, Susan; Mellott, Susan

2015-02-01

High-fidelity simulation has become a growing educational modality among institutions of higher learning ever since the Institute of Medicine recommended that it be used to improve patient safety in 2000. However, there is limited research on the effect of high-fidelity simulation on psychomotor clinical performance improvement of undergraduate nursing students being evaluated by experts using reliable and valid appraisal instruments. The purpose of this integrative review and meta-analysis is to explore what researchers have established about the impact of high-fidelity simulation on improving the psychomotor clinical performance of undergraduate nursing students. Only eight of the 1120 references met inclusion criteria. A meta-analysis using Hedges' g to compute the effect size and direction of impact yielded a range of -0.26 to +3.39. A positive effect was shown in seven of eight studies; however, there were five different research designs and six unique appraisal instruments used among these studies. More research is necessary to determine if high-fidelity simulation improves psychomotor clinical performance in undergraduate nursing students. Nursing programs from multiple sites having a standardized curriculum and using the same appraisal instruments with established reliability and validity are ideal for this work.

Assessing fidelity of delivery of smoking cessation behavioural support in practice.

PubMed

Lorencatto, Fabiana; West, Robert; Christopherson, Charlotte; Michie, Susan

2013-04-04

Effectiveness of evidence-based behaviour change interventions is likely to be undermined by failure to deliver interventions as planned. Behavioural support for smoking cessation can be a highly cost-effective, life-saving intervention. However, in practice, outcomes are highly variable. Part of this may be due to variability in fidelity of intervention implementation. To date, there have been no published studies on this. The present study aimed to: evaluate a method for assessing fidelity of behavioural support; assess fidelity of delivery in two English Stop-Smoking Services; and compare the extent of fidelity according to session types, duration, individual practitioners, and component behaviour change techniques (BCTs). Treatment manuals and transcripts of 34 audio-recorded behavioural support sessions were obtained from two Stop-Smoking Services and coded into component BCTs using a taxonomy of 43 BCTs. Inter-rater reliability was assessed using percentage agreement. Fidelity was assessed by examining the proportion of BCTs specified in the manuals that were delivered in individual sessions. This was assessed by session type (i.e., pre-quit, quit, post-quit), duration, individual practitioner, and BCT. Inter-coder reliability was high (87.1%). On average, 66% of manual-specified BCTs were delivered per session (SD 15.3, range: 35% to 90%). In Service 1, average fidelity was highest for post-quit sessions (69%) and lowest for pre-quit (58%). In Service 2, fidelity was highest for quit-day (81%) and lowest for post-quit sessions (56%). Session duration was not significantly correlated with fidelity. Individual practitioner fidelity ranged from 55% to 78%. Individual manual-specified BCTs were delivered on average 63% of the time (SD 28.5, range: 0 to 100%). The extent to which smoking cessation behavioural support is delivered as specified in treatment manuals can be reliably assessed using transcripts of audiotaped sessions. This allows the investigation of the implementation of evidence-based practice in relation to smoking cessation, a first step in designing interventions to improve it. There are grounds for believing that fidelity in the English Stop-Smoking Services may be low and that routine monitoring is warranted.

Detailed Measurement of ORSC Main Chamber Injector Dynamics

NASA Astrophysics Data System (ADS)

Bedard, Michael J.

Improving fidelity in simulation of combustion dynamics in rocket combustors requires an increase in experimental measurement fidelity for validation. In a model rocket combustor, a chemiluminescence based spectroscopy technique was used to capture flame light emissions for direct comparison to a computational simulation of the production of chemiluminescent species. The comparison indicated that high fidelity models of rocket combustors can predict spatio-temporal distribution of chemiluminescent species with trend-wise accuracy. The comparison also indicated the limited ability of OH* and CH* emission to indicate flame heat release. Based on initial spectroscopy experiments, a photomultiplier based chemiluminescence sensor was designed to increase the temporal resolution of flame emission measurements. To apply developed methodologies, an experiment was designed to investigate the flow and combustion dynamics associated with main chamber injector elements typical of the RD-170 rocket engine. A unique feature of the RD-170 injector element is the beveled expansion between the injector recess and combustion chamber. To investigate effects of this geometry, a scaling methodology was applied to increase the physical scale of a single injector element while maintaining traceability to the RD-170 design. Two injector configurations were tested, one including a beveled injector face and the other a flat injector face. This design enabled improved spatial resolution of pressure and light emission measurements densely arranged in the injector recess and near-injector region of the chamber. Experimental boundary conditions were designed to closely replicate boundary conditions in simulations. Experimental results showed that the beveled injector face had a damping effect on pressure fluctuations occurring near the longitudinal resonant acoustic modes of the chamber, implying a mechanism for improved overall combustion stability. Near the injector, the beveled geometry resulted in more acoustic energy into higher frequency modes, while the flat-face geometry excited modes closer to the fundamental longitudinal mode frequency and its harmonics. Multi-scale analysis techniques were used to investigate intermittency and the range of physical scales present in measured signals. Flame light emission measurements confirmed the presence of flame holding in the injector recess in both configurations. Analysis of dynamics in light emission signals showed flame response at the chamber acoustic resonance frequency in addition to non-acoustic modes associated with mixing shear layer dynamics in the injector recess. The first known benchmark quality data sets of such injector dynamics were recorded in each configuration to enable pressure-based validation of high fidelity models of gas-centered swirl coaxial injectors. This work presents a critical contribution to development of validated combustion dynamics predictive tools and to the understanding of gas-centered swirl coaxial injector elements.

Uracil DNA glycosylase BKRF3 contributes to Epstein-Barr virus DNA replication through physical interactions with proteins in viral DNA replication complex.

PubMed

Su, Mei-Tzu; Liu, I-Hua; Wu, Chia-Wei; Chang, Shu-Ming; Tsai, Ching-Hwa; Yang, Pei-Wen; Chuang, Yu-Chia; Lee, Chung-Pei; Chen, Mei-Ru

2014-08-01

Epstein-Barr virus (EBV) BKRF3 shares sequence homology with members of the uracil-N-glycosylase (UNG) protein family and has DNA glycosylase activity. Here, we explored how BKRF3 participates in the DNA replication complex and contributes to viral DNA replication. Exogenously expressed Flag-BKRF3 was distributed mostly in the cytoplasm, whereas BKRF3 was translocated into the nucleus and colocalized with the EBV DNA polymerase BALF5 in the replication compartment during EBV lytic replication. The expression level of BKRF3 increased gradually during viral replication, coupled with a decrease of cellular UNG2, suggesting BKRF3 enzyme activity compensates for UNG2 and ensures the fidelity of viral DNA replication. In immunoprecipitation-Western blotting, BKRF3 was coimmuno-precipitated with BALF5, the polymerase processivity factor BMRF1, and the immediate-early transactivator Rta. Coexpression of BMRF1 appeared to facilitate the nuclear targeting of BKRF3 in immunofluorescence staining. Residues 164 to 255 of BKRF3 were required for interaction with Rta and BALF5, whereas residues 81 to 166 of BKRF3 were critical for BMRF1 interaction in glutathione S-transferase (GST) pulldown experiments. Viral DNA replication was defective in cells harboring BKRF3 knockout EBV bacmids. In complementation assays, the catalytic mutant BKRF3(Q90L,D91N) restored viral DNA replication, whereas the leucine loop mutant BKRF3(H213L) only partially rescued viral DNA replication, coupled with a reduced ability to interact with the viral DNA polymerase and Rta. Our data suggest that BKRF3 plays a critical role in viral DNA synthesis predominantly through its interactions with viral proteins in the DNA replication compartment, while its enzymatic activity may be supplementary for uracil DNA glycosylase (UDG) function during virus replication. Catalytic activities of both cellular UDG UNG2 and viral UDGs contribute to herpesviral DNA replication. To ensure that the enzyme activity executes at the right time and the right place in DNA replication forks, complex formation with other components in the DNA replication machinery provides an important regulation for UDG function. In this study, we provide the mechanism for EBV UDG BKRF3 nuclear targeting and the interacting domains of BKRF3 with viral DNA replication proteins. Through knockout and complementation approaches, we further demonstrate that in addition to UDG activity, the interaction of BKRF3 with viral proteins in the replication compartment is crucial for efficient viral DNA replication. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Fidelity and outcomes in six integrated dual disorders treatment programs.

PubMed

Chandler, Daniel W

2011-02-01

Fidelity scores and outcomes were measured in six outpatient programs in California which implemented Integrated Dual Disorders Treatment (IDDT). Outcomes were measured for 1 year in four sites and 2 years in two sites; fidelity was assessed at 6 month intervals. Three of the six sites achieved high fidelity (at least a 4 on a 5 point fidelity scale) and three moderate fidelity (at least a 3). Retention in treatment, mental health functioning, stage of substance abuse treatment, abstinence, and psychiatric hospitalization were measured. Outcomes for individual programs were generally positive but not consistent within programs or across programs. Using pooled data in a longitudinal regression model with random effects at person level and adjustment of standard errors for clustering by site, change over time was not statistically significant for the primary outcomes. Fidelity scores had limited association with positive outcomes.

Assessing the fidelity of the Kin KeeperSM prevention intervention in African American, Latina and Arab women

PubMed Central

Ford, Sabrina; Meghea, Cristian; Estes, Tamika; Hamade, Hiam; Lockett, Murlisa; Williams, Karen Patricia

2014-01-01

Background: We evaluated a randomized controlled treatment, utilizing Community Health Workers (CHW) to deliver breast and cervical cancer education intervention to African American, Latina, and Arab women in Detroit and Dearborn, Michigan. The main objectives of the study are to: (1) examine fidelity and consistency of treatment delivery and (2) assess qualitative elements of the intervention. Methods: We surveyed 305 women who received the intervention and 16 CHWs Survey included questions regarding the treatment integrity, treatment received, and training provided. Surveys included both quantitative and questions. Results: The intervention group (n = 305) was made up of 48% Black, 11% Latina, and 41% Arab women. Almost all (≥ 90%) women agreed that they received the treatment in the way that it was intended. Sixteen CHWs responded affirmatively as well. Conclusions: Both participants and CHWs indicated that the program was mutually rewarding, indicating that there was “cross fertilization and cross benefit” of working with each other. These benefits served to endorse and confirm that CHWs are a very important mechanism in increasing health literacy in the community and referring underserved individuals to health providers. Second, with strong treatment fidelity the Kin KeeperSM program and has the potential to be replicated for a number of diseases in a variety of venues especially for those facing health disparities. PMID:24122323

Commentary: Learning from Variations in Fidelity of Implementation

ERIC Educational Resources Information Center

Balu, Rekha; Doolittle, Fred

2016-01-01

The articles in this special issue discuss efforts to improve academic reading outcomes for students and ways to achieve high implementation fidelity of promising strategies. At times the authors discuss if--and how--strong fidelity is associated with strong outcomes and potentially even impacts (the difference between program and control group…

Preschool Children's Development in Classic Montessori, Supplemented Montessori, and Conventional Programs

ERIC Educational Resources Information Center

Lillard, Angeline S.

2012-01-01

Research on the outcomes of Montessori education is scarce and results are inconsistent. One possible reason for the inconsistency is variations in Montessori implementation fidelity. To test whether outcomes vary according to implementation fidelity, we examined preschool children enrolled in high fidelity classic Montessori programs, lower…

Uncertainty quantification for PZT bimorph actuators

NASA Astrophysics Data System (ADS)

Bravo, Nikolas; Smith, Ralph C.; Crews, John

2018-03-01

In this paper, we discuss the development of a high fidelity model for a PZT bimorph actuator used for micro-air vehicles, which includes the Robobee. We developed a high-fidelity model for the actuator using the homogenized energy model (HEM) framework, which quantifies the nonlinear, hysteretic, and rate-dependent behavior inherent to PZT in dynamic operating regimes. We then discussed an inverse problem on the model. We included local and global sensitivity analysis of the parameters in the high-fidelity model. Finally, we will discuss the results of Bayesian inference and uncertainty quantification on the HEM.

Variation, "evolution", immortality and genetic instabilities in tumour cells.

PubMed

Bignold, L P

2007-08-18

The pathological characteristics of tumour cells often include variation of their histopathological features (i.e. "degrees of de-differentiation") between cases of the same tumour type and between different foci within individual tumours. Usually, only a few cell lines from tumours are immortal. Currently, somatic mutation, replicative infidelity of DNA and aneuploidy are suggested as alternative mechanisms of genomic disturbance underlying tumours. Nevertheless, apart from Hansemann's ideas of "anaplasia" and "de-differentiation" (proposed in the 1890s), and supposed "evolutionary themes" in cancer cell biology, little has been published concerning how histopathologic variation and immortality in tumour cells might arise. This paper reviews applications of the concepts of "variation" to tumours, including concepts of "evolution" and "cellular Darwinism". It is proposed that combinations of somatic mutation, DNA replicative infidelity and aneuploidy may explain the variabilities in tumours, and provide immortality in occasional tumour cells. A possible model involves (i) an initial somatic mutation causing reduced replicative fidelity of DNA, which could be variable in intensity, and thus give rise to variations between cases; (ii) a phase of replicative infidelity of DNA causing daughter cells lines to develop various abnormalities to different degrees, and hence provide for variation between areas of the same tumour. As a last event (iii) occasional asymmetric chromosomal distributions (aneuploidy) might "refresh" the ability of a daughter cell to replicate DNA faithfully causing them to become immortal. Thus extensively mutant and variable, hyperploid, and occasionally immortal cells might arise.

DNA polymerase ɛ and δ exonuclease domain mutations in endometrial cancer

PubMed Central

Church, David N.; Briggs, Sarah E.W.; Palles, Claire; Domingo, Enric; Kearsey, Stephen J.; Grimes, Jonathon M.; Gorman, Maggie; Martin, Lynn; Howarth, Kimberley M.; Hodgson, Shirley V.; Kaur, Kulvinder; Taylor, Jenny; Tomlinson, Ian P.M.

2013-01-01

Accurate duplication of DNA prior to cell division is essential to suppress mutagenesis and tumour development. The high fidelity of eukaryotic DNA replication is due to a combination of accurate incorporation of nucleotides into the nascent DNA strand by DNA polymerases, the recognition and removal of mispaired nucleotides (proofreading) by the exonuclease activity of DNA polymerases δ and ɛ, and post-replication surveillance and repair of newly synthesized DNA by the mismatch repair (MMR) apparatus. While the contribution of defective MMR to neoplasia is well recognized, evidence that faulty DNA polymerase activity is important in cancer development has been limited. We have recently shown that germline POLE and POLD1 exonuclease domain mutations (EDMs) predispose to colorectal cancer (CRC) and, in the latter case, to endometrial cancer (EC). Somatic POLE mutations also occur in 5–10% of sporadic CRCs and underlie a hypermutator, microsatellite-stable molecular phenotype. We hypothesized that sporadic ECs might also acquire somatic POLE and/or POLD1 mutations. Here, we have found that missense POLE EDMs with good evidence of pathogenic effects are present in 7% of a set of 173 endometrial cancers, although POLD1 EDMs are uncommon. The POLE mutations localized to highly conserved residues and were strongly predicted to affect proofreading. Consistent with this, POLE-mutant tumours were hypermutated, with a high frequency of base substitutions, and an especially large relative excess of G:C>T:A transversions. All POLE EDM tumours were microsatellite stable, suggesting that defects in either DNA proofreading or MMR provide alternative mechanisms to achieve genomic instability and tumourigenesis. PMID:23528559

Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability.

PubMed

Galanos, Panagiotis; Pappas, George; Polyzos, Alexander; Kotsinas, Athanassios; Svolaki, Ioanna; Giakoumakis, Nickolaos N; Glytsou, Christina; Pateras, Ioannis S; Swain, Umakanta; Souliotis, Vassilis L; Georgakilas, Alexandros G; Geacintov, Nicholas; Scorrano, Luca; Lukas, Claudia; Lukas, Jiri; Livneh, Zvi; Lygerou, Zoi; Chowdhury, Dipanjan; Sørensen, Claus Storgaard; Bartek, Jiri; Gorgoulis, Vassilis G

2018-03-16

Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design of appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property of p21 WAF1/Cip1 , showing that its chronic expression in a p53-deficient environment causes genomic instability by deregulation of the replication licensing machinery. We now demonstrate that p21 WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low- and high-fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we find that the DSBs are repaired by Rad52-dependent break-induced replication (BIR) and single-strand annealing (SSA) repair pathways. Conversely, the error-free synthesis-dependent strand annealing (SDSA) repair route is deficient. Surprisingly, Rad52 is activated transcriptionally in an E2F1-dependent manner, rather than post-translationally as is common for DNA repair factor activation. Our results signify the importance of mutational signatures as guides to disclose the repair history leading to genomic instability. We unveil how chronic p21 WAF1/Cip1 expression rewires the repair process and identifies Rad52 as a source of genomic instability and a candidate therapeutic target.

Benefits of computer screen-based simulation in learning cardiac arrest procedures.

PubMed

Bonnetain, Elodie; Boucheix, Jean-Michel; Hamet, Maël; Freysz, Marc

2010-07-01

What is the best way to train medical students early so that they acquire basic skills in cardiopulmonary resuscitation as effectively as possible? Studies have shown the benefits of high-fidelity patient simulators, but have also demonstrated their limits. New computer screen-based multimedia simulators have fewer constraints than high-fidelity patient simulators. In this area, as yet, there has been no research on the effectiveness of transfer of learning from a computer screen-based simulator to more realistic situations such as those encountered with high-fidelity patient simulators. We tested the benefits of learning cardiac arrest procedures using a multimedia computer screen-based simulator in 28 Year 2 medical students. Just before the end of the traditional resuscitation course, we compared two groups. An experiment group (EG) was first asked to learn to perform the appropriate procedures in a cardiac arrest scenario (CA1) in the computer screen-based learning environment and was then tested on a high-fidelity patient simulator in another cardiac arrest simulation (CA2). While the EG was learning to perform CA1 procedures in the computer screen-based learning environment, a control group (CG) actively continued to learn cardiac arrest procedures using practical exercises in a traditional class environment. Both groups were given the same amount of practice, exercises and trials. The CG was then also tested on the high-fidelity patient simulator for CA2, after which it was asked to perform CA1 using the computer screen-based simulator. Performances with both simulators were scored on a precise 23-point scale. On the test on a high-fidelity patient simulator, the EG trained with a multimedia computer screen-based simulator performed significantly better than the CG trained with traditional exercises and practice (16.21 versus 11.13 of 23 possible points, respectively; p<0.001). Computer screen-based simulation appears to be effective in preparing learners to use high-fidelity patient simulators, which present simulations that are closer to real-life situations.

High-fidelity data embedding for image annotation.

PubMed

He, Shan; Kirovski, Darko; Wu, Min

2009-02-01

High fidelity is a demanding requirement for data hiding, especially for images with artistic or medical value. This correspondence proposes a high-fidelity image watermarking for annotation with robustness to moderate distortion. To achieve the high fidelity of the embedded image, we introduce a visual perception model that aims at quantifying the local tolerance to noise for arbitrary imagery. Based on this model, we embed two kinds of watermarks: a pilot watermark that indicates the existence of the watermark and an information watermark that conveys a payload of several dozen bits. The objective is to embed 32 bits of metadata into a single image in such a way that it is robust to JPEG compression and cropping. We demonstrate the effectiveness of the visual model and the application of the proposed annotation technology using a database of challenging photographic and medical images that contain a large amount of smooth regions.

High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation

NASA Astrophysics Data System (ADS)

Sim, Kyoseung; Chen, Song; Li, Yuhang; Kammoun, Mejdi; Peng, Yun; Xu, Minwei; Gao, Yang; Song, Jizhou; Zhang, Yingchun; Ardebili, Haleh; Yu, Cunjiang

2015-11-01

Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing(TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated.

Surrogate based wind farm layout optimization using manifold mapping

NASA Astrophysics Data System (ADS)

Kaja Kamaludeen, Shaafi M.; van Zuijle, Alexander; Bijl, Hester

2016-09-01

High computational cost associated with the high fidelity wake models such as RANS or LES serves as a primary bottleneck to perform a direct high fidelity wind farm layout optimization (WFLO) using accurate CFD based wake models. Therefore, a surrogate based multi-fidelity WFLO methodology (SWFLO) is proposed. The surrogate model is built using an SBO method referred as manifold mapping (MM). As a verification, optimization of spacing between two staggered wind turbines was performed using the proposed surrogate based methodology and the performance was compared with that of direct optimization using high fidelity model. Significant reduction in computational cost was achieved using MM: a maximum computational cost reduction of 65%, while arriving at the same optima as that of direct high fidelity optimization. The similarity between the response of models, the number of mapping points and its position, highly influences the computational efficiency of the proposed method. As a proof of concept, realistic WFLO of a small 7-turbine wind farm is performed using the proposed surrogate based methodology. Two variants of Jensen wake model with different decay coefficients were used as the fine and coarse model. The proposed SWFLO method arrived at the same optima as that of the fine model with very less number of fine model simulations.

High-fidelity teleportation beyond the no-cloning limit and entanglement swapping for continuous variables.

PubMed

Takei, Nobuyuki; Yonezawa, Hidehiro; Aoki, Takao; Furusawa, Akira

2005-06-10

We experimentally demonstrate continuous-variable quantum teleportation beyond the no-cloning limit. We teleport a coherent state and achieve the fidelity of 0.70 +/- 0.02 that surpasses the no-cloning limit of 2/3. Surpassing the limit is necessary to transfer the nonclassicality of an input quantum state. By using our high-fidelity teleporter, we demonstrate entanglement swapping, namely, teleportation of quantum entanglement, as an example of transfer of nonclassicality.

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

McInerney, Peter; Adams, Paul; Hadi, Masood Z.

As larger-scale cloning projects become more prevalent, there is an increasing need for comparisons among high fidelity DNA polymerases used for PCR amplification. All polymerases marketed for PCR applications are tested for fidelity properties (i.e., error rate determination) by vendors, and numerous literature reports have addressed PCR enzyme fidelity. Nonetheless, it is often difficult to make direct comparisons among different enzymes due to numerous methodological and analytical differences from study to study. We have measured the error rates for 6 DNA polymerases commonly used in PCR applications, including 3 polymerases typically used for cloning applications requiring high fidelity. Error ratemore » measurement values reported here were obtained by direct sequencing of cloned PCR products. The strategy employed here allows interrogation of error rate across a very large DNA sequence space, since 94 unique DNA targets were used as templates for PCR cloning. The six enzymes included in the study, Taq polymerase, AccuPrime-Taq High Fidelity, KOD Hot Start, cloned Pfu polymerase, Phusion Hot Start, and Pwo polymerase, we find the lowest error rates with Pfu , Phusion, and Pwo polymerases. Error rates are comparable for these 3 enzymes and are >10x lower than the error rate observed with Taq polymerase. Mutation spectra are reported, with the 3 high fidelity enzymes displaying broadly similar types of mutations. For these enzymes, transition mutations predominate, with little bias observed for type of transition.« less

Error Rate Comparison during Polymerase Chain Reaction by DNA Polymerase

DOE PAGES

McInerney, Peter; Adams, Paul; Hadi, Masood Z.

2014-01-01

As larger-scale cloning projects become more prevalent, there is an increasing need for comparisons among high fidelity DNA polymerases used for PCR amplification. All polymerases marketed for PCR applications are tested for fidelity properties (i.e., error rate determination) by vendors, and numerous literature reports have addressed PCR enzyme fidelity. Nonetheless, it is often difficult to make direct comparisons among different enzymes due to numerous methodological and analytical differences from study to study. We have measured the error rates for 6 DNA polymerases commonly used in PCR applications, including 3 polymerases typically used for cloning applications requiring high fidelity. Error ratemore » measurement values reported here were obtained by direct sequencing of cloned PCR products. The strategy employed here allows interrogation of error rate across a very large DNA sequence space, since 94 unique DNA targets were used as templates for PCR cloning. The six enzymes included in the study, Taq polymerase, AccuPrime-Taq High Fidelity, KOD Hot Start, cloned Pfu polymerase, Phusion Hot Start, and Pwo polymerase, we find the lowest error rates with Pfu , Phusion, and Pwo polymerases. Error rates are comparable for these 3 enzymes and are >10x lower than the error rate observed with Taq polymerase. Mutation spectra are reported, with the 3 high fidelity enzymes displaying broadly similar types of mutations. For these enzymes, transition mutations predominate, with little bias observed for type of transition.« less

Trapped Ion Qubits

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

Maunz, Peter; Wilhelm, Lukas

Qubits can be encoded in clock states of trapped ions. These states are well isolated from the environment resulting in long coherence times [1] while enabling efficient high-fidelity qubit interactions mediated by the Coulomb coupled motion of the ions in the trap. Quantum states can be prepared with high fidelity and measured efficiently using fluorescence detection. State preparation and detection with 99.93% fidelity have been realized in multiple systems [1,2]. Single qubit gates have been demonstrated below rigorous fault-tolerance thresholds [1,3]. Two qubit gates have been realized with more than 99.9% fidelity [4,5]. Quantum algorithms have been demonstrated on systemsmore » of 5 to 15 qubits [6–8].« less

Driving many distant atoms into high-fidelity steady state entanglement via Lyapunov control.

PubMed

Li, Chuang; Song, Jie; Xia, Yan; Ding, Weiqiang

2018-01-22

Based on Lyapunov control theory in closed and open systems, we propose a scheme to generate W state of many distant atoms in the cavity-fiber-cavity system. In the closed system, the W state is generated successfully even when the coupling strength between the cavity and fiber is extremely weak. In the presence of atomic spontaneous emission or cavity and fiber decay, the photon-measurement and quantum feedback approaches are proposed to improve the fidelity, which enable efficient generation of high-fidelity W state in the case of large dissipation. Furthermore, the time-optimal Lyapunov control is investigated to shorten the evolution time and improve the fidelity in open systems.

Multi-fidelity machine learning models for accurate bandgap predictions of solids

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

Pilania, Ghanshyam; Gubernatis, James E.; Lookman, Turab

Here, we present a multi-fidelity co-kriging statistical learning framework that combines variable-fidelity quantum mechanical calculations of bandgaps to generate a machine-learned model that enables low-cost accurate predictions of the bandgaps at the highest fidelity level. Additionally, the adopted Gaussian process regression formulation allows us to predict the underlying uncertainties as a measure of our confidence in the predictions. In using a set of 600 elpasolite compounds as an example dataset and using semi-local and hybrid exchange correlation functionals within density functional theory as two levels of fidelities, we demonstrate the excellent learning performance of the method against actual high fidelitymore » quantum mechanical calculations of the bandgaps. The presented statistical learning method is not restricted to bandgaps or electronic structure methods and extends the utility of high throughput property predictions in a significant way.« less

Multi-fidelity machine learning models for accurate bandgap predictions of solids

DOE PAGES

Pilania, Ghanshyam; Gubernatis, James E.; Lookman, Turab

2016-12-28

Here, we present a multi-fidelity co-kriging statistical learning framework that combines variable-fidelity quantum mechanical calculations of bandgaps to generate a machine-learned model that enables low-cost accurate predictions of the bandgaps at the highest fidelity level. Additionally, the adopted Gaussian process regression formulation allows us to predict the underlying uncertainties as a measure of our confidence in the predictions. In using a set of 600 elpasolite compounds as an example dataset and using semi-local and hybrid exchange correlation functionals within density functional theory as two levels of fidelities, we demonstrate the excellent learning performance of the method against actual high fidelitymore » quantum mechanical calculations of the bandgaps. The presented statistical learning method is not restricted to bandgaps or electronic structure methods and extends the utility of high throughput property predictions in a significant way.« less

Hydropower Optimization Using Artificial Neural Network Surrogate Models of a High-Fidelity Hydrodynamics and Water Quality Model

NASA Astrophysics Data System (ADS)

Shaw, Amelia R.; Smith Sawyer, Heather; LeBoeuf, Eugene J.; McDonald, Mark P.; Hadjerioua, Boualem

2017-11-01

Hydropower operations optimization subject to environmental constraints is limited by challenges associated with dimensionality and spatial and temporal resolution. The need for high-fidelity hydrodynamic and water quality models within optimization schemes is driven by improved computational capabilities, increased requirements to meet specific points of compliance with greater resolution, and the need to optimize operations of not just single reservoirs but systems of reservoirs. This study describes an important advancement for computing hourly power generation schemes for a hydropower reservoir using high-fidelity models, surrogate modeling techniques, and optimization methods. The predictive power of the high-fidelity hydrodynamic and water quality model CE-QUAL-W2 is successfully emulated by an artificial neural network, then integrated into a genetic algorithm optimization approach to maximize hydropower generation subject to constraints on dam operations and water quality. This methodology is applied to a multipurpose reservoir near Nashville, Tennessee, USA. The model successfully reproduced high-fidelity reservoir information while enabling 6.8% and 6.6% increases in hydropower production value relative to actual operations for dissolved oxygen (DO) limits of 5 and 6 mg/L, respectively, while witnessing an expected decrease in power generation at more restrictive DO constraints. Exploration of simultaneous temperature and DO constraints revealed capability to address multiple water quality constraints at specified locations. The reduced computational requirements of the new modeling approach demonstrated an ability to provide decision support for reservoir operations scheduling while maintaining high-fidelity hydrodynamic and water quality information as part of the optimization decision support routines.

Barriers and enablers to the use of high-fidelity patient simulation manikins in nurse education: an integrative review.

PubMed

Al-Ghareeb, Amal Z; Cooper, Simon J

2016-01-01

This integrative review identified, critically appraised and synthesised the existing evidence on the barriers and enablers to using high-fidelity human patient simulator manikins (HPSMs) in undergraduate nursing education. In nursing education, specifically at the undergraduate level, a range of low to high-fidelity simulations have been used as teaching aids. However, nursing educators encounter challenges when introducing new teaching methods or technology, despite the prevalence of high-fidelity HPSMs in nursing education. An integrative review adapted a systematic approach. Medline, CINAHL plus, ERIC, PsychINFO, EMBASE, SCOPUS, Science Direct, Cochrane database, Joanna Brigge Institute, ProQuest, California Simulation Alliance, Simulation Innovative Recourses Center and the search engine Google Scholar were searched. Keywords were selected and specific inclusion/exclusion criteria were applied. The review included all research designs for papers published between 2000 and 2015 that identified the barriers and enablers to using high-fidelity HPSMs in undergraduate nursing education. Studies were appraised using the Critical Appraisal Skills Programme criteria. Thematic analysis was undertaken and emergent themes were extracted. Twenty-one studies were included in the review. These studies adopted quasi-experimental, prospective non-experimental and descriptive designs. Ten barriers were identified, including "lack of time," "fear of technology" and "workload issues." Seven enablers were identified, including "faculty training," "administrative support" and a "dedicated simulation coordinator." Barriers to simulation relate specifically to the complex technologies inherent in high-fidelity HPSMs approaches. Strategic approaches that support up-skilling and provide dedicated technological support may overcome these barriers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydropower Optimization Using Artificial Neural Network Surrogate Models of a High-Fidelity Hydrodynamics and Water Quality Model

DOE PAGES

Shaw, Amelia R.; Sawyer, Heather Smith; LeBoeuf, Eugene J.; ...

2017-10-24

Hydropower operations optimization subject to environmental constraints is limited by challenges associated with dimensionality and spatial and temporal resolution. The need for high-fidelity hydrodynamic and water quality models within optimization schemes is driven by improved computational capabilities, increased requirements to meet specific points of compliance with greater resolution, and the need to optimize operations of not just single reservoirs but systems of reservoirs. This study describes an important advancement for computing hourly power generation schemes for a hydropower reservoir using high-fidelity models, surrogate modeling techniques, and optimization methods. The predictive power of the high-fidelity hydrodynamic and water quality model CE-QUAL-W2more » is successfully emulated by an artificial neural network, then integrated into a genetic algorithm optimization approach to maximize hydropower generation subject to constraints on dam operations and water quality. This methodology is applied to a multipurpose reservoir near Nashville, Tennessee, USA. The model successfully reproduced high-fidelity reservoir information while enabling 6.8% and 6.6% increases in hydropower production value relative to actual operations for dissolved oxygen (DO) limits of 5 and 6 mg/L, respectively, while witnessing an expected decrease in power generation at more restrictive DO constraints. Exploration of simultaneous temperature and DO constraints revealed capability to address multiple water quality constraints at specified locations. Here, the reduced computational requirements of the new modeling approach demonstrated an ability to provide decision support for reservoir operations scheduling while maintaining high-fidelity hydrodynamic and water quality information as part of the optimization decision support routines.« less

Utilizing Three-Dimensional Printing Technology to Assess the Feasibility of High-Fidelity Synthetic Ventricular Septal Defect Models for Simulation in Medical Education.

PubMed

Costello, John P; Olivieri, Laura J; Krieger, Axel; Thabit, Omar; Marshall, M Blair; Yoo, Shi-Joon; Kim, Peter C; Jonas, Richard A; Nath, Dilip S

2014-07-01

The current educational approach for teaching congenital heart disease (CHD) anatomy to students involves instructional tools and techniques that have significant limitations. This study sought to assess the feasibility of utilizing present-day three-dimensional (3D) printing technology to create high-fidelity synthetic heart models with ventricular septal defect (VSD) lesions and applying these models to a novel, simulation-based educational curriculum for premedical and medical students. Archived, de-identified magnetic resonance images of five common VSD subtypes were obtained. These cardiac images were then segmented and built into 3D computer-aided design models using Mimics Innovation Suite software. An Objet500 Connex 3D printer was subsequently utilized to print a high-fidelity heart model for each VSD subtype. Next, a simulation-based educational curriculum using these heart models was developed and implemented in the instruction of 29 premedical and medical students. Assessment of this curriculum was undertaken with Likert-type questionnaires. High-fidelity VSD models were successfully created utilizing magnetic resonance imaging data and 3D printing. Following instruction with these high-fidelity models, all students reported significant improvement in knowledge acquisition (P < .0001), knowledge reporting (P < .0001), and structural conceptualization (P < .0001) of VSDs. It is feasible to use present-day 3D printing technology to create high-fidelity heart models with complex intracardiac defects. Furthermore, this tool forms the foundation for an innovative, simulation-based educational approach to teach students about CHD and creates a novel opportunity to stimulate their interest in this field. © The Author(s) 2014.

Hydropower Optimization Using Artificial Neural Network Surrogate Models of a High-Fidelity Hydrodynamics and Water Quality Model

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

Shaw, Amelia R.; Sawyer, Heather Smith; LeBoeuf, Eugene J.

Hydropower operations optimization subject to environmental constraints is limited by challenges associated with dimensionality and spatial and temporal resolution. The need for high-fidelity hydrodynamic and water quality models within optimization schemes is driven by improved computational capabilities, increased requirements to meet specific points of compliance with greater resolution, and the need to optimize operations of not just single reservoirs but systems of reservoirs. This study describes an important advancement for computing hourly power generation schemes for a hydropower reservoir using high-fidelity models, surrogate modeling techniques, and optimization methods. The predictive power of the high-fidelity hydrodynamic and water quality model CE-QUAL-W2more » is successfully emulated by an artificial neural network, then integrated into a genetic algorithm optimization approach to maximize hydropower generation subject to constraints on dam operations and water quality. This methodology is applied to a multipurpose reservoir near Nashville, Tennessee, USA. The model successfully reproduced high-fidelity reservoir information while enabling 6.8% and 6.6% increases in hydropower production value relative to actual operations for dissolved oxygen (DO) limits of 5 and 6 mg/L, respectively, while witnessing an expected decrease in power generation at more restrictive DO constraints. Exploration of simultaneous temperature and DO constraints revealed capability to address multiple water quality constraints at specified locations. Here, the reduced computational requirements of the new modeling approach demonstrated an ability to provide decision support for reservoir operations scheduling while maintaining high-fidelity hydrodynamic and water quality information as part of the optimization decision support routines.« less

Aerodynamic design applying automatic differentiation and using robust variable fidelity optimization

NASA Astrophysics Data System (ADS)

Takemiya, Tetsushi

In modern aerospace engineering, the physics-based computational design method is becoming more important, as it is more efficient than experiments and because it is more suitable in designing new types of aircraft (e.g., unmanned aerial vehicles or supersonic business jets) than the conventional design method, which heavily relies on historical data. To enhance the reliability of the physics-based computational design method, researchers have made tremendous efforts to improve the fidelity of models. However, high-fidelity models require longer computational time, so the advantage of efficiency is partially lost. This problem has been overcome with the development of variable fidelity optimization (VFO). In VFO, different fidelity models are simultaneously employed in order to improve the speed and the accuracy of convergence in an optimization process. Among the various types of VFO methods, one of the most promising methods is the approximation management framework (AMF). In the AMF, objective and constraint functions of a low-fidelity model are scaled at a design point so that the scaled functions, which are referred to as "surrogate functions," match those of a high-fidelity model. Since scaling functions and the low-fidelity model constitutes surrogate functions, evaluating the surrogate functions is faster than evaluating the high-fidelity model. Therefore, in the optimization process, in which gradient-based optimization is implemented and thus many function calls are required, the surrogate functions are used instead of the high-fidelity model to obtain a new design point. The best feature of the AMF is that it may converge to a local optimum of the high-fidelity model in much less computational time than the high-fidelity model. However, through literature surveys and implementations of the AMF, the author xx found that (1) the AMF is very vulnerable when the computational analysis models have numerical noise, which is very common in high-fidelity models, and that (2) the AMF terminates optimization erroneously when the optimization problems have constraints. The first problem is due to inaccuracy in computing derivatives in the AMF, and the second problem is due to erroneous treatment of the trust region ratio, which sets the size of the domain for an optimization in the AMF. In order to solve the first problem of the AMF, automatic differentiation (AD) technique, which reads the codes of analysis models and automatically generates new derivative codes based on some mathematical rules, is applied. If derivatives are computed with the generated derivative code, they are analytical, and the required computational time is independent of the number of design variables, which is very advantageous for realistic aerospace engineering problems. However, if analysis models implement iterative computations such as computational fluid dynamics (CFD), which solves system partial differential equations iteratively, computing derivatives through the AD requires a massive memory size. The author solved this deficiency by modifying the AD approach and developing a more efficient implementation with CFD, and successfully applied the AD to general CFD software. In order to solve the second problem of the AMF, the governing equation of the trust region ratio, which is very strict against the violation of constraints, is modified so that it can accept the violation of constraints within some tolerance. By accepting violations of constraints during the optimization process, the AMF can continue optimization without terminating immaturely and eventually find the true optimum design point. With these modifications, the AMF is referred to as "Robust AMF," and it is applied to airfoil and wing aerodynamic design problems using Euler CFD software. The former problem has 21 design variables, and the latter 64. In both problems, derivatives computed with the proposed AD method are first compared with those computed with the finite differentiation (FD) method, and then, the Robust AMF is implemented along with the sequential quadratic programming (SQP) optimization method with only high-fidelity models. The proposed AD method computes derivatives more accurately and faster than the FD method, and the Robust AMF successfully optimizes shapes of the airfoil and the wing in a much shorter time than SQP with only high-fidelity models. These results clearly show the effectiveness of the Robust AMF. Finally, the feasibility of reducing computational time for calculating derivatives and the necessity of AMF with an optimum design point always in the feasible region are discussed as future work.

Effect of laser pulse shaping parameters on the fidelity of quantum logic gates.

PubMed

Zaari, Ryan R; Brown, Alex

2012-09-14

The effect of varying parameters specific to laser pulse shaping instruments on resulting fidelities for the ACNOT(1), NOT(2), and Hadamard(2) quantum logic gates are studied for the diatomic molecule (12)C(16)O. These parameters include varying the frequency resolution, adjusting the number of frequency components and also varying the amplitude and phase at each frequency component. A time domain analytic form of the original discretized frequency domain laser pulse function is derived, providing a useful means to infer the resulting pulse shape through variations to the aforementioned parameters. We show that amplitude variation at each frequency component is a crucial requirement for optimal laser pulse shaping, whereas phase variation provides minimal contribution. We also show that high fidelity laser pulses are dependent upon the frequency resolution and increasing the number of frequency components provides only a small incremental improvement to quantum gate fidelity. Analysis through use of the pulse area theorem confirms the resulting population dynamics for one or two frequency high fidelity laser pulses and implies similar dynamics for more complex laser pulse shapes. The ability to produce high fidelity laser pulses that provide both population control and global phase alignment is attributed greatly to the natural evolution phase alignment of the qubits involved within the quantum logic gate operation.

Limited copy number - high resolution melting (LCN-HRM) enables the detection and identification by sequencing of low level mutations in cancer biopsies

PubMed Central

Do, Hongdo; Dobrovic, Alexander

2009-01-01

Background Mutation detection in clinical tumour samples is challenging when the proportion of tumour cells, and thus mutant alleles, is low. The limited sensitivity of conventional sequencing necessitates the adoption of more sensitive approaches. High resolution melting (HRM) is more sensitive than sequencing but identification of the mutation is desirable, particularly when it is important to discriminate false positives due to PCR errors or template degradation from true mutations. We thus developed limited copy number - high resolution melting (LCN-HRM) which applies limiting dilution to HRM. Multiple replicate reactions with a limited number of target sequences per reaction allow low level mutations to be detected. The dilutions used (based on Ct values) are chosen such that mutations, if present, can be detected by the direct sequencing of amplicons with aberrant melting patterns. Results Using cell lines heterozygous for mutations, we found that the mutations were not readily detected when they comprised 10% of total alleles (20% tumour cells) by sequencing, whereas they were readily detectable at 5% total alleles by standard HRM. LCN-HRM allowed these mutations to be identified by direct sequencing of those positive reactions. LCN-HRM was then used to review formalin-fixed paraffin-embedded (FFPE) clinical samples showing discordant findings between sequencing and HRM for KRAS exon 2 and EGFR exons 19 and 21. Both true mutations present at low levels and sequence changes due to artefacts were detected by LCN-HRM. The use of high fidelity polymerases showed that the majority of the artefacts were derived from the damaged template rather than replication errors during amplification. Conclusion LCN-HRM bridges the sensitivity gap between HRM and sequencing and is effective in distinguishing between artefacts and true mutations. PMID:19811662

Limited copy number-high resolution melting (LCN-HRM) enables the detection and identification by sequencing of low level mutations in cancer biopsies.

PubMed

Do, Hongdo; Dobrovic, Alexander

2009-10-08

Mutation detection in clinical tumour samples is challenging when the proportion of tumour cells, and thus mutant alleles, is low. The limited sensitivity of conventional sequencing necessitates the adoption of more sensitive approaches. High resolution melting (HRM) is more sensitive than sequencing but identification of the mutation is desirable, particularly when it is important to discriminate false positives due to PCR errors or template degradation from true mutations.We thus developed limited copy number - high resolution melting (LCN-HRM) which applies limiting dilution to HRM. Multiple replicate reactions with a limited number of target sequences per reaction allow low level mutations to be detected. The dilutions used (based on Ct values) are chosen such that mutations, if present, can be detected by the direct sequencing of amplicons with aberrant melting patterns. Using cell lines heterozygous for mutations, we found that the mutations were not readily detected when they comprised 10% of total alleles (20% tumour cells) by sequencing, whereas they were readily detectable at 5% total alleles by standard HRM. LCN-HRM allowed these mutations to be identified by direct sequencing of those positive reactions.LCN-HRM was then used to review formalin-fixed paraffin-embedded (FFPE) clinical samples showing discordant findings between sequencing and HRM for KRAS exon 2 and EGFR exons 19 and 21. Both true mutations present at low levels and sequence changes due to artefacts were detected by LCN-HRM. The use of high fidelity polymerases showed that the majority of the artefacts were derived from the damaged template rather than replication errors during amplification. LCN-HRM bridges the sensitivity gap between HRM and sequencing and is effective in distinguishing between artefacts and true mutations.

State resolved vibrational relaxation modeling for strongly nonequilibrium flows

NASA Astrophysics Data System (ADS)

Boyd, Iain D.; Josyula, Eswar

2011-05-01

Vibrational relaxation is an important physical process in hypersonic flows. Activation of the vibrational mode affects the fundamental thermodynamic properties and finite rate relaxation can reduce the degree of dissociation of a gas. Low fidelity models of vibrational activation employ a relaxation time to capture the process at a macroscopic level. High fidelity, state-resolved models have been developed for use in continuum gas dynamics simulations based on computational fluid dynamics (CFD). By comparison, such models are not as common for use with the direct simulation Monte Carlo (DSMC) method. In this study, a high fidelity, state-resolved vibrational relaxation model is developed for the DSMC technique. The model is based on the forced harmonic oscillator approach in which multi-quantum transitions may become dominant at high temperature. Results obtained for integrated rate coefficients from the DSMC model are consistent with the corresponding CFD model. Comparison of relaxation results obtained with the high-fidelity DSMC model shows significantly less excitation of upper vibrational levels in comparison to the standard, lower fidelity DSMC vibrational relaxation model. Application of the new DSMC model to a Mach 7 normal shock wave in carbon monoxide provides better agreement with experimental measurements than the standard DSMC relaxation model.

Effects of Low- Versus High-Fidelity Simulations on the Cognitive Burden and Performance of Entry-Level Paramedicine Students: A Mixed-Methods Comparison Trial Using Eye-Tracking, Continuous Heart Rate, Difficulty Rating Scales, Video Observation and Interviews.

PubMed

Mills, Brennen W; Carter, Owen B-J; Rudd, Cobie J; Claxton, Louise A; Ross, Nathan P; Strobel, Natalie A

2016-02-01

High-fidelity simulation-based training is often avoided for early-stage students because of the assumption that while practicing newly learned skills, they are ill suited to processing multiple demands, which can lead to "cognitive overload" and poorer learning outcomes. We tested this assumption using a mixed-methods experimental design manipulating psychological immersion. Thirty-nine randomly assigned first-year paramedicine students completed low- or high-environmental fidelity simulations [low-environmental fidelity simulations (LF(en)S) vs. high-environmental fidelity simulation (HF(en)S)] involving a manikin with obstructed airway (SimMan3G). Psychological immersion and cognitive burden were determined via continuous heart rate, eye tracking, self-report questionnaire (National Aeronautics and Space Administration Task Load Index), independent observation, and postsimulation interviews. Performance was assessed by successful location of obstruction and time-to-termination. Eye tracking confirmed that students attended to multiple, concurrent stimuli in HF(en)S and interviews consistently suggested that they experienced greater psychological immersion and cognitive burden than their LF(en)S counterparts. This was confirmed by significantly higher mean heart rate (P < 0.001) and National Aeronautics and Space Administration Task Load Index mental demand (P < 0.05). Although group allocation did not influence the proportion of students who ultimately revived the patient (58% vs. 30%, P < 0.10), the HF(en)S students did so significantly more quickly (P < 0.01). The LF(en)S students had low immersion resulting in greater assessment anxiety. High-environmental fidelity simulation engendered immersion and a sense of urgency in students, whereas LF(en)S created assessment anxiety and slower performance. We conclude that once early-stage students have learned the basics of a clinical skill, throwing them in the "deep end" of high-fidelity simulation creates significant additional cognitive burden but this has considerable educational merit.

Final Environmental Assessment for the Installation of New JDAM and High Fidelity Targets for the Nevada Test and Training Range

DTIC Science & Technology

2004-11-01

Target Centroid 98 RANW / R SC GIS 04071 Data valid as of 11 Mar 04 rogertargets_a#2.apr Figure 2-3. Chemical/Industrial and High Fidelity Urban...existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding...Fidelity Targets, NTTR Nevada Division of Wildlife – Nevada Test and Training Range JDAM Targets Nevada Natural Heritage Program – Data Request received 8

High-fidelity frequency down-conversion of visible entangled photon pairs with superconducting single-photon detectors

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

Ikuta, Rikizo; Kato, Hiroshi; Kusaka, Yoshiaki

We experimentally demonstrate a high-fidelity visible-to-telecommunicationwavelength conversion of a photon by using a solid-state-based difference frequency generation. In the experiment, one half of a pico-second visible entangled photon pair at 780 nm is converted to a 1522-nm photon. Using superconducting single-photon detectors with low dark count rates and small timing jitters, we observed a fidelity of 0.93±0.04 after the wavelength conversion.

Comparison of intervention fidelity between COPE TEEN and an attention-control program in a randomized controlled trial

PubMed Central

Kelly, Stephanie A.; Oswalt, Krista; Melnyk, Bernadette Mazurek; Jacobson, Diana

2015-01-01

Fidelity in implementing an intervention is critical to accurately determine and interpret the effects of an intervention. It is important to monitor the manner in which the behavioral intervention is implemented (e.g. adaptations, delivery as intended and dose). Few interventions are implemented with 100% fidelity. In this study, high school health teachers implemented the intervention. To attribute study findings to the intervention, it was vital to know to what degree the intervention was implemented. Therefore, the purposes of this study were to evaluate intervention fidelity and to compare implementation fidelity between the creating opportunities for personal empowerment (COPE) Healthy Lifestyles TEEN (thinking, emotions, exercise, and nutrition) program, the experimental intervention and Healthy Teens, an attention-control intervention, in a randomized controlled trial with 779 adolescents from 11 high schools in the southwest region of the United States. Thirty teachers participated in this study. Findings indicated that the attention-control teachers implemented their intervention with greater fidelity than COPE TEEN teachers. It is possible due to the novel intervention and the teachers’ unfamiliarity with cognitive-behavioral skills building, COPE TEEN teachers had less fidelity. It is important to assess novel skill development prior to the commencement of experimental interventions and to provide corrective feedback during the course of implementation. PMID:25355179

Orbit Stability of OSIRIS-REx in the Vicinity of Bennu Using a High-Fidelity Solar Radiation Model

NASA Technical Reports Server (NTRS)

Williams, Trevor; Hughes, Kyle; Mashiku, Alinda; Longuski, James

2015-01-01

The OSIRIS-REx mission (Origins Spectral Interpretation Resource Identification Security Regolith EXPlorer) is an asteroid sample return mission to Bennu (RQ36) that is scheduled to launch in 2016. The planned science operations precluding the small retrieval involve operations in terminator orbits (orbit plane is perpendicular to the sun). Over longer durations the solar radiation pressure (SRP) perturbs the orbit causing it to precess. Our work involves: modeling high fidelity SRP model to capture the perturbations during attitude changes; design a stable orbit from the high fidelity models to analyze the stability over time.

Lattice Boltzmann for Airframe Noise Predictions

NASA Technical Reports Server (NTRS)

Barad, Michael; Kocheemoolayil, Joseph; Kiris, Cetin

2017-01-01

Increase predictive use of High-Fidelity Computational Aero- Acoustics (CAA) capabilities for NASA's next generation aviation concepts. CFD has been utilized substantially in analysis and design for steady-state problems (RANS). Computational resources are extremely challenged for high-fidelity unsteady problems (e.g. unsteady loads, buffet boundary, jet and installation noise, fan noise, active flow control, airframe noise, etc) ü Need novel techniques for reducing the computational resources consumed by current high-fidelity CAA Need routine acoustic analysis of aircraft components at full-scale Reynolds number from first principles Need an order of magnitude reduction in wall time to solution!

Testing the Predictive Capability of the High-Fidelity Generalized Method of Cells Using an Efficient Reformulation

NASA Technical Reports Server (NTRS)

Arnold, Steven M. (Technical Monitor); Bansal, Yogesh; Pindera, Marek-Jerzy

2004-01-01

The High-Fidelity Generalized Method of Cells is a new micromechanics model for unidirectionally reinforced periodic multiphase materials that was developed to overcome the original model's shortcomings. The high-fidelity version predicts the local stress and strain fields with dramatically greater accuracy relative to the original model through the use of a better displacement field representation. Herein, we test the high-fidelity model's predictive capability in estimating the elastic moduli of periodic composites characterized by repeating unit cells obtained by rotation of an infinite square fiber array through an angle about the fiber axis. Such repeating unit cells may contain a few or many fibers, depending on the rotation angle. In order to analyze such multi-inclusion repeating unit cells efficiently, the high-fidelity micromechanics model's framework is reformulated using the local/global stiffness matrix approach. The excellent agreement with the corresponding results obtained from the standard transformation equations confirms the new model's predictive capability for periodic composites characterized by multi-inclusion repeating unit cells lacking planes of material symmetry. Comparison of the effective moduli and local stress fields with the corresponding results obtained from the original Generalized Method of Cells dramatically highlights the original model's shortcomings for certain classes of unidirectional composites.

High fidelity quasi steady-state aerodynamic model effects on race vehicle performance predictions using multi-body simulation

NASA Astrophysics Data System (ADS)

Mohrfeld-Halterman, J. A.; Uddin, M.

2016-07-01

We described in this paper the development of a high fidelity vehicle aerodynamic model to fit wind tunnel test data over a wide range of vehicle orientations. We also present a comparison between the effects of this proposed model and a conventional quasi steady-state aerodynamic model on race vehicle simulation results. This is done by implementing both of these models independently in multi-body quasi steady-state simulations to determine the effects of the high fidelity aerodynamic model on race vehicle performance metrics. The quasi steady state vehicle simulation is developed with a multi-body NASCAR Truck vehicle model, and simulations are conducted for three different types of NASCAR race tracks, a short track, a one and a half mile intermediate track, and a higher speed, two mile intermediate race track. For each track simulation, the effects of the aerodynamic model on handling, maximum corner speed, and drive force metrics are analysed. The accuracy of the high-fidelity model is shown to reduce the aerodynamic model error relative to the conventional aerodynamic model, and the increased accuracy of the high fidelity aerodynamic model is found to have realisable effects on the performance metric predictions on the intermediate tracks resulting from the quasi steady-state simulation.

Evaluating Amazon's Mechanical Turk as a Tool for Experimental Behavioral Research

PubMed Central

Crump, Matthew J. C.; McDonnell, John V.; Gureckis, Todd M.

2013-01-01

Amazon Mechanical Turk (AMT) is an online crowdsourcing service where anonymous online workers complete web-based tasks for small sums of money. The service has attracted attention from experimental psychologists interested in gathering human subject data more efficiently. However, relative to traditional laboratory studies, many aspects of the testing environment are not under the experimenter's control. In this paper, we attempt to empirically evaluate the fidelity of the AMT system for use in cognitive behavioral experiments. These types of experiment differ from simple surveys in that they require multiple trials, sustained attention from participants, comprehension of complex instructions, and millisecond accuracy for response recording and stimulus presentation. We replicate a diverse body of tasks from experimental psychology including the Stroop, Switching, Flanker, Simon, Posner Cuing, attentional blink, subliminal priming, and category learning tasks using participants recruited using AMT. While most of replications were qualitatively successful and validated the approach of collecting data anonymously online using a web-browser, others revealed disparity between laboratory results and online results. A number of important lessons were encountered in the process of conducting these replications that should be of value to other researchers. PMID:23516406

dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

PubMed

Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

2015-05-12

Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

Direct NMR Evidence that Transient Tautomeric and Anionic States in dG·dT Form Watson-Crick-like Base Pairs.

PubMed

Szymanski, Eric S; Kimsey, Isaac J; Al-Hashimi, Hashim M

2017-03-29

The replicative and translational machinery utilizes the unique geometry of canonical G·C and A·T/U Watson-Crick base pairs to discriminate against DNA and RNA mismatches in order to ensure high fidelity replication, transcription, and translation. There is growing evidence that spontaneous errors occur when mismatches adopt a Watson-Crick-like geometry through tautomerization and/or ionization of the bases. Studies employing NMR relaxation dispersion recently showed that wobble dG·dT and rG·rU mismatches in DNA and RNA duplexes transiently form tautomeric and anionic species with probabilities (≈0.01-0.40%) that are in concordance with replicative and translational errors. Although computational studies indicate that these exceptionally short-lived and low-abundance species form Watson-Crick-like base pairs, their conformation could not be directly deduced from the experimental data, and alternative pairing geometries could not be ruled out. Here, we report direct NMR evidence that the transient tautomeric and anionic species form hydrogen-bonded Watson-Crick-like base pairs. A guanine-to-inosine substitution, which selectively knocks out a Watson-Crick-type (G)N2H 2 ···O2(T) hydrogen bond, significantly destabilized the transient tautomeric and anionic species, as assessed by lack of any detectable chemical exchange by imino nitrogen rotating frame spin relaxation (R 1ρ ) experiments. An 15 N R 1ρ NMR experiment targeting the amino nitrogen of guanine (dG-N2) provides direct evidence for Watson-Crick (G)N2H 2 ···O2(T) hydrogen bonding in the transient tautomeric state. The strategy presented in this work can be generally applied to examine hydrogen-bonding patterns in nucleic acid transient states including in other tautomeric and anionic species that are postulated to play roles in replication and translational errors.

A possible role for chromium(III) in genotoxicity.

PubMed

Snow, E T

1991-05-01

Chromium is found in the environment in two major forms: reduced CrIII and CrVI, or chromate. Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable CrIII species. CrIII, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular CrIII can react slowly with both nucleic acids and proteins and can be genotoxic. We have investigated the genotoxicity of CrIII in vitro using a DNA replication assay and in vivo by CaCl2-mediated transfection of chromium-treated DNA into Escherichia coli. When DNA replication was measured on a CrIII-treated template using purified DNA polymerases (either bacterial or mammalian), both the rate of DNA replication and the amount of incorporation per polymerase binding event (processivity) were greatly increased relative to controls. When transfected into E. coli, CrIII-treated M13mp2 bacteriophage DNA showed a dose-dependent increase in mutation frequency. These results suggest that CrIII alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that CrIII can contribute to chromium-mediated carcinogenesis.

Spatial Models of Prebiotic Evolution: Soup Before Pizza?

NASA Astrophysics Data System (ADS)

Scheuring, István; Czárán, Tamás; Szabó, Péter; Károlyi, György; Toroczkai, Zoltán

2003-10-01

The problem of information integration and resistance to the invasion of parasitic mutants in prebiotic replicator systems is a notorious issue of research on the origin of life. Almost all theoretical studies published so far have demonstrated that some kind of spatial structure is indispensable for the persistence and/or the parasite resistance of any feasible replicator system. Based on a detailed critical survey of spatial models on prebiotic information integration, we suggest a possible scenario for replicator system evolution leading to the emergence of the first protocells capable of independent life. We show that even the spatial versions of the hypercycle model are vulnerable to selfish parasites in heterogeneous habitats. Contrary, the metabolic system remains persistent and coexistent with its parasites both on heterogeneous surfaces and in chaotically mixing flowing media. Persistent metabolic parasites can be converted to metabolic cooperators, or they can gradually obtain replicase activity. Our simulations show that, once replicase activity emerged, a gradual and simultaneous evolutionary improvement of replicase functionality (speed and fidelity) and template efficiency is possible only on a surface that constrains the mobility of macromolecule replicators. Based on the results of the models reviewed, we suggest that open chaotic flows (`soup') and surface dynamics (`pizza') both played key roles in the sequence of evolutionary events ultimately concluding in the appearance of the first living cell on Earth.

Defect of Fe-S cluster binding by DNA polymerase δ in yeast suppresses UV-induced mutagenesis, but enhances DNA polymerase ζ - dependent spontaneous mutagenesis.

PubMed

Stepchenkova, E I; Tarakhovskaya, E R; Siebler, H M; Pavlov, Y I

2017-01-01

Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance mechanism dependent on pol ζ prevents DNA/genome instability and cell death at the expense of increased mutation rates. The pol switches occurring during this specialized replication are not fully understood. The loss of pol ζ results in the absence of induced mutagenesis and suppression of spontaneous mutagenesis. Disruption of the Fe-S cluster motif that abolish the interaction of the C-terminal domain (CTD) of the catalytic subunit of pol ζ with its accessory subunits, which are shared with pol δ, leads to a similar defect in induced mutagenesis. Intriguingly, the pol3-13 mutation that affects the Fe-S cluster in the CTD of the catalytic subunit of pol δ also leads to defective induced mutagenesis, suggesting the possibility that Fe-S clusters are essential for the pol switches during replication of damaged DNA. We confirmed that yeast strains with the pol3-13 mutation are UV-sensitive and defective in UV-induced mutagenesis. However, they have increased spontaneous mutation rates. We found that this increase is dependent on functional pol ζ. In the pol3-13 mutant strain with defective pol δ, there is a sharp increase in transversions and complex mutations, which require functional pol ζ, and an increase in the occurrence of large deletions, whose size is controlled by pol ζ. Therefore, the pol3-13 mutation abrogates pol ζ-dependent induced mutagenesis, but allows for pol ζ recruitment for the generation of spontaneous mutations and prevention of larger deletions. These results reveal differential control of the two major types of pol ζ-dependent mutagenesis by the Fe-S cluster present in replicative pol δ. Copyright © 2016 Elsevier B.V. All rights reserved.

Feasibility and fidelity of practising surgical fixation on a virtual ulna bone

PubMed Central

LeBlanc, Justin; Hutchison, Carol; Hu, Yaoping; Donnon, Tyrone

2013-01-01

Background Surgical simulators provide a safe environment to learn and practise psychomotor skills. A goal for these simulators is to achieve high levels of fidelity. The purpose of this study was to develop a reliable surgical simulator fidelity questionnaire and to assess whether a newly developed virtual haptic simulator for fixation of an ulna has comparable levels of fidelity as Sawbones. Methods Simulator fidelity questionnaires were developed. We performed a stratified randomized study with surgical trainees. They performed fixation of the ulna using a virtual simulator and Sawbones. They completed the fidelity questionnaires after each procedure. Results Twenty-two trainees participated in the study. The reliability of the fidelity questionnaire for each separate domain (environment, equipment, psychological) was Cronbach α greater than 0.70, except for virtual environment. The Sawbones had significantly higher levels of fidelity than the virtual simulator (p < 0.001) with a large effect size difference (Cohen d < 1.3). Conclusion The newly developed fidelity questionnaire is a reliable tool that can potentially be used to determine the fidelity of other surgical simulators. Increasing the fidelity of this virtual simulator is required before its use as a training tool for surgical fixation. The virtual simulator brings with it the added benefits of repeated, independent safe use with immediate, objective feedback and the potential to alter the complexity of the skill. PMID:23883510

Ground-to-satellite quantum teleportation.

PubMed

Ren, Ji-Gang; Xu, Ping; Yong, Hai-Lin; Zhang, Liang; Liao, Sheng-Kai; Yin, Juan; Liu, Wei-Yue; Cai, Wen-Qi; Yang, Meng; Li, Li; Yang, Kui-Xing; Han, Xuan; Yao, Yong-Qiang; Li, Ji; Wu, Hai-Yan; Wan, Song; Liu, Lei; Liu, Ding-Quan; Kuang, Yao-Wu; He, Zhi-Ping; Shang, Peng; Guo, Cheng; Zheng, Ru-Hua; Tian, Kai; Zhu, Zhen-Cai; Liu, Nai-Le; Lu, Chao-Yang; Shu, Rong; Chen, Yu-Ao; Peng, Cheng-Zhi; Wang, Jian-Yu; Pan, Jian-Wei

2017-09-07

An arbitrary unknown quantum state cannot be measured precisely or replicated perfectly. However, quantum teleportation enables unknown quantum states to be transferred reliably from one object to another over long distances, without physical travelling of the object itself. Long-distance teleportation is a fundamental element of protocols such as large-scale quantum networks and distributed quantum computation. But the distances over which transmission was achieved in previous teleportation experiments, which used optical fibres and terrestrial free-space channels, were limited to about 100 kilometres, owing to the photon loss of these channels. To realize a global-scale 'quantum internet' the range of quantum teleportation needs to be greatly extended. A promising way of doing so involves using satellite platforms and space-based links, which can connect two remote points on Earth with greatly reduced channel loss because most of the propagation path of the photons is in empty space. Here we report quantum teleportation of independent single-photon qubits from a ground observatory to a low-Earth-orbit satellite, through an uplink channel, over distances of up to 1,400 kilometres. To optimize the efficiency of the link and to counter the atmospheric turbulence in the uplink, we use a compact ultra-bright source of entangled photons, a narrow beam divergence and high-bandwidth and high-accuracy acquiring, pointing and tracking. We demonstrate successful quantum teleportation of six input states in mutually unbiased bases with an average fidelity of 0.80 ± 0.01, well above the optimal state-estimation fidelity on a single copy of a qubit (the classical limit). Our demonstration of a ground-to-satellite uplink for reliable and ultra-long-distance quantum teleportation is an essential step towards a global-scale quantum internet.

Ground-to-satellite quantum teleportation

NASA Astrophysics Data System (ADS)

Ren, Ji-Gang; Xu, Ping; Yong, Hai-Lin; Zhang, Liang; Liao, Sheng-Kai; Yin, Juan; Liu, Wei-Yue; Cai, Wen-Qi; Yang, Meng; Li, Li; Yang, Kui-Xing; Han, Xuan; Yao, Yong-Qiang; Li, Ji; Wu, Hai-Yan; Wan, Song; Liu, Lei; Liu, Ding-Quan; Kuang, Yao-Wu; He, Zhi-Ping; Shang, Peng; Guo, Cheng; Zheng, Ru-Hua; Tian, Kai; Zhu, Zhen-Cai; Liu, Nai-Le; Lu, Chao-Yang; Shu, Rong; Chen, Yu-Ao; Peng, Cheng-Zhi; Wang, Jian-Yu; Pan, Jian-Wei

2017-09-01

An arbitrary unknown quantum state cannot be measured precisely or replicated perfectly. However, quantum teleportation enables unknown quantum states to be transferred reliably from one object to another over long distances, without physical travelling of the object itself. Long-distance teleportation is a fundamental element of protocols such as large-scale quantum networks and distributed quantum computation. But the distances over which transmission was achieved in previous teleportation experiments, which used optical fibres and terrestrial free-space channels, were limited to about 100 kilometres, owing to the photon loss of these channels. To realize a global-scale ‘quantum internet’ the range of quantum teleportation needs to be greatly extended. A promising way of doing so involves using satellite platforms and space-based links, which can connect two remote points on Earth with greatly reduced channel loss because most of the propagation path of the photons is in empty space. Here we report quantum teleportation of independent single-photon qubits from a ground observatory to a low-Earth-orbit satellite, through an uplink channel, over distances of up to 1,400 kilometres. To optimize the efficiency of the link and to counter the atmospheric turbulence in the uplink, we use a compact ultra-bright source of entangled photons, a narrow beam divergence and high-bandwidth and high-accuracy acquiring, pointing and tracking. We demonstrate successful quantum teleportation of six input states in mutually unbiased bases with an average fidelity of 0.80 ± 0.01, well above the optimal state-estimation fidelity on a single copy of a qubit (the classical limit). Our demonstration of a ground-to-satellite uplink for reliable and ultra-long-distance quantum teleportation is an essential step towards a global-scale quantum internet.

Applying the Five-Step Model of Fidelity Assessment to a Randomized Experiment of a High School STEM Intervention

ERIC Educational Resources Information Center

Kopp, Jason P.; Hulleman, Chris S.; Harackiewicz, Judith M.; Rozek, Chris

2012-01-01

Assessing fidelity of implementation is becoming increasingly important in education research, in particular as a tool for understanding variations in treatment effectiveness. Fidelity of implementation is defined as "the determination of how well an intervention is implemented in comparison with the original program design during an efficacy…

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

Prospective randomized comparison of standard didactic lecture versus high-fidelity simulation for radiology resident contrast reaction management training.

PubMed

Wang, Carolyn L; Schopp, Jennifer G; Petscavage, Jonelle M; Paladin, Angelisa M; Richardson, Michael L; Bush, William H

2011-06-01

The objective of our study was to assess whether high-fidelity simulation-based training is more effective than traditional didactic lecture to train radiology residents in the management of contrast reactions. This was a prospective study of 44 radiology residents randomized into a simulation group versus a lecture group. All residents attended a contrast reaction didactic lecture. Four months later, baseline knowledge was assessed with a written test, which we refer to as the "pretest." After the pretest, the 21 residents in the lecture group attended a repeat didactic lecture and the 23 residents in the simulation group underwent high-fidelity simulation-based training with five contrast reaction scenarios. Next, all residents took a second written test, which we refer to as the "posttest." Two months after the posttest, both groups took a third written test, which we refer to as the "delayed posttest," and underwent performance testing with a high-fidelity severe contrast reaction scenario graded on predefined critical actions. There was no statistically significant difference between the simulation and lecture group pretest, immediate posttest, or delayed posttest scores. The simulation group performed better than the lecture group on the severe contrast reaction simulation scenario (p = 0.001). The simulation group reported improved comfort in identifying and managing contrast reactions and administering medications after the simulation training (p ≤ 0.04) and was more comfortable than the control group (p = 0.03), which reported no change in comfort level after the repeat didactic lecture. When compared with didactic lecture, high-fidelity simulation-based training of contrast reaction management shows equal results on written test scores but improved performance during a high-fidelity severe contrast reaction simulation scenario.

High-Fidelity Simulation Meets Athletic Training Education: An Innovative Collaborative Teaching Project

ERIC Educational Resources Information Center

Palmer, Elizabeth; Edwards, Taylor; Racchini, James

2014-01-01

High-fidelity simulation is frequently used in nursing education to provide students with simulated experiences prior to and throughout clinical coursework that involves direct patient care. These high-tech exercises take advantage of the benefits of a standardized patient or mock patient encounter, while eliminating some of the drawbacks…

High fidelity quantum teleportation assistance with quantum neural network

NASA Astrophysics Data System (ADS)

Huang, Chunhui; Wu, Bichun

2014-09-01

In this paper, a high fidelity scheme of quantum teleportation based on quantum neural network (QNN) is proposed. The QNN is composed of multi-bit control-not gates. The quantum teleportation of a qubit state via two-qubit entangled channels is investigated by solving the master equation in Lindblad operators with a noisy environment. To ensure the security of quantum teleportation, the indirect training of QNN is employed. Only 10% of teleported information is extracted for the training of QNN parameters. Then the outputs are corrected by the other QNN at Bob's side. We build a random series of numbers ranged in [0, π] as inputs and simulate the properties of our teleportation scheme. The results show that the fidelity of quantum teleportation system is significantly improved to approach 1 by the error-correction of QNN. It illustrates that the distortion can be eliminated perfectly and the high fidelity of quantum teleportation could be implemented.

High-fidelity quantum gates on quantum-dot-confined electron spins in low-Q optical microcavities

NASA Astrophysics Data System (ADS)

Li, Tao; Gao, Jian-Cun; Deng, Fu-Guo; Long, Gui-Lu

2018-04-01

We propose some high-fidelity quantum circuits for quantum computing on electron spins of quantum dots (QD) embedded in low-Q optical microcavities, including the two-qubit controlled-NOT gate and the multiple-target-qubit controlled-NOT gate. The fidelities of both quantum gates can, in principle, be robust to imperfections involved in a practical input-output process of a single photon by converting the infidelity into a heralded error. Furthermore, the influence of two different decay channels is detailed. By decreasing the quality factor of the present microcavity, we can largely increase the efficiencies of these quantum gates while their high fidelities remain unaffected. This proposal also has another advantage regarding its experimental feasibility, in that both quantum gates can work faithfully even when the QD-cavity systems are non-identical, which is of particular importance in current semiconductor QD technology.

Site fidelity, mate fidelity, and breeding dispersal in American kestrels

USGS Publications Warehouse

Steenhof, K.; Peterson, B.E.

2009-01-01

We assessed mate fidelity, nest-box fidelity, and breeding dispersal distances of American Kestrels (falco sparverius) nesting in boxes in southwestern Idaho from 1990 through 2006. Seventy-seven percent of boxes had different males and 87% had different females where nest-box occupants were identified in consecutive years. High turnover rates were partly a result of box-switching. Forty-eight percent of males and 58% of females that nested within the study area in successive years used different boxes. The probability of changing boxes was unrelated to gender, nesting success in the prior year, or years of nesting experience. Breeding dispersal distances for birds that moved to different boxes averaged 2.2 km for males (max = 22 km) and 3.2 km for females (max = 32 km). Approximately 70% of birds that nested in consecutive years on the study area had a different mate in the second year. Mate fidelity was related to box fidelity but not to prior nesting success or years of nesting experience. Mate changes occurred 32% of the time when the previous mate was known to be alive and nesting in the area. Kestrels that switched mates and boxes did not improve or decrease their subsequent nesting success. Kestrels usually switched to mates with less experience and lower lifetime productivity than their previous mates. The costs of switching boxes and mates were low, and there were no obvious benefits to fidelity. The cost of "waiting" for a previous mate that might have died could be high in species with high annual mortality.

Enhancement of human DNA polymerase η activity and fidelity is dependent upon a bipartite interaction with the Werner syndrome protein.

PubMed

Maddukuri, Leena; Ketkar, Amit; Eddy, Sarah; Zafar, Maroof K; Griffin, Wezley C; Eoff, Robert L

2012-12-07

We have investigated the interaction between human DNA polymerase η (hpol η) and the Werner syndrome protein (WRN). Functional assays revealed that the WRN exonuclease and RecQ C-terminal (RQC) domains are necessary for full stimulation of hpol η-catalyzed formation of correct base pairs. We find that WRN does not stimulate hpol η-catalyzed formation of mispairs. Moreover, the exonuclease activity of WRN prevents stable mispair formation by hpol η. These results are consistent with a proofreading activity for WRN during single-nucleotide additions. ATP hydrolysis by WRN appears to attenuate stimulation of hpol η. Pre-steady-state kinetic results show that k(pol) is increased 4-fold by WRN. Finally, pulldown assays reveal a bipartite physical interaction between hpol η and WRN that is mediated by the exonuclease and RQC domains. Taken together, these results are consistent with alteration of the rate-limiting step in polymerase catalysis by direct protein-protein interactions between WRN and hpol η. In summary, WRN improves the efficiency and fidelity of hpol η to promote more effective replication of DNA.

Training for shoulder dystocia: a trial of simulation using low-fidelity and high-fidelity mannequins.

PubMed

Crofts, Joanna F; Bartlett, Christine; Ellis, Denise; Hunt, Linda P; Fox, Robert; Draycott, Timothy J

2006-12-01

To evaluate the effectiveness of simulation training for shoulder dystocia management and compare training using a high-fidelity mannequin with that using traditional devices. Training was undertaken in six hospitals and a medical simulation center in the United Kingdom. Midwives and obstetricians working for participating hospitals were eligible for inclusion. One hundred forty participants (45 doctors, 95 midwives) were randomized to training with a high-fidelity training mannequin (incorporating force perception training) or traditional low-fidelity mannequins. Performance was assessed pre- and posttraining, using a videoed, standardized shoulder dystocia simulation. Outcome measures were delivery, head-to-body delivery time, use of appropriate and inappropriate actions, force applied, and communication. One hundred thirty-two participants completed the posttraining assessment. All training was associated with improved performance: use of basic maneuvers 114 of 140 (81.4%) to 125 of 132 (94.7%) (P=.002), successful deliveries 60 of 140 (42.9%) to 110 of 132 (83.3%) (P<.001), good communication with the patient 79 of 139 (56.8%) to 109 of 132 (82.6%) (P<.001), pre- and posttraining, respectively. Training with the high-fidelity mannequin was associated with a higher successful delivery rate than training with traditional devices: 94% compared with 72% (odds ratio 6.53, 95% confidence interval 2.05-20.81; P=.002). Total applied force was significantly lower for those who had undergone force training (2,030 Newton seconds versus 2,916 Newton seconds; P=.006) but there was no significant difference in the peak applied force 102 Newtons versus 112 Newtons (P=.242). This study verifies the need for shoulder dystocia training; before training only 43% participants could achieve delivery. All training with mannequins improved the management of simulated shoulder dystocia. Training on a high-fidelity mannequin, including force perception teaching, offered additional training benefits. I.

Progress in the Utilization of High-Fidelity Simulation in Basic Science Education

ERIC Educational Resources Information Center

Helyer, Richard; Dickens, Peter

2016-01-01

High-fidelity patient simulators are mainly used to teach clinical skills and remain underutilized in teaching basic sciences. This article summarizes our current views on the use of simulation in basic science education and identifies pitfalls and opportunities for progress.

GIS Data Based Automatic High-Fidelity 3D Road Network Modeling

NASA Technical Reports Server (NTRS)

Wang, Jie; Shen, Yuzhong

2011-01-01

3D road models are widely used in many computer applications such as racing games and driving simulations_ However, almost all high-fidelity 3D road models were generated manually by professional artists at the expense of intensive labor. There are very few existing methods for automatically generating 3D high-fidelity road networks, especially those existing in the real world. This paper presents a novel approach thai can automatically produce 3D high-fidelity road network models from real 2D road GIS data that mainly contain road. centerline in formation. The proposed method first builds parametric representations of the road centerlines through segmentation and fitting . A basic set of civil engineering rules (e.g., cross slope, superelevation, grade) for road design are then selected in order to generate realistic road surfaces in compliance with these rules. While the proposed method applies to any types of roads, this paper mainly addresses automatic generation of complex traffic interchanges and intersections which are the most sophisticated elements in the road networks

Hybrid surrogate-model-based multi-fidelity efficient global optimization applied to helicopter blade design

NASA Astrophysics Data System (ADS)

Ariyarit, Atthaphon; Sugiura, Masahiko; Tanabe, Yasutada; Kanazaki, Masahiro

2018-06-01

A multi-fidelity optimization technique by an efficient global optimization process using a hybrid surrogate model is investigated for solving real-world design problems. The model constructs the local deviation using the kriging method and the global model using a radial basis function. The expected improvement is computed to decide additional samples that can improve the model. The approach was first investigated by solving mathematical test problems. The results were compared with optimization results from an ordinary kriging method and a co-kriging method, and the proposed method produced the best solution. The proposed method was also applied to aerodynamic design optimization of helicopter blades to obtain the maximum blade efficiency. The optimal shape obtained by the proposed method achieved performance almost equivalent to that obtained using the high-fidelity, evaluation-based single-fidelity optimization. Comparing all three methods, the proposed method required the lowest total number of high-fidelity evaluation runs to obtain a converged solution.

Comparison of Intervention Fidelity between COPE TEEN and an Attention-Control Program in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Kelly, Stephanie A.; Oswalt, Krista; Melnyk, Bernadette Mazurek; Jacobson, Diana

2015-01-01

Fidelity in implementing an intervention is critical to accurately determine and interpret the effects of an intervention. It is important to monitor the manner in which the behavioral intervention is implemented (e.g. adaptations, delivery as intended and dose). Few interventions are implemented with 100% fidelity. In this study, high school…

A high-throughput assay for the comprehensive profiling of DNA ligase fidelity

PubMed Central

Lohman, Gregory J. S.; Bauer, Robert J.; Nichols, Nicole M.; Mazzola, Laurie; Bybee, Joanna; Rivizzigno, Danielle; Cantin, Elizabeth; Evans, Thomas C.

2016-01-01

DNA ligases have broad application in molecular biology, from traditional cloning methods to modern synthetic biology and molecular diagnostics protocols. Ligation-based detection of polynucleotide sequences can be achieved by the ligation of probe oligonucleotides when annealed to a complementary target sequence. In order to achieve a high sensitivity and low background, the ligase must efficiently join correctly base-paired substrates, while discriminating against the ligation of substrates containing even one mismatched base pair. In the current study, we report the use of capillary electrophoresis to rapidly generate mismatch fidelity profiles that interrogate all 256 possible base-pair combinations at a ligation junction in a single experiment. Rapid screening of ligase fidelity in a 96-well plate format has allowed the study of ligase fidelity in unprecedented depth. As an example of this new method, herein we report the ligation fidelity of Thermus thermophilus DNA ligase at a range of temperatures, buffer pH and monovalent cation strength. This screen allows the selection of reaction conditions that maximize fidelity without sacrificing activity, while generating a profile of specific mismatches that ligate detectably under each set of conditions. PMID:26365241

A high-throughput assay for the comprehensive profiling of DNA ligase fidelity.

PubMed

Lohman, Gregory J S; Bauer, Robert J; Nichols, Nicole M; Mazzola, Laurie; Bybee, Joanna; Rivizzigno, Danielle; Cantin, Elizabeth; Evans, Thomas C

2016-01-29

DNA ligases have broad application in molecular biology, from traditional cloning methods to modern synthetic biology and molecular diagnostics protocols. Ligation-based detection of polynucleotide sequences can be achieved by the ligation of probe oligonucleotides when annealed to a complementary target sequence. In order to achieve a high sensitivity and low background, the ligase must efficiently join correctly base-paired substrates, while discriminating against the ligation of substrates containing even one mismatched base pair. In the current study, we report the use of capillary electrophoresis to rapidly generate mismatch fidelity profiles that interrogate all 256 possible base-pair combinations at a ligation junction in a single experiment. Rapid screening of ligase fidelity in a 96-well plate format has allowed the study of ligase fidelity in unprecedented depth. As an example of this new method, herein we report the ligation fidelity of Thermus thermophilus DNA ligase at a range of temperatures, buffer pH and monovalent cation strength. This screen allows the selection of reaction conditions that maximize fidelity without sacrificing activity, while generating a profile of specific mismatches that ligate detectably under each set of conditions. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Spawning site fidelity of wild and hatchery lake trout (Salvelinus namaycush) in northern Lake Huron

USGS Publications Warehouse

Binder, Thomas; Riley, Stephen C.; Holbrook, Christopher; Hansen, Michael J.; Bergstedt, Roger A.; Bronte, Charles R.; He, Ji; Krueger, Charles C.

2016-01-01

Fidelity to high-quality spawning sites helps ensure that adults repeatedly spawn at sites that maximize reproductive success. Fidelity is also an important behavioural characteristic to consider when hatchery-reared individuals are stocked for species restoration, because artificial rearing environments may interfere with cues that guide appropriate spawning site selection. Acoustic telemetry was used in conjunction with Cormack–Jolly–Seber capture–recapture models to compare degree of spawning site fidelity of wild and hatchery-reared lake trout (Salvelinus namaycush) in northern Lake Huron. Annual survival was estimated to be between 77% and 81% and did not differ among wild and hatchery males and females. Site fidelity estimates were high in both wild and hatchery-reared lake trout (ranging from 0.78 to 0.94, depending on group and time filter), but were slightly lower in hatchery-reared fish than in wild fish. The ecological implication of the small difference in site fidelity between wild and hatchery-reared lake trout is unclear, but similarities in estimates suggest that many hatchery-reared fish use similar spawning sites to wild fish and that most return to those sites annually for spawning.

High-fidelity readout in circuit quantum electrodynamics using the Jaynes-Cummings nonlinearity.

PubMed

Reed, M D; DiCarlo, L; Johnson, B R; Sun, L; Schuster, D I; Frunzio, L; Schoelkopf, R J

2010-10-22

We demonstrate a qubit readout scheme that exploits the Jaynes-Cummings nonlinearity of a superconducting cavity coupled to transmon qubits. We find that, in the strongly driven dispersive regime of this system, there is the unexpected onset of a high-transmission "bright" state at a critical power which depends sensitively on the initial qubit state. A simple and robust measurement protocol exploiting this effect achieves a single-shot fidelity of 87% using a conventional sample design and experimental setup, and at least 61% fidelity to joint correlations of three qubits.

Evolving a polymerase for hydrophobic base analogues.

PubMed

Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

2009-10-21

Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity.

Thomas Gold's Intense Solar Wind; It's evidence in prehistoric petroglyphs recorded along rivers in North and South America

NASA Astrophysics Data System (ADS)

Peratt, A. L.

2008-11-01

A past intense solar outburst and its effect on Earth circa 8,000 BCE was proposed by Gold who based his hypotheses on astronomical and geophysical evidence [1]. The discovery of high-current Z-pinch patterns in Neolithic petroglyphs provides evidence for this occurrence and insight into the origin and meaning of these ancient symbols produced by mankind. These correspond to mankind's visual observations of ancient aurora if the solar wind had increased between one and two orders of magnitude millennia ago [2]. Our data show identical MHD patterns from surveys along 300 km of the Orinoco River (Venezuela), the Chuluut River (Mongolia), the Columbia River (USA), Red Gorge (South Australia) and the Urubamba River (Peru). Three-dimensional, high-fidelity PIC simulations of intense Z-pinches replicate the carved data [3]. 1. T. Gold, Pontificiae Academiae Scientiarvm Scripta Varia, 25, 159, 1962. 2. A. L. Peratt. Trans. Plasma Sci. 35. 778. 2007. 3. A. L. Peratt and W. F. Yao, Physica Scripta, T130, August 2008.

Simulated full-waveform lidar compared to Riegl VZ-400 terrestrial laser scans

NASA Astrophysics Data System (ADS)

Kim, Angela M.; Olsen, Richard C.; Béland, Martin

2016-05-01

A 3-D Monte Carlo ray-tracing simulation of LiDAR propagation models the reflection, transmission and ab- sorption interactions of laser energy with materials in a simulated scene. In this presentation, a model scene consisting of a single Victorian Boxwood (Pittosporum undulatum) tree is generated by the high-fidelity tree voxel model VoxLAD using high-spatial resolution point cloud data from a Riegl VZ-400 terrestrial laser scanner. The VoxLAD model uses terrestrial LiDAR scanner data to determine Leaf Area Density (LAD) measurements for small volume voxels (20 cm sides) of a single tree canopy. VoxLAD is also used in a non-traditional fashion in this case to generate a voxel model of wood density. Information from the VoxLAD model is used within the LiDAR simulation to determine the probability of LiDAR energy interacting with materials at a given voxel location. The LiDAR simulation is defined to replicate the scanning arrangement of the Riegl VZ-400; the resulting simulated full-waveform LiDAR signals compare favorably to those obtained with the Riegl VZ-400 terrestrial laser scanner.

Long-term effects of inducible mutagenic DNA repair on relative fitness and phenotypic diversification in Pseudomonas cichorii 302959.

PubMed

Weigand, Michael R; Sundin, George W

2009-01-01

Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for approximately 500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of "round" and "fuzzy" colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.

The Human Performance Envelope: Past Research, Present Activities and Future Directions

NASA Technical Reports Server (NTRS)

Edwards, Tamsyn

2017-01-01

Air traffic controllers (ATCOs) must maintain a consistently high level of human performance in order to maintain flight safety and efficiency. In current control environments, performance-influencing factors such as workload, fatigue and situation awareness can co-occur, and interact, to effect performance. However, multifactor influences and the association with performance are under-researched. This study utilized a high fidelity human in the loop enroute air traffic control simulation to investigate the relationship between workload, situation awareness and ATCO performance. The study aimed to replicate and extend Edwards, Sharples, Wilson and Kirwans (2012) previous study and confirm multifactor interactions with a participant sample of ex-controllers. The study also aimed to extend Edwards et als previous research by comparing multifactor relationships across 4 automation conditions. Results suggest that workload and SA may interact to produce a cumulative impact on controller performance, although the effect of the interaction on performance may be dependent on the context and amount of automation present. Findings have implications for human-automation teaming in air traffic control, and the potential prediction and support of ATCO performance.

Lethal mutagenesis: targeting the mutator phenotype in cancer.

PubMed

Fox, Edward J; Loeb, Lawrence A

2010-10-01

The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Experimental test of fidelity limits in six-photon interferometry and of rotational invariance properties of the photonic six-qubit entanglement singlet state.

PubMed

Rådmark, Magnus; Zukowski, Marek; Bourennane, Mohamed

2009-10-09

Quantum multiphoton interferometry has now reached the six-photon stage. Thus far, the observed fidelities of entangled states never reached 2/3. We report a high fidelity (estimated at 88%) experiment in which six-qubit singlet correlations were observed. With such a high fidelity we are able to demonstrate the central property of these "singlet" correlations, their "rotational invariance," by performing a full set of measurements in three complementary polarization bases. The patterns are almost indistinguishable. The data reveal genuine six-photon entanglement. We also study several five-photon states, which result upon detection of one of the photons. Multiphoton singlet states survive some types of depolarization and are thus important in quantum communication schemes.

Multiple displacement amplification in combination with high-fidelity PCR improves detection of bacteria from single females or eggs of Metaseiulus occidentalis (Nesbitt) (Acari: Phytoseiidae).

PubMed

Jeyaprakash, Ayyamperumal; Hoy, Marjorie A

2004-07-01

Amplifying microbial DNA by the polymerase chain reaction (PCR) from single phytoseiid mites has been difficult, perhaps due to the low titer of bacteria and to interference by the relatively larger amounts of mite genomic DNA. In this paper we evaluate the efficiency of standard and high-fidelity PCR protocols subsequent to amplification of the whole genome by a multiple displacement amplification (MDA) procedure developed by Dean et al. DNA from the phytoseiid Phytoseiulus persimilis (Athias-Henriot) was tested because it lacks a Cytophaga-like organism (CLO) and we could add known amounts of a plasmid containing a cloned 16S rRNA gene fragment from a CLO from Metaseiulus occidentalis (Nesbitt). P. persimilis genomic DNA was mixed with the serially diluted plasmid and amplified using MDA followed by either standard or high-fidelity PCR. MDA followed by high-fidelity PCR was most efficient and successfully amplified an expected 1.5-kb band from as little as 0.01fg of the plasmid, which is equivalent to about 1 copy. MDA followed by high-fidelity PCR also consistently amplified Wolbachia- or CLO-specific products from naturally infected single females or eggs of M. occidentalis, which will allow detailed studies of infection frequency and transmission of several microorganisms associated with this predatory mite.

Degrees of reality: airway anatomy of high-fidelity human patient simulators and airway trainers.

PubMed

Schebesta, Karl; Hüpfl, Michael; Rössler, Bernhard; Ringl, Helmut; Müller, Michael P; Kimberger, Oliver

2012-06-01

Human patient simulators and airway training manikins are widely used to train airway management skills to medical professionals. Furthermore, these patient simulators are employed as standardized "patients" to evaluate airway devices. However, little is known about how realistic these patient simulators and airway-training manikins really are. This trial aimed to evaluate the upper airway anatomy of four high-fidelity patient simulators and two airway trainers in comparison with actual patients by means of radiographic measurements. The volume of the pharyngeal airspace was the primary outcome parameter. Computed tomography scans of 20 adult trauma patients without head or neck injuries were compared with computed tomography scans of four high-fidelity patient simulators and two airway trainers. By using 14 predefined distances, two cross-sectional areas and three volume parameters of the upper airway, the manikins' similarity to a human patient was assessed. The pharyngeal airspace of all manikins differed significantly from the patients' pharyngeal airspace. The HPS Human Patient Simulator (METI®, Sarasota, FL) was the most realistic high-fidelity patient simulator (6/19 [32%] of all parameters were within the 95% CI of human airway measurements). The airway anatomy of four high-fidelity patient simulators and two airway trainers does not reflect the upper airway anatomy of actual patients. This finding may impact airway training and confound comparative airway device studies.

A weighted variational gradient-based fusion method for high-fidelity thin cloud removal of Landsat images

NASA Astrophysics Data System (ADS)

Huang, Wei; Chen, Xiu; Wang, Yueyun

2018-03-01

Landsat data are widely used in various earth observations, but the clouds interfere with the applications of the images. This paper proposes a weighted variational gradient-based fusion method (WVGBF) for high-fidelity thin cloud removal of Landsat images, which is an improvement of the variational gradient-based fusion (VGBF) method. The VGBF method integrates the gradient information from the reference band into visible bands of cloudy image to enable spatial details and remove thin clouds. The VGBF method utilizes the same gradient constraints to the entire image, which causes the color distortion in cloudless areas. In our method, a weight coefficient is introduced into the gradient approximation term to ensure the fidelity of image. The distribution of weight coefficient is related to the cloud thickness map. The map is built on Independence Component Analysis (ICA) by using multi-temporal Landsat images. Quantitatively, we use R value to evaluate the fidelity in the cloudless regions and metric Q to evaluate the clarity in the cloud areas. The experimental results indicate that the proposed method has the better ability to remove thin cloud and achieve high fidelity.

Development and validation of the ASPIRE-VA coaching fidelity checklist (ACFC): a tool to help ensure delivery of high-quality weight management interventions.

PubMed

Damschroder, Laura J; Goodrich, David E; Kim, Hyungjin Myra; Holleman, Robert; Gillon, Leah; Kirsh, Susan; Richardson, Caroline R; Lutes, Lesley D

2016-09-01

Practical and valid instruments are needed to assess fidelity of coaching for weight loss. The purpose of this study was to develop and validate the ASPIRE Coaching Fidelity Checklist (ACFC). Classical test theory guided ACFC development. Principal component analyses were used to determine item groupings. Psychometric properties, internal consistency, and inter-rater reliability were evaluated for each subscale. Criterion validity was tested by predicting weight loss as a function of coaching fidelity. The final 19-item ACFC consists of two domains (session process and session structure) and five subscales (sets goals and monitor progress, assess and personalize self-regulatory content, manages the session, creates a supportive and empathetic climate, and stays on track). Four of five subscales showed high internal consistency (Cronbach alphas > 0.70) for group-based coaching; only two of five subscales had high internal reliability for phone-based coaching. All five sub-scales were positively and significantly associated with weight loss for group- but not for phone-based coaching. The ACFC is a reliable and valid instrument that can be used to assess fidelity and guide skill-building for weight management interventionists.

The use of virtual patient scenarios as a vehicle for teaching professionalism.

PubMed

Marei, H F; Al-Eraky, M M; Almasoud, N N; Donkers, J; Van Merrienboer, J J G

2018-05-01

This study aimed to measure students' perceptions of virtual patient scenarios (VPs) for developing ethical reasoning skills and to explore features in VP design that are necessary to promote professionalism. Sixty-five dental students participated in learning sessions that involved collaborative practice with five VPs (four high fidelity and one low fidelity), followed by reflection sessions. Students' perceptions towards the use of VPs in developing ethical reasoning skills were assessed using a questionnaire that involved 10 closed and three open-ended questions. High-fidelity VPs were perceived as significantly better for developing ethical reasoning skills than low-fidelity VPs. Analyses of answers to open-ended questions revealed two new features that are specific for VPs intended for teaching professionalism, which are VP dramatic structure and how it should end. VPs intended for teaching professionalism need to have high fidelity, follow a specific dramatic structure and should include multiple plausible endings. The use of VPs as part of a collaborative activity that is followed by a reflection session is perceived as an effective tool for the development of ethical reasoning skills in dental education. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-Fidelity Multidisciplinary Design Optimization of Aircraft Configurations

NASA Technical Reports Server (NTRS)

Martins, Joaquim R. R. A.; Kenway, Gaetan K. W.; Burdette, David; Jonsson, Eirikur; Kennedy, Graeme J.

2017-01-01

To evaluate new airframe technologies we need design tools based on high-fidelity models that consider multidisciplinary interactions early in the design process. The overarching goal of this NRA is to develop tools that enable high-fidelity multidisciplinary design optimization of aircraft configurations, and to apply these tools to the design of high aspect ratio flexible wings. We develop a geometry engine that is capable of quickly generating conventional and unconventional aircraft configurations including the internal structure. This geometry engine features adjoint derivative computation for efficient gradient-based optimization. We also added overset capability to a computational fluid dynamics solver, complete with an adjoint implementation and semiautomatic mesh generation. We also developed an approach to constraining buffet and started the development of an approach for constraining utter. On the applications side, we developed a new common high-fidelity model for aeroelastic studies of high aspect ratio wings. We performed optimal design trade-o s between fuel burn and aircraft weight for metal, conventional composite, and carbon nanotube composite wings. We also assessed a continuous morphing trailing edge technology applied to high aspect ratio wings. This research resulted in the publication of 26 manuscripts so far, and the developed methodologies were used in two other NRAs. 1

What Information is Stored in DNA: Does it Contain Digital Error Correcting Codes?

NASA Astrophysics Data System (ADS)

Liebovitch, Larry

1998-03-01

The longest term correlations in living systems are the information stored in DNA which reflects the evolutionary history of an organism. The 4 bases (A,T,G,C) encode sequences of amino acids as well as locations of binding sites for proteins that regulate DNA. The fidelity of this important information is maintained by ANALOG error check mechanisms. When a single strand of DNA is replicated the complementary base is inserted in the new strand. Sometimes the wrong base is inserted that sticks out disrupting the phosphate backbone. The new base is not yet methylated, so repair enzymes, that slide along the DNA, can tear out the wrong base and replace it with the right one. The bases in DNA form a sequence of 4 different symbols and so the information is encoded in a DIGITAL form. All the digital codes in our society (ISBN book numbers, UPC product codes, bank account numbers, airline ticket numbers) use error checking code, where some digits are functions of other digits to maintain the fidelity of transmitted informaiton. Does DNA also utitlize a DIGITAL error chekcing code to maintain the fidelity of its information and increase the accuracy of replication? That is, are some bases in DNA functions of other bases upstream or downstream? This raises the interesting mathematical problem: How does one determine whether some symbols in a sequence of symbols are a function of other symbols. It also bears on the issue of determining algorithmic complexity: What is the function that generates the shortest algorithm for reproducing the symbol sequence. The error checking codes most used in our technology are linear block codes. We developed an efficient method to test for the presence of such codes in DNA. We coded the 4 bases as (0,1,2,3) and used Gaussian elimination, modified for modulus 4, to test if some bases are linear combinations of other bases. We used this method to analyze the base sequence in the genes from the lac operon and cytochrome C. We did not find evidence for such error correcting codes in these genes. However, we analyzed only a small amount of DNA and if digitial error correcting schemes are present in DNA, they may be more subtle than such simple linear block codes. The basic issue we raise here, is how information is stored in DNA and an appreciation that digital symbol sequences, such as DNA, admit of interesting schemes to store and protect the fidelity of their information content. Liebovitch, Tao, Todorov, Levine. 1996. Biophys. J. 71:1539-1544. Supported by NIH grant EY6234.

Competency: Does High Fidelity Simulation Make a Difference?

ERIC Educational Resources Information Center

Valente, Alice M.

2010-01-01

High fidelity simulation is a well documented adjunctive teaching method in medical and nurse practitioner programs, but few studies of effectiveness on this technology on the development of competency have emphasized pre-licensure associate degree level programs. This study explored student competency in the application of the nursing process…

Using nonfaculty registered nurses to facilitate high-fidelity human patient simulation activities.

PubMed

Foster, Janet G; Sheriff, Susan; Cheney, Susan

2008-01-01

Maximizing faculty resources using nonfaculty registered nurses to supervise high-fidelity human-patient simulation is an innovative strategy for addressing the nursing faculty shortage and preparing graduates to practice safely in hospitals. The authors describe their use of nonfaculty registered nurses and its outcomes.

Tidal Energy Resource Assessment for McMurdo Station, Antarctica

DTIC Science & Technology

2016-12-01

highest power coefficient possible, only to provide a high- fidelity data set for a simple geometry turbine model at reasonably high blade chord Reynolds...highest power coefficient possible, only to provide a high-fidelity data set for a simple geometry turbine model at reasonably high blade chord...Reynolds numbers. Tip speed ratio, , is defined as = where is the anglular velocity of the blade and is the

Web-Based versus High-Fidelity Simulation Training for Certified Registered Nurse Anesthetists in the Management of High Risk/Low Occurrence Anesthesia Events

ERIC Educational Resources Information Center

Kimemia, Judy

2017-01-01

Purpose: The purpose of this project was to compare web-based to high-fidelity simulation training in the management of high risk/low occurrence anesthesia related events, to enhance knowledge acquisition for Certified Registered Nurse Anesthetists (CRNAs). This project was designed to answer the question: Is web-based training as effective as…

Understanding DNA Repair in Hyperthermophilic Archaea: Persistent Gaps and Other Reasons to Focus on the Fork

PubMed Central

Grogan, Dennis W.

2015-01-01

Although hyperthermophilic archaea arguably have a great need for efficient DNA repair, they lack members of several DNA repair protein families broadly conserved among bacteria and eukaryotes. Conversely, the putative DNA repair genes that do occur in these archaea often do not generate the expected phenotype when deleted. The prospect that hyperthermophilic archaea have some unique strategies for coping with DNA damage and replication errors has intellectual and technological appeal, but resolving this question will require alternative coping mechanisms to be proposed and tested experimentally. This review evaluates a combination of four enigmatic properties that distinguishes the hyperthermophilic archaea from all other organisms: DNA polymerase stalling at dU, apparent lack of conventional NER, lack of MutSL homologs, and apparent essentiality of homologous recombination proteins. Hypothetical damage-coping strategies that could explain this set of properties may provide new starting points for efforts to define how archaea differ from conventional models of DNA repair and replication fidelity. PMID:26146487

In-line characterization of nanostructured mass-produced polymer components using scatterometry

NASA Astrophysics Data System (ADS)

Skovlund Madsen, Jonas; Højlund Thamdrup, Lasse; Czolkos, Ilja; Hansen, Poul Erik; Johansson, Alicia; Garnaes, Jørgen; Nygård, Jesper; Hannibal Madsen, Morten

2017-08-01

Scatterometry is used as an in-line metrology solution for injection molded nanostructures to evaluate the pattern replication fidelity. The method is used to give direct feedback to an operator when testing new molding parameters and for continuous quality control. A compact scatterometer has been built and tested at a fabrication facility. The scatterometry measurements, including data analysis and handling of the samples, are much faster than the injection molding cycle time, and thus, characterization does not slow down the production rate. Fabrication and characterization of 160 plastic parts with line gratings are presented here, and the optimal molding temperatures for replication of nanostructures are found for two polymers. Scatterometry results are compared to state of the art metrology solutions: atomic force and scanning electron microscopy. It is demonstrated that the scatterometer can determine the structural parameters of the samples with an accuracy of a few nanometers in less than a second, thereby enabling in-line characterization.

Regulation of error-prone translesion synthesis by Spartan/C1orf124

PubMed Central

Kim, Myoung Shin; Machida, Yuka; Vashisht, Ajay A.; Wohlschlegel, James A.; Pang, Yuan-Ping; Machida, Yuichi J.

2013-01-01

Translesion synthesis (TLS) employs low fidelity polymerases to replicate past damaged DNA in a potentially error-prone process. Regulatory mechanisms that prevent TLS-associated mutagenesis are unknown; however, our recent studies suggest that the PCNA-binding protein Spartan plays a role in suppression of damage-induced mutagenesis. Here, we show that Spartan negatively regulates error-prone TLS that is dependent on POLD3, the accessory subunit of the replicative DNA polymerase Pol δ. We demonstrate that the putative zinc metalloprotease domain SprT in Spartan directly interacts with POLD3 and contributes to suppression of damage-induced mutagenesis. Depletion of Spartan induces complex formation of POLD3 with Rev1 and the error-prone TLS polymerase Pol ζ, and elevates mutagenesis that relies on POLD3, Rev1 and Pol ζ. These results suggest that Spartan negatively regulates POLD3 function in Rev1/Pol ζ-dependent TLS, revealing a previously unrecognized regulatory step in error-prone TLS. PMID:23254330

Environmental-stress-induced Chromatin Regulation and its Heritability

PubMed Central

Fang, Lei; Wuptra, Kenly; Chen, Danqi; Li, Hongjie; Huang, Shau-Ku; Jin, Chunyuan; Yokoyama, Kazunari K

2014-01-01

Chromatin is subject to proofreading and repair mechanisms during the process of DNA replication, as well as repair to maintain genetic and epigenetic information and genome stability. The dynamic structure of chromatin modulates various nuclear processes, including transcription and replication, by altering the accessibility of the DNA to regulatory factors. Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodeling of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by controlling stochastic switching of chromatin structure and dynamics in response to the environmental disruptors and endogenous stresses. The dynamic chromatin remodeling can, therefore, serve as a sensor, through which environmental and/or metabolic agents can alter gene expression, leading to global cellular changes involving multiple interactive networks. Furthermore its recent evidence also suggests that the epigenetic changes are heritable during the development. This review will discuss the environmental sensing system for chromatin regulation and genetic and epigenetic controls from developmental perspectives. PMID:25045581

CTF (Subchannel) Calculations and Validation L3:VVI.H2L.P15.01

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

Gordon, Natalie

The goal of the Verification and Validation Implementation (VVI) High to Low (Hi2Lo) process is utilizing a validated model in a high resolution code to generate synthetic data for improvement of the same model in a lower resolution code. This process is useful in circumstances where experimental data does not exist or it is not sufficient in quantity or resolution. Data from the high-fidelity code is treated as calibration data (with appropriate uncertainties and error bounds) which can be used to train parameters that affect solution accuracy in the lower-fidelity code model, thereby reducing uncertainty. This milestone presents a demonstrationmore » of the Hi2Lo process derived in the VVI focus area. The majority of the work performed herein describes the steps of the low-fidelity code used in the process with references to the work detailed in the companion high-fidelity code milestone (Reference 1). The CASL low-fidelity code used to perform this work was Cobra Thermal Fluid (CTF) and the high-fidelity code was STAR-CCM+ (STAR). The master branch version of CTF (pulled May 5, 2017 – Reference 2) was utilized for all CTF analyses performed as part of this milestone. The statistical and VVUQ components of the Hi2Lo framework were performed using Dakota version 6.6 (release date May 15, 2017 – Reference 3). Experimental data from Westinghouse Electric Company (WEC – Reference 4) was used throughout the demonstrated process to compare with the high-fidelity STAR results. A CTF parameter called Beta was chosen as the calibration parameter for this work. By default, Beta is defined as a constant mixing coefficient in CTF and is essentially a tuning parameter for mixing between subchannels. Since CTF does not have turbulence models like STAR, Beta is the parameter that performs the most similar function to the turbulence models in STAR. The purpose of the work performed in this milestone is to tune Beta to an optimal value that brings the CTF results closer to those measured in the WEC experiments.« less

Evaluation of Intervention Fidelity in a Multisite Clinical Trial in Persons With Multiple Sclerosis.

PubMed

Morrison, Janet D; Becker, Heather; Stuifbergen, Alexa K

2017-12-01

Careful consideration of intervention fidelity is critical to establishing the validity and reliability of research findings, yet such reports are often lacking in the research literature. It is imperative that intervention fidelity be methodically evaluated and reported to promote the translation of effective interventions into sound evidence-based practice. The purpose of this article is to explore strategies used to promote intervention fidelity, incorporating examples from a multisite clinical trial, that illustrate the National Institutes of Health Behavior Change Consortium's 5 domains for recommended treatment practices: (1) study design, (2) facilitator training, (3) intervention delivery, (4) intervention receipt, and (5) intervention enactment. A multisite randomized clinical trial testing the efficacy of a computer-assisted cognitive rehabilitation intervention for adults with multiple sclerosis is used to illustrate strategies promoting intervention fidelity. Data derived from audiotapes of intervention classes, audits of computer exercises completed by participants, participant class attendance, and goal attainment scaling suggested relatively high fidelity to the intervention protocol. This study illustrates how to report intervention fidelity in the literature guided by best practice strategies, which may serve to promote fidelity monitoring and reporting in future studies.

RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

PubMed Central

Xu, Liang; Wang, Wei; Chong, Jenny; Shin, Ji Hyun; Xu, Jun; Wang, Dong

2016-01-01

Accurate genetic information transfer is essential for life. As a key enzyme involved in the first step of gene expression, RNA polymerase II (Pol II) must maintain high transcriptional fidelity while it reads along DNA template and synthesizes RNA transcript in a stepwise manner during transcription elongation. DNA lesions or modifications may lead to significant changes in transcriptional fidelity or transcription elongation dynamics. In this review, we will summarize recent progress towards understanding the molecular basis of RNA Pol II transcriptional fidelity control and impacts of DNA lesions and modifications on Pol II transcription elongation. PMID:26392149

High fidelity simulations of infrared imagery with animated characters

NASA Astrophysics Data System (ADS)

Näsström, F.; Persson, A.; Bergström, D.; Berggren, J.; Hedström, J.; Allvar, J.; Karlsson, M.

2012-06-01

High fidelity simulations of IR signatures and imagery tend to be slow and do not have effective support for animation of characters. Simplified rendering methods based on computer graphics methods can be used to overcome these limitations. This paper presents a method to combine these tools and produce simulated high fidelity thermal IR data of animated people in terrain. Infrared signatures for human characters have been calculated using RadThermIR. To handle multiple character models, these calculations use a simplified material model for the anatomy and clothing. Weather and temperature conditions match the IR-texture used in the terrain model. The calculated signatures are applied to the animated 3D characters that, together with the terrain model, are used to produce high fidelity IR imagery of people or crowds. For high level animation control and crowd simulations, HLAS (High Level Animation System) has been developed. There are tools available to create and visualize skeleton based animations, but tools that allow control of the animated characters on a higher level, e.g. for crowd simulation, are usually expensive and closed source. We need the flexibility of HLAS to add animation into an HLA enabled sensor system simulation framework.

Developing an instrument for assessing fidelity of motivational care planning: The Aboriginal and Islander Mental health initiative adherence scale.

PubMed

Prowse, Phuong-Tu; Nagel, Tricia

2014-01-01

The aim of this study was to design and trial an Adherence Scale to measure fidelity of Motivational Care Planning (MCP) within a clinical trial. This culturally adapted therapy MCP uses a client centered holistic approach that emphasises family and culture to motivate healthy life style changes. The Motivational Care Planning-Adherence Scale (MCP-AS) was developed through consultation with Aboriginal and Islander Mental Health Initiative (AIMhi) Indigenous and non-Indigenous trainers, and review of MCP training resources. The resultant ten-item scale incorporates a 9-Point Likert Scale with a supporting protocol manual and uses objective, behaviourally anchored criteria for each scale point. A fidelity assessor piloted the tool through analysis of four audio-recordings of MCP (conducted by Indigenous researchers within a study in remote communities in Northern Australia). File audits of the remote therapy sessions were utilised as an additional source of information. A Gold Standard Motivational Care Planning training video was also assessed using the MCP-AS. The Motivational Care Planning-Adherence Scale contains items measuring both process and content of therapy sessions. This scale was used successfully to assess therapy through observation of audio or video-recorded sessions and review of clinical notes. Treatment fidelity measured by the MCP-AS within the pilot study indicated high fidelity ratings. Ratings were high across the three domains of rapport, motivation, and self-management with especially high ratings for positive feedback and engagement, review of stressors and goal setting. The Motivational Care Planning-Adherence Scale has the potential to provide a measure of quality of delivery of Motivation Care Planning. The pilot findings suggest that despite challenges within the remote Indigenous community setting, Indigenous therapists delivered therapy that was of high fidelity. While developed as a research tool, the scale has the potential to support fidelity of delivery of Motivation Care Planning in clinical, supervision and training settings. Larger studies are needed to establish inter-rater reliability and internal and external validity.

END-DIASTOLIC FLOW REVERSAL LIMITS THE EFFICACY OF PEDIATRIC INTRAAORTIC BALLOON PUMP COUNTERPULSATION

PubMed Central

Bartoli, Carlo R.; Rogers, Benjamin D.; Ionan, Constantine E.; Koenig, Steven C.; Pantalos, George M.

2013-01-01

OBJECTIVE Counterpulsation with an intraaortic balloon pump (IABP) has not achieved the same successes or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. METHODS In Yorkshire piglets (n=19, 13.0±0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7cc) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with microspheres. RESULTS Despite significant suprasystolic diastolic augmentation and afterload reduction at heart rates of 105±3bmp, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. CONCLUSIONS Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted. PMID:24139614

End-diastolic flow reversal limits the efficacy of pediatric intra-aortic balloon pump counterpulsation.

PubMed

Bartoli, Carlo R; Rogers, Benjamin D; Ionan, Constantine E; Pantalos, George M

2014-05-01

Counterpulsation with an intra-aortic balloon pump (IABP) has not achieved the same success or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. In Yorkshire piglets (n = 19; weight, 13.0 ± 0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7 mL) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with microspheres. Despite significant suprasystolic diastolic augmentation and afterload reduction at heart rates of 105 ± 3 beats per minute, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Multifunctional Collaborative Modeling and Analysis Methods in Engineering Science

NASA Technical Reports Server (NTRS)

Ransom, Jonathan B.; Broduer, Steve (Technical Monitor)

2001-01-01

Engineers are challenged to produce better designs in less time and for less cost. Hence, to investigate novel and revolutionary design concepts, accurate, high-fidelity results must be assimilated rapidly into the design, analysis, and simulation process. This assimilation should consider diverse mathematical modeling and multi-discipline interactions necessitated by concepts exploiting advanced materials and structures. Integrated high-fidelity methods with diverse engineering applications provide the enabling technologies to assimilate these high-fidelity, multi-disciplinary results rapidly at an early stage in the design. These integrated methods must be multifunctional, collaborative, and applicable to the general field of engineering science and mechanics. Multifunctional methodologies and analysis procedures are formulated for interfacing diverse subdomain idealizations including multi-fidelity modeling methods and multi-discipline analysis methods. These methods, based on the method of weighted residuals, ensure accurate compatibility of primary and secondary variables across the subdomain interfaces. Methods are developed using diverse mathematical modeling (i.e., finite difference and finite element methods) and multi-fidelity modeling among the subdomains. Several benchmark scalar-field and vector-field problems in engineering science are presented with extensions to multidisciplinary problems. Results for all problems presented are in overall good agreement with the exact analytical solution or the reference numerical solution. Based on the results, the integrated modeling approach using the finite element method for multi-fidelity discretization among the subdomains is identified as most robust. The multiple-method approach is advantageous when interfacing diverse disciplines in which each of the method's strengths are utilized. The multifunctional methodology presented provides an effective mechanism by which domains with diverse idealizations are interfaced. This capability rapidly provides the high-fidelity results needed in the early design phase. Moreover, the capability is applicable to the general field of engineering science and mechanics. Hence, it provides a collaborative capability that accounts for interactions among engineering analysis methods.

High-Fidelity Rapid Initialization and Read-Out of an Electron Spin via the Single Donor D(-) Charge State.

PubMed

Watson, T F; Weber, B; House, M G; Büch, H; Simmons, M Y

2015-10-16

We demonstrate high-fidelity electron spin read-out of a precision placed single donor in silicon via spin selective tunneling to either the D(+) or D(-) charge state of the donor. By performing read-out at the stable two electron D(0)↔D(-) charge transition we can increase the tunnel rates to a nearby single electron transistor charge sensor by nearly 2 orders of magnitude, allowing faster qubit read-out (1 ms) with minimum loss in read-out fidelity (98.4%) compared to read-out at the D(+)↔D(0) transition (99.6%). Furthermore, we show that read-out via the D(-) charge state can be used to rapidly initialize the electron spin qubit in its ground state with a fidelity of F(I)=99.8%.

Measures of fidelity of delivery of, and engagement with, complex, face-to-face health behaviour change interventions: A systematic review of measure quality.

PubMed

Walton, Holly; Spector, Aimee; Tombor, Ildiko; Michie, Susan

2017-11-01

Understanding the effectiveness of complex, face-to-face health behaviour change interventions requires high-quality measures to assess fidelity of delivery and engagement. This systematic review aimed to (1) identify the types of measures used to monitor fidelity of delivery of, and engagement with, complex, face-to-face health behaviour change interventions and (2) describe the reporting of psychometric and implementation qualities. Electronic databases were searched, systematic reviews and reference lists were hand-searched, and 21 experts were contacted to identify articles. Studies that quantitatively measured fidelity of delivery of, and/or engagement with, a complex, face-to-face health behaviour change intervention for adults were included. Data on interventions, measures, and psychometric and implementation qualities were extracted and synthesized using narrative analysis. Sixty-six studies were included: 24 measured both fidelity of delivery and engagement, 20 measured fidelity of delivery, and 22 measured engagement. Measures of fidelity of delivery included observation (n = 17; 38.6%), self-report (n = 15; 34%), quantitatively rated qualitative interviews (n = 1; 2.3%), or multiple measures (n = 11; 25%). Measures of engagement included self-report (n = 18; 39.1%), intervention records (n = 11; 24%), or multiple measures (n = 17; 37%). Fifty-one studies (77%) reported at least one psychometric or implementation quality; 49 studies (74.2%) reported at least one psychometric quality, and 17 studies (25.8%) reported at least one implementation quality. Fewer than half of the reviewed studies measured both fidelity of delivery of, and engagement with complex, face-to-face health behaviour change interventions. More studies reported psychometric qualities than implementation qualities. Interpretation of intervention outcomes from fidelity of delivery and engagement measurements may be limited due to a lack of reporting of psychometric and implementation qualities. Statement of contribution What is already known on this subject? Evidence of fidelity and engagement is needed to understand effectiveness of complex interventions Evidence of fidelity and engagement are rarely reported High-quality measures are needed to measure fidelity and engagement What does this study add? Evidence that indicators of quality of measures are reported in some studies Evidence that psychometric qualities are reported more frequently than implementation qualities A recommendation for intervention evaluations to report indicators of quality of fidelity and engagement measures. © 2017 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Spin qubit transport in a double quantum dot

NASA Astrophysics Data System (ADS)

Zhao, Xinyu; Hu, Xuedong

Long distance spin communication is a crucial ingredient to scalable quantum computer architectures based on electron spin qubits. One way to transfer spin information over a long distance on chip is via electron transport. Here we study the transport of an electron spin qubit in a double quantum dot by tuning the interdot detuning voltage. We identify a parameter regime where spin relaxation hot-spots can be avoided and high-fidelity spin transport is possible. Within this parameter space, the spin transfer fidelity is determined by the operation speed and the applied magnetic field. In particular, near zero detuning, a proper choice of operation speed is essential to high fidelity. In addition, we also investigate the modification of the effective g-factor by the interdot detuning, which could lead to a phase error between spin up and down states. The results presented in this work could be a useful guidance for experimentally achieving high-fidelity spin qubit transport. We thank financial support by US ARO via Grant W911NF1210609.

The Relationship Between Fidelity and Learning in Aviation Training and Assessment

NASA Technical Reports Server (NTRS)

Noble, Cliff

2002-01-01

Flight simulators can be designed to train pilots or assess their flight performance. Low-Fidelity simulators maximize the initial learning rate of novice pilots and minimize initial costs; whereas, expensive, high-fidelity simulators predict the realworld in-flight performance of expert pilots (Fink & Shriver, 1978 Hays & Singer 1989; Kinkade & Wheaton. 1972). Although intuitively appealing and intellectually convenient to generalize concepts of learning and assessment, what holds true for the role of fidelity in assessment may not always hold true for learning, and vice versa. To bring clarity to this issue, the author distinguishes the role of fidelity in learning from its role in assessment as a function of skill level by applying the hypothesis of Alessi (1988) and reviewing the Laughery, Ditzian, and Houtman (1982) study on simulator validity. Alessi hypothesized that there is it point beyond which one additional unit of flight-simulator fidelity results in a diminished rate of learning. The author of this current paper also suggests the existence of an optimal point beyond which one additional unit of flight-simulator fidelity results in a diminished rate of practical assessment of nonexpert pilot performance.

High fidelity quantum gates with vibrational qubits.

PubMed

Berrios, Eduardo; Gruebele, Martin; Shyshlov, Dmytro; Wang, Lei; Babikov, Dmitri

2012-11-26

Physical implementation of quantum gates acting on qubits does not achieve a perfect fidelity of 1. The actual output qubit may not match the targeted output of the desired gate. According to theoretical estimates, intrinsic gate fidelities >99.99% are necessary so that error correction codes can be used to achieve perfect fidelity. Here we test what fidelity can be accomplished for a CNOT gate executed by a shaped ultrafast laser pulse interacting with vibrational states of the molecule SCCl(2). This molecule has been used as a test system for low-fidelity calculations before. To make our test more stringent, we include vibrational levels that do not encode the desired qubits but are close enough in energy to interfere with population transfer by the laser pulse. We use two complementary approaches: optimal control theory determines what the best possible pulse can do; a more constrained physical model calculates what an experiment likely can do. Optimal control theory finds pulses with fidelity >0.9999, in excess of the quantum error correction threshold with 8 × 10(4) iterations. On the other hand, the physical model achieves only 0.9992 after 8 × 10(4) iterations. Both calculations converge as an inverse power law toward unit fidelity after >10(2) iterations/generations. In principle, the fidelities necessary for quantum error correction are reachable with qubits encoded by molecular vibrations. In practice, it will be challenging with current laboratory instrumentation because of slow convergence past fidelities of 0.99.

Achieving pattern uniformity in plasmonic lithography by spatial frequency selection

NASA Astrophysics Data System (ADS)

Liang, Gaofeng; Chen, Xi; Zhao, Qing; Guo, L. Jay

2018-01-01

The effects of the surface roughness of thin films and defects on photomasks are investigated in two representative plasmonic lithography systems: thin silver film-based superlens and multilayer-based hyperbolic metamaterial (HMM). Superlens can replicate arbitrary patterns because of its broad evanescent wave passband, which also makes it inherently vulnerable to the roughness of the thin film and imperfections of the mask. On the other hand, the HMM system has spatial frequency filtering characteristics and its pattern formation is based on interference, producing uniform and stable periodic patterns. In this work, we show that the HMM system is more immune to such imperfections due to its function of spatial frequency selection. The analyses are further verified by an interference lithography system incorporating the photoresist layer as an optical waveguide to improve the aspect ratio of the pattern. It is concluded that a system capable of spatial frequency selection is a powerful method to produce deep-subwavelength periodic patterns with high degree of uniformity and fidelity.

Lessons learned: a pilot study on occupational therapy effectiveness for children with sensory modulation disorder.

PubMed

Miller, Lucy Jane; Schoen, Sarah A; James, Katherine; Schaaf, Roseann C

2007-01-01

The purpose of this pilot study was to prepare for a randomized controlled study of the effectiveness of occupational therapy using a sensory integration approach (OT-SI) with children who have sensory processing disorders (SPD). A one-group pretest, posttest design with 30 children was completed with a subset of children with SPD, those with sensory modulation disorder. Lessons learned relate to (a) identifying a homogeneous sample with quantifiable inclusion criteria, (b) developing an intervention manual for study replication and a fidelity to treatment measure, (c) determining which outcomes are sensitive to change and relate to parents' priorities, and (d) clarifying rigorous methodologies (e.g., blinded examiners, randomization, power). A comprehensive program of research is needed, including multiple pilot studies to develop enough knowledge that high-quality effectiveness research in occupational therapy can be completed. Previous effectiveness studies in OT-SI have been single projects not based on a unified long-term program of research.

Rapid evolution of the human mutation spectrum

PubMed Central

Harris, Kelley; Pritchard, Jonathan K

2017-01-01

DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely related populations. Close examination of one signal, an increased TCC→TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate. Our results suggest that mutation rates can evolve markedly over short evolutionary timescales and suggest the possibility of mapping mutational modifiers. DOI: http://dx.doi.org/10.7554/eLife.24284.001 PMID:28440220

Transfer molding processes for nanoscale patterning of poly-L-lactic acid (PLLA) films

NASA Astrophysics Data System (ADS)

Dhakal, Rabin; Peer, Akshit; Biswas, Rana; Kim, Jaeyoun

2016-03-01

Nanoscale patterned structures composed of biomaterials exhibit great potential for the fabrication of functional biostructures. In this paper, we report cost-effective, rapid, and highly reproducible soft lithographic transfer-molding techniques for creating periodic micro- and nano-scale textures on poly (L-lactic acid) (PLLA) surface. These artificial textures can increase the overall surface area and change the release dynamics of the therapeutic agents coated on it. Specifically, we use the double replication technique in which the master pattern is first transferred to the PDMS mold and the pattern on PDMS is then transferred to the PLLA films through drop-casting as well as nano-imprinting. The ensuing comparison studies reveal that the drop-cast PLLA allows pattern transfer at higher levels of fidelity, enabling the realization of nano-hole and nano-cone arrays with pitch down to ~700 nm. The nano-patterned PLLA film was then coated with rapamycin to make it drug-eluting.

RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.

PubMed

Xiao, Yinghong; Rouzine, Igor M; Bianco, Simone; Acevedo, Ashley; Goldstein, Elizabeth Faul; Farkov, Mikhail; Brodsky, Leonid; Andino, Raul

2016-04-13

Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

High Fidelity: Investing in Evaluation Training. Ask the Team

ERIC Educational Resources Information Center

Fetters, Jenni

2013-01-01

High-quality training is a crucial investment in establishing and maintaining implementation fidelity as well as building educators' trust in the new process. Training approaches for educator evaluation vary both in format (i.e., how it's delivered) and content (i.e., what is provided). Train-the-trainer sessions, online professional learning…

76 FR 60047 - Agency Information Collection Activities; Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... Response: Periodic. Total Annual Labor Cost: $18,300 per year ($12,900 for testing + $5,400 for disclosures... and Estimated Burden: (a) Testing--High fidelity manufacturers--300 new products/year x 1 hour each = 300 hours; and (b) Disclosures--High fidelity manufacturers--[(300 new products/ year x 1...

Exploring Interprofessional Education through a High-Fidelity Human Patient Simulation Scenario: A Mixed Methods Study

ERIC Educational Resources Information Center

Rossler, Kelly Lynn

2013-01-01

High-fidelity human patient simulation has emerged as a valuable medium to reinforce educational content within programs of nursing. As simulation learning experiences have been identified as augmenting both didactic lecture content and clinical learning, these experiences have expanded to incorporate interprofessional education. Review of…

The Impact of Human Patient Simulation on the Attainment of Learning Outcomes

ERIC Educational Resources Information Center

Re, Antonio

2011-01-01

Human patient simulation, and more specifically, high fidelity patient simulation is a growing teaching technique that enables students in medical and health related professions to learn through interacting with a simulator. This study examined the uses of high fidelity simulation with 106 students enrolled in nursing and respiratory therapist…

The Development of the Simulation Thinking Rubric

ERIC Educational Resources Information Center

Doolen, Jessica

2012-01-01

High fidelity simulation has become a widespread and costly learning strategy in nursing education because it can fill the gap left by a shortage of clinical sites. In addition, high fidelity simulation is an active learning strategy that is thought to increase higher order thinking such as clinical reasoning and judgment skills in nursing…

Framework for Multidisciplinary Analysis, Design, and Optimization with High-Fidelity Analysis Tools

NASA Technical Reports Server (NTRS)

Orr, Stanley A.; Narducci, Robert P.

2009-01-01

A plan is presented for the development of a high fidelity multidisciplinary optimization process for rotorcraft. The plan formulates individual disciplinary design problems, identifies practical high-fidelity tools and processes that can be incorporated in an automated optimization environment, and establishes statements of the multidisciplinary design problem including objectives, constraints, design variables, and cross-disciplinary dependencies. Five key disciplinary areas are selected in the development plan. These are rotor aerodynamics, rotor structures and dynamics, fuselage aerodynamics, fuselage structures, and propulsion / drive system. Flying qualities and noise are included as ancillary areas. Consistency across engineering disciplines is maintained with a central geometry engine that supports all multidisciplinary analysis. The multidisciplinary optimization process targets the preliminary design cycle where gross elements of the helicopter have been defined. These might include number of rotors and rotor configuration (tandem, coaxial, etc.). It is at this stage that sufficient configuration information is defined to perform high-fidelity analysis. At the same time there is enough design freedom to influence a design. The rotorcraft multidisciplinary optimization tool is built and substantiated throughout its development cycle in a staged approach by incorporating disciplines sequentially.

High-Fidelity Buckling Analysis of Composite Cylinders Using the STAGS Finite Element Code

NASA Technical Reports Server (NTRS)

Hilburger, Mark W.

2014-01-01

Results from previous shell buckling studies are presented that illustrate some of the unique and powerful capabilities in the STAGS finite element analysis code that have made it an indispensable tool in structures research at NASA over the past few decades. In particular, prototypical results from the development and validation of high-fidelity buckling simulations are presented for several unstiffened thin-walled compression-loaded graphite-epoxy cylindrical shells along with a discussion on the specific methods and user-defined subroutines in STAGS that are used to carry out the high-fidelity simulations. These simulations accurately account for the effects of geometric shell-wall imperfections, shell-wall thickness variations, local shell-wall ply-gaps associated with the fabrication process, shell-end geometric imperfections, nonuniform applied end loads, and elastic boundary conditions. The analysis procedure uses a combination of nonlinear quasi-static and transient dynamic solution algorithms to predict the prebuckling and unstable collapse response characteristics of the cylinders. Finally, the use of high-fidelity models in the development of analysis-based shell-buckling knockdown (design) factors is demonstrated.

Investigation of Control Inceptor Dynamics and Effect on Human Subject Performance

NASA Technical Reports Server (NTRS)

Stanco, Anthony A.; Cardullo, Frank M.; Houck, Jacob A.; Grube, Richard C.; Kelly, Lon C.

2013-01-01

The control inceptor used in a vehicle simulation is an important part of adequately representing the dynamics of the vehicle. The inceptor characteristics are typically based on a second order spring mass damper system with damping, force gradient, breakout force, and natural frequency parameters. Changing these parameters can have a great effect on pilot control of the vehicle. A quasi transfer of training experiment was performed employing a high fidelity and a low fidelity control inceptor. A disturbance compensatory task was employed which involved a simple horizon line disturbed in roll by a sum of sinusoids presented in an out-the-window display. Vehicle dynamics were modeled as 1/s and 1/s2. The task was to maintain level flight. Twenty subjects were divided between the high and the low fidelity training groups. Each group was trained to a performance asymptote, and then transferred to the high fidelity simulation. RMS tracking error, a PSD analysis, and a workload analysis were performed to quantify the transfer of training effect. Quantitative results of the experiments show that there is no significant difference between the high and low fidelity training groups for 1/s plant dynamics. For 1/s2 plant dynamics there is a greater difference in tracking performance and PSD; and the subjects are less correlated with the input disturbance function

A quasispecies approach to the evolution of sexual replication in unicellular organisms.

PubMed

Tannenbaum, Emmanuel; Fontanari, José F

2008-03-01

This study develops a simplified model describing the evolutionary dynamics of a population composed of obligate sexually and asexually reproducing, unicellular organisms. The model assumes that the organisms have diploid genomes consisting of two chromosomes, and that the sexual organisms replicate by first dividing into haploid intermediates, which then combine with other haploids, followed by the normal mitotic division of the resulting diploid into two new daughter cells. We assume that the fitness landscape of the diploids is analogous to the single-fitness-peak approach often used in single-chromosome studies. That is, we assume a master chromosome that becomes defective with just one point mutation. The diploid fitness then depends on whether the genome has zero, one, or two copies of the master chromosome. We also assume that only pairs of haploids with a master chromosome are capable of combining so as to produce sexual diploid cells, and that this process is described by second-order kinetics. We find that, in a range of intermediate values of the replication fidelity, sexually reproducing cells can outcompete asexual ones, provided the initial abundance of sexual cells is above some threshold value. The range of values where sexual reproduction outcompetes asexual reproduction increases with decreasing replication rate and increasing population density. We critically evaluate a common approach, based on a group selection perspective, used to study the competition between populations and show its flaws in addressing the evolution of sex problem.

Zero-Fidelity Simulation: Engaging Team Coordination without Physical, Functional, or Psychological Re-Creation

NASA Technical Reports Server (NTRS)

Toups, Zachary O.; Hamilton, William A.; Kerne, Andruid

2012-01-01

Team coordination is essential across domains, enabling efficiency and safety. As technology improves, our temptation is to simulate with ever-higher fidelity, by making simulators re-create reality through their physical interfaces, functionality, and by making participants believe they are undertaking the simulated task. However, high-fidelity simulations often miss salient human-human work practices. We introduce the concept of zero-fidelity simulation (ZFS), a move away from literal high-fidelity mimesis of the concrete environment. ZFS alternatively models cooperation and communication as the basis of simulation. The ZFS Team Coordination Game (TeC) is developed from observation of fire emergency response work practice. We identify ways in which team members are mutually dependent on one another for information, and use these as the basis for the ZFS game design. The design creates a need for cooperation by restricting individual activity and requiring communication. The present research analyzes the design of interdependence in the validated ZFS TeC game. We successfully simulate interdependence between roles in emergency response without simulating the concrete environment.

High-speed and high-fidelity system and method for collecting network traffic

DOEpatents

Weigle, Eric H [Los Alamos, NM

2010-08-24

A system is provided for the high-speed and high-fidelity collection of network traffic. The system can collect traffic at gigabit-per-second (Gbps) speeds, scale to terabit-per-second (Tbps) speeds, and support additional functions such as real-time network intrusion detection. The present system uses a dedicated operating system for traffic collection to maximize efficiency, scalability, and performance. A scalable infrastructure and apparatus for the present system is provided by splitting the work performed on one host onto multiple hosts. The present system simultaneously addresses the issues of scalability, performance, cost, and adaptability with respect to network monitoring, collection, and other network tasks. In addition to high-speed and high-fidelity network collection, the present system provides a flexible infrastructure to perform virtually any function at high speeds such as real-time network intrusion detection and wide-area network emulation for research purposes.

Point-of-care ultrasound education: the increasing role of simulation and multimedia resources.

PubMed

Lewiss, Resa E; Hoffmann, Beatrice; Beaulieu, Yanick; Phelan, Mary Beth

2014-01-01

This article reviews the current technology, literature, teaching models, and methods associated with simulation-based point-of-care ultrasound training. Patient simulation appears particularly well suited for learning point-of-care ultrasound, which is a required core competency for emergency medicine and other specialties. Work hour limitations have reduced the opportunities for clinical practice, and simulation enables practicing a skill multiple times before it may be used on patients. Ultrasound simulators can be categorized into 2 groups: low and high fidelity. Low-fidelity simulators are usually static simulators, meaning that they have nonchanging anatomic examples for sonographic practice. Advantages are that the model may be reused over time, and some simulators can be homemade. High-fidelity simulators are usually high-tech and frequently consist of many computer-generated cases of virtual sonographic anatomy that can be scanned with a mock probe. This type of equipment is produced commercially and is more expensive. High-fidelity simulators provide students with an active and safe learning environment and make a reproducible standardized assessment of many different ultrasound cases possible. The advantages and disadvantages of using low- versus high-fidelity simulators are reviewed. An additional concept used in simulation-based ultrasound training is blended learning. Blended learning may include face-to-face or online learning often in combination with a learning management system. Increasingly, with simulation and Web-based learning technologies, tools are now available to medical educators for the standardization of both ultrasound skills training and competency assessment.

Highly sensitive detection of mutations in CHO cell recombinant DNA using multi-parallel single molecule real-time DNA sequencing.

PubMed

Cartwright, Joseph F; Anderson, Karin; Longworth, Joseph; Lobb, Philip; James, David C

2018-06-01

High-fidelity replication of biologic-encoding recombinant DNA sequences by engineered mammalian cell cultures is an essential pre-requisite for the development of stable cell lines for the production of biotherapeutics. However, immortalized mammalian cells characteristically exhibit an increased point mutation frequency compared to mammalian cells in vivo, both across their genomes and at specific loci (hotspots). Thus unforeseen mutations in recombinant DNA sequences can arise and be maintained within producer cell populations. These may affect both the stability of recombinant gene expression and give rise to protein sequence variants with variable bioactivity and immunogenicity. Rigorous quantitative assessment of recombinant DNA integrity should therefore form part of the cell line development process and be an essential quality assurance metric for instances where synthetic/multi-component assemblies are utilized to engineer mammalian cells, such as the assessment of recombinant DNA fidelity or the mutability of single-site integration target loci. Based on Pacific Biosciences (Menlo Park, CA) single molecule real-time (SMRT™) circular consensus sequencing (CCS) technology we developed a rDNA sequence analysis tool to process the multi-parallel sequencing of ∼40,000 single recombinant DNA molecules. After statistical filtering of raw sequencing data, we show that this analytical method is capable of detecting single point mutations in rDNA to a minimum single mutation frequency of 0.0042% (<1/24,000 bases). Using a stable CHO transfectant pool harboring a randomly integrated 5 kB plasmid construct encoding GFP we found that 28% of recombinant plasmid copies contained at least one low frequency (<0.3%) point mutation. These mutations were predominantly found in GC base pairs (85%) and that there was no positional bias in mutation across the plasmid sequence. There was no discernable difference between the mutation frequencies of coding and non-coding DNA. The putative ratio of non-synonymous and synonymous changes within the open reading frames (ORFs) in the plasmid sequence indicates that natural selection does not impact upon the prevalence of these mutations. Here we have demonstrated the abundance of mutations that fall outside of the reported range of detection of next generation sequencing (NGS) and second generation sequencing (SGS) platforms, providing a methodology capable of being utilized in cell line development platforms to identify the fidelity of recombinant genes throughout the production process. © 2018 Wiley Periodicals, Inc.

Experiments towards establishing of design rules for R2R-UV-NIL with polymer working shims

NASA Astrophysics Data System (ADS)

Nees, Dieter; Ruttloff, Stephan; Palfinger, Ursula; Stadlober, Barbara

2016-03-01

Roll-to-Roll-UV-nanoimprint lithography (R2R-UV-NIL) enables high resolution large area patterning of flexible substrates and is therefore of increasing industrial interest. We have set up a custom-made R2R-UV-NIL pilot machine which is able to convert 10 inch wide web with velocities of up to 30 m/min. In addition, we have developed self-replicable UV-curable resins with tunable surface energy and Young's modulus for UV-imprint material as well as for polymer working stamp/shim manufacturing. Now we have designed test patterns for the evaluation of the impact of structure shape, critical dimension, pitch, depth, side wall angle and orientation relative to the web movement onto the imprint fidelity and working shim life time. We have used female (recessed structures) silicon masters of that design with critical dimensions between CD = 200 nm and 1600 nm, and structure depths of d = 500 nm and 1000 nm - all with vertical as well as inclined side walls. These entire master patterns have been transferred onto single male (protruding structures) R2R polymer working shims. The polymer working shims have been used for R2R-UV-NIL runs of several hundred meters and the imprint fidelity and process stability of the various test patterns have been compared. This study is intended as a first step towards establishing of design rules and developing of nanoimprint proximity correction strategies for industrial R2R-UV-NIL processes using polymer working shims.

Three-dimensional brain arteriovenous malformation models for clinical use and resident training.

PubMed

Dong, Mengqi; Chen, Guangzhong; Li, Jianyi; Qin, Kun; Ding, Xiaowen; Peng, Chao; Zhou, Dong; Lin, Xiaofeng

2018-01-01

To fabricate three-dimensional (3D) models of brain arteriovenous malformation (bAVM) and report our experience with customized 3D printed models of patients with bAVM as an educational and clinical tool for patients, doctors, and surgical residents. Using computerized tomography angiography (CTA) or digital subtraction angiography (DSA) images, the rapid prototyping process was completed with specialized software and "in-house" 3D printing service. Intraoperative validation of model fidelity was performed by comparing to DSA images of the same patient during the endovascular treatment process. 3D bAVM models were used for preoperative patient education and consultation, surgical planning, and resident training. 3D printed bAVM models were successful made. By neurosurgeons' evaluation, the printed models precisely replicated the actual bAVM structure of the same patients (n = 7, 97% concordance, range 95%-99% with average of < 2 mm variation). The use of 3D models was associated shorter time for preoperative patient education and consultation, higher acceptable of the procedure for patients and relatives, shorter time between obtaining intraoperative DSA data and the start of endovascular treatment. Thirty surgical residents from residency programs tested the bAVM models and provided feedback on their resemblance to real bAVM structures and the usefulness of printed solid model as an educational tool. Patient-specific 3D printed models of bAVM can be constructed with high fidelity. 3D printed bAVM models were proven to be helpful in preoperative patient consultation, surgical planning, and resident training. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Blending Qualitative and Computational Linguistics Methods for Fidelity Assessment: Experience with the Familias Unidas Preventive Intervention.

PubMed

Gallo, Carlos; Pantin, Hilda; Villamar, Juan; Prado, Guillermo; Tapia, Maria; Ogihara, Mitsunori; Cruden, Gracelyn; Brown, C Hendricks

2015-09-01

Careful fidelity monitoring and feedback are critical to implementing effective interventions. A wide range of procedures exist to assess fidelity; most are derived from observational assessments (Schoenwald and Garland, Psycholog Assess 25:146-156, 2013). However, these fidelity measures are resource intensive for research teams in efficacy/effectiveness trials, and are often unattainable or unmanageable for the host organization to rate when the program is implemented on a large scale. We present a first step towards automated processing of linguistic patterns in fidelity monitoring of a behavioral intervention using an innovative mixed methods approach to fidelity assessment that uses rule-based, computational linguistics to overcome major resource burdens. Data come from an effectiveness trial of the Familias Unidas intervention, an evidence-based, family-centered preventive intervention found to be efficacious in reducing conduct problems, substance use and HIV sexual risk behaviors among Hispanic youth. This computational approach focuses on "joining," which measures the quality of the working alliance of the facilitator with the family. Quantitative assessments of reliability are provided. Kappa scores between a human rater and a machine rater for the new method for measuring joining reached 0.83. Early findings suggest that this approach can reduce the high cost of fidelity measurement and the time delay between fidelity assessment and feedback to facilitators; it also has the potential for improving the quality of intervention fidelity ratings.

Blending Qualitative and Computational Linguistics Methods for Fidelity Assessment: Experience with the Familias Unidas Preventive Intervention

PubMed Central

Gallo, Carlos; Pantin, Hilda; Villamar, Juan; Prado, Guillermo; Tapia, Maria; Ogihara, Mitsunori; Cruden, Gracelyn; Brown, C Hendricks

2014-01-01

Careful fidelity monitoring and feedback are critical to implementing effective interventions. A wide range of procedures exist to assess fidelity; most are derived from observational assessments (Schoenwald et al, 2013). However, these fidelity measures are resource intensive for research teams in efficacy/effectiveness trials, and are often unattainable or unmanageable for the host organization to rate when the program is implemented on a large scale. We present a first step towards automated processing of linguistic patterns in fidelity monitoring of a behavioral intervention using an innovative mixed methods approach to fidelity assessment that uses rule-based, computational linguistics to overcome major resource burdens. Data come from an effectiveness trial of the Familias Unidas intervention, an evidence-based, family-centered preventive intervention found to be efficacious in reducing conduct problems, substance use and HIV sexual risk behaviors among Hispanic youth. This computational approach focuses on “joining,” which measures the quality of the working alliance of the facilitator with the family. Quantitative assessments of reliability are provided. Kappa scores between a human rater and a machine rater for the new method for measuring joining reached .83. Early findings suggest that this approach can reduce the high cost of fidelity measurement and the time delay between fidelity assessment and feedback to facilitators; it also has the potential for improving the quality of intervention fidelity ratings. PMID:24500022

Development and Implementation of CFD-Informed Models for the Advanced Subchannel Code CTF

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

Blyth, Taylor S.; Avramova, Maria

The research described in this PhD thesis contributes to the development of efficient methods for utilization of high-fidelity models and codes to inform low-fidelity models and codes in the area of nuclear reactor core thermal-hydraulics. The objective is to increase the accuracy of predictions of quantities of interests using high-fidelity CFD models while preserving the efficiency of low-fidelity subchannel core calculations. An original methodology named Physics- based Approach for High-to-Low Model Information has been further developed and tested. The overall physical phenomena and corresponding localized effects, which are introduced by the presence of spacer grids in light water reactor (LWR)more » cores, are dissected in corresponding four building basic processes, and corresponding models are informed using high-fidelity CFD codes. These models are a spacer grid-directed cross-flow model, a grid-enhanced turbulent mixing model, a heat transfer enhancement model, and a spacer grid pressure loss model. The localized CFD-models are developed and tested using the CFD code STAR-CCM+, and the corresponding global model development and testing in sub-channel formulation is performed in the thermal- hydraulic subchannel code CTF. The improved CTF simulations utilize data-files derived from CFD STAR-CCM+ simulation results covering the spacer grid design desired for inclusion in the CTF calculation. The current implementation of these models is examined and possibilities for improvement and further development are suggested. The validation experimental database is extended by including the OECD/NRC PSBT benchmark data. The outcome is an enhanced accuracy of CTF predictions while preserving the computational efficiency of a low-fidelity subchannel code.« less

Development and Implementation of CFD-Informed Models for the Advanced Subchannel Code CTF

NASA Astrophysics Data System (ADS)

Blyth, Taylor S.

The research described in this PhD thesis contributes to the development of efficient methods for utilization of high-fidelity models and codes to inform low-fidelity models and codes in the area of nuclear reactor core thermal-hydraulics. The objective is to increase the accuracy of predictions of quantities of interests using high-fidelity CFD models while preserving the efficiency of low-fidelity subchannel core calculations. An original methodology named Physics-based Approach for High-to-Low Model Information has been further developed and tested. The overall physical phenomena and corresponding localized effects, which are introduced by the presence of spacer grids in light water reactor (LWR) cores, are dissected in corresponding four building basic processes, and corresponding models are informed using high-fidelity CFD codes. These models are a spacer grid-directed cross-flow model, a grid-enhanced turbulent mixing model, a heat transfer enhancement model, and a spacer grid pressure loss model. The localized CFD-models are developed and tested using the CFD code STAR-CCM+, and the corresponding global model development and testing in sub-channel formulation is performed in the thermal-hydraulic subchannel code CTF. The improved CTF simulations utilize data-files derived from CFD STAR-CCM+ simulation results covering the spacer grid design desired for inclusion in the CTF calculation. The current implementation of these models is examined and possibilities for improvement and further development are suggested. The validation experimental database is extended by including the OECD/NRC PSBT benchmark data. The outcome is an enhanced accuracy of CTF predictions while preserving the computational efficiency of a low-fidelity subchannel code.

Simulation Learning PC Screen-Based vs. High Fidelity

DTIC Science & Technology

2011-08-01

D., Burgess, L., Berg, B . and Connolly, K . (2009). Teaching mass casualty triage skills using iterative multimanikin simulations. Prehospital...SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U...learning PC screen-based vs. high fidelity – progress chart Attachment B . Approved Protocol - Simulation Learning: PC-Screen Based (PCSB) versus High

Effect of diatomic molecular properties on binary laser pulse optimizations of quantum gate operations.

PubMed

Zaari, Ryan R; Brown, Alex

2011-07-28

The importance of the ro-vibrational state energies on the ability to produce high fidelity binary shaped laser pulses for quantum logic gates is investigated. The single frequency 2-qubit ACNOT(1) and double frequency 2-qubit NOT(2) quantum gates are used as test cases to examine this behaviour. A range of diatomics is sampled. The laser pulses are optimized using a genetic algorithm for binary (two amplitude and two phase parameter) variation on a discretized frequency spectrum. The resulting trends in the fidelities were attributed to the intrinsic molecular properties and not the choice of method: a discretized frequency spectrum with genetic algorithm optimization. This is verified by using other common laser pulse optimization methods (including iterative optimal control theory), which result in the same qualitative trends in fidelity. The results differ from other studies that used vibrational state energies only. Moreover, appropriate choice of diatomic (relative ro-vibrational state arrangement) is critical for producing high fidelity optimized quantum logic gates. It is also suggested that global phase alignment imposes a significant restriction on obtaining high fidelity regions within the parameter search space. Overall, this indicates a complexity in the ability to provide appropriate binary laser pulse control of diatomics for molecular quantum computing. © 2011 American Institute of Physics

Fidelity of the representation of value in decision-making

PubMed Central

Dowding, Ben A.

2017-01-01

The ability to make optimal decisions depends on evaluating the expected rewards associated with different potential actions. This process is critically dependent on the fidelity with which reward value information can be maintained in the nervous system. Here we directly probe the fidelity of value representation following a standard reinforcement learning task. The results demonstrate a previously-unrecognized bias in the representation of value: extreme reward values, both low and high, are stored significantly more accurately and precisely than intermediate rewards. The symmetry between low and high rewards pertained despite substantially higher frequency of exposure to high rewards, resulting from preferential exploitation of more rewarding options. The observed variation in fidelity of value representation retrospectively predicted performance on the reinforcement learning task, demonstrating that the bias in representation has an impact on decision-making. A second experiment in which one or other extreme-valued option was omitted from the learning sequence showed that representational fidelity is primarily determined by the relative position of an encoded value on the scale of rewards experienced during learning. Both variability and guessing decreased with the reduction in the number of options, consistent with allocation of a limited representational resource. These findings have implications for existing models of reward-based learning, which typically assume defectless representation of reward value. PMID:28248958

The Fundamentals of Laparoscopic Surgery and LapVR evaluation metrics may not correlate with operative performance in a novice cohort

PubMed Central

Steigerwald, Sarah N.; Park, Jason; Hardy, Krista M.; Gillman, Lawrence; Vergis, Ashley S.

2015-01-01

Background Considerable resources have been invested in both low- and high-fidelity simulators in surgical training. The purpose of this study was to investigate if the Fundamentals of Laparoscopic Surgery (FLS, low-fidelity box trainer) and LapVR (high-fidelity virtual reality) training systems correlate with operative performance on the Global Operative Assessment of Laparoscopic Skills (GOALS) global rating scale using a porcine cholecystectomy model in a novice surgical group with minimal laparoscopic experience. Methods Fourteen postgraduate year 1 surgical residents with minimal laparoscopic experience performed tasks from the FLS program and the LapVR simulator as well as a live porcine laparoscopic cholecystectomy. Performance was evaluated using standardized FLS metrics, automatic computer evaluations, and a validated global rating scale. Results Overall, FLS score did not show an association with GOALS global rating scale score on the porcine cholecystectomy. None of the five LapVR task scores were significantly associated with GOALS score on the porcine cholecystectomy. Conclusions Neither the low-fidelity box trainer or the high-fidelity virtual simulator demonstrated significant correlation with GOALS operative scores. These findings offer caution against the use of these modalities for brief assessments of novice surgical trainees, especially for predictive or selection purposes. PMID:26641071

Demonstration of a High-Fidelity Predictive/Preview Display Technique for Telerobotic Servicing in Space

NASA Technical Reports Server (NTRS)

Kim, Won S.; Bejczy, Antal K.

1993-01-01

A highly effective predictive/preview display technique for telerobotic servicing in space under several seconds communication time delay has been demonstrated on a large laboratory scale in May 1993, involving the Jet Propulsion Laboratory as the simulated ground control station and, 2500 miles away, the Goddard Space Flight Center as the simulated satellite servicing set-up. The technique is based on a high-fidelity calibration procedure that enables a high-fidelity overlay of 3-D graphics robot arm and object models over given 2-D TV camera images of robot arm and objects. To generate robot arm motions, the operator can confidently interact in real time with the graphics models of the robot arm and objects overlaid on an actual camera view of the remote work site. The technique also enables the operator to generate high-fidelity synthetic TV camera views showing motion events that are hidden in a given TV camera view or for which no TV camera views are available. The positioning accuracy achieved by this technique for a zoomed-in camera setting was about +/-5 mm, well within the allowable +/-12 mm error margin at the insertion of a 45 cm long tool in the servicing task.

DDDAMS-based Urban Surveillance and Crowd Control via UAVs and UGVs

DTIC Science & Technology

2015-12-04

for crowd dynamics modeling by incorporating multi-resolution data, where a grid-based method is used to model crowd motion with UAVs’ low -resolution...information and more computational intensive (and time-consuming). Given that the deployment of fidelity selection results in simulation faces computational... low fidelity information FOV y (A) DR x (A) DR y (A) Not detected high fidelity information Table 1: Parameters for UAV and UGV for their detection

EBT Fidelity Trajectories Across Training Cohorts Using the Interagency Collaborative Team Strategy

PubMed Central

Hecht, Debra; Aarons, Greg; Fettes, Danielle; Hurlburt, Michael; Ledesma, Karla

2015-01-01

The Interdisciplinary Collaborative Team (ICT) strategy uses front-line providers as adaptation, training and quality control agents for multi-agency EBT implementation. This study tests whether an ICT transmits fidelity to subsequent provider cohorts. SafeCare was implemented by home visitors from multiple community-based agencies contracting with child welfare. Client-reported fidelity trajectories for 5,769 visits, 957 clients and 45 providers were compared using three-level growth models. Provider cohorts trained and live-coached by the ICT attained benchmark fidelity after 12 weeks, and this was sustained. Hispanic clients reported high cultural competency, supporting a cultural adaptation crafted by the ICT. PMID:25586878

EBT Fidelity Trajectories Across Training Cohorts Using the Interagency Collaborative Team Strategy.

PubMed

Chaffin, Mark; Hecht, Debra; Aarons, Greg; Fettes, Danielle; Hurlburt, Michael; Ledesma, Karla

2016-03-01

The Interdisciplinary Collaborative Team (ICT) strategy uses front-line providers as adaptation, training and quality control agents for multi-agency EBT implementation. This study tests whether an ICT transmits fidelity to subsequent provider cohorts. SafeCare was implemented by home visitors from multiple community-based agencies contracting with child welfare. Client-reported fidelity trajectories for 5,769 visits, 957 clients and 45 providers were compared using three-level growth models. Provider cohorts trained and live-coached by the ICT attained benchmark fidelity after 12 weeks, and this was sustained. Hispanic clients reported high cultural competency, supporting a cultural adaptation crafted by the ICT.

How to Measure Motivational Interviewing Fidelity in Randomized Controlled Trials: Practical Recommendations.

PubMed

Jelsma, Judith G M; Mertens, Vera-Christina; Forsberg, Lisa; Forsberg, Lars

2015-07-01

Many randomized controlled trials in which motivational interviewing (MI) is a key intervention make no provision for the assessment of treatment fidelity. This methodological shortcoming makes it impossible to distinguish between high- and low-quality MI interventions, and, consequently, to know whether MI provision has contributed to any intervention effects. This article makes some practical recommendations for the collection, selection, coding and reporting of MI fidelity data, as measured using the Motivational Interviewing Treatment Integrity Code. We hope that researchers will consider these recommendations and include MI fidelity measures in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Commentary: Learning from Variations in Fidelity of Implementation.

PubMed

Balu, Rekha; Doolittle, Fred

2016-12-01

The articles in this special issue discuss efforts to improve academic reading outcomes for students and ways to achieve high implementation fidelity of promising strategies. At times the authors discuss if-and how-strong fidelity is associated with strong outcomes and potentially even impacts (the difference between program and control group outcomes). We want to explore this theme in two ways: (a) learning from the variation in fidelity to think about potential points of entry and levers for improvement in implementation, and (b) broadening the evaluation focus to include "service contrast" as a factor driving impacts on student outcomes. We conclude with suggestions for future research. © 2016 Wiley Periodicals, Inc.

A method for assessing fidelity of delivery of telephone behavioral support for smoking cessation.

PubMed

Lorencatto, Fabiana; West, Robert; Bruguera, Carla; Michie, Susan

2014-06-01

Behavioral support for smoking cessation is delivered through different modalities, often guided by treatment manuals. Recently developed methods for assessing fidelity of delivery have shown that face-to-face behavioral support is often not delivered as specified in the service treatment manual. This study aimed to extend this method to evaluate fidelity of telephone-delivered behavioral support. A treatment manual and transcripts of 75 audio-recorded behavioral support sessions were obtained from the United Kingdom's national Quitline service and coded into component behavior change techniques (BCTs) using a taxonomy of 45 smoking cessation BCTs. Interrater reliability was assessed using percentage agreement. Fidelity was assessed by comparing the number of BCTs identified in the manual with those delivered in telephone sessions by 4 counselors. Fidelity was assessed according to session type, duration, counselor, and BCT. Differences between self-reported and actual BCT use were examined. Average coding reliability was high (81%). On average, 41.8% of manual-specified BCTs were delivered per session (SD = 16.2), with fidelity varying by counselor from 32% to 49%. Fidelity was highest in pre-quit sessions (46%) and for BCT "give options for additional support" (95%). Fidelity was lowest for quit-day sessions (35%) and BCT "set graded tasks" (0%). Session duration was positively correlated with fidelity (r = .585; p < .01). Significantly fewer BCTs were used than were reported as being used, t(15) = -5.52, p < .001. The content of telephone-delivered behavioral support can be reliably coded in terms of BCTs. This can be used to assess fidelity to treatment manuals and to in turn identify training needs. The observed low fidelity underlines the need to establish routine procedures for monitoring delivery of behavioral support. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Early Influences and Later Outcomes Associated With Developmental Trajectories of Eriksonian Fidelity

PubMed Central

Brittian, Aerika S.; Lerner, Richard M.

2014-01-01

Although Eriksonian theory suggests that adolescents’ sense of fidelity is a key component of healthy development, research on this psychosocial construct has been limited. The current study developed an index of youth fidelity, examined the developmental course of this construct, explored the influence of contextual factors on different fidelity trajectories, and tested if trajectories were associated with later indicators of adolescents’ positive development. Participants included 1,941 ethnically diverse youth (61% female) participants in the 4-H Study of Positive Youth Development who were recruited from schools and youth development programs across the United States. Results suggested that three types of developmental trajectories existed among youth: high and increasing, moderate and increasing, and low and decreasing. Fidelity group membership varied in relation to social relationships and psychosocial and behavioral characteristics (i.e., contribution, substance use, and delinquency). Girls were more likely than boys to be in the highest fidelity trajectories. Directions for future research and implications for enhancing the thriving of adolescents are discussed. PMID:22545838

Construction of nested maximin designs based on successive local enumeration and modified novel global harmony search algorithm

NASA Astrophysics Data System (ADS)

Yi, Jin; Li, Xinyu; Xiao, Mi; Xu, Junnan; Zhang, Lin

2017-01-01

Engineering design often involves different types of simulation, which results in expensive computational costs. Variable fidelity approximation-based design optimization approaches can realize effective simulation and efficiency optimization of the design space using approximation models with different levels of fidelity and have been widely used in different fields. As the foundations of variable fidelity approximation models, the selection of sample points of variable-fidelity approximation, called nested designs, is essential. In this article a novel nested maximin Latin hypercube design is constructed based on successive local enumeration and a modified novel global harmony search algorithm. In the proposed nested designs, successive local enumeration is employed to select sample points for a low-fidelity model, whereas the modified novel global harmony search algorithm is employed to select sample points for a high-fidelity model. A comparative study with multiple criteria and an engineering application are employed to verify the efficiency of the proposed nested designs approach.

Debriefing after High-Fidelity Simulation and Knowledge Retention: A Quasi-Experimental Study

ERIC Educational Resources Information Center

Olson, Susan L.

2013-01-01

High-fidelity simulation (HFS) use in nursing education has been a frequent research topic in recent years. Previous research included studies on the use of HFS with nursing students, focusing on their feelings of self-confidence and anxiety. However, research focused specifically on the debriefing portion of HFS was limited. This quantitative,…

Capacity Development and Multi-Tiered Systems of Support: Guiding Principles

ERIC Educational Resources Information Center

Sugai, George; Simonsen, Brandi; Freeman, Jennifer; La Salle, Tamika

2016-01-01

Implementation of multi-tiered systems of support is occurring within and across a number of countries with an increased recent focus on the development of local system capacity to maintain high levels of practice implementation fidelity. The purpose of this paper is to describe the importance of local capacity development in the high fidelity and…

High-Fidelity Patient Simulators to Expose Undergraduate Students to the Clinical Relevance of Physiology Concepts

ERIC Educational Resources Information Center

Harris, David M.; Bellew, Christine; Cheng, Zixi J.; Cendán, Juan C.; Kibble, Jonathan D.

2014-01-01

The use of high-fidelity patient simulators (HFPSs) has expanded throughout medical, nursing, and allied health professions education in the last decades. These manikins can be programmed to represent pathological states and are used to teach clinical skills as well as clinical reasoning. First, the students are typically oriented either to the…

The Effect of Learning Styles, Critical Thinking Disposition, and Critical Thinking on Clinical Judgment in Senior Baccalaureate Nursing Students during Human Patient Simulation

ERIC Educational Resources Information Center

McCormick, Kiyan

2014-01-01

Simulated learning experiences using high-fidelity human patient simulators (HPS) are increasingly being integrated into baccalaureate nursing programs. Thus, the purpose of this study was to examine relationships among learning style, critical thinking disposition, critical thinking, and clinical judgment during high-fidelity human patient…

The Effect of High-Fidelity Cardiopulmonary Resuscitation (CPR) Simulation on Athletic Training Student Knowledge, Confidence, Emotions, and Experiences

ERIC Educational Resources Information Center

Tivener, Kristin Ann; Gloe, Donna Sue

2015-01-01

Context: High-fidelity simulation is widely used in healthcare for the training and professional education of students though literature of its application to athletic training education remains sparse. Objective: This research attempts to address a wide-range of data. This includes athletic training student knowledge acquisition from…

Evaluating Outcomes of High Fidelity Simulation Curriculum in a Community College Nursing Program

ERIC Educational Resources Information Center

Denlea, Gregory Richard

2017-01-01

This study took place at a Wake Technical Community College, a multi-campus institution in Raleigh, North Carolina. An evaluation of the return on investment in high fidelity simulation used by an associate degree of nursing program was conducted with valid and reliable instruments. The study demonstrated that comparable student outcomes are…

Physics and Psychophysics of High-Fidelity Sound. Part III: The Components of a Sound-Reproducing System: Amplifiers and Loudspeakers.

ERIC Educational Resources Information Center

Rossing, Thomas D.

1980-01-01

Described are the components for a high-fidelity sound-reproducing system which focuses on various program sources, the amplifier, and loudspeakers. Discussed in detail are amplifier power and distortion, air suspension, loudspeaker baffles and enclosures, bass-reflex enclosure, drone cones, rear horn and acoustic labyrinth enclosures, horn…

Developing High-Fidelity Health Care Simulation Scenarios: A Guide for Educators and Professionals

ERIC Educational Resources Information Center

Alinier, Guillaume

2011-01-01

The development of appropriate scenarios is critical in high-fidelity simulation training. They need to be developed to address specific learning objectives, while not preventing other learning points from emerging. Buying a patient simulator, finding a volunteer to act as the patient, or even obtaining ready-made scenarios from another simulation…

Becoming a High-Fidelity--"Super"--Imitator: What Are the Contributions of Social and Individual Learning?

ERIC Educational Resources Information Center

Subiaul, Francys; Patterson, Eric M.; Schilder, Brian; Renner, Elizabeth; Barr, Rachel

2015-01-01

In contrast to other primates, human children's imitation performance goes from low to high fidelity soon after infancy. Are such changes associated with the development of other forms of learning? We addressed this question by testing 215 children (26-59 months) on two social conditions (imitation, emulation)--involving a demonstration--and two…

Orbit Stability of OSIRIS-REx in the Vicinity of Bennu Using a High-Fidelity Solar Radiation Model

NASA Technical Reports Server (NTRS)

Williams, Trevor W.; Hughes, Kyle M.; Mashiku, Alinda K.; Longuski, James M.

2015-01-01

Solar radiation pressure is one of the largest perturbing forces on the OSIRISRex trajectory as it orbits the asteroid Bennu. In this work, we investigate how forces due to solar radiation perturb the OSIRIS-REx trajectory in a high-fidelity model. The model accounts for Bennu's non-spherical gravity field, third-body gravity forces from the Sun and Jupiter, as well as solar radiation forces acting on a simplified spacecraft model. Such high-fidelity simulations indicate significant solar radiation pressure perturbations from the nominal orbit. Modifications to the initial design of the nominal orbit are found using a variation of parameters approach that reduce the perturbation in eccentricity by a factor of one-half.

Fast, high-fidelity readout of multiple qubits

NASA Astrophysics Data System (ADS)

Bronn, N. T.; Abdo, B.; Inoue, K.; Lekuch, S.; Córcoles, A. D.; Hertzberg, J. B.; Takita, M.; Bishop, L. S.; Gambetta, J. M.; Chow, J. M.

2017-05-01

Quantum computing requires a delicate balance between coupling quantum systems to external instruments for control and readout, while providing enough isolation from sources of decoherence. Circuit quantum electrodynamics has been a successful method for protecting superconducting qubits, while maintaining the ability to perform readout [1, 2]. Here, we discuss improvements to this method that allow for fast, high-fidelity readout. Specifically, the integration of a Purcell filter, which allows us to increase the resonator bandwidth for fast readout, the incorporation of a Josephson parametric converter, which enables us to perform high-fidelity readout by amplifying the readout signal while adding the minimum amount of noise required by quantum mechanics, and custom control electronics, which provide us with the capability of fast decision and control.

High-fidelity cluster state generation for ultracold atoms in an optical lattice.

PubMed

Inaba, Kensuke; Tokunaga, Yuuki; Tamaki, Kiyoshi; Igeta, Kazuhiro; Yamashita, Makoto

2014-03-21

We propose a method for generating high-fidelity multipartite spin entanglement of ultracold atoms in an optical lattice in a short operation time with a scalable manner, which is suitable for measurement-based quantum computation. To perform the desired operations based on the perturbative spin-spin interactions, we propose to actively utilize the extra degrees of freedom (DOFs) usually neglected in the perturbative treatment but included in the Hubbard Hamiltonian of atoms, such as, (pseudo-)charge and orbital DOFs. Our method simultaneously achieves high fidelity, short operation time, and scalability by overcoming the following fundamental problem: enhancing the interaction strength for shortening the operation time breaks the perturbative condition of the interaction and inevitably induces unwanted correlations among the spin and extra DOFs.

A peer education program: delivering highly reliable sexual health promotion messages in schools.

PubMed

Layzer, Carolyn; Rosapep, Lauren; Barr, Sherry

2014-03-01

This article describes preliminary findings from an implementation study of a school-based peer education program on sexual health for high-school youth. The responses of youth participants are described. Qualitative data were collected across one semester in two successive waves of participants (N = 4 schools), including observations of program activities, in-depth interviews of stakeholders, focus groups with youth participants (N = 62 peer educators and 60 ninth graders), and brief surveys of youth participants (N = 678). Grounded theory methodology informed data collection and analysis. Teen Prevention Education Program (Teen PEP) was adapted and replicated with fidelity to the model in North Carolina high schools. All program "inputs" and five core model components (outputs) were implemented. The principal accommodation made was to implement the entire curriculum within one half of a school year rather than across the entire school year although still using the same amount of instructional time. Youth participants attributed high value to the experience, noting that the sexual health information they received was both new and important for their lives and that they felt they learned it better from their peers than from instruction in traditional health class. The majority of participants reported that the program helped them across a range of areas related to both social well-being and sexual health. Teen PEP developers have been able to successfully adapt and replicate it in North Carolina, in settings that need sexual health education services for youth both because of the paucity of existing services in many areas and because of the evidence of risk in the form of high rates of pregnancy and sexually transmitted infections, including human immunodeficiency virus or AIDS in youth 15-19 years of age. Youth reported benefits across a range of social and sexual health-related areas. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Long lifetime and high-fidelity quantum memory of photonic polarization qubit by lifting zeeman degeneracy.

PubMed

Xu, Zhongxiao; Wu, Yuelong; Tian, Long; Chen, Lirong; Zhang, Zhiying; Yan, Zhihui; Li, Shujing; Wang, Hai; Xie, Changde; Peng, Kunchi

2013-12-13

Long-lived and high-fidelity memory for a photonic polarization qubit (PPQ) is crucial for constructing quantum networks. We present a millisecond storage system based on electromagnetically induced transparency, in which a moderate magnetic field is applied on a cold-atom cloud to lift Zeeman degeneracy and, thus, the PPQ states are stored as two magnetic-field-insensitive spin waves. Especially, the influence of magnetic-field-sensitive spin waves on the storage performances is almost totally avoided. The measured average fidelities of the polarization states are 98.6% at 200  μs and 78.4% at 4.5 ms, respectively.

Investigating variations in implementation fidelity of an organizational-level occupational health intervention.

PubMed

Augustsson, Hanna; von Thiele Schwarz, Ulrica; Stenfors-Hayes, Terese; Hasson, Henna

2015-06-01

The workplace has been suggested as an important arena for health promotion, but little is known about how the organizational setting influences the implementation of interventions. The aims of this study are to evaluate implementation fidelity in an organizational-level occupational health intervention and to investigate possible explanations for variations in fidelity between intervention units. The intervention consisted of an integration of health promotion, occupational health and safety, and a system for continuous improvements (Kaizen) and was conducted in a quasi-experimental design at a Swedish hospital. Implementation fidelity was evaluated with the Conceptual Framework for Implementation Fidelity and implementation factors used to investigate variations in fidelity with the Framework for Evaluating Organizational-level Interventions. A multi-method approach including interviews, Kaizen notes, and questionnaires was applied. Implementation fidelity differed between units even though the intervention was introduced and supported in the same way. Important differences in all elements proposed in the model for evaluating organizational-level interventions, i.e., context, intervention, and mental models, were found to explain the differences in fidelity. Implementation strategies may need to be adapted depending on the local context. Implementation fidelity, as well as pre-intervention implementation elements, is likely to affect the implementation success and needs to be assessed in intervention research. The high variation in fidelity across the units indicates the need for adjustments to the type of designs used to assess the effects of interventions. Thus, rather than using designs that aim to control variation, it may be necessary to use those that aim at exploring and explaining variation, such as adapted study designs.

Site fidelity, territory fidelity, and natal philopatry in Willow Flycatchers (Empidonax traillii)

USGS Publications Warehouse

Sedgwick, James A.

2004-01-01

I investigated the causes and consequences of adult breeding-site fidelity, territory fidelity, and natal philopatry in Willow Flycatchers (Empidonax traillii) in southeastern Oregon over a 10-year period, testing the general hypothesis that fidelity and dispersal distances are influenced by previous breeding performance. Willow Flycatchers adhered to the generally observed tendencies of passerine birds for low natal philopatry and high breedingsite fidelity. Site fidelity (return to the study area) of adult males (52.0%) and females (51.3%), and median dispersal distances between seasons (16 m vs. 19 m) were similar. Previous breeding performance and residency (age-experience), but not study-site quality, explained site fidelity in females. Site fidelity of females rearing 4–5 young (64.4%) exceeded that of unsuccessful females (40.0%), breeding dispersal was less (successful: 15 m; unsuccessful: 33 m), and novice residents were more site-faithful than former residents. Probability of site fidelity was higher for previously successful females (odds ratio = 4.76), those with greater seasonal fecundity (odds ratio = 1.58), novice residents (odds ratio = 1.41), and unparasitized females (odds ratio = 2.76). Male site fidelity was not related to residency, site quality, or previous breeding performance. Territory fidelity (return to the previous territory) in females was best explained by previous breeding performance, but not by site quality or residency. Previously successful females were more likely to return to their territory of the previous season than either unsuccessful (odds ratio = 14.35) or parasitized birds (odds ratio = 6.38). Male territory fidelity was not related to residency, site quality, or previous breeding performance. Natal philopatry was low (7.8%) and similar for males and females. Site quality appeared to influence philopatry, given that no birds reared at a low-quality study site returned there to breed, and birds reared there dispersed farther than birds reared at two other study sites. My results partially support the hypothesis that site fidelity is an adaptive response: (1) previously successful females that switched territories underperformed those that did not switch (P = 0.01); and (2) previously unsuccessful females that switched territories outperformed those that did not switch, but not significantly (P = 0.22).

Developing effective serious games: the effect of background sound on visual fidelity perception with varying texture resolution.

PubMed

Rojas, David; Kapralos, Bill; Cristancho, Sayra; Collins, Karen; Hogue, Andrew; Conati, Cristina; Dubrowski, Adam

2012-01-01

Despite the benefits associated with virtual learning environments and serious games, there are open, fundamental issues regarding simulation fidelity and multi-modal cue interaction and their effect on immersion, transfer of knowledge, and retention. Here we describe the results of a study that examined the effect of ambient (background) sound on the perception of visual fidelity (defined with respect to texture resolution). Results suggest that the perception of visual fidelity is dependent on ambient sound and more specifically, white noise can have detrimental effects on our perception of high quality visuals. The results of this study will guide future studies that will ultimately aid in developing an understanding of the role that fidelity, and multi-modal interactions play with respect to knowledge transfer and retention for users of virtual simulations and serious games.

Multifamily Group Psychoeducation in New York State: Implementation and Fidelity Outcomes.

PubMed

Kealey, Edith M; Leckman-Westin, Emily; Jewell, Thomas C; Finnerty, Molly T

2015-11-01

The study examined implementation outcomes from a large state initiative to support dissemination of multifamily group (MFG) psychoeducation in outpatient mental health settings. Thirty-one sites participated in the project. Baseline training in the MFG model was followed by monthly expert consultation delivered in either a group (16 sites) or individual format (15 sites). Research staff assessed fidelity to the MFG model by telephone at baseline and 12, 18, and 24 months and documented time to completion of three key milestones: holding a family joining session, a family educational workshop, and an MFG meeting. Intent-to-train analyses found that 12 sites (39%) achieved high fidelity to the MFG model, and 20 (65%) achieved moderate or high fidelity. Mean scores on the Family Psychoeducation Fidelity Assessment Scale increased over time. Twenty-five sites (81%) conducted at least one joining session, and 20 (65%) conducted at least one MFG. Mean±SD time from baseline to the first group was 11.75±4.78 months. Programs that held the first joining session within four to 12 months after training were significantly more likely than programs that did not to conduct a group (p<.05). No significant differences were found by consultation format. Implementation of moderate- to high-fidelity MFG programs in routine outpatient mental health settings is feasible. Sites that moved very quickly or very slowly in early implementation stages were less likely to be successful in conducting an MFG. More research on the efficiency and effectiveness of consultation formats is needed to guide future implementation efforts.

Use of VR Technology and Passive Haptics for MANPADS Training System

DTIC Science & Technology

2017-09-01

this setup also does not offer a variety of challenging scenarios needed for good training as the aircraft are mostly flying in landing or take-off... customized high-fidelity immersive training facilities are limited. Moreover, low trainee throughput from such high-end facilities is an ongoing obstacle...opportunities allow few operators to fire during live exercises. Simulation training is effective, but customized high-fidelity immersive training

Development and Delivery of a Physical Activity Intervention for People With Huntington Disease: Facilitating Translation to Clinical Practice

PubMed Central

Quinn, Lori; Trubey, Rob; Gobat, Nina; Dawes, Helen; Edwards, Rhiannon Tudor; Jones, Carys; Townson, Julia; Drew, Cheney; Kelson, Mark; Poile, Vincent; Rosser, Anne; Hood, Kerenza

2016-01-01

Background and Purpose: We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process. Methods: Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory. Intervention Delivery: Key components underpinning the delivery of the intervention were implemented including a defined coach training program and intervention fidelity assessment methods. Training of coaches (physical therapists, occupational therapists, research nurses, and exercise trainers) was delivered via group and 1:1 training sessions using a detailed coach's manual, and with ongoing support via video calls, and e-mail communication as needed. Detailed documentation was provided to determine costs of intervention development and coach training. Results: Intervention delivery coaches at 8 sites across the United Kingdom participated in the face-to-face training. Self-report checklists completed by each of the coaches indicated that all components of the intervention were delivered in accordance with the protocol. Mean (standard deviation) intervention fidelity scores (n = 15), as measured using a purpose-developed rating scale, was 11 (2.4) (out of 16 possible points). Coaches' perceptions of intervention fidelity were similarly high. The total cost of developing the intervention and providing training was £30,773 ($47,042 USD). Discussion and Conclusions: An important consideration in promoting translation of clinical research into practice is the ability to convey the detailed components of how the intervention was delivered to facilitate replication if the results are favorable. This report presents an illustrative example of a physical activity intervention, including the development and the training required to deliver it. This approach has the potential to facilitate reproducibility, evidence synthesis, and implementation in clinical practice. Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A122). PMID:26863152

Development of Adaptive Model Refinement (AMoR) for Multiphysics and Multifidelity Problems

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

Turinsky, Paul

This project investigated the development and utilization of Adaptive Model Refinement (AMoR) for nuclear systems simulation applications. AMoR refers to utilization of several models of physical phenomena which differ in prediction fidelity. If the highest fidelity model is judged to always provide or exceeded the desired fidelity, than if one can determine the difference in a Quantity of Interest (QoI) between the highest fidelity model and lower fidelity models, one could utilize the fidelity model that would just provide the magnitude of the QoI desired. Assuming lower fidelity models require less computational resources, in this manner computational efficiency can bemore » realized provided the QoI value can be accurately and efficiently evaluated. This work utilized Generalized Perturbation Theory (GPT) to evaluate the QoI, by convoluting the GPT solution with the residual of the highest fidelity model determined using the solution from lower fidelity models. Specifically, a reactor core neutronics problem and thermal-hydraulics problem were studied to develop and utilize AMoR. The highest fidelity neutronics model was based upon the 3D space-time, two-group, nodal diffusion equations as solved in the NESTLE computer code. Added to the NESTLE code was the ability to determine the time-dependent GPT neutron flux. The lower fidelity neutronics model was based upon the point kinetics equations along with utilization of a prolongation operator to determine the 3D space-time, two-group flux. The highest fidelity thermal-hydraulics model was based upon the space-time equations governing fluid flow in a closed channel around a heat generating fuel rod. The Homogenous Equilibrium Mixture (HEM) model was used for the fluid and Finite Difference Method was applied to both the coolant and fuel pin energy conservation equations. The lower fidelity thermal-hydraulic model was based upon the same equations as used for the highest fidelity model but now with coarse spatial meshing, corrected somewhat by employing effective fuel heat conduction values. The effectiveness of switching between the highest fidelity model and lower fidelity model as a function of time was assessed using the neutronics problem. Based upon work completed to date, one concludes that the time switching is effective in annealing out differences between the highest and lower fidelity solutions. The effectiveness of using a lower fidelity GPT solution, along with a prolongation operator, to estimate the QoI was also assessed. The utilization of a lower fidelity GPT solution was done in an attempt to avoid the high computational burden associated with solving for the highest fidelity GPT solution. Based upon work completed to date, one concludes that the lower fidelity adjoint solution is not sufficiently accurate with regard to estimating the QoI; however, a formulation has been revealed that may provide a path for addressing this shortcoming.« less

Long Live Love+: evaluation of the implementation of an online school-based sexuality education program in the Netherlands.

PubMed

van Lieshout, Sanne; Mevissen, Fraukje; de Waal, Esri; Kok, Gerjo

2017-06-01

Schools are a common setting for adolescents to receive health education, but implementation of these programs with high levels of completeness and fidelity is not self-evident. Programs that are only partially implemented (completeness) or not implemented as instructed (fidelity) are unlikely to be effective. Therefore, it is important to identify which determinants affect completeness and fidelity of program implementation. As part of the launch of Long Live Love+ (LLL+), an online school-based sexuality education program for adolescents aged 15-17, we performed a process evaluation among teachers and students to measure the levels of completeness and fidelity, identify factors influencing teachers' implementation, and to evaluate the students' response. Sixteen Biology teachers from nine secondary schools throughout the Netherlands who implemented LLL+ were interviewed and 60 students participated in 13 focus group discussions. Results showed that teachers' completeness ranged between 22-100% (M = 75%). Fidelity was high, but many teachers added elements. Teachers and students enjoyed LLL+, particularly the diversity in the exercises and its interactive character. The most important factors that influenced implementation were time and organizational constraints, lack of awareness on the impact of completeness and fidelity, and student response. These factors should be taken into account when developing school-based prevention programs. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Fidelity assessment of a UH-60A simulation on the NASA Ames vertical motion simulator

NASA Technical Reports Server (NTRS)

Atencio, Adolph, Jr.

1993-01-01

Helicopter handling qualities research requires that a ground-based simulation be a high-fidelity representation of the actual helicopter, especially over the frequency range of the investigation. This experiment was performed to assess the current capability to simulate the UH-60A Black Hawk helicopter on the Vertical Motion Simulator (VMS) at NASA Ames, to develop a methodology for assessing the fidelity of a simulation, and to find the causes for lack of fidelity. The approach used was to compare the simulation to the flight vehicle for a series of tasks performed in flight and in the simulator. The results show that subjective handling qualities ratings from flight to simulator overlap, and the mathematical model matches the UH-60A helicopter very well over the range of frequencies critical to handling qualities evaluation. Pilot comments, however, indicate a need for improvement in the perceptual fidelity of the simulation in the areas of motion and visual cuing. The methodology used to make the fidelity assessment proved useful in showing differences in pilot work load and strategy, but additional work is needed to refine objective methods for determining causes of lack of fidelity.

Unbiased multi-fidelity estimate of failure probability of a free plane jet

NASA Astrophysics Data System (ADS)

Marques, Alexandre; Kramer, Boris; Willcox, Karen; Peherstorfer, Benjamin

2017-11-01

Estimating failure probability related to fluid flows is a challenge because it requires a large number of evaluations of expensive models. We address this challenge by leveraging multiple low fidelity models of the flow dynamics to create an optimal unbiased estimator. In particular, we investigate the effects of uncertain inlet conditions in the width of a free plane jet. We classify a condition as failure when the corresponding jet width is below a small threshold, such that failure is a rare event (failure probability is smaller than 0.001). We estimate failure probability by combining the frameworks of multi-fidelity importance sampling and optimal fusion of estimators. Multi-fidelity importance sampling uses a low fidelity model to explore the parameter space and create a biasing distribution. An unbiased estimate is then computed with a relatively small number of evaluations of the high fidelity model. In the presence of multiple low fidelity models, this framework offers multiple competing estimators. Optimal fusion combines all competing estimators into a single estimator with minimal variance. We show that this combined framework can significantly reduce the cost of estimating failure probabilities, and thus can have a large impact in fluid flow applications. This work was funded by DARPA.

High Fidelity Measurement and Modeling of Interactions between Acoustics and Heat Release in Highly-Compact, High-Pressure Flames

DTIC Science & Technology

2016-05-24

experimental data. However, the time and length scales, and energy deposition rates in the canonical laboratory flames that have been studied over the...is to obtain high-fidelity experimental data critically needed to validate research codes at relevant conditions, and to develop systematic and...validated with experimental data. However, the time and length scales, and energy deposition rates in the canonical laboratory flames that have been

Fluid/Structure Interaction Studies of Aircraft Using High Fidelity Equations on Parallel Computers

NASA Technical Reports Server (NTRS)

Guruswamy, Guru; VanDalsem, William (Technical Monitor)

1994-01-01

Abstract Aeroelasticity which involves strong coupling of fluids, structures and controls is an important element in designing an aircraft. Computational aeroelasticity using low fidelity methods such as the linear aerodynamic flow equations coupled with the modal structural equations are well advanced. Though these low fidelity approaches are computationally less intensive, they are not adequate for the analysis of modern aircraft such as High Speed Civil Transport (HSCT) and Advanced Subsonic Transport (AST) which can experience complex flow/structure interactions. HSCT can experience vortex induced aeroelastic oscillations whereas AST can experience transonic buffet associated structural oscillations. Both aircraft may experience a dip in the flutter speed at the transonic regime. For accurate aeroelastic computations at these complex fluid/structure interaction situations, high fidelity equations such as the Navier-Stokes for fluids and the finite-elements for structures are needed. Computations using these high fidelity equations require large computational resources both in memory and speed. Current conventional super computers have reached their limitations both in memory and speed. As a result, parallel computers have evolved to overcome the limitations of conventional computers. This paper will address the transition that is taking place in computational aeroelasticity from conventional computers to parallel computers. The paper will address special techniques needed to take advantage of the architecture of new parallel computers. Results will be illustrated from computations made on iPSC/860 and IBM SP2 computer by using ENSAERO code that directly couples the Euler/Navier-Stokes flow equations with high resolution finite-element structural equations.

The Effects of Moderate- and High-Fidelity Patient Simulator Use on Critical Thinking in Associate Degree Nursing Students

ERIC Educational Resources Information Center

Vieck, Jana

2013-01-01

The purpose of this study was to examine the impact of moderate- and high-fidelity patient simulator use on the critical thinking skills of associate degree nursing students. This quantitative study used a quasi-experimental design and the Health Sciences Reasoning Test (HSRT) to evaluate the critical thinking skills of third semester nursing…

Using a High-Fidelity Patient Simulator with First-Year Medical Students to Facilitate Learning of Cardiovascular Function Curves

ERIC Educational Resources Information Center

Harris, David M.; Ryan, Kathleen; Rabuck, Cynthia

2012-01-01

Students are relying on technology for learning more than ever, and educators need to adapt to facilitate student learning. High-fidelity patient simulators (HFPS) are usually reserved for the clinical years of medical education and are geared to improve clinical decision skills, teamwork, and patient safety. Finding ways to incorporate HFPS into…

Modeling of Passive Acoustic Liners from High Fidelity Numerical Simulations

NASA Astrophysics Data System (ADS)

Ferrari, Marcello do Areal Souto

Noise reduction in aviation has been an important focus of study in the last few decades. One common solution is setting up acoustic liners in the internal walls of the engines. However, measurements in the laboratory with liners are expensive and time consuming. The present work proposes a nonlinear physics-based time domain model to predict the acoustic behavior of a given liner in a defined flow condition. The parameters of the model are defined by analysis of accurate numerical solutions of the flow obtained from a high-fidelity numerical code. The length of the cavity is taken into account by using an analytical procedure to account for internal reflections in the interior of the cavity. Vortices and jets originated from internal flow separations are confirmed to be important mechanisms of sound absorption, which defines the overall efficiency of the liner. Numerical simulations at different frequency, geometry and sound pressure level are studied in detail to define the model parameters. Comparisons with high-fidelity numerical simulations show that the proposed model is accurate, robust, and can be used to define a boundary condition simulating a liner in a high-fidelity code.

Comparison of Low-Thrust Control Laws for Application in Planetocentric Space

NASA Technical Reports Server (NTRS)

Falck, Robert D.; Sjauw, Waldy K.; Smith, David A.

2014-01-01

Recent interest at NASA for the application of solar electric propulsion for the transfer of significant payloads in cislunar space has led to the development of high-fidelity simulations of such missions. With such transfers involving transfer times on the order of months, simulation time can be significant. In the past, the examination of such missions typically began with the use of lower-fidelity trajectory optimization tools such as SEPSPOT to develop and tune guidance laws which delivered optimal or near- optimal trajectories, where optimal is generally defined as minimizing propellant expenditure or time of flight. The transfer of these solutions to a high-fidelity simulation is typically an iterative process whereby the initial solution may nearly, but not precisely, meet mission objectives. Further tuning of the guidance algorithm is typically necessary when accounting for high-fidelity perturbations such as those due to more detailed gravity models, secondary-body effects, solar radiation pressure, etc. While trajectory optimization is a useful method for determining optimal performance metrics, algorithms which deliver nearly optimal performance with minimal tuning are an attractive alternative.

An adaptive sampling method for variable-fidelity surrogate models using improved hierarchical kriging

NASA Astrophysics Data System (ADS)

Hu, Jiexiang; Zhou, Qi; Jiang, Ping; Shao, Xinyu; Xie, Tingli

2018-01-01

Variable-fidelity (VF) modelling methods have been widely used in complex engineering system design to mitigate the computational burden. Building a VF model generally includes two parts: design of experiments and metamodel construction. In this article, an adaptive sampling method based on improved hierarchical kriging (ASM-IHK) is proposed to refine the improved VF model. First, an improved hierarchical kriging model is developed as the metamodel, in which the low-fidelity model is varied through a polynomial response surface function to capture the characteristics of a high-fidelity model. Secondly, to reduce local approximation errors, an active learning strategy based on a sequential sampling method is introduced to make full use of the already required information on the current sampling points and to guide the sampling process of the high-fidelity model. Finally, two numerical examples and the modelling of the aerodynamic coefficient for an aircraft are provided to demonstrate the approximation capability of the proposed approach, as well as three other metamodelling methods and two sequential sampling methods. The results show that ASM-IHK provides a more accurate metamodel at the same simulation cost, which is very important in metamodel-based engineering design problems.

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

Zahn, Karl E.; Averill, April; Wallace, Susan S.

5-Hydroxycytosine (5-OHC) is a stable oxidation product of cytosine associated with an increased frequency of C {yields} T transition mutations. When this lesion escapes recognition by the base excision repair pathway and persists to serve as a templating base during DNA synthesis, replicative DNA polymerases often misincorporate dAMP at the primer terminus, which can lead to fixation of mutations and subsequent disease. To characterize the dynamics of DNA synthesis opposite 5-OHC, we initiated a comparison of unmodified dCMP to 5-OHC, 5-fluorocytosine (5-FC), and 5-methylcytosine (5-MEC) in which these bases act as templates in the active site of RB69 gp43, amore » high-fidelity DNA polymerase sharing homology with human replicative DNA polymerases. This study presents the first crystal structure of any DNA polymerase binding this physiologically important premutagenic DNA lesion, showing that while dGMP is stabilized by 5-OHC through normal Watson-Crick base pairing, incorporation of dAMP leads to unstacking and instability in the template. Furthermore, the electronegativity of the C5 substituent appears to be important in the miscoding potential of these cytosine-like templates. While dAMP is incorporated opposite 5-OHC {approx}5 times more efficiently than opposite unmodified dCMP, an elevated level of incorporation is also observed opposite 5-FC but not 5-MEC. Taken together, these data imply that the nonuniform templating by 5-OHC is due to weakened stacking capabilities, which allows dAMP incorporation to proceed in a manner similar to that observed opposite abasic sites.« less

Presynaptic Filament Dynamics in Homologous Recombination and DNA Repair

PubMed Central

Liu, Jie; Ehmsen, Kirk T.; Heyer, Wolf-Dietrich; Morrical, Scott W.

2014-01-01

Homologous Recombination (HR) is an essential genome stability mechanism used for high-fidelity repair of DNA double-strand breaks and for the recovery of stalled or collapsed DNA replication forks. The crucial homology search and DNA strand exchange steps of HR are catalyzed by presynaptic filaments—helical filaments of a recombinase enzyme bound to single-stranded DNA. Presynaptic filaments are fundamentally dynamic structures, the assembly, catalytic turnover, and disassembly of which must be closely coordinated with other elements of the DNA recombination, repair, and replication machinery in order for genome maintenance functions to be effective. Here, we review the major dynamic elements controlling the assembly, activity, and disassembly of presynaptic filaments: some intrinsic such as recombinase ATP binding and hydrolytic activities, others extrinsic such as ssDNA-binding proteins, mediator proteins, and DNA motor proteins. We examine dynamic behavior on multiple levels, including atomic- and filament-level structural changes associated with ATP binding and hydrolysis as evidenced in crystal structures, as well as subunit binding and dissociation events driven by intrinsic and extrinsic factors. We examine the biochemical properties of recombination proteins from four model systems (T4 phage, E. coli, S. cerevisiae, and H. sapiens), demonstrating how their properties are tailored for the context-specific requirements in these diverse species. We propose that the presynaptic filament has evolved to rely on multiple external factors for increased multi-level regulation of HR processes in genomes with greater structural and sequence complexity. PMID:21599536

Creation of a High-fidelity, Low-cost Pediatric Skull Fracture Ultrasound Phantom.

PubMed

Soucy, Zachary P; Mills, Lisa; Rose, John S; Kelley, Kenneth; Ramirez, Francisco; Kuppermann, Nathan

2015-08-01

Over the past decade, point-of-care ultrasound has become a common tool used for both procedures and diagnosis. Developing high-fidelity phantoms is critical for training in new and novel point-of-care ultrasound applications. Detecting skull fractures on ultrasound imaging in the younger-than-2-year-old patient is an emerging area of point-of-care ultrasound research. Identifying a skull fracture on ultrasound imaging in this age group requires knowledge of the appearance and location of sutures to distinguish them from fractures. There are currently no commercially available pediatric skull fracture models. We outline a novel approach to building a cost-effective, simple, high-fidelity pediatric skull fracture phantom to meet a unique training requirement. © 2015 by the American Institute of Ultrasound in Medicine.

Measuring Implementation Fidelity in a Community-Based Parenting Intervention

PubMed Central

Breitenstein, Susan M.; Fogg, Louis; Garvey, Christine; Hill, Carri; Resnick, Barbara; Gross, Deborah

2012-01-01

Background Establishing the feasibility and validity of implementation fidelity monitoring strategies is an important methodological step in implementing evidence-based interventions on a large scale. Objectives The objective of the study was to examine the reliability and validity of the Fidelity Checklist, a measure designed to assess group leader adherence and competence delivering a parent training intervention (the Chicago Parent Program) in child care centers serving low-income families. Method The sample included 9 parent groups (12 group sessions each), 12 group leaders, and 103 parents. Independent raters reviewed 106 audiotaped parent group sessions and coded group leaders’ fidelity on the Adherence and Competence Scales of the Fidelity Checklist. Group leaders completed self-report adherence checklists and a measure of parent engagement in the intervention. Parents completed measures of consumer satisfaction and child behavior. Results High interrater agreement (Adherence Scale = 94%, Competence Scale = 85%) and adequate intraclass correlation coefficients (Adherence Scale = .69, Competence Scale = .91) were achieved for the Fidelity Checklist. Group leader adherence changed over time, but competence remained stable. Agreement between group leader self-report and independent ratings on the Adherence Scale was 85%; disagreements were more frequently due to positive bias in group leader self-report. Positive correlations were found between group leader adherence and parent attendance and engagement in the intervention and between group leader competence and parent satisfaction. Although child behavior problems improved, improvements were not related to fidelity. Discussion The results suggest that the Fidelity Checklist is a feasible, reliable, and valid measure of group leader implementation fidelity in a group-based parenting intervention. Future research will be focused on testing the Fidelity Checklist with diverse and larger samples and generalizing to other group-based interventions using a similar intervention model. PMID:20404777

Cloning SU8 silicon masters using epoxy resins to increase feature replicability and production for cell culture devices.

PubMed

Kamande, J W; Wang, Y; Taylor, A M

2015-05-01

In recent years, there has been a dramatic increase in the use of poly(dimethylsiloxane) (PDMS) devices for cell-based studies. Commonly, the negative tone photoresist, SU8, is used to pattern features onto silicon wafers to create masters (SU8-Si) for PDMS replica molding. However, the complexity in the fabrication process, low feature reproducibility (master-to-master variability), silane toxicity, and short life span of these masters have been deterrents for using SU8-Si masters for the production of cell culture based PDMS microfluidic devices. While other techniques have demonstrated the ability to generate multiple devices from a single master, they often do not match the high feature resolution (∼0.1 μm) and low surface roughness that soft lithography masters offer. In this work, we developed a method to fabricate epoxy-based masters that allows for the replication of features with high fidelity directly from SU8-Si masters via their PDMS replicas. By this method, we show that we could obtain many epoxy based masters with equivalent features to a single SU8-Si master with a low feature variance of 1.54%. Favorable feature transfer resolutions were also obtained by using an appropriate Tg epoxy based system to ensure minimal shrinkage of features ranging in size from ∼100 μm to <10 μm in height. We further show that surface coating epoxy masters with Cr/Au lead to effective demolding and yield PDMS chambers that are suitable for long-term culturing of sensitive primary hippocampal neurons. Finally, we incorporated pillars within the Au-epoxy masters to eliminate the process of punching media reservoirs and thereby reducing substantial artefacts and wastage.

Cloning SU8 silicon masters using epoxy resins to increase feature replicability and production for cell culture devices

PubMed Central

Kamande, J. W.; Wang, Y.; Taylor, A. M.

2015-01-01

In recent years, there has been a dramatic increase in the use of poly(dimethylsiloxane) (PDMS) devices for cell-based studies. Commonly, the negative tone photoresist, SU8, is used to pattern features onto silicon wafers to create masters (SU8-Si) for PDMS replica molding. However, the complexity in the fabrication process, low feature reproducibility (master-to-master variability), silane toxicity, and short life span of these masters have been deterrents for using SU8-Si masters for the production of cell culture based PDMS microfluidic devices. While other techniques have demonstrated the ability to generate multiple devices from a single master, they often do not match the high feature resolution (∼0.1 μm) and low surface roughness that soft lithography masters offer. In this work, we developed a method to fabricate epoxy-based masters that allows for the replication of features with high fidelity directly from SU8-Si masters via their PDMS replicas. By this method, we show that we could obtain many epoxy based masters with equivalent features to a single SU8-Si master with a low feature variance of 1.54%. Favorable feature transfer resolutions were also obtained by using an appropriate Tg epoxy based system to ensure minimal shrinkage of features ranging in size from ∼100 μm to <10 μm in height. We further show that surface coating epoxy masters with Cr/Au lead to effective demolding and yield PDMS chambers that are suitable for long-term culturing of sensitive primary hippocampal neurons. Finally, we incorporated pillars within the Au-epoxy masters to eliminate the process of punching media reservoirs and thereby reducing substantial artefacts and wastage. PMID:26180572

Housing first on a large scale: Fidelity strengths and challenges in the VA's HUD-VASH program.

PubMed

Kertesz, Stefan G; Austin, Erika L; Holmes, Sally K; DeRussy, Aerin J; Van Deusen Lukas, Carol; Pollio, David E

2017-05-01

Housing First (HF) combines permanent supportive housing and supportive services for homeless individuals and removes traditional treatment-related preconditions for housing entry. There has been little research describing strengths and shortfalls of HF implementation outside of research demonstration projects. The U.S. Department of Veterans Affairs (VA) has transitioned to an HF approach in a supportive housing program serving over 85,000 persons. This offers a naturalistic window to study fidelity when HF is adopted on a large scale. We operationalized HF into 20 criteria grouped into 5 domains. We assessed 8 VA medical centers twice (1 year apart), scoring each criterion using a scale ranging from 1 ( low fidelity ) to 4 ( high fidelity ). There were 2 HF domains (no preconditions and rapidly offering permanent housing) for which high fidelity was readily attained. There was uneven progress in prioritizing the most vulnerable clients for housing support. Two HF domains (sufficient supportive services and a modern recovery philosophy) had considerably lower fidelity. Interviews suggested that operational issues such as shortfalls in staffing and training likely hindered performance in these 2 domains. In this ambitious national HF program, the largest to date, we found substantial fidelity in focusing on permanent housing and removal of preconditions to housing entry. Areas of concern included the adequacy of supportive services and adequacy in deployment of a modern recovery philosophy. Under real-world conditions, large-scale implementation of HF is likely to require significant additional investment in client service supports to assure that results are concordant with those found in research studies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

High-Fidelity Design of Multimodal Restorative Interventions in Gulf War Illness

DTIC Science & Technology

2017-10-01

Bockmayr A, Klarner H, Siebert H. Time series dependent analysis of unparametrized Thomas networks. IEEE/ACM Transactions on Computational Biology and...Award Number: W81XWH-15-1-0582 TITLE:High-Fidelity Design of Multimodal Restorative Interventions in Gulf War Illness PRINCIPAL INVESTIGATOR...not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT

Effects of High Fidelity Simulation on Knowledge Acquisition, Self-Confidence, and Satisfaction with Baccalaureate Nursing Students Using the Solomon-Four Research Design

ERIC Educational Resources Information Center

Hall, Rachel Mattson

2013-01-01

High Fidelity Simulation is a teaching strategy that is becoming well-entrenched in the world of nursing education and is rapidly expanding due to the challenges and demands of the health care environment. The problem addressed in this study is the conflicting research results regarding the effectiveness of HFS for students' knowledge acquisition…

Effects of High-Fidelity Human Patient Simulation Experience on Self-Efficacy, Motivation and Learning of First Semester Associate Degree Nursing Students

ERIC Educational Resources Information Center

Kuznar, Kathleen A.

2009-01-01

One of the newest methodologies in nursing education is high-fidelity human patient simulation (HPS). Many nursing educators have embraced the method as it offers a strategy to facilitate cognitive, affective, and psychomotor outcomes. Despite their popularity, however, HPS systems are costly and, in an era of cost containment and tuition…

SITE FIDELITY AND EPHEMERAL HABITAT OCCUPANCY: NORTHERN WATERTHRUSH USE OF PUERTO RICAN BLACK MANGROVES DURING THE NONBREEDING SEASON.

Treesearch

LEONARD REITSMA; PAMELA HUNT; SHERMAN L. BURSON III; BENJAMIN B. STEELE

2002-01-01

We studied the dispersion of Northern Waterthrushes (Seiurus novaboracensis) in southwestern Puerto Rico during four nonbreeding seasons, 1996–1999. Densities were high (up to 13 birds/ha) on a 3-ha mature black mangrove (Avicennia germinans) study plot, but were significantly lower during periods of high water levels. Individuals exhibited site fidelity within and...

Comparison of Satisfaction, Self-Confidence, and Engagement of Baccalaureate Nursing Students Using Defined Observational Roles and Expectations versus Traditional Role Assignments in High Fidelity Simulation and Debriefing

ERIC Educational Resources Information Center

Howard, Sheri

2017-01-01

The purpose of this study is to compare satisfaction, self-confidence, and engagement of baccalaureate nursing students using defined observational roles and expectations versus traditional observer role assignments in high fidelity simulation and debriefing and to evaluate student perceptions of these constructs. The NLN/Jeffries Simulation…

An Evaluation of Immediate Outcomes and Fidelity of a Drug Abuse Prevention Program in Continuation High Schools: Project towards No Drug Abuse (TND)

ERIC Educational Resources Information Center

Lisha, Nadra E.; Sun, Ping; Rohrbach, Louise A.; Spruijt-Metz, Donna; Unger, Jennifer B.; Sussman, Steve

2012-01-01

The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n = 1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational…

Motivation and Technological Readiness in the Use of High-Fidelity Simulation: A Descriptive Comparative Study of Nurse Educators

ERIC Educational Resources Information Center

Duvall, Judy Jo

2012-01-01

There are many driving forces to increase the use of high-fidelity simulation (HFS) in nursing education, as well as many factors that may influence the implementation of this teaching strategy. These include the motivation of nurse educators to use HFS, the technological readiness of nurse educators to use HFS and the changing demographics of the…

Evaluation of high fidelity patient simulator in assessment of performance of anaesthetists.

PubMed

Weller, J M; Bloch, M; Young, S; Maze, M; Oyesola, S; Wyner, J; Dob, D; Haire, K; Durbridge, J; Walker, T; Newble, D

2003-01-01

There is increasing emphasis on performance-based assessment of clinical competence. The High Fidelity Patient Simulator (HPS) may be useful for assessment of clinical practice in anaesthesia, but needs formal evaluation of validity, reliability, feasibility and effect on learning. We set out to assess the reliability of a global rating scale for scoring simulator performance in crisis management. Using a global rating scale, three judges independently rated videotapes of anaesthetists in simulated crises in the operating theatre. Five anaesthetists then independently rated subsets of these videotapes. There was good agreement between raters for medical management, behavioural attributes and overall performance. Agreement was high for both the initial judges and the five additional raters. Using a global scale to assess simulator performance, we found good inter-rater reliability for scoring performance in a crisis. We estimate that two judges should provide a reliable assessment. High fidelity simulation should be studied further for assessing clinical performance.

Enhanced fidelity of an educational intervention on skin self-examination through surveillance and standardization

PubMed Central

Gaber, Rikki; Mallett, Kimberly A.; Hultgren, Brittney; Turrisi, Rob; Gilbertsen, Margaret L.; Martini, Mary C.; Robinson, June K.

2014-01-01

Background Melanoma can metastasize but is often successfully treated when discovered in an early stage. Melanoma patients and their skin check partners can learn skin self-examination (SSE) skills and these skills can be improved by practice. The purpose of this study is to determine the degree of fidelity with which educational in-person SSE intervention can be delivered by trained research coordinators to patients at risk of developing another melanoma and their skin check partners. Methods The in-person intervention was performed in two iterations. In phase 1 (2006-2008), the research coordinators were trained to perform the intervention using a written script. In phase 2 (2011-2013), the research coordinators were trained to perform the intervention with a PowerPoint aid. Each research coordinator was individually counseled by one of the authors (KM) to insure standardization and enhance fidelity of intervention delivery. Phase 1 and Phase 2 were compared on 16 fidelity components. Further, Phase 2 fidelity was assessed by comparing mean scores of fidelity across the five research coordinators who delivered the intervention. Results Phase 2, which utilized a PowerPoint aid, was delivered with a higher degree of fidelity compared to phase 1with four fidelity components with significantly higher fidelity than Phase 1: 1) Explained details of melanoma, χ2 (1, n = 199)= 96.31, p < .001, 2) Discussed when to call doctor, χ2 (1, n = 199) = 53.68, p < .001 3) Explained assessment at month 1, χ2 (1, n = 199)= 12.39, p < .01, and 4) Explained assessment at month 2, χ2 (1, n = 199) = 117.75, p < .001. Further, no significant differences on mean fidelity were found across research coordinators in Phase 2. Discussion When using the PowerPoint aide, the research coordinators delivered the intervention with high fidelity (all scores >14) and there were no mean differences in fidelity across research coordinators, indicating consistency in fidelity. This can be attributed to the standardization and cueing that the PowerPoint program offered. Supervision was also a key component in establishing and maintaining fidelity of the patient educational process. This method of intervention delivery enables trained healthcare professionals to deliver an educational intervention in an effective, consistent manner. PMID:25414761

Enhanced fidelity of an educational intervention on skin self-examination through surveillance and standardization.

PubMed

Gaber, Rikki; Mallett, Kimberly A; Hultgren, Brittney; Turrisi, Rob; Gilbertsen, Margaret L; Martini, Mary C; Robinson, June K

2014-01-01

Melanoma can metastasize but is often successfully treated when discovered in an early stage. Melanoma patients and their skin check partners can learn skin self-examination (SSE) skills and these skills can be improved by practice. The purpose of this study is to determine the degree of fidelity with which educational in-person SSE intervention can be delivered by trained research coordinators to patients at risk of developing another melanoma and their skin check partners. The in-person intervention was performed in two iterations. In phase 1 (2006-2008), the research coordinators were trained to perform the intervention using a written script. In phase 2 (2011-2013), the research coordinators were trained to perform the intervention with a PowerPoint aid. Each research coordinator was individually counseled by one of the authors (KM) to insure standardization and enhance fidelity of intervention delivery. Phase 1 and Phase 2 were compared on 16 fidelity components. Further, Phase 2 fidelity was assessed by comparing mean scores of fidelity across the five research coordinators who delivered the intervention. Phase 2, which utilized a PowerPoint aid, was delivered with a higher degree of fidelity compared to phase 1with four fidelity components with significantly higher fidelity than Phase 1: 1) Explained details of melanoma, χ 2 (1, n = 199)= 96.31, p < .001, 2) Discussed when to call doctor, χ 2 (1, n = 199) = 53.68, p < .001 3) Explained assessment at month 1, χ 2 (1, n = 199)= 12.39, p < .01, and 4) Explained assessment at month 2, χ 2 (1, n = 199) = 117.75, p < .001. Further, no significant differences on mean fidelity were found across research coordinators in Phase 2. When using the PowerPoint aide, the research coordinators delivered the intervention with high fidelity (all scores >14) and there were no mean differences in fidelity across research coordinators, indicating consistency in fidelity. This can be attributed to the standardization and cueing that the PowerPoint program offered. Supervision was also a key component in establishing and maintaining fidelity of the patient educational process. This method of intervention delivery enables trained healthcare professionals to deliver an educational intervention in an effective, consistent manner.

The Simplified Aircraft-Based Paired Approach With the ALAS Alerting Algorithm

NASA Technical Reports Server (NTRS)

Perry, Raleigh B.; Madden, Michael M.; Torres-Pomales, Wilfredo; Butler, Ricky W.

2013-01-01

This paper presents the results of an investigation of a proposed concept for closely spaced parallel runways called the Simplified Aircraft-based Paired Approach (SAPA). This procedure depends upon a new alerting algorithm called the Adjacent Landing Alerting System (ALAS). This study used both low fidelity and high fidelity simulations to validate the SAPA procedure and test the performance of the new alerting algorithm. The low fidelity simulation enabled a determination of minimum approach distance for the worst case over millions of scenarios. The high fidelity simulation enabled an accurate determination of timings and minimum approach distance in the presence of realistic trajectories, communication latencies, and total system error for 108 test cases. The SAPA procedure and the ALAS alerting algorithm were applied to the 750-ft parallel spacing (e.g., SFO 28L/28R) approach problem. With the SAPA procedure as defined in this paper, this study concludes that a 750-ft application does not appear to be feasible, but preliminary results for 1000-ft parallel runways look promising.

Biophysical stimulation for in vitro engineering of functional cardiac tissues.

PubMed

Korolj, Anastasia; Wang, Erika Yan; Civitarese, Robert A; Radisic, Milica

2017-07-01

Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Probabilistic Metrology Attains Macroscopic Cloning of Quantum Clocks

NASA Astrophysics Data System (ADS)

Gendra, B.; Calsamiglia, J.; Muñoz-Tapia, R.; Bagan, E.; Chiribella, G.

2014-12-01

It has recently been shown that probabilistic protocols based on postselection boost the performances of the replication of quantum clocks and phase estimation. Here we demonstrate that the improvements in these two tasks have to match exactly in the macroscopic limit where the number of clones grows to infinity, preserving the equivalence between asymptotic cloning and state estimation for arbitrary values of the success probability. Remarkably, the cloning fidelity depends critically on the number of rationally independent eigenvalues of the clock Hamiltonian. We also prove that probabilistic metrology can simulate cloning in the macroscopic limit for arbitrary sets of states when the performance of the simulation is measured by testing small groups of clones.

Critical thinking skills in nursing students: comparison of simulation-based performance with metrics.

PubMed

Fero, Laura J; O'Donnell, John M; Zullo, Thomas G; Dabbs, Annette DeVito; Kitutu, Julius; Samosky, Joseph T; Hoffman, Leslie A

2010-10-01

This paper is a report of an examination of the relationship between metrics of critical thinking skills and performance in simulated clinical scenarios. Paper and pencil assessments are commonly used to assess critical thinking but may not reflect simulated performance. In 2007, a convenience sample of 36 nursing students participated in measurement of critical thinking skills and simulation-based performance using videotaped vignettes, high-fidelity human simulation, the California Critical Thinking Disposition Inventory and California Critical Thinking Skills Test. Simulation-based performance was rated as 'meeting' or 'not meeting' overall expectations. Test scores were categorized as strong, average, or weak. Most (75.0%) students did not meet overall performance expectations using videotaped vignettes or high-fidelity human simulation; most difficulty related to problem recognition and reporting findings to the physician. There was no difference between overall performance based on method of assessment (P = 0.277). More students met subcategory expectations for initiating nursing interventions (P ≤ 0.001) using high-fidelity human simulation. The relationship between videotaped vignette performance and critical thinking disposition or skills scores was not statistically significant, except for problem recognition and overall critical thinking skills scores (Cramer's V = 0.444, P = 0.029). There was a statistically significant relationship between overall high-fidelity human simulation performance and overall critical thinking disposition scores (Cramer's V = 0.413, P = 0.047). Students' performance reflected difficulty meeting expectations in simulated clinical scenarios. High-fidelity human simulation performance appeared to approximate scores on metrics of critical thinking best. Further research is needed to determine if simulation-based performance correlates with critical thinking skills in the clinical setting. © 2010 The Authors. Journal of Advanced Nursing © 2010 Blackwell Publishing Ltd.

Critical thinking skills in nursing students: comparison of simulation-based performance with metrics

PubMed Central

Fero, Laura J.; O’Donnell, John M.; Zullo, Thomas G.; Dabbs, Annette DeVito; Kitutu, Julius; Samosky, Joseph T.; Hoffman, Leslie A.

2018-01-01

Aim This paper is a report of an examination of the relationship between metrics of critical thinking skills and performance in simulated clinical scenarios. Background Paper and pencil assessments are commonly used to assess critical thinking but may not reflect simulated performance. Methods In 2007, a convenience sample of 36 nursing students participated in measurement of critical thinking skills and simulation-based performance using videotaped vignettes, high-fidelity human simulation, the California Critical Thinking Disposition Inventory and California Critical Thinking Skills Test. Simulation- based performance was rated as ‘meeting’ or ‘not meeting’ overall expectations. Test scores were categorized as strong, average, or weak. Results Most (75·0%) students did not meet overall performance expectations using videotaped vignettes or high-fidelity human simulation; most difficulty related to problem recognition and reporting findings to the physician. There was no difference between overall performance based on method of assessment (P = 0·277). More students met subcategory expectations for initiating nursing interventions (P ≤ 0·001) using high-fidelity human simulation. The relationship between video-taped vignette performance and critical thinking disposition or skills scores was not statistically significant, except for problem recognition and overall critical thinking skills scores (Cramer’s V = 0·444, P = 0·029). There was a statistically significant relationship between overall high-fidelity human simulation performance and overall critical thinking disposition scores (Cramer’s V = 0·413, P = 0·047). Conclusion Students’ performance reflected difficulty meeting expectations in simulated clinical scenarios. High-fidelity human simulation performance appeared to approximate scores on metrics of critical thinking best. Further research is needed to determine if simulation-based performance correlates with critical thinking skills in the clinical setting. PMID:20636471

High-fidelity simulation of transcutaneous cardiac pacing: characteristics and limitations of available high-fidelity simulators, and description of an alternative two-mannequin model.

PubMed

Robitaille, Arnaud; Perron, Roger; Germain, Jean-François; Tanoubi, Issam; Georgescu, Mihai

2015-04-01

Transcutaneous cardiac pacing (TCP) is a potentially lifesaving technique that is part of the recommended treatment for symptomatic bradycardia. Transcutaneous cardiac pacing however is used uncommonly, and its successful application is not straightforward. Simulation could, therefore, play an important role in the teaching and assessment of TCP competence. However, even the highest-fidelity mannequins available on the market have important shortcomings, which limit the potential of simulation. Six criteria defining clinical competency in TCP were established and used as a starting point in the creation of an improved TCP simulator. The goal was a model that could be used to assess experienced clinicians, an objective that justifies the additional effort required by the increased fidelity. The proposed 2-mannequin model (TMM) combines a highly modified Human Patient Simulator with a SimMan 3G, the latter being used solely to provide the electrocardiography (ECG) tracing. The TMM improves the potential of simulation to assess experienced clinicians (1) by reproducing key features of TCP, like using the same multifunctional pacing electrodes used clinically, allowing dual ECG monitoring, and responding with upper body twitching when stimulated, but equally importantly (2) by reproducing key pitfalls of the technique, like allowing pacing electrode misplacement and reproducing false signs of ventricular capture, commonly, but erroneously, used clinically to establish that effective pacing has been achieved (like body twitching, electrical artifact on the ECG, and electrical capture without ventricular capture). The proposed TMM uses a novel combination of 2 high-fidelity mannequins to improve TCP simulation until upgraded mannequins become commercially available.

Brownian Ratchet Mechanism for Faithful Segregation of Low-Copy-Number Plasmids.

PubMed

Hu, Longhua; Vecchiarelli, Anthony G; Mizuuchi, Kiyoshi; Neuman, Keir C; Liu, Jian

2017-04-11

Bacterial plasmids are extrachromosomal DNA that provides selective advantages for bacterial survival. Plasmid partitioning can be remarkably robust. For high-copy-number plasmids, diffusion ensures that both daughter cells inherit plasmids after cell division. In contrast, most low-copy-number plasmids need to be actively partitioned by a conserved tripartite ParA-type system. ParA is an ATPase that binds to chromosomal DNA; ParB is the stimulator of the ParA ATPase and specifically binds to the plasmid at a centromere-like site, parS. ParB stimulation of the ParA ATPase releases ParA from the bacterial chromosome, after which it takes a long time to reset its DNA-binding affinity. We previously demonstrated in vitro that the ParA system can exploit this biochemical asymmetry for directed cargo transport. Multiple ParA-ParB bonds can bridge a parS-coated cargo to a DNA carpet, and they can work collectively as a Brownian ratchet that directs persistent cargo movement with a ParA-depletion zone trailing behind. By extending this model, we suggest that a similar Brownian ratchet mechanism recapitulates the full range of actively segregated plasmid motilities observed in vivo. We demonstrate that plasmid motility is tuned as the replenishment rate of the ParA-depletion zone progressively increases relative to the cargo speed, evolving from diffusion to pole-to-pole oscillation, local excursions, and, finally, immobility. When the plasmid replicates, the daughters largely display motilities similar to that of their mother, except that when the single-focus progenitor is locally excursive, the daughter foci undergo directed segregation. We show that directed segregation maximizes the fidelity of plasmid partition. Given that local excursion and directed segregation are the most commonly observed modes of plasmid motility in vivo, we suggest that the operation of the ParA-type partition system has been shaped by evolution for high fidelity of plasmid segregation. Published by Elsevier Inc.

Three-Dimensional Engineered High Fidelity Normal Human Lung Tissue-Like Assemblies (TLA) as Targets for Human Respiratory Virus Infections

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Deatly, A. M.; Suderman, M. T.; Lin, Y.-H.; Chen, W.; Gupta, C. K.; Randolph, V. B.; Udem, S. A.

2003-01-01

Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) tissue-like assemblies (TLA) (Goodwin et aI, 1992, 1993, 2000 and Nickerson et aI. , 2001,2002) offer high organ fidelity with the potential to emulate the infective dynamics of viruses and bacteria in vivo. Thus, utilizing NASA micro gravity Rotating Wall Vessel (RWV) technology, in vitro human broncho-epithelial (HBE) TLAs were engineered to mimic in vivo tissue for study of human respiratory viruses. These 3D HBE TLAs were propagated from a human broncho-tracheal cell line with a mesenchymal component (HBTC) as the foundation matrix and either an adult human broncho-epithelial cell (BEAS-2B) or human neonatal epithelial cell (16HBE140-) as the overlying element. Resulting TLAs share several characteristic features with in vivo human respiratory epithelium including tight junctions, desmosomes and cilia (SEM, TEM). The presence of epithelium and specific lung epithelium markers furthers the contention that these HBE cells differentiate into TLAs paralleling in vivo tissues. A time course of infection of these 3D HBE TLAs with human respiratory syncytial virus (hRSV) wild type A2 strain, indicates that virus replication and virus budding are supported and manifested by increasing virus titer and detection of membrane-bound F and G glycoproteins. Infected 3D HBE TLAs remain intact for up to 12 days compared to infected 2D cultures that are destroyed in 2-3 days. Infected cells show an increased vacuolation and cellular destruction (by transmission electron microscopy) by day 9; whereas, uninfected cells remain robust and morphologically intact. Therefore, the 3D HBE TLAs mimic aspects of human respiratory epithelium providing a unique opportunity to analyze, for the first time, simulated in vivo viral infection independent of host immune response.

Simulator technology as a tool for education in cardiac care.

PubMed

Hravnak, Marilyn; Beach, Michael; Tuite, Patricia

2007-01-01

Assisting nurses in gaining the cognitive and psychomotor skills necessary to safely and effectively care for patients with cardiovascular disease can be challenging for educators. Ideally, nurses would have the opportunity to synthesize and practice these skills in a protected training environment before application in the dynamic clinical setting. Recently, a technology known as high fidelity human simulation was introduced, which permits learners to interact with a simulated patient. The dynamic physiologic parameters and physical assessment capabilities of the simulated patient provide for a realistic learning environment. This article describes the High Fidelity Human Simulation Laboratory at the University of Pittsburgh School of Nursing and presents strategies for using this technology as a tool in teaching complex cardiac nursing care at the basic and advanced practice nursing levels. The advantages and disadvantages of high fidelity human simulation in learning are discussed.

Autonomous Aerobraking: Thermal Analysis and Response Surface Development

NASA Technical Reports Server (NTRS)

Dec, John A.; Thornblom, Mark N.

2011-01-01

A high-fidelity thermal model of the Mars Reconnaissance Orbiter was developed for use in an autonomous aerobraking simulation study. Response surface equations were derived from the high-fidelity thermal model and integrated into the autonomous aerobraking simulation software. The high-fidelity thermal model was developed using the Thermal Desktop software and used in all phases of the analysis. The use of Thermal Desktop exclusively, represented a change from previously developed aerobraking thermal analysis methodologies. Comparisons were made between the Thermal Desktop solutions and those developed for the previous aerobraking thermal analyses performed on the Mars Reconnaissance Orbiter during aerobraking operations. A variable sensitivity screening study was performed to reduce the number of variables carried in the response surface equations. Thermal analysis and response surface equation development were performed for autonomous aerobraking missions at Mars and Venus.

Band-selective shaped pulse for high fidelity quantum control in diamond

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

Chang, Yan-Chun; Xing, Jian; Liu, Gang-Qin

High fidelity quantum control of qubits is crucially important for realistic quantum computing, and it becomes more challenging when there are inevitable interactions between qubits. We introduce a band-selective shaped pulse, refocusing BURP (REBURP) pulse, to cope with the problems. The electron spin of nitrogen-vacancy centers in diamond is flipped with high fidelity by the REBURP pulse. In contrast with traditional rectangular pulses, the shaped pulse has almost equal excitation effect in a sharply edged region (in frequency domain). So the three sublevels of host {sup 14}N nuclear spin can be flipped accurately simultaneously, while unwanted excitations of other sublevelsmore » (e.g., of a nearby {sup 13}C nuclear spin) is well suppressed. Our scheme can be used for various applications such as quantum metrology, quantum sensing, and quantum information process.« less

Experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction.

PubMed

Lim, Hyang-Tag; Hong, Kang-Hee; Kim, Yoon-Ho

2015-10-21

Quantum coherence and entanglement, which are essential resources for quantum information, are often degraded and lost due to decoherence. Here, we report a proof-of-principle experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction. By unitarily switching the initial qubit encoding to another, which is insensitive to particular forms of decoherence, we have demonstrated that it is possible to avoid the effect of decoherence completely. In particular, we demonstrate high-fidelity distribution of photonic polarization entanglement over quantum channels with two types of decoherence, amplitude damping and polarization-mode dispersion, via qubit transduction between polarization qubits and dual-rail qubits. These results represent a significant breakthrough in quantum communication over decoherence channels as the protocol is input-state independent, requires no ancillary photons and symmetries, and has near-unity success probability.

Experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction

PubMed Central

Lim, Hyang-Tag; Hong, Kang-Hee; Kim, Yoon-Ho

2015-01-01

Quantum coherence and entanglement, which are essential resources for quantum information, are often degraded and lost due to decoherence. Here, we report a proof-of-principle experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction. By unitarily switching the initial qubit encoding to another, which is insensitive to particular forms of decoherence, we have demonstrated that it is possible to avoid the effect of decoherence completely. In particular, we demonstrate high-fidelity distribution of photonic polarization entanglement over quantum channels with two types of decoherence, amplitude damping and polarization-mode dispersion, via qubit transduction between polarization qubits and dual-rail qubits. These results represent a significant breakthrough in quantum communication over decoherence channels as the protocol is input-state independent, requires no ancillary photons and symmetries, and has near-unity success probability. PMID:26487083

Motivational Interviewing or Reminders for Glaucoma Medication Adherence? Results of a Multi-Site Randomized Controlled Trial

PubMed Central

Schmiege, Sarah J.; Mansberger, Steven L.; Sheppler, Christina; Kammer, Jeffrey; Fitzgerald, Timothy; Kahook, Malik Y.

2017-01-01

Objective Nonadherence reduces glaucoma treatment efficacy. Motivational interviewing (MI) is a well-studied adherence intervention, but has not been tested in glaucoma. Reminder interventions also may improve adherence. Design 201 patients with glaucoma or ocular hypertension were urn-randomized to receive MI delivered by an ophthalmic technician (OT), usual care, or a minimal behavioral intervention (reminder calls). Main Outcome Measures Outcomes included electronic monitoring with Medication Event Monitoring System (MEMS) bottles, two self-report adherence measures, patient satisfaction, and clinical outcomes. Multilevel modeling was used to test differences in MEMS results by group over time; ANCOVA was used to compare groups on other measures. Results Reminder calls increased adherence compared to usual care based on MEMS, p = .005, and self-report, p = .04. MI had a nonsignificant effect but produced higher satisfaction than reminder calls, p = .007. Treatment fidelity was high on most measures, with observable differences in behavior between groups. All groups had high baseline adherence that limited opportunities for change. Conclusion Reminder calls, but not MI, led to better adherence than usual care. Although a large literature supports MI, reminder calls might be a cost-effective intervention for patients with high baseline adherence. Replication is needed with less adherent participants. PMID:27701902

Design and fabrication of label-free biochip using a guided mode resonance filter with nano grating structures by injection molding process.

PubMed

Cho, E; Kim, B; Choi, S; Han, J; Jin, J; Han, J; Lim, J; Heo, Y; Kim, S; Sung, G Y; Kang, S

2011-01-01

This paper introduces technology to fabricate a guided mode resonance filter biochip using injection molding. Of the various nanofabrication processes that exist, injection molding is the most suitable for the mass production of polymer nanostructures. Fabrication of a nanograting pattern for guided mode resonance filters by injection molding requires a durable metal stamp, because of the high injection temperature and pressure. Careful consideration of the optimized process parameters is also required to achieve uniform sub-wavelength gratings with high fidelity. In this study, a metallic nanostructure pattern to be used as the stamp for the injection molding process was fabricated using electron beam lithography, a UV nanoimprinting process, and an electroforming process. A one-dimensional nanograting substrate was replicated by injection molding, during which the process parameters were controlled. To evaluate the geometric quality of the injection molded nanograting patterns, the surface profile of the fabricated nanograting for different processing conditions was analyzed using an atomic force microscope and a scanning electron microscope. Finally, to demonstrate the feasibility of the proposed process for fabricating guided mode resonance filter biochips, a high-refractive-index material was deposited on the polymer nanograting and its guided mode resonance characteristics were analyzed.

SOWFA Super-Controller: A High-Fidelity Tool for Evaluating Wind Plant Control Approaches

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

Fleming, P.; Gebraad, P.; van Wingerden, J. W.

2013-01-01

This paper presents a new tool for testing wind plant controllers in the Simulator for Offshore Wind Farm Applications (SOWFA). SOWFA is a high-fidelity simulator for the interaction between wind turbine dynamics and the fluid flow in a wind plant. The new super-controller testing environment in SOWFA allows for the implementation of the majority of the wind plant control strategies proposed in the literature.

Simulation Learning: PC-Screen Based (PCSB) versus High Fidelity Simulation (HFS)

DTIC Science & Technology

2012-08-01

methods for the use of simulation for teaching clinical skills to military and civilian clinicians . High fidelity simulation is an expensive method of...without the knowledge and approval of the IRB. Changes include, but not limited to, modifications in study design, recruitment process and number of...Person C-Collar simulation algorithm Pathway A Scenario A - Spinal stabilization: Sub processes Legend: Pathway Points Complex task to be performed by

Compact Single Site Resolution Cold Atom Experiment for Adiabatic Quantum Computing

DTIC Science & Technology

2016-02-03

goal of our scientific investigation is to demonstrate high fidelity and fast atom-atom entanglement between physically 1. REPORT DATE (DD-MM-YYYY) 4...of our scientific investigation is to demonstrate high fidelity and fast atom-atom entanglement between physically separated and optically addressed...Specifically, we will design and construct a set of compact single atom traps with integrated optics, suitable for heralded entanglement and loophole

High-fidelity patient simulation in nursing education: an integrative review.

PubMed

Weaver, Amy

2011-01-01

An integrative review was undertaken to analyze studies published since 1998 on the use of high-fidelity patient simulation (HFPS) in undergraduate nursing education. This review found that HFPS benefits nursing students in terms of knowledge, value, realism, and learner satisfaction;findings were mixed in the areas of student confidence, knowledge transfer, and stress. Further research in these and other areas will determine whether its increased use is warranted.

Rapidly reconfigurable high-fidelity optical arbitrary waveform generation in heterogeneous photonic integrated circuits.

PubMed

Feng, Shaoqi; Qin, Chuan; Shang, Kuanping; Pathak, Shibnath; Lai, Weicheng; Guan, Binbin; Clements, Matthew; Su, Tiehui; Liu, Guangyao; Lu, Hongbo; Scott, Ryan P; Ben Yoo, S J

2017-04-17

This paper demonstrates rapidly reconfigurable, high-fidelity optical arbitrary waveform generation (OAWG) in a heterogeneous photonic integrated circuit (PIC). The heterogeneous PIC combines advantages of high-speed indium phosphide (InP) modulators and low-loss, high-contrast silicon nitride (Si₃N₄) arrayed waveguide gratings (AWGs) so that high-fidelity optical waveform syntheses with rapid waveform updates are possible. The generated optical waveforms spanned a 160 GHz spectral bandwidth starting from an optical frequency comb consisting of eight comb lines separated by 20 GHz channel spacing. The Error Vector Magnitude (EVM) values of the generated waveforms were approximately 16.4%. The OAWG module can rapidly and arbitrarily reconfigure waveforms upon every pulse arriving at 2 ns repetition time. The result of this work indicates the feasibility of truly dynamic optical arbitrary waveform generation where the reconfiguration rate or the modulator bandwidth must exceed the channel spacing of the AWG and the optical frequency comb.

High-fidelity spin entanglement using optimal control.

PubMed

Dolde, Florian; Bergholm, Ville; Wang, Ya; Jakobi, Ingmar; Naydenov, Boris; Pezzagna, Sébastien; Meijer, Jan; Jelezko, Fedor; Neumann, Philipp; Schulte-Herbrüggen, Thomas; Biamonte, Jacob; Wrachtrup, Jörg

2014-02-28

Precise control of quantum systems is of fundamental importance in quantum information processing, quantum metrology and high-resolution spectroscopy. When scaling up quantum registers, several challenges arise: individual addressing of qubits while suppressing cross-talk, entangling distant nodes and decoupling unwanted interactions. Here we experimentally demonstrate optimal control of a prototype spin qubit system consisting of two proximal nitrogen-vacancy centres in diamond. Using engineered microwave pulses, we demonstrate single electron spin operations with a fidelity F≈0.99. With additional dynamical decoupling techniques, we further realize high-quality, on-demand entangled states between two electron spins with F>0.82, mostly limited by the coherence time and imperfect initialization. Crosstalk in a crowded spectrum and unwanted dipolar couplings are simultaneously eliminated to a high extent. Finally, by high-fidelity entanglement swapping to nuclear spin quantum memory, we demonstrate nuclear spin entanglement over a length scale of 25 nm. This experiment underlines the importance of optimal control for scalable room temperature spin-based quantum information devices.

Validation of a Low-Thrust Mission Design Tool Using Operational Navigation Software

NASA Technical Reports Server (NTRS)

Englander, Jacob A.; Knittel, Jeremy M.; Williams, Ken; Stanbridge, Dale; Ellison, Donald H.

2017-01-01

Design of flight trajectories for missions employing solar electric propulsion requires a suitably high-fidelity design tool. In this work, the Evolutionary Mission Trajectory Generator (EMTG) is presented as a medium-high fidelity design tool that is suitable for mission proposals. EMTG is validated against the high-heritage deep-space navigation tool MIRAGE, demonstrating both the accuracy of EMTG's model and an operational mission design and navigation procedure using both tools. The validation is performed using a benchmark mission to the Jupiter Trojans.

The Representational Consequences of Intentional Forgetting: Impairments to Both the Probability and Fidelity of Long-Term Memory

PubMed Central

2016-01-01

We investigated whether intentional forgetting impacts only the likelihood of later retrieval from long-term memory or whether it also impacts the fidelity of those representations that are successfully retrieved. We accomplished this by combining an item-method directed forgetting task with a testing procedure and modeling approach inspired by the delayed-estimation paradigm used in the study of visual short-term memory (STM). Abstract or concrete colored images were each followed by a remember (R) or forget (F) instruction and sometimes by a visual probe requiring a speeded detection response (E1–E3). Memory was tested using an old–new (E1–E2) or remember-know-no (E3) recognition task followed by a continuous color judgment task (E2–E3); a final experiment included only the color judgment task (E4). Replicating the existing literature, more “old” or “remember” responses were made to R than F items and RTs to postinstruction visual probes were longer following F than R instructions. Color judgments were more accurate for successfully recognized or recollected R than F items (E2–E3); a mixture model confirmed a decrease to both the probability of retrieving the F items as well as the fidelity of the representation of those F items that were retrieved (E4). We conclude that intentional forgetting is an effortful process that not only reduces the likelihood of successfully encoding an item for later retrieval, but also produces an impoverished memory trace even when those items are retrieved; these findings draw a parallel between the control of memory representations within working and long-term memory. PMID:26709589

Are physical activity interventions for healthy inactive adults effective in promoting behavior change and maintenance, and which behavior change techniques are effective? A systematic review and meta-analysis.

PubMed

Howlett, Neil; Trivedi, Daksha; Troop, Nicholas A; Chater, Angel Marie

2018-02-28

Physical inactivity and sedentary behavior relate to poor health outcomes independently. Healthy inactive adults are a key target population for prevention. This systematic review and meta-analysis aimed to evaluate the effectiveness of physical activity and/or sedentary behavior interventions, measured postintervention (behavior change) and at follow-up (behavior change maintenance), to identify behavior change techniques (BCT) within, and report on fidelity. Included studies were randomized controlled trials, targeting healthy inactive adults, aiming to change physical activity and/or sedentary behavior, with a minimum postintervention follow-up of 6 months, using 16 databases from 1990. Two reviewers independently coded risk of bias, the "Template for Intervention Description and Replication" (TIDieR) checklist, and BCTs. Twenty-six studies were included; 16 pooled for meta-analysis. Physical activity interventions were effective at changing behavior (d = 0.32, 95% confidence intervals = 0.16-0.48, n = 2,346) and maintaining behavior change after 6 months or more (d = 0.21, 95% confidence intervals = 0.12-0.30, n = 2,190). Sedentary behavior interventions (n = 2) were not effective. At postintervention, physical activity intervention effectiveness was associated with the BCTs "Biofeedback," "Demonstration of the behavior," "Behavior practice/rehearsal," and "Graded tasks." At follow-up, effectiveness was associated with using "Action planning," "Instruction on how to perform the behavior," "Prompts/cues," "Behavior practice/rehearsal," "Graded tasks," and "Self-reward." Fidelity was only documented in one study. Good evidence was found for behavior change maintenance effects in healthy inactive adults, and underlying BCTs. This review provides translational evidence to improve research, intervention design, and service delivery in physical activity interventions, while highlighting the lack of fidelity measurement.

The representational consequences of intentional forgetting: Impairments to both the probability and fidelity of long-term memory.

PubMed

Fawcett, Jonathan M; Lawrence, Michael A; Taylor, Tracy L

2016-01-01

We investigated whether intentional forgetting impacts only the likelihood of later retrieval from long-term memory or whether it also impacts the fidelity of those representations that are successfully retrieved. We accomplished this by combining an item-method directed forgetting task with a testing procedure and modeling approach inspired by the delayed-estimation paradigm used in the study of visual short-term memory (STM). Abstract or concrete colored images were each followed by a remember (R) or forget (F) instruction and sometimes by a visual probe requiring a speeded detection response (E1-E3). Memory was tested using an old-new (E1-E2) or remember-know-no (E3) recognition task followed by a continuous color judgment task (E2-E3); a final experiment included only the color judgment task (E4). Replicating the existing literature, more "old" or "remember" responses were made to R than F items and RTs to postinstruction visual probes were longer following F than R instructions. Color judgments were more accurate for successfully recognized or recollected R than F items (E2-E3); a mixture model confirmed a decrease to both the probability of retrieving the F items as well as the fidelity of the representation of those F items that were retrieved (E4). We conclude that intentional forgetting is an effortful process that not only reduces the likelihood of successfully encoding an item for later retrieval, but also produces an impoverished memory trace even when those items are retrieved; these findings draw a parallel between the control of memory representations within working and long-term memory. (c) 2015 APA, all rights reserved).

Intervention Fidelity in Family-Based Prevention Counseling for Adolescent Problem Behaviors

ERIC Educational Resources Information Center

Hogue, Aaron; Liddle, Howard A.; Singer, Alisa; Leckrone, Jodi

2005-01-01

This study examined fidelity in multidimensional family prevention (MDFP), a family-based prevention counseling model for adolescents at high risk for substance abuse and related behavior problems, in comparison to two empirically based treatments for adolescent drug abuse: multidimensional family therapy (MDFT) and cognitive-behavioral therapy…

Progress towards a microwave-based high-fidelity Toffoli gate with superconducting qubits

NASA Astrophysics Data System (ADS)

Rigetti, Chad; Chow, Jerry; Corcoles, Antonio; Rozen, Jim; Keefe, George; Rothwell, Mary Beth; Rohrs, Jack; Borstelmann, Mark; Divincenzo, David; Ketchen, Mark; Steffen, Matthias

2011-03-01

We describe recent progress at IBM towards a microwave-based implementation of the Toffoli gate using three capacitively shunted flux qubits dispersively coupled to a resonator. We discuss the device architecture and the microwave protocol, along with expected limits to gate fidelity and scaling.

Effect of improving the realism of simulated clinical judgement tasks on nurses' overconfidence and underconfidence: evidence from a comparative confidence calibration analysis.

PubMed

Yang, Huiqin; Thompson, Carl; Bland, Martin

2012-12-01

Apparent overconfidence and underconfidence in clinicians making clinical judgements could be a feature of evaluative research designs that fail to accurately represent clinical environments. To test the effect of improved realism of clinical judgement tasks on confidence calibration performance of nurses and student nurses. A comparative confidence calibration analysis. The study was conducted in a large university of Northern England. Ninety-seven participants rated their confidence - using a scale that ranged from 0 (no confidence) to 100 (totally confident) on dichotomous clinical judgements of critical event risk. The judgements were in response to 25 paper-based and 25 higher fidelity scenarios using a computerised patient simulator and clinical equipment. Scenarios, and judgement criteria of 'correctness', were generated from real patient cases. Using a series of calibration measures (calibration, resolution and over/underconfidence), participants' confidence was calibrated against the proportion of correct judgements. The calibration measures generated by the paper-based and high fidelity clinical simulation conditions were compared. Participants made significantly less accurate clinical judgements of risk in the high fidelity clinical simulations compared to the paper simulations (P=0.0002). They were significantly less confident in high fidelity clinical simulations than paper simulations (P=0.03). However, there was no significant difference of over/underconfidence for participants between the two simulated settings (P=0.06). Participants were no better calibrated in the high fidelity clinical simulations than paper simulations, P=0.85. Likewise, participants had no better ability of discriminating correct judgements from incorrect judgements as measured by the resolution statistic in high fidelity clinical simulations than paper simulations, P=0.76. Improving the realism of simulated judgement tasks led to reduced confidence and judgement accuracy in participants but did not alter confidence calibration. These findings suggest that judgemental miscalibration of confidence in nurses may be a systematic cognitive bias and that simply making scenarios more realistic may not be a sufficient condition for correction. Copyright © 2012 Elsevier Ltd. All rights reserved.

A simple, rapid, high-fidelity and cost-effective PCR-based two-step DNA synthesis method for long gene sequences.

PubMed

Xiong, Ai-Sheng; Yao, Quan-Hong; Peng, Ri-He; Li, Xian; Fan, Hui-Qin; Cheng, Zong-Ming; Li, Yi

2004-07-07

Chemical synthesis of DNA sequences provides a powerful tool for modifying genes and for studying gene function, structure and expression. Here, we report a simple, high-fidelity and cost-effective PCR-based two-step DNA synthesis (PTDS) method for synthesis of long segments of DNA. The method involves two steps. (i) Synthesis of individual fragments of the DNA of interest: ten to twelve 60mer oligonucleotides with 20 bp overlap are mixed and a PCR reaction is carried out with high-fidelity DNA polymerase Pfu to produce DNA fragments that are approximately 500 bp in length. (ii) Synthesis of the entire sequence of the DNA of interest: five to ten PCR products from the first step are combined and used as the template for a second PCR reaction using high-fidelity DNA polymerase pyrobest, with the two outermost oligonucleotides as primers. Compared with the previously published methods, the PTDS method is rapid (5-7 days) and suitable for synthesizing long segments of DNA (5-6 kb) with high G + C contents, repetitive sequences or complex secondary structures. Thus, the PTDS method provides an alternative tool for synthesizing and assembling long genes with complex structures. Using the newly developed PTDS method, we have successfully obtained several genes of interest with sizes ranging from 1.0 to 5.4 kb.

Numerical study of phase conjugation in stimulated Brillouin scattering from an optical waveguide

NASA Astrophysics Data System (ADS)

Lehmberg, R. H.

1983-05-01

Stimulated Brillouin scattering (SBS) in a multimode optical waveguide is examined, and the parameters that affect the wavefront conjugation fidelity are studied. The nonlinear propagation code is briefly described and the calculated quantities are defined. The parameter study in the low reflectivity limit is described, and the effects of pump depletion are considered. The waveguide produced significantly higher fidelities than the focused configuration, in agreement with several experimental studies. The light scattered back through the phase aberrator exhibited a farfield intenstiy profile closely matching that of the incident beam; however, the nearfield intensity exhibited large and rapid spatial inhomogeneities across the entire aberrator, even for conjugation fidelities as high as 98 percent. In the absence of pump depletion, the fidelity increased with average pump intensity for amplitude gains up to around e to the 10th and then decreased slowly and monotonically with higher intensity. For all cases, pump depletion significantly enhanced the fidelity of the wavefront conjugation by inhibiting the small-scale pulling effect.

Short-term prey field lability constrains individual specialisation in resource selection and foraging site fidelity in a marine predator.

PubMed

Courbin, Nicolas; Besnard, Aurélien; Péron, Clara; Saraux, Claire; Fort, Jérôme; Perret, Samuel; Tornos, Jérémy; Grémillet, David

2018-04-16

Spatio-temporally stable prey distributions coupled with individual foraging site fidelity are predicted to favour individual resource specialisation. Conversely, predators coping with dynamic prey distributions should diversify their individual diet and/or shift foraging areas to increase net intake. We studied individual specialisation in Scopoli's shearwaters (Calonectris diomedea) from the highly dynamic Western Mediterranean, using daily prey distributions together with resource selection, site fidelity and trophic-level analyses. As hypothesised, we found dietary diversification, low foraging site fidelity and almost no individual specialisation in resource selection. Crucially, shearwaters switched daily foraging tactics, selecting areas with contrasting prey of varying trophic levels. Overall, information use and plastic resource selection of individuals with reduced short-term foraging site fidelity allow predators to overcome prey field lability. Our study is an essential step towards a better understanding of individual responses to enhanced environmental stochasticity driven by global changes, and of pathways favouring population persistence. © 2018 John Wiley & Sons Ltd/CNRS.

Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y-Family DNA Polymerase

PubMed Central

Vyas, Rajan; Efthimiopoulos, Georgia; Tokarsky, E. John; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

2015-01-01

1-Nitropyrene (1-NP), an environmental pollutant, induces DNA damage in vivo and is considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall replicative DNA polymerases but are presumably bypassed by error-prone Y-family DNA polymerases at the expense of replication fidelity and efficiency in vivo. Our running start assays confirmed that a site-specifically placed 8-(deoxyguanosin-N2-yl)-1-aminopyrene (dG1,8), one of the DNA adducts derived from 1-NP, can be bypassed by Sulfolobus solfataricus DNA polymerase IV (Dpo4), although this representative Y-family enzyme was paused strongly by the lesion. Pre-steady-state kinetic assays were employed to determine the low nucleotide incorporation fidelity and establish a minimal kinetic mechanism for the dG1,8 bypass by Dpo4. To reveal a structural basis for dCTP incorporation opposite dG1,8, we solved the crystal structures of the complexes of Dpo4 and DNA containing a templating dG1,8 lesion in the absence or presence of dCTP. The Dpo4·DNA-dG1,8 binary structure shows that the aminopyrene moiety of the lesion stacks against the primer/template junction pair, while its dG moiety projected into the cleft between the Finger and Little Finger domains of Dpo4. In the Dpo4·DNA-dG1,8·dCTP ternary structure, the aminopyrene moiety of the dG1,8 lesion, is sandwiched between the nascent and junction base pairs, while its base is present in the major groove. Moreover, dCTP forms a Watson–Crick base pair with dG, two nucleotides upstream from the dG1,8 site, creating a complex for “-2” frameshift mutation. Mechanistically, these crystal structures provide additional insight into the aforementioned minimal kinetic mechanism. PMID:26327169

Direct measurement of the poliovirus RNA polymerase error frequency in vitro

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

Ward, C.D.; Stokes, M.A.M.; Flanegan, J.B.

1988-02-01

The fidelity of RNA replication by the poliovirus-RNA-dependent RNA polymerase was examined by copying homopolymeric RNA templates in vitro. The poliovirus RNA polymerase was extensively purified and used to copy poly(A), poly(C), or poly(I) templates with equimolar concentrations of noncomplementary and complementary ribonucleotides. The error frequency was expressed as the amount of a noncomplementary nucleotide incorporated divided by the total amount of complementary and noncomplementary nucleotide incorporated. The polymerase error frequencies were very high, depending on the specific reaction conditions. The activity of the polymerase on poly(U) and poly(G) was too low to measure error frequencies on these templates. Amore » fivefold increase in the error frequency was observed when the reaction conditions were changed from 3.0 mM Mg{sup 2+} (pH 7.0) to 7.0 mM Mg{sup 2+} (pH 8.0). This increase in the error frequency correlates with an eightfold increase in the elongation rate that was observed under the same conditions in a previous study.« less

Infusing Social Justice in Undergraduate Nursing Education: Fostering Praxis Through Simulation.

PubMed

Caldwell, Robyn; Cochran, Courtney

Forensic clinical experiences are often inconsistent in undergraduate nursing education. Nursing students are not included in the process of forensic evidence collection, often because of the sensitive nature of the situation. Unfortunately, nursing students are forced to rely on theoretical knowledge provided by the nurse educator to understand the complexities of forensic nursing care. Nursing students must be able to identify and provide appropriate nursing care for individuals in all forensic situations. Comprehensive clinical laboratory experiences should be provided through active teaching-learning strategies, which replicate nursing care of the forensic patient. Simulated patient experiences provide a unique opportunity to explore the sensitive nature of sexual trauma in a safe learning environment. This strategy facilitates the application of theoretical forensic principles by utilizing live actors or high-fidelity manikins in laboratory settings. The application of theory to each simulated patient infuses conceptual knowledge at the point of care. Change in social consciousness begins at the bedside. The moral imperative of nursing continues to be the preparation of socially responsible, professional nurses who strive to end social injustices.

Development and Utility of a Piloted Flight Simulator for Icing Effects Training

NASA Technical Reports Server (NTRS)

Ratvasky, Thomas P.; Ranaudo, Richard J.; Barnhart, Billy P.; Dickes, Edward G.; Gingras, David R.

2003-01-01

A piloted flight simulator called the Ice Contamination Effects Flight Training Device (ICEFTD), which uses low cost desktop components and a generic cockpit replication is being developed. The purpose of this device is to demonstrate the effectiveness of its use for training pilots to recognize and recover from aircraft handling anomalies that result from airframe ice formations. High-fidelity flight simulation models for various baseline (non-iced) and iced configurations were developed from wind tunnel tests of a subscale DeHavilland DHC-6 Twin Otter aircraft model. These simulation models were validated with flight test data from the NASA Twin Otter Icing Research Aircraft, which included the effects of ice on wing and tail stall characteristics. These simulation models are being implemented into an ICEFTD that will provide representative aircraft characteristics due to airframe icing. Scenario-based exercises are being constructed to give an operational-flavor to the simulation. Training pilots will learn to recognize iced aircraft characteristics from the baseline, and will practice and apply appropriate recovery procedures to a handling event.

[Stress-induced cellular adaptive mutagenesis].

PubMed

Zhu, Linjiang; Li, Qi

2014-04-01

The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

High-Fidelity Single-Shot Readout for a Spin Qubit via an Enhanced Latching Mechanism

NASA Astrophysics Data System (ADS)

Harvey-Collard, Patrick; D'Anjou, Benjamin; Rudolph, Martin; Jacobson, N. Tobias; Dominguez, Jason; Ten Eyck, Gregory A.; Wendt, Joel R.; Pluym, Tammy; Lilly, Michael P.; Coish, William A.; Pioro-Ladrière, Michel; Carroll, Malcolm S.

2018-04-01

The readout of semiconductor spin qubits based on spin blockade is fast but suffers from a small charge signal. Previous work suggested large benefits from additional charge mapping processes; however, uncertainties remain about the underlying mechanisms and achievable fidelity. In this work, we study the single-shot fidelity and limiting mechanisms for two variations of an enhanced latching readout. We achieve average single-shot readout fidelities greater than 99.3% and 99.86% for the conventional and enhanced readout, respectively, the latter being the highest to date for spin blockade. The signal amplitude is enhanced to a full one-electron signal while preserving the readout speed. Furthermore, layout constraints are relaxed because the charge sensor signal is no longer dependent on being aligned with the conventional (2,0)-(1,1) charge dipole. Silicon donor-quantum-dot qubits are used for this study, for which the dipole insensitivity substantially relaxes donor placement requirements. One of the readout variations also benefits from a parametric lifetime enhancement by replacing the spin-relaxation process with a charge-metastable one. This provides opportunities to further increase the fidelity. The relaxation mechanisms in the different regimes are investigated. This work demonstrates a readout that is fast, has a one-electron signal, and results in higher fidelity. It further predicts that going beyond 99.9% fidelity in a few microseconds of measurement time is within reach.

Advances in High-Fidelity Multi-Physics Simulation Techniques

DTIC Science & Technology

2008-01-01

predictor - corrector method is used to advance the solution in time. 33 x (m) y (m ) 0 1 2 3.00001 0 1 2 3 4 5 40 x 50 Grid 3 Figure 17: Typical...Unclassified c . THIS PAGE Unclassified 17. LIMITATION OF ABSTRACT: SAR 18. NUMBER OF PAGES 60 Datta Gaitonde 19b. TELEPHONE...advanced parallel computing platforms. The motivation to develop high-fidelity algorithms derives from considerations in various areas of current

ARC integration into the NEAMS Workbench

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

Stauff, N.; Gaughan, N.; Kim, T.

2017-01-01

One of the objectives of the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Integration Product Line (IPL) is to facilitate the deployment of the high-fidelity codes developed within the program. The Workbench initiative was launched in FY-2017 by the IPL to facilitate the transition from conventional tools to high fidelity tools. The Workbench provides a common user interface for model creation, real-time validation, execution, output processing, and visualization for integrated codes.

High-Fidelity Simulation for Advanced Cardiac Life Support Training

PubMed Central

Davis, Lindsay E.; Storjohann, Tara D.; Spiegel, Jacqueline J.; Beiber, Kellie M.

2013-01-01

Objective. To determine whether a high-fidelity simulation technique compared with lecture would produce greater improvement in advanced cardiac life support (ACLS) knowledge, confidence, and overall satisfaction with the training method. Design. This sequential, parallel-group, crossover trial randomized students into 2 groups distinguished by the sequence of teaching technique delivered for ACLS instruction (ie, classroom lecture vs high-fidelity simulation exercise). Assessment. Test scores on a written examination administered at baseline and after each teaching technique improved significantly from baseline in all groups but were highest when lecture was followed by simulation. Simulation was associated with a greater degree of overall student satisfaction compared with lecture. Participation in a simulation exercise did not improve pharmacy students’ knowledge of ACLS more than attending a lecture, but it was associated with improved student confidence in skills and satisfaction with learning and application. Conclusions. College curricula should incorporate simulation to complement but not replace lecture for ACLS education. PMID:23610477

Implementing a strand of a scalable fault-tolerant quantum computing fabric.

PubMed

Chow, Jerry M; Gambetta, Jay M; Magesan, Easwar; Abraham, David W; Cross, Andrew W; Johnson, B R; Masluk, Nicholas A; Ryan, Colm A; Smolin, John A; Srinivasan, Srikanth J; Steffen, M

2014-06-24

With favourable error thresholds and requiring only nearest-neighbour interactions on a lattice, the surface code is an error-correcting code that has garnered considerable attention. At the heart of this code is the ability to perform a low-weight parity measurement of local code qubits. Here we demonstrate high-fidelity parity detection of two code qubits via measurement of a third syndrome qubit. With high-fidelity gates, we generate entanglement distributed across three superconducting qubits in a lattice where each code qubit is coupled to two bus resonators. Via high-fidelity measurement of the syndrome qubit, we deterministically entangle the code qubits in either an even or odd parity Bell state, conditioned on the syndrome qubit state. Finally, to fully characterize this parity readout, we develop a measurement tomography protocol. The lattice presented naturally extends to larger networks of qubits, outlining a path towards fault-tolerant quantum computing.

General solution to inhomogeneous dephasing and smooth pulse dynamical decoupling

NASA Astrophysics Data System (ADS)

Zeng, Junkai; Deng, Xiu-Hao; Russo, Antonio; Barnes, Edwin

2018-03-01

In order to achieve the high-fidelity quantum control needed for a broad range of quantum information technologies, reducing the effects of noise and system inhomogeneities is an essential task. It is well known that a system can be decoupled from noise or made insensitive to inhomogeneous dephasing dynamically by using carefully designed pulse sequences based on square or delta-function waveforms such as Hahn spin echo or CPMG. However, such ideal pulses are often challenging to implement experimentally with high fidelity. Here, we uncover a new geometrical framework for visualizing all possible driving fields, which enables one to generate an unlimited number of smooth, experimentally feasible pulses that perform dynamical decoupling or dynamically corrected gates to arbitrarily high order. We demonstrate that this scheme can significantly enhance the fidelity of single-qubit operations in the presence of noise and when realistic limitations on pulse rise times and amplitudes are taken into account.

High-fidelity simulation for advanced cardiac life support training.

PubMed

Davis, Lindsay E; Storjohann, Tara D; Spiegel, Jacqueline J; Beiber, Kellie M; Barletta, Jeffrey F

2013-04-12

OBJECTIVE. To determine whether a high-fidelity simulation technique compared with lecture would produce greater improvement in advanced cardiac life support (ACLS) knowledge, confidence, and overall satisfaction with the training method. DESIGN. This sequential, parallel-group, crossover trial randomized students into 2 groups distinguished by the sequence of teaching technique delivered for ACLS instruction (ie, classroom lecture vs high-fidelity simulation exercise). ASSESSMENT. Test scores on a written examination administered at baseline and after each teaching technique improved significantly from baseline in all groups but were highest when lecture was followed by simulation. Simulation was associated with a greater degree of overall student satisfaction compared with lecture. Participation in a simulation exercise did not improve pharmacy students' knowledge of ACLS more than attending a lecture, but it was associated with improved student confidence in skills and satisfaction with learning and application. CONCLUSIONS. College curricula should incorporate simulation to complement but not replace lecture for ACLS education.

Terascale High-Fidelity Simulations of Turbulent Combustion with Detailed Chemistry: Spray Simulations

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

Rutland, Christopher J.

2009-04-26

The Terascale High-Fidelity Simulations of Turbulent Combustion (TSTC) project is a multi-university collaborative effort to develop a high-fidelity turbulent reacting flow simulation capability utilizing terascale, massively parallel computer technology. The main paradigm of the approach is direct numerical simulation (DNS) featuring the highest temporal and spatial accuracy, allowing quantitative observations of the fine-scale physics found in turbulent reacting flows as well as providing a useful tool for development of sub-models needed in device-level simulations. Under this component of the TSTC program the simulation code named S3D, developed and shared with coworkers at Sandia National Laboratories, has been enhanced with newmore » numerical algorithms and physical models to provide predictive capabilities for turbulent liquid fuel spray dynamics. Major accomplishments include improved fundamental understanding of mixing and auto-ignition in multi-phase turbulent reactant mixtures and turbulent fuel injection spray jets.« less

Self-Reflection of Video-Recorded High-Fidelity Simulations and Development of Clinical Judgment.

PubMed

Bussard, Michelle E

2016-09-01

Nurse educators are increasingly using high-fidelity simulators to improve prelicensure nursing students' ability to develop clinical judgment. Traditionally, oral debriefing sessions have immediately followed the simulation scenarios as a method for students to connect theory to practice and therefore develop clinical judgment. Recently, video recording of the simulation scenarios is being incorporated. This qualitative, interpretive description study was conducted to identify whether self-reflection on video-recorded high-fidelity simulation (HFS) scenarios helped prelicensure nursing students to develop clinical judgment. Tanner's clinical judgment model was the framework for this study. Four themes emerged from this study: Confidence, Communication, Decision Making, and Change in Clinical Practice. This study indicated that self-reflection of video-recorded HFS scenarios is beneficial for prelicensure nursing students to develop clinical judgment. [J Nurs Educ. 2016;55(9):522-527.]. Copyright 2016, SLACK Incorporated.

Evaluating intervention fidelity: an example from a high-intensity interval training study.

PubMed

Taylor, Kathryn L; Weston, Matthew; Batterham, Alan M

2015-01-01

Intervention fidelity refers to the degree to which an experimental manipulation has been implemented as intended, but simple, robust methods for quantifying fidelity have not been well documented. Therefore, we aim to illustrate a rigorous quantitative evaluation of intervention fidelity, using data collected during a high-intensity interval training intervention. Single-group measurement study. Seventeen adolescents (mean age ± standard deviation [SD] 14.0 ± 0.3 years) attended a 10-week high-intensity interval training intervention, comprising two exercise sessions per week. Sessions consisted of 4-7 45-s maximal effort repetitions, interspersed with 90-s rest. We collected heart rate data at 5-s intervals and recorded the peak heart rate for each repetition. The high-intensity exercise criterion was ≥ 90% of individual maximal heart rate. For each participant, we calculated the proportion of total exercise repetitions exceeding this threshold. A linear mixed model was applied to properly separate the variability in peak heart rate between- and within-subjects. Results are presented both as intention to treat (including missed sessions) and per protocol (only participants with 100% attendance; n=8). For intention to treat, the median (interquartile range) proportion of repetitions meeting the high-intensity criterion was 58% (42% to 68%). The mean peak heart rate was 85% of maximal, with a between-subject SD of 7.8 (95% confidence interval 5.4 to 11.3) percentage points and a within-subject SD of 15.1 (14.6 to 15.6) percentage points. For the per protocol analysis, the median proportion of high-intensity repetitions was 68% (47% to 86%). The mean peak heart rate was 91% of maximal, with between- and within-subject SDs of 3.1 (-1.3 to 4.6) and 3.4 (3.2 to 3.6) percentage points, respectively. Synthesising information on exercise session attendance and compliance (exercise intensity) quantifies the intervention dose and informs evaluations of treatment fidelity.

Development of a measure of model fidelity for mental health Crisis Resolution Teams.

PubMed

Lloyd-Evans, Brynmor; Bond, Gary R; Ruud, Torleif; Ivanecka, Ada; Gray, Richard; Osborn, David; Nolan, Fiona; Henderson, Claire; Mason, Oliver; Goater, Nicky; Kelly, Kathleen; Ambler, Gareth; Morant, Nicola; Onyett, Steve; Lamb, Danielle; Fahmy, Sarah; Brown, Ellie; Paterson, Beth; Sweeney, Angela; Hindle, David; Fullarton, Kate; Frerichs, Johanna; Johnson, Sonia

2016-12-01

Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence. A concept mapping process was used to develop a CRT fidelity scale. Participants (n = 68) from a range of stakeholder groups prioritised and grouped statements (n = 72) about important components of the CRT model, generated from a literature review, national survey and qualitative interviews. These data were analysed using Ariadne software and the resultant cluster solution informed item selection for a CRT fidelity scale. Operational criteria and scoring anchor points were developed for each item. The CORE CRT fidelity scale was then piloted in 75 CRTs in the UK to assess the range of scores achieved and feasibility for use in a 1-day fidelity review process. Trained reviewers (n = 16) rated CRT service fidelity in a vignette exercise to test the scale's inter-rater reliability. There were high levels of agreement within and between stakeholder groups regarding the most important components of the CRT model. A 39-item measure of CRT model fidelity was developed. Piloting indicated that the scale was feasible for use to assess CRT model fidelity and had good face validity. The wide range of item scores and total scores across CRT services in the pilot demonstrate the measure can distinguish lower and higher fidelity services. Moderately good inter-rater reliability was found, with an estimated correlation between individual ratings of 0.65 (95% CI: 0.54 to 0.76). The CORE CRT Fidelity Scale has been developed through a rigorous and systematic process. Promising initial testing indicates its value in assessing adherence to a model of CRT best practice and to support service improvement monitoring and planning. Further research is required to establish its psychometric properties and international applicability.

Evaluating the Implementation Fidelity of Technology Immersion and Its Relationship with Student Achievement

ERIC Educational Resources Information Center

Shapley, Kelly S.; Sheehan, Daniel; Maloney, Catherine; Caranikas-Walker, Fanny

2010-01-01

In a pilot study of the Technology Immersion model, high-need middle schools were "immersed" in technology by providing a laptop for each student and teacher, wireless Internet access, curricular and assessment resources, professional development, and technical and pedagogical support. This article examines the fidelity of model…

Attenuation of foot-and-mouth disease virus by engineered viral polymerase fidelity

USDA-ARS?s Scientific Manuscript database

The foot-and-mouth disease virus (FMDV) RNA dependent RNA polymerase (RdRp or 3Dpol) catalyzes viral RNA synthesis. The 3Dpol is a low fidelity enzyme incapable of proofreading which results in a high mutation frequencies that allow the virus to rapidly adapt to different environments. In this study...

Nursing Simulation: A Review of the Past 40 Years

ERIC Educational Resources Information Center

Nehring, Wendy M.; Lashley, Felissa R.

2009-01-01

Simulation, in its many forms, has been a part of nursing education and practice for many years. The use of games, computer-assisted instruction, standardized patients, virtual reality, and low-fidelity to high-fidelity mannequins have appeared in the past 40 years, whereas anatomical models, partial task trainers, and role playing were used…

Administrator Strategies that Support High Fidelity Implementation of the Pyramid Model for Promoting Social-Emotional Competence & Addressing Challenging Behavior

ERIC Educational Resources Information Center

Mincic, Melissa; Smith, Barbara J.; Strain, Phil

2009-01-01

Implementing the Pyramid Model with fidelity and achieving positive outcomes for children and their families requires that administrators understand their roles in the implementation process. Every administrative decision impacts program quality and sustainability. This Policy Brief underscores the importance of facilitative administrative…

A Randomized Controlled Study of Manikin Simulator Fidelity on Neonatal Resuscitation Program Learning Outcomes

ERIC Educational Resources Information Center

Curran, Vernon; Fleet, Lisa; White, Susan; Bessell, Clare; Deshpandey, Akhil; Drover, Anne; Hayward, Mark; Valcour, James

2015-01-01

The neonatal resuscitation program (NRP) has been developed to educate physicians and other health care providers about newborn resuscitation and has been shown to improve neonatal resuscitation skills. Simulation-based training is recommended as an effective modality for instructing neonatal resuscitation and both low and high-fidelity manikin…

Fidelity and over-wintering of sea turtles.

PubMed

Broderick, Annette C; Coyne, Michael S; Fuller, Wayne J; Glen, Fiona; Godley, Brendan J

2007-06-22

While fidelity to breeding sites is well demonstrated in marine turtles, emerging knowledge of migratory routes and key foraging sites is of limited conservation value unless levels of fidelity can be established. We tracked green (Chelonia mydas, n=10) and loggerhead (Caretta caretta, n=10) turtles during their post-nesting migration from the island of Cyprus to their foraging grounds. After intervals of 2-5 years, five of these females were recaptured at the nesting beach and tracked for a second migration. All five used highly similar migratory routes to return to the same foraging and over-wintering areas. None of the females visited other foraging habitats over the study period (units lasted on average 305 days; maximum, 1356 days), moving only to deeper waters during the winter months where they demonstrated extremely long resting dives of up to 10.2h (the longest breath-holding dive recorded for a marine vertebrate). High levels of fidelity and the relatively discrete nature of the home ranges demonstrate that protection of key migratory pathways, foraging and over-wintering sites can serve as an important tool for the future conservation of marine turtles.

Optimization of a solid-state electron spin qubit using Gate Set Tomography

DOE PAGES

Dehollain, Juan P.; Muhonen, Juha T.; Blume-Kohout, Robin J.; ...

2016-10-13

Here, state of the art qubit systems are reaching the gate fidelities required for scalable quantum computation architectures. Further improvements in the fidelity of quantum gates demands characterization and benchmarking protocols that are efficient, reliable and extremely accurate. Ideally, a benchmarking protocol should also provide information on how to rectify residual errors. Gate Set Tomography (GST) is one such protocol designed to give detailed characterization of as-built qubits. We implemented GST on a high-fidelity electron-spin qubit confined by a single 31P atom in 28Si. The results reveal systematic errors that a randomized benchmarking analysis could measure but not identify, whereasmore » GST indicated the need for improved calibration of the length of the control pulses. After introducing this modification, we measured a new benchmark average gate fidelity of 99.942(8)%, an improvement on the previous value of 99.90(2)%. Furthermore, GST revealed high levels of non-Markovian noise in the system, which will need to be understood and addressed when the qubit is used within a fault-tolerant quantum computation scheme.« less

A study on model fidelity for model predictive control-based obstacle avoidance in high-speed autonomous ground vehicles

NASA Astrophysics Data System (ADS)

Liu, Jiechao; Jayakumar, Paramsothy; Stein, Jeffrey L.; Ersal, Tulga

2016-11-01

This paper investigates the level of model fidelity needed in order for a model predictive control (MPC)-based obstacle avoidance algorithm to be able to safely and quickly avoid obstacles even when the vehicle is close to its dynamic limits. The context of this work is large autonomous ground vehicles that manoeuvre at high speed within unknown, unstructured, flat environments and have significant vehicle dynamics-related constraints. Five different representations of vehicle dynamics models are considered: four variations of the two degrees-of-freedom (DoF) representation as lower fidelity models and a fourteen DoF representation with combined-slip Magic Formula tyre model as a higher fidelity model. It is concluded that the two DoF representation that accounts for tyre nonlinearities and longitudinal load transfer is necessary for the MPC-based obstacle avoidance algorithm in order to operate the vehicle at its limits within an environment that includes large obstacles. For less challenging environments, however, the two DoF representation with linear tyre model and constant axle loads is sufficient.

Broken symmetry in a two-qubit quantum control landscape

NASA Astrophysics Data System (ADS)

Bukov, Marin; Day, Alexandre G. R.; Weinberg, Phillip; Polkovnikov, Anatoli; Mehta, Pankaj; Sels, Dries

2018-05-01

We analyze the physics of optimal protocols to prepare a target state with high fidelity in a symmetrically coupled two-qubit system. By varying the protocol duration, we find a discontinuous phase transition, which is characterized by a spontaneous breaking of a Z2 symmetry in the functional form of the optimal protocol, and occurs below the quantum speed limit. We study in detail this phase and demonstrate that even though high-fidelity protocols come degenerate with respect to their fidelity, they lead to final states of different entanglement entropy shared between the qubits. Consequently, while globally both optimal protocols are equally far away from the target state, one is locally closer than the other. An approximate variational mean-field theory which captures the physics of the different phases is developed.

Experimental magic state distillation for fault-tolerant quantum computing.

PubMed

Souza, Alexandre M; Zhang, Jingfu; Ryan, Colm A; Laflamme, Raymond

2011-01-25

Any physical quantum device for quantum information processing (QIP) is subject to errors in implementation. In order to be reliable and efficient, quantum computers will need error-correcting or error-avoiding methods. Fault-tolerance achieved through quantum error correction will be an integral part of quantum computers. Of the many methods that have been discovered to implement it, a highly successful approach has been to use transversal gates and specific initial states. A critical element for its implementation is the availability of high-fidelity initial states, such as |0〉 and the 'magic state'. Here, we report an experiment, performed in a nuclear magnetic resonance (NMR) quantum processor, showing sufficient quantum control to improve the fidelity of imperfect initial magic states by distilling five of them into one with higher fidelity.

High-Fidelity Preservation of Quantum Information During Trapped-Ion Transport

NASA Astrophysics Data System (ADS)

Kaufmann, Peter; Gloger, Timm F.; Kaufmann, Delia; Johanning, Michael; Wunderlich, Christof

2018-01-01

A promising scheme for building scalable quantum simulators and computers is the synthesis of a scalable system using interconnected subsystems. A prerequisite for this approach is the ability to faithfully transfer quantum information between subsystems. With trapped atomic ions, this can be realized by transporting ions with quantum information encoded into their internal states. Here, we measure with high precision the fidelity of quantum information encoded into hyperfine states of a Yb171 + ion during ion transport in a microstructured Paul trap. Ramsey spectroscopy of the ion's internal state is interleaved with up to 4000 transport operations over a distance of 280 μ m each taking 12.8 μ s . We obtain a state fidelity of 99.9994 (-7+6) % per ion transport.

Optimal control of fast and high-fidelity quantum state transfer in spin-1/2 chains

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

Zhang, Xiong-Peng; Shao, Bin, E-mail: sbin610@bit.edu.cn; Hu, Shuai

Spin chains are promising candidates for quantum communication and computation. Using quantum optimal control (OC) theory based on the Krotov method, we present a protocol to perform quantum state transfer with fast and high fidelity by only manipulating the boundary spins in a quantum spin-1/2 chain. The achieved speed is about one order of magnitude faster than that is possible in the Lyapunov control case for comparable fidelities. Additionally, it has a fundamental limit for OC beyond which optimization is not possible. The controls are exerted only on the couplings between the boundary spins and their neighbors, so that themore » scheme has good scalability. We also demonstrate that the resulting OC scheme is robust against disorder in the chain.« less

High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation.

PubMed

Bowman, D; Harte, T L; Chardonnet, V; De Groot, C; Denny, S J; Le Goc, G; Anderson, M; Ireland, P; Cassettari, D; Bruce, G D

2017-05-15

We demonstrate simultaneous control of both the phase and amplitude of light using a conjugate gradient minimisation-based hologram calculation technique and a single phase-only spatial light modulator (SLM). A cost function, which incorporates the inner product of the light field with a chosen target field within a defined measure region, is efficiently minimised to create high fidelity patterns in the Fourier plane of the SLM. A fidelity of F = 0.999997 is achieved for a pattern resembling an LG10 mode with a calculated light-usage efficiency of 41.5%. Possible applications of our method in optical trapping and ultracold atoms are presented and we show uncorrected experimental realisation of our patterns with F = 0.97 and 7.8% light efficiency.

Generation of a high-fidelity antibody against nerve growth factor using library scanning mutagenesis and validation with structures of the initial and optimized Fab-antigen complexes

PubMed Central

La Porte, Sherry L; Eigenbrot, Charles; Ultsch, Mark; Ho, Wei-Hsien; Foletti, Davide; Forgie, Alison; Lindquist, Kevin C; Shelton, David L; Pons, Jaume

2014-01-01

Nerve growth factor (NGF) is indispensable during normal embryonic development and critical for the amplification of pain signals in adults. Intervention in NGF signaling holds promise for the alleviation of pain resulting from human diseases such as osteoarthritis, cancer and chronic lower back disorders. We developed a fast, high-fidelity method to convert a hybridoma-derived NGF-targeted mouse antibody into a clinical candidate. This method, termed Library Scanning Mutagenesis (LSM), resulted in the ultra-high affinity antibody tanezumab, a first-in-class anti-hyperalgesic specific for an NGF epitope. Functional and structural comparisons between tanezumab and the mouse 911 precursor antibody using neurotrophin-specific cell survival assays and X-ray crystal structures of both Fab-antigen complexes illustrated high fidelity retention of the NGF epitope. These results suggest the potential for wide applicability of the LSM method for optimization of well-characterized antibodies during humanization. PMID:24830649

Developing Capture Mechanisms and High-Fidelity Dynamic Models for the MXER Tether System

NASA Technical Reports Server (NTRS)

Canfield, Steven L.

2007-01-01

A team consisting of collaborators from Tennessee Technological University (TTU), Marshall Space Flight Center, BD Systems, and the University of Delaware (herein called the TTU team) conducted specific research and development activities in MXER tether systems during the base period of May 15, 2004 through September 30, 2006 under contract number NNM04AB13C. The team addressed two primary topics related to the MXER tether system: 1) Development of validated high-fidelity dynamic models of an elastic rotating tether and 2) development of feasible mechanisms to enable reliable rendezvous and capture. This contractor report will describe in detail the activities that were performed during the base period of this cycle-2 MXER tether activity and will summarize the results of this funded activity. The primary deliverables of this project were the quad trap, a robust capture mechanism proposed, developed, tested, and demonstrated with a high degree of feasibility and the detailed development of a validated high-fidelity elastic tether dynamic model provided through multiple formulations.

Multiplex Preamplification of Serum DNA to Facilitate Reliable Detection of Extremely Rare Cancer Mutations in Circulating DNA by Digital PCR.

PubMed

Jackson, Jennifer B; Choi, Daniel S; Luketich, James D; Pennathur, Arjun; Ståhlberg, Anders; Godfrey, Tony E

2016-03-01

Tumor-specific mutations can be identified in circulating, cell-free DNA in plasma or serum and may serve as a clinically relevant alternative to biopsy. Detection of tumor-specific mutations in the plasma, however, is technically challenging. First, mutant allele fractions are typically low in a large background of wild-type circulating, cell-free DNA. Second, the amount of circulating, cell-free DNA acquired from plasma is also low. Even when using digital PCR (dPCR), rare mutation detection is challenging because there is not enough circulating, cell-free DNA to run technical replicates and assay or instrument noise does not easily allow for mutation detection <0.1%. This study was undertaken to improve on the robustness of dPCR for mutation detection. A multiplexed, preamplification step using a high-fidelity polymerase before dPCR was developed to increase total DNA and the number of targets and technical replicates that can be assayed from a single sample. We were able to detect multiple cancer-relevant mutations within tumor-derived samples down to 0.01%. Importantly, the signal/noise ratio was improved for all preamplified targets, allowing for easier discrimination of low-abundance mutations against false-positive signal. Furthermore, we used this protocol on clinical samples to detect known, tumor-specific mutations in patient sera. This study provides a protocol for robust, sensitive detection of circulating tumor DNA for future clinical applications. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Compressed Sensing Quantum Process Tomography for Superconducting Quantum Gates

NASA Astrophysics Data System (ADS)

Rodionov, Andrey

An important challenge in quantum information science and quantum computing is the experimental realization of high-fidelity quantum operations on multi-qubit systems. Quantum process tomography (QPT) is a procedure devised to fully characterize a quantum operation. We first present the results of the estimation of the process matrix for superconducting multi-qubit quantum gates using the full data set employing various methods: linear inversion, maximum likelihood, and least-squares. To alleviate the problem of exponential resource scaling needed to characterize a multi-qubit system, we next investigate a compressed sensing (CS) method for QPT of two-qubit and three-qubit quantum gates. Using experimental data for two-qubit controlled-Z gates, taken with both Xmon and superconducting phase qubits, we obtain estimates for the process matrices with reasonably high fidelities compared to full QPT, despite using significantly reduced sets of initial states and measurement configurations. We show that the CS method still works when the amount of data is so small that the standard QPT would have an underdetermined system of equations. We also apply the CS method to the analysis of the three-qubit Toffoli gate with simulated noise, and similarly show that the method works well for a substantially reduced set of data. For the CS calculations we use two different bases in which the process matrix is approximately sparse (the Pauli-error basis and the singular value decomposition basis), and show that the resulting estimates of the process matrices match with reasonably high fidelity. For both two-qubit and three-qubit gates, we characterize the quantum process by its process matrix and average state fidelity, as well as by the corresponding standard deviation defined via the variation of the state fidelity for different initial states. We calculate the standard deviation of the average state fidelity both analytically and numerically, using a Monte Carlo method. Overall, we show that CS QPT offers a significant reduction in the needed amount of experimental data for two-qubit and three-qubit quantum gates.

Left Ventricular, Systemic Arterial and Baroreflex Responses to Ketamine and TEE in Chronically Instrumented Monkeys

DTIC Science & Technology

2001-12-01

instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to...isoflurane in 100% oxy- gen) prior to insertion of the high -fidelity pressure micromanome- ters during cardiac fluoroscopy. Once the micromanometer trans...and allowed to fully recover from the isoflurane seda- tion for a period of 60 min, during which blood pressure and aortic flow were monitored to ensure

Solar Sail Spaceflight Simulation

NASA Technical Reports Server (NTRS)

Lisano, Michael; Evans, James; Ellis, Jordan; Schimmels, John; Roberts, Timothy; Rios-Reyes, Leonel; Scheeres, Daniel; Bladt, Jeff; Lawrence, Dale; Piggott, Scott

2007-01-01

The Solar Sail Spaceflight Simulation Software (S5) toolkit provides solar-sail designers with an integrated environment for designing optimal solar-sail trajectories, and then studying the attitude dynamics/control, navigation, and trajectory control/correction of sails during realistic mission simulations. Unique features include a high-fidelity solar radiation pressure model suitable for arbitrarily-shaped solar sails, a solar-sail trajectory optimizer, capability to develop solar-sail navigation filter simulations, solar-sail attitude control models, and solar-sail high-fidelity force models.

High-fidelity large area nano-patterning of silicon with femtosecond light sheet

NASA Astrophysics Data System (ADS)

Sidhu, Mehra S.; Munjal, Pooja; Singh, Kamal P.

2018-01-01

We employ a femtosecond light sheet generated by a cylindrical lens to rapidly produce high-fidelity nano-structures over large area on silicon surface. The Fourier analysis of electron microscopy images of the laser-induced surface structures reveals sharp peaks indicating good homogeneity. We observed an emergence of second-order spatial periodicity on increasing the scan speed. Our reliable approach may rapidly nano-pattern curved solid surfaces and tiny objects for diverse potential applications in optical devices, structural coloring, plasmonic substrates and in high-harmonic generation.

Interprofessional education in pharmacology using high-fidelity simulation.

PubMed

Meyer, Brittney A; Seefeldt, Teresa M; Ngorsuraches, Surachat; Hendrickx, Lori D; Lubeck, Paula M; Farver, Debra K; Heins, Jodi R

2017-11-01

This study examined the feasibility of an interprofessional high-fidelity pharmacology simulation and its impact on pharmacy and nursing students' perceptions of interprofessionalism and pharmacology knowledge. Pharmacy and nursing students participated in a pharmacology simulation using a high-fidelity patient simulator. Faculty-facilitated debriefing included discussion of the case and collaboration. To determine the impact of the activity on students' perceptions of interprofessionalism and their ability to apply pharmacology knowledge, surveys were administered to students before and after the simulation. Attitudes Toward Health Care Teams scale (ATHCT) scores improved from 4.55 to 4.72 on a scale of 1-6 (p = 0.005). Almost all (over 90%) of the students stated their pharmacology knowledge and their ability to apply that knowledge improved following the simulation. A simulation in pharmacology is feasible and favorably affected students' interprofessionalism and pharmacology knowledge perceptions. Pharmacology is a core science course required by multiple health professions in early program curricula, making it favorable for incorporation of interprofessional learning experiences. However, reports of high-fidelity interprofessional simulation in pharmacology courses are limited. This manuscript contributes to the literature in the field of interprofessional education by demonstrating that an interprofessional simulation in pharmacology is feasible and can favorably affect students' perceptions of interprofessionalism. This manuscript provides an example of a pharmacology interprofessional simulation that faculty in other programs can use to build similar educational activities. Copyright © 2017 Elsevier Inc. All rights reserved.

High-Fidelity Simulation: Preparing Dental Hygiene Students for Managing Medical Emergencies.

PubMed

Bilich, Lisa A; Jackson, Sarah C; Bray, Brenda S; Willson, Megan N

2015-09-01

Medical emergencies can occur at any time in the dental office, so being prepared to properly manage the situation can be the difference between life and death. The entire dental team must be properly trained regarding all aspects of emergency management in the dental clinic. The aim of this study was to evaluate a new educational approach using a high-fidelity simulator to prepare dental hygiene students for medical emergencies. This study utilized high-fidelity simulation (HFS) to evaluate the abilities of junior dental hygiene students at Eastern Washington University to handle a medical emergency in the dental hygiene clinic. Students were given a medical emergency scenario requiring them to assess the emergency and implement life-saving protocols in a simulated "real-life" situation using a high-fidelity manikin. Retrospective data were collected for four years from the classes of 2010 through 2013 (N=114). The results indicated that learning with simulation was effective in helping the students identify the medical emergency in a timely manner, implement emergency procedures correctly, locate and correctly utilize contents of the emergency kit, administer appropriate intervention/treatment for a specific patient, and provide the patient with appropriate follow-up instructions. For dental hygiene programs seeking to enhance their curricula in the area of medical emergencies, this study suggests that HFS is an effective tool to prepare students to appropriately handle medical emergencies. Faculty calibration is essential to standardize simulation.

Plastic masters-rigid templates for soft lithography.

PubMed

Desai, Salil P; Freeman, Dennis M; Voldman, Joel

2009-06-07

We demonstrate a simple process for the fabrication of rigid plastic master molds for soft lithography directly from (poly)dimethysiloxane devices. Plastics masters (PMs) provide a cost-effective alternative to silicon-based masters and can be easily replicated without the need for cleanroom facilities. We have successfully demonstrated the use of plastics micromolding to generate both single and dual-layer plastic structures, and have characterized the fidelity of the molding process. Using the PM fabrication technique, world-to-chip connections can be integrated directly into the master enabling devices with robust, well-aligned fluidic ports directly after molding. PMs provide an easy technique for the fabrication of microfluidic devices and a simple route for the scaling-up of fabrication of robust masters for soft lithography.

Virtual Reality Compared with Bench-Top Simulation in the Acquisition of Arthroscopic Skill: A Randomized Controlled Trial.

PubMed

Banaszek, Daniel; You, Daniel; Chang, Justues; Pickell, Michael; Hesse, Daniel; Hopman, Wilma M; Borschneck, Daniel; Bardana, Davide

2017-04-05

Work-hour restrictions as set forth by the Accreditation Council for Graduate Medical Education (ACGME) and other governing bodies have forced training programs to seek out new learning tools to accelerate acquisition of both medical skills and knowledge. As a result, competency-based training has become an important part of residency training. The purpose of this study was to directly compare arthroscopic skill acquisition in both high-fidelity and low-fidelity simulator models and to assess skill transfer from either modality to a cadaveric specimen, simulating intraoperative conditions. Forty surgical novices (pre-clerkship-level medical students) voluntarily participated in this trial. Baseline demographic data, as well as data on arthroscopic knowledge and skill, were collected prior to training. Subjects were randomized to 5-week independent training sessions on a high-fidelity virtual reality arthroscopic simulator or on a bench-top arthroscopic setup, or to an untrained control group. Post-training, subjects were asked to perform a diagnostic arthroscopy on both simulators and in a simulated intraoperative environment on a cadaveric knee. A more difficult surprise task was also incorporated to evaluate skill transfer. Subjects were evaluated using the Global Rating Scale (GRS), the 14-point arthroscopic checklist, and a timer to determine procedural efficiency (time per task). Secondary outcomes focused on objective measures of virtual reality simulator motion analysis. Trainees on both simulators demonstrated a significant improvement (p < 0.05) in arthroscopic skills compared with baseline scores and untrained controls, both in and ex vivo. The virtual reality simulation group consistently outperformed the bench-top model group in the diagnostic arthroscopy crossover tests and in the simulated cadaveric setup. Furthermore, the virtual reality group demonstrated superior skill transfer in the surprise skill transfer task. Both high-fidelity and low-fidelity simulation trainings were effective in arthroscopic skill acquisition. High-fidelity virtual reality simulation was superior to bench-top simulation in the acquisition of arthroscopic skills, both in the laboratory and in vivo. Further clinical investigation is needed to interpret the importance of these results.

Fidelity and persistence of Ring-billed (Larus delawarensis) and Herring (Larus argentatus) gulls to wintering sites

USGS Publications Warehouse

Clark, Daniel E.; Koenen, Kiana K. G.; Whitney, Jillian J.; MacKenzie, Kenneth G.; DeStefano, Stephen

2016-01-01

While the breeding ecology of gulls (Laridae) has been well studied, their movements and spatial organization during the non-breeding season is poorly understood. The seasonal movements, winter-site fidelity, and site persistence of Ring-billed (Larus delawarensis) and Herring (L. argentatus) gulls to wintering areas were studied from 2008–2012. Satellite transmitters were deployed on Ring-billed Gulls (n = 21) and Herring Gulls (n = 14). Ten Ring-billed and six Herring gulls were tracked over multiple winters and > 300 wing-tagged Ring-billed Gulls were followed to determine winter-site fidelity and persistence. Home range overlap for individuals between years ranged between 0–1.0 (95% minimum convex polygon) and 0.31–0.79 (kernel utilization distributions). Ringbilled and Herring gulls remained at local wintering sites during the non-breeding season from 20–167 days and 74–161 days, respectively. The probability of a tagged Ring-billed Gull returning to the same site in subsequent winters was high; conversely, there was a low probability of a Ring-billed Gull returning to a different site. Ring-billed and Herring gulls exhibited high winter-site fidelity, but exhibited variable site persistence during the winter season, leading to a high probability of encountering the same individuals in subsequent winters.

Thermal Protection System Mass Estimating Relationships for Blunt-Body, Earth Entry Spacecraft

NASA Technical Reports Server (NTRS)

Sepka, Steven A.; Samareh, Jamshid A.

2015-01-01

System analysis and design of any entry system must balance the level fidelity for each discipline against the project timeline. One way to inject high fidelity analysis earlier in the design effort is to develop surrogate models for the high-fidelity disciplines. Surrogate models for the Thermal Protection System (TPS) are formulated as Mass Estimating Relationships (MERs). The TPS MERs are presented that predict the amount of TPS necessary for safe Earth entry for blunt-body spacecraft using simple correlations that closely match estimates from NASA's high-fidelity ablation modeling tool, the Fully Implicit Ablation and Thermal Analysis Program (FIAT). These MERs provide a first order estimate for rapid feasibility studies. There are 840 different trajectories considered in this study, and each TPS MER has a peak heating limit. MERs for the vehicle forebody include the ablators Phenolic Impregnated Carbon Ablator (PICA) and Carbon Phenolic atop Advanced Carbon-Carbon. For the aftbody, the materials are Silicone Impregnated Reusable Ceramic Ablator (SIRCA), Acusil II, SLA-561V, and LI-900. The MERs are accurate to within 14% (at one standard deviation) of FIAT prediction, and the most any MER under predicts FIAT TPS thickness is 18.7%. This work focuses on the development of these MERs, the resulting equations, model limitations, and model accuracy.

Implementation fidelity of a computer-assisted intervention for children with speech sound disorders.

PubMed

McCormack, Jane; Baker, Elise; Masso, Sarah; Crowe, Kathryn; McLeod, Sharynne; Wren, Yvonne; Roulstone, Sue

2017-06-01

Implementation fidelity refers to the degree to which an intervention or programme adheres to its original design. This paper examines implementation fidelity in the Sound Start Study, a clustered randomised controlled trial of computer-assisted support for children with speech sound disorders (SSD). Sixty-three children with SSD in 19 early childhood centres received computer-assisted support (Phoneme Factory Sound Sorter [PFSS] - Australian version). Educators facilitated the delivery of PFSS targeting phonological error patterns identified by a speech-language pathologist. Implementation data were gathered via (1) the computer software, which recorded when and how much intervention was completed over 9 weeks; (2) educators' records of practice sessions; and (3) scoring of fidelity (intervention procedure, competence and quality of delivery) from videos of intervention sessions. Less than one-third of children received the prescribed number of days of intervention, while approximately one-half participated in the prescribed number of intervention plays. Computer data differed from educators' data for total number of days and plays in which children participated; the degree of match was lower as data became more specific. Fidelity to intervention procedures, competency and quality of delivery was high. Implementation fidelity may impact intervention outcomes and so needs to be measured in intervention research; however, the way in which it is measured may impact on data.