[Exploration of the concept of genetic drift in genetics teaching of undergraduates].

PubMed

Wang, Chun-ming

2016-01-01

Genetic drift is one of the difficulties in teaching genetics due to its randomness and probability which could easily cause conceptual misunderstanding. The “sampling error" in its definition is often misunderstood because of the research method of “sampling", which disturbs the results and causes the random changes in allele frequency. I analyzed and compared the definitions of genetic drift in domestic and international genetic textbooks, and found that the definitions containing “sampling error" are widely adopted but are interpreted correctly in only a few textbooks. Here, the history of research on genetic drift, i.e., the contributions of Wright, Fisher and Kimura, is introduced. Moreover, I particularly describe two representative articles recently published about genetic drift teaching of undergraduates, which point out that misconceptions are inevitable for undergraduates during the studying process and also provide a preliminary solution. Combined with my own teaching practice, I suggest that the definition of genetic drift containing “sampling error" can be adopted with further interpretation, i.e., “sampling error" is random sampling among gametes when generating the next generation of alleles which is equivalent to a random sampling of all gametes participating in mating in gamete pool and has no relationship with artificial sampling in general genetics studies. This article may provide some help in genetics teaching.

Evaluating alternate models to estimate genetic parameters of calving traits in United Kingdom Holstein-Friesian dairy cattle.

PubMed

Eaglen, Sophie A E; Coffey, Mike P; Woolliams, John A; Wall, Eileen

2012-07-28

The focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle. Data from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (-maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models. On average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (-maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (-maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence. For the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (-maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions.

Evaluating alternate models to estimate genetic parameters of calving traits in United Kingdom Holstein-Friesian dairy cattle

PubMed Central

2012-01-01

Background The focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle. Methods Data from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (−maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models. Results and discussion On average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (−maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (−maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence. Conclusions For the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (−maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions. PMID:22839757

Genetic parameters for calving ease, gestation length, and birth weight in Charolais cattle.

PubMed

Mujibi, F D N; Crews, D H

2009-09-01

In this study, a 3-trait linear model was used to obtain genetic parameters for direct and maternal components of calving ease (CE), gestation length (GEST), and birth weight (BWT). Calving ease scores were transformed into Snell scores and expressed as percent unassisted calving (SC), ranging from 0 to 100% (least to greatest ease). A total of 40,420 records (n = 14,403 for CE) were obtained from the Canadian Charolais Association field database. The animal model included fixed effects of contemporary group (herd x year of birth combinations), age of heifer, and sex of calf (only for CE), whereas random effects included direct and maternal genetic effects, residual error, and permanent environmental effects (for CE). The BWT and GEST were preadjusted for age of dam and sex of calf effects. Variance components were estimated using REML. Mean SC was 83.31% (SD = 23.30) and ranged from 3.44 to 100%. Mean BWT was 46.54 kg (SD = 4.79), whereas mean GEST was 286.48 d (SD = 4.93). Direct heritability estimates for SC, BWT, and GEST were 0.14 +/- 0.02, 0.46 +/- 0.03, and 0.62 +/- 0.04, respectively, and maternal heritability estimates were 0.06 +/- 0.02, 0.14 +/- 0.02, and 0.10 +/- 0.02, respectively. The permanent environmental effect as a proportion of SC phenotypic variance was 0.35 +/- 0.11, indicating a large influence on CE. Genetic correlations of direct SC with direct BWT and GEST were -0.93 +/- 0.04 and -0.38 +/- 0.08, respectively, whereas maternal correlations were -0.69 +/- 0.14 and -0.49 +/- 0.17, respectively, illustrating the importance of including both traits in CE evaluations. Within trait direct x maternal genetic correlations were substantial and negative. Regression of average direct and average maternal EBV on year of birth yielded significant genetic trends for the direct effects of BWT, GEST, and CE, whereas no trends were detected for maternal effects. Even though CE is routinely analyzed, no study has evaluated transformed CE scores with 2 correlated traits. In these data, the large negative genetic correlation between BWT and CE suggests that increasing SC would also decrease BWT. Genetic improvement programs, therefore, should consider both CE and growth.

Does responsibility affect the public's valuation of health care interventions? A relative valuation approach to health care safety.

PubMed

Singh, Jeshika; Lord, Joanne; Longworth, Louise; Orr, Shepley; McGarry, Teresa; Sheldon, Rob; Buxton, Martin

2012-01-01

Health services often spend more on safety interventions than seems cost-effective. This study investigates whether the public value safety-related health care improvements more highly than the same improvements in contexts where the health care system is not responsible. An online survey was conducted to elicit the relative importance placed on preventing harms caused by 1) health care (hospital-acquired infections, drug administration errors, injuries to health care staff), 2) individuals (personal lifestyle choices, sports-related injuries), and 3) nature (genetic disorders). Direct valuations were obtained from members of the public by using a person trade-off or "matching" method. Participants were asked to choose between two preventative interventions of equal cost and equal health benefit per person for the same number of people, but differing in causation. If participants indicated a preference, their strength of preference was measured by using person trade-off. Responses were obtained from 1030 people, reflecting the sociodemographic mix of the UK population. Participants valued interventions preventing hospital-acquired infections (1.31) more highly than genetic disorders (1.0), although drug errors were valued similarly to genetic disorders (1.07), and interventions to prevent injury to health care staff were given less weight than genetic disorders (0.71). Less weight was also given to interventions related to lifestyle (0.65) and sports injuries (0.41). Our results suggest that people do not attach a simple fixed premium to "safety-related" interventions but that preferences depend more subtly on context. The use of the results of such public preference surveys to directly inform policy would therefore be premature. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

INVOLVEMENT OF MULTIPLE MOLECULAR PATHWAYS IN THE GENETICS OF OCULAR REFRACTION AND MYOPIA.

PubMed

Wojciechowski, Robert; Cheng, Ching-Yu

2018-01-01

The prevalence of myopia has increased dramatically worldwide within the last three decades. Recent studies have shown that refractive development is influenced by environmental, behavioral, and inherited factors. This review aims to analyze recent progress in the genetics of refractive error and myopia. A comprehensive literature search of PubMed and OMIM was conducted to identify relevant articles in the genetics of refractive error. Genome-wide association and sequencing studies have increased our understanding of the genetics involved in refractive error. These studies have identified interesting candidate genes. All genetic loci discovered to date indicate that refractive development is a heterogeneous process mediated by a number of overlapping biological processes. The exact mechanisms by which these biological networks regulate eye growth are poorly understood. Although several individual genes and/or molecular pathways have been investigated in animal models, a systematic network-based approach in modeling human refractive development is necessary to understand the complex interplay between genes and environment in refractive error. New biomedical technologies and better-designed studies will continue to refine our understanding of the genetics and molecular pathways of refractive error, and may lead to preventative and therapeutic measures to combat the myopia epidemic.

Estimation of genetic connectedness diagnostics based on prediction errors without the prediction error variance-covariance matrix.

PubMed

Holmes, John B; Dodds, Ken G; Lee, Michael A

2017-03-02

An important issue in genetic evaluation is the comparability of random effects (breeding values), particularly between pairs of animals in different contemporary groups. This is usually referred to as genetic connectedness. While various measures of connectedness have been proposed in the literature, there is general agreement that the most appropriate measure is some function of the prediction error variance-covariance matrix. However, obtaining the prediction error variance-covariance matrix is computationally demanding for large-scale genetic evaluations. Many alternative statistics have been proposed that avoid the computational cost of obtaining the prediction error variance-covariance matrix, such as counts of genetic links between contemporary groups, gene flow matrices, and functions of the variance-covariance matrix of estimated contemporary group fixed effects. In this paper, we show that a correction to the variance-covariance matrix of estimated contemporary group fixed effects will produce the exact prediction error variance-covariance matrix averaged by contemporary group for univariate models in the presence of single or multiple fixed effects and one random effect. We demonstrate the correction for a series of models and show that approximations to the prediction error matrix based solely on the variance-covariance matrix of estimated contemporary group fixed effects are inappropriate in certain circumstances. Our method allows for the calculation of a connectedness measure based on the prediction error variance-covariance matrix by calculating only the variance-covariance matrix of estimated fixed effects. Since the number of fixed effects in genetic evaluation is usually orders of magnitudes smaller than the number of random effect levels, the computational requirements for our method should be reduced.

Implementing and Improving Automated Electronic Tumor Molecular Profiling

PubMed Central

Staggs, David B.; Hackett, Lauren; Haberman, Erich; Tod, Mike; Levy, Mia; Warner, Jeremy

2016-01-01

Oncology practice increasingly requires the use of molecular profiling of tumors to inform the use of targeted therapeutics. However, many oncologists use third-party laboratories to perform tumor genomic testing, and these laboratories may not have electronic interfaces with the provider’s electronic medical record (EMR) system. The resultant reporting mechanisms, such as plain-paper faxing, can reduce report fidelity, slow down reporting procedures for a physician’s practice, and make reports less accessible. Vanderbilt University Medical Center and its genomic laboratory testing partner have collaborated to create an automated electronic reporting system that incorporates genetic testing results directly into the clinical EMR. This system was iteratively tested, and causes of failure were discovered and addressed. Most errors were attributable to data entry or typographical errors that made reports unable to be linked to the correct patient in the EMR. By providing direct feedback to providers, we were able to significantly decrease the rate of transmission errors (from 6.29% to 3.84%; P < .001). The results and lessons of 1 year of using the system and transmitting 832 tumor genomic testing reports are reported. PMID:26813927

High-precision approach to localization scheme of visible light communication based on artificial neural networks and modified genetic algorithms

NASA Astrophysics Data System (ADS)

Guan, Weipeng; Wu, Yuxiang; Xie, Canyu; Chen, Hao; Cai, Ye; Chen, Yingcong

2017-10-01

An indoor positioning algorithm based on visible light communication (VLC) is presented. This algorithm is used to calculate a three-dimensional (3-D) coordinate of an indoor optical wireless environment, which includes sufficient orders of multipath reflections from reflecting surfaces of the room. Leveraging the global optimization ability of the genetic algorithm (GA), an innovative framework for 3-D position estimation based on a modified genetic algorithm is proposed. Unlike other techniques using VLC for positioning, the proposed system can achieve indoor 3-D localization without making assumptions about the height or acquiring the orientation angle of the mobile terminal. Simulation results show that an average localization error of less than 1.02 cm can be achieved. In addition, in most VLC-positioning systems, the effect of reflection is always neglected and its performance is limited by reflection, which makes the results not so accurate for a real scenario and the positioning errors at the corners are relatively larger than other places. So, we take the first-order reflection into consideration and use artificial neural network to match the model of a nonlinear channel. The studies show that under the nonlinear matching of direct and reflected channels the average positioning errors of four corners decrease from 11.94 to 0.95 cm. The employed algorithm is emerged as an effective and practical method for indoor localization and outperform other existing indoor wireless localization approaches.

Genetic Local Search for Optimum Multiuser Detection Problem in DS-CDMA Systems

NASA Astrophysics Data System (ADS)

Wang, Shaowei; Ji, Xiaoyong

Optimum multiuser detection (OMD) in direct-sequence code-division multiple access (DS-CDMA) systems is an NP-complete problem. In this paper, we present a genetic local search algorithm, which consists of an evolution strategy framework and a local improvement procedure. The evolution strategy searches the space of feasible, locally optimal solutions only. A fast iterated local search algorithm, which employs the proprietary characteristics of the OMD problem, produces local optima with great efficiency. Computer simulations show the bit error rate (BER) performance of the GLS outperforms other multiuser detectors in all cases discussed. The computation time is polynomial complexity in the number of users.

From Heuristic to Mathematical Modeling of Drugs Dissolution Profiles: Application of Artificial Neural Networks and Genetic Programming

PubMed Central

Mendyk, Aleksander; Güres, Sinan; Szlęk, Jakub; Wiśniowska, Barbara; Kleinebudde, Peter

2015-01-01

The purpose of this work was to develop a mathematical model of the drug dissolution (Q) from the solid lipid extrudates based on the empirical approach. Artificial neural networks (ANNs) and genetic programming (GP) tools were used. Sensitivity analysis of ANNs provided reduction of the original input vector. GP allowed creation of the mathematical equation in two major approaches: (1) direct modeling of Q versus extrudate diameter (d) and the time variable (t) and (2) indirect modeling through Weibull equation. ANNs provided also information about minimum achievable generalization error and the way to enhance the original dataset used for adjustment of the equations' parameters. Two inputs were found important for the drug dissolution: d and t. The extrudates length (L) was found not important. Both GP modeling approaches allowed creation of relatively simple equations with their predictive performance comparable to the ANNs (root mean squared error (RMSE) from 2.19 to 2.33). The direct mode of GP modeling of Q versus d and t resulted in the most robust model. The idea of how to combine ANNs and GP in order to escape ANNs' black-box drawback without losing their superior predictive performance was demonstrated. Open Source software was used to deliver the state-of-the-art models and modeling strategies. PMID:26101544

From Heuristic to Mathematical Modeling of Drugs Dissolution Profiles: Application of Artificial Neural Networks and Genetic Programming.

PubMed

Mendyk, Aleksander; Güres, Sinan; Jachowicz, Renata; Szlęk, Jakub; Polak, Sebastian; Wiśniowska, Barbara; Kleinebudde, Peter

2015-01-01

The purpose of this work was to develop a mathematical model of the drug dissolution (Q) from the solid lipid extrudates based on the empirical approach. Artificial neural networks (ANNs) and genetic programming (GP) tools were used. Sensitivity analysis of ANNs provided reduction of the original input vector. GP allowed creation of the mathematical equation in two major approaches: (1) direct modeling of Q versus extrudate diameter (d) and the time variable (t) and (2) indirect modeling through Weibull equation. ANNs provided also information about minimum achievable generalization error and the way to enhance the original dataset used for adjustment of the equations' parameters. Two inputs were found important for the drug dissolution: d and t. The extrudates length (L) was found not important. Both GP modeling approaches allowed creation of relatively simple equations with their predictive performance comparable to the ANNs (root mean squared error (RMSE) from 2.19 to 2.33). The direct mode of GP modeling of Q versus d and t resulted in the most robust model. The idea of how to combine ANNs and GP in order to escape ANNs' black-box drawback without losing their superior predictive performance was demonstrated. Open Source software was used to deliver the state-of-the-art models and modeling strategies.

Accurate recapture identification for genetic mark–recapture studies with error-tolerant likelihood-based match calling and sample clustering

USGS Publications Warehouse

Sethi, Suresh; Linden, Daniel; Wenburg, John; Lewis, Cara; Lemons, Patrick R.; Fuller, Angela K.; Hare, Matthew P.

2016-01-01

Error-tolerant likelihood-based match calling presents a promising technique to accurately identify recapture events in genetic mark–recapture studies by combining probabilities of latent genotypes and probabilities of observed genotypes, which may contain genotyping errors. Combined with clustering algorithms to group samples into sets of recaptures based upon pairwise match calls, these tools can be used to reconstruct accurate capture histories for mark–recapture modelling. Here, we assess the performance of a recently introduced error-tolerant likelihood-based match-calling model and sample clustering algorithm for genetic mark–recapture studies. We assessed both biallelic (i.e. single nucleotide polymorphisms; SNP) and multiallelic (i.e. microsatellite; MSAT) markers using a combination of simulation analyses and case study data on Pacific walrus (Odobenus rosmarus divergens) and fishers (Pekania pennanti). A novel two-stage clustering approach is demonstrated for genetic mark–recapture applications. First, repeat captures within a sampling occasion are identified. Subsequently, recaptures across sampling occasions are identified. The likelihood-based matching protocol performed well in simulation trials, demonstrating utility for use in a wide range of genetic mark–recapture studies. Moderately sized SNP (64+) and MSAT (10–15) panels produced accurate match calls for recaptures and accurate non-match calls for samples from closely related individuals in the face of low to moderate genotyping error. Furthermore, matching performance remained stable or increased as the number of genetic markers increased, genotyping error notwithstanding.

Detecting genotyping errors and describing black bear movement in northern Idaho

Treesearch

Michael K. Schwartz; Samuel A. Cushman; Kevin S. McKelvey; Jim Hayden; Cory Engkjer

2006-01-01

Non-invasive genetic sampling has become a favored tool to enumerate wildlife. Genetic errors, caused by poor quality samples, can lead to substantial biases in numerical estimates of individuals. We demonstrate how the computer program DROPOUT can detect amplification errors (false alleles and allelic dropout) in a black bear (Ursus americanus) dataset collected in...

Analysis of Errors Made by Students Solving Genetics Problems.

ERIC Educational Resources Information Center

Costello, Sandra Judith

The purpose of this study was to analyze the errors made by students solving genetics problems. A sample of 10 non-science undergraduate students was obtained from a private college in Northern New Jersey. The results support prior research in the area of genetics education and show that a weak understanding of the relationship of meiosis to…

Pollutant source identification model for water pollution incidents in small straight rivers based on genetic algorithm

NASA Astrophysics Data System (ADS)

Zhang, Shou-ping; Xin, Xiao-kang

2017-07-01

Identification of pollutant sources for river pollution incidents is an important and difficult task in the emergency rescue, and an intelligent optimization method can effectively compensate for the weakness of traditional methods. An intelligent model for pollutant source identification has been established using the basic genetic algorithm (BGA) as an optimization search tool and applying an analytic solution formula of one-dimensional unsteady water quality equation to construct the objective function. Experimental tests show that the identification model is effective and efficient: the model can accurately figure out the pollutant amounts or positions no matter single pollution source or multiple sources. Especially when the population size of BGA is set as 10, the computing results are sound agree with analytic results for a single source amount and position identification, the relative errors are no more than 5 %. For cases of multi-point sources and multi-variable, there are some errors in computing results for the reasons that there exist many possible combinations of the pollution sources. But, with the help of previous experience to narrow the search scope, the relative errors of the identification results are less than 5 %, which proves the established source identification model can be used to direct emergency responses.

An engineer's view on genetic information and biological evolution.

PubMed

Battail, Gérard

2004-01-01

We develop ideas on genome replication introduced in Battail [Europhys. Lett. 40 (1997) 343]. Starting with the hypothesis that the genome replication process uses error-correcting means, and the auxiliary one that nested codes are used to this end, we first review the concepts of redundancy and error-correcting codes. Then we show that these hypotheses imply that: distinct species exist with a hierarchical taxonomy, there is a trend of evolution towards complexity, and evolution proceeds by discrete jumps. At least the first two features above may be considered as biological facts so, in the absence of direct evidence, they provide an indirect proof in favour of the hypothesized error-correction system. The very high redundancy of genomes makes it possible. In order to explain how it is implemented, we suggest that soft codes and replication decoding, to be briefly described, are plausible candidates. Experimentally proven properties of long-range correlation of the DNA message substantiate this claim.

Random mutagenesis by error-prone pol plasmid replication in Escherichia coli.

PubMed

Alexander, David L; Lilly, Joshua; Hernandez, Jaime; Romsdahl, Jillian; Troll, Christopher J; Camps, Manel

2014-01-01

Directed evolution is an approach that mimics natural evolution in the laboratory with the goal of modifying existing enzymatic activities or of generating new ones. The identification of mutants with desired properties involves the generation of genetic diversity coupled with a functional selection or screen. Genetic diversity can be generated using PCR or using in vivo methods such as chemical mutagenesis or error-prone replication of the desired sequence in a mutator strain. In vivo mutagenesis methods facilitate iterative selection because they do not require cloning, but generally produce a low mutation density with mutations not restricted to specific genes or areas within a gene. For this reason, this approach is typically used to generate new biochemical properties when large numbers of mutants can be screened or selected. Here we describe protocols for an advanced in vivo mutagenesis method that is based on error-prone replication of a ColE1 plasmid bearing the gene of interest. Compared to other in vivo mutagenesis methods, this plasmid-targeted approach allows increased mutation loads and facilitates iterative selection approaches. We also describe the mutation spectrum for this mutagenesis methodology in detail, and, using cycle 3 GFP as a target for mutagenesis, we illustrate the phenotypic diversity that can be generated using our method. In sum, error-prone Pol I replication is a mutagenesis method that is ideally suited for the evolution of new biochemical activities when a functional selection is available.

Performance Analysis of Combined Methods of Genetic Algorithm and K-Means Clustering in Determining the Value of Centroid

NASA Astrophysics Data System (ADS)

Adya Zizwan, Putra; Zarlis, Muhammad; Budhiarti Nababan, Erna

2017-12-01

The determination of Centroid on K-Means Algorithm directly affects the quality of the clustering results. Determination of centroid by using random numbers has many weaknesses. The GenClust algorithm that combines the use of Genetic Algorithms and K-Means uses a genetic algorithm to determine the centroid of each cluster. The use of the GenClust algorithm uses 50% chromosomes obtained through deterministic calculations and 50% is obtained from the generation of random numbers. This study will modify the use of the GenClust algorithm in which the chromosomes used are 100% obtained through deterministic calculations. The results of this study resulted in performance comparisons expressed in Mean Square Error influenced by centroid determination on K-Means method by using GenClust method, modified GenClust method and also classic K-Means.

Estimation of Genetic Parameters from Longitudinal Records of Body Weight of Berkshire Pigs

PubMed Central

Lee, Dong-Hee; Do, Chang-Hee

2012-01-01

Direct and maternal genetic heritabilities and their correlations with body weight at 5 stages in the life span of purebred Berkshire pigs, from birth to harvest, were estimated to scrutinize body weight development with the records for 5,088 purebred Berkshire pigs in a Korean farm, using the REML based on an animal model. Body weights were measured at birth (Birth), at weaning (Weaning: mean 22.9 d), at the beginning of a performance test (On: mean 72.7 d), at the end of a performance test (Off: mean 152.4 d), and at harvest (Finish: mean 174.3 d). Ordinary polynomials and Legendre with order 1, 2, and 3 were adopted to adjust body weight with age in the multivariate animal models. Legendre with order 3 fitted best concerning prediction error deviation (PED) and yielded the lowest AIC for multivariate analysis of longitudinal body weights. Direct genetic correlations between body weight at Birth and body weight at Weaning, On, Off, and Finish were 0.48, 0.36, 0.10, and 0.10, respectively. The estimated maternal genetic correlations of body weight at Finish with body weight at Birth, Weaning, On, and Off were 0.39, 0.49, 0.65, and 0.90, respectively. Direct genetic heritabilities progressively increased from birth to harvest and were 0.09, 0.11, 0.20, 0.31, and 0.43 for body weight at Birth, Weaning, On, Off, and Finish, respectively. Maternal genetic heritabilities generally decreased and were 0.26, 0.34, 0.15, 0.10, and 0.10 for body weight at Birth, Weaning, On, Off, and Finish, respectively. As pigs age, maternal genetic effects on growth are reduced and pigs begin to rely more on the expression of their own genes. Although maternal genetic effects on body weight may not be large, they are sustained through life. PMID:25049624

Crystal Genetics, Inc.

PubMed

Kermani, Bahram G

2016-07-01

Crystal Genetics, Inc. is an early-stage genetic test company, focused on achieving the highest possible clinical-grade accuracy and comprehensiveness for detecting germline (e.g., in hereditary cancer) and somatic (e.g., in early cancer detection) mutations. Crystal's mission is to significantly improve the health status of the population, by providing high accuracy, comprehensive, flexible and affordable genetic tests, primarily in cancer. Crystal's philosophy is that when it comes to detecting mutations that are strongly correlated with life-threatening diseases, the detection accuracy of every single mutation counts: a single false-positive error could cause severe anxiety for the patient. And, more importantly, a single false-negative error could potentially cost the patient's life. Crystal's objective is to eliminate both of these error types.

Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions.

PubMed

Lo, Te-Wen; Pickle, Catherine S; Lin, Steven; Ralston, Edward J; Gurling, Mark; Schartner, Caitlin M; Bian, Qian; Doudna, Jennifer A; Meyer, Barbara J

2013-10-01

Exploitation of custom-designed nucleases to induce DNA double-strand breaks (DSBs) at genomic locations of choice has transformed our ability to edit genomes, regardless of their complexity. DSBs can trigger either error-prone repair pathways that induce random mutations at the break sites or precise homology-directed repair pathways that generate specific insertions or deletions guided by exogenously supplied DNA. Prior editing strategies using site-specific nucleases to modify the Caenorhabditis elegans genome achieved only the heritable disruption of endogenous loci through random mutagenesis by error-prone repair. Here we report highly effective strategies using TALE nucleases and RNA-guided CRISPR/Cas9 nucleases to induce error-prone repair and homology-directed repair to create heritable, precise insertion, deletion, or substitution of specific DNA sequences at targeted endogenous loci. Our robust strategies are effective across nematode species diverged by 300 million years, including necromenic nematodes (Pristionchus pacificus), male/female species (Caenorhabditis species 9), and hermaphroditic species (C. elegans). Thus, genome-editing tools now exist to transform nonmodel nematode species into genetically tractable model organisms. We demonstrate the utility of our broadly applicable genome-editing strategies by creating reagents generally useful to the nematode community and reagents specifically designed to explore the mechanism and evolution of X chromosome dosage compensation. By developing an efficient pipeline involving germline injection of nuclease mRNAs and single-stranded DNA templates, we engineered precise, heritable nucleotide changes both close to and far from DSBs to gain or lose genetic function, to tag proteins made from endogenous genes, and to excise entire loci through targeted FLP-FRT recombination.

Developing approaches for linear mixed modeling in landscape genetics through landscape-directed dispersal simulations

USGS Publications Warehouse

Row, Jeffrey R.; Knick, Steven T.; Oyler-McCance, Sara J.; Lougheed, Stephen C.; Fedy, Bradley C.

2017-01-01

Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R2 values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.

Age-related variation in genetic control of height growth in Douglas-fir.

PubMed

Namkoong, G; Usanis, R A; Silen, R R

1972-01-01

The development of genetic variances in height growth of Douglas-fir over a 53-year period is analyzed and found to fall into three periods. In the juvenile period, variances in environmental error increase logarithmically, genetic variance within populations exists at moderate levels, and variance among populations is low but increasing. In the early reproductive period, the response to environmental sources of error variance is restricted, genetic variance within populations disappears, and populational differences strongly emerge but do not increase as expected. In the later period, environmental error again increases rapidly, but genetic variance within populations does not reappear and population differences are maintained at about the same level as established in the early reproductive period. The change between the juvenile and early reproductive periods is perhaps associated with the onset of ecological dominance and significant allocations of energy to reproduction.

Template-Directed Copolymerization, Random Walks along Disordered Tracks, and Fractals

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-12-01

In biology, template-directed copolymerization is the fundamental mechanism responsible for the synthesis of DNA, RNA, and proteins. More than 50 years have passed since the discovery of DNA structure and its role in coding genetic information. Yet, the kinetics and thermodynamics of information processing in DNA replication, transcription, and translation remain poorly understood. Challenging issues are the facts that DNA or RNA sequences constitute disordered media for the motion of polymerases or ribosomes while errors occur in copying the template. Here, it is shown that these issues can be addressed and sequence heterogeneity effects can be quantitatively understood within a framework revealing universal aspects of information processing at the molecular scale. In steady growth regimes, the local velocities of polymerases or ribosomes along the template are distributed as the continuous or fractal invariant set of a so-called iterated function system, which determines the copying error probabilities. The growth may become sublinear in time with a scaling exponent that can also be deduced from the iterated function system.

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper reveals that nearly 25 years after the used Russell's dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment, Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it to incorrectly adopt the LNT model, which was a decision that profoundly changed the course of risk assessment for radiation and chemicals to the present. -- Highlights: • The BEAR I Genetics Panel made an error in denying dose rate for mutation. •more » The BEIR I Genetics Subcommittee attempted to correct this dose rate error. • The control group used for risk assessment by BEIR I is now known to be in error. • Correcting this error contradicts the LNT, supporting a threshold model.« less

Accurate construction of consensus genetic maps via integer linear programming.

PubMed

Wu, Yonghui; Close, Timothy J; Lonardi, Stefano

2011-01-01

We study the problem of merging genetic maps, when the individual genetic maps are given as directed acyclic graphs. The computational problem is to build a consensus map, which is a directed graph that includes and is consistent with all (or, the vast majority of) the markers in the input maps. However, when markers in the individual maps have ordering conflicts, the resulting consensus map will contain cycles. Here, we formulate the problem of resolving cycles in the context of a parsimonious paradigm that takes into account two types of errors that may be present in the input maps, namely, local reshuffles and global displacements. The resulting combinatorial optimization problem is, in turn, expressed as an integer linear program. A fast approximation algorithm is proposed, and an additional speedup heuristic is developed. Our algorithms were implemented in a software tool named MERGEMAP which is freely available for academic use. An extensive set of experiments shows that MERGEMAP consistently outperforms JOINMAP, which is the most popular tool currently available for this task, both in terms of accuracy and running time. MERGEMAP is available for download at http://www.cs.ucr.edu/~yonghui/mgmap.html.

Assumption-free estimation of the genetic contribution to refractive error across childhood.

PubMed

Guggenheim, Jeremy A; St Pourcain, Beate; McMahon, George; Timpson, Nicholas J; Evans, David M; Williams, Cathy

2015-01-01

Studies in relatives have generally yielded high heritability estimates for refractive error: twins 75-90%, families 15-70%. However, because related individuals often share a common environment, these estimates are inflated (via misallocation of unique/common environment variance). We calculated a lower-bound heritability estimate for refractive error free from such bias. Between the ages 7 and 15 years, participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent non-cycloplegic autorefraction at regular research clinics. At each age, an estimate of the variance in refractive error explained by single nucleotide polymorphism (SNP) genetic variants was calculated using genome-wide complex trait analysis (GCTA) using high-density genome-wide SNP genotype information (minimum N at each age=3,404). The variance in refractive error explained by the SNPs ("SNP heritability") was stable over childhood: Across age 7-15 years, SNP heritability averaged 0.28 (SE=0.08, p<0.001). The genetic correlation for refractive error between visits varied from 0.77 to 1.00 (all p<0.001) demonstrating that a common set of SNPs was responsible for the genetic contribution to refractive error across this period of childhood. Simulations suggested lack of cycloplegia during autorefraction led to a small underestimation of SNP heritability (adjusted SNP heritability=0.35; SE=0.09). To put these results in context, the variance in refractive error explained (or predicted) by the time participants spent outdoors was <0.005 and by the time spent reading was <0.01, based on a parental questionnaire completed when the child was aged 8-9 years old. Genetic variation captured by common SNPs explained approximately 35% of the variation in refractive error between unrelated subjects. This value sets an upper limit for predicting refractive error using existing SNP genotyping arrays, although higher-density genotyping in larger samples and inclusion of interaction effects is expected to raise this figure toward twin- and family-based heritability estimates. The same SNPs influenced refractive error across much of childhood. Notwithstanding the strong evidence of association between time outdoors and myopia, and time reading and myopia, less than 1% of the variance in myopia at age 15 was explained by crude measures of these two risk factors, indicating that their effects may be limited, at least when averaged over the whole population.

Interpreting findings from Mendelian randomization using the MR-Egger method.

PubMed

Burgess, Stephen; Thompson, Simon G

2017-05-01

Mendelian randomization-Egger (MR-Egger) is an analysis method for Mendelian randomization using summarized genetic data. MR-Egger consists of three parts: (1) a test for directional pleiotropy, (2) a test for a causal effect, and (3) an estimate of the causal effect. While conventional analysis methods for Mendelian randomization assume that all genetic variants satisfy the instrumental variable assumptions, the MR-Egger method is able to assess whether genetic variants have pleiotropic effects on the outcome that differ on average from zero (directional pleiotropy), as well as to provide a consistent estimate of the causal effect, under a weaker assumption-the InSIDE (INstrument Strength Independent of Direct Effect) assumption. In this paper, we provide a critical assessment of the MR-Egger method with regard to its implementation and interpretation. While the MR-Egger method is a worthwhile sensitivity analysis for detecting violations of the instrumental variable assumptions, there are several reasons why causal estimates from the MR-Egger method may be biased and have inflated Type 1 error rates in practice, including violations of the InSIDE assumption and the influence of outlying variants. The issues raised in this paper have potentially serious consequences for causal inferences from the MR-Egger approach. We give examples of scenarios in which the estimates from conventional Mendelian randomization methods and MR-Egger differ, and discuss how to interpret findings in such cases.

Software for Quantifying and Simulating Microsatellite Genotyping Error

PubMed Central

Johnson, Paul C.D.; Haydon, Daniel T.

2007-01-01

Microsatellite genetic marker data are exploited in a variety of fields, including forensics, gene mapping, kinship inference and population genetics. In all of these fields, inference can be thwarted by failure to quantify and account for data errors, and kinship inference in particular can benefit from separating errors into two distinct classes: allelic dropout and false alleles. Pedant is MS Windows software for estimating locus-specific maximum likelihood rates of these two classes of error. Estimation is based on comparison of duplicate error-prone genotypes: neither reference genotypes nor pedigree data are required. Other functions include: plotting of error rate estimates and confidence intervals; simulations for performing power analysis and for testing the robustness of error rate estimates to violation of the underlying assumptions; and estimation of expected heterozygosity, which is a required input. The program, documentation and source code are available from http://www.stats.gla.ac.uk/~paulj/pedant.html. PMID:20066126

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

Allen, J; Velsko, S

This report explores the question of whether meaningful conclusions can be drawn regarding the transmission relationship between two microbial samples on the basis of differences observed between the two sample's respective genomes. Unlike similar forensic applications using human DNA, the rapid rate of microbial genome evolution combined with the dynamics of infectious disease require a shift in thinking on what it means for two samples to 'match' in support of a forensic hypothesis. Previous outbreaks for SARS-CoV, FMDV and HIV were examined to investigate the question of how microbial sequence data can be used to draw inferences that link twomore » infected individuals by direct transmission. The results are counter intuitive with respect to human DNA forensic applications in that some genetic change rather than exact matching improve confidence in inferring direct transmission links, however, too much genetic change poses challenges, which can weaken confidence in inferred links. High rates of infection coupled with relatively weak selective pressure observed in the SARS-CoV and FMDV data lead to fairly low confidence for direct transmission links. Confidence values for forensic hypotheses increased when testing for the possibility that samples are separated by at most a few intermediate hosts. Moreover, the observed outbreak conditions support the potential to provide high confidence values for hypothesis that exclude direct transmission links. Transmission inferences are based on the total number of observed or inferred genetic changes separating two sequences rather than uniquely weighing the importance of any one genetic mismatch. Thus, inferences are surprisingly robust in the presence of sequencing errors provided the error rates are randomly distributed across all samples in the reference outbreak database and the novel sequence samples in question. When the number of observed nucleotide mutations are limited due to characteristics of the outbreak or the availability of only partial rather than whole genome sequencing, indel information was shown to have the potential to improve performance but only for select outbreak conditions. In examined HIV transmission cases, extended evolution proved to be the limiting factor in assigning high confidence to transmission links, however, the potential to correct for extended evolution not associated with transmission events is demonstrated. Outbreak specific conditions such as selective pressure (in the form of varying mutation rate), are shown to impact the strength of inference made and a Monte Carlo simulation tool is introduced, which is used to provide upper and lower bounds on the confidence values associated with a forensic hypothesis.« less

Analytical Plug-In Method for Kernel Density Estimator Applied to Genetic Neutrality Study

NASA Astrophysics Data System (ADS)

Troudi, Molka; Alimi, Adel M.; Saoudi, Samir

2008-12-01

The plug-in method enables optimization of the bandwidth of the kernel density estimator in order to estimate probability density functions (pdfs). Here, a faster procedure than that of the common plug-in method is proposed. The mean integrated square error (MISE) depends directly upon [InlineEquation not available: see fulltext.] which is linked to the second-order derivative of the pdf. As we intend to introduce an analytical approximation of [InlineEquation not available: see fulltext.], the pdf is estimated only once, at the end of iterations. These two kinds of algorithm are tested on different random variables having distributions known for their difficult estimation. Finally, they are applied to genetic data in order to provide a better characterisation in the mean of neutrality of Tunisian Berber populations.

Optimization of the ANFIS using a genetic algorithm for physical work rate classification.

PubMed

Habibi, Ehsanollah; Salehi, Mina; Yadegarfar, Ghasem; Taheri, Ali

2018-03-13

Recently, a new method was proposed for physical work rate classification based on an adaptive neuro-fuzzy inference system (ANFIS). This study aims to present a genetic algorithm (GA)-optimized ANFIS model for a highly accurate classification of physical work rate. Thirty healthy men participated in this study. Directly measured heart rate and oxygen consumption of the participants in the laboratory were used for training the ANFIS classifier model in MATLAB version 8.0.0 using a hybrid algorithm. A similar process was done using the GA as an optimization technique. The accuracy, sensitivity and specificity of the ANFIS classifier model were increased successfully. The mean accuracy of the model was increased from 92.95 to 97.92%. Also, the calculated root mean square error of the model was reduced from 5.4186 to 3.1882. The maximum estimation error of the optimized ANFIS during the network testing process was ± 5%. The GA can be effectively used for ANFIS optimization and leads to an accurate classification of physical work rate. In addition to high accuracy, simple implementation and inter-individual variability consideration are two other advantages of the presented model.

State space truncation with quantified errors for accurate solutions to discrete Chemical Master Equation

PubMed Central

Cao, Youfang; Terebus, Anna; Liang, Jie

2016-01-01

The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEG), we truncate the state space by limiting the total molecular copy numbers in each MEG. We further describe a theoretical framework for analysis of the truncation error in the steady state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an overall error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we also introduce an a priori method to estimate the upper bound of its truncation error. This a priori estimate can be rapidly computed from reaction rates of the network, without the need of costly trial solutions of the dCME. As examples, we show results of applying our methods to the four stochastic networks of 1) the birth and death model, 2) the single gene expression model, 3) the genetic toggle switch model, and 4) the phage lambda bistable epigenetic switch model. We demonstrate how truncation errors and steady state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate out theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large number of stochastic networks. PMID:27105653

State Space Truncation with Quantified Errors for Accurate Solutions to Discrete Chemical Master Equation

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

Cao, Youfang; Terebus, Anna; Liang, Jie

The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEGs), we truncate the state space by limiting the total molecular copy numbers in each MEG. Wemore » further describe a theoretical framework for analysis of the truncation error in the steady-state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an overall error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we also introduce an a priori method to estimate the upper bound of its truncation error. This a priori estimate can be rapidly computed from reaction rates of the network, without the need of costly trial solutions of the dCME. As examples, we show results of applying our methods to the four stochastic networks of (1) the birth and death model, (2) the single gene expression model, (3) the genetic toggle switch model, and (4) the phage lambda bistable epigenetic switch model. We demonstrate how truncation errors and steady-state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate our theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large number of stochastic networks.« less

State Space Truncation with Quantified Errors for Accurate Solutions to Discrete Chemical Master Equation

DOE PAGES

Cao, Youfang; Terebus, Anna; Liang, Jie

2016-04-22

The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEGs), we truncate the state space by limiting the total molecular copy numbers in each MEG. Wemore » further describe a theoretical framework for analysis of the truncation error in the steady-state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an overall error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we also introduce an a priori method to estimate the upper bound of its truncation error. This a priori estimate can be rapidly computed from reaction rates of the network, without the need of costly trial solutions of the dCME. As examples, we show results of applying our methods to the four stochastic networks of (1) the birth and death model, (2) the single gene expression model, (3) the genetic toggle switch model, and (4) the phage lambda bistable epigenetic switch model. We demonstrate how truncation errors and steady-state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate our theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large number of stochastic networks.« less

Primer ID Validates Template Sampling Depth and Greatly Reduces the Error Rate of Next-Generation Sequencing of HIV-1 Genomic RNA Populations

PubMed Central

Zhou, Shuntai; Jones, Corbin; Mieczkowski, Piotr

2015-01-01

ABSTRACT Validating the sampling depth and reducing sequencing errors are critical for studies of viral populations using next-generation sequencing (NGS). We previously described the use of Primer ID to tag each viral RNA template with a block of degenerate nucleotides in the cDNA primer. We now show that low-abundance Primer IDs (offspring Primer IDs) are generated due to PCR/sequencing errors. These artifactual Primer IDs can be removed using a cutoff model for the number of reads required to make a template consensus sequence. We have modeled the fraction of sequences lost due to Primer ID resampling. For a typical sequencing run, less than 10% of the raw reads are lost to offspring Primer ID filtering and resampling. The remaining raw reads are used to correct for PCR resampling and sequencing errors. We also demonstrate that Primer ID reveals bias intrinsic to PCR, especially at low template input or utilization. cDNA synthesis and PCR convert ca. 20% of RNA templates into recoverable sequences, and 30-fold sequence coverage recovers most of these template sequences. We have directly measured the residual error rate to be around 1 in 10,000 nucleotides. We use this error rate and the Poisson distribution to define the cutoff to identify preexisting drug resistance mutations at low abundance in an HIV-infected subject. Collectively, these studies show that >90% of the raw sequence reads can be used to validate template sampling depth and to dramatically reduce the error rate in assessing a genetically diverse viral population using NGS. IMPORTANCE Although next-generation sequencing (NGS) has revolutionized sequencing strategies, it suffers from serious limitations in defining sequence heterogeneity in a genetically diverse population, such as HIV-1 due to PCR resampling and PCR/sequencing errors. The Primer ID approach reveals the true sampling depth and greatly reduces errors. Knowing the sampling depth allows the construction of a model of how to maximize the recovery of sequences from input templates and to reduce resampling of the Primer ID so that appropriate multiplexing can be included in the experimental design. With the defined sampling depth and measured error rate, we are able to assign cutoffs for the accurate detection of minority variants in viral populations. This approach allows the power of NGS to be realized without having to guess about sampling depth or to ignore the problem of PCR resampling, while also being able to correct most of the errors in the data set. PMID:26041299

Application of genetic algorithm in the evaluation of the profile error of archimedes helicoid surface

NASA Astrophysics Data System (ADS)

Zhu, Lianqing; Chen, Yunfang; Chen, Qingshan; Meng, Hao

2011-05-01

According to minimum zone condition, a method for evaluating the profile error of Archimedes helicoid surface based on Genetic Algorithm (GA) is proposed. The mathematic model of the surface is provided and the unknown parameters in the equation of surface are acquired through least square method. Principle of GA is explained. Then, the profile error of Archimedes Helicoid surface is obtained through GA optimization method. To validate the proposed method, the profile error of an Archimedes helicoid surface, Archimedes Cylindrical worm (ZA worm) surface, is evaluated. The results show that the proposed method is capable of correctly evaluating the profile error of Archimedes helicoid surface and satisfy the evaluation standard of the Minimum Zone Method. It can be applied to deal with the measured data of profile error of complex surface obtained by three coordinate measurement machines (CMM).

Dissociable Genetic Contributions to Error Processing: A Multimodal Neuroimaging Study

PubMed Central

Agam, Yigal; Vangel, Mark; Roffman, Joshua L.; Gallagher, Patience J.; Chaponis, Jonathan; Haddad, Stephen; Goff, Donald C.; Greenberg, Jennifer L.; Wilhelm, Sabine; Smoller, Jordan W.; Manoach, Dara S.

2014-01-01

Background Neuroimaging studies reliably identify two markers of error commission: the error-related negativity (ERN), an event-related potential, and functional MRI activation of the dorsal anterior cingulate cortex (dACC). While theorized to reflect the same neural process, recent evidence suggests that the ERN arises from the posterior cingulate cortex not the dACC. Here, we tested the hypothesis that these two error markers also have different genetic mediation. Methods We measured both error markers in a sample of 92 comprised of healthy individuals and those with diagnoses of schizophrenia, obsessive-compulsive disorder or autism spectrum disorder. Participants performed the same task during functional MRI and simultaneously acquired magnetoencephalography and electroencephalography. We examined the mediation of the error markers by two single nucleotide polymorphisms: dopamine D4 receptor (DRD4) C-521T (rs1800955), which has been associated with the ERN and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), which has been associated with error-related dACC activation. We then compared the effects of each polymorphism on the two error markers modeled as a bivariate response. Results We replicated our previous report of a posterior cingulate source of the ERN in healthy participants in the schizophrenia and obsessive-compulsive disorder groups. The effect of genotype on error markers did not differ significantly by diagnostic group. DRD4 C-521T allele load had a significant linear effect on ERN amplitude, but not on dACC activation, and this difference was significant. MTHFR C677T allele load had a significant linear effect on dACC activation but not ERN amplitude, but the difference in effects on the two error markers was not significant. Conclusions DRD4 C-521T, but not MTHFR C677T, had a significant differential effect on two canonical error markers. Together with the anatomical dissociation between the ERN and error-related dACC activation, these findings suggest that these error markers have different neural and genetic mediation. PMID:25010186

Statistical power and utility of meta-analysis methods for cross-phenotype genome-wide association studies.

PubMed

Zhu, Zhaozhong; Anttila, Verneri; Smoller, Jordan W; Lee, Phil H

2018-01-01

Advances in recent genome wide association studies (GWAS) suggest that pleiotropic effects on human complex traits are widespread. A number of classic and recent meta-analysis methods have been used to identify genetic loci with pleiotropic effects, but the overall performance of these methods is not well understood. In this work, we use extensive simulations and case studies of GWAS datasets to investigate the power and type-I error rates of ten meta-analysis methods. We specifically focus on three conditions commonly encountered in the studies of multiple traits: (1) extensive heterogeneity of genetic effects; (2) characterization of trait-specific association; and (3) inflated correlation of GWAS due to overlapping samples. Although the statistical power is highly variable under distinct study conditions, we found the superior power of several methods under diverse heterogeneity. In particular, classic fixed-effects model showed surprisingly good performance when a variant is associated with more than a half of study traits. As the number of traits with null effects increases, ASSET performed the best along with competitive specificity and sensitivity. With opposite directional effects, CPASSOC featured the first-rate power. However, caution is advised when using CPASSOC for studying genetically correlated traits with overlapping samples. We conclude with a discussion of unresolved issues and directions for future research.

Genetic and Environmental Influences on Writing and their Relations to Language and Reading

PubMed Central

Olson, Richard K.; Hulslander, Jacqueline; Christopher, Micaela; Keenan, Janice M.; Wadsworth, Sally J.; Willcutt, Erik G.; Pennington, Bruce F.; DeFries, John C.

2011-01-01

Identical and fraternal twins (N = 540, age 8 to 18 years) were tested on three different measures of writing (Woodcock-Johnson III Tests of Achievement-Writing Samples and Writing Fluency; Handwriting Copy from the Group Diagnostic Reading and Aptitude Achievement Tests), three different language skills (Phonological Awareness, Rapid Naming, and Vocabulary), and three different reading skills (Word Recognition, Spelling, and Reading Comprehension). Substantial genetic influence was found on two of the writing measures, Writing Samples and Handwriting Copy, and all of the language and reading measures. Shared environment influences were generally not significant, except for vocabulary. Non-shared environment estimates, including measurement error, were significant for all variables. Genetic influences among the writing measures were significantly correlated (highest between the speeded measures Writing Fluency and Handwriting Copy), but there were also significant independent genetic influences between Copy and Samples and between Fluency and Samples. Genetic influences on writing were significantly correlated with genetic influences on all of the language and reading skills, but significant independent genetic influences were also found for Copy and Samples, whose genetic correlations were significantly less than 1.0 with the reading and language skills. The genetic correlations varied significantly in strength depending on the overlap between the writing, language, and reading task demands. We discuss implications of our results for education, limitations of the study, and new directions for research on writing and its relations to language and reading. PMID:21842316

A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

PubMed

Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

2009-12-01

Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors. 2009 Wiley-Liss, Inc.

EvolQG - An R package for evolutionary quantitative genetics

PubMed Central

Melo, Diogo; Garcia, Guilherme; Hubbe, Alex; Assis, Ana Paula; Marroig, Gabriel

2016-01-01

We present an open source package for performing evolutionary quantitative genetics analyses in the R environment for statistical computing. Evolutionary theory shows that evolution depends critically on the available variation in a given population. When dealing with many quantitative traits this variation is expressed in the form of a covariance matrix, particularly the additive genetic covariance matrix or sometimes the phenotypic matrix, when the genetic matrix is unavailable and there is evidence the phenotypic matrix is sufficiently similar to the genetic matrix. Given this mathematical representation of available variation, the \\textbf{EvolQG} package provides functions for calculation of relevant evolutionary statistics; estimation of sampling error; corrections for this error; matrix comparison via correlations, distances and matrix decomposition; analysis of modularity patterns; and functions for testing evolutionary hypotheses on taxa diversification. PMID:27785352

Assimilating concentration observations for transport and dispersion modeling in a meandering wind field

NASA Astrophysics Data System (ADS)

Haupt, Sue Ellen; Beyer-Lout, Anke; Long, Kerrie J.; Young, George S.

Assimilating concentration data into an atmospheric transport and dispersion model can provide information to improve downwind concentration forecasts. The forecast model is typically a one-way coupled set of equations: the meteorological equations impact the concentration, but the concentration does not generally affect the meteorological field. Thus, indirect methods of using concentration data to influence the meteorological variables are required. The problem studied here involves a simple wind field forcing Gaussian dispersion. Two methods of assimilating concentration data to infer the wind direction are demonstrated. The first method is Lagrangian in nature and treats the puff as an entity using feature extraction coupled with nudging. The second method is an Eulerian field approach akin to traditional variational approaches, but minimizes the error by using a genetic algorithm (GA) to directly optimize the match between observations and predictions. Both methods show success at inferring the wind field. The GA-variational method, however, is more accurate but requires more computational time. Dynamic assimilation of a continuous release modeled by a Gaussian plume is also demonstrated using the genetic algorithm approach.

Education influences the association between genetic variants and refractive error: a meta-analysis of five Singapore studies

PubMed Central

Fan, Qiao; Wojciechowski, Robert; Kamran Ikram, M.; Cheng, Ching-Yu; Chen, Peng; Zhou, Xin; Pan, Chen-Wei; Khor, Chiea-Chuen; Tai, E-Shyong; Aung, Tin; Wong, Tien-Yin; Teo, Yik-Ying; Saw, Seang-Mei

2014-01-01

Refractive error is a complex ocular trait governed by both genetic and environmental factors and possibly their interplay. Thus far, data on the interaction between genetic variants and environmental risk factors for refractive errors are largely lacking. By using findings from recent genome-wide association studies, we investigated whether the main environmental factor, education, modifies the effect of 40 single nucleotide polymorphisms on refractive error among 8461 adults from five studies including ethnic Chinese, Malay and Indian residents of Singapore. Three genetic loci SHISA6-DNAH9, GJD2 and ZMAT4-SFRP1 exhibited a strong association with myopic refractive error in individuals with higher secondary or university education (SHISA6-DNAH9: rs2969180 A allele, β = −0.33 D, P = 3.6 × 10–6; GJD2: rs524952 A allele, β = −0.31 D, P = 1.68 × 10−5; ZMAT4-SFRP1: rs2137277 A allele, β = −0.47 D, P = 1.68 × 10−4), whereas the association at these loci was non-significant or of borderline significance in those with lower secondary education or below (P for interaction: 3.82 × 10−3–4.78 × 10−4). The evidence for interaction was strengthened when combining the genetic effects of these three loci (P for interaction = 4.40 × 10−8), and significant interactions with education were also observed for axial length and myopia. Our study shows that low level of education may attenuate the effect of risk alleles on myopia. These findings further underline the role of gene–environment interactions in the pathophysiology of myopia. PMID:24014484

Circumpolar Genetic Structure and Recent Gene Flow of Polar Bears: A Reanalysis.

PubMed

Malenfant, René M; Davis, Corey S; Cullingham, Catherine I; Coltman, David W

2016-01-01

Recently, an extensive study of 2,748 polar bears (Ursus maritimus) from across their circumpolar range was published in PLOS ONE, which used microsatellites and mitochondrial haplotypes to apparently show altered population structure and a dramatic change in directional gene flow towards the Canadian Archipelago-an area believed to be a future refugium for polar bears as their southernmost habitats decline under climate change. Although this study represents a major international collaborative effort and promised to be a baseline for future genetics work, methodological shortcomings and errors of interpretation undermine some of the study's main conclusions. Here, we present a reanalysis of this data in which we address some of these issues, including: (1) highly unbalanced sample sizes and large amounts of systematically missing data; (2) incorrect calculation of FST and of significance levels; (3) misleading estimates of recent gene flow resulting from non-convergence of the program BayesAss. In contrast to the original findings, in our reanalysis we find six genetic clusters of polar bears worldwide: the Hudson Bay Complex, the Western and Eastern Canadian Arctic Archipelago, the Western and Eastern Polar Basin, and-importantly-we reconfirm the presence of a unique and possibly endangered cluster of bears in Norwegian Bay near Canada's expected last sea-ice refugium. Although polar bears' abundance, distribution, and population structure will certainly be negatively affected by ongoing-and increasingly rapid-loss of Arctic sea ice, these genetic data provide no evidence of strong directional gene flow in response to recent climate change.

Genetic parameters of body weight and ascites in broilers: effect of different incidence rates of ascites syndrome.

PubMed

Ahmadpanah, J; Ghavi Hossein-Zadeh, N; Shadparvar, A A; Pakdel, A

2017-02-01

1. The objectives of the current study were to investigate the effect of incidence rate (5%, 10%, 20%, 30% and 50%) of ascites syndrome on the expression of genetic characteristics for body weight at 5 weeks of age (BW5) and AS and to compare different methods of genetic parameter estimation for these traits. 2. Based on stochastic simulation, a population with discrete generations was created in which random mating was used for 10 generations. Two methods of restricted maximum likelihood and Bayesian approach via Gibbs sampling were used for the estimation of genetic parameters. A bivariate model including maternal effects was used. The root mean square error for direct heritabilities was also calculated. 3. The results showed that when incidence rates of ascites increased from 5% to 30%, the heritability of AS increased from 0.013 and 0.005 to 0.110 and 0.162 for linear and threshold models, respectively. 4. Maternal effects were significant for both BW5 and AS. Genetic correlations were decreased by increasing incidence rates of ascites in the population from 0.678 and 0.587 at 5% level of ascites to 0.393 and -0.260 at 50% occurrence for linear and threshold models, respectively. 5. The RMSE of direct heritability from true values for BW5 was greater based on a linear-threshold model compared with the linear model of analysis (0.0092 vs. 0.0015). The RMSE of direct heritability from true values for AS was greater based on a linear-linear model (1.21 vs. 1.14). 6. In order to rank birds for ascites incidence, it is recommended to use a threshold model because it resulted in higher heritability estimates compared with the linear model and that BW5 could be one of the main components of selection goals.

78 FR 9060 - Request for Nominations for Voting Members on Public Advisory Panels or Committees

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... diagnostic assays, e.g., hepatologists; molecular biologists. Molecular and Clinical 2 June 1, 2013. Genetics.... Individuals with training in inborn errors of metabolism, biochemical and/or molecular genetics, population genetics, epidemiology and related statistical training, and clinical molecular genetics testing (e.g...

The effects of training on errors of perceived direction in perspective displays

NASA Technical Reports Server (NTRS)

Tharp, Gregory K.; Ellis, Stephen R.

1990-01-01

An experiment was conducted to determine the effects of training on the characteristic direction errors that are observed when subjects estimate exocentric directions on perspective displays. Changes in five subjects' perceptual errors were measured during a training procedure designed to eliminate the error. The training was provided by displaying to each subject both the sign and the direction of his judgment error. The feedback provided by the error display was found to decrease but not eliminate the error. A lookup table model of the source of the error was developed in which the judgement errors were attributed to overestimates of both the pitch and the yaw of the viewing direction used to produce the perspective projection. The model predicts the quantitative characteristics of the data somewhat better than previous models did. A mechanism is proposed for the observed learning, and further tests of the model are suggested.

Neural markers of errors as endophenotypes in neuropsychiatric disorders

PubMed Central

Manoach, Dara S.; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach. PMID:23882201

Neural markers of errors as endophenotypes in neuropsychiatric disorders.

PubMed

Manoach, Dara S; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

Improving the value of costly genetic reference laboratory testing with active utilization management.

PubMed

Dickerson, Jane A; Cole, Bonnie; Conta, Jessie H; Wellner, Monica; Wallace, Stephanie E; Jack, Rhona M; Rutledge, Joe; Astion, Michael L

2014-01-01

Tests that are performed outside of the ordering institution, send-out tests, represent an area of risk to patients because of complexity associated with sending tests out. Risks related to send-out tests include increased number of handoffs, ordering the wrong or unnecessary test, specimen delays, data entry errors, preventable delays in reporting and acknowledging results, and excess financial liability. Many of the most expensive and most misunderstood tests are send-out genetic tests. To design and develop an active utilization management program to reduce the risk to patients and improve value of genetic send-out tests. Send-out test requests that met defined criteria were reviewed by a rotating team of doctoral-level consultants and a genetic counselor in a pediatric tertiary care center. Two hundred fifty-one cases were reviewed during an 8-month period. After review, nearly one-quarter of genetic test requests were modified in the downward direction, saving a total of 2% of the entire send-out bill and 19% of the test requests under management. Ultimately, these savings were passed on to patients. Implementing an active utilization strategy for expensive send-out tests can be achieved with minimal technical resources and results in improved value of testing to patients.

Genotype by production environment interaction for birth and weaning weights in a population of composite beef cattle.

PubMed

Santana, M L; Eler, J P; Bignardi, A B; Ferraz, J B S

2014-03-01

The objectives of the present study were: (1) to evaluate the importance of genotype × production environment interaction for the genetic evaluation of birth weight (BW) and weaning weight (WW) in a population of composite beef cattle in Brazil, and (2) to investigate the importance of sire × contemporary group interaction (S × CG) to model G × E and improve the accuracy of prediction in routine genetic evaluations of this population. Analyses were performed with one, two (favorable and unfavorable) or three (favorable, intermediate, unfavorable) different definitions of production environments. Thus, BW and WW records of animals in a favorable environment were assigned to either trait 1, in an intermediate environment to trait 2 or in an unfavorable environment to trait 3. The (co)variance components were estimated using Gibbs sampling in single-, bi- or three-trait animal models according to the definition of number of production environments. In general, the estimates of genetic parameters for BW and WW were similar between environments. The additive genetic correlations between production environments were close to unity for BW; however, when examining the highest posterior density intervals, the correlation between favorable and unfavorable environments reached a value of only 0.70, a fact that may lead to changes in the ranking of sires across environments. The posterior mean genetic correlation between direct effects was 0.63 in favorable and unfavorable environments for WW. When S × CG was included in two- or three-trait analyses, all direct genetic correlations were close to unity, suggesting that there was no evidence of a genotype × production environment interaction. Furthermore, the model including S × CG contributed to prevent overestimation of the accuracy of breeding values of sires, provided a lower error of prediction for both direct and maternal breeding values, lower squared bias, residual variance and deviance information criterion than the model omitting S × CG. Thus, the model that included S × CG can therefore be considered the best model on the basis of these criteria. The genotype × production environment interaction should not be neglected in the genetic evaluation of BW and WW in the present population of beef cattle. The inclusion of S × CG in the model is a feasible and plausible alternative to model the effects of G × E in the genetic evaluations.

First-order approximation error analysis of Risley-prism-based beam directing system.

PubMed

Zhao, Yanyan; Yuan, Yan

2014-12-01

To improve the performance of a Risley-prism system for optical detection and measuring applications, it is necessary to be able to determine the direction of the outgoing beam with high accuracy. In previous works, error sources and their impact on the performance of the Risley-prism system have been analyzed, but their numerical approximation accuracy was not high. Besides, pointing error analysis of the Risley-prism system has provided results for the case when the component errors, prism orientation errors, and assembly errors are certain. In this work, the prototype of a Risley-prism system was designed. The first-order approximations of the error analysis were derived and compared with the exact results. The directing errors of a Risley-prism system associated with wedge-angle errors, prism mounting errors, and bearing assembly errors were analyzed based on the exact formula and the first-order approximation. The comparisons indicated that our first-order approximation is accurate. In addition, the combined errors produced by the wedge-angle errors and mounting errors of the two prisms together were derived and in both cases were proved to be the sum of errors caused by the first and the second prism separately. Based on these results, the system error of our prototype was estimated. The derived formulas can be implemented to evaluate beam directing errors of any Risley-prism beam directing system with a similar configuration.

Heritability analyses of IQ scores: science or numerology?

PubMed

Layzer, D

1974-03-29

Estimates of IQ heritability are subject to a variety of systematic errors. The IQ scores themselves contain uncontrollable, systematic errors of unknown magnitude. These arise because IQ scores, unlike conventional physical and biological measurements, have a purely instrumental definition. The effects of these errors are apparent in the very large discrepancies among IQ correlations measured by different investigators. Genotype-environment correlations, whose effects can sometimes be minimized, if not wholly eliminated, in experiments with plants and animals, are nearly always important in human populations. The absence of significant effects arising from genotype-environment correlations is a necessary condition for the applicability of conventional heritability analysis to phenotypically plastic traits. When this condition fails, no quantitative inferences about heritability can be drawn from measured phenotypic variances and covariances, except under special conditions that are unlikely to be satisfied by phenotypically plastic traits in human populations. Inadequate understanding of the precise environmental factors relevant to the development of specific behavioral traits is an important source of systematic errors, as is the inability to allow adequately for the effects of assortative mating and gene-gene interaction. Systematic cultural differences and differences in psychological environment among races and among sociocco-nomic groups vitiate any attempt to draw from IQ data meaningful inferences about genetic differences. Estimates based on phenotypic correlations between separated monozygotic twins-usually considered to be the most reliable kind of estimates-are vitiated by systematic errors inherent in IQ tests, by the presence of genotype-environment correlation, and by the lack of detailed understanding of environmental factors relevant to the development of behavioral traits. Other kinds of estimates are beset, in addition, by systematic errors arising from incomplete allowance for the effects of assortative mating and from gene-gene interactions. The only potentially useful data are phenotypic correlations between unrelated foster children reared together, which could, in principle, yield lower limits for e(2). Available data indicate that, for unrelated foster children reared together, the broad heritability (h(2)) may lie between 0.0 and 0.5. This estimate does not apply to populations composed of children reared by their biological parents or by near relatives. For such populations the heritability of IQ remains undefined. The only data that might yield meaningful estimates ot narrow heritability are phenotypic correlations between half-sibs reared in statistically independent environments. No useful data of this kind are available. Intervention studies like Heber's Milwaukee Project afford an alternative and comparatively direct way of studying the plasticity of cognitive and other behavioral traits in human populations. Results obtained so far strongly suggest that the development of cognitive skills is highly sensitive to variations in environmental factors. These conclusions have three obvious implications for the broader issues mentioned at the beginning of this article. 1) Published analyses of IQ data provide no support whatever for Jensen's thesis that inequalities in cognitive performance are due largely to genetic differences. As Lewontin (8) has clearly shown, the value of the broad heritability of IQ is in any case only marginally relevant to this question. I have argued that conventional estimates of the broad heritability of IQ are invalid and that the only data on which potentially valid estimates might be based are consistent with a broad heritability of less than 0.5. On the other hand, intervention studies, if their findings prove to be replicable, would directly establish that, under suitable conditions, the offspring of parents whose cognitive skills are so poorly developed as to exclude them from all but the most menial occupations can achieve what are regarded as distinctly high levels of cognitive performance. Thus, despite the fact that children differ suibstantially in cognitive aptitudes and appetites, and despite the very high probability that these differences have a substantial genetic component, available scientific evidence strongly suggests that environmental factors are responsible for the failure of children not suffering from specific neurological disorders to achieve adequate levels of cognitive performance. 2) Under prevailing social conditions, no valid inferences can be drawn from IQ data concerning systematic genetic differences among races or socioeconomic groups. Research along present lines directed toward this end-whatever its ethical status-is scientifically worthless. 3) Since there are no suitable data for estimating the narrow heritability of IQ, it seems pointless to speculate about the prospects for a hereditary meritocracy based on IQ.

The Promises and Pitfalls of Genoeconomics*

PubMed Central

Benjamin, Daniel J.; Cesarini, David; Chabris, Christopher F.; Glaeser, Edward L.; Laibson, David I.; Guðnason, Vilmundur; Harris, Tamara B.; Launer, Lenore J.; Purcell, Shaun; Smith, Albert Vernon; Johannesson, Magnus; Magnusson, Patrik K.E.; Beauchamp, Jonathan P.; Christakis, Nicholas A.; Atwood, Craig S.; Hebert, Benjamin; Freese, Jeremy; Hauser, Robert M.; Hauser, Taissa S.; Grankvist, Alexander; Hultman, Christina M.; Lichtenstein, Paul

2012-01-01

This article reviews existing research at the intersection of genetics and economics, presents some new findings that illustrate the state of genoeconomics research, and surveys the prospects of this emerging field. Twin studies suggest that economic outcomes and preferences, once corrected for measurement error, appear to be about as heritable as many medical conditions and personality traits. Consistent with this pattern, we present new evidence on the heritability of permanent income and wealth. Turning to genetic association studies, we survey the main ways that the direct measurement of genetic variation across individuals is likely to contribute to economics, and we outline the challenges that have slowed progress in making these contributions. The most urgent problem facing researchers in this field is that most existing efforts to find associations between genetic variation and economic behavior are based on samples that are too small to ensure adequate statistical power. This has led to many false positives in the literature. We suggest a number of possible strategies to improve and remedy this problem: (a) pooling data sets, (b) using statistical techniques that exploit the greater information content of many genes considered jointly, and (c) focusing on economically relevant traits that are most proximate to known biological mechanisms. PMID:23482589

Multiple testing and power calculations in genetic association studies.

PubMed

So, Hon-Cheong; Sham, Pak C

2011-01-01

Modern genetic association studies typically involve multiple single-nucleotide polymorphisms (SNPs) and/or multiple genes. With the development of high-throughput genotyping technologies and the reduction in genotyping cost, investigators can now assay up to a million SNPs for direct or indirect association with disease phenotypes. In addition, some studies involve multiple disease or related phenotypes and use multiple methods of statistical analysis. The combination of multiple genetic loci, multiple phenotypes, and multiple methods of evaluating associations between genotype and phenotype means that modern genetic studies often involve the testing of an enormous number of hypotheses. When multiple hypothesis tests are performed in a study, there is a risk of inflation of the type I error rate (i.e., the chance of falsely claiming an association when there is none). Several methods for multiple-testing correction are in popular use, and they all have strengths and weaknesses. Because no single method is universally adopted or always appropriate, it is important to understand the principles, strengths, and weaknesses of the methods so that they can be applied appropriately in practice. In this article, we review the three principle methods for multiple-testing correction and provide guidance for calculating statistical power.

Refractive errors and schizophrenia.

PubMed

Caspi, Asaf; Vishne, Tali; Reichenberg, Abraham; Weiser, Mark; Dishon, Ayelet; Lubin, Gadi; Shmushkevitz, Motti; Mandel, Yossi; Noy, Shlomo; Davidson, Michael

2009-02-01

Refractive errors (myopia, hyperopia and amblyopia), like schizophrenia, have a strong genetic cause, and dopamine has been proposed as a potential mediator in their pathophysiology. The present study explored the association between refractive errors in adolescence and schizophrenia, and the potential familiality of this association. The Israeli Draft Board carries a mandatory standardized visual accuracy assessment. 678,674 males consecutively assessed by the Draft Board and found to be psychiatrically healthy at age 17 were followed for psychiatric hospitalization with schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Sib-ships were also identified within the cohort. There was a negative association between refractive errors and later hospitalization for schizophrenia. Future male schizophrenia patients were two times less likely to have refractive errors compared with never-hospitalized individuals, controlling for intelligence, years of education and socioeconomic status [adjusted Hazard Ratio=.55; 95% confidence interval .35-.85]. The non-schizophrenic male siblings of schizophrenia patients also had lower prevalence of refractive errors compared to never-hospitalized individuals. Presence of refractive errors in adolescence is related to lower risk for schizophrenia. The familiality of this association suggests that refractive errors may be associated with the genetic liability to schizophrenia.

Measure Liver Fat Content After ISIS 301012 (Mipomersen) Administration

ClinicalTrials.gov

2016-09-09

Lipid Metabolism, Inborn Errors; Hyperlipidemias; Metabolic Diseases; Hypolipoproteinemia; Hypolipoproteinemias; Hypobetalipoproteinemias; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Congenital Abnormalities; Metabolic Disorder; Hypercholesterolemia; Dyslipidemias; Lipid Metabolism Disorders

Severe infectious diseases of childhood as monogenic inborn errors of immunity

PubMed Central

Casanova, Jean-Laurent

2015-01-01

This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications. PMID:26621750

Precise orbit determination using the batch filter based on particle filtering with genetic resampling approach

NASA Astrophysics Data System (ADS)

Kim, Young-Rok; Park, Eunseo; Choi, Eun-Jung; Park, Sang-Young; Park, Chandeok; Lim, Hyung-Chul

2014-09-01

In this study, genetic resampling (GRS) approach is utilized for precise orbit determination (POD) using the batch filter based on particle filtering (PF). Two genetic operations, which are arithmetic crossover and residual mutation, are used for GRS of the batch filter based on PF (PF batch filter). For POD, Laser-ranging Precise Orbit Determination System (LPODS) and satellite laser ranging (SLR) observations of the CHAMP satellite are used. Monte Carlo trials for POD are performed by one hundred times. The characteristics of the POD results by PF batch filter with GRS are compared with those of a PF batch filter with minimum residual resampling (MRRS). The post-fit residual, 3D error by external orbit comparison, and POD repeatability are analyzed for orbit quality assessments. The POD results are externally checked by NASA JPL’s orbits using totally different software, measurements, and techniques. For post-fit residuals and 3D errors, both MRRS and GRS give accurate estimation results whose mean root mean square (RMS) values are at a level of 5 cm and 10-13 cm, respectively. The mean radial orbit errors of both methods are at a level of 5 cm. For POD repeatability represented as the standard deviations of post-fit residuals and 3D errors by repetitive PODs, however, GRS yields 25% and 13% more robust estimation results than MRRS for post-fit residual and 3D error, respectively. This study shows that PF batch filter with GRS approach using genetic operations is superior to PF batch filter with MRRS in terms of robustness in POD with SLR observations.

Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

PubMed

Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

2016-04-01

To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes.

Motor impulsivity during childhood and adolescence: a longitudinal biometric analysis of the go/no-go task in 9- to 18-year-old twins.

PubMed

Bezdjian, Serena; Tuvblad, Catherine; Wang, Pan; Raine, Adrian; Baker, Laura A

2014-11-01

In the present study, we investigated genetic and environmental effects on motor impulsivity from childhood to late adolescence using a longitudinal sample of twins from ages 9 to 18 years. Motor impulsivity was assessed using errors of commission (no-go errors) in a visual go/no-go task at 4 time points: ages 9-10, 11-13, 14-15, and 16-18 years. Significant genetic and nonshared environmental effects on motor impulsivity were found at each of the 4 waves of assessment with genetic factors explaining 22%-41% of the variance within each of the 4 waves. Phenotypically, children's average performance improved across age (i.e., fewer no-go errors during later assessments). Multivariate biometric analyses revealed that common genetic factors influenced 12%-40% of the variance in motor impulsivity across development, whereas nonshared environmental factors common to all time points contributed to 2%-52% of the variance. Nonshared environmental influences specific to each time point also significantly influenced motor impulsivity. Overall, results demonstrated that although genetic factors were critical to motor impulsivity across development, both common and specific nonshared environmental factors played a strong role in the development of motor impulsivity across age. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Impact and quantification of the sources of error in DNA pooling designs.

PubMed

Jawaid, A; Sham, P

2009-01-01

The analysis of genome wide variation offers the possibility of unravelling the genes involved in the pathogenesis of disease. Genome wide association studies are also particularly useful for identifying and validating targets for therapeutic intervention as well as for detecting markers for drug efficacy and side effects. The cost of such large-scale genetic association studies may be reduced substantially by the analysis of pooled DNA from multiple individuals. However, experimental errors inherent in pooling studies lead to a potential increase in the false positive rate and a loss in power compared to individual genotyping. Here we quantify various sources of experimental error using empirical data from typical pooling experiments and corresponding individual genotyping counts using two statistical methods. We provide analytical formulas for calculating these different errors in the absence of complete information, such as replicate pool formation, and for adjusting for the errors in the statistical analysis. We demonstrate that DNA pooling has the potential of estimating allele frequencies accurately, and adjusting the pooled allele frequency estimates for differential allelic amplification considerably improves accuracy. Estimates of the components of error show that differential allelic amplification is the most important contributor to the error variance in absolute allele frequency estimation, followed by allele frequency measurement and pool formation errors. Our results emphasise the importance of minimising experimental errors and obtaining correct error estimates in genetic association studies.

Circumpolar Genetic Structure and Recent Gene Flow of Polar Bears: A Reanalysis

PubMed Central

Malenfant, René M.; Davis, Corey S.; Cullingham, Catherine I.; Coltman, David W.

2016-01-01

Recently, an extensive study of 2,748 polar bears (Ursus maritimus) from across their circumpolar range was published in PLOS ONE, which used microsatellites and mitochondrial haplotypes to apparently show altered population structure and a dramatic change in directional gene flow towards the Canadian Archipelago—an area believed to be a future refugium for polar bears as their southernmost habitats decline under climate change. Although this study represents a major international collaborative effort and promised to be a baseline for future genetics work, methodological shortcomings and errors of interpretation undermine some of the study’s main conclusions. Here, we present a reanalysis of this data in which we address some of these issues, including: (1) highly unbalanced sample sizes and large amounts of systematically missing data; (2) incorrect calculation of FST and of significance levels; (3) misleading estimates of recent gene flow resulting from non-convergence of the program BayesAss. In contrast to the original findings, in our reanalysis we find six genetic clusters of polar bears worldwide: the Hudson Bay Complex, the Western and Eastern Canadian Arctic Archipelago, the Western and Eastern Polar Basin, and—importantly—we reconfirm the presence of a unique and possibly endangered cluster of bears in Norwegian Bay near Canada’s expected last sea-ice refugium. Although polar bears’ abundance, distribution, and population structure will certainly be negatively affected by ongoing—and increasingly rapid—loss of Arctic sea ice, these genetic data provide no evidence of strong directional gene flow in response to recent climate change. PMID:26974333

Competence in Streptococcus pneumoniae is regulated by the rate of ribosomal decoding errors.

PubMed

Stevens, Kathleen E; Chang, Diana; Zwack, Erin E; Sebert, Michael E

2011-01-01

Competence for genetic transformation in Streptococcus pneumoniae develops in response to accumulation of a secreted peptide pheromone and was one of the initial examples of bacterial quorum sensing. Activation of this signaling system induces not only expression of the proteins required for transformation but also the production of cellular chaperones and proteases. We have shown here that activity of this pathway is sensitively responsive to changes in the accuracy of protein synthesis that are triggered by either mutations in ribosomal proteins or exposure to antibiotics. Increasing the error rate during ribosomal decoding promoted competence, while reducing the error rate below the baseline level repressed the development of both spontaneous and antibiotic-induced competence. This pattern of regulation was promoted by the bacterial HtrA serine protease. Analysis of strains with the htrA (S234A) catalytic site mutation showed that the proteolytic activity of HtrA selectively repressed competence when translational fidelity was high but not when accuracy was low. These findings redefine the pneumococcal competence pathway as a response to errors during protein synthesis. This response has the capacity to address the immediate challenge of misfolded proteins through production of chaperones and proteases and may also be able to address, through genetic exchange, upstream coding errors that cause intrinsic protein folding defects. The competence pathway may thereby represent a strategy for dealing with lesions that impair proper protein coding and for maintaining the coding integrity of the genome. The signaling pathway that governs competence in the human respiratory tract pathogen Streptococcus pneumoniae regulates both genetic transformation and the production of cellular chaperones and proteases. The current study shows that this pathway is sensitively controlled in response to changes in the accuracy of protein synthesis. Increasing the error rate during ribosomal decoding induced competence, while decreasing the error rate repressed competence. This pattern of regulation was promoted by the HtrA protease, which selectively repressed competence when translational fidelity was high but not when accuracy was low. Our findings demonstrate that this organism is able to monitor the accuracy of information used for protein biosynthesis and suggest that errors trigger a response addressing both the immediate challenge of misfolded proteins and, through genetic exchange, upstream coding errors that may underlie protein folding defects. This pathway may represent an evolutionary strategy for maintaining the coding integrity of the genome.

Estimating population genetic parameters and comparing model goodness-of-fit using DNA sequences with error

PubMed Central

Liu, Xiaoming; Fu, Yun-Xin; Maxwell, Taylor J.; Boerwinkle, Eric

2010-01-01

It is known that sequencing error can bias estimation of evolutionary or population genetic parameters. This problem is more prominent in deep resequencing studies because of their large sample size n, and a higher probability of error at each nucleotide site. We propose a new method based on the composite likelihood of the observed SNP configurations to infer population mutation rate θ = 4Neμ, population exponential growth rate R, and error rate ɛ, simultaneously. Using simulation, we show the combined effects of the parameters, θ, n, ɛ, and R on the accuracy of parameter estimation. We compared our maximum composite likelihood estimator (MCLE) of θ with other θ estimators that take into account the error. The results show the MCLE performs well when the sample size is large or the error rate is high. Using parametric bootstrap, composite likelihood can also be used as a statistic for testing the model goodness-of-fit of the observed DNA sequences. The MCLE method is applied to sequence data on the ANGPTL4 gene in 1832 African American and 1045 European American individuals. PMID:19952140

Directional control-response compatibility relationships assessed by physical simulation of an underground bolting machine.

PubMed

Steiner, Lisa; Burgess-Limerick, Robin; Porter, William

2014-03-01

The authors examine the pattern of direction errors made during the manipulation of a physical simulation of an underground coal mine bolting machine to assess the directional control-response compatibility relationships associated with the device and to compare these results to data obtained from a virtual simulation of a generic device. Directional errors during the manual control of underground coal roof bolting equipment are associated with serious injuries. Directional control-response relationships have previously been examined using a virtual simulation of a generic device; however, the applicability of these results to a specific physical device may be questioned. Forty-eight participants randomly assigned to different directional control-response relationships manipulated horizontal or vertical control levers to move a simulated bolter arm in three directions (elevation, slew, and sump) as well as to cause a light to become illuminated and raise or lower a stabilizing jack. Directional errors were recorded during the completion of 240 trials by each participant Directional error rates are increased when the control and response are in opposite directions or if the direction of the control and response are perpendicular.The pattern of direction error rates was consistent with experiments obtained from a generic device in a virtual environment. Error rates are increased by incompatible directional control-response relationships. Ensuring that the design of equipment controls maintains compatible directional control-response relationships has potential to reduce the errors made in high-risk situations, such as underground coal mining.

Remediating Common Math Errors.

ERIC Educational Resources Information Center

Wagner, Rudolph F.

1981-01-01

Explanations and remediation suggestions for five types of mathematics errors due either to perceptual or cognitive difficulties are given. Error types include directionality problems, mirror writing, visually misperceived signs, diagnosed directionality problems, and mixed process errors. (CL)

Genetics Home Reference: sialuria

MedlinePlus

... inheritance of sialuria, an inborn error of feedback inhibition. Am J Hum Genet. 2001 Jun;68(6): ... Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players ...

Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

On the value of Mendelian laws of segregation in families: data quality control, imputation and beyond

PubMed Central

Blue, Elizabeth Marchani; Sun, Lei; Tintle, Nathan L.; Wijsman, Ellen M.

2014-01-01

When analyzing family data, we dream of perfectly informative data, even whole genome sequences (WGS) for all family members. Reality intervenes, and we find next-generation sequence (NGS) data have error, and are often too expensive or impossible to collect on everyone. Genetic Analysis Workshop 18 groups “Quality Control” and “Dropping WGS through families using GWAS framework” focused on finding, correcting, and using errors within the available sequence and family data, developing methods to infer and analyze missing sequence data among relatives, and testing for linkage and association with simulated blood pressure. We found that single nucleotide polymorphisms, NGS, and imputed data are generally concordant, but that errors are particularly likely at rare variants, homozygous genotypes, within regions with repeated sequences or structural variants, and within sequence data imputed from unrelateds. Admixture complicated identification of cryptic relatedness, but information from Mendelian transmission improved error detection and provided an estimate of the de novo mutation rate. Both genotype and pedigree errors had an adverse effect on subsequent analyses. Computationally fast rules-based imputation was accurate, but could not cover as many loci or subjects as more computationally demanding probability-based methods. Incorporating population-level data into pedigree-based imputation methods improved results. Observed data outperformed imputed data in association testing, but imputed data were also useful. We discuss the strengths and weaknesses of existing methods, and suggest possible future directions. Topics include improving communication between those performing data collection and analysis, establishing thresholds for and improving imputation quality, and incorporating error into imputation and analytical models. PMID:25112184

Reproducibility of Illumina platform deep sequencing errors allows accurate determination of DNA barcodes in cells.

PubMed

Beltman, Joost B; Urbanus, Jos; Velds, Arno; van Rooij, Nienke; Rohr, Jan C; Naik, Shalin H; Schumacher, Ton N

2016-04-02

Next generation sequencing (NGS) of amplified DNA is a powerful tool to describe genetic heterogeneity within cell populations that can both be used to investigate the clonal structure of cell populations and to perform genetic lineage tracing. For applications in which both abundant and rare sequences are biologically relevant, the relatively high error rate of NGS techniques complicates data analysis, as it is difficult to distinguish rare true sequences from spurious sequences that are generated by PCR or sequencing errors. This issue, for instance, applies to cellular barcoding strategies that aim to follow the amount and type of offspring of single cells, by supplying these with unique heritable DNA tags. Here, we use genetic barcoding data from the Illumina HiSeq platform to show that straightforward read threshold-based filtering of data is typically insufficient to filter out spurious barcodes. Importantly, we demonstrate that specific sequencing errors occur at an approximately constant rate across different samples that are sequenced in parallel. We exploit this observation by developing a novel approach to filter out spurious sequences. Application of our new method demonstrates its value in the identification of true sequences amongst spurious sequences in biological data sets.

Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study.

PubMed

Dirani, Mohamed; Chamberlain, Matthew; Shekar, Sri N; Islam, Amirul F M; Garoufalis, Pam; Chen, Christine Y; Guymer, Robyn H; Baird, Paul N

2006-11-01

A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P < 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P < 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters.

Fine-scale landscape genetics of the American badger (Taxidea taxus): disentangling landscape effects and sampling artifacts in a poorly understood species

PubMed Central

Kierepka, E M; Latch, E K

2016-01-01

Landscape genetics is a powerful tool for conservation because it identifies landscape features that are important for maintaining genetic connectivity between populations within heterogeneous landscapes. However, using landscape genetics in poorly understood species presents a number of challenges, namely, limited life history information for the focal population and spatially biased sampling. Both obstacles can reduce power in statistics, particularly in individual-based studies. In this study, we genotyped 233 American badgers in Wisconsin at 12 microsatellite loci to identify alternative statistical approaches that can be applied to poorly understood species in an individual-based framework. Badgers are protected in Wisconsin owing to an overall lack in life history information, so our study utilized partial redundancy analysis (RDA) and spatially lagged regressions to quantify how three landscape factors (Wisconsin River, Ecoregions and land cover) impacted gene flow. We also performed simulations to quantify errors created by spatially biased sampling. Statistical analyses first found that geographic distance was an important influence on gene flow, mainly driven by fine-scale positive spatial autocorrelations. After controlling for geographic distance, both RDA and regressions found that Wisconsin River and Agriculture were correlated with genetic differentiation. However, only Agriculture had an acceptable type I error rate (3–5%) to be considered biologically relevant. Collectively, this study highlights the benefits of combining robust statistics and error assessment via simulations and provides a method for hypothesis testing in individual-based landscape genetics. PMID:26243136

Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

PubMed

Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

2017-06-01

Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

Design of thrust vectoring exhaust nozzles for real-time applications using neural networks

NASA Technical Reports Server (NTRS)

Prasanth, Ravi K.; Markin, Robert E.; Whitaker, Kevin W.

1991-01-01

Thrust vectoring continues to be an important issue in military aircraft system designs. A recently developed concept of vectoring aircraft thrust makes use of flexible exhaust nozzles. Subtle modifications in the nozzle wall contours produce a non-uniform flow field containing a complex pattern of shock and expansion waves. The end result, due to the asymmetric velocity and pressure distributions, is vectored thrust. Specification of the nozzle contours required for a desired thrust vector angle (an inverse design problem) has been achieved with genetic algorithms. This approach is computationally intensive and prevents the nozzles from being designed in real-time, which is necessary for an operational aircraft system. An investigation was conducted into using genetic algorithms to train a neural network in an attempt to obtain, in real-time, two-dimensional nozzle contours. Results show that genetic algorithm trained neural networks provide a viable, real-time alternative for designing thrust vectoring nozzles contours. Thrust vector angles up to 20 deg were obtained within an average error of 0.0914 deg. The error surfaces encountered were highly degenerate and thus the robustness of genetic algorithms was well suited for minimizing global errors.

Direct Animal Calorimetry, the Underused Gold Standard for Quantifying the Fire of Life*

PubMed Central

Kaiyala, Karl J.; Ramsay, Douglas S.

2012-01-01

Direct animal calorimetry, the gold standard method for quantifying animal heat production (HP), has been largely supplanted by respirometric indirect calorimetry owing to the relative ease and ready commercial availability of the latter technique. Direct calorimetry, however, can accurately quantify HP and thus metabolic rate (MR) in both metabolically normal and abnormal states, whereas respirometric indirect calorimetry relies on important assumptions that apparently have never been tested in animals with genetic or pharmacologically-induced alterations that dysregulate metabolic fuel partitioning and storage so as to promote obesity and/or diabetes. Contemporary obesity and diabetes research relies heavily on metabolically abnormal animals. Recent data implicating individual and group variation in the gut microbiome in obesity and diabetes raise important questions about transforming aerobic gas exchange into HP because 99% of gut bacteria are anaerobic and they outnumber eukaryotic cells in the body by ~10-fold. Recent credible work in non-standard laboratory animals documents substantial errors in respirometry-based estimates of HP. Accordingly, it seems obvious that new research employing simultaneous direct and indirect calorimetry (total calorimetry) will be essential to validate respirometric MR phenotyping in existing and future pharmacological and genetic models of obesity and diabetes. We also detail the use of total calorimetry with simultaneous core temperature assessment as a model for studying homeostatic control in a variety of experimental situations, including acute and chronic drug administration. Finally, we offer some tips on performing direct calorimetry, both singly and in combination with indirect calorimetry and core temperature assessment. PMID:20427023

Next-generation sequencing shows West Nile virus quasispecies diversification after a single passage in a carrion crow (Corvus corone) in vivo infection model.

PubMed

Dridi, M; Rosseel, T; Orton, R; Johnson, P; Lecollinet, S; Muylkens, B; Lambrecht, B; Van Borm, S

2015-10-01

West Nile virus (WNV) occurs as a population of genetic variants (quasispecies) infecting a single animal. Previous low-resolution viral genetic diversity estimates in sampled wild birds and mosquitoes, and in multiple-passage adaptation studies in vivo or in cell culture, suggest that WNV genetic diversification is mostly limited to the mosquito vector. This study investigated genetic diversification of WNV in avian hosts during a single passage using next-generation sequencing. Wild-captured carrion crows were subcutaneously infected using a clonal Middle-East WNV. Blood samples were collected 2 and 4 days post-infection. A reverse-transcription (RT)-PCR approach was used to amplify the WNV genome directly from serum samples prior to next-generation sequencing resulting in an average depth of at least 700 ×  in each sample. Appropriate controls were sequenced to discriminate biologically relevant low-frequency variants from experimentally introduced errors. The WNV populations in the wild crows showed significant diversification away from the inoculum virus quasispecies structure. By contrast, WNV populations in intracerebrally infected day-old chickens did not diversify from that of the inoculum. Where previous studies concluded that WNV genetic diversification is only experimentally demonstrated in its permissive insect vector species, we have experimentally shown significant diversification of WNV populations in a wild bird reservoir species.

Lost in Translation? A Comparison of Cancer-Genetics Reporting in the Press Release and its Subsequent Coverage in Lay Press1

PubMed Central

Brechman, Jean M.; Lee, Chul-joo; Cappella, Joseph N.

2014-01-01

Understanding how genetic science is communicated to the lay public is of great import, given that media coverage of genetics is increasing exponentially and that the ways in which discoveries are presented in the news can have significant effects on a variety of health outcomes. To address this issue, this study examines the presentation of genetic research relating to cancer outcomes and behaviors (i.e., prostate cancer, breast cancer, colon cancer, smoking and obesity) in both the press release (N = 23) and its subsequent news coverage (N = 71) by using both quantitative content analysis and qualitative textual analysis. In contrast to earlier studies reporting that news stories often misrepresent genetics by presenting biologically deterministic and simplified portrayals (e.g., Mountcastle-Shah et al., 2003; Ten Eych & Williment, 2003), our data shows no clear trends in the direction of distortion toward deterministic claims in news articles. Also, other errors commonly attributed to science journalism, such as lack of qualifying details and use of oversimplified language (e.g., “fat gene”) are observed in press releases. These findings suggest that the intermediary press release rather than news coverage may serve as a source of distortion in the dissemination of science to the lay public. The implications of this study for future research in this area are discussed. PMID:25568611

Design quadrilateral apertures in binary computer-generated holograms of large space bandwidth product.

PubMed

Wang, Jing; Sheng, Yunlong

2016-09-20

A new approach for designing the binary computer-generated hologram (CGH) of a very large number of pixels is proposed. Diffraction of the CGH apertures is computed by the analytical Abbe transform and by considering the aperture edges as the basic diffracting elements. The computation cost is independent of the CGH size. The arbitrary-shaped polygonal apertures in the CGH consist of quadrilateral apertures, which are designed by assigning the binary phases using the parallel genetic algorithm with a local search, followed by optimizing the locations of the co-vertices with a direct search. The design results in high performance with low image reconstruction error.

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

PubMed Central

Fan, Qiao; Guo, Xiaobo; Tideman, J. Willem L.; Williams, Katie M.; Yazar, Seyhan; Hosseini, S. Mohsen; Howe, Laura D.; Pourcain, Beaté St; Evans, David M.; Timpson, Nicholas J.; McMahon, George; Hysi, Pirro G.; Krapohl, Eva; Wang, Ya Xing; Jonas, Jost B.; Baird, Paul Nigel; Wang, Jie Jin; Cheng, Ching-Yu; Teo, Yik-Ying; Wong, Tien-Yin; Ding, Xiaohu; Wojciechowski, Robert; Young, Terri L.; Pärssinen, Olavi; Oexle, Konrad; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Paterson, Andrew D.; Klaver, Caroline C. W.; Plomin, Robert; Hammond, Christopher J.; Mackey, David A.; He, Mingguang; Saw, Seang-Mei; Williams, Cathy; Guggenheim, Jeremy A.; Meguro, Akira; Wright, Alan F.; Hewitt, Alex W.; Young, Alvin L.; Veluchamy, Amutha Barathi; Metspalu, Andres; Paterson, Andrew D.; Döring, Angela; Khawaja, Anthony P.; Klein, Barbara E.; Pourcain, Beate St; Fleck, Brian; Klaver, Caroline C. W.; Hayward, Caroline; Williams, Cathy; Delcourt, Cécile; Pang, Chi Pui; Khor, Chiea-Chuen; Cheng, Ching-Yu; Gieger, Christian; Hammond, Christopher J.; Simpson, Claire L.; van Duijn, Cornelia M.; Mackey, David A.; Evans, David M.; Stambolian, Dwight; Chew, Emily; Tai, E-Shyong; Krapohl, Eva; Mihailov, Evelin; Smith, George Davey; McMahon, George; Biino, Ginevra; Campbell, Harry; Rudan, Igor; Seppälä, Ilkka; Kaprio, Jaakko; Wilson, James F.; Craig, Jamie E.; Tideman, J. Willem L.; Ried, Janina S.; Korobelnik, Jean-François; Guggenheim, Jeremy A.; Fondran, Jeremy R.; Wang, Jie Jin; Liao, Jiemin; Zhao, Jing Hua; Xie, Jing; Bailey-Wilson, Joan E.; Kemp, John P.; Lass, Jonathan H.; Jonas, Jost B.; Rahi, Jugnoo S.; Wedenoja, Juho; Mäkelä, Kari-Matti; Burdon, Kathryn P.; Williams, Katie M; Khaw, Kay-Tee; Yamashiro, Kenji; Oexle, Konrad; Howe, Laura D.; Chen, Li Jia; Xu, Liang; Farrer, Lindsay; Ikram, M. Kamran; Deangelis, Margaret M.; Morrison, Margaux; Schache, Maria; Pirastu, Mario; Miyake, Masahiro; Yap, Maurice K. H.; Fossarello, Maurizio; Kähönen, Mika; Tedja, Milly S.; He, Mingguang; Yoshimura, Nagahisa; Martin, Nicholas G.; Timpson, Nicholas J.; Wareham, Nick J.; Mizuki, Nobuhisa; Pfeiffer, Norbert; Pärssinen, Olavi; Raitakari, Olli; Polasek, Ozren; Tam, Pancy O.; Foster, Paul J.; Mitchell, Paul; Baird, Paul Nigel; Chen, Peng; Hysi, Pirro G.; Cumberland, Phillippa; Gharahkhani, Puya; Fan, Qiao; Höhn, René; Fogarty, Rhys D.; Luben, Robert N.; Igo Jr, Robert P.; Plomin, Robert; Wojciechowski, Robert; Klein, Ronald; Mohsen Hosseini, S.; Janmahasatian, Sarayut; Saw, Seang-Mei; Yazar, Seyhan; Ping Yip, Shea; Feng, Sheng; Vaccargiu, Simona; Panda-Jonas, Songhomitra; MacGregor, Stuart; Iyengar, Sudha K.; Rantanen, Taina; Lehtimäki, Terho; Young, Terri L.; Meitinger, Thomas; Wong, Tien-Yin; Aung, Tin; Haller, Toomas; Vitart, Veronique; Nangia, Vinay; Verhoeven, Virginie J. M.; Jhanji, Vishal; Zhao, Wanting; Chen, Wei; Zhou, Xiangtian; Guo, Xiaobo; Ding, Xiaohu; Wang, Ya Xing; Lu, Yi; Teo, Yik-Ying; Vatavuk, Zoran

2016-01-01

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E–04). PMID:27174397

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.

PubMed

Fan, Qiao; Guo, Xiaobo; Tideman, J Willem L; Williams, Katie M; Yazar, Seyhan; Hosseini, S Mohsen; Howe, Laura D; Pourcain, Beaté St; Evans, David M; Timpson, Nicholas J; McMahon, George; Hysi, Pirro G; Krapohl, Eva; Wang, Ya Xing; Jonas, Jost B; Baird, Paul Nigel; Wang, Jie Jin; Cheng, Ching-Yu; Teo, Yik-Ying; Wong, Tien-Yin; Ding, Xiaohu; Wojciechowski, Robert; Young, Terri L; Pärssinen, Olavi; Oexle, Konrad; Pfeiffer, Norbert; Bailey-Wilson, Joan E; Paterson, Andrew D; Klaver, Caroline C W; Plomin, Robert; Hammond, Christopher J; Mackey, David A; He, Mingguang; Saw, Seang-Mei; Williams, Cathy; Guggenheim, Jeremy A

2016-05-13

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Direct-to-consumer genetic testing: an assessment of genetic counselors' knowledge and beliefs

PubMed Central

Hock, Kathryn T.; Christensen, Kurt D.; Yashar, Beverly M.; Roberts, J. Scott; Gollust, Sarah E.; Uhlmann, Wendy R.

2013-01-01

Purpose Direct-to-consumer genetic testing is a new means of obtaining genetic testing outside of a traditional clinical setting. This study assesses genetic counselors’ experience, knowledge, and beliefs regarding direct-to-consumer genetic testing for tests that would currently be offered in genetics clinics. Methods Members of the National Society of Genetic Counselors completed a web-administered survey in February 2008. Results Response rate was 36%; the final data analysis included 312 respondents. Eighty-three percent of respondents had two or fewer inquiries about direct-to-consumer genetic testing, and 14% had received requests for test interpretation or discussion. Respondents believed that genetic counselors have a professional obligation to be knowledgeable about direct-to-consumer genetic testing (55%) and interpret results (48%). Fifty-one percent of respondents thought genetic testing should be limited to a clinical setting; 56% agreed direct-to-consumer genetic testing is acceptable if genetic counseling is provided. More than 70% of respondents would definitely or possibly consider direct-to-consumer testing for patients who (1) have concerns about genetic discrimination, (2) want anonymous testing, or (3) have geographic constraints. Conclusions Results indicate that genetic counselors have limited patient experiences with direct-to-consumer genetic testing and are cautiously considering if and under what circumstances this approach should be used PMID:21233722

Performance Metrics, Error Modeling, and Uncertainty Quantification

NASA Technical Reports Server (NTRS)

Tian, Yudong; Nearing, Grey S.; Peters-Lidard, Christa D.; Harrison, Kenneth W.; Tang, Ling

2016-01-01

A common set of statistical metrics has been used to summarize the performance of models or measurements-­ the most widely used ones being bias, mean square error, and linear correlation coefficient. They assume linear, additive, Gaussian errors, and they are interdependent, incomplete, and incapable of directly quantifying un­certainty. The authors demonstrate that these metrics can be directly derived from the parameters of the simple linear error model. Since a correct error model captures the full error information, it is argued that the specification of a parametric error model should be an alternative to the metrics-based approach. The error-modeling meth­odology is applicable to both linear and nonlinear errors, while the metrics are only meaningful for linear errors. In addition, the error model expresses the error structure more naturally, and directly quantifies uncertainty. This argument is further explained by highlighting the intrinsic connections between the performance metrics, the error model, and the joint distribution between the data and the reference.

Toward diagnostic and phenotype markers for genetically transmitted speech delay.

PubMed

Shriberg, Lawrence D; Lewis, Barbara A; Tomblin, J Bruce; McSweeny, Jane L; Karlsson, Heather B; Scheer, Alison R

2005-08-01

Converging evidence supports the hypothesis that the most common subtype of childhood speech sound disorder (SSD) of currently unknown origin is genetically transmitted. We report the first findings toward a set of diagnostic markers to differentiate this proposed etiological subtype (provisionally termed speech delay-genetic) from other proposed subtypes of SSD of unknown origin. Conversational speech samples from 72 preschool children with speech delay of unknown origin from 3 research centers were selected from an audio archive. Participants differed on the number of biological, nuclear family members (0 or 2+) classified as positive for current and/or prior speech-language disorder. Although participants in the 2 groups were found to have similar speech competence, as indexed by their Percentage of Consonants Correct scores, their speech error patterns differed significantly in 3 ways. Compared with children who may have reduced genetic load for speech delay (no affected nuclear family members), children with possibly higher genetic load (2+ affected members) had (a) a significantly higher proportion of relative omission errors on the Late-8 consonants; (b) a significantly lower proportion of relative distortion errors on these consonants, particularly on the sibilant fricatives /s/, /z/, and //; and (c) a significantly lower proportion of backed /s/ distortions, as assessed by both perceptual and acoustic methods. Machine learning routines identified a 3-part classification rule that included differential weightings of these variables. The classification rule had diagnostic accuracy value of 0.83 (95% confidence limits = 0.74-0.92), with positive and negative likelihood ratios of 9.6 (95% confidence limits = 3.1-29.9) and 0.40 (95% confidence limits = 0.24-0.68), respectively. The diagnostic accuracy findings are viewed as promising. The error pattern for this proposed subtype of SSD is viewed as consistent with the cognitive-linguistic processing deficits that have been reported for genetically transmitted verbal disorders.

Modeling congenital disease and inborn errors of development in Drosophila melanogaster

PubMed Central

Moulton, Matthew J.; Letsou, Anthea

2016-01-01

ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Cost-efficient selection of a marker panel in genetic studies

Treesearch

Jamie S. Sanderlin; Nicole Lazar; Michael J. Conroy; Jaxk Reeves

2012-01-01

Genetic techniques are frequently used to sample and monitor wildlife populations. The goal of these studies is to maximize the ability to distinguish individuals for various genetic inference applications, a process which is often complicated by genotyping error. However, wildlife studies usually have fixed budgets, which limit the number of geneticmarkers available...

Estimation of genetic parameters and their sampling variances of quantitative traits in the type 2 modified augmented design

USDA-ARS?s Scientific Manuscript database

We proposed a method to estimate the error variance among non-replicated genotypes, thus to estimate the genetic parameters by using replicated controls. We derived formulas to estimate sampling variances of the genetic parameters. Computer simulation indicated that the proposed methods of estimatin...

Levels of asymmetry in Formica pratensis Retz. (Hymenoptera, Insecta) from a chronic metal-contaminated site

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

Rabitsch, W.B.

1997-07-01

Asymmetries of bilaterally symmetrical morphological traits in workers of the ant Formica pratensis Retzius were compared at sites with different levels of metal contamination and between mature and pre-mature colonies. Statistical analyses of the right-minus-left differences revealed that their distributions fit assumptions of fluctuating asymmetry (FA). No direct asymmetry or antisymmetry were present. Mean measurement error accounts for a third of the variation, but the maximum measurement error was 65%. Although significant differences of FA in ants were observed, the inconsistent results render uncovering a clear pattern difficult. Lead, cadmium, and zinc concentrations in the ants decreased with the distancemore » from the contamination source, but no relation was found between FA and the heavy metal levels. Ants from the premature colonies were more asymmetrical than those from mature colonies but accumulated less metals. The use of asymmetry measures in ecotoxicology and biomonitoring is criticized, but should remain widely applicable if statistical assumptions are complemented by genetic and historical data.« less

Evaluating mixed samples as a source of error in non-invasive genetic studies using microsatellites

USGS Publications Warehouse

Roon, David A.; Thomas, M.E.; Kendall, K.C.; Waits, L.P.

2005-01-01

The use of noninvasive genetic sampling (NGS) for surveying wild populations is increasing rapidly. Currently, only a limited number of studies have evaluated potential biases associated with NGS. This paper evaluates the potential errors associated with analysing mixed samples drawn from multiple animals. Most NGS studies assume that mixed samples will be identified and removed during the genotyping process. We evaluated this assumption by creating 128 mixed samples of extracted DNA from brown bear (Ursus arctos) hair samples. These mixed samples were genotyped and screened for errors at six microsatellite loci according to protocols consistent with those used in other NGS studies. Five mixed samples produced acceptable genotypes after the first screening. However, all mixed samples produced multiple alleles at one or more loci, amplified as only one of the source samples, or yielded inconsistent electropherograms by the final stage of the error-checking process. These processes could potentially reduce the number of individuals observed in NGS studies, but errors should be conservative within demographic estimates. Researchers should be aware of the potential for mixed samples and carefully design gel analysis criteria and error checking protocols to detect mixed samples.

Determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparations using UV-visible spectrophotometry and genetic algorithm based multivariate calibration methods.

PubMed

Ozdemir, Durmus; Dinc, Erdal

2004-07-01

Simultaneous determination of binary mixtures pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination using UV-visible spectrophotometry and classical least squares (CLS) and three newly developed genetic algorithm (GA) based multivariate calibration methods was demonstrated. The three genetic multivariate calibration methods are Genetic Classical Least Squares (GCLS), Genetic Inverse Least Squares (GILS) and Genetic Regression (GR). The sample data set contains the UV-visible spectra of 30 synthetic mixtures (8 to 40 microg/ml) of these vitamins and 10 tablets containing 250 mg from each vitamin. The spectra cover the range from 200 to 330 nm in 0.1 nm intervals. Several calibration models were built with the four methods for the two components. Overall, the standard error of calibration (SEC) and the standard error of prediction (SEP) for the synthetic data were in the range of <0.01 and 0.43 microg/ml for all the four methods. The SEP values for the tablets were in the range of 2.91 and 11.51 mg/tablets. A comparison of genetic algorithm selected wavelengths for each component using GR method was also included.

Methods for meta-analysis of multiple traits using GWAS summary statistics.

PubMed

Ray, Debashree; Boehnke, Michael

2018-03-01

Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses. Evidence from larger studies suggest that the variants additionally detected by our test are, indeed, associated with lipid levels in humans. In summary, metaUSAT can provide novel insights into the genetic architecture of a common disease or traits. © 2017 WILEY PERIODICALS, INC.

Nature and Nurture: the complex genetics of myopia and refractive error

PubMed Central

Wojciechowski, Robert

2010-01-01

The refractive errors, myopia and hyperopia, are optical defects of the visual system that can cause blurred vision. Uncorrected refractive errors are the most common causes of visual impairment worldwide. It is estimated that 2.5 billion people will be affected by myopia alone with in the next decade. Experimental, epidemiological and clinical research has shown that refractive development is influenced by both environmental and genetic factors. Animal models have demonstrated that eye growth and refractive maturation during infancy are tightly regulated by visually-guided mechanisms. Observational data in human populations provide compelling evidence that environmental influences and individual behavioral factors play crucial roles in myopia susceptibility. Nevertheless, the majority of the variance of refractive error within populations is thought to be due to hereditary factors. Genetic linkage studies have mapped two dozen loci, while association studies have implicated more than 25 different genes in refractive variation. Many of these genes are involved in common biological pathways known to mediate extracellular matrix composition and regulate connective tissue remodeling. Other associated genomic regions suggest novel mechanisms in the etiology of human myopia, such as mitochondrial-mediated cell death or photoreceptor-mediated visual signal transmission. Taken together, observational and experimental studies have revealed the complex nature of human refractive variation, which likely involves variants in several genes and functional pathways. Multiway interactions between genes and/or environmental factors may also be important in determining individual risks of myopia, and may help explain the complex pattern of refractive error in human populations. PMID:21155761

Influence of wheelchair front caster wheel on reverse directional stability.

PubMed

Guo, Songfeng; Cooper, Rory A; Corfman, Tom; Ding, Dan; Grindle, Garrett

2003-01-01

The purpose of this research was to study directional stability during reversing of rear-wheel drive, electric powered wheelchairs (EPW) under different initial front caster orientations. Specifically, the weight distribution differences caused by certain initial caster orientations were examined as a possible mechanism for causing directional instability that could lead to accidents. Directional stability was quantified by measuring the drive direction error of the EPW by a motion analysis system. The ground reaction forces were collected to determine the load on the front casters, as well as back-emf data to attain the speed of the motors. The drive direction error was found to be different for various initial caster orientations. Drive direction error was greatest when both casters were oriented 90 degrees to the left or right, and least when both casters were oriented forward. The results show that drive direction error corresponds to the loading difference on the casters. The data indicates that loading differences may cause asymmetric drag on the casters, which in turn causes unbalanced torque load on the motors. This leads to a difference in motor speed and drive direction error.

What Is Direct-to-Consumer Genetic Testing?

MedlinePlus

... consumer genetic testing? What is direct-to-consumer genetic testing? Most of the time, genetic testing is ... testing. For more information about direct-to-consumer genetic testing: Centers for Disease Control and Prevention (CDC) ...

A simulation test of the effectiveness of several methods for error-checking non-invasive genetic data

USGS Publications Warehouse

Roon, David A.; Waits, L.P.; Kendall, K.C.

2005-01-01

Non-invasive genetic sampling (NGS) is becoming a popular tool for population estimation. However, multiple NGS studies have demonstrated that polymerase chain reaction (PCR) genotyping errors can bias demographic estimates. These errors can be detected by comprehensive data filters such as the multiple-tubes approach, but this approach is expensive and time consuming as it requires three to eight PCR replicates per locus. Thus, researchers have attempted to correct PCR errors in NGS datasets using non-comprehensive error checking methods, but these approaches have not been evaluated for reliability. We simulated NGS studies with and without PCR error and 'filtered' datasets using non-comprehensive approaches derived from published studies and calculated mark-recapture estimates using CAPTURE. In the absence of data-filtering, simulated error resulted in serious inflations in CAPTURE estimates; some estimates exceeded N by ??? 200%. When data filters were used, CAPTURE estimate reliability varied with per-locus error (E??). At E?? = 0.01, CAPTURE estimates from filtered data displayed < 5% deviance from error-free estimates. When E?? was 0.05 or 0.09, some CAPTURE estimates from filtered data displayed biases in excess of 10%. Biases were positive at high sampling intensities; negative biases were observed at low sampling intensities. We caution researchers against using non-comprehensive data filters in NGS studies, unless they can achieve baseline per-locus error rates below 0.05 and, ideally, near 0.01. However, we suggest that data filters can be combined with careful technique and thoughtful NGS study design to yield accurate demographic information. ?? 2005 The Zoological Society of London.

The effects of center of rotation errors on cardiac SPECT imaging

NASA Astrophysics Data System (ADS)

Bai, Chuanyong; Shao, Ling; Ye, Jinghan; Durbin, M.

2003-10-01

In SPECT imaging, center of rotation (COR) errors lead to the misalignment of projection data and can potentially degrade the quality of the reconstructed images. In this work, we study the effects of COR errors on cardiac SPECT imaging using simulation, point source, cardiac phantom, and patient studies. For simulation studies, we generate projection data using a uniform MCAT phantom first without modeling any physical effects (NPH), then with the modeling of detector response effect (DR) alone. We then corrupt the projection data with simulated sinusoid and step COR errors. For other studies, we introduce sinusoid COR errors to projection data acquired on SPECT systems. An OSEM algorithm is used for image reconstruction without detector response correction, but with nonuniform attenuation correction when needed. The simulation studies show that, when COR errors increase from 0 to 0.96 cm: 1) sinusoid COR errors in axial direction lead to intensity decrease in the inferoapical region; 2) step COR errors in axial direction lead to intensity decrease in the distal anterior region. The intensity decrease is more severe in images reconstructed from projection data with NPH than with DR; and 3) the effects of COR errors in transaxial direction seem to be insignificant. In other studies, COR errors slightly degrade point source resolution; COR errors of 0.64 cm or above introduce visible but insignificant nonuniformity in the images of uniform cardiac phantom; COR errors up to 0.96 cm in transaxial direction affect the lesion-to-background contrast (LBC) insignificantly in the images of cardiac phantom with defects, and COR errors up to 0.64 cm in axial direction only slightly decrease the LBC. For the patient studies with COR errors up to 0.96 cm, images have the same diagnostic/prognostic values as those without COR errors. This work suggests that COR errors of up to 0.64 cm are not likely to change the clinical applications of cardiac SPECT imaging when using iterative reconstruction algorithm without detector response correction.

Parental mosaicism is a pitfall in preimplantation genetic diagnosis of dominant disorders.

PubMed

Steffann, Julie; Michot, Caroline; Borghese, Roxana; Baptista-Fernandes, Marcia; Monnot, Sophie; Bonnefont, Jean-Paul; Munnich, Arnold

2014-05-01

PCR amplification on single cells is prone to allele drop-out (PCR failure of one allele), a cause of misdiagnosis in preimplantation genetic diagnosis (PGD). Owing to this error risk, PGD usually relies on both direct and indirect genetic analyses. When the affected partner is the sporadic case of a dominant disorder, building haplotypes require spermatozoon or polar body testing prior to PGD, but these procedures are cost and time-consuming. A couple requested PGD because the male partner suffered from a dominant Cowden syndrome (CS). He was a sporadic case, but the couple had a first unaffected child and the non-mutated paternal haplotype was tentatively deduced. The couple had a second spontaneous pregnancy and the fetus was found to carry the at-risk haplotype but not the PTEN mutation. The mutation was present in blood from the affected father, but at low level, confirming the somatic mosaicism. Ignoring the possibility of mosaicism in the CS patient would have potentially led to selection of affected embryos. This observation emphasizes the risk of PGD in families at risk to transmit autosomal-dominant disorder when the affected partner is a sporadic case.

Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns.

PubMed

Enge, Martin; Arda, H Efsun; Mignardi, Marco; Beausang, John; Bottino, Rita; Kim, Seung K; Quake, Stephen R

2017-10-05

As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Gender-Specific Gene–Environment Interaction in Alcohol Dependence: The Impact of Daily Life Events and GABRA2

PubMed Central

Perry, Brea L.; Pescosolido, Bernice A.; Bucholz, Kathleen; Edenberg, Howard; Kramer, John; Kuperman, Samuel; Schuckit, Marc Alan; Nurnberger, John I.

2015-01-01

Gender-moderated gene–environment interactions are rarely explored, raising concerns about inaccurate specification of etiological models and inferential errors. The current study examined the influence of gender, negative and positive daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence, testing two- and three-way interactions between these variables using multilevel regression models fit to data from 2,281 White participants in the Collaborative Study on the Genetics of Alcoholism. Significant direct effects of variables of interest were identified, as well as gender-specific moderation of genetic risk on this SNP by social experiences. Higher levels of positive life events were protective for men with the high-risk genotype, but not among men with the low-risk genotype or women, regardless of genotype. Our findings support the disinhibition theory of alcohol dependence, suggesting that gender differences in social norms, constraints and opportunities, and behavioral undercontrol may explain men and women’s distinct patterns of association. PMID:23974430

Genetics Home Reference: arginine:glycine amidinotransferase deficiency

MedlinePlus

... amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001 Nov;69(5):1127-33. Epub 2001 Sep 10. Citation on PubMed or Free article on PubMed Central Nasrallah F, Feki M, Kaabachi ...

Accounting for Relatedness in Family Based Genetic Association Studies

PubMed Central

McArdle, P.F.; O’Connell, J.R.; Pollin, T.I.; Baumgarten, M.; Shuldiner, A.R.; Peyser, P.A.; Mitchell, B.D.

2007-01-01

Objective Assess the differences in point estimates, power and type 1 error rates when accounting for and ignoring family structure in genetic tests of association. Methods We compare by simulation the performance of analytic models using variance components to account for family structure and regression models that ignore relatedness for a range of possible family based study designs (i.e., sib pairs vs. large sibships vs. nuclear families vs. extended families). Results Our analyses indicate that effect size estimates and power are not significantly affected by ignoring family structure. Type 1 error rates increase when family structure is ignored, as density of family structures increases, and as trait heritability increases. For discrete traits with moderate levels of heritability and across many common sampling designs, type 1 error rates rise from a nominal 0.05 to 0.11. Conclusion Ignoring family structure may be useful in screening although it comes at a cost of a increased type 1 error rate, the magnitude of which depends on trait heritability and pedigree configuration. PMID:17570925

DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts.

PubMed

Lee, Donghyung; Bigdeli, T Bernard; Williamson, Vernell S; Vladimirov, Vladimir I; Riley, Brien P; Fanous, Ayman H; Bacanu, Silviu-Alin

2015-10-01

To increase the signal resolution for large-scale meta-analyses of genome-wide association studies, genotypes at unmeasured single nucleotide polymorphisms (SNPs) are commonly imputed using large multi-ethnic reference panels. However, the ever increasing size and ethnic diversity of both reference panels and cohorts makes genotype imputation computationally challenging for moderately sized computer clusters. Moreover, genotype imputation requires subject-level genetic data, which unlike summary statistics provided by virtually all studies, is not publicly available. While there are much less demanding methods which avoid the genotype imputation step by directly imputing SNP statistics, e.g. Directly Imputing summary STatistics (DIST) proposed by our group, their implicit assumptions make them applicable only to ethnically homogeneous cohorts. To decrease computational and access requirements for the analysis of cosmopolitan cohorts, we propose DISTMIX, which extends DIST capabilities to the analysis of mixed ethnicity cohorts. The method uses a relevant reference panel to directly impute unmeasured SNP statistics based only on statistics at measured SNPs and estimated/user-specified ethnic proportions. Simulations show that the proposed method adequately controls the Type I error rates. The 1000 Genomes panel imputation of summary statistics from the ethnically diverse Psychiatric Genetic Consortium Schizophrenia Phase 2 suggests that, when compared to genotype imputation methods, DISTMIX offers comparable imputation accuracy for only a fraction of computational resources. DISTMIX software, its reference population data, and usage examples are publicly available at http://code.google.com/p/distmix. dlee4@vcu.edu Supplementary Data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Improved classification accuracy by feature extraction using genetic algorithms

NASA Astrophysics Data System (ADS)

Patriarche, Julia; Manduca, Armando; Erickson, Bradley J.

2003-05-01

A feature extraction algorithm has been developed for the purposes of improving classification accuracy. The algorithm uses a genetic algorithm / hill-climber hybrid to generate a set of linearly recombined features, which may be of reduced dimensionality compared with the original set. The genetic algorithm performs the global exploration, and a hill climber explores local neighborhoods. Hybridizing the genetic algorithm with a hill climber improves both the rate of convergence, and the final overall cost function value; it also reduces the sensitivity of the genetic algorithm to parameter selection. The genetic algorithm includes the operators: crossover, mutation, and deletion / reactivation - the last of these effects dimensionality reduction. The feature extractor is supervised, and is capable of deriving a separate feature space for each tissue (which are reintegrated during classification). A non-anatomical digital phantom was developed as a gold standard for testing purposes. In tests with the phantom, and with images of multiple sclerosis patients, classification with feature extractor derived features yielded lower error rates than using standard pulse sequences, and with features derived using principal components analysis. Using the multiple sclerosis patient data, the algorithm resulted in a mean 31% reduction in classification error of pure tissues.

Energy Consumption Forecasting Using Semantic-Based Genetic Programming with Local Search Optimizer.

PubMed

Castelli, Mauro; Trujillo, Leonardo; Vanneschi, Leonardo

2015-01-01

Energy consumption forecasting (ECF) is an important policy issue in today's economies. An accurate ECF has great benefits for electric utilities and both negative and positive errors lead to increased operating costs. The paper proposes a semantic based genetic programming framework to address the ECF problem. In particular, we propose a system that finds (quasi-)perfect solutions with high probability and that generates models able to produce near optimal predictions also on unseen data. The framework blends a recently developed version of genetic programming that integrates semantic genetic operators with a local search method. The main idea in combining semantic genetic programming and a local searcher is to couple the exploration ability of the former with the exploitation ability of the latter. Experimental results confirm the suitability of the proposed method in predicting the energy consumption. In particular, the system produces a lower error with respect to the existing state-of-the art techniques used on the same dataset. More importantly, this case study has shown that including a local searcher in the geometric semantic genetic programming system can speed up the search process and can result in fitter models that are able to produce an accurate forecasting also on unseen data.

Mendelian randomization with fine-mapped genetic data: Choosing from large numbers of correlated instrumental variables.

PubMed

Burgess, Stephen; Zuber, Verena; Valdes-Marquez, Elsa; Sun, Benjamin B; Hopewell, Jemma C

2017-12-01

Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be used to assess this causal relationship. However, using too many genetic variants in the analysis can lead to spurious estimates and inflated Type 1 error rates. But if only a few genetic variants are used, then the majority of the data is ignored and estimates are highly sensitive to the particular choice of variants. We propose an approach based on summarized data only (genetic association and correlation estimates) that uses principal components analysis to form instruments. This approach has desirable theoretical properties: it takes the totality of data into account and does not suffer from numerical instabilities. It also has good properties in simulation studies: it is not particularly sensitive to varying the genetic variants included in the analysis or the genetic correlation matrix, and it does not have greatly inflated Type 1 error rates. Overall, the method gives estimates that are less precise than those from variable selection approaches (such as using a conditional analysis or pruning approach to select variants), but are more robust to seemingly arbitrary choices in the variable selection step. Methods are illustrated by an example using genetic associations with testosterone for 320 genetic variants to assess the effect of sex hormone related pathways on coronary artery disease risk, in which variable selection approaches give inconsistent inferences. © 2017 The Authors Genetic Epidemiology Published by Wiley Periodicals, Inc.

Determination of Cole-Cole parameters using only the real part of electrical impedivity measurements.

PubMed

Miranda, David A; Rivera, S A López

2008-05-01

An algorithm is presented to determine the Cole-Cole parameters of electrical impedivity using only measurements of its real part. The algorithm is based on two multi-fold direct inversion methods for the Cole-Cole and Debye equations, respectively, and a genetic algorithm for the optimization of the mean square error between experimental and calculated data. The algorithm has been developed to obtain the Cole-Cole parameters from experimental data, which were used to screen cervical intra-epithelial neoplasia. The proposed algorithm was compared with different numerical integrations of the Kramers-Kronig relation and the result shows that this algorithm is the best. A high immunity to noise was obtained.

Rapid, Accurate, and Non-Invasive Measurement of Zebrafish Axial Length and Other Eye Dimensions Using SD-OCT Allows Longitudinal Analysis of Myopia and Emmetropization

PubMed Central

Collery, Ross F.; Veth, Kerry N.; Dubis, Adam M.; Carroll, Joseph; Link, Brian A.

2014-01-01

Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R2 = 0.9548, R2 = 0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of −0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of −0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors. PMID:25334040

[Application of genetic algorithm in blending technology for extractions of Cortex Fraxini].

PubMed

Yang, Ming; Zhou, Yinmin; Chen, Jialei; Yu, Minying; Shi, Xiufeng; Gu, Xijun

2009-10-01

To explore the feasibility of genetic algorithm (GA) on multiple objective blending technology for extractions of Cortex Fraxini. According to that the optimization objective was the combination of fingerprint similarity and the root-mean-square error of multiple key constituents, a new multiple objective optimization model of 10 batches extractions of Cortex Fraxini was built. The blending coefficient was obtained by genetic algorithm. The quality of 10 batches extractions of Cortex Fraxini that after blending was evaluated with the finger print similarity and root-mean-square error as indexes. The quality of 10 batches extractions of Cortex Fraxini that after blending was well improved. Comparing with the fingerprint of the control sample, the similarity was up, but the degree of variation is down. The relative deviation of the key constituents was less than 10%. It is proved that genetic algorithm works well on multiple objective blending technology for extractions of Cortex Fraxini. This method can be a reference to control the quality of extractions of Cortex Fraxini. Genetic algorithm in blending technology for extractions of Chinese medicines is advisable.

Phenotypic Graphs and Evolution Unfold the Standard Genetic Code as the Optimal

NASA Astrophysics Data System (ADS)

Zamudio, Gabriel S.; José, Marco V.

2018-03-01

In this work, we explicitly consider the evolution of the Standard Genetic Code (SGC) by assuming two evolutionary stages, to wit, the primeval RNY code and two intermediate codes in between. We used network theory and graph theory to measure the connectivity of each phenotypic graph. The connectivity values are compared to the values of the codes under different randomization scenarios. An error-correcting optimal code is one in which the algebraic connectivity is minimized. We show that the SGC is optimal in regard to its robustness and error-tolerance when compared to all random codes under different assumptions.

The Impact of Gene-Environment Dependence and Misclassification in Genetic Association Studies Incorporating Gene-Environment Interactions

PubMed Central

Lindström, Sara; Yen, Yu-Chun; Spiegelman, Donna; Kraft, Peter

2009-01-01

The possibility of gene-environment interaction can be exploited to identify genetic variants associated with disease using a joint test of genetic main effect and gene-environment interaction. We consider how exposure misclassification and dependence between the true exposure E and the tested genetic variant G affect this joint test in absolute terms and relative to three other tests: the marginal test (G), the standard test for multiplicative gene-environment interaction (GE), and the case-only test for interaction (GE-CO). All tests can have inflated Type I error rate when E and G are correlated in the underlying population. For the GE and G-GE tests this inflation is only noticeable when the gene-environment dependence is unusually strong; the inflation can be large for the GE-CO test even for modest correlation. The joint G-GE test has greater power than the GE test generally, and greater power than the G test when there is no genetic main effect and the measurement error is small to moderate. The joint G-GE test is an attractive test for assessing genetic association when there is limited knowledge about casual mechanisms a priori, even in the presence of misclassification in environmental exposure measurement and correlation between exposure and genetic variants. PMID:19521099

The use of a covariate reduces experimental error in nutrient digestion studies in growing pigs

USDA-ARS?s Scientific Manuscript database

Covariance analysis limits error, the degree of nuisance variation, and overparameterizing factors to accurately measure treatment effects. Data dealing with growth, carcass composition, and genetics often utilize covariates in data analysis. In contrast, nutritional studies typically do not. The ob...

The NASA F-15 Intelligent Flight Control Systems: Generation II

NASA Technical Reports Server (NTRS)

Buschbacher, Mark; Bosworth, John

2006-01-01

The Second Generation (Gen II) control system for the F-15 Intelligent Flight Control System (IFCS) program implements direct adaptive neural networks to demonstrate robust tolerance to faults and failures. The direct adaptive tracking controller integrates learning neural networks (NNs) with a dynamic inversion control law. The term direct adaptive is used because the error between the reference model and the aircraft response is being compensated or directly adapted to minimize error without regard to knowing the cause of the error. No parameter estimation is needed for this direct adaptive control system. In the Gen II design, the feedback errors are regulated with a proportional-plus-integral (PI) compensator. This basic compensator is augmented with an online NN that changes the system gains via an error-based adaptation law to improve aircraft performance at all times, including normal flight, system failures, mispredicted behavior, or changes in behavior resulting from damage.

Spiral-bevel geometry and gear train precision

NASA Technical Reports Server (NTRS)

Litvin, F. L.; Coy, J. J.

1983-01-01

A new aproach to the solution of determination of surface principal curvatures and directions is proposed. Direct relationships between the principal curvatures and directions of the tool surface and those of the principal curvatures and directions of generated gear surface are obtained. The principal curvatures and directions of geartooth surface are obtained without using the complicated equations of these surfaces. A general theory of the train kinematical errors exerted by manufacturing and assembly errors is discussed. Two methods for the determination of the train kinematical errors can be worked out: (1) with aid of a computer, and (2) with a approximate method. Results from noise and vibration measurement conducted on a helicopter transmission are used to illustrate the principals contained in the theory of kinematic errors.

Amelogenin test: From forensics to quality control in clinical and biochemical genomics.

PubMed

Francès, F; Portolés, O; González, J I; Coltell, O; Verdú, F; Castelló, A; Corella, D

2007-01-01

The increasing number of samples from the biomedical genetic studies and the number of centers participating in the same involves increasing risk of mistakes in the different sample handling stages. We have evaluated the usefulness of the amelogenin test for quality control in sample identification. Amelogenin test (frequently used in forensics) was undertaken on 1224 individuals participating in a biomedical study. Concordance between referred sex in the database and amelogenin test was estimated. Additional sex-error genetic detecting systems were developed. The overall concordance rate was 99.84% (1222/1224). Two samples showed a female amelogenin test outcome, being codified as males in the database. The first, after checking sex-specific biochemical and clinical profile data was found to be due to a codification error in the database. In the second, after checking the database, no apparent error was discovered because a correct male profile was found. False negatives in amelogenin male sex determination were discarded by additional tests, and feminine sex was confirmed. A sample labeling error was revealed after a new DNA extraction. The amelogenin test is a useful quality control tool for detecting sex-identification errors in large genomic studies, and can contribute to increase its validity.

Heritability of lenticular myopia in English Springer spaniels.

PubMed

Kubai, Melissa A; Labelle, Amber L; Hamor, Ralph E; Mutti, Donald O; Famula, Thomas R; Murphy, Christopher J

2013-11-08

We determined whether naturally-occurring lenticular myopia in English Springer spaniels (ESS) has a genetic component. Streak retinoscopy was performed on 226 related ESS 30 minutes after the onset of pharmacologic mydriasis and cycloplegia. A pedigree was constructed to determine relationships between affected offspring and parents. Estimation of heritability was done in a Bayesian analysis (facilitated by the MCMCglmm package of R) of refractive error in a model, including terms for sex and coat color. Myopia was defined as ≤-0.5 diopters (D) spherical equivalent. The median refractive error for ESS was 0.25 D (range, -3.5 to +4.5 D). Median age was 0.2 years (range, 0.1-15 years). The prevalence of myopia in related ESS was 19% (42/226). The ESS had a strong correlation (r = 0.95) for refractive error between the two eyes. Moderate heritability was present for refractive error with a mean value of 0.29 (95% highest probability density, 0.07-0.50). The distribution of refractive error, and subsequently lenticular myopia, has a moderate genetic component in ESS. Further investigation of genes responsible for regulation of the development of refractive ocular components in canines is warranted.

An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Author Correction: Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos.

PubMed

Floros, Vasileios I; Pyle, Angela; Dietmann, Sabine; Wei, Wei; Tang, Walfred W C; Irie, Naoko; Payne, Brendan; Capalbo, Antonio; Noli, Laila; Coxhead, Jonathan; Hudson, Gavin; Crosier, Moira; Strahl, Henrik; Khalaf, Yacoub; Saitou, Mitinori; Ilic, Dusko; Surani, M Azim; Chinnery, Patrick F

2018-04-19

In the version of this Letter originally published, an author error led to the affiliations for Brendan Payne, Jonathan Coxhead and Gavin Hudson being incorrect. The correct affiliations are: Brendan Payne: 3 Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. 6 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; this is a new affiliation 6 and subsequent existing affiliations have been renumbered. Jonathan Coxhead: 11 Genomic Core Facility, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; this is a new affiliation 11 and subsequent existing affiliations have been renumbered. Gavin Hudson: 3 Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. In addition, in Fig. 2d, the numbers on the x-axis of the left plot were incorrectly labelled as negative; they should have been positive. These errors have now been corrected in all online versions of the Letter.

Modeling of mouse eye and errors in ocular parameters affecting refractive state

NASA Astrophysics Data System (ADS)

Bawa, Gurinder

Rodents eye are particularly used to study refractive error state of an eye and development of refractive eye. Genetic organization of rodents is similar to that of humans, which makes them interesting candidates to be researched upon. From rodents family mice models are encouraged over rats because of availability of genetically engineered models. Despite of extensive work that has been performed on mice and rat models, still no one is able to quantify an optical model, due to variability in the reported ocular parameters. In this Dissertation, we have extracted ocular parameters and generated schematics of eye from the raw data from School of Medicine, Detroit. In order to see how the rays would travel through an eye and the defects associated with an eye; ray tracing has been performed using ocular parameters. Finally we have systematically evaluated the contribution of various ocular parameters, such as radii of curvature of ocular surfaces, thicknesses of ocular components, and refractive indices of ocular refractive media, using variational analysis and a computational model of the rodent eye. Variational analysis revealed that variation in all the ocular parameters does affect the refractive status of the eye, but depending upon the magnitude of the impact those parameters are listed as critical or non critical. Variation in the depth of the vitreous chamber, thickness of the lens, radius of the anterior surface of the cornea, radius of the anterior surface of the lens, as well as refractive indices for the lens and vitreous, appears to have the largest impact on the refractive error and thus are categorized as critical ocular parameters. The radii of the posterior surfaces of the cornea and lens have much smaller contributions to the refractive state, while the radii of the anterior and posterior surfaces of the retina have no effect on the refractive error. These data provide the framework for further refinement of the optical models of the rat and mouse eye and suggest that extra efforts should be directed towards increasing the linear resolution of the rodent eye biometry and obtaining more accurate data for the refractive indices of the lens and vitreous.

Context-dependent sequential effects of target selection for action.

PubMed

Moher, Jeff; Song, Joo-Hyun

2013-07-11

Humans exhibit variation in behavior from moment to moment even when performing a simple, repetitive task. Errors are typically followed by cautious responses, minimizing subsequent distractor interference. However, less is known about how variation in the execution of an ultimately correct response affects subsequent behavior. We asked participants to reach toward a uniquely colored target presented among distractors and created two categories to describe participants' responses in correct trials based on analyses of movement trajectories; partial errors referred to trials in which observers initially selected a nontarget for action before redirecting the movement and accurately pointing to the target, and direct movements referred to trials in which the target was directly selected for action. We found that latency to initiate a hand movement was shorter in trials following partial errors compared to trials following direct movements. Furthermore, when the target and distractor colors were repeated, movement time and reach movement curvature toward distractors were greater following partial errors compared to direct movements. Finally, when the colors were repeated, partial errors were more frequent than direct movements following partial-error trials, and direct movements were more frequent following direct-movement trials. The dependence of these latter effects on repeated-task context indicates the involvement of higher-level cognitive mechanisms in an integrated attention-action system in which execution of a partial-error or direct-movement response affects memory representations that bias performance in subsequent trials. Altogether, these results demonstrate that whether a nontarget is selected for action or not has a measurable impact on subsequent behavior.

Robust Flight Path Determination for Mars Precision Landing Using Genetic Algorithms

NASA Technical Reports Server (NTRS)

Bayard, David S.; Kohen, Hamid

1997-01-01

This paper documents the application of genetic algorithms (GAs) to the problem of robust flight path determination for Mars precision landing. The robust flight path problem is defined here as the determination of the flight path which delivers a low-lift open-loop controlled vehicle to its desired final landing location while minimizing the effect of perturbations due to uncertainty in the atmospheric model and entry conditions. The genetic algorithm was capable of finding solutions which reduced the landing error from 111 km RMS radial (open-loop optimal) to 43 km RMS radial (optimized with respect to perturbations) using 200 hours of computation on an Ultra-SPARC workstation. Further reduction in the landing error is possible by going to closed-loop control which can utilize the GA optimized paths as nominal trajectories for linearization.

Comparison of spatial association approaches for landscape mapping of soil organic carbon stocks

NASA Astrophysics Data System (ADS)

Miller, B. A.; Koszinski, S.; Wehrhan, M.; Sommer, M.

2015-03-01

The distribution of soil organic carbon (SOC) can be variable at small analysis scales, but consideration of its role in regional and global issues demands the mapping of large extents. There are many different strategies for mapping SOC, among which is to model the variables needed to calculate the SOC stock indirectly or to model the SOC stock directly. The purpose of this research is to compare direct and indirect approaches to mapping SOC stocks from rule-based, multiple linear regression models applied at the landscape scale via spatial association. The final products for both strategies are high-resolution maps of SOC stocks (kg m-2), covering an area of 122 km2, with accompanying maps of estimated error. For the direct modelling approach, the estimated error map was based on the internal error estimations from the model rules. For the indirect approach, the estimated error map was produced by spatially combining the error estimates of component models via standard error propagation equations. We compared these two strategies for mapping SOC stocks on the basis of the qualities of the resulting maps as well as the magnitude and distribution of the estimated error. The direct approach produced a map with less spatial variation than the map produced by the indirect approach. The increased spatial variation represented by the indirect approach improved R2 values for the topsoil and subsoil stocks. Although the indirect approach had a lower mean estimated error for the topsoil stock, the mean estimated error for the total SOC stock (topsoil + subsoil) was lower for the direct approach. For these reasons, we recommend the direct approach to modelling SOC stocks be considered a more conservative estimate of the SOC stocks' spatial distribution.

Comparison of spatial association approaches for landscape mapping of soil organic carbon stocks

NASA Astrophysics Data System (ADS)

Miller, B. A.; Koszinski, S.; Wehrhan, M.; Sommer, M.

2014-11-01

The distribution of soil organic carbon (SOC) can be variable at small analysis scales, but consideration of its role in regional and global issues demands the mapping of large extents. There are many different strategies for mapping SOC, among which are to model the variables needed to calculate the SOC stock indirectly or to model the SOC stock directly. The purpose of this research is to compare direct and indirect approaches to mapping SOC stocks from rule-based, multiple linear regression models applied at the landscape scale via spatial association. The final products for both strategies are high-resolution maps of SOC stocks (kg m-2), covering an area of 122 km2, with accompanying maps of estimated error. For the direct modelling approach, the estimated error map was based on the internal error estimations from the model rules. For the indirect approach, the estimated error map was produced by spatially combining the error estimates of component models via standard error propagation equations. We compared these two strategies for mapping SOC stocks on the basis of the qualities of the resulting maps as well as the magnitude and distribution of the estimated error. The direct approach produced a map with less spatial variation than the map produced by the indirect approach. The increased spatial variation represented by the indirect approach improved R2 values for the topsoil and subsoil stocks. Although the indirect approach had a lower mean estimated error for the topsoil stock, the mean estimated error for the total SOC stock (topsoil + subsoil) was lower for the direct approach. For these reasons, we recommend the direct approach to modelling SOC stocks be considered a more conservative estimate of the SOC stocks' spatial distribution.

Using genetic markers to orient the edges in quantitative trait networks: the NEO software.

PubMed

Aten, Jason E; Fuller, Tova F; Lusis, Aldons J; Horvath, Steve

2008-04-15

Systems genetic studies have been used to identify genetic loci that affect transcript abundances and clinical traits such as body weight. The pairwise correlations between gene expression traits and/or clinical traits can be used to define undirected trait networks. Several authors have argued that genetic markers (e.g expression quantitative trait loci, eQTLs) can serve as causal anchors for orienting the edges of a trait network. The availability of hundreds of thousands of genetic markers poses new challenges: how to relate (anchor) traits to multiple genetic markers, how to score the genetic evidence in favor of an edge orientation, and how to weigh the information from multiple markers. We develop and implement Network Edge Orienting (NEO) methods and software that address the challenges of inferring unconfounded and directed gene networks from microarray-derived gene expression data by integrating mRNA levels with genetic marker data and Structural Equation Model (SEM) comparisons. The NEO software implements several manual and automatic methods for incorporating genetic information to anchor traits. The networks are oriented by considering each edge separately, thus reducing error propagation. To summarize the genetic evidence in favor of a given edge orientation, we propose Local SEM-based Edge Orienting (LEO) scores that compare the fit of several competing causal graphs. SEM fitting indices allow the user to assess local and overall model fit. The NEO software allows the user to carry out a robustness analysis with regard to genetic marker selection. We demonstrate the utility of NEO by recovering known causal relationships in the sterol homeostasis pathway using liver gene expression data from an F2 mouse cross. Further, we use NEO to study the relationship between a disease gene and a biologically important gene co-expression module in liver tissue. The NEO software can be used to orient the edges of gene co-expression networks or quantitative trait networks if the edges can be anchored to genetic marker data. R software tutorials, data, and supplementary material can be downloaded from: http://www.genetics.ucla.edu/labs/horvath/aten/NEO.

Genes and inheritance.

PubMed

Middelton, L A; Peters, K F

2001-10-01

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

Determination of errors in derived magnetic field directions in geosynchronous orbit: results from a statistical approach

NASA Astrophysics Data System (ADS)

Chen, Yue; Cunningham, Gregory; Henderson, Michael

2016-09-01

This study aims to statistically estimate the errors in local magnetic field directions that are derived from electron directional distributions measured by Los Alamos National Laboratory geosynchronous (LANL GEO) satellites. First, by comparing derived and measured magnetic field directions along the GEO orbit to those calculated from three selected empirical global magnetic field models (including a static Olson and Pfitzer 1977 quiet magnetic field model, a simple dynamic Tsyganenko 1989 model, and a sophisticated dynamic Tsyganenko 2001 storm model), it is shown that the errors in both derived and modeled directions are at least comparable. Second, using a newly developed proxy method as well as comparing results from empirical models, we are able to provide for the first time circumstantial evidence showing that derived magnetic field directions should statistically match the real magnetic directions better, with averaged errors < ˜ 2°, than those from the three empirical models with averaged errors > ˜ 5°. In addition, our results suggest that the errors in derived magnetic field directions do not depend much on magnetospheric activity, in contrast to the empirical field models. Finally, as applications of the above conclusions, we show examples of electron pitch angle distributions observed by LANL GEO and also take the derived magnetic field directions as the real ones so as to test the performance of empirical field models along the GEO orbits, with results suggesting dependence on solar cycles as well as satellite locations. This study demonstrates the validity and value of the method that infers local magnetic field directions from particle spin-resolved distributions.

Determination of errors in derived magnetic field directions in geosynchronous orbit: results from a statistical approach

DOE PAGES

Chen, Yue; Cunningham, Gregory; Henderson, Michael

2016-09-21

Our study aims to statistically estimate the errors in local magnetic field directions that are derived from electron directional distributions measured by Los Alamos National Laboratory geosynchronous (LANL GEO) satellites. First, by comparing derived and measured magnetic field directions along the GEO orbit to those calculated from three selected empirical global magnetic field models (including a static Olson and Pfitzer 1977 quiet magnetic field model, a simple dynamic Tsyganenko 1989 model, and a sophisticated dynamic Tsyganenko 2001 storm model), it is shown that the errors in both derived and modeled directions are at least comparable. Furthermore, using a newly developedmore » proxy method as well as comparing results from empirical models, we are able to provide for the first time circumstantial evidence showing that derived magnetic field directions should statistically match the real magnetic directions better, with averaged errors < ~2°, than those from the three empirical models with averaged errors > ~5°. In addition, our results suggest that the errors in derived magnetic field directions do not depend much on magnetospheric activity, in contrast to the empirical field models. Finally, as applications of the above conclusions, we show examples of electron pitch angle distributions observed by LANL GEO and also take the derived magnetic field directions as the real ones so as to test the performance of empirical field models along the GEO orbits, with results suggesting dependence on solar cycles as well as satellite locations. Finally, this study demonstrates the validity and value of the method that infers local magnetic field directions from particle spin-resolved distributions.« less

Determination of errors in derived magnetic field directions in geosynchronous orbit: results from a statistical approach

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

Chen, Yue; Cunningham, Gregory; Henderson, Michael

Our study aims to statistically estimate the errors in local magnetic field directions that are derived from electron directional distributions measured by Los Alamos National Laboratory geosynchronous (LANL GEO) satellites. First, by comparing derived and measured magnetic field directions along the GEO orbit to those calculated from three selected empirical global magnetic field models (including a static Olson and Pfitzer 1977 quiet magnetic field model, a simple dynamic Tsyganenko 1989 model, and a sophisticated dynamic Tsyganenko 2001 storm model), it is shown that the errors in both derived and modeled directions are at least comparable. Furthermore, using a newly developedmore » proxy method as well as comparing results from empirical models, we are able to provide for the first time circumstantial evidence showing that derived magnetic field directions should statistically match the real magnetic directions better, with averaged errors < ~2°, than those from the three empirical models with averaged errors > ~5°. In addition, our results suggest that the errors in derived magnetic field directions do not depend much on magnetospheric activity, in contrast to the empirical field models. Finally, as applications of the above conclusions, we show examples of electron pitch angle distributions observed by LANL GEO and also take the derived magnetic field directions as the real ones so as to test the performance of empirical field models along the GEO orbits, with results suggesting dependence on solar cycles as well as satellite locations. Finally, this study demonstrates the validity and value of the method that infers local magnetic field directions from particle spin-resolved distributions.« less

Genetic parameters for carcass and meat quality traits and their relationships to liveweight and wool production in hogget Merino rams.

PubMed

Greeff, J C; Safari, E; Fogarty, N M; Hopkins, D L; Brien, F D; Atkins, K D; Mortimer, S I; van der Werf, J H J

2008-06-01

Genetic parameters for carcass and meat quality traits of about 18-month-old Merino rams (n = 5870), the progeny of 543 sires from three research resource flocks, were estimated. The estimates of heritability for hot carcass weight (HCW) and the various fat and muscle dimension measurements were moderate and ranged from 0.20 to 0.37. The brightness of meat (colour L*, 0.18 +/- 0.03 standard error) and meat pH (0.22 +/- 0.03) also had moderate estimates of heritability, although meat relative redness (colour a*, 0.10 +/- 0.03) and relative yellowness (colour b*, 0.10 +/- 0.03) were lower. Heritability estimates for live weights were moderate and ranged from 0.29 to 0.41 with significant permanent maternal environmental effects (0.13 to 0.10). The heritability estimates for the hogget wool traits were moderate to high and ranged from 0.27 to 0.60. The ultrasound measurements of fat depth (FATUS) and eye muscle depth (EMDUS) on live animals were highly genetically correlated with the corresponding carcass measurements (0.69 +/- 0.09 FATC and 0.77 +/- 0.07 EMD). Carcass tissue depth (FATGR) had moderate to low genetic correlations with carcass muscle measurements [0.18 +/- 0.10 EMD and 0.05 +/- 0.10 eye muscle area (EMA)], while those with FATC were negative. The genetic correlation between EMD and eye muscle width (EMW) was 0.41 +/- 0.08, while EMA was highly correlated with EMD (0.89 +/- 0.0) and EMW (0.78 +/- 0.04). The genetic correlations for muscle colour with muscle measurements were moderately negative, while those with fat measurements were close to zero. Meat pH was positively correlated with muscle measurements (0.14 to 0.17) and negatively correlated with fat measurements (-0.06 to -0.18). EMDUS also showed a similar pattern of correlations to EMD with meat quality indicator traits, although FATUS had positive correlations with these traits which were generally smaller than their standard error. The genetic correlations among the meat colour traits were high and positive while those with meat pH were high and negative, which were all in the favourable direction. Generally, phenotypic correlations were similar or slightly lower than the corresponding genetic correlations. There were generally small to moderate negative genetic correlations between clean fleece weight (CFW) and carcass fat traits while those with muscle traits were close to zero. As the Merino is already a relatively lean breed, this implies that particular attention should be given to this relationship in Merino breeding programmes to prevent the reduction of fat reserves as a correlated response to selection for increased fleece weight. The ultrasound scan traits generally showed a similar pattern to the corresponding carcass fat and muscle traits. There was a small unfavourable genetic correlation between CFW and meat pH (0.19 +/- 0.07).

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

PubMed Central

Loughman, James; Wildsoet, Christine F.; Williams, Cathy; Guggenheim, Jeremy A.

2018-01-01

Purpose To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Methods Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests. Results Pathway analysis identified several biological processes already implicated in refractive error development through prior GWAS analyses and animal studies, including extracellular matrix remodeling, focal adhesion, and axon guidance, supporting the research hypothesis. Novel pathways also implicated in myopia development included mannosylation, glycosylation, lens development, gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked to a different pattern of biological processes, mostly related to organogenesis. Comparison with GWAS findings further confirmed that syndromic myopia genes were enriched for genetic variants that influence refractive errors in the general population. Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1, GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469). Conclusions Common genetic variants within or nearby genes that cause syndromic myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis of syndromic forms of refractive errors can provide new insights into the etiology of myopia and additional potential targets for therapeutic interventions. PMID:29346494

Genetic Algorithm for Optimization: Preprocessing with n Dimensional Bisection and Error Estimation

NASA Technical Reports Server (NTRS)

Sen, S. K.; Shaykhian, Gholam Ali

2006-01-01

A knowledge of the appropriate values of the parameters of a genetic algorithm (GA) such as the population size, the shrunk search space containing the solution, crossover and mutation probabilities is not available a priori for a general optimization problem. Recommended here is a polynomial-time preprocessing scheme that includes an n-dimensional bisection and that determines the foregoing parameters before deciding upon an appropriate GA for all problems of similar nature and type. Such a preprocessing is not only fast but also enables us to get the global optimal solution and its reasonably narrow error bounds with a high degree of confidence.

Assessing the Relationship of Ancient and Modern Populations

PubMed Central

Schraiber, Joshua G.

2018-01-01

Genetic material sequenced from ancient samples is revolutionizing our understanding of the recent evolutionary past. However, ancient DNA is often degraded, resulting in low coverage, error-prone sequencing. Several solutions exist to this problem, ranging from simple approach, such as selecting a read at random for each site, to more complicated approaches involving genotype likelihoods. In this work, we present a novel method for assessing the relationship of an ancient sample with a modern population, while accounting for sequencing error and postmortem damage by analyzing raw reads from multiple ancient individuals simultaneously. We show that, when analyzing SNP data, it is better to sequence more ancient samples to low coverage: two samples sequenced to 0.5× coverage provide better resolution than a single sample sequenced to 2× coverage. We also examined the power to detect whether an ancient sample is directly ancestral to a modern population, finding that, with even a few high coverage individuals, even ancient samples that are very slightly diverged from the modern population can be detected with ease. When we applied our approach to European samples, we found that no ancient samples represent direct ancestors of modern Europeans. We also found that, as shown previously, the most ancient Europeans appear to have had the smallest effective population sizes, indicating a role for agriculture in modern population growth. PMID:29167200

Smoothing of the bivariate LOD score for non-normal quantitative traits.

PubMed

Buil, Alfonso; Dyer, Thomas D; Almasy, Laura; Blangero, John

2005-12-30

Variance component analysis provides an efficient method for performing linkage analysis for quantitative traits. However, type I error of variance components-based likelihood ratio testing may be affected when phenotypic data are non-normally distributed (especially with high values of kurtosis). This results in inflated LOD scores when the normality assumption does not hold. Even though different solutions have been proposed to deal with this problem with univariate phenotypes, little work has been done in the multivariate case. We present an empirical approach to adjust the inflated LOD scores obtained from a bivariate phenotype that violates the assumption of normality. Using the Collaborative Study on the Genetics of Alcoholism data available for the Genetic Analysis Workshop 14, we show how bivariate linkage analysis with leptokurtotic traits gives an inflated type I error. We perform a novel correction that achieves acceptable levels of type I error.

Estimation of genetic effects in the presence of multicollinearity in multibreed beef cattle evaluation.

PubMed

Roso, V M; Schenkel, F S; Miller, S P; Schaeffer, L R

2005-08-01

Breed additive, dominance, and epistatic loss effects are of concern in the genetic evaluation of a multibreed population. Multiple regression equations used for fitting these effects may show a high degree of multicollinearity among predictor variables. Typically, when strong linear relationships exist, the regression coefficients have large SE and are sensitive to changes in the data file and to the addition or deletion of variables in the model. Generalized ridge regression methods were applied to obtain stable estimates of direct and maternal breed additive, dominance, and epistatic loss effects in the presence of multicollinearity among predictor variables. Preweaning weight gains of beef calves in Ontario, Canada, from 1986 to 1999 were analyzed. The genetic model included fixed direct and maternal breed additive, dominance, and epistatic loss effects, fixed environmental effects of age of the calf, contemporary group, and age of the dam x sex of the calf, random additive direct and maternal genetic effects, and random maternal permanent environment effect. The degree and the nature of the multicollinearity were identified and ridge regression methods were used as an alternative to ordinary least squares (LS). Ridge parameters were obtained using two different objective methods: 1) generalized ridge estimator of Hoerl and Kennard (R1); and 2) bootstrap in combination with cross-validation (R2). Both ridge regression methods outperformed the LS estimator with respect to mean squared error of predictions (MSEP) and variance inflation factors (VIF) computed over 100 bootstrap samples. The MSEP of R1 and R2 were similar, and they were 3% less than the MSEP of LS. The average VIF of LS, R1, and R2 were equal to 26.81, 6.10, and 4.18, respectively. Ridge regression methods were particularly effective in decreasing the multicollinearity involving predictor variables of breed additive effects. Because of a high degree of confounding between estimates of maternal dominance and direct epistatic loss effects, it was not possible to compare the relative importance of these effects with a high level of confidence. The inclusion of epistatic loss effects in the additive-dominance model did not cause noticeable reranking of sires, dams, and calves based on across-breed EBV. More precise estimates of breed effects as a result of this study may result in more stable across-breed estimated breeding values over the years.

CBrowse: a SAM/BAM-based contig browser for transcriptome assembly visualization and analysis.

PubMed

Li, Pei; Ji, Guoli; Dong, Min; Schmidt, Emily; Lenox, Douglas; Chen, Liangliang; Liu, Qi; Liu, Lin; Zhang, Jie; Liang, Chun

2012-09-15

To address the impending need for exploring rapidly increased transcriptomics data generated for non-model organisms, we developed CBrowse, an AJAX-based web browser for visualizing and analyzing transcriptome assemblies and contigs. Designed in a standard three-tier architecture with a data pre-processing pipeline, CBrowse is essentially a Rich Internet Application that offers many seamlessly integrated web interfaces and allows users to navigate, sort, filter, search and visualize data smoothly. The pre-processing pipeline takes the contig sequence file in FASTA format and its relevant SAM/BAM file as the input; detects putative polymorphisms, simple sequence repeats and sequencing errors in contigs and generates image, JSON and database-compatible CSV text files that are directly utilized by different web interfaces. CBowse is a generic visualization and analysis tool that facilitates close examination of assembly quality, genetic polymorphisms, sequence repeats and/or sequencing errors in transcriptome sequencing projects. CBrowse is distributed under the GNU General Public License, available at http://bioinfolab.muohio.edu/CBrowse/ liangc@muohio.edu or liangc.mu@gmail.com; glji@xmu.edu.cn Supplementary data are available at Bioinformatics online.

An improved 10-SSR pyrus fingerprinting DNA test to confirm parentage [abstract

USDA-ARS?s Scientific Manuscript database

Pedigree confirmation is a critical part of breeding, managing genetic resources, and developing genetic mapping populations for out-crossing plants, such as the genus Pyrus. Individuals which are not progeny of a biparental cross can cause mapping errors or result in the costly genotyping of indivi...

Correction to: Genetic diversity of arsenic accumulation in rice and QTL analysis of methylated arsenic in rice grains.

PubMed

Kuramata, Masato; Abe, Tadashi; Kawasaki, Akira; Ebana, Kaworu; Shibaya, Taeko; Yano, Masahiro; Ishikawa, Satoru

2018-04-24

The authors of article "Genetic diversity of arsenic accumulation in rice and QTL analysis of methylated arsenic in rice grains" (Kuramata et al. 2013) would like to note that the original version of the article online unfortunately contains the following errors.

Genetic and Environmental Contributions to Educational Attainment in Australia.

ERIC Educational Resources Information Center

Miller, Paul; Mulvey, Charles; Martin, Nick

2001-01-01

Data from a large sample of Australian twins indicate that 50 to 65 percent of variance in educational attainments can be attributed to genetic endowments. Only about 25 to 40 percent may be due to environmental factors, depending on adjustments for measurement error and assortative mating. (Contains 51 references.) (MLH)

A Microcomputer Exercise on Genetic Transcription and Translation.

ERIC Educational Resources Information Center

Meisenheimer, John L.

1985-01-01

Describes a microcomputer program (written for the Apple II+) which can serve as a lecture demonstration aid in explaining genetic transcription and translation. The program provides unemotional information on student errors, thus serving as a review drill to supplement the classroom. Student participation and instructor options are discussed. (DH)

SOFIA: an R package for enhancing genetic visualization with Circos

USDA-ARS?s Scientific Manuscript database

Visualization of data from any stage of genetic and genomic research is one of the most useful approaches for detecting potential errors, ensuring accuracy and reproducibility, and presentation of the resulting data. Currently software such as Circos, ClicO FS, and RCircos, among others, provide too...

CAP/ACMG proficiency testing for biochemical genetics laboratories: a summary of performance.

PubMed

Oglesbee, Devin; Cowan, Tina M; Pasquali, Marzia; Wood, Timothy C; Weck, Karen E; Long, Thomas; Palomaki, Glenn E

2018-01-01

PurposeTesting for inborn errors of metabolism is performed by clinical laboratories worldwide, each utilizing laboratory-developed procedures. We sought to summarize performance in the College of American Pathologists' (CAP) proficiency testing (PT) program and identify opportunities for improving laboratory quality. When evaluating PT data, we focused on a subset of laboratories that have participated in at least one survey since 2010.MethodsAn analysis of laboratory performance (2004 to 2014) on the Biochemical Genetics PT Surveys, a program administered by CAP and the American College of Medical Genetics and Genomics. Analytical and interpretive performance was evaluated for four tests: amino acids, organic acids, acylcarnitines, and mucopolysaccharides.ResultsSince 2010, 150 laboratories have participated in at least one of four PT surveys. Analytic sensitivities ranged from 88.2 to 93.4%, while clinical sensitivities ranged from 82.4 to 91.0%. Performance was higher for US participants and for more recent challenges. Performance was lower for challenges with subtle findings or complex analytical patterns.ConclusionUS clinical biochemical genetics laboratory proficiency is satisfactory, with a minority of laboratories accounting for the majority of errors. Our findings underscore the complex nature of clinical biochemical genetics testing and highlight the necessity of continuous quality management.

Building synthetic gene circuits from combinatorial libraries: screening and selection strategies.

PubMed

Schaerli, Yolanda; Isalan, Mark

2013-07-01

The promise of wide-ranging biotechnology applications inspires synthetic biologists to design novel genetic circuits. However, building such circuits rationally is still not straightforward and often involves painstaking trial-and-error. Mimicking the process of natural selection can help us to bridge the gap between our incomplete understanding of nature's design rules and our desire to build functional networks. By adopting the powerful method of directed evolution, which is usually applied to protein engineering, functional networks can be obtained through screening or selecting from randomised combinatorial libraries. This review first highlights the practical options to introduce combinatorial diversity into gene circuits and then examines strategies for identifying the potentially rare library members with desired functions, either by screening or selection.

Phylomemetics—Evolutionary Analysis beyond the Gene

PubMed Central

Howe, Christopher J.; Windram, Heather F.

2011-01-01

Genes are propagated by error-prone copying, and the resulting variation provides the basis for phylogenetic reconstruction of evolutionary relationships. Horizontal gene transfer may be superimposed on a tree-like evolutionary pattern, with some relationships better depicted as networks. The copying of manuscripts by scribes is very similar to the replication of genes, and phylogenetic inference programs can be used directly for reconstructing the copying history of different versions of a manuscript text. Phylogenetic methods have also been used for some time to analyse the evolution of languages and the development of physical cultural artefacts. These studies can help to answer a range of anthropological questions. We propose the adoption of the term “phylomemetics” for phylogenetic analysis of reproducing non-genetic elements. PMID:21655311

Participation and performance in INSTAND multi-analyte molecular genetics external quality assessment schemes from 2006 to 2012.

PubMed

Maly, Friedrich E; Fried, Roman; Spannagl, Michael

2014-01-01

INSTAND e.V. has provided Molecular Genetics Multi-Analyte EQA schemes since 2006. EQA participation and performance were assessed from 2006 - 2012. From 2006 to 2012, the number of analytes in the Multi-Analyte EQA schemes rose from 17 to 53. Total number of results returned rose from 168 in January 2006 to 824 in August 2012. The overall error rate was 1.40 +/- 0.84% (mean +/- SD, N = 24 EQA dates). From 2006 to 2012, no analyte was reported 100% correctly. Individual participant performance was analysed for one common analyte, Lactase (LCT) T-13910C. From 2006 to 2012, 114 laboratories participated in this EQA. Of these, 10 laboratories (8.8%) reported at least one wrong result during the whole observation period. All laboratories reported correct results after their failure incident. In spite of the low overall error rate, EQA will continue to be important for Molecular Genetics.

[Analytic methods for seed models with genotype x environment interactions].

PubMed

Zhu, J

1996-01-01

Genetic models with genotype effect (G) and genotype x environment interaction effect (GE) are proposed for analyzing generation means of seed quantitative traits in crops. The total genetic effect (G) is partitioned into seed direct genetic effect (G0), cytoplasm genetic of effect (C), and maternal plant genetic effect (Gm). Seed direct genetic effect (G0) can be further partitioned into direct additive (A) and direct dominance (D) genetic components. Maternal genetic effect (Gm) can also be partitioned into maternal additive (Am) and maternal dominance (Dm) genetic components. The total genotype x environment interaction effect (GE) can also be partitioned into direct genetic by environment interaction effect (G0E), cytoplasm genetic by environment interaction effect (CE), and maternal genetic by environment interaction effect (GmE). G0E can be partitioned into direct additive by environment interaction (AE) and direct dominance by environment interaction (DE) genetic components. GmE can also be partitioned into maternal additive by environment interaction (AmE) and maternal dominance by environment interaction (DmE) genetic components. Partitions of genetic components are listed for parent, F1, F2 and backcrosses. A set of parents, their reciprocal F1 and F2 seeds is applicable for efficient analysis of seed quantitative traits. MINQUE(0/1) method can be used for estimating variance and covariance components. Unbiased estimation for covariance components between two traits can also be obtained by the MINQUE(0/1) method. Random genetic effects in seed models are predictable by the Adjusted Unbiased Prediction (AUP) approach with MINQUE(0/1) method. The jackknife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects, which can be further used in a t-test for parameter. Unbiasedness and efficiency for estimating variance components and predicting genetic effects are tested by Monte Carlo simulations.

Comparison of direct and heterodyne detection optical intersatellite communication links

NASA Technical Reports Server (NTRS)

Chen, C. C.; Gardner, C. S.

1987-01-01

The performance of direct and heterodyne detection optical intersatellite communication links are evaluated and compared. It is shown that the performance of optical links is very sensitive to the pointing and tracking errors at the transmitter and receiver. In the presence of random pointing and tracking errors, optimal antenna gains exist that will minimize the required transmitter power. In addition to limiting the antenna gains, random pointing and tracking errors also impose a power penalty in the link budget. This power penalty is between 1.6 to 3 dB for a direct detection QPPM link, and 3 to 5 dB for a heterodyne QFSK system. For the heterodyne systems, the carrier phase noise presents another major factor of performance degradation that must be considered. In contrast, the loss due to synchronization error is small. The link budgets for direct and heterodyne detection systems are evaluated. It is shown that, for systems with large pointing and tracking errors, the link budget is dominated by the spatial tracking error, and the direct detection system shows a superior performance because it is less sensitive to the spatial tracking error. On the other hand, for systems with small pointing and tracking jitters, the antenna gains are in general limited by the launch cost, and suboptimal antenna gains are often used in practice. In which case, the heterodyne system has a slightly higher power margin because of higher receiver sensitivity.

General model for the pointing error analysis of Risley-prism system based on ray direction deviation in light refraction

NASA Astrophysics Data System (ADS)

Zhang, Hao; Yuan, Yan; Su, Lijuan; Huang, Fengzhen; Bai, Qing

2016-09-01

The Risley-prism-based light beam steering apparatus delivers superior pointing accuracy and it is used in imaging LIDAR and imaging microscopes. A general model for pointing error analysis of the Risley prisms is proposed in this paper, based on ray direction deviation in light refraction. This model captures incident beam deviation, assembly deflections, and prism rotational error. We derive the transmission matrixes of the model firstly. Then, the independent and cumulative effects of different errors are analyzed through this model. Accuracy study of the model shows that the prediction deviation of pointing error for different error is less than 4.1×10-5° when the error amplitude is 0.1°. Detailed analyses of errors indicate that different error sources affect the pointing accuracy to varying degree, and the major error source is the incident beam deviation. The prism tilting has a relative big effect on the pointing accuracy when prism tilts in the principal section. The cumulative effect analyses of multiple errors represent that the pointing error can be reduced by tuning the bearing tilting in the same direction. The cumulative effect of rotational error is relative big when the difference of these two prism rotational angles equals 0 or π, while it is relative small when the difference equals π/2. The novelty of these results suggests that our analysis can help to uncover the error distribution and aid in measurement calibration of Risley-prism systems.

Methods and apparatus for reducing peak wind turbine loads

DOEpatents

Moroz, Emilian Mieczyslaw

2007-02-13

A method for reducing peak loads of wind turbines in a changing wind environment includes measuring or estimating an instantaneous wind speed and direction at the wind turbine and determining a yaw error of the wind turbine relative to the measured instantaneous wind direction. The method further includes comparing the yaw error to a yaw error trigger that has different values at different wind speeds and shutting down the wind turbine when the yaw error exceeds the yaw error trigger corresponding to the measured or estimated instantaneous wind speed.

Inclusion of the fitness sharing technique in an evolutionary algorithm to analyze the fitness landscape of the genetic code adaptability.

PubMed

Santos, José; Monteagudo, Ángel

2017-03-27

The canonical code, although prevailing in complex genomes, is not universal. It was shown the canonical genetic code superior robustness compared to random codes, but it is not clearly determined how it evolved towards its current form. The error minimization theory considers the minimization of point mutation adverse effect as the main selection factor in the evolution of the code. We have used simulated evolution in a computer to search for optimized codes, which helps to obtain information about the optimization level of the canonical code in its evolution. A genetic algorithm searches for efficient codes in a fitness landscape that corresponds with the adaptability of possible hypothetical genetic codes. The lower the effects of errors or mutations in the codon bases of a hypothetical code, the more efficient or optimal is that code. The inclusion of the fitness sharing technique in the evolutionary algorithm allows the extent to which the canonical genetic code is in an area corresponding to a deep local minimum to be easily determined, even in the high dimensional spaces considered. The analyses show that the canonical code is not in a deep local minimum and that the fitness landscape is not a multimodal fitness landscape with deep and separated peaks. Moreover, the canonical code is clearly far away from the areas of higher fitness in the landscape. Given the non-presence of deep local minima in the landscape, although the code could evolve and different forces could shape its structure, the fitness landscape nature considered in the error minimization theory does not explain why the canonical code ended its evolution in a location which is not an area of a localized deep minimum of the huge fitness landscape.

The effect of saccade metrics on the corollary discharge contribution to perceived eye location

PubMed Central

Bansal, Sonia; Jayet Bray, Laurence C.; Peterson, Matthew S.

2015-01-01

Corollary discharge (CD) is hypothesized to provide the movement information (direction and amplitude) required to compensate for the saccade-induced disruptions to visual input. Here, we investigated to what extent these conveyed metrics influence perceptual stability in human subjects with a target-displacement detection task. Subjects made saccades to targets located at different amplitudes (4°, 6°, or 8°) and directions (horizontal or vertical). During the saccade, the target disappeared and then reappeared at a shifted location either in the same direction or opposite to the movement vector. Subjects reported the target displacement direction, and from these reports we determined the perceptual threshold for shift detection and estimate of target location. Our results indicate that the thresholds for all amplitudes and directions generally scaled with saccade amplitude. Additionally, subjects on average produced hypometric saccades with an estimated CD gain <1. Finally, we examined the contribution of different error signals to perceptual performance, the saccade error (movement-to-movement variability in saccade amplitude) and visual error (distance between the fovea and the shifted target location). Perceptual judgment was not influenced by the fluctuations in movement amplitude, and performance was largely the same across movement directions for different magnitudes of visual error. Importantly, subjects reported the correct direction of target displacement above chance level for very small visual errors (<0.75°), even when these errors were opposite the target-shift direction. Collectively, these results suggest that the CD-based compensatory mechanisms for visual disruptions are highly accurate and comparable for saccades with different metrics. PMID:25761955

Direct-to-consumer sales of genetic services on the Internet.

PubMed

Gollust, Sarah E; Wilfond, Benjamin S; Hull, Sara Chandros

2003-01-01

PURPOSE The increasing use of the Internet to obtain genetics information and to order medical services without a prescription, combined with a rise in direct-to-consumer marketing for genetic testing, suggests the potential for the Internet to be used to sell genetic services. METHODS A systematic World Wide Web search was conducted in May 2002 to assess the availability of genetic services sold directly to consumers on the Internet. RESULTS Out of 105 sites that offered genetic services directly, most offered non-health-related services, including parentage confirmation testing (83%), identity testing (56%), and DNA banking (24%); however, health-related genetic tests were offered through 14 sites (13%). The health-related genetic tests available ranged from standard tests, such as hemochromatosis and cystic fibrosis, to more unconventional tests related to nutrition, behavior, and aging. Of these 14 sites, 5 described risks associated with the genetic services and 6 described the availability of counseling. CONCLUSIONS The availability of direct sales of health-related genetic tests creates the potential for inadequate pretest decision making, misunderstanding test results, and access to tests of questionable clinical value.

Direct-to-consumer sales of genetic services on the Internet

PubMed Central

Gollust, Sarah E.; Wilfond, Benjamin S.; Hull, Sara Chandros

2016-01-01

Purpose The increasing use of the Internet to obtain genetics information and to order medical services without a prescription, combined with a rise in direct-to-consumer marketing for genetic testing, suggests the potential for the Internet to be used to sell genetic services. Methods A systematic World Wide Web search was conducted in May 2002 to assess the availability of genetic services sold directly to consumers on the Internet. Results Out of 105 sites that offered genetic services directly, most offered non–health-related services, including parentage confirmation testing (83%), identity testing (56%), and DNA banking (24%); however, health-related genetic tests were offered through 14 sites (13%). The health-related genetic tests available ranged from standard tests, such as hemochromatosis and cystic fibrosis, to more unconventional tests related to nutrition, behavior, and aging. Of these 14 sites, 5 described risks associated with the genetic services and 6 described the availability of counseling. Conclusions The availability of direct sales of health-related genetic tests creates the potential for inadequate pretest decision making, misunderstanding test results, and access to tests of questionable clinical value. PMID:12865763

Problems with the Use of Terminology in Genetics Education: 1, A Literature Review and Classification Scheme.

ERIC Educational Resources Information Center

Pearson, J. T.; Hughes, W. J.

1988-01-01

Examines the technical vocabulary of genetics as a source of error and confusion. Suggests that it is necessary to identify different types of problems associated with terminology and to organize them into logical classes to deal effectively with the difficulties. Highlights terms misused in textbooks. (RT)

Nature, Nurture, and Attention Deficit Hyperactivity Disorder.

ERIC Educational Resources Information Center

Faraone, Stephen V.; Biederman, Joseph

2000-01-01

Comments on Joseph's review of the genetics of attention deficit disorder, demonstrating errors of scientific logic and oversight of relevant research in Joseph's argument. Argues for the validity of twin studies in supporting a genetic link for ADHD and for the complementary role of nature and nurture in the etiology of the disorder. (JPB)

Economic selection index development for Beefmaster cattle II: General-purpose breeding objective.

PubMed

Ochsner, K P; MacNeil, M D; Lewis, R M; Spangler, M L

2017-05-01

An economic selection index was developed for Beefmaster cattle in a general-purpose production system in which bulls are mated to a combination of heifers and mature cows, with resulting progeny retained as replacements or sold at weaning. National average prices from 2010 to 2014 were used to establish income and expenses for the system. Genetic parameters were obtained from the literature. Economic values were estimated by simulating 100,000 animals and approximating the partial derivatives of the profit function by perturbing traits 1 at a time, by 1 unit, while holding the other traits constant at their respective means. Relative economic values for the objective traits calving difficultly direct (CDd), calving difficulty maternal (CDm), weaning weight direct (WWd), weaning weight maternal (WWm), mature cow weight (MW), and heifer pregnancy (HP) were -2.11, -1.53, 18.49, 11.28, -33.46, and 1.19, respectively. Consequently, under the scenario assumed herein, the greatest improvements in profitability could be made by decreasing maintenance energy costs associated with MW followed by improvements in weaning weight. The accuracy of the index lies between 0.218 (phenotypic-based index selection) and 0.428 (breeding values known without error). Implementation of this index would facilitate genetic improvement and increase profitability of Beefmaster cattle operations with a general-purpose breeding objective when replacement females are retained and with weaned calves as the sale end point.

A geometricla error in some Computer Programs based on the Aki-Christofferson-Husebye (ACH) Method of Teleseismic Tomography

USGS Publications Warehouse

Julian, B.R.; Evans, J.R.; Pritchard, M.J.; Foulger, G.R.

2000-01-01

Some computer programs based on the Aki-Christofferson-Husebye (ACH) method of teleseismic tomography contain an error caused by identifying local grid directions with azimuths on the spherical Earth. This error, which is most severe in high latitudes, introduces systematic errors into computed ray paths and distorts inferred Earth models. It is best dealt with by explicity correcting for the difference between true and grid directions. Methods for computing these directions are presented in this article and are likely to be useful in many other kinds of regional geophysical studies that use Cartesian coordinates and flat-earth approximations.

Epigenetics as an answer to Darwin’s “special difficulty,” Part 2: natural selection of metastable epialleles in honeybee castes

PubMed Central

Ruden, Douglas M.; Cingolani, Pablo E.; Sen, Arko; Qu, Wen; Wang, Luan; Senut, Marie-Claude; Garfinkel, Mark D.; Sollars, Vincent E.; Lu, Xiangyi

2015-01-01

In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mechanism to circumvent Charles Darwin’s “special difficulty” in using natural selection to explain the existence of the sterile-fertile dimorphism in eusocial insects. Darwin’s classic book “On the Origin of Species by Means of Natural Selection” explains how natural selection of the fittest individuals in a population can allow a species to adapt to a novel or changing environment. However, in bees and other eusocial insects, such as ants and termites, there exist two or more castes of genetically similar females, from fertile queens to multiple sub-castes of sterile workers, with vastly different phenotypes, lifespans, and behaviors. This necessitates the selection of groups (or kin) rather than individuals in the evolution of honeybee hives, but group and kin selection theories of evolution are controversial and mechanistically uncertain. Also, group selection would seem to be prohibitively inefficient because the effective population size of a colony is reduced from thousands to a single breeding queen. In this follow-up perspective, we elaborate on possible mechanisms for how a combination of both epigenetics, specifically, the selection of metastable epialleles, and genetics, the selection of mutations generated by the selected metastable epialleles, allows for a combined means for selection amongst the fertile members of a species to increase colony fitness. This “intra-caste evolution” hypothesis is a variation of the epigenetic directed genetic error hypothesis, which proposes that selected metastable epialleles increase genetic variability by directing mutations specifically to the epialleles. Natural selection of random metastable epialleles followed by a second round of natural selection of random mutations generated by the metastable epialleles would allow a way around the small effective population size of eusocial insects. PMID:25759717

A defect in homologous recombination leads to increased translesion synthesis in E. coli

PubMed Central

Naiman, Karel; Pagès, Vincent; Fuchs, Robert P.

2016-01-01

DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli. In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the ‘SOS signal’. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination. PMID:27257075

Modeling the directivity of parametric loudspeaker

NASA Astrophysics Data System (ADS)

Shi, Chuang; Gan, Woon-Seng

2012-09-01

The emerging applications of the parametric loudspeaker, such as 3D audio, demands accurate directivity control at the audible frequency (i.e. the difference frequency). Though the delay-and-sum beamforming has been proven adequate to adjust the steering angles of the parametric loudspeaker, accurate prediction of the mainlobe and sidelobes remains a challenging problem. It is mainly because of the approximations that are used to derive the directivity of the difference frequency from the directivity of the primary frequency, and the mismatches between the theoretical directivity and the measured directivity caused by system errors incurred at different stages of the implementation. In this paper, we propose a directivity model of the parametric loudspeaker. The directivity model consists of two tuning vectors corresponding to the spacing error and the weight error for the primary frequency. The directivity model adopts a modified form of the product directivity principle for the difference frequency to further improve the modeling accuracy.

Function of the Plant DNA Polymerase Epsilon in Replicative Stress Sensing, a Genetic Analysis.

PubMed

Pedroza-García, José-Antonio; Mazubert, Christelle; Del Olmo, Ivan; Bourge, Mickael; Domenichini, Séverine; Bounon, Rémi; Tariq, Zakia; Delannoy, Etienne; Piñeiro, Manuel; Jarillo, José A; Bergounioux, Catherine; Benhamed, Moussa; Raynaud, Cécile

2017-03-01

Faithful transmission of the genetic information is essential in all living organisms. DNA replication is therefore a critical step of cell proliferation, because of the potential occurrence of replication errors or DNA damage when progression of a replication fork is hampered causing replicative stress. Like other types of DNA damage, replicative stress activates the DNA damage response, a signaling cascade allowing cell cycle arrest and repair of lesions. The replicative DNA polymerase ε (Pol ε) was shown to activate the S-phase checkpoint in yeast in response to replicative stress, but whether this mechanism functions in multicellular eukaryotes remains unclear. Here, we explored the genetic interaction between Pol ε and the main elements of the DNA damage response in Arabidopsis ( Arabidopsis thaliana ). We found that mutations affecting the polymerase domain of Pol ε trigger ATR-dependent signaling leading to SOG1 activation, WEE1-dependent cell cycle inhibition, and tolerance to replicative stress induced by hydroxyurea, but result in enhanced sensitivity to a wide range of DNA damaging agents. Using knock-down lines, we also provide evidence for the direct role of Pol ε in replicative stress sensing. Together, our results demonstrate that the role of Pol ε in replicative stress sensing is conserved in plants, and provide, to our knowledge, the first genetic dissection of the downstream signaling events in a multicellular eukaryote. © 2017 American Society of Plant Biologists. All Rights Reserved.

Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation

PubMed Central

Nikolaitchik, Olga A.; Burdick, Ryan C.; Gorelick, Robert J.; Keele, Brandon F.; Hu, Wei-Shau; Pathak, Vinay K.

2016-01-01

Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10−5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10−21 and1 × 10−11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic variation is substantially lower than that from mutations during error-prone replication. PMID:27186986

Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

PubMed

Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C; Gorelick, Robert J; Keele, Brandon F; Hu, Wei-Shau; Pathak, Vinay K

2016-05-01

Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic variation is substantially lower than that from mutations during error-prone replication.

Scientific Impacts of Wind Direction Errors

NASA Technical Reports Server (NTRS)

Liu, W. Timothy; Kim, Seung-Bum; Lee, Tong; Song, Y. Tony; Tang, Wen-Qing; Atlas, Robert

2004-01-01

An assessment on the scientific impact of random errors in wind direction (less than 45 deg) retrieved from space-based observations under weak wind (less than 7 m/s ) conditions was made. averages, and these weak winds cover most of the tropical, sub-tropical, and coastal oceans. Introduction of these errors in the semi-daily winds causes, on average, 5% changes of the yearly mean Ekman and Sverdrup volume transports computed directly from the winds, respectively. These poleward movements of water are the main mechanisms to redistribute heat from the warmer tropical region to the colder high- latitude regions, and they are the major manifestations of the ocean's function in modifying Earth's climate. Simulation by an ocean general circulation model shows that the wind errors introduce a 5% error in the meridional heat transport at tropical latitudes. The simulation also shows that the erroneous winds cause a pile-up of warm surface water in the eastern tropical Pacific, similar to the conditions during El Nino episode. Similar wind directional errors cause significant change in sea-surface temperature and sea-level patterns in coastal oceans in a coastal model simulation. Previous studies have shown that assimilation of scatterometer winds improves 3-5 day weather forecasts in the Southern Hemisphere. When directional information below 7 m/s was withheld, approximately 40% of the improvement was lost

Genetic programs constructed from layered logic gates in single cells

PubMed Central

Moon, Tae Seok; Lou, Chunbo; Tamsir, Alvin; Stanton, Brynne C.; Voigt, Christopher A.

2014-01-01

Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics1. These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits2–6, and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits1,7. Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator–chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directed evolution is applied to increase the dynamic range and orthogonality of the circuits. These gates are connected in different permutations to form programs, the largest of which is a 4-input AND gate that consists of 3 circuits that integrate 4 inducible systems, thus requiring 11 regulatory proteins. Measuring the performance of individual gates is sufficient to capture the behaviour of the complete program. Errors in the output due to delays (faults), a common problem for layered circuits, are not observed. This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells. PMID:23041931

Direct-to-consumer genetic testing: where and how does genetic counseling fit?

PubMed

Middleton, Anna; Mendes, Álvaro; Benjamin, Caroline M; Howard, Heidi Carmen

2017-05-01

Direct-to-consumer genetic testing for disease ranges from well-validated diagnostic and predictive tests to 'research' results conferring increased risks. While being targeted at public curious about their health, they are also marketed for use in reproductive decision-making or management of disease. By virtue of being 'direct-to-consumer' much of this testing bypasses traditional healthcare systems. We argue that direct-to-consumer genetic testing companies should make genetic counseling available, pre- as well as post-test. While we do not advocate that mandatory genetic counseling should gate-keep access to direct-to-consumer genetic testing, if the testing process has the potential to cause psychological distress, then companies have a responsibility to provide support and should not rely on traditional healthcare systems to pick up the pieces. A video abstract is available for this article via this link .

A report template for molecular genetic tests designed to improve communication between the clinician and laboratory.

PubMed

Scheuner, Maren T; Hilborne, Lee; Brown, Julie; Lubin, Ira M

2012-07-01

Errors are most likely to occur during the pre- and postanalytic phases of the genetic testing process, which can contribute to underuse, overuse, and misuse of genetic tests. To mitigate these errors, we created a template for molecular genetic test reports that utilizes the combined features of synoptic reporting and narrative interpretation. A variation of the Delphi consensus process with an expert panel was used to create a draft report template, which was further informed by focus group discussions with primary care physicians. There was agreement that molecular genetic test reports should present information in groupings that flow in a logical manner, and most participants preferred the following order of presentation: patient and physician information, test performed, test results and interpretation, guidance on next steps, and supplemental information. We define data elements for the report as "required," "optional," "possible," and "not necessary"; provide recommendations regarding the grouping of these data elements; and describe the ideal design of the report template, including the preferred order of the report sections, formatting of data, and length of the report. With input from key stakeholders and building upon prior work, we created a template for molecular genetic test reports designed to improve clinical decision making at the point of care. The template design should lead to more effective communication between the laboratory and ordering clinician. Studies are needed to assess the usefulness and effectiveness of molecular genetic test reports generated using this template.

MetaGenyo: a web tool for meta-analysis of genetic association studies.

PubMed

Martorell-Marugan, Jordi; Toro-Dominguez, Daniel; Alarcon-Riquelme, Marta E; Carmona-Saez, Pedro

2017-12-16

Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise. We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results. MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/ .

Approximate error conjugation gradient minimization methods

DOEpatents

Kallman, Jeffrey S

2013-05-21

In one embodiment, a method includes selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, calculating an approximate error using the subset of rays, and calculating a minimum in a conjugate gradient direction based on the approximate error. In another embodiment, a system includes a processor for executing logic, logic for selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, logic for calculating an approximate error using the subset of rays, and logic for calculating a minimum in a conjugate gradient direction based on the approximate error. In other embodiments, computer program products, methods, and systems are described capable of using approximate error in constrained conjugate gradient minimization problems.

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.

PubMed

Li, Qing; Wojciechowski, Robert; Simpson, Claire L; Hysi, Pirro G; Verhoeven, Virginie J M; Ikram, Mohammad Kamran; Höhn, René; Vitart, Veronique; Hewitt, Alex W; Oexle, Konrad; Mäkelä, Kari-Matti; MacGregor, Stuart; Pirastu, Mario; Fan, Qiao; Cheng, Ching-Yu; St Pourcain, Beaté; McMahon, George; Kemp, John P; Northstone, Kate; Rahi, Jugnoo S; Cumberland, Phillippa M; Martin, Nicholas G; Sanfilippo, Paul G; Lu, Yi; Wang, Ya Xing; Hayward, Caroline; Polašek, Ozren; Campbell, Harry; Bencic, Goran; Wright, Alan F; Wedenoja, Juho; Zeller, Tanja; Schillert, Arne; Mirshahi, Alireza; Lackner, Karl; Yip, Shea Ping; Yap, Maurice K H; Ried, Janina S; Gieger, Christian; Murgia, Federico; Wilson, James F; Fleck, Brian; Yazar, Seyhan; Vingerling, Johannes R; Hofman, Albert; Uitterlinden, André; Rivadeneira, Fernando; Amin, Najaf; Karssen, Lennart; Oostra, Ben A; Zhou, Xin; Teo, Yik-Ying; Tai, E Shyong; Vithana, Eranga; Barathi, Veluchamy; Zheng, Yingfeng; Siantar, Rosalynn Grace; Neelam, Kumari; Shin, Youchan; Lam, Janice; Yonova-Doing, Ekaterina; Venturini, Cristina; Hosseini, S Mohsen; Wong, Hoi-Suen; Lehtimäki, Terho; Kähönen, Mika; Raitakari, Olli; Timpson, Nicholas J; Evans, David M; Khor, Chiea-Chuen; Aung, Tin; Young, Terri L; Mitchell, Paul; Klein, Barbara; van Duijn, Cornelia M; Meitinger, Thomas; Jonas, Jost B; Baird, Paul N; Mackey, David A; Wong, Tien Yin; Saw, Seang-Mei; Pärssinen, Olavi; Stambolian, Dwight; Hammond, Christopher J; Klaver, Caroline C W; Williams, Cathy; Paterson, Andrew D; Bailey-Wilson, Joan E; Guggenheim, Jeremy A

2015-02-01

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Cognitive performance and BMI in childhood: Shared genetic influences between reaction time but not response inhibition

USDA-ARS?s Scientific Manuscript database

The aim of this work is to understand whether shared genetic influences can explain the associationbetween obesity and cognitive performance, including slower and more variable reaction times(RTs) and worse response inhibition. RT on a four-choice RT task and the go/no-go task, and commission errors...

Genetics Home Reference: Lynch syndrome

MedlinePlus

... or EPCAM gene increase the risk of developing Lynch syndrome . The MLH1 , MSH2 , MSH6 , and PMS2 genes are involved in the repair of errors that ... B, Eisinger F, Hutter P, Olschwang S. Clinical utility gene card for: Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) - update 2012. Eur J Hum Genet. 2013 ...

Genetic screening: programs, principles, and research--thirty years later. Reviewing the recommendations of the Committee for the Study of Inborn Errors of Metabolism (SIEM).

PubMed

Simopoulos, A P

2009-01-01

Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. 'Genetic Screening: Programs, Principles, and Research' is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee's modus operandi and bring the Committee's recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee's report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: 'As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.' What a prophetic statement that was. If the Committee's recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information. Copyright 2008 S. Karger AG, Basel.

Characterizing the SWOT discharge error budget on the Sacramento River, CA

NASA Astrophysics Data System (ADS)

Yoon, Y.; Durand, M. T.; Minear, J. T.; Smith, L.; Merry, C. J.

2013-12-01

The Surface Water and Ocean Topography (SWOT) is an upcoming satellite mission (2020 year) that will provide surface-water elevation and surface-water extent globally. One goal of SWOT is the estimation of river discharge directly from SWOT measurements. SWOT discharge uncertainty is due to two sources. First, SWOT cannot measure channel bathymetry and determine roughness coefficient data necessary for discharge calculations directly; these parameters must be estimated from the measurements or from a priori information. Second, SWOT measurement errors directly impact the discharge estimate accuracy. This study focuses on characterizing parameter and measurement uncertainties for SWOT river discharge estimation. A Bayesian Markov Chain Monte Carlo scheme is used to calculate parameter estimates, given the measurements of river height, slope and width, and mass and momentum constraints. The algorithm is evaluated using simulated both SWOT and AirSWOT (the airborne version of SWOT) observations over seven reaches (about 40 km) of the Sacramento River. The SWOT and AirSWOT observations are simulated by corrupting the ';true' HEC-RAS hydraulic modeling results with the instrument error. This experiment answers how unknown bathymetry and roughness coefficients affect the accuracy of the river discharge algorithm. From the experiment, the discharge error budget is almost completely dominated by unknown bathymetry and roughness; 81% of the variance error is explained by uncertainties in bathymetry and roughness. Second, we show how the errors in water surface, slope, and width observations influence the accuracy of discharge estimates. Indeed, there is a significant sensitivity to water surface, slope, and width errors due to the sensitivity of bathymetry and roughness to measurement errors. Increasing water-surface error above 10 cm leads to a corresponding sharper increase of errors in bathymetry and roughness. Increasing slope error above 1.5 cm/km leads to a significant degradation due to direct error in the discharge estimates. As the width error increases past 20%, the discharge error budget is dominated by the width error. Above two experiments are performed based on AirSWOT scenarios. In addition, we explore the sensitivity of the algorithm to the SWOT scenarios.

Rare disease landscape in Brazil: report of a successful experience in inborn errors of metabolism.

PubMed

Giugliani, Roberto; Vairo, Filippo P; Riegel, Mariluce; de Souza, Carolina F M; Schwartz, Ida V D; Pena, Sérgio D J

2016-06-10

Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the "Policy for the Integral Attention to Subjects with Rare Diseases", establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center.

Powerful Inference with the D-Statistic on Low-Coverage Whole-Genome Data

PubMed Central

Soraggi, Samuele; Wiuf, Carsten; Albrechtsen, Anders

2017-01-01

The detection of ancient gene flow between human populations is an important issue in population genetics. A common tool for detecting ancient admixture events is the D-statistic. The D-statistic is based on the hypothesis of a genetic relationship that involves four populations, whose correctness is assessed by evaluating specific coincidences of alleles between the groups. When working with high-throughput sequencing data, calling genotypes accurately is not always possible; therefore, the D-statistic currently samples a single base from the reads of one individual per population. This implies ignoring much of the information in the data, an issue especially striking in the case of ancient genomes. We provide a significant improvement to overcome the problems of the D-statistic by considering all reads from multiple individuals in each population. We also apply type-specific error correction to combat the problems of sequencing errors, and show a way to correct for introgression from an external population that is not part of the supposed genetic relationship, and how this leads to an estimate of the admixture rate. We prove that the D-statistic is approximated by a standard normal distribution. Furthermore, we show that our method outperforms the traditional D-statistic in detecting admixtures. The power gain is most pronounced for low and medium sequencing depth (1–10×), and performances are as good as with perfectly called genotypes at a sequencing depth of 2×. We show the reliability of error correction in scenarios with simulated errors and ancient data, and correct for introgression in known scenarios to estimate the admixture rates. PMID:29196497

Clinical Metabolomics: The New Metabolic Window for Inborn Errors of Metabolism Investigations in the Post-Genomic Era

PubMed Central

Tebani, Abdellah; Abily-Donval, Lenaig; Afonso, Carlos; Marret, Stéphane; Bekri, Soumeya

2016-01-01

Inborn errors of metabolism (IEM) represent a group of about 500 rare genetic diseases with an overall estimated incidence of 1/2500. The diversity of metabolic pathways involved explains the difficulties in establishing their diagnosis. However, early diagnosis is usually mandatory for successful treatment. Given the considerable clinical overlap between some inborn errors, biochemical and molecular tests are crucial in making a diagnosis. Conventional biological diagnosis procedures are based on a time-consuming series of sequential and segmented biochemical tests. The rise of “omic” technologies offers holistic views of the basic molecules that build a biological system at different levels. Metabolomics is the most recent “omic” technology based on biochemical characterization of metabolites and their changes related to genetic and environmental factors. This review addresses the principles underlying metabolomics technologies that allow them to comprehensively assess an individual biochemical profile and their reported applications for IEM investigations in the precision medicine era. PMID:27447622

Comparison of genetic algorithm and imperialist competitive algorithms in predicting bed load transport in clean pipe.

PubMed

Ebtehaj, Isa; Bonakdari, Hossein

2014-01-01

The existence of sediments in wastewater greatly affects the performance of the sewer and wastewater transmission systems. Increased sedimentation in wastewater collection systems causes problems such as reduced transmission capacity and early combined sewer overflow. The article reviews the performance of the genetic algorithm (GA) and imperialist competitive algorithm (ICA) in minimizing the target function (mean square error of observed and predicted Froude number). To study the impact of bed load transport parameters, using four non-dimensional groups, six different models have been presented. Moreover, the roulette wheel selection method is used to select the parents. The ICA with root mean square error (RMSE) = 0.007, mean absolute percentage error (MAPE) = 3.5% show better results than GA (RMSE = 0.007, MAPE = 5.6%) for the selected model. All six models return better results than the GA. Also, the results of these two algorithms were compared with multi-layer perceptron and existing equations.

Internally-generated error signals in monkey frontal eye field during an inferred motion task

PubMed Central

Ferrera, Vincent P.; Barborica, Andrei

2010-01-01

An internal model for predictive saccades in frontal cortex was investigated by recording neurons in monkey frontal eye field during an inferred motion task. Monkeys were trained to make saccades to the extrapolated position of a small moving target that was rendered temporarily invisible and whose trajectory was altered. On roughly two-thirds of the trials, monkeys made multiple saccades while the target was invisible. Primary saccades were correlated with extrapolated target position. Secondary saccades significantly reduced residual errors resulting from imperfect accuracy of the first saccade. These observations suggest that the second saccade was corrective. As there was no visual feedback, corrective saccades could only be driven by an internally generated error signal. Neuronal activity in the frontal eye field was directionally tuned prior to both primary and secondary saccades. Separate subpopulations of cells encoded either saccade direction or direction error prior to the second saccade. These results suggest that FEF neurons encode the error after the first saccade, as well as the direction of the second saccade. Hence, FEF appears to contribute to detecting and correcting movement errors based on internally generated signals. PMID:20810882

Data driven CAN node reliability assessment for manufacturing system

NASA Astrophysics Data System (ADS)

Zhang, Leiming; Yuan, Yong; Lei, Yong

2017-01-01

The reliability of the Controller Area Network(CAN) is critical to the performance and safety of the system. However, direct bus-off time assessment tools are lacking in practice due to inaccessibility of the node information and the complexity of the node interactions upon errors. In order to measure the mean time to bus-off(MTTB) of all the nodes, a novel data driven node bus-off time assessment method for CAN network is proposed by directly using network error information. First, the corresponding network error event sequence for each node is constructed using multiple-layer network error information. Then, the generalized zero inflated Poisson process(GZIP) model is established for each node based on the error event sequence. Finally, the stochastic model is constructed to predict the MTTB of the node. The accelerated case studies with different error injection rates are conducted on a laboratory network to demonstrate the proposed method, where the network errors are generated by a computer controlled error injection system. Experiment results show that the MTTB of nodes predicted by the proposed method agree well with observations in the case studies. The proposed data driven node time to bus-off assessment method for CAN networks can successfully predict the MTTB of nodes by directly using network error event data.

Geolocation error tracking of ZY-3 three line cameras

NASA Astrophysics Data System (ADS)

Pan, Hongbo

2017-01-01

The high-accuracy geolocation of high-resolution satellite images (HRSIs) is a key issue for mapping and integrating multi-temporal, multi-sensor images. In this manuscript, we propose a new geometric frame for analysing the geometric error of a stereo HRSI, in which the geolocation error can be divided into three parts: the epipolar direction, cross base direction, and height direction. With this frame, we proved that the height error of three line cameras (TLCs) is independent of nadir images, and that the terrain effect has a limited impact on the geolocation errors. For ZY-3 error sources, the drift error in both the pitch and roll angle and its influence on the geolocation accuracy are analysed. Epipolar and common tie-point constraints are proposed to study the bundle adjustment of HRSIs. Epipolar constraints explain that the relative orientation can reduce the number of compensation parameters in the cross base direction and have a limited impact on the height accuracy. The common tie points adjust the pitch-angle errors to be consistent with each other for TLCs. Therefore, free-net bundle adjustment of a single strip cannot significantly improve the geolocation accuracy. Furthermore, the epipolar and common tie-point constraints cause the error to propagate into the adjacent strip when multiple strips are involved in the bundle adjustment, which results in the same attitude uncertainty throughout the whole block. Two adjacent strips-Orbit 305 and Orbit 381, covering 7 and 12 standard scenes separately-and 308 ground control points (GCPs) were used for the experiments. The experiments validate the aforementioned theory. The planimetric and height root mean square errors were 2.09 and 1.28 m, respectively, when two GCPs were settled at the beginning and end of the block.

Poster - 49: Assessment of Synchrony respiratory compensation error for CyberKnife liver treatment

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

Liu, Ming; Cygler,

The goal of this work is to quantify respiratory motion compensation errors for liver tumor patients treated by the CyberKnife system with Synchrony tracking, to identify patients with the smallest tracking errors and to eventually help coach patient’s breathing patterns to minimize dose delivery errors. The accuracy of CyberKnife Synchrony respiratory motion compensation was assessed for 37 patients treated for liver lesions by analyzing data from system logfiles. A predictive model is used to modulate the direction of individual beams during dose delivery based on the positions of internally implanted fiducials determined using an orthogonal x-ray imaging system and themore » current location of LED external markers. For each x-ray pair acquired, system logfiles report the prediction error, the difference between the measured and predicted fiducial positions, and the delivery error, which is an estimate of the statistical error in the model overcoming the latency between x-ray acquisition and robotic repositioning. The total error was calculated at the time of each x-ray pair, for the number of treatment fractions and the number of patients, giving the average respiratory motion compensation error in three dimensions. The 99{sup th} percentile for the total radial error is 3.85 mm, with the highest contribution of 2.79 mm in superior/inferior (S/I) direction. The absolute mean compensation error is 1.78 mm radially with a 1.27 mm contribution in the S/I direction. Regions of high total error may provide insight into features predicting groups of patients with larger or smaller total errors.« less

Pointing control using a moving base of support.

PubMed

Hondzinski, Jan M; Kwon, Taegyong

2009-07-01

The purposes of this study were to determine whether gaze direction provides a control signal for movement direction for a pointing task requiring a step and to gain insight into why discrepancies previously identified in the literature for endpoint accuracy with gaze directed eccentrically exist. Straight arm pointing movements were performed to real and remembered target locations, either toward or 30 degrees eccentric to gaze direction. Pointing occurred in normal room lighting or darkness while subjects sat, stood still or side-stepped left or right. Trunk rotation contributed 22-65% to gaze orientations when it was not constrained. Error differences for different target locations explained discrepancies among previous experiments. Variable pointing errors were influenced by gaze direction, while mean systematic pointing errors and trunk orientations were influenced by step direction. These data support the use of a control strategy that relies on gaze direction and equilibrium inputs for whole-body goal-directed movements.

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.

Effects of a direct refill program for automated dispensing cabinets on medication-refill errors.

PubMed

Helmons, Pieter J; Dalton, Ashley J; Daniels, Charles E

2012-10-01

The effects of a direct refill program for automated dispensing cabinets (ADCs) on medication-refill errors were studied. This study was conducted in designated acute care areas of a 386-bed academic medical center. A wholesaler-to-ADC direct refill program, consisting of prepackaged delivery of medications and bar-code-assisted ADC refilling, was implemented in the inpatient pharmacy of the medical center in September 2009. Medication-refill errors in 26 ADCs from the general medicine units, the infant special care unit, the surgical and burn intensive care units, and intermediate units were assessed before and after the implementation of this program. Medication-refill errors were defined as an ADC pocket containing the wrong drug, wrong strength, or wrong dosage form. ADC refill errors decreased by 77%, from 62 errors per 6829 refilled pockets (0.91%) to 8 errors per 3855 refilled pockets (0.21%) (p < 0.0001). The predominant error type detected before the intervention was the incorrect medication (wrong drug, wrong strength, or wrong dosage form) in the ADC pocket. Of the 54 incorrect medications found before the intervention, 38 (70%) were loaded in a multiple-drug drawer. After the implementation of the new refill process, 3 of the 5 incorrect medications were loaded in a multiple-drug drawer. There were 3 instances of expired medications before and only 1 expired medication after implementation of the program. A redesign of the ADC refill process using a wholesaler-to-ADC direct refill program that included delivery of prepackaged medication and bar-code-assisted refill significantly decreased the occurrence of ADC refill errors.

Clover: Compiler directed lightweight soft error resilience

DOE PAGES

Liu, Qingrui; Lee, Dongyoon; Jung, Changhee; ...

2015-05-01

This paper presents Clover, a compiler directed soft error detection and recovery scheme for lightweight soft error resilience. The compiler carefully generates soft error tolerant code based on idem-potent processing without explicit checkpoint. During program execution, Clover relies on a small number of acoustic wave detectors deployed in the processor to identify soft errors by sensing the wave made by a particle strike. To cope with DUE (detected unrecoverable errors) caused by the sensing latency of error detection, Clover leverages a novel selective instruction duplication technique called tail-DMR (dual modular redundancy). Once a soft error is detected by either themore » sensor or the tail-DMR, Clover takes care of the error as in the case of exception handling. To recover from the error, Clover simply redirects program control to the beginning of the code region where the error is detected. Lastly, the experiment results demonstrate that the average runtime overhead is only 26%, which is a 75% reduction compared to that of the state-of-the-art soft error resilience technique.« less

Impact of time-of-flight on indirect 3D and direct 4D parametric image reconstruction in the presence of inconsistent dynamic PET data.

PubMed

Kotasidis, F A; Mehranian, A; Zaidi, H

2016-05-07

Kinetic parameter estimation in dynamic PET suffers from reduced accuracy and precision when parametric maps are estimated using kinetic modelling following image reconstruction of the dynamic data. Direct approaches to parameter estimation attempt to directly estimate the kinetic parameters from the measured dynamic data within a unified framework. Such image reconstruction methods have been shown to generate parametric maps of improved precision and accuracy in dynamic PET. However, due to the interleaving between the tomographic and kinetic modelling steps, any tomographic or kinetic modelling errors in certain regions or frames, tend to spatially or temporally propagate. This results in biased kinetic parameters and thus limits the benefits of such direct methods. Kinetic modelling errors originate from the inability to construct a common single kinetic model for the entire field-of-view, and such errors in erroneously modelled regions could spatially propagate. Adaptive models have been used within 4D image reconstruction to mitigate the problem, though they are complex and difficult to optimize. Tomographic errors in dynamic imaging on the other hand, can originate from involuntary patient motion between dynamic frames, as well as from emission/transmission mismatch. Motion correction schemes can be used, however, if residual errors exist or motion correction is not included in the study protocol, errors in the affected dynamic frames could potentially propagate either temporally, to other frames during the kinetic modelling step or spatially, during the tomographic step. In this work, we demonstrate a new strategy to minimize such error propagation in direct 4D image reconstruction, focusing on the tomographic step rather than the kinetic modelling step, by incorporating time-of-flight (TOF) within a direct 4D reconstruction framework. Using ever improving TOF resolutions (580 ps, 440 ps, 300 ps and 160 ps), we demonstrate that direct 4D TOF image reconstruction can substantially prevent kinetic parameter error propagation either from erroneous kinetic modelling, inter-frame motion or emission/transmission mismatch. Furthermore, we demonstrate the benefits of TOF in parameter estimation when conventional post-reconstruction (3D) methods are used and compare the potential improvements to direct 4D methods. Further improvements could possibly be achieved in the future by combining TOF direct 4D image reconstruction with adaptive kinetic models and inter-frame motion correction schemes.

Impact of time-of-flight on indirect 3D and direct 4D parametric image reconstruction in the presence of inconsistent dynamic PET data

NASA Astrophysics Data System (ADS)

Kotasidis, F. A.; Mehranian, A.; Zaidi, H.

2016-05-01

Kinetic parameter estimation in dynamic PET suffers from reduced accuracy and precision when parametric maps are estimated using kinetic modelling following image reconstruction of the dynamic data. Direct approaches to parameter estimation attempt to directly estimate the kinetic parameters from the measured dynamic data within a unified framework. Such image reconstruction methods have been shown to generate parametric maps of improved precision and accuracy in dynamic PET. However, due to the interleaving between the tomographic and kinetic modelling steps, any tomographic or kinetic modelling errors in certain regions or frames, tend to spatially or temporally propagate. This results in biased kinetic parameters and thus limits the benefits of such direct methods. Kinetic modelling errors originate from the inability to construct a common single kinetic model for the entire field-of-view, and such errors in erroneously modelled regions could spatially propagate. Adaptive models have been used within 4D image reconstruction to mitigate the problem, though they are complex and difficult to optimize. Tomographic errors in dynamic imaging on the other hand, can originate from involuntary patient motion between dynamic frames, as well as from emission/transmission mismatch. Motion correction schemes can be used, however, if residual errors exist or motion correction is not included in the study protocol, errors in the affected dynamic frames could potentially propagate either temporally, to other frames during the kinetic modelling step or spatially, during the tomographic step. In this work, we demonstrate a new strategy to minimize such error propagation in direct 4D image reconstruction, focusing on the tomographic step rather than the kinetic modelling step, by incorporating time-of-flight (TOF) within a direct 4D reconstruction framework. Using ever improving TOF resolutions (580 ps, 440 ps, 300 ps and 160 ps), we demonstrate that direct 4D TOF image reconstruction can substantially prevent kinetic parameter error propagation either from erroneous kinetic modelling, inter-frame motion or emission/transmission mismatch. Furthermore, we demonstrate the benefits of TOF in parameter estimation when conventional post-reconstruction (3D) methods are used and compare the potential improvements to direct 4D methods. Further improvements could possibly be achieved in the future by combining TOF direct 4D image reconstruction with adaptive kinetic models and inter-frame motion correction schemes.

Fourth order Douglas implicit scheme for solving three dimension reaction diffusion equation with non-linear source term

NASA Astrophysics Data System (ADS)

Hasnain, Shahid; Saqib, Muhammad; Mashat, Daoud Suleiman

2017-07-01

This research paper represents a numerical approximation to non-linear three dimension reaction diffusion equation with non-linear source term from population genetics. Since various initial and boundary value problems exist in three dimension reaction diffusion phenomena, which are studied numerically by different numerical methods, here we use finite difference schemes (Alternating Direction Implicit and Fourth Order Douglas Implicit) to approximate the solution. Accuracy is studied in term of L2, L∞ and relative error norms by random selected grids along time levels for comparison with analytical results. The test example demonstrates the accuracy, efficiency and versatility of the proposed schemes. Numerical results showed that Fourth Order Douglas Implicit scheme is very efficient and reliable for solving 3-D non-linear reaction diffusion equation.

Programmed Cell Death and Caspase Functions During Neural Development.

PubMed

Yamaguchi, Yoshifumi; Miura, Masayuki

2015-01-01

Programmed cell death (PCD) is a fundamental component of nervous system development. PCD serves as the mechanism for quantitative matching of the number of projecting neurons and their target cells through direct competition for neurotrophic factors in the vertebrate peripheral nervous system. In addition, PCD plays roles in regulating neural cell numbers, canceling developmental errors or noise, and tissue remodeling processes. These findings are mainly derived from genetic studies that prevent cells from dying by apoptosis, which is a major form of PCD and is executed by activation of evolutionarily conserved cysteine protease caspases. Recent studies suggest that caspase activation can be coordinated in time and space at multiple levels, which might underlie nonapoptotic roles of caspases in neural development in addition to apoptotic roles. © 2015 Elsevier Inc. All rights reserved.

Spatial averaging errors in creating hemispherical reflectance (albedo) maps from directional reflectance data

NASA Technical Reports Server (NTRS)

Kimes, D. S.; Kerber, A. G.; Sellers, P. J.

1993-01-01

Spatial averaging errors which may occur when creating hemispherical reflectance maps for different cover types from direct nadir technique to estimate the hemispherical reflectance are assessed by comparing the results with those obtained with a knowledge-based system called VEG (Kimes et al., 1991, 1992). It was found that hemispherical reflectance errors provided by using VEG are much less than those using the direct nadir techniques, depending on conditions. Suggestions are made concerning sampling and averaging strategies for creating hemispherical reflectance maps for photosynthetic, carbon cycle, and climate change studies.

Direction Dependent Effects In Widefield Wideband Full Stokes Radio Imaging

NASA Astrophysics Data System (ADS)

Jagannathan, Preshanth; Bhatnagar, Sanjay; Rau, Urvashi; Taylor, Russ

2015-01-01

Synthesis imaging in radio astronomy is affected by instrumental and atmospheric effects which introduce direction dependent gains.The antenna power pattern varies both as a function of time and frequency. The broad band time varying nature of the antenna power pattern when not corrected leads to gross errors in full stokes imaging and flux estimation. In this poster we explore the errors that arise in image deconvolution while not accounting for the time and frequency dependence of the antenna power pattern. Simulations were conducted with the wideband full stokes power pattern of the Very Large Array(VLA) antennas to demonstrate the level of errors arising from direction-dependent gains. Our estimate is that these errors will be significant in wide-band full-pol mosaic imaging as well and algorithms to correct these errors will be crucial for many up-coming large area surveys (e.g. VLASS)

Validation of simplified centre of mass models during gait in individuals with chronic stroke.

PubMed

Huntley, Andrew H; Schinkel-Ivy, Alison; Aqui, Anthony; Mansfield, Avril

2017-10-01

The feasibility of using a multiple segment (full-body) kinematic model in clinical gait assessment is difficult when considering obstacles such as time and cost constraints. While simplified gait models have been explored in healthy individuals, no such work to date has been conducted in a stroke population. The aim of this study was to quantify the errors of simplified kinematic models for chronic stroke gait assessment. Sixteen individuals with chronic stroke (>6months), outfitted with full body kinematic markers, performed a series of gait trials. Three centre of mass models were computed: (i) 13-segment whole-body model, (ii) 3 segment head-trunk-pelvis model, and (iii) 1 segment pelvis model. Root mean squared error differences were compared between models, along with correlations to measures of stroke severity. Error differences revealed that, while both models were similar in the mediolateral direction, the head-trunk-pelvis model had less error in the anteroposterior direction and the pelvis model had less error in the vertical direction. There was some evidence that the head-trunk-pelvis model error is influenced in the mediolateral direction for individuals with more severe strokes, as a few significant correlations were observed between the head-trunk-pelvis model and measures of stroke severity. These findings demonstrate the utility and robustness of the pelvis model for clinical gait assessment in individuals with chronic stroke. Low error in the mediolateral and vertical directions is especially important when considering potential stability analyses during gait for this population, as lateral stability has been previously linked to fall risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

VIPER: a visualisation tool for exploring inheritance inconsistencies in genotyped pedigrees

PubMed Central

2012-01-01

Background Pedigree genotype datasets are used for analysing genetic inheritance and to map genetic markers and traits. Such datasets consist of hundreds of related animals genotyped for thousands of genetic markers and invariably contain multiple errors in both the pedigree structure and in the associated individual genotype data. These errors manifest as apparent inheritance inconsistencies in the pedigree, and invalidate analyses of marker inheritance patterns across the dataset. Cleaning raw datasets of bad data points (incorrect pedigree relationships, unreliable marker assays, suspect samples, bad genotype results etc.) requires expert exploration of the patterns of exposed inconsistencies in the context of the inheritance pedigree. In order to assist this process we are developing VIPER (Visual Pedigree Explorer), a software tool that integrates an inheritance-checking algorithm with a novel space-efficient pedigree visualisation, so that reported inheritance inconsistencies are overlaid on an interactive, navigable representation of the pedigree structure. Methods and results This paper describes an evaluation of how VIPER displays the different scales and types of dataset that occur experimentally, with a description of how VIPER's display interface and functionality meet the challenges presented by such data. We examine a range of possible error types found in real and simulated pedigree genotype datasets, demonstrating how these errors are exposed and explored using the VIPER interface and we evaluate the utility and usability of the interface to the domain expert. Evaluation was performed as a two stage process with the assistance of domain experts (geneticists). The initial evaluation drove the iterative implementation of further features in the software prototype, as required by the users, prior to a final functional evaluation of the pedigree display for exploring the various error types, data scales and structures. Conclusions The VIPER display was shown to effectively expose the range of errors found in experimental genotyped pedigrees, allowing users to explore the underlying causes of reported inheritance inconsistencies. This interface will provide the basis for a full data cleaning tool that will allow the user to remove isolated bad data points, and reversibly test the effect of removing suspect genotypes and pedigree relationships. PMID:22607476

Applying Intelligent Algorithms to Automate the Identification of Error Factors.

PubMed

Jin, Haizhe; Qu, Qingxing; Munechika, Masahiko; Sano, Masataka; Kajihara, Chisato; Duffy, Vincent G; Chen, Han

2018-05-03

Medical errors are the manifestation of the defects occurring in medical processes. Extracting and identifying defects as medical error factors from these processes are an effective approach to prevent medical errors. However, it is a difficult and time-consuming task and requires an analyst with a professional medical background. The issues of identifying a method to extract medical error factors and reduce the extraction difficulty need to be resolved. In this research, a systematic methodology to extract and identify error factors in the medical administration process was proposed. The design of the error report, extraction of the error factors, and identification of the error factors were analyzed. Based on 624 medical error cases across four medical institutes in both Japan and China, 19 error-related items and their levels were extracted. After which, they were closely related to 12 error factors. The relational model between the error-related items and error factors was established based on a genetic algorithm (GA)-back-propagation neural network (BPNN) model. Additionally, compared to GA-BPNN, BPNN, partial least squares regression and support vector regression, GA-BPNN exhibited a higher overall prediction accuracy, being able to promptly identify the error factors from the error-related items. The combination of "error-related items, their different levels, and the GA-BPNN model" was proposed as an error-factor identification technology, which could automatically identify medical error factors.

The influence of landscape characteristics and home-range size on the quantification of landscape-genetics relationships

Treesearch

Tabitha A. Graves; Tzeidle N. Wasserman; Milton Cezar Ribeiro; Erin L. Landguth; Stephen F. Spear; Niko Balkenhol; Colleen B. Higgins; Marie-Josee Fortin; Samuel A. Cushman; Lisette P. Waits

2012-01-01

A common approach used to estimate landscape resistance involves comparing correlations of ecological and genetic distances calculated among individuals of a species. However, the location of sampled individuals may contain some degree of spatial uncertainty due to the natural variation of animals moving through their home range ormeasurement error in plant or animal...

Quantum biological channel modeling and capacity calculation.

PubMed

Djordjevic, Ivan B

2012-12-10

Quantum mechanics has an important role in photosynthesis, magnetoreception, and evolution. There were many attempts in an effort to explain the structure of genetic code and transfer of information from DNA to protein by using the concepts of quantum mechanics. The existing biological quantum channel models are not sufficiently general to incorporate all relevant contributions responsible for imperfect protein synthesis. Moreover, the problem of determination of quantum biological channel capacity is still an open problem. To solve these problems, we construct the operator-sum representation of biological channel based on codon basekets (basis vectors), and determine the quantum channel model suitable for study of the quantum biological channel capacity and beyond. The transcription process, DNA point mutations, insertions, deletions, and translation are interpreted as the quantum noise processes. The various types of quantum errors are classified into several broad categories: (i) storage errors that occur in DNA itself as it represents an imperfect storage of genetic information, (ii) replication errors introduced during DNA replication process, (iii) transcription errors introduced during DNA to mRNA transcription, and (iv) translation errors introduced during the translation process. By using this model, we determine the biological quantum channel capacity and compare it against corresponding classical biological channel capacity. We demonstrate that the quantum biological channel capacity is higher than the classical one, for a coherent quantum channel model, suggesting that quantum effects have an important role in biological systems. The proposed model is of crucial importance towards future study of quantum DNA error correction, developing quantum mechanical model of aging, developing the quantum mechanical models for tumors/cancer, and study of intracellular dynamics in general.

Simple Sample Preparation Method for Direct Microbial Identification and Susceptibility Testing From Positive Blood Cultures.

PubMed

Pan, Hong-Wei; Li, Wei; Li, Rong-Guo; Li, Yong; Zhang, Yi; Sun, En-Hua

2018-01-01

Rapid identification and determination of the antibiotic susceptibility profiles of the infectious agents in patients with bloodstream infections are critical steps in choosing an effective targeted antibiotic for treatment. However, there has been minimal effort focused on developing combined methods for the simultaneous direct identification and antibiotic susceptibility determination of bacteria in positive blood cultures. In this study, we constructed a lysis-centrifugation-wash procedure to prepare a bacterial pellet from positive blood cultures, which can be used directly for identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and antibiotic susceptibility testing by the Vitek 2 system. The method was evaluated using a total of 129 clinical bacteria-positive blood cultures. The whole sample preparation process could be completed in <15 min. The correct rate of direct MALDI-TOF MS identification was 96.49% for gram-negative bacteria and 97.22% for gram-positive bacteria. Vitek 2 antimicrobial susceptibility testing of gram-negative bacteria showed an agreement rate of antimicrobial categories of 96.89% with a minor error, major error, and very major error rate of 2.63, 0.24, and 0.24%, respectively. Category agreement of antimicrobials against gram-positive bacteria was 92.81%, with a minor error, major error, and very major error rate of 4.51, 1.22, and 1.46%, respectively. These results indicated that our direct antibiotic susceptibility analysis method worked well compared to the conventional culture-dependent laboratory method. Overall, this fast, easy, and accurate method can facilitate the direct identification and antibiotic susceptibility testing of bacteria in positive blood cultures.

A genetic algorithms approach for altering the membership functions in fuzzy logic controllers

NASA Technical Reports Server (NTRS)

Shehadeh, Hana; Lea, Robert N.

1992-01-01

Through previous work, a fuzzy control system was developed to perform translational and rotational control of a space vehicle. This problem was then re-examined to determine the effectiveness of genetic algorithms on fine tuning the controller. This paper explains the problems associated with the design of this fuzzy controller and offers a technique for tuning fuzzy logic controllers. A fuzzy logic controller is a rule-based system that uses fuzzy linguistic variables to model human rule-of-thumb approaches to control actions within a given system. This 'fuzzy expert system' features rules that direct the decision process and membership functions that convert the linguistic variables into the precise numeric values used for system control. Defining the fuzzy membership functions is the most time consuming aspect of the controller design. One single change in the membership functions could significantly alter the performance of the controller. This membership function definition can be accomplished by using a trial and error technique to alter the membership functions creating a highly tuned controller. This approach can be time consuming and requires a great deal of knowledge from human experts. In order to shorten development time, an iterative procedure for altering the membership functions to create a tuned set that used a minimal amount of fuel for velocity vector approach and station-keep maneuvers was developed. Genetic algorithms, search techniques used for optimization, were utilized to solve this problem.

Novel applications of multitask learning and multiple output regression to multiple genetic trait prediction.

PubMed

He, Dan; Kuhn, David; Parida, Laxmi

2016-06-15

Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait prediction is usually represented as linear regression models. In many cases, for the same set of samples and markers, multiple traits are observed. Some of these traits might be correlated with each other. Therefore, modeling all the multiple traits together may improve the prediction accuracy. In this work, we view the multitrait prediction problem from a machine learning angle: as either a multitask learning problem or a multiple output regression problem, depending on whether different traits share the same genotype matrix or not. We then adapted multitask learning algorithms and multiple output regression algorithms to solve the multitrait prediction problem. We proposed a few strategies to improve the least square error of the prediction from these algorithms. Our experiments show that modeling multiple traits together could improve the prediction accuracy for correlated traits. The programs we used are either public or directly from the referred authors, such as MALSAR (http://www.public.asu.edu/~jye02/Software/MALSAR/) package. The Avocado data set has not been published yet and is available upon request. dhe@us.ibm.com. © The Author 2016. Published by Oxford University Press.

Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

Cancer.gov

Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

Characterization of Hepatitis C Virus (HCV) Envelope Diversification from Acute to Chronic Infection within a Sexually Transmitted HCV Cluster by Using Single-Molecule, Real-Time Sequencing

PubMed Central

Ho, Cynthia K. Y.; Raghwani, Jayna; Koekkoek, Sylvie; Liang, Richard H.; Van der Meer, Jan T. M.; Van Der Valk, Marc; De Jong, Menno; Pybus, Oliver G.

2016-01-01

ABSTRACT In contrast to other available next-generation sequencing platforms, PacBio single-molecule, real-time (SMRT) sequencing has the advantage of generating long reads albeit with a relatively higher error rate in unprocessed data. Using this platform, we longitudinally sampled and sequenced the hepatitis C virus (HCV) envelope genome region (1,680 nucleotides [nt]) from individuals belonging to a cluster of sexually transmitted cases. All five subjects were coinfected with HIV-1 and a closely related strain of HCV genotype 4d. In total, 50 samples were analyzed by using SMRT sequencing. By using 7 passes of circular consensus sequencing, the error rate was reduced to 0.37%, and the median number of sequences was 612 per sample. A further reduction of insertions was achieved by alignment against a sample-specific reference sequence. However, in vitro recombination during PCR amplification could not be excluded. Phylogenetic analysis supported close relationships among HCV sequences from the four male subjects and subsequent transmission from one subject to his female partner. Transmission was characterized by a strong genetic bottleneck. Viral genetic diversity was low during acute infection and increased upon progression to chronicity but subsequently fluctuated during chronic infection, caused by the alternate detection of distinct coexisting lineages. SMRT sequencing combines long reads with sufficient depth for many phylogenetic analyses and can therefore provide insights into within-host HCV evolutionary dynamics without the need for haplotype reconstruction using statistical algorithms. IMPORTANCE Next-generation sequencing has revolutionized the study of genetically variable RNA virus populations, but for phylogenetic and evolutionary analyses, longer sequences than those generated by most available platforms, while minimizing the intrinsic error rate, are desired. Here, we demonstrate for the first time that PacBio SMRT sequencing technology can be used to generate full-length HCV envelope sequences at the single-molecule level, providing a data set with large sequencing depth for the characterization of intrahost viral dynamics. The selection of consensus reads derived from at least 7 full circular consensus sequencing rounds significantly reduced the intrinsic high error rate of this method. We used this method to genetically characterize a unique transmission cluster of sexually transmitted HCV infections, providing insight into the distinct evolutionary pathways in each patient over time and identifying the transmission-associated genetic bottleneck as well as fluctuations in viral genetic diversity over time, accompanied by dynamic shifts in viral subpopulations. PMID:28077634

Setup deviations for whole-breast radiotherapy with TomoDirect: A comparison of weekly and biweekly image-guided protocols

NASA Astrophysics Data System (ADS)

Jung, Jae Hong; Jung, Joo-Young; Bae, Sun Hyun; Moon, Seong Kwon; Cho, Kwang Hwan

2016-10-01

The purpose of this study was to compare patient setup deviations for different image-guided protocols (weekly vs. biweekly) that are used in TomoDirect three-dimensional conformal radiotherapy (TD-3DCRT) for whole-breast radiation therapy (WBRT). A total of 138 defined megavoltage computed tomography (MVCT) image sets from 46 breast cancer cases were divided into two groups based on the imaging acquisition times: weekly or biweekly. The mean error, three-dimensional setup displacement error (3D-error), systematic error (Σ), and random error (σ) were calculated for each group. The 3D-errors were 4.29 ± 1.11 mm and 5.02 ± 1.85 mm for the weekly and biweekly groups, respectively; the biweekly error was 14.6% higher than the weekly error. The systematic errors in the roll angle and the x, y, and z directions were 0.48°, 1.72 mm, 2.18 mm, and 1.85 mm for the weekly protocol and 0.21°, 1.24 mm, 1.39 mm, and 1.85 mm for the biweekly protocol. Random errors in the roll angle and the x, y, and z directions were 25.7%, 40.6%, 40.0%, and 40.8% higher in the biweekly group than in the weekly group. For the x, y, and z directions, the distributions of the treatment frequency at less than 5 mm were 98.6%, 91.3%, and 94.2% in the weekly group and 94.2%, 89.9%, and 82.6% in the biweekly group. Moreover, the roll angles with 0 - 1° were 79.7% and 89.9% in the weekly and the biweekly groups, respectively. Overall, the evaluation of setup deviations for the two protocols revealed no significant differences (p > 0.05). Reducing the frequency of MVCT imaging could have promising effects on imaging doses and machine times during treatment. However, the biweekly protocol was associated with increased random setup deviations in the treatment. We have demonstrated a biweekly protocol of TD-3DCRT for WBRT, and we anticipate that our method may provide an alternative approach for considering the uncertainties in the patient setup.

Robustness of meta-analyses in finding gene × environment interactions

PubMed Central

Shi, Gang; Nehorai, Arye

2017-01-01

Meta-analyses that synthesize statistical evidence across studies have become important analytical tools for genetic studies. Inspired by the success of genome-wide association studies of the genetic main effect, researchers are searching for gene × environment interactions. Confounders are routinely included in the genome-wide gene × environment interaction analysis as covariates; however, this does not control for any confounding effects on the results if covariate × environment interactions are present. We carried out simulation studies to evaluate the robustness to the covariate × environment confounder for meta-regression and joint meta-analysis, which are two commonly used meta-analysis methods for testing the gene × environment interaction or the genetic main effect and interaction jointly. Here we show that meta-regression is robust to the covariate × environment confounder while joint meta-analysis is subject to the confounding effect with inflated type I error rates. Given vast sample sizes employed in genome-wide gene × environment interaction studies, non-significant covariate × environment interactions at the study level could substantially elevate the type I error rate at the consortium level. When covariate × environment confounders are present, type I errors can be controlled in joint meta-analysis by including the covariate × environment terms in the analysis at the study level. Alternatively, meta-regression can be applied, which is robust to potential covariate × environment confounders. PMID:28362796

eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

PubMed

Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

2010-03-09

Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

PubMed Central

2010-01-01

Background Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt. PMID:20214782

Powerful Inference with the D-Statistic on Low-Coverage Whole-Genome Data.

PubMed

Soraggi, Samuele; Wiuf, Carsten; Albrechtsen, Anders

2018-02-02

The detection of ancient gene flow between human populations is an important issue in population genetics. A common tool for detecting ancient admixture events is the D-statistic. The D-statistic is based on the hypothesis of a genetic relationship that involves four populations, whose correctness is assessed by evaluating specific coincidences of alleles between the groups. When working with high-throughput sequencing data, calling genotypes accurately is not always possible; therefore, the D-statistic currently samples a single base from the reads of one individual per population. This implies ignoring much of the information in the data, an issue especially striking in the case of ancient genomes. We provide a significant improvement to overcome the problems of the D-statistic by considering all reads from multiple individuals in each population. We also apply type-specific error correction to combat the problems of sequencing errors, and show a way to correct for introgression from an external population that is not part of the supposed genetic relationship, and how this leads to an estimate of the admixture rate. We prove that the D-statistic is approximated by a standard normal distribution. Furthermore, we show that our method outperforms the traditional D-statistic in detecting admixtures. The power gain is most pronounced for low and medium sequencing depth (1-10×), and performances are as good as with perfectly called genotypes at a sequencing depth of 2×. We show the reliability of error correction in scenarios with simulated errors and ancient data, and correct for introgression in known scenarios to estimate the admixture rates. Copyright © 2018 Soraggi et al.

Data Based Prediction of Blood Glucose Concentrations Using Evolutionary Methods.

PubMed

Hidalgo, J Ignacio; Colmenar, J Manuel; Kronberger, Gabriel; Winkler, Stephan M; Garnica, Oscar; Lanchares, Juan

2017-08-08

Predicting glucose values on the basis of insulin and food intakes is a difficult task that people with diabetes need to do daily. This is necessary as it is important to maintain glucose levels at appropriate values to avoid not only short-term, but also long-term complications of the illness. Artificial intelligence in general and machine learning techniques in particular have already lead to promising results in modeling and predicting glucose concentrations. In this work, several machine learning techniques are used for the modeling and prediction of glucose concentrations using as inputs the values measured by a continuous monitoring glucose system as well as also previous and estimated future carbohydrate intakes and insulin injections. In particular, we use the following four techniques: genetic programming, random forests, k-nearest neighbors, and grammatical evolution. We propose two new enhanced modeling algorithms for glucose prediction, namely (i) a variant of grammatical evolution which uses an optimized grammar, and (ii) a variant of tree-based genetic programming which uses a three-compartment model for carbohydrate and insulin dynamics. The predictors were trained and tested using data of ten patients from a public hospital in Spain. We analyze our experimental results using the Clarke error grid metric and see that 90% of the forecasts are correct (i.e., Clarke error categories A and B), but still even the best methods produce 5 to 10% of serious errors (category D) and approximately 0.5% of very serious errors (category E). We also propose an enhanced genetic programming algorithm that incorporates a three-compartment model into symbolic regression models to create smoothed time series of the original carbohydrate and insulin time series.

The albino chick as a model for studying ocular developmental anomalies, including refractive errors, associated with albinism.

PubMed

Rymer, Jodi; Choh, Vivian; Bharadwaj, Shrikant; Padmanabhan, Varuna; Modilevsky, Laura; Jovanovich, Elizabeth; Yeh, Brenda; Zhang, Zhan; Guan, Huanxian; Payne, W; Wildsoet, Christine F

2007-10-01

Albinism is associated with a variety of ocular anomalies including refractive errors. The purpose of this study was to investigate the ocular development of an albino chick line. The ocular development of both albino and normally pigmented chicks was monitored using retinoscopy to measure refractive errors and high frequency A-scan ultrasonography to measure axial ocular dimensions. Functional tests included an optokinetic nystagmus paradigm to assess visual acuity, and flash ERGs to assess retinal function. The underlying genetic abnormality was characterized using a gene microarray, PCR and a tyrosinase assay. The ultrastructure of the retinal pigment epithelium (RPE) was examined using transmission electron microscopy. PCR confirmed that the genetic abnormality in this line is a deletion in exon 1 of the tyrosinase gene. Tyrosinase gene expression in isolated RPE cells was minimally detectable, and there was minimal enzyme activity in albino feather bulbs. The albino chicks had pink eyes and their eyes transilluminated, reflecting the lack of melanin in all ocular tissues. All three main components, anterior chamber, crystalline lens and vitreous chamber, showed axial expansion over time in both normal and albino animals, but the anterior chambers of albino chicks were consistently shallower than those of normal chicks, while in contrast, their vitreous chambers were longer. Albino chicks remained relatively myopic, with higher astigmatism than the normally pigmented chicks, even though both groups underwent developmental emmetropization. Albino chicks had reduced visual acuity yet the ERG a- and b-wave components had larger amplitudes and shorter than normal implicit times. Developmental emmetropization occurs in the albino chick but is impaired, likely because of functional abnormalities in the RPE and/or retina as well as optical factors. In very young chicks the underlying genetic mutation may also contribute to refractive error and eye shape abnormalities.

Crucial steps to life: From chemical reactions to code using agents.

PubMed

Witzany, Guenther

2016-02-01

The concepts of the origin of the genetic code and the definitions of life changed dramatically after the RNA world hypothesis. Main narratives in molecular biology and genetics such as the "central dogma," "one gene one protein" and "non-coding DNA is junk" were falsified meanwhile. RNA moved from the transition intermediate molecule into centre stage. Additionally the abundance of empirical data concerning non-random genetic change operators such as the variety of mobile genetic elements, persistent viruses and defectives do not fit with the dominant narrative of error replication events (mutations) as being the main driving forces creating genetic novelty and diversity. The reductionistic and mechanistic views on physico-chemical properties of the genetic code are no longer convincing as appropriate descriptions of the abundance of non-random genetic content operators which are active in natural genetic engineering and natural genome editing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

PubMed

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

Assessment of spatial discordance of primary and effective seed dispersal of European beech (Fagus sylvatica L.) by ecological and genetic methods.

PubMed

Millerón, M; López de Heredia, U; Lorenzo, Z; Alonso, J; Dounavi, A; Gil, L; Nanos, N

2013-03-01

Spatial discordance between primary and effective dispersal in plant populations indicates that postdispersal processes erase the seed rain signal in recruitment patterns. Five different models were used to test the spatial concordance of the primary and effective dispersal patterns in a European beech (Fagus sylvatica) population from central Spain. An ecological method was based on classical inverse modelling (SSS), using the number of seed/seedlings as input data. Genetic models were based on direct kernel fitting of mother-to-offspring distances estimated by a parentage analysis or were spatially explicit models based on the genotype frequencies of offspring (competing sources model and Moran-Clark's Model). A fully integrated mixed model was based on inverse modelling, but used the number of genotypes as input data (gene shadow model). The potential sources of error and limitations of each seed dispersal estimation method are discussed. The mean dispersal distances for seeds and saplings estimated with these five methods were higher than those obtained by previous estimations for European beech forests. All the methods show strong discordance between primary and effective dispersal kernel parameters, and for dispersal directionality. While seed rain was released mostly under the canopy, saplings were established far from mother trees. This discordant pattern may be the result of the action of secondary dispersal by animals or density-dependent effects; that is, the Janzen-Connell effect. © 2013 Blackwell Publishing Ltd.

Computational fluid dynamics analysis and experimental study of a low measurement error temperature sensor used in climate observation.

PubMed

Yang, Jie; Liu, Qingquan; Dai, Wei

2017-02-01

To improve the air temperature observation accuracy, a low measurement error temperature sensor is proposed. A computational fluid dynamics (CFD) method is implemented to obtain temperature errors under various environmental conditions. Then, a temperature error correction equation is obtained by fitting the CFD results using a genetic algorithm method. The low measurement error temperature sensor, a naturally ventilated radiation shield, a thermometer screen, and an aspirated temperature measurement platform are characterized in the same environment to conduct the intercomparison. The aspirated platform served as an air temperature reference. The mean temperature errors of the naturally ventilated radiation shield and the thermometer screen are 0.74 °C and 0.37 °C, respectively. In contrast, the mean temperature error of the low measurement error temperature sensor is 0.11 °C. The mean absolute error and the root mean square error between the corrected results and the measured results are 0.008 °C and 0.01 °C, respectively. The correction equation allows the temperature error of the low measurement error temperature sensor to be reduced by approximately 93.8%. The low measurement error temperature sensor proposed in this research may be helpful to provide a relatively accurate air temperature result.

MS-READ: Quantitative measurement of amino acid incorporation.

PubMed

Mohler, Kyle; Aerni, Hans-Rudolf; Gassaway, Brandon; Ling, Jiqiang; Ibba, Michael; Rinehart, Jesse

2017-11-01

Ribosomal protein synthesis results in the genetically programmed incorporation of amino acids into a growing polypeptide chain. Faithful amino acid incorporation that accurately reflects the genetic code is critical to the structure and function of proteins as well as overall proteome integrity. Errors in protein synthesis are generally detrimental to cellular processes yet emerging evidence suggest that proteome diversity generated through mistranslation may be beneficial under certain conditions. Cumulative translational error rates have been determined at the organismal level, however codon specific error rates and the spectrum of misincorporation errors from system to system remain largely unexplored. In particular, until recently technical challenges have limited the ability to detect and quantify comparatively rare amino acid misincorporation events, which occur orders of magnitude less frequently than canonical amino acid incorporation events. We now describe a technique for the quantitative analysis of amino acid incorporation that provides the sensitivity necessary to detect mistranslation events during translation of a single codon at frequencies as low as 1 in 10,000 for all 20 proteinogenic amino acids, as well as non-proteinogenic and modified amino acids. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

ON MODEL SELECTION STRATEGIES TO IDENTIFY GENES UNDERLYING BINARY TRAITS USING GENOME-WIDE ASSOCIATION DATA.

PubMed

Wu, Zheyang; Zhao, Hongyu

2012-01-01

For more fruitful discoveries of genetic variants associated with diseases in genome-wide association studies, it is important to know whether joint analysis of multiple markers is more powerful than the commonly used single-marker analysis, especially in the presence of gene-gene interactions. This article provides a statistical framework to rigorously address this question through analytical power calculations for common model search strategies to detect binary trait loci: marginal search, exhaustive search, forward search, and two-stage screening search. Our approach incorporates linkage disequilibrium, random genotypes, and correlations among score test statistics of logistic regressions. We derive analytical results under two power definitions: the power of finding all the associated markers and the power of finding at least one associated marker. We also consider two types of error controls: the discovery number control and the Bonferroni type I error rate control. After demonstrating the accuracy of our analytical results by simulations, we apply them to consider a broad genetic model space to investigate the relative performances of different model search strategies. Our analytical study provides rapid computation as well as insights into the statistical mechanism of capturing genetic signals under different genetic models including gene-gene interactions. Even though we focus on genetic association analysis, our results on the power of model selection procedures are clearly very general and applicable to other studies.

ON MODEL SELECTION STRATEGIES TO IDENTIFY GENES UNDERLYING BINARY TRAITS USING GENOME-WIDE ASSOCIATION DATA

PubMed Central

Wu, Zheyang; Zhao, Hongyu

2013-01-01

For more fruitful discoveries of genetic variants associated with diseases in genome-wide association studies, it is important to know whether joint analysis of multiple markers is more powerful than the commonly used single-marker analysis, especially in the presence of gene-gene interactions. This article provides a statistical framework to rigorously address this question through analytical power calculations for common model search strategies to detect binary trait loci: marginal search, exhaustive search, forward search, and two-stage screening search. Our approach incorporates linkage disequilibrium, random genotypes, and correlations among score test statistics of logistic regressions. We derive analytical results under two power definitions: the power of finding all the associated markers and the power of finding at least one associated marker. We also consider two types of error controls: the discovery number control and the Bonferroni type I error rate control. After demonstrating the accuracy of our analytical results by simulations, we apply them to consider a broad genetic model space to investigate the relative performances of different model search strategies. Our analytical study provides rapid computation as well as insights into the statistical mechanism of capturing genetic signals under different genetic models including gene-gene interactions. Even though we focus on genetic association analysis, our results on the power of model selection procedures are clearly very general and applicable to other studies. PMID:23956610

Adapt-Mix: learning local genetic correlation structure improves summary statistics-based analyses

PubMed Central

Park, Danny S.; Brown, Brielin; Eng, Celeste; Huntsman, Scott; Hu, Donglei; Torgerson, Dara G.; Burchard, Esteban G.; Zaitlen, Noah

2015-01-01

Motivation: Approaches to identifying new risk loci, training risk prediction models, imputing untyped variants and fine-mapping causal variants from summary statistics of genome-wide association studies are playing an increasingly important role in the human genetics community. Current summary statistics-based methods rely on global ‘best guess’ reference panels to model the genetic correlation structure of the dataset being studied. This approach, especially in admixed populations, has the potential to produce misleading results, ignores variation in local structure and is not feasible when appropriate reference panels are missing or small. Here, we develop a method, Adapt-Mix, that combines information across all available reference panels to produce estimates of local genetic correlation structure for summary statistics-based methods in arbitrary populations. Results: We applied Adapt-Mix to estimate the genetic correlation structure of both admixed and non-admixed individuals using simulated and real data. We evaluated our method by measuring the performance of two summary statistics-based methods: imputation and joint-testing. When using our method as opposed to the current standard of ‘best guess’ reference panels, we observed a 28% decrease in mean-squared error for imputation and a 73.7% decrease in mean-squared error for joint-testing. Availability and implementation: Our method is publicly available in a software package called ADAPT-Mix available at https://github.com/dpark27/adapt_mix. Contact: noah.zaitlen@ucsf.edu PMID:26072481

Use of Positive Blood Cultures for Direct Identification and Susceptibility Testing with the Vitek 2 System

PubMed Central

de Cueto, Marina; Ceballos, Esther; Martinez-Martinez, Luis; Perea, Evelio J.; Pascual, Alvaro

2004-01-01

In order to further decrease the time lapse between initial inoculation of blood culture media and the reporting of results of identification and antimicrobial susceptibility tests for microorganisms causing bacteremia, we performed a prospective study in which specially processed fluid from positive blood culture bottles from Bactec 9240 (Becton Dickinson, Cockeysville, Md.) containing aerobic media were directly inoculated into Vitek 2 system cards (bio-Mérieux, France). Organism identification and susceptibility results were compared with those obtained from cards inoculated with a standardized bacterial suspension obtained following subculture to agar; 100 consecutive positive monomicrobic blood cultures, consisting of 50 gram-negative rods and 50 gram-positive cocci, were included in the study. For gram-negative organisms, 31 of the 50 (62%) showed complete agreement with the standard method for species identification, while none of the 50 gram-positive cocci were correctly identified by the direct method. For gram-negative rods, there were 50% categorical agreements between the direct and standard methods for all drugs tested. The very major error rate was 2.4%, and the major error rate was 0.6%. The overall error rate for gram-negatives was 6.6%. Complete agreement in clinical categories of all antimicrobial agents evaluated was obtained for 19 of 50 (38%) gram-positive cocci evaluated; the overall error rate was 8.4%, with 2.8% minor errors, 2.4% major errors, and 3.2% very major errors. These findings suggest that the Vitek 2 cards inoculated directly from positive Bactec 9240 bottles do not provide acceptable bacterial identification or susceptibility testing in comparison with corresponding cards tested by a standard method. PMID:15297523

Genetic Algorithms Evolve Optimized Transforms for Signal Processing Applications

DTIC Science & Technology

2005-04-01

coefficient sets describing inverse transforms and matched forward/ inverse transform pairs that consistently outperform wavelets for image compression and reconstruction applications under conditions subject to quantization error.

High-Throughput Identification of Loss-of-Function Mutations for Anti-Interferon Activity in the Influenza A Virus NS Segment

PubMed Central

Wu, Nicholas C.; Young, Arthur P.; Al-Mawsawi, Laith Q.; Olson, C. Anders; Feng, Jun; Qi, Hangfei; Luan, Harding H.; Li, Xinmin; Wu, Ting-Ting

2014-01-01

ABSTRACT Viral proteins often display several functions which require multiple assays to dissect their genetic basis. Here, we describe a systematic approach to screen for loss-of-function mutations that confer a fitness disadvantage under a specified growth condition. Our methodology was achieved by genetically monitoring a mutant library under two growth conditions, with and without interferon, by deep sequencing. We employed a molecular tagging technique to distinguish true mutations from sequencing error. This approach enabled us to identify mutations that were negatively selected against, in addition to those that were positively selected for. Using this technique, we identified loss-of-function mutations in the influenza A virus NS segment that were sensitive to type I interferon in a high-throughput fashion. Mechanistic characterization further showed that a single substitution, D92Y, resulted in the inability of NS to inhibit RIG-I ubiquitination. The approach described in this study can be applied under any specified condition for any virus that can be genetically manipulated. IMPORTANCE Traditional genetics focuses on a single genotype-phenotype relationship, whereas high-throughput genetics permits phenotypic characterization of numerous mutants in parallel. High-throughput genetics often involves monitoring of a mutant library with deep sequencing. However, deep sequencing suffers from a high error rate (∼0.1 to 1%), which is usually higher than the occurrence frequency for individual point mutations within a mutant library. Therefore, only mutations that confer a fitness advantage can be identified with confidence due to an enrichment in the occurrence frequency. In contrast, it is impossible to identify deleterious mutations using most next-generation sequencing techniques. In this study, we have applied a molecular tagging technique to distinguish true mutations from sequencing errors. It enabled us to identify mutations that underwent negative selection, in addition to mutations that experienced positive selection. This study provides a proof of concept by screening for loss-of-function mutations on the influenza A virus NS segment that are involved in its anti-interferon activity. PMID:24965464

An ABC estimate of pedigree error rate: application in dog, sheep and cattle breeds.

PubMed

Leroy, G; Danchin-Burge, C; Palhiere, I; Baumung, R; Fritz, S; Mériaux, J C; Gautier, M

2012-06-01

On the basis of correlations between pairwise individual genealogical kinship coefficients and allele sharing distances computed from genotyping data, we propose an approximate Bayesian computation (ABC) approach to assess pedigree file reliability through gene-dropping simulations. We explore the features of the method using simulated data sets and show precision increases with the number of markers. An application is further made with five dog breeds, four sheep breeds and one cattle breed raised in France and displaying various characteristics and population sizes, using microsatellite or SNP markers. Depending on the breeds, pedigree error estimations range between 1% and 9% in dog breeds, 1% and 10% in sheep breeds and 4% in cattle breeds. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data.

PubMed

Fan, Yu; Xi, Liu; Hughes, Daniel S T; Zhang, Jianjun; Zhang, Jianhua; Futreal, P Andrew; Wheeler, David A; Wang, Wenyi

2016-08-24

Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using next-generation sequencing remains challenging. We develop MuSE ( http://bioinformatics.mdanderson.org/main/MuSE ), Mutation calling using a Markov Substitution model for Evolution, a novel approach for modeling the evolution of the allelic composition of the tumor and normal tissue at each reference base. MuSE adopts a sample-specific error model that reflects the underlying tumor heterogeneity to greatly improve the overall accuracy. We demonstrate the accuracy of MuSE in calling subclonal mutations in the context of large-scale tumor sequencing projects using whole exome and whole genome sequencing.

Inverse problem of HIV cell dynamics using Genetic Algorithms

NASA Astrophysics Data System (ADS)

González, J. A.; Guzmán, F. S.

2017-01-01

In order to describe the cell dynamics of T-cells in a patient infected with HIV, we use a flavour of Perelson's model. This is a non-linear system of Ordinary Differential Equations that describes the evolution of healthy, latently infected, infected T-cell concentrations and the free viral cells. Different parameters in the equations give different dynamics. Considering the concentration of these types of cells is known for a particular patient, the inverse problem consists in estimating the parameters in the model. We solve this inverse problem using a Genetic Algorithm (GA) that minimizes the error between the solutions of the model and the data from the patient. These errors depend on the parameters of the GA, like mutation rate and population, although a detailed analysis of this dependence will be described elsewhere.

Analysis of difference between direct and geodetic mass balance measurements at South Cascade Glacier, Washington

USGS Publications Warehouse

Krimmel, R.M.

1999-01-01

Net mass balance has been measured since 1958 at South Cascade Glacier using the 'direct method,' e.g. area averages of snow gain and firn and ice loss at stakes. Analysis of cartographic vertical photography has allowed measurement of mass balance using the 'geodetic method' in 1970, 1975, 1977, 1979-80, and 1985-97. Water equivalent change as measured by these nearly independent methods should give similar results. During 1970-97, the direct method shows a cumulative balance of about -15 m, and the geodetic method shows a cumulative balance of about -22 m. The deviation between the two methods is fairly consistent, suggesting no gross errors in either, but rather a cumulative systematic error. It is suspected that the cumulative error is in the direct method because the geodetic method is based on a non-changing reference, the bedrock control, whereas the direct method is measured with reference to only the previous year's summer surface. Possible sources of mass loss that are missing from the direct method are basal melt, internal melt, and ablation on crevasse walls. Possible systematic measurement errors include under-estimation of the density of lost material, sinking stakes, or poorly represented areas.

Tilt Error in Cryospheric Surface Radiation Measurements at High Latitudes: A Model Study

NASA Astrophysics Data System (ADS)

Bogren, W.; Kylling, A.; Burkhart, J. F.

2015-12-01

We have evaluated the magnitude and makeup of error in cryospheric radiation observations due to small sensor misalignment in in-situ measurements of solar irradiance. This error is examined through simulation of diffuse and direct irradiance arriving at a detector with a cosine-response foreoptic. Emphasis is placed on assessing total error over the solar shortwave spectrum from 250nm to 4500nm, as well as supporting investigation over other relevant shortwave spectral ranges. The total measurement error introduced by sensor tilt is dominated by the direct component. For a typical high latitude albedo measurement with a solar zenith angle of 60◦, a sensor tilted by 1, 3, and 5◦ can respectively introduce up to 2.6, 7.7, and 12.8% error into the measured irradiance and similar errors in the derived albedo. Depending on the daily range of solar azimuth and zenith angles, significant measurement error can persist also in integrated daily irradiance and albedo.

Simulations in site error estimation for direction finders

NASA Astrophysics Data System (ADS)

López, Raúl E.; Passi, Ranjit M.

1991-08-01

The performance of an algorithm for the recovery of site-specific errors of direction finder (DF) networks is tested under controlled simulated conditions. The simulations show that the algorithm has some inherent shortcomings for the recovery of site errors from the measured azimuth data. These limitations are fundamental to the problem of site error estimation using azimuth information. Several ways for resolving or ameliorating these basic complications are tested by means of simulations. From these it appears that for the effective implementation of the site error determination algorithm, one should design the networks with at least four DFs, improve the alignment of the antennas, and increase the gain of the DFs as much as it is compatible with other operational requirements. The use of a nonzero initial estimate of the site errors when working with data from networks of four or more DFs also improves the accuracy of the site error recovery. Even for networks of three DFs, reasonable site error corrections could be obtained if the antennas could be well aligned.

Finite Element A Posteriori Error Estimation for Heat Conduction. Degree awarded by George Washington Univ.

NASA Technical Reports Server (NTRS)

Lang, Christapher G.; Bey, Kim S. (Technical Monitor)

2002-01-01

This research investigates residual-based a posteriori error estimates for finite element approximations of heat conduction in single-layer and multi-layered materials. The finite element approximation, based upon hierarchical modelling combined with p-version finite elements, is described with specific application to a two-dimensional, steady state, heat-conduction problem. Element error indicators are determined by solving an element equation for the error with the element residual as a source, and a global error estimate in the energy norm is computed by collecting the element contributions. Numerical results of the performance of the error estimate are presented by comparisons to the actual error. Two methods are discussed and compared for approximating the element boundary flux. The equilibrated flux method provides more accurate results for estimating the error than the average flux method. The error estimation is applied to multi-layered materials with a modification to the equilibrated flux method to approximate the discontinuous flux along a boundary at the material interfaces. A directional error indicator is developed which distinguishes between the hierarchical modeling error and the finite element error. Numerical results are presented for single-layered materials which show that the directional indicators accurately determine which contribution to the total error dominates.

Robust logistic regression to narrow down the winner's curse for rare and recessive susceptibility variants.

PubMed

Kesselmeier, Miriam; Lorenzo Bermejo, Justo

2017-11-01

Logistic regression is the most common technique used for genetic case-control association studies. A disadvantage of standard maximum likelihood estimators of the genotype relative risk (GRR) is their strong dependence on outlier subjects, for example, patients diagnosed at unusually young age. Robust methods are available to constrain outlier influence, but they are scarcely used in genetic studies. This article provides a non-intimidating introduction to robust logistic regression, and investigates its benefits and limitations in genetic association studies. We applied the bounded Huber and extended the R package 'robustbase' with the re-descending Hampel functions to down-weight outlier influence. Computer simulations were carried out to assess the type I error rate, mean squared error (MSE) and statistical power according to major characteristics of the genetic study and investigated markers. Simulations were complemented with the analysis of real data. Both standard and robust estimation controlled type I error rates. Standard logistic regression showed the highest power but standard GRR estimates also showed the largest bias and MSE, in particular for associated rare and recessive variants. For illustration, a recessive variant with a true GRR=6.32 and a minor allele frequency=0.05 investigated in a 1000 case/1000 control study by standard logistic regression resulted in power=0.60 and MSE=16.5. The corresponding figures for Huber-based estimation were power=0.51 and MSE=0.53. Overall, Hampel- and Huber-based GRR estimates did not differ much. Robust logistic regression may represent a valuable alternative to standard maximum likelihood estimation when the focus lies on risk prediction rather than identification of susceptibility variants. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Deep sequencing of hepatitis C virus hypervariable region 1 reveals no correlation between genetic heterogeneity and antiviral treatment outcome

PubMed Central

2014-01-01

Background Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-α (pegylated interferon α) and ribavirin treatment. Methods HVR1 sequences were amplified from pretreatment serum samples of 25 patients infected with genotype 1b HCV (12 responders and 13 non-responders) and were subjected to pyrosequencing (GS Junior, 454/Roche). Reads were corrected for sequencing error using ShoRAH software, while population reconstruction was done using three different minimal variant frequency cut-offs of 1%, 2% and 5%. Statistical analysis was done using Mann–Whitney and Fisher’s exact tests. Results Complexity, Shannon entropy, nucleotide diversity per site, genetic distance and the number of genetic substitutions were not significantly different between responders and non-responders, when analyzing viral populations at any of the three frequencies (≥1%, ≥2% and ≥5%). When clonal sample was used to determine pyrosequencing error, 4% of reads were found to be incorrect and the most abundant variant was present at a frequency of 1.48%. Use of ShoRAH reduced the sequencing error to 1%, with the most abundant erroneous variant present at frequency of 0.5%. Conclusions While deep sequencing revealed complex genetic heterogeneity of HVR1 in chronic hepatitis C patients, there was no correlation between treatment outcome and any of the analyzed quasispecies parameters. PMID:25016390

Instruction-matrix-based genetic programming.

PubMed

Li, Gang; Wang, Jin Feng; Lee, Kin Hong; Leung, Kwong-Sak

2008-08-01

In genetic programming (GP), evolving tree nodes separately would reduce the huge solution space. However, tree nodes are highly interdependent with respect to their fitness. In this paper, we propose a new GP framework, namely, instruction-matrix (IM)-based GP (IMGP), to handle their interactions. IMGP maintains an IM to evolve tree nodes and subtrees separately. IMGP extracts program trees from an IM and updates the IM with the information of the extracted program trees. As the IM actually keeps most of the information of the schemata of GP and evolves the schemata directly, IMGP is effective and efficient. Our experimental results on benchmark problems have verified that IMGP is not only better than those of canonical GP in terms of the qualities of the solutions and the number of program evaluations, but they are also better than some of the related GP algorithms. IMGP can also be used to evolve programs for classification problems. The classifiers obtained have higher classification accuracies than four other GP classification algorithms on four benchmark classification problems. The testing errors are also comparable to or better than those obtained with well-known classifiers. Furthermore, an extended version, called condition matrix for rule learning, has been used successfully to handle multiclass classification problems.

Inborn Errors in Immunity

PubMed Central

Lionakis, M.S.; Hajishengallis, G.

2015-01-01

In recent years, the study of genetic defects arising from inborn errors in immunity has resulted in the discovery of new genes involved in the function of the immune system and in the elucidation of the roles of known genes whose importance was previously unappreciated. With the recent explosion in the field of genomics and the increasing number of genetic defects identified, the study of naturally occurring mutations has become a powerful tool for gaining mechanistic insight into the functions of the human immune system. In this concise perspective, we discuss emerging evidence that inborn errors in immunity constitute real-life models that are indispensable both for the in-depth understanding of human biology and for obtaining critical insights into common diseases, such as those affecting oral health. In the field of oral mucosal immunity, through the study of patients with select gene disruptions, the interleukin-17 (IL-17) pathway has emerged as a critical element in oral immune surveillance and susceptibility to inflammatory disease, with disruptions in the IL-17 axis now strongly linked to mucosal fungal susceptibility, whereas overactivation of the same pathways is linked to inflammatory periodontitis. PMID:25900229

SU-E-T-195: Gantry Angle Dependency of MLC Leaf Position Error

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

Ju, S; Hong, C; Kim, M

Purpose: The aim of this study was to investigate the gantry angle dependency of the multileaf collimator (MLC) leaf position error. Methods: An automatic MLC quality assurance system (AutoMLCQA) was developed to evaluate the gantry angle dependency of the MLC leaf position error using an electronic portal imaging device (EPID). To eliminate the EPID position error due to gantry rotation, we designed a reference maker (RM) that could be inserted into the wedge mount. After setting up the EPID, a reference image was taken of the RM using an open field. Next, an EPID-based picket-fence test (PFT) was performed withoutmore » the RM. These procedures were repeated at every 45° intervals of the gantry angle. A total of eight reference images and PFT image sets were analyzed using in-house software. The average MLC leaf position error was calculated at five pickets (-10, -5, 0, 5, and 10 cm) in accordance with general PFT guidelines using in-house software. This test was carried out for four linear accelerators. Results: The average MLC leaf position errors were within the set criterion of <1 mm (actual errors ranged from -0.7 to 0.8 mm) for all gantry angles, but significant gantry angle dependency was observed in all machines. The error was smaller at a gantry angle of 0° but increased toward the positive direction with gantry angle increments in the clockwise direction. The error reached a maximum value at a gantry angle of 90° and then gradually decreased until 180°. In the counter-clockwise rotation of the gantry, the same pattern of error was observed but the error increased in the negative direction. Conclusion: The AutoMLCQA system was useful to evaluate the MLC leaf position error for various gantry angles without the EPID position error. The Gantry angle dependency should be considered during MLC leaf position error analysis.« less

Evidence for heritability of adult men's sexual interest in youth under age 16 from a population-based extended twin design.

PubMed

Alanko, Katarina; Salo, Benny; Mokros, Andreas; Santtila, Pekka

2013-04-01

Sexual interest in children resembles sexual gender orientation in terms of early onset and stability across the life span. Although a genetic component to sexual interest in children seems possible, no research has addressed this question to date. Prior research showing familial transmission of pedophilia remains inconclusive about shared environmental or genetic factors. Studies from the domains of sexual orientation and sexually problematic behavior among children pointed toward genetic components. Adult men's sexual interest in youthfulness-related cues may be genetically influenced. The aim of the present study was to test whether male sexual interest in children and youth under age 16 involves a heritable component. The main outcome measure was responses in a confidential survey concerning sexual interest, fantasies, or activity pertaining to children under the age of 16 years during the previous 12 months. The present study used an extended family design within behavioral genetic modeling to estimate the contributions of genetic and environmental factors in the occurrence of adult men's sexual interest in children and youth under age 16. Participants were male twins and their male siblings from a population-based Finnish cohort sample aged 21-43 years (N = 3,967). The incidence of sexual interest in children under age was 3%. Twin correlations were higher for monozygotic than for dizygotic twins. Behavioral genetic model fitting indicated that a model including genetic effects as well as nonshared environmental influences (including measurement error), but not common environmental influences, fits the data best. The amount of variance attributable to nonadditive genetic influences (heritability) was estimated at 14.6%. The present study provides the first indication that genetic influences may play a role in shaping sexual interest toward children and adolescents among adult men. Compared with the variance attributable to nonshared environmental effects (plus measurement error), the contribution of any genetic factors seems comparatively weak. Future research should address the possible interplay of genetic with environmental risk factors, such as own sexual victimization in childhood. © 2013 International Society for Sexual Medicine.

Fourier decomposition of spatial localization errors reveals an idiotropic dominance of an internal model of gravity.

PubMed

De Sá Teixeira, Nuno Alexandre

2014-12-01

Given its conspicuous nature, gravity has been acknowledged by several research lines as a prime factor in structuring the spatial perception of one's environment. One such line of enquiry has focused on errors in spatial localization aimed at the vanishing location of moving objects - it has been systematically reported that humans mislocalize spatial positions forward, in the direction of motion (representational momentum) and downward in the direction of gravity (representational gravity). Moreover, spatial localization errors were found to evolve dynamically with time in a pattern congruent with an anticipated trajectory (representational trajectory). The present study attempts to ascertain the degree to which vestibular information plays a role in these phenomena. Human observers performed a spatial localization task while tilted to varying degrees and referring to the vanishing locations of targets moving along several directions. A Fourier decomposition of the obtained spatial localization errors revealed that although spatial errors were increased "downward" mainly along the body's longitudinal axis (idiotropic dominance), the degree of misalignment between the latter and physical gravity modulated the time course of the localization responses. This pattern is surmised to reflect increased uncertainty about the internal model when faced with conflicting cues regarding the perceived "downward" direction.

The high accuracy data processing system of laser interferometry signals based on MSP430

NASA Astrophysics Data System (ADS)

Qi, Yong-yue; Lin, Yu-chi; Zhao, Mei-rong

2009-07-01

Generally speaking there are two orthogonal signals used in single-frequency laser interferometer for differentiating direction and electronic subdivision. However there usually exist three errors with the interferential signals: zero offsets error, unequal amplitude error and quadrature phase shift error. These three errors have a serious impact on subdivision precision. Based on Heydemann error compensation algorithm, it is proposed to achieve compensation of the three errors. Due to complicated operation of the Heydemann mode, a improved arithmetic is advanced to decrease the calculating time effectively in accordance with the special characteristic that only one item of data will be changed in each fitting algorithm operation. Then a real-time and dynamic compensatory circuit is designed. Taking microchip MSP430 as the core of hardware system, two input signals with the three errors are turned into digital quantity by the AD7862. After data processing in line with improved arithmetic, two ideal signals without errors are output by the AD7225. At the same time two original signals are turned into relevant square wave and imported to the differentiating direction circuit. The impulse exported from the distinguishing direction circuit is counted by the timer of the microchip. According to the number of the pulse and the soft subdivision the final result is showed by LED. The arithmetic and the circuit are adopted to test the capability of a laser interferometer with 8 times optical path difference and the measuring accuracy of 12-14nm is achieved.

Tilt error in cryospheric surface radiation measurements at high latitudes: a model study

NASA Astrophysics Data System (ADS)

Bogren, Wiley Steven; Faulkner Burkhart, John; Kylling, Arve

2016-03-01

We have evaluated the magnitude and makeup of error in cryospheric radiation observations due to small sensor misalignment in in situ measurements of solar irradiance. This error is examined through simulation of diffuse and direct irradiance arriving at a detector with a cosine-response fore optic. Emphasis is placed on assessing total error over the solar shortwave spectrum from 250 to 4500 nm, as well as supporting investigation over other relevant shortwave spectral ranges. The total measurement error introduced by sensor tilt is dominated by the direct component. For a typical high-latitude albedo measurement with a solar zenith angle of 60°, a sensor tilted by 1, 3, and 5° can, respectively introduce up to 2.7, 8.1, and 13.5 % error into the measured irradiance and similar errors in the derived albedo. Depending on the daily range of solar azimuth and zenith angles, significant measurement error can persist also in integrated daily irradiance and albedo. Simulations including a cloud layer demonstrate decreasing tilt error with increasing cloud optical depth.

An a-posteriori finite element error estimator for adaptive grid computation of viscous incompressible flows

NASA Astrophysics Data System (ADS)

Wu, Heng

2000-10-01

In this thesis, an a-posteriori error estimator is presented and employed for solving viscous incompressible flow problems. In an effort to detect local flow features, such as vortices and separation, and to resolve flow details precisely, a velocity angle error estimator e theta which is based on the spatial derivative of velocity direction fields is designed and constructed. The a-posteriori error estimator corresponds to the antisymmetric part of the deformation-rate-tensor, and it is sensitive to the second derivative of the velocity angle field. Rationality discussions reveal that the velocity angle error estimator is a curvature error estimator, and its value reflects the accuracy of streamline curves. It is also found that the velocity angle error estimator contains the nonlinear convective term of the Navier-Stokes equations, and it identifies and computes the direction difference when the convective acceleration direction and the flow velocity direction have a disparity. Through benchmarking computed variables with the analytic solution of Kovasznay flow or the finest grid of cavity flow, it is demonstrated that the velocity angle error estimator has a better performance than the strain error estimator. The benchmarking work also shows that the computed profile obtained by using etheta can achieve the best matching outcome with the true theta field, and that it is asymptotic to the true theta variation field, with a promise of fewer unknowns. Unstructured grids are adapted by employing local cell division as well as unrefinement of transition cells. Using element class and node class can efficiently construct a hierarchical data structure which provides cell and node inter-reference at each adaptive level. Employing element pointers and node pointers can dynamically maintain the connection of adjacent elements and adjacent nodes, and thus avoids time-consuming search processes. The adaptive scheme is applied to viscous incompressible flow at different Reynolds numbers. It is found that the velocity angle error estimator can detect most flow characteristics and produce dense grids in the regions where flow velocity directions have abrupt changes. In addition, the e theta estimator makes the derivative error dilutely distribute in the whole computational domain and also allows the refinement to be conducted at regions of high error. Through comparison of the velocity angle error across the interface with neighbouring cells, it is verified that the adaptive scheme in using etheta provides an optimum mesh which can clearly resolve local flow features in a precise way. The adaptive results justify the applicability of the etheta estimator and prove that this error estimator is a valuable adaptive indicator for the automatic refinement of unstructured grids.

GPS measurement error gives rise to spurious 180 degree turning angles and strong directional biases in animal movement data.

PubMed

Hurford, Amy

2009-05-20

Movement data are frequently collected using Global Positioning System (GPS) receivers, but recorded GPS locations are subject to errors. While past studies have suggested methods to improve location accuracy, mechanistic movement models utilize distributions of turning angles and directional biases and these data present a new challenge in recognizing and reducing the effect of measurement error. I collected locations from a stationary GPS collar, analyzed a probabilistic model and used Monte Carlo simulations to understand how measurement error affects measured turning angles and directional biases. Results from each of the three methods were in complete agreement: measurement error gives rise to a systematic bias where a stationary animal is most likely to be measured as turning 180 degrees or moving towards a fixed point in space. These spurious effects occur in GPS data when the measured distance between locations is <20 meters. Measurement error must be considered as a possible cause of 180 degree turning angles in GPS data. Consequences of failing to account for measurement error are predicting overly tortuous movement, numerous returns to previously visited locations, inaccurately predicting species range, core areas, and the frequency of crossing linear features. By understanding the effect of GPS measurement error, ecologists are able to disregard false signals to more accurately design conservation plans for endangered wildlife.

Mathematical fundamentals for the noise immunity of the genetic code.

PubMed

Fimmel, Elena; Strüngmann, Lutz

2018-02-01

Symmetry is one of the essential and most visible patterns that can be seen in nature. Starting from the left-right symmetry of the human body, all types of symmetry can be found in crystals, plants, animals and nature as a whole. Similarly, principals of symmetry are also some of the fundamental and most useful tools in modern mathematical natural science that play a major role in theory and applications. As a consequence, it is not surprising that the desire to understand the origin of life, based on the genetic code, forces us to involve symmetry as a mathematical concept. The genetic code can be seen as a key to biological self-organisation. All living organisms have the same molecular bases - an alphabet consisting of four letters (nitrogenous bases): adenine, cytosine, guanine, and thymine. Linearly ordered sequences of these bases contain the genetic information for synthesis of proteins in all forms of life. Thus, one of the most fascinating riddles of nature is to explain why the genetic code is as it is. Genetic coding possesses noise immunity which is the fundamental feature that allows to pass on the genetic information from parents to their descendants. Hence, since the time of the discovery of the genetic code, scientists have tried to explain the noise immunity of the genetic information. In this chapter we will discuss recent results in mathematical modelling of the genetic code with respect to noise immunity, in particular error-detection and error-correction. We will focus on two central properties: Degeneracy and frameshift correction. Different amino acids are encoded by different quantities of codons and a connection between this degeneracy and the noise immunity of genetic information is a long standing hypothesis. Biological implications of the degeneracy have been intensively studied and whether the natural code is a frozen accident or a highly optimised product of evolution is still controversially discussed. Symmetries in the structure of degeneracy of the genetic code are essential and give evidence of substantial advantages of the natural code over other possible ones. In the present chapter we will present a recent approach to explain the degeneracy of the genetic code by algorithmic methods from bioinformatics, and discuss its biological consequences. The biologists recognised this problem immediately after the detection of the non-overlapping structure of the genetic code, i.e., coding sequences are to be read in a unique way determined by their reading frame. But how does the reading head of the ribosome recognises an error in the grouping of codons, caused by e.g. insertion or deletion of a base, that can be fatal during the translation process and may result in nonfunctional proteins? In this chapter we will discuss possible solutions to the frameshift problem with a focus on the theory of so-called circular codes that were discovered in large gene populations of prokaryotes and eukaryotes in the early 90s. Circular codes allow to detect a frameshift of one or two positions and recently a beautiful theory of such codes has been developed using statistics, group theory and graph theory. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Antibiotics and antibiotic resistance: a bitter fight against evolution.

PubMed

Rodríguez-Rojas, Alexandro; Rodríguez-Beltrán, Jerónimo; Couce, Alejandro; Blázquez, Jesús

2013-08-01

One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance. Copyright © 2013 Elsevier GmbH. All rights reserved.

Initializing a Mesoscale Boundary-Layer Model with Radiosonde Observations

NASA Astrophysics Data System (ADS)

Berri, Guillermo J.; Bertossa, Germán

2018-01-01

A mesoscale boundary-layer model is used to simulate low-level regional wind fields over the La Plata River of South America, a region characterized by a strong daily cycle of land-river surface-temperature contrast and low-level circulations of sea-land breeze type. The initial and boundary conditions are defined from a limited number of local observations and the upper boundary condition is taken from the only radiosonde observations available in the region. The study considers 14 different upper boundary conditions defined from the radiosonde data at standard levels, significant levels, level of the inversion base and interpolated levels at fixed heights, all of them within the first 1500 m. The period of analysis is 1994-2008 during which eight daily observations from 13 weather stations of the region are used to validate the 24-h surface-wind forecast. The model errors are defined as the root-mean-square of relative error in wind-direction frequency distribution and mean wind speed per wind sector. Wind-direction errors are greater than wind-speed errors and show significant dispersion among the different upper boundary conditions, not present in wind speed, revealing a sensitivity to the initialization method. The wind-direction errors show a well-defined daily cycle, not evident in wind speed, with the minimum at noon and the maximum at dusk, but no systematic deterioration with time. The errors grow with the height of the upper boundary condition level, in particular wind direction, and double the errors obtained when the upper boundary condition is defined from the lower levels. The conclusion is that defining the model upper boundary condition from radiosonde data closer to the ground minimizes the low-level wind-field errors throughout the region.

Estimation of genetic parameters for milk yield in Murrah buffaloes by Bayesian inference.

PubMed

Breda, F C; Albuquerque, L G; Euclydes, R F; Bignardi, A B; Baldi, F; Torres, R A; Barbosa, L; Tonhati, H

2010-02-01

Random regression models were used to estimate genetic parameters for test-day milk yield in Murrah buffaloes using Bayesian inference. Data comprised 17,935 test-day milk records from 1,433 buffaloes. Twelve models were tested using different combinations of third-, fourth-, fifth-, sixth-, and seventh-order orthogonal polynomials of weeks of lactation for additive genetic and permanent environmental effects. All models included the fixed effects of contemporary group, number of daily milkings and age of cow at calving as covariate (linear and quadratic effect). In addition, residual variances were considered to be heterogeneous with 6 classes of variance. Models were selected based on the residual mean square error, weighted average of residual variance estimates, and estimates of variance components, heritabilities, correlations, eigenvalues, and eigenfunctions. Results indicated that changes in the order of fit for additive genetic and permanent environmental random effects influenced the estimation of genetic parameters. Heritability estimates ranged from 0.19 to 0.31. Genetic correlation estimates were close to unity between adjacent test-day records, but decreased gradually as the interval between test-days increased. Results from mean squared error and weighted averages of residual variance estimates suggested that a model considering sixth- and seventh-order Legendre polynomials for additive and permanent environmental effects, respectively, and 6 classes for residual variances, provided the best fit. Nevertheless, this model presented the largest degree of complexity. A more parsimonious model, with fourth- and sixth-order polynomials, respectively, for these same effects, yielded very similar genetic parameter estimates. Therefore, this last model is recommended for routine applications. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).

PubMed

Williams, Robert C; Elston, Robert C; Kumar, Pankaj; Knowler, William C; Abboud, Hanna E; Adler, Sharon; Bowden, Donald W; Divers, Jasmin; Freedman, Barry I; Igo, Robert P; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Klag, Michael J; Kohn, Orly; Langefeld, Carl D; Leehey, David J; Nelson, Robert G; Nicholas, Susanne B; Pahl, Madeleine V; Parekh, Rulan S; Rotter, Jerome I; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Smith, Michael W; Taylor, Kent D; Thameem, Farook; Thornley-Brown, Denyse; Winkler, Cheryl A; Guo, Xiuqing; Zager, Phillip; Hanson, Robert L

2016-05-04

The presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample. A fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy. The identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.

Modeling for Military Operational Medicine Scientific and Technical Objectives

DTIC Science & Technology

2005-09-01

measurements and less error in interpreting the measurements since the sensor units are placed directly under armor ; and (3) new material that matches the...more accurate measurements and less error in interpreting the measurements, since the sensor units are placed directly under armor ; and (3) new

Effects of Error Correction during Assessment Probes on the Acquisition of Sight Words for Students with Moderate Intellectual Disabilities

ERIC Educational Resources Information Center

Waugh, Rebecca E.

2010-01-01

Simultaneous prompting is an errorless learning strategy designed to reduce the number of errors students make; however, research has shown a disparity in the number of errors students make during instructional versus probe trials. This study directly examined the effects of error correction versus no error correction during probe trials on the…

Effects of Error Correction during Assessment Probes on the Acquisition of Sight Words for Students with Moderate Intellectual Disabilities

ERIC Educational Resources Information Center

Waugh, Rebecca E.; Alberto, Paul A.; Fredrick, Laura D.

2011-01-01

Simultaneous prompting is an errorless learning strategy designed to reduce the number of errors students make; however, research has shown a disparity in the number of errors students make during instructional versus probe trials. This study directly examined the effects of error correction versus no error correction during probe trials on the…

Dominance genetic variance for traits under directional selection in Drosophila serrata.

PubMed

Sztepanacz, Jacqueline L; Blows, Mark W

2015-05-01

In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait-fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. Copyright © 2015 by the Genetics Society of America.

Skills, rules and knowledge in aircraft maintenance: errors in context

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Williamson, Ann

2002-01-01

Automatic or skill-based behaviour is generally considered to be less prone to error than behaviour directed by conscious control. However, researchers who have applied Rasmussen's skill-rule-knowledge human error framework to accidents and incidents have sometimes found that skill-based errors appear in significant numbers. It is proposed that this is largely a reflection of the opportunities for error which workplaces present and does not indicate that skill-based behaviour is intrinsically unreliable. In the current study, 99 errors reported by 72 aircraft mechanics were examined in the light of a task analysis based on observations of the work of 25 aircraft mechanics. The task analysis identified the opportunities for error presented at various stages of maintenance work packages and by the job as a whole. Once the frequency of each error type was normalized in terms of the opportunities for error, it became apparent that skill-based performance is more reliable than rule-based performance, which is in turn more reliable than knowledge-based performance. The results reinforce the belief that industrial safety interventions designed to reduce errors would best be directed at those aspects of jobs that involve rule- and knowledge-based performance.

Health care providers and direct-to-consumer access and advertising of genetic testing in the United States

PubMed Central

2011-01-01

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers. PMID:22204616

Health care providers and direct-to-consumer access and advertising of genetic testing in the United States.

PubMed

Myers, Melanie F

2011-12-28

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers.

Consumers' views of direct-to-consumer genetic information.

PubMed

McBride, Colleen M; Wade, Christopher H; Kaphingst, Kimberly A

2010-01-01

In this report, we describe the evolution and types of genetic information provided directly to consumers, discuss potential advantages and disadvantages of these products, and review research evaluating consumer responses to direct-to-consumer (DTC) genetic testing. The available evidence to date has focused on predictive tests and does not suggest that individuals, health care providers, or health care systems have been harmed by a DTC provision of genetic information. An understanding of consumer responses to susceptibility tests has lagged behind. The Multiplex Initiative is presented as a case study of research to understand consumers' responses to DTC susceptibility tests. Three priority areas are recommended for accelerated research activities to inform public policy regarding DTC genetic information: (a) exploring consumer's long-term responses to DTC genetic testing on a comprehensive set of outcomes, (b) evaluating optimal services to support decision making about genetic testing, and (c) evaluating best practices in promoting genetic competencies among health providers.

Variations of Human DNA Polymerase Genes as Biomarkers of Prostate Cancer Progression

DTIC Science & Technology

2013-07-01

discovery , cancer genetics 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC...variations identified (including all single and double mutant combinations of the Triple mutant), and some POLK mutants • Discovery of a novel...Athens, Greece, 07/10 Makridakis N. Error-prone polymerase mutations and prostate cancer progression, COBRE /Cancer Genetics group seminar, Tulane

Huntington’s Disease

DTIC Science & Technology

2012-05-01

testing due to the inheritance pattern of the disease. The airman’s father and brother were both negative for the Huntington gene; however, both the...airman and his mother were found to be positive and underwent further genetic counseling. The airman had discussed the results and his concern with his...but modern genetic testing can now detect the defect in the HTT allele of chromosome #4.3 In affected individuals, errors in DNA replication occur

How Darwinian reductionism refutes genetic determinism.

PubMed

Rosoff, Philip M; Rosenberg, Alex

2006-03-01

Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light of what is now known about the inborn error of metabolism phenylketonuria (PKU), which has for so long been the poster child 'simple' argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises.

Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism

PubMed Central

Yubero, Dèlia; Brandi, Núria; Ormazabal, Aida; Garcia-Cazorla, Àngels; Pérez-Dueñas, Belén; Campistol, Jaime; Ribes, Antonia; Palau, Francesc

2016-01-01

Background Next-generation sequencing (NGS) technology has allowed the promotion of genetic diagnosis and are becoming increasingly inexpensive and faster. To evaluate the utility of NGS in the clinical field, a targeted genetic panel approach was designed for the diagnosis of a set of inborn errors of metabolism (IEM). The final aim of the study was to compare the findings for the diagnostic yield of NGS in patients who presented with consistent clinical and biochemical suspicion of IEM with those obtained for patients who did not have specific biomarkers. Methods The subjects studied (n = 146) were classified into two categories: Group 1 (n = 81), which consisted of patients with clinical and biochemical suspicion of IEM, and Group 2 (n = 65), which consisted of IEM cases with clinical suspicion and unspecific biomarkers. A total of 171 genes were analyzed using a custom targeted panel of genes followed by Sanger validation. Results Genetic diagnosis was achieved in 50% of patients (73/146). In addition, the diagnostic yield obtained for Group 1 was 78% (63/81), and this rate decreased to 15.4% (10/65) in Group 2 (X2 = 76.171; p < 0.0001). Conclusions A rapid and effective genetic diagnosis was achieved in our cohort, particularly the group that had both clinical and biochemical indications for the diagnosis. PMID:27243974

Short communication: Multi-trait estimation of genetic parameters for milk protein composition in the Danish Holstein.

PubMed

Gebreyesus, G; Lund, M S; Janss, L; Poulsen, N A; Larsen, L B; Bovenhuis, H; Buitenhuis, A J

2016-04-01

Genetic parameters were estimated for the major milk proteins using bivariate and multi-trait models based on genomic relationships between animals. The analyses included, apart from total protein percentage, αS1-casein (CN), αS2-CN, β-CN, κ-CN, α-lactalbumin, and β-lactoglobulin, as well as the posttranslational sub-forms of glycosylated κ-CN and αS1-CN-8P (phosphorylated). Standard errors of the estimates were used to compare the models. In total, 650 Danish Holstein cows across 4 parities and days in milk ranging from 9 to 481d were selected from 21 herds. The multi-trait model generally resulted in lower standard errors of heritability estimates, suggesting that genetic parameters can be estimated with high accuracy using multi-trait analyses with genomic relationships for scarcely recorded traits. The heritability estimates from the multi-trait model ranged from low (0.05 for β-CN) to high (0.78 for κ-CN). Genetic correlations between the milk proteins and the total milk protein percentage were generally low, suggesting the possibility to alter protein composition through selective breeding with little effect on total milk protein percentage. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Application of a soft computing technique in predicting the percentage of shear force carried by walls in a rectangular channel with non-homogeneous roughness.

PubMed

Khozani, Zohreh Sheikh; Bonakdari, Hossein; Zaji, Amir Hossein

2016-01-01

Two new soft computing models, namely genetic programming (GP) and genetic artificial algorithm (GAA) neural network (a combination of modified genetic algorithm and artificial neural network methods) were developed in order to predict the percentage of shear force in a rectangular channel with non-homogeneous roughness. The ability of these methods to estimate the percentage of shear force was investigated. Moreover, the independent parameters' effectiveness in predicting the percentage of shear force was determined using sensitivity analysis. According to the results, the GP model demonstrated superior performance to the GAA model. A comparison was also made between the GP program determined as the best model and five equations obtained in prior research. The GP model with the lowest error values (root mean square error ((RMSE) of 0.0515) had the best function compared with the other equations presented for rough and smooth channels as well as smooth ducts. The equation proposed for rectangular channels with rough boundaries (RMSE of 0.0642) outperformed the prior equations for smooth boundaries.

A study of the genetic relationships within and among wolf packs using DNA fingerprinting and mitochondrial DNA

USGS Publications Warehouse

Lehman, Niles; Clarkson, Peter; Mech, L. David; Meier, Thomas J.; Wayne, Robert K.

1992-01-01

DNA fingerprinting and mitochondrial DNA analyses have not been used in combination to study relatedness in natural populations. We present an approach that involves defining the mean fingerprint similarities among individuals thought to be unrelated because they have different mtDNA genotypes. Two classes of related individuals are identified by their distance in standard errors above this mean value. The number of standard errors is determined by analysis of the association between fingerprint similarity and relatedness in a population with a known genealogy. We apply this approach to gray wolf packs from Minnesota, Alaska, and the Northwest Territories. Our results show that: (1) wolf packs consist primarily of individuals that are closely related genetically, but some packs contain unrelated, non-reproducing individuals; (2) dispersal among packs within the same area is common; and (3) short-range dispersal appears more common for female than male wolves. The first two of these genetically-based observations are consistent with behavioral data on pack structure and dispersal in wolves, while the apparent sex bias in dispersal was not expected.

Indoor high precision three-dimensional positioning system based on visible light communication using modified genetic algorithm

NASA Astrophysics Data System (ADS)

Chen, Hao; Guan, Weipeng; Li, Simin; Wu, Yuxiang

2018-04-01

To improve the precision of indoor positioning and actualize three-dimensional positioning, a reversed indoor positioning system based on visible light communication (VLC) using genetic algorithm (GA) is proposed. In order to solve the problem of interference between signal sources, CDMA modulation is used. Each light-emitting diode (LED) in the system broadcasts a unique identity (ID) code using CDMA modulation. Receiver receives mixed signal from every LED reference point, by the orthogonality of spreading code in CDMA modulation, ID information and intensity attenuation information from every LED can be obtained. According to positioning principle of received signal strength (RSS), the coordinate of the receiver can be determined. Due to system noise and imperfection of device utilized in the system, distance between receiver and transmitters will deviate from the real value resulting in positioning error. By introducing error correction factors to global parallel search of genetic algorithm, coordinates of the receiver in three-dimensional space can be determined precisely. Both simulation results and experimental results show that in practical application scenarios, the proposed positioning system can realize high precision positioning service.

Modeling misidentification errors that result from use of genetic tags in capture-recapture studies

USGS Publications Warehouse

Yoshizaki, J.; Brownie, C.; Pollock, K.H.; Link, W.A.

2011-01-01

Misidentification of animals is potentially important when naturally existing features (natural tags) such as DNA fingerprints (genetic tags) are used to identify individual animals. For example, when misidentification leads to multiple identities being assigned to an animal, traditional estimators tend to overestimate population size. Accounting for misidentification in capture-recapture models requires detailed understanding of the mechanism. Using genetic tags as an example, we outline a framework for modeling the effect of misidentification in closed population studies when individual identification is based on natural tags that are consistent over time (non-evolving natural tags). We first assume a single sample is obtained per animal for each capture event, and then generalize to the case where multiple samples (such as hair or scat samples) are collected per animal per capture occasion. We introduce methods for estimating population size and, using a simulation study, we show that our new estimators perform well for cases with moderately high capture probabilities or high misidentification rates. In contrast, conventional estimators can seriously overestimate population size when errors due to misidentification are ignored. ?? 2009 Springer Science+Business Media, LLC.

Investigation of interfractional shape variations based on statistical point distribution model for prostate cancer radiation therapy.

PubMed

Shibayama, Yusuke; Arimura, Hidetaka; Hirose, Taka-Aki; Nakamoto, Takahiro; Sasaki, Tomonari; Ohga, Saiji; Matsushita, Norimasa; Umezu, Yoshiyuki; Nakamura, Yasuhiko; Honda, Hiroshi

2017-05-01

The setup errors and organ motion errors pertaining to clinical target volume (CTV) have been considered as two major causes of uncertainties in the determination of the CTV-to-planning target volume (PTV) margins for prostate cancer radiation treatment planning. We based our study on the assumption that interfractional target shape variations are not negligible as another source of uncertainty for the determination of precise CTV-to-PTV margins. Thus, we investigated the interfractional shape variations of CTVs based on a point distribution model (PDM) for prostate cancer radiation therapy. To quantitate the shape variations of CTVs, the PDM was applied for the contours of 4 types of CTV regions (low-risk, intermediate- risk, high-risk CTVs, and prostate plus entire seminal vesicles), which were delineated by considering prostate cancer risk groups on planning computed tomography (CT) and cone beam CT (CBCT) images of 73 fractions of 10 patients. The standard deviations (SDs) of the interfractional random errors for shape variations were obtained from covariance matrices based on the PDMs, which were generated from vertices of triangulated CTV surfaces. The correspondences between CTV surface vertices were determined based on a thin-plate spline robust point matching algorithm. The systematic error for shape variations was defined as the average deviation between surfaces of an average CTV and planning CTVs, and the random error as the average deviation of CTV surface vertices for fractions from an average CTV surface. The means of the SDs of the systematic errors for the four types of CTVs ranged from 1.0 to 2.0 mm along the anterior direction, 1.2 to 2.6 mm along the posterior direction, 1.0 to 2.5 mm along the superior direction, 0.9 to 1.9 mm along the inferior direction, 0.9 to 2.6 mm along the right direction, and 1.0 to 3.0 mm along the left direction. Concerning the random errors, the means of the SDs ranged from 0.9 to 1.2 mm along the anterior direction, 1.0 to 1.4 mm along the posterior direction, 0.9 to 1.3 mm along the superior direction, 0.8 to 1.0 mm along the inferior direction, 0.8 to 0.9 mm along the right direction, and 0.8 to 1.0 mm along the left direction. Since the shape variations were not negligible for intermediate and high-risk CTVs, they should be taken into account for the determination of the CTV-to-PTV margins in radiation treatment planning of prostate cancer. © 2017 American Association of Physicists in Medicine.

Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

PubMed Central

Sztepanacz, Jacqueline L.; Blows, Mark W.

2015-01-01

In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

Atmospheric refraction effects on baseline error in satellite laser ranging systems

NASA Technical Reports Server (NTRS)

Im, K. E.; Gardner, C. S.

1982-01-01

Because of the mathematical complexities involved in exact analyses of baseline errors, it is not easy to isolate atmospheric refraction effects; however, by making certain simplifying assumptions about the ranging system geometry, relatively simple expressions can be derived which relate the baseline errors directly to the refraction errors. The results indicate that even in the absence of other errors, the baseline error for intercontinental baselines can be more than an order of magnitude larger than the refraction error.

SU-E-J-88: The Study of Setup Error Measured by CBCT in Postoperative Radiotherapy for Cervical Carcinoma

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

Runxiao, L; Aikun, W; Xiaomei, F

2015-06-15

Purpose: To compare two registration methods in the CBCT guided radiotherapy for cervical carcinoma, analyze the setup errors and registration methods, determine the margin required for clinical target volume(CTV) extending to planning target volume(PTV). Methods: Twenty patients with cervical carcinoma were enrolled. All patients were underwent CT simulation in the supine position. Transfering the CT images to the treatment planning system and defining the CTV, PTV and the organs at risk (OAR), then transmit them to the XVI workshop. CBCT scans were performed before radiotherapy and registered to planning CT images according to bone and gray value registration methods. Comparedmore » two methods and obtain left-right(X), superior-inferior(Y), anterior-posterior (Z) setup errors, the margin required for CTV to PTV were calculated. Results: Setup errors were unavoidable in postoperative cervical carcinoma irradiation. The setup errors measured by method of bone (systemic ± random) on X(1eft.right),Y(superior.inferior),Z(anterior.posterior) directions were(0.24±3.62),(0.77±5.05) and (0.13±3.89)mm, respectively, the setup errors measured by method of grey (systemic ± random) on X(1eft-right), Y(superior-inferior), Z(anterior-posterior) directions were(0.31±3.93), (0.85±5.16) and (0.21±4.12)mm, respectively.The spatial distributions of setup error was maximum in Y direction. The margins were 4 mm in X axis, 6 mm in Y axis, 4 mm in Z axis respectively.These two registration methods were similar and highly recommended. Conclusion: Both bone and grey registration methods could offer an accurate setup error. The influence of setup errors of a PTV margin would be suggested by 4mm, 4mm and 6mm on X, Y and Z directions for postoperative radiotherapy for cervical carcinoma.« less

Ethical Considerations on Disclosure When Medical Error Is Discovered During Medicolegal Death Investigation.

PubMed

Wolf, Dwayne A; Drake, Stacy A; Snow, Francine K

2017-12-01

In the course of fulfilling their statutory role, physicians performing medicolegal investigations may recognize clinical colleagues' medical errors. If the error is found to have led directly to the patient's death (missed diagnosis or incorrect diagnosis, for example), then the forensic pathologist has a professional responsibility to include the information in the autopsy report and make sure that the family is appropriately informed. When the error is significant but did not lead directly to the patient's demise, ethical questions may arise regarding the obligations of the medical examiner to disclose the error to the clinicians or to the family. This case depicts the discovery of medical error likely unrelated to the cause of death and describes one possible ethical approach to disclosure derived from an ethical reasoning model addressing ethical principles of respect for persons/autonomy, beneficence, nonmaleficence, and justice.

Development of multiple-eye PIV using mirror array

NASA Astrophysics Data System (ADS)

Maekawa, Akiyoshi; Sakakibara, Jun

2018-06-01

In order to reduce particle image velocimetry measurement error, we manufactured an ellipsoidal polyhedral mirror and placed it between a camera and flow target to capture n images of identical particles from n (=80 maximum) different directions. The 3D particle positions were determined from the ensemble average of n C2 intersecting points of a pair of line-of-sight back-projected points from a particle found in any combination of two images in the n images. The method was then applied to a rigid-body rotating flow and a turbulent pipe flow. In the former measurement, bias error and random error fell in a range of  ±0.02 pixels and 0.02–0.05 pixels, respectively; additionally, random error decreased in proportion to . In the latter measurement, in which the measured value was compared to direct numerical simulation, bias error was reduced and random error also decreased in proportion to .

Imaging genetics approach to predict progression of Parkinson's diseases.

PubMed

Mansu Kim; Seong-Jin Son; Hyunjin Park

2017-07-01

Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123 I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.

Measurement-based quantum communication with resource states generated by entanglement purification

NASA Astrophysics Data System (ADS)

Wallnöfer, J.; Dür, W.

2017-01-01

We investigate measurement-based quantum communication with noisy resource states that are generated by entanglement purification. We consider the transmission of encoded information via noisy quantum channels using a measurement-based implementation of encoding, error correction, and decoding. We show that such an approach offers advantages over direct transmission, gate-based error correction, and measurement-based schemes with direct generation of resource states. We analyze the noise structure of resource states generated by entanglement purification and show that a local error model, i.e., noise acting independently on all qubits of the resource state, is a good approximation in general, and provides an exact description for Greenberger-Horne-Zeilinger states. The latter are resources for a measurement-based implementation of error-correction codes for bit-flip or phase-flip errors. This provides an approach to link the recently found very high thresholds for fault-tolerant measurement-based quantum information processing based on local error models for resource states with error thresholds for gate-based computational models.

Genetics Home Reference: essential pentosuria

MedlinePlus

... MacCoss MJ, Levy-Lahad E, King MC, Motulsky AG. Garrod's fourth inborn error of metabolism solved by ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease.

PubMed

Kapur, Mridu; Ackerman, Susan L

2018-03-01

Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of the translational defects observed in these diseases. Finally, we emphasize the importance of tRNA, their associated enzymes, and the inextricable link between accuracy and efficiency in the maintenance of translational fidelity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The GEnes in Myopia (GEM) study in understanding the aetiology of refractive errors.

PubMed

Baird, Paul N; Schäche, Maria; Dirani, Mohamed

2010-11-01

Refractive errors represent the leading cause of correctable vision impairment and blindness in the world with an estimated 2 billion people affected. Refractive error refers to a group of refractive conditions including hypermetropia, myopia, astigmatism and presbyopia but relatively little is known about their aetiology. In order to explore the potential role of genetic determinants in refractive error the "GEnes in Myopia (GEM) study" was established in 2004. The findings that have resulted from this study have not only provided greater insight into the role of genes and other factors involved in myopia but have also gone some way to uncovering the aetiology of other refractive errors. This review will describe some of the major findings of the GEM study and their relative contribution to the literature, illuminate where the deficiencies are in our understanding of the development of refractive errors and how we will advance this field in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.

Random measurement error: Why worry? An example of cardiovascular risk factors.

PubMed

Brakenhoff, Timo B; van Smeden, Maarten; Visseren, Frank L J; Groenwold, Rolf H H

2018-01-01

With the increased use of data not originally recorded for research, such as routine care data (or 'big data'), measurement error is bound to become an increasingly relevant problem in medical research. A common view among medical researchers on the influence of random measurement error (i.e. classical measurement error) is that its presence leads to some degree of systematic underestimation of studied exposure-outcome relations (i.e. attenuation of the effect estimate). For the common situation where the analysis involves at least one exposure and one confounder, we demonstrate that the direction of effect of random measurement error on the estimated exposure-outcome relations can be difficult to anticipate. Using three example studies on cardiovascular risk factors, we illustrate that random measurement error in the exposure and/or confounder can lead to underestimation as well as overestimation of exposure-outcome relations. We therefore advise medical researchers to refrain from making claims about the direction of effect of measurement error in their manuscripts, unless the appropriate inferential tools are used to study or alleviate the impact of measurement error from the analysis.

Study of parameter identification using hybrid neural-genetic algorithm in electro-hydraulic servo system

NASA Astrophysics Data System (ADS)

Moon, Byung-Young

2005-12-01

The hybrid neural-genetic multi-model parameter estimation algorithm was demonstrated. This method can be applied to structured system identification of electro-hydraulic servo system. This algorithms consist of a recurrent incremental credit assignment(ICRA) neural network and a genetic algorithm. The ICRA neural network evaluates each member of a generation of model and genetic algorithm produces new generation of model. To evaluate the proposed method, electro-hydraulic servo system was designed and manufactured. The experiment was carried out to figure out the hybrid neural-genetic multi-model parameter estimation algorithm. As a result, the dynamic characteristics were obtained such as the parameters(mass, damping coefficient, bulk modulus, spring coefficient), which minimize total square error. The result of this study can be applied to hydraulic systems in industrial fields.

[Comparison of Google and Yahoo applications for geocoding of postal addresses in epidemiological studies].

PubMed

Quesada, Jose Antonio; Nolasco, Andreu; Moncho, Joaquín

2013-01-01

Geocoding is the assignment of geographic coordinates to spatial points, which often are postal addresses. The error made in applying this process can introduce bias in estimates of spatiotemporal models in epidemiological studies. No studies have been found to measure the error made in applying this process in Spanish cities. The objective is to evaluate the errors in magnitude and direction from two free sources (Google and Yahoo) with regard to a GPS in two Spanish cities. 30 addresses were geocoded with those two sources and the GPS in Santa Pola (Alicante) and Alicante city. The distances were calculated in metres (median, CI95%) between the sources and the GPS, globally and according to the status reported by each source. The directionality of the error was evaluated by calculating the location quadrant and applying a Chi-Square test. The GPS error was evaluated by geocoding 11 addresses twice at 4 days interval. The overall median in Google-GPS was 23,2 metres (16,0-32,1) for Santa Pola, and 21,4 meters (14,9-31,1) for Alicante. The overall median in Yahoo was 136,0 meters (19,2-318,5) for Santa Pola, and 23,8 meters (13,6- 29,2) for Alicante. Between the 73% and 90% were geocoded by status as "exact or interpolated" (minor error), where Goggle and Yahoo had a median error between 19 and 23 metres in the two cities. The GPS had a median error of 13.8 meters (6,7-17,8). No error directionality was detected. Google error is acceptable and stable in the two cities, so that it is a reliable source for Para medir elgeocoding addresses in Spain in epidemiological studies.

Gene Level Meta-Analysis of Quantitative Traits by Functional Linear Models.

PubMed

Fan, Ruzong; Wang, Yifan; Boehnke, Michael; Chen, Wei; Li, Yun; Ren, Haobo; Lobach, Iryna; Xiong, Momiao

2015-08-01

Meta-analysis of genetic data must account for differences among studies including study designs, markers genotyped, and covariates. The effects of genetic variants may differ from population to population, i.e., heterogeneity. Thus, meta-analysis of combining data of multiple studies is difficult. Novel statistical methods for meta-analysis are needed. In this article, functional linear models are developed for meta-analyses that connect genetic data to quantitative traits, adjusting for covariates. The models can be used to analyze rare variants, common variants, or a combination of the two. Both likelihood-ratio test (LRT) and F-distributed statistics are introduced to test association between quantitative traits and multiple variants in one genetic region. Extensive simulations are performed to evaluate empirical type I error rates and power performance of the proposed tests. The proposed LRT and F-distributed statistics control the type I error very well and have higher power than the existing methods of the meta-analysis sequence kernel association test (MetaSKAT). We analyze four blood lipid levels in data from a meta-analysis of eight European studies. The proposed methods detect more significant associations than MetaSKAT and the P-values of the proposed LRT and F-distributed statistics are usually much smaller than those of MetaSKAT. The functional linear models and related test statistics can be useful in whole-genome and whole-exome association studies. Copyright © 2015 by the Genetics Society of America.

Scope of Gradient and Genetic Algorithms in Multivariable Function Optimization

NASA Technical Reports Server (NTRS)

Shaykhian, Gholam Ali; Sen, S. K.

2007-01-01

Global optimization of a multivariable function - constrained by bounds specified on each variable and also unconstrained - is an important problem with several real world applications. Deterministic methods such as the gradient algorithms as well as the randomized methods such as the genetic algorithms may be employed to solve these problems. In fact, there are optimization problems where a genetic algorithm/an evolutionary approach is preferable at least from the quality (accuracy) of the results point of view. From cost (complexity) point of view, both gradient and genetic approaches are usually polynomial-time; there are no serious differences in this regard, i.e., the computational complexity point of view. However, for certain types of problems, such as those with unacceptably erroneous numerical partial derivatives and those with physically amplified analytical partial derivatives whose numerical evaluation involves undesirable errors and/or is messy, a genetic (stochastic) approach should be a better choice. We have presented here the pros and cons of both the approaches so that the concerned reader/user can decide which approach is most suited for the problem at hand. Also for the function which is known in a tabular form, instead of an analytical form, as is often the case in an experimental environment, we attempt to provide an insight into the approaches focusing our attention toward accuracy. Such an insight will help one to decide which method, out of several available methods, should be employed to obtain the best (least error) output. *

Understanding error generation in fused deposition modeling

NASA Astrophysics Data System (ADS)

Bochmann, Lennart; Bayley, Cindy; Helu, Moneer; Transchel, Robert; Wegener, Konrad; Dornfeld, David

2015-03-01

Additive manufacturing offers completely new possibilities for the manufacturing of parts. The advantages of flexibility and convenience of additive manufacturing have had a significant impact on many industries, and optimizing part quality is crucial for expanding its utilization. This research aims to determine the sources of imprecision in fused deposition modeling (FDM). Process errors in terms of surface quality, accuracy and precision are identified and quantified, and an error-budget approach is used to characterize errors of the machine tool. It was determined that accuracy and precision in the y direction (0.08-0.30 mm) are generally greater than in the x direction (0.12-0.62 mm) and the z direction (0.21-0.57 mm). Furthermore, accuracy and precision tend to decrease at increasing axis positions. The results of this work can be used to identify possible process improvements in the design and control of FDM technology.

Effects of Cloud on Goddard Lidar Observatory for Wind (GLOW) Performance and Analysis of Associated Errors

NASA Astrophysics Data System (ADS)

Bacha, Tulu

The Goddard Lidar Observatory for Wind (GLOW), a mobile direct detection Doppler LIDAR based on molecular backscattering for measurement of wind in the troposphere and lower stratosphere region of atmosphere is operated and its errors characterized. It was operated at Howard University Beltsville Center for Climate Observation System (BCCOS) side by side with other operating instruments: the NASA/Langely Research Center Validation Lidar (VALIDAR), Leosphere WLS70, and other standard wind sensing instruments. The performance of Goddard Lidar Observatory for Wind (GLOW) is presented for various optical thicknesses of cloud conditions. It was also compared to VALIDAR under various conditions. These conditions include clear and cloudy sky regions. The performance degradation due to the presence of cirrus clouds is quantified by comparing the wind speed error to cloud thickness. The cloud thickness is quantified in terms of aerosol backscatter ratio (ASR) and cloud optical depth (COD). ASR and COD are determined from Howard University Raman Lidar (HURL) operating at the same station as GLOW. The wind speed error of GLOW was correlated with COD and aerosol backscatter ratio (ASR) which are determined from HURL data. The correlation related in a weak linear relationship. Finally, the wind speed measurements of GLOW were corrected using the quantitative relation from the correlation relations. Using ASR reduced the GLOW wind error from 19% to 8% in a thin cirrus cloud and from 58% to 28% in a relatively thick cloud. After correcting for cloud induced error, the remaining error is due to shot noise and atmospheric variability. Shot-noise error is the statistical random error of backscattered photons detected by photon multiplier tube (PMT) can only be minimized by averaging large number of data recorded. The atmospheric backscatter measured by GLOW along its line-of-sight direction is also used to analyze error due to atmospheric variability within the volume of measurement. GLOW scans in five different directions (vertical and at elevation angles of 45° in north, south, east, and west) to generate wind profiles. The non-uniformity of the atmosphere in all scanning directions is a factor contributing to the measurement error of GLOW. The atmospheric variability in the scanning region leads to difference in the intensity of backscattered signals for scanning directions. Taking the ratio of the north (east) to south (west) and comparing the statistical differences lead to a weak linear relation between atmospheric variability and line-of-sights wind speed differences. This relation was used to make correction which reduced by about 50%.

Test of Shi et al. Method to Infer the Magnetic Reconnection Geometry from Spacecraft Data: MHD Simulation with Guide Field and Antiparallel Kinetic Simulation

NASA Technical Reports Server (NTRS)

Denton, R.; Sonnerup, B. U. O.; Swisdak, M.; Birn, J.; Drake, J. F.; Heese, M.

2012-01-01

When analyzing data from an array of spacecraft (such as Cluster or MMS) crossing a site of magnetic reconnection, it is desirable to be able to accurately determine the orientation of the reconnection site. If the reconnection is quasi-two dimensional, there are three key directions, the direction of maximum inhomogeneity (the direction across the reconnection site), the direction of the reconnecting component of the magnetic field, and the direction of rough invariance (the "out of plane" direction). Using simulated spacecraft observations of magnetic reconnection in the geomagnetic tail, we extend our previous tests of the direction-finding method developed by Shi et al. (2005) and the method to determine the structure velocity relative to the spacecraft Vstr. These methods require data from four proximate spacecraft. We add artificial noise and calibration errors to the simulation fields, and then use the perturbed gradient of the magnetic field B and perturbed time derivative dB/dt, as described by Denton et al. (2010). Three new simulations are examined: a weakly three-dimensional, i.e., quasi-two-dimensional, MHD simulation without a guide field, a quasi-two-dimensional MHD simulation with a guide field, and a two-dimensional full dynamics kinetic simulation with inherent noise so that the apparent minimum gradient was not exactly zero, even without added artificial errors. We also examined variations of the spacecraft trajectory for the kinetic simulation. The accuracy of the directions found varied depending on the simulation and spacecraft trajectory, but all the directions could be found within about 10 for all cases. Various aspects of the method were examined, including how to choose averaging intervals and the best intervals for determining the directions and velocity. For the kinetic simulation, we also investigated in detail how the errors in the inferred gradient directions from the unmodified Shi et al. method (using the unperturbed gradient) depended on the amplitude of the calibration errors. For an accuracy of 3 for the maximum gradient direction, the calibration errors could be as large as 3% of reconnection magnetic field, while for the same accuracy for the minimum gradient direction, the calibration errors could only be as large as 0.03% of the reconnection magnetic field. These results suggest that the maximum gradient direction can normally be determined by the unmodified Shi et al. method, while the modified method or some other method must be used to accurately determine the minimum gradient direction. The structure velocity was found with magnitude accurate to 2% and direction accurate to within 5%.

Analysis of case-only studies accounting for genotyping error.

PubMed

Cheng, K F

2007-03-01

The case-only design provides one approach to assess possible interactions between genetic and environmental factors. It has been shown that if these factors are conditionally independent, then a case-only analysis is not only valid but also very efficient. However, a drawback of the case-only approach is that its conclusions may be biased by genotyping errors. In this paper, our main aim is to propose a method for analysis of case-only studies when these errors occur. We show that the bias can be adjusted through the use of internal validation data, which are obtained by genotyping some sampled individuals twice. Our analysis is based on a simple and yet highly efficient conditional likelihood approach. Simulation studies considered in this paper confirm that the new method has acceptable performance under genotyping errors.

Motor Impulsivity during Childhood and Adolescence: A Longitudinal Biometric Analysis of the Go/No-Go Task in 9- to 18-Year-Old Twins

ERIC Educational Resources Information Center

Bezdjian, Serena; Tuvblad, Catherine; Wang, Pan; Raine, Adrian; Baker, Laura A.

2014-01-01

In the present study, we investigated genetic and environmental effects on motor impulsivity from childhood to late adolescence using a longitudinal sample of twins from ages 9 to 18 years. Motor impulsivity was assessed using errors of commission (no-go errors) in a visual go/no-go task at 4 time points: ages 9-10, 11-13, 14-15, and 16-18 years.…

Power and type I error results for a bias-correction approach recently shown to provide accurate odds ratios of genetic variants for the secondary phenotypes associated with primary diseases.

PubMed

Wang, Jian; Shete, Sanjay

2011-11-01

We recently proposed a bias correction approach to evaluate accurate estimation of the odds ratio (OR) of genetic variants associated with a secondary phenotype, in which the secondary phenotype is associated with the primary disease, based on the original case-control data collected for the purpose of studying the primary disease. As reported in this communication, we further investigated the type I error probabilities and powers of the proposed approach, and compared the results to those obtained from logistic regression analysis (with or without adjustment for the primary disease status). We performed a simulation study based on a frequency-matching case-control study with respect to the secondary phenotype of interest. We examined the empirical distribution of the natural logarithm of the corrected OR obtained from the bias correction approach and found it to be normally distributed under the null hypothesis. On the basis of the simulation study results, we found that the logistic regression approaches that adjust or do not adjust for the primary disease status had low power for detecting secondary phenotype associated variants and highly inflated type I error probabilities, whereas our approach was more powerful for identifying the SNP-secondary phenotype associations and had better-controlled type I error probabilities. © 2011 Wiley Periodicals, Inc.

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

PubMed Central

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Background Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation. PMID:21760939

Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.

PubMed Central

Thompson, J A; Haudenschild, C C; Anderson, K D; DiPietro, J M; Anderson, W F; Maciag, T

1989-01-01

One of the promises of modern molecular biology has been the opportunity to use genetically modified human cells in a patient to permanently restore inborn errors of metabolism. Although it has been possible to introduce genes into mammalian cells and to control their expression, it has proven difficult to introduce mammalian cells as carriers of the modified genetic information into hosts. The successful implantation of selective cells cannot be achieved without adequate vascular support, an essential step toward integration and reconstitution of a new biological function. Although a partial solution to this problem has been found by inducing specific site-directed neovessel formation using heparin-binding growth factor 1 (HBGF-1) adsorbed to a collagen matrix, these implants function for only a short period (weeks). We now report the formation of organoid neovascular structures using polytetrafluoroethylene fibers coated with collagen and HBGF-1 implanted in the peritoneal cavity of the rat. The organoid structures contained readily visible vascular lumina and nonvascular structures that resemble nerve tissue. It was also possible to demonstrate that the vascular system on the implant is continuous with the vascular tree of the host. This feature was used to demonstrate that the organoid structures are capable of sustaining the biological function of implanted normal rat hepatocytes over long periods of time (months) in the homozygous Gunn rat, thereby facilitating future applications involving the delivery of new genetic information. Images PMID:2479012

A general geometric theory of attitude determination from directional sensing

NASA Technical Reports Server (NTRS)

Fang, B. T.

1976-01-01

A general geometric theory of spacecraft attitude determination from external reference direction sensors was presented. Outputs of different sensors are reduced to two kinds of basic directional measurements. Errors in these measurement equations are studied in detail. The partial derivatives of measurements with respect to the spacecraft orbit, the spacecraft attitude, and the error parameters form the basis for all orbit and attitude determination schemes and error analysis programs and are presented in a series of tables. The question of attitude observability is studied with the introduction of a graphical construction which provides a great deal of physical insight. The result is applied to the attitude observability of the IMP-8 spacecraft.

Estimating directional epistasis

PubMed Central

Le Rouzic, Arnaud

2014-01-01

Epistasis, i.e., the fact that gene effects depend on the genetic background, is a direct consequence of the complexity of genetic architectures. Despite this, most of the models used in evolutionary and quantitative genetics pay scant attention to genetic interactions. For instance, the traditional decomposition of genetic effects models epistasis as noise around the evolutionarily-relevant additive effects. Such an approach is only valid if it is assumed that there is no general pattern among interactions—a highly speculative scenario. Systematic interactions generate directional epistasis, which has major evolutionary consequences. In spite of its importance, directional epistasis is rarely measured or reported by quantitative geneticists, not only because its relevance is generally ignored, but also due to the lack of simple, operational, and accessible methods for its estimation. This paper describes conceptual and statistical tools that can be used to estimate directional epistasis from various kinds of data, including QTL mapping results, phenotype measurements in mutants, and artificial selection responses. As an illustration, I measured directional epistasis from a real-life example. I then discuss the interpretation of the estimates, showing how they can be used to draw meaningful biological inferences. PMID:25071828

Correlates of male fitness in captive zebra finches--a comparison of methods to disentangle genetic and environmental effects.

PubMed

Bolund, Elisabeth; Schielzeth, Holger; Forstmeier, Wolfgang

2011-11-08

It is a common observation in evolutionary studies that larger, more ornamented or earlier breeding individuals have higher fitness, but that body size, ornamentation or breeding time does not change despite of sometimes substantial heritability for these traits. A possible explanation for this is that these traits do not causally affect fitness, but rather happen to be indirectly correlated with fitness via unmeasured non-heritable aspects of condition (e.g. undernourished offspring grow small and have low fitness as adults due to poor health). Whether this explanation applies to a specific case can be examined by decomposing the covariance between trait and fitness into its genetic and environmental components using pedigree-based animal models. We here examine different methods of doing this for a captive zebra finch population where male fitness was measured in communal aviaries in relation to three phenotypic traits (tarsus length, beak colour and song rate). Our case study illustrates how methods that regress fitness over breeding values for phenotypic traits yield biased estimates as well as anti-conservative standard errors. Hence, it is necessary to estimate the genetic and environmental covariances between trait and fitness directly from a bivariate model. This method, however, is very demanding in terms of sample sizes. In our study parameter estimates of selection gradients for tarsus were consistent with the hypothesis of environmentally induced bias (βA=0.035±0.25 (SE), βE=0.57±0.28 (SE)), yet this differences between genetic and environmental selection gradients falls short of statistical significance. To examine the generality of the idea that phenotypic selection gradients for certain traits (like size) are consistently upwardly biased by environmental covariance a meta-analysis across study systems will be needed.

Correlates of male fitness in captive zebra finches - a comparison of methods to disentangle genetic and environmental effects

PubMed Central

2011-01-01

Backgound It is a common observation in evolutionary studies that larger, more ornamented or earlier breeding individuals have higher fitness, but that body size, ornamentation or breeding time does not change despite of sometimes substantial heritability for these traits. A possible explanation for this is that these traits do not causally affect fitness, but rather happen to be indirectly correlated with fitness via unmeasured non-heritable aspects of condition (e.g. undernourished offspring grow small and have low fitness as adults due to poor health). Whether this explanation applies to a specific case can be examined by decomposing the covariance between trait and fitness into its genetic and environmental components using pedigree-based animal models. We here examine different methods of doing this for a captive zebra finch population where male fitness was measured in communal aviaries in relation to three phenotypic traits (tarsus length, beak colour and song rate). Results Our case study illustrates how methods that regress fitness over breeding values for phenotypic traits yield biased estimates as well as anti-conservative standard errors. Hence, it is necessary to estimate the genetic and environmental covariances between trait and fitness directly from a bivariate model. This method, however, is very demanding in terms of sample sizes. In our study parameter estimates of selection gradients for tarsus were consistent with the hypothesis of environmentally induced bias (βA = 0.035 ± 0.25 (SE), βE = 0.57 ± 0.28 (SE)), yet this differences between genetic and environmental selection gradients falls short of statistical significance. Conclusions To examine the generality of the idea that phenotypic selection gradients for certain traits (like size) are consistently upwardly biased by environmental covariance a meta-analysis across study systems will be needed. PMID:22067225

Evaluation of resolution and periodic errors of a flatbed scanner used for digitizing spectroscopic photographic plates

PubMed Central

Wyatt, Madison; Nave, Gillian

2017-01-01

We evaluated the use of a commercial flatbed scanner for digitizing photographic plates used for spectroscopy. The scanner has a bed size of 420 mm by 310 mm and a pixel size of about 0.0106 mm. Our tests show that the closest line pairs that can be resolved with the scanner are 0.024 mm apart, only slightly larger than the Nyquist resolution of 0.021 mm expected by the 0.0106 mm pixel size. We measured periodic errors in the scanner using both a calibrated length scale and a photographic plate. We find no noticeable periodic errors in the direction parallel to the linear detector in the scanner, but errors with an amplitude of 0.03 mm to 0.05 mm in the direction perpendicular to the detector. We conclude that large periodic errors in measurements of spectroscopic plates using flatbed scanners can be eliminated by scanning the plates with the dispersion direction parallel to the linear detector by placing the plate along the short side of the scanner. PMID:28463262

Genetic counseling and the ethical issues around direct to consumer genetic testing.

PubMed

Hawkins, Alice K; Ho, Anita

2012-06-01

Over the last several years, direct to consumer(DTC) genetic testing has received increasing attention in the public, healthcare and academic realms. DTC genetic testing companies face considerable criticism and scepticism,particularly from the medical and genetic counseling community. This raises the question of what specific aspects of DTC genetic testing provoke concerns, and conversely,promises, for genetic counselors. This paper addresses this question by exploring DTC genetic testing through an ethic allens. By considering the fundamental ethical approaches influencing genetic counseling (the ethic of care and principle-based ethics) we highlight the specific ethical concerns raised by DTC genetic testing companies. Ultimately,when considering the ethics of DTC testing in a genetic counseling context, we should think of it as a balancing act. We need careful and detailed consideration of the risks and troubling aspects of such testing, as well as the potentially beneficial direct and indirect impacts of the increased availability of DTC genetic testing. As a result it is essential that genetic counselors stay informed and involved in the ongoing debate about DTC genetic testing and DTC companies. Doing so will ensure that the ethical theories and principles fundamental to the profession of genetic counseling are promoted not just in traditional counseling sessions,but also on a broader level. Ultimately this will help ensure that the public enjoys the benefits of an increasingly genetic based healthcare system.

Health-related direct-to-consumer genetic testing: a review of companies' policies with regard to genetic testing in minors.

PubMed

Borry, Pascal; Howard, Heidi C; Sénécal, Karine; Avard, Denise

2010-03-01

More and more companies are advertising and selling genetic tests directly to consumers. Considering the ethical, legal, and psychological concerns surrounding genetic testing in minors, a study of companies' websites was performed in order to describe and analyze their policies with respect to this issue. Of the 29 companies analyzed, 13 did not provide any information about this matter, eight companies allowed genetic testing upon parental request, four companies stated that their website is not directed to children under 18 years, and four companies suggested that in order to be tested, applicants should have reached the age of legal majority. If private companies offer genetic tests which are also offered in a clinical setting, can they be expected to adhere to the existing clinical guidelines with regard to these tests? If so, a certain ambiguity exists. Many companies are emphasizing in their disclaimers that their services are not medical services and should not be used as a basis for making medical decisions. Nonetheless, it remains debatable whether genetic testing in minors would be appropriate in this context. In line with the Advisory Committee on Genetic Testing, the Human Genetics Commission addressed the problem of non-consensual testing and recommended not to supply genetic testing services directly to those under the age of 16 or to those not able to make a competent decision regarding testing.

Henry Friesen Award Lecture. Work, the clinician-scientist and human biochemical genetics.

PubMed

Scriver, C R

2001-08-01

The pursuit of human biochemical genetics has allowed us to understand better how the person with the (genetic) disease differs from the disease the person has and to develop the concept that genetics belongs in all aspects of health care. It is a perspective that comes quite readily to the clinician-scientist, and the restoration of that "species" in the era of functional genomics is strongly recommended. Garrod, the initial founder of human "biochemical genetics" belonged to the clinician-scientist community. Archibald Edward Garrod introduced a paradigm, new for its day, in medicine: biochemistry is dynamic and different from the static nature of organic chemistry. It led him to think about metabolic pathways and to recognize that variation in Mendelian heredity could explain an "inborn error of metabolism." At the time, Garrod had no idea about the nature of a gene. Genes are now well understood; genomes are being described for one organism after another (including Homo sapiens) and it is understood that genomes "speak biochemistry (not phenotype)." Accordingly, in the era of genomics, biochemistry and physiology become the bases of functional genomics, and it is possible to appreciate why "nothing in biology makes sense without evolution" (and nothing in medicine will make sense without biology). Mendelian, biochemical and molecular genetics together have revealed what lies behind the 4 canonical inborn errors described by Garrod (albinisn, alkaptonuria, cystinuria and pentosuria). Both older and newer ideas in genetics, new tools for applying them (and renewed respect for the clinician-scientist) will enhance our understanding of the human biological variation that accounts for variant states of health and overt disease. A so-called monogenic phenotype (phenylketonuria) is used to illustrate, in some detail, that all disease phenotypes are, in one way or another, likely to be complex in nature. What can be known and what ought to be done, with knowledge about human genetics, to benefit individuals, families and communities (society), is both opportunity and challenge.

Meta sequence analysis of human blood peptides and their parent proteins.

PubMed

Bowden, Peter; Pendrak, Voitek; Zhu, Peihong; Marshall, John G

2010-04-18

Sequence analysis of the blood peptides and their qualities will be key to understanding the mechanisms that contribute to error in LC-ESI-MS/MS. Analysis of peptides and their proteins at the level of sequences is much more direct and informative than the comparison of disparate accession numbers. A portable database of all blood peptide and protein sequences with descriptor fields and gene ontology terms might be useful for designing immunological or MRM assays from human blood. The results of twelve studies of human blood peptides and/or proteins identified by LC-MS/MS and correlated against a disparate array of genetic libraries were parsed and matched to proteins from the human ENSEMBL, SwissProt and RefSeq databases by SQL. The reported peptide and protein sequences were organized into an SQL database with full protein sequences and up to five unique peptides in order of prevalence along with the peptide count for each protein. Structured query language or BLAST was used to acquire descriptive information in current databases. Sampling error at the level of peptides is the largest source of disparity between groups. Chi Square analysis of peptide to protein distributions confirmed the significant agreement between groups on identified proteins. Copyright 2010. Published by Elsevier B.V.

Pulse retrieval algorithm for interferometric frequency-resolved optical gating based on differential evolution.

PubMed

Hyyti, Janne; Escoto, Esmerando; Steinmeyer, Günter

2017-10-01

A novel algorithm for the ultrashort laser pulse characterization method of interferometric frequency-resolved optical gating (iFROG) is presented. Based on a genetic method, namely, differential evolution, the algorithm can exploit all available information of an iFROG measurement to retrieve the complex electric field of a pulse. The retrieval is subjected to a series of numerical tests to prove the robustness of the algorithm against experimental artifacts and noise. These tests show that the integrated error-correction mechanisms of the iFROG method can be successfully used to remove the effect from timing errors and spectrally varying efficiency in the detection. Moreover, the accuracy and noise resilience of the new algorithm are shown to outperform retrieval based on the generalized projections algorithm, which is widely used as the standard method in FROG retrieval. The differential evolution algorithm is further validated with experimental data, measured with unamplified three-cycle pulses from a mode-locked Ti:sapphire laser. Additionally introducing group delay dispersion in the beam path, the retrieval results show excellent agreement with independent measurements with a commercial pulse measurement device based on spectral phase interferometry for direct electric-field retrieval. Further experimental tests with strongly attenuated pulses indicate resilience of differential-evolution-based retrieval against massive measurement noise.

Patient safety: honoring advanced directives.

PubMed

Tice, Martha A

2007-02-01

Healthcare providers typically think of patient safety in the context of preventing iatrogenic injury. Prevention of falls and medication or treatment errors is the typical focus of adverse event analyses. If healthcare providers are committed to honoring the wishes of patients, then perhaps failures to honor advanced directives should be viewed as reportable medical errors.

Progress in the improved lattice calculation of direct CP-violation in the Standard Model

NASA Astrophysics Data System (ADS)

Kelly, Christopher

2018-03-01

We discuss the ongoing effort by the RBC & UKQCD collaborations to improve our lattice calculation of the measure of Standard Model direct CP violation, ɛ', with physical kinematics. We present our progress in decreasing the (dominant) statistical error and discuss other related activities aimed at reducing the systematic errors.

An Introduction to the Sources of Delivery Error for Direct-Fire Ballistic Projectiles

DTIC Science & Technology

2013-07-01

Ballistic mismatch has also been used to quantify the difference in target impacts using different gun tubes ...the angle between the local “upwards” direction of the gun tube and the vertical direction as defined by gravity. Cant results from the gun tube ...Determining Optimal Tube Shape for Reduction of Jump Error for Tank Fleets Using Fleet Zero. Presented at the 20th International Symposium on Ballistics

Forensic genetics and genomics: Much more than just a human affair.

PubMed

Arenas, Miguel; Pereira, Filipe; Oliveira, Manuela; Pinto, Nadia; Lopes, Alexandra M; Gomes, Veronica; Carracedo, Angel; Amorim, Antonio

2017-09-01

While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material-including other animal species, plants, or microorganisms-is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities.

Forensic genetics and genomics: Much more than just a human affair

PubMed Central

Oliveira, Manuela; Pinto, Nadia; Carracedo, Angel

2017-01-01

While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material—including other animal species, plants, or microorganisms—is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities. PMID:28934201

Defining the Relationship Between Human Error Classes and Technology Intervention Strategies

NASA Technical Reports Server (NTRS)

Wiegmann, Douglas A.; Rantanen, Esa; Crisp, Vicki K. (Technical Monitor)

2002-01-01

One of the main factors in all aviation accidents is human error. The NASA Aviation Safety Program (AvSP), therefore, has identified several human-factors safety technologies to address this issue. Some technologies directly address human error either by attempting to reduce the occurrence of errors or by mitigating the negative consequences of errors. However, new technologies and system changes may also introduce new error opportunities or even induce different types of errors. Consequently, a thorough understanding of the relationship between error classes and technology "fixes" is crucial for the evaluation of intervention strategies outlined in the AvSP, so that resources can be effectively directed to maximize the benefit to flight safety. The purpose of the present project, therefore, was to examine the repositories of human factors data to identify the possible relationship between different error class and technology intervention strategies. The first phase of the project, which is summarized here, involved the development of prototype data structures or matrices that map errors onto "fixes" (and vice versa), with the hope of facilitating the development of standards for evaluating safety products. Possible follow-on phases of this project are also discussed. These additional efforts include a thorough and detailed review of the literature to fill in the data matrix and the construction of a complete database and standards checklists.

Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

PubMed

Sherer, Eric A; Sale, Mark E; Pollock, Bruce G; Belani, Chandra P; Egorin, Merrill J; Ivy, Percy S; Lieberman, Jeffrey A; Manuck, Stephen B; Marder, Stephen R; Muldoon, Matthew F; Scher, Howard I; Solit, David B; Bies, Robert R

2012-08-01

A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three compounds. The root mean squared error and absolute mean prediction error of the best single-objective hybrid genetic algorithm candidates were a median of 0.2 points higher (range of 38.9 point decrease to 27.3 point increase) and 0.02 points lower (range of 0.98 point decrease to 0.74 point increase), respectively, than that of the final stepwise models. In addition, the best single-objective, hybrid genetic algorithm candidate models had successful convergence and covariance steps for each compound, used the same compartment structure as the manual stepwise approach for 6 of 7 (86 %) compounds, and identified 54 % (7 of 13) of covariates included by the manual stepwise approach and 16 covariate relationships not included by manual stepwise models. The model parameter values between the final manual stepwise and best single-objective, hybrid genetic algorithm models differed by a median of 26.7 % (q₁ = 4.9 % and q₃ = 57.1 %). Finally, the single-objective, hybrid genetic algorithm approach was able to identify models capable of estimating absorption rate parameters for four compounds that the manual stepwise approach did not identify. The single-objective, hybrid genetic algorithm represents a general pharmacokinetic model building methodology whose ability to rapidly search the feasible solution space leads to nearly equivalent or superior model fits to pharmacokinetic data.

An Analysis of Computational Errors in the Use of Division Algorithms by Fourth-Grade Students.

ERIC Educational Resources Information Center

Stefanich, Greg P.; Rokusek, Teri

1992-01-01

Presents a study that analyzed errors made by randomly chosen fourth grade students (25 of 57) while using the division algorithm and investigated the effect of remediation on identified systematic errors. Results affirm that error pattern diagnosis and directed remediation lead to new learning and long-term retention. (MDH)

Blood pool and tissue phase patient motion effects on 82rubidium PET myocardial blood flow quantification.

PubMed

Lee, Benjamin C; Moody, Jonathan B; Poitrasson-Rivière, Alexis; Melvin, Amanda C; Weinberg, Richard L; Corbett, James R; Ficaro, Edward P; Murthy, Venkatesh L

2018-03-23

Patient motion can lead to misalignment of left ventricular volumes of interest and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to identify the prevalence of patient motion in both blood and tissue phases and analyze the effects of this motion on MBF and MFR estimates. We selected 225 consecutive patients that underwent dynamic stress/rest rubidium-82 chloride ( 82 Rb) PET imaging. Dynamic image series were iteratively reconstructed with 5- to 10-second frame durations over the first 2 minutes for the blood phase and 10 to 80 seconds for the tissue phase. Motion shifts were assessed by 3 physician readers from the dynamic series and analyzed for frequency, magnitude, time, and direction of motion. The effects of this motion isolated in time, direction, and magnitude on global and regional MBF and MFR estimates were evaluated. Flow estimates derived from the motion corrected images were used as the error references. Mild to moderate motion (5-15 mm) was most prominent in the blood phase in 63% and 44% of the stress and rest studies, respectively. This motion was observed with frequencies of 75% in the septal and inferior directions for stress and 44% in the septal direction for rest. Images with blood phase isolated motion had mean global MBF and MFR errors of 2%-5%. Isolating blood phase motion in the inferior direction resulted in mean MBF and MFR errors of 29%-44% in the RCA territory. Flow errors due to tissue phase isolated motion were within 1%. Patient motion was most prevalent in the blood phase and MBF and MFR errors increased most substantially with motion in the inferior direction. Motion correction focused on these motions is needed to reduce MBF and MFR errors.

Opioid errors in inpatient palliative care services: a retrospective review.

PubMed

Heneka, Nicole; Shaw, Tim; Rowett, Debra; Lapkin, Samuel; Phillips, Jane L

2018-06-01

Opioids are a high-risk medicine frequently used to manage palliative patients' cancer-related pain and other symptoms. Despite the high volume of opioid use in inpatient palliative care services, and the potential for patient harm, few studies have focused on opioid errors in this population. To (i) identify the number of opioid errors reported by inpatient palliative care services, (ii) identify reported opioid error characteristics and (iii) determine the impact of opioid errors on palliative patient outcomes. A 24-month retrospective review of opioid errors reported in three inpatient palliative care services in one Australian state. Of the 55 opioid errors identified, 84% reached the patient. Most errors involved morphine (35%) or hydromorphone (29%). Opioid administration errors accounted for 76% of reported opioid errors, largely due to omitted dose (33%) or wrong dose (24%) errors. Patients were more likely to receive a lower dose of opioid than ordered as a direct result of an opioid error (57%), with errors adversely impacting pain and/or symptom management in 42% of patients. Half (53%) of the affected patients required additional treatment and/or care as a direct consequence of the opioid error. This retrospective review has provided valuable insights into the patterns and impact of opioid errors in inpatient palliative care services. Iatrogenic harm related to opioid underdosing errors contributed to palliative patients' unrelieved pain. Better understanding the factors that contribute to opioid errors and the role of safety culture in the palliative care service context warrants further investigation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The association between scalp hair-whorl direction, handedness and hemispheric language dominance: is there a common genetic basis of lateralization?

PubMed

Jansen, Andreas; Lohmann, Hubertus; Scharfe, Stefanie; Sehlmeyer, Christina; Deppe, Michael; Knecht, Stefan

2007-04-01

The hemispheres of the human brain are functionally asymmetric. The left hemisphere tends to be dominant for language and superior in the control of manual dexterity. The mechanisms underlying these asymmetries are not known. Genetic as well as environmental factors are discussed. Recently, atypical anticlockwise hair-whorl direction has been related to an increased probability for non-right-handedness and atypical hemispheric language dominance. These findings are fascinating and important since hair-whorl direction is a structural marker of lateralization and could provide a readily observable anatomical clue to functional brain lateralization. Based on data on handedness and hair-whorl direction, Amar Klar proposed a genetic model ("random-recessive model") in that a single gene with two alleles controls both handedness and hair-whorl orientation (Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 165, 269-276). The present study was designed to further investigate the relationship between scalp hair-whorl direction with handedness and hemispheric language dominance. 1212 subjects were investigated for scalp hair-whorl direction and handedness. Additionally, we determined hemispheric language dominance (as assessed by a word generation task) in a subgroup of 212 subjects using functional transcranial Doppler sonography (fTCD). As for the single attributes - hair-whorl direction, handedness, and language dominance - we reproduced previously published results. However, we found no association between hair-whorl direction and either language dominance or handedness. These results strongly argue against a common genetic basis of handedness or language lateralization with scalp hair-whorl direction. Inspection of hair patterns will not help us to determine language dominance.

Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence.

PubMed

Kendler, K S; Gardner, C O

2017-07-01

This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD). Our sample was 2153 members of female-female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves. The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors. Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

Analysis of East Asia Genetic Substructure Using Genome-Wide SNP Arrays

PubMed Central

Tian, Chao; Kosoy, Roman; Lee, Annette; Ransom, Michael; Belmont, John W.; Gregersen, Peter K.; Seldin, Michael F.

2008-01-01

Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies. PMID:19057645

Generalized ray tracing method for the calculation of the peripheral refraction induced by an ophthalmic lens

NASA Astrophysics Data System (ADS)

Rojo, Pilar; Royo, Santiago; Caum, Jesus; Ramírez, Jorge; Madariaga, Ines

2015-02-01

Peripheral refraction, the refractive error present outside the main direction of gaze, has lately attracted interest due to its alleged relationship with the progression of myopia. The ray tracing procedures involved in its calculation need to follow an approach different from those used in conventional ophthalmic lens design, where refractive errors are compensated only in the main direction of gaze. We present a methodology for the evaluation of the peripheral refractive error in ophthalmic lenses, adapting the conventional generalized ray tracing approach to the requirements of the evaluation of peripheral refraction. The nodal point of the eye and a retinal conjugate surface will be used to evaluate the three-dimensional distribution of refractive error around the fovea. The proposed approach enables us to calculate the three-dimensional peripheral refraction induced by any ophthalmic lens at any direction of gaze and to personalize the lens design to the requirements of the user. The complete evaluation process for a given user prescribed with a -5.76D ophthalmic lens for foveal vision is detailed, and comparative results obtained when the geometry of the lens is modified and when the central refractive error is over- or undercorrected. The methodology is also applied for an emmetropic eye to show its application for refractive errors other than myopia.

Performance consequences of alternating directional control-response compatibility: evidence from a coal mine shuttle car simulator.

PubMed

Zupanc, Christine M; Burgess-Limerick, Robin J; Wallis, Guy

2007-08-01

To investigate error and reaction time consequences of alternating compatible and incompatible steering arrangements during a simulated obstacle avoidance task. Underground coal mine shuttle cars provide an example of a vehicle in which operators are required to alternate between compatible and incompatible steering configurations. This experiment examines the performance of 48 novice participants in a virtual analogy of an underground coal mine shuttle car. Participants were randomly assigned to a compatible condition, an incompatible condition, an alternating condition in which compatibility alternated within and between hands, or an alternating condition in which compatibility alternated between hands. Participants made fewer steering direction errors and made correct steering responses more quickly in the compatible condition. Error rate decreased over time in the incompatible condition. A compatibility effect for both errors and reaction time was also found when the control-response relationship alternated; however, performance improvements over time were not consistent. Isolating compatibility to a hand resulted in reduced error rate and faster reaction time than when compatibility alternated within and between hands. The consequences of alternating control-response relationships are higher error rates and slower responses, at least in the early stages of learning. This research highlights the importance of ensuring consistently compatible human-machine directional control-response relationships.

Further Improvements to Linear Mixed Models for Genome-Wide Association Studies

PubMed Central

Widmer, Christian; Lippert, Christoph; Weissbrod, Omer; Fusi, Nicolo; Kadie, Carl; Davidson, Robert; Listgarten, Jennifer; Heckerman, David

2014-01-01

We examine improvements to the linear mixed model (LMM) that better correct for population structure and family relatedness in genome-wide association studies (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which encodes the pairwise similarity between every two individuals in a cohort. These similarities are estimated from single nucleotide polymorphisms (SNPs) or other genetic variants. Traditionally, all available SNPs are used to estimate the GSM. In empirical studies across a wide range of synthetic and real data, we find that modifications to this approach improve GWAS performance as measured by type I error control and power. Specifically, when only population structure is present, a GSM constructed from SNPs that well predict the phenotype in combination with principal components as covariates controls type I error and yields more power than the traditional LMM. In any setting, with or without population structure or family relatedness, a GSM consisting of a mixture of two component GSMs, one constructed from all SNPs and another constructed from SNPs that well predict the phenotype again controls type I error and yields more power than the traditional LMM. Software implementing these improvements and the experimental comparisons are available at http://microsoft.com/science. PMID:25387525

Further Improvements to Linear Mixed Models for Genome-Wide Association Studies

NASA Astrophysics Data System (ADS)

Widmer, Christian; Lippert, Christoph; Weissbrod, Omer; Fusi, Nicolo; Kadie, Carl; Davidson, Robert; Listgarten, Jennifer; Heckerman, David

2014-11-01

We examine improvements to the linear mixed model (LMM) that better correct for population structure and family relatedness in genome-wide association studies (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which encodes the pairwise similarity between every two individuals in a cohort. These similarities are estimated from single nucleotide polymorphisms (SNPs) or other genetic variants. Traditionally, all available SNPs are used to estimate the GSM. In empirical studies across a wide range of synthetic and real data, we find that modifications to this approach improve GWAS performance as measured by type I error control and power. Specifically, when only population structure is present, a GSM constructed from SNPs that well predict the phenotype in combination with principal components as covariates controls type I error and yields more power than the traditional LMM. In any setting, with or without population structure or family relatedness, a GSM consisting of a mixture of two component GSMs, one constructed from all SNPs and another constructed from SNPs that well predict the phenotype again controls type I error and yields more power than the traditional LMM. Software implementing these improvements and the experimental comparisons are available at http://microsoft.com/science.

Further improvements to linear mixed models for genome-wide association studies.

PubMed

Widmer, Christian; Lippert, Christoph; Weissbrod, Omer; Fusi, Nicolo; Kadie, Carl; Davidson, Robert; Listgarten, Jennifer; Heckerman, David

2014-11-12

We examine improvements to the linear mixed model (LMM) that better correct for population structure and family relatedness in genome-wide association studies (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which encodes the pairwise similarity between every two individuals in a cohort. These similarities are estimated from single nucleotide polymorphisms (SNPs) or other genetic variants. Traditionally, all available SNPs are used to estimate the GSM. In empirical studies across a wide range of synthetic and real data, we find that modifications to this approach improve GWAS performance as measured by type I error control and power. Specifically, when only population structure is present, a GSM constructed from SNPs that well predict the phenotype in combination with principal components as covariates controls type I error and yields more power than the traditional LMM. In any setting, with or without population structure or family relatedness, a GSM consisting of a mixture of two component GSMs, one constructed from all SNPs and another constructed from SNPs that well predict the phenotype again controls type I error and yields more power than the traditional LMM. Software implementing these improvements and the experimental comparisons are available at http://microsoft.com/science.

Dynamic nigrostriatal dopamine biases action selection

PubMed Central

Howard, Christopher D.; Li, Hao; Geddes, Claire E.; Jin, Xin

2017-01-01

Summary Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here, we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons, or optogenetic manipulation of dopamine concentration, alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions and have important implications for neurological disorders including Parkinson’s disease and substance dependence. PMID:28285820

Dynamic Nigrostriatal Dopamine Biases Action Selection.

PubMed

Howard, Christopher D; Li, Hao; Geddes, Claire E; Jin, Xin

2017-03-22

Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson's disease and substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary Immunodeficiencies: “New” Disease in an Old Country

PubMed Central

Lee, Pamela P W; Lau, Yu-Lung

2009-01-01

Primary immunodeficiency disorders (PIDs) are rare inborn errors of the immune system. Patients with PIDs are unique models that exemplify the functional and phenotypic consequences of various immune defects underlying infections, autoimmunity, lymphoproliferation, allergy and cancer. Over 150 PID syndromes were characterized in the past 60 years, with an ever growing list of new entities being discovered. Because of their rarity, multi-center collaboration for pooled data analysis and molecular studies is important to gain meaningful insights into the phenotypic and genetic diversities of PIDs. In this article, we summarize our research findings on PIDs in Chinese population in the past 20 years. Close collaboration among various immunology centers, cross-referrals and systematic data analysis constitute the foundation for research on PIDs. Future directions include establishment of a national PID registry, raising awareness of PIDs and securing sufficient resources for patient care and scientific research. PMID:20003815

Coherent spectroscopic methods for monitoring pathogens, genetically modified products and nanostructured materials in colloidal solution

NASA Astrophysics Data System (ADS)

Moguilnaya, T.; Suminov, Y.; Botikov, A.; Ignatov, S.; Kononenko, A.; Agibalov, A.

2017-01-01

We developed the new automatic method that combines the method of forced luminescence and stimulated Brillouin scattering. This method is used for monitoring pathogens, genetically modified products and nanostructured materials in colloidal solution. We carried out the statistical spectral analysis of pathogens, genetically modified soy and nano-particles of silver in water from different regions in order to determine the statistical errors of the method. We studied spectral characteristics of these objects in water to perform the initial identification with 95% probability. These results were used for creation of the model of the device for monitor of pathogenic organisms and working model of the device to determine the genetically modified soy in meat.

North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

ClinicalTrials.gov

2018-06-06

Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly

Genetics Home Reference: glutathione synthetase deficiency

MedlinePlus

... Ristoff E, Larsson A. Inborn errors in the metabolism of glutathione. Orphanet J Rare Dis. 2007 Mar 30;2:16. Review. Citation on PubMed or Free article on PubMed Central Wu G, Fang YZ, Yang S, ...

Approximation of state variables for discrete-time stochastic genetic regulatory networks with leakage, distributed, and probabilistic measurement delays: a robust stability problem.

PubMed

Pandiselvi, S; Raja, R; Cao, Jinde; Rajchakit, G; Ahmad, Bashir

2018-01-01

This work predominantly labels the problem of approximation of state variables for discrete-time stochastic genetic regulatory networks with leakage, distributed, and probabilistic measurement delays. Here we design a linear estimator in such a way that the absorption of mRNA and protein can be approximated via known measurement outputs. By utilizing a Lyapunov-Krasovskii functional and some stochastic analysis execution, we obtain the stability formula of the estimation error systems in the structure of linear matrix inequalities under which the estimation error dynamics is robustly exponentially stable. Further, the obtained conditions (in the form of LMIs) can be effortlessly solved by some available software packages. Moreover, the specific expression of the desired estimator is also shown in the main section. Finally, two mathematical illustrative examples are accorded to show the advantage of the proposed conceptual results.

Multisynchronization of Coupled Heterogeneous Genetic Oscillator Networks via Partial Impulsive Control.

PubMed

He, Ding-Xin; Ling, Guang; Guan, Zhi-Hong; Hu, Bin; Liao, Rui-Quan

2018-02-01

This paper focuses on the collective dynamics of multisynchronization among heterogeneous genetic oscillators under a partial impulsive control strategy. The coupled nonidentical genetic oscillators are modeled by differential equations with uncertainties. The definition of multisynchronization is proposed to describe some more general synchronization behaviors in the real. Considering that each genetic oscillator consists of a large number of biochemical molecules, we design a more manageable impulsive strategy for dynamic networks to achieve multisynchronization. Not all the molecules but only a small fraction of them in each genetic oscillator are controlled at each impulsive instant. Theoretical analysis of multisynchronization is carried out by the control theory approach, and a sufficient condition of partial impulsive controller for multisynchronization with given error bounds is established. At last, numerical simulations are exploited to demonstrate the effectiveness of our results.

Predictive and Feedback Performance Errors are Signaled in the Simple Spike Discharge of Individual Purkinje Cells

PubMed Central

Popa, Laurentiu S.; Hewitt, Angela L.; Ebner, Timothy J.

2012-01-01

The cerebellum has been implicated in processing motor errors required for online control of movement and motor learning. The dominant view is that Purkinje cell complex spike discharge signals motor errors. This study investigated whether errors are encoded in the simple spike discharge of Purkinje cells in monkeys trained to manually track a pseudo-randomly moving target. Four task error signals were evaluated based on cursor movement relative to target movement. Linear regression analyses based on firing residuals ensured that the modulation with a specific error parameter was independent of the other error parameters and kinematics. The results demonstrate that simple spike firing in lobules IV–VI is significantly correlated with position, distance and directional errors. Independent of the error signals, the same Purkinje cells encode kinematics. The strongest error modulation occurs at feedback timing. However, in 72% of cells at least one of the R2 temporal profiles resulting from regressing firing with individual errors exhibit two peak R2 values. For these bimodal profiles, the first peak is at a negative τ (lead) and a second peak at a positive τ (lag), implying that Purkinje cells encode both prediction and feedback about an error. For the majority of the bimodal profiles, the signs of the regression coefficients or preferred directions reverse at the times of the peaks. The sign reversal results in opposing simple spike modulation for the predictive and feedback components. Dual error representations may provide the signals needed to generate sensory prediction errors used to update a forward internal model. PMID:23115173

Learning time-dependent noise to reduce logical errors: real time error rate estimation in quantum error correction

NASA Astrophysics Data System (ADS)

Huo, Ming-Xia; Li, Ying

2017-12-01

Quantum error correction is important to quantum information processing, which allows us to reliably process information encoded in quantum error correction codes. Efficient quantum error correction benefits from the knowledge of error rates. We propose a protocol for monitoring error rates in real time without interrupting the quantum error correction. Any adaptation of the quantum error correction code or its implementation circuit is not required. The protocol can be directly applied to the most advanced quantum error correction techniques, e.g. surface code. A Gaussian processes algorithm is used to estimate and predict error rates based on error correction data in the past. We find that using these estimated error rates, the probability of error correction failures can be significantly reduced by a factor increasing with the code distance.

Local blur analysis and phase error correction method for fringe projection profilometry systems.

PubMed

Rao, Li; Da, Feipeng

2018-05-20

We introduce a flexible error correction method for fringe projection profilometry (FPP) systems in the presence of local blur phenomenon. Local blur caused by global light transport such as camera defocus, projector defocus, and subsurface scattering will cause significant systematic errors in FPP systems. Previous methods, which adopt high-frequency patterns to separate the direct and global components, fail when the global light phenomenon occurs locally. In this paper, the influence of local blur on phase quality is thoroughly analyzed, and a concise error correction method is proposed to compensate the phase errors. For defocus phenomenon, this method can be directly applied. With the aid of spatially varying point spread functions and local frontal plane assumption, experiments show that the proposed method can effectively alleviate the system errors and improve the final reconstruction accuracy in various scenes. For a subsurface scattering scenario, if the translucent object is dominated by multiple scattering, the proposed method can also be applied to correct systematic errors once the bidirectional scattering-surface reflectance distribution function of the object material is measured.

Navigator alignment using radar scan

DOEpatents

Doerry, Armin W.; Marquette, Brandeis

2016-04-05

The various technologies presented herein relate to the determination of and correction of heading error of platform. Knowledge of at least one of a maximum Doppler frequency or a minimum Doppler bandwidth pertaining to a plurality of radar echoes can be utilized to facilitate correction of the heading error. Heading error can occur as a result of component drift. In an ideal situation, a boresight direction of an antenna or the front of an aircraft will have associated therewith at least one of a maximum Doppler frequency or a minimum Doppler bandwidth. As the boresight direction of the antenna strays from a direction of travel at least one of the maximum Doppler frequency or a minimum Doppler bandwidth will shift away, either left or right, from the ideal situation.

Genetic parameter estimation for pre- and post-weaning traits in Brahman cattle in Brazil.

PubMed

Vargas, Giovana; Buzanskas, Marcos Eli; Guidolin, Diego Gomes Freire; Grossi, Daniela do Amaral; Bonifácio, Alexandre da Silva; Lôbo, Raysildo Barbosa; da Fonseca, Ricardo; Oliveira, João Ademir de; Munari, Danísio Prado

2014-10-01

Beef cattle producers in Brazil use body weight traits as breeding program selection criteria due to their great economic importance. The objectives of this study were to evaluate different animal models, estimate genetic parameters, and define the most fitting model for Brahman cattle body weight standardized at 120 (BW120), 210 (BW210), 365 (BW365), 450 (BW450), and 550 (BW550) days of age. To estimate genetic parameters, single-, two-, and multi-trait analyses were performed using the animal model. The likelihood ratio test was verified between all models. For BW120 and BW210, additive direct genetic, maternal genetic, maternal permanent environment, and residual effects were considered, while for BW365 and BW450, additive direct genetic, maternal genetic, and residual effects were considered. Finally, for BW550, additive direct genetic and residual effects were considered. Estimates of direct heritability for BW120 were similar in all analyses; however, for the other traits, multi-trait analysis resulted in higher estimates. The maternal heritability and proportion of maternal permanent environmental variance to total variance were minimal in multi-trait analyses. Genetic, environmental, and phenotypic correlations were of high magnitude between all traits. Multi-trait analyses would aid in the parameter estimation for body weight at older ages because they are usually affected by a lower number of animals with phenotypic information due to culling and mortality.

The Measurement and Correction of the Periodic Error of the LX200-16 Telescope Driving System

NASA Astrophysics Data System (ADS)

Jeong, Jang Hae; Lee, Young Sam; Lee, Chung Uk

2000-06-01

We examined and corrected the periodic error of the LX200-16 Telescope driving system of Chungbuk National University Campus Observatory. Before correcting, the standard deviation of the periodic error in the direction of East-West was = 7.''2. After correcting,we found that the periodic error was reduced to = 1.''2.

78 FR 28597 - State Median Income Estimates for a Four-Person Household: Notice of the Federal Fiscal Year (FFY...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

....gov/acs/www/ or contact the Census Bureau's Social, Economic, and Housing Statistics Division at (301...) Sampling Error, which consists of the error that arises from the use of probability sampling to create the... direction; and (2) Sampling Error, which consists of the error that arises from the use of probability...

Heritability of neural reactions to social exclusion and prosocial compensation in middle childhood.

PubMed

van der Meulen, Mara; Steinbeis, Nikolaus; Achterberg, Michelle; van IJzendoorn, Marinus H; Crone, Eveline A

2018-06-07

Experiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent these processes and their neural correlates differ in heritability. We investigated influences of genetics and environment on experiencing social exclusion and compensating for social exclusion of others with the Prosocial Cyberball Game using fMRI in a twin sample (aged 7-9; N = 500). Neuroimaging analyses (N = 283) revealed that experiencing possible self-exclusion resulted in activity in inferior frontal gyrus and medial prefrontal cortex, which was influenced by genetics and unique environment. Experiencing self-inclusion was associated with activity in anterior cingulate cortex, insula and striatum, but this was not significantly explained by genetics or shared environment. We found that children show prosocial compensating behavior when observing social exclusion. Prosocial compensating behavior was associated with activity in posterior cingulate cortex/precuneus, and showed unique environmental effects or measurement error at both behavioral and neural level. Together, these findings show that in children neural activation for experiencing possible self-exclusion and self-inclusion, and for displaying prosocial compensating behavior, is accounted for by unique environmental factors and measurement error, with a small genetic effect on possible self-exclusion. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Operating Characteristics of Statistical Methods for Detecting Gene-by-Measured Environment Interaction in the Presence of Gene-Environment Correlation under Violations of Distributional Assumptions.

PubMed

Van Hulle, Carol A; Rathouz, Paul J

2015-02-01

Accurately identifying interactions between genetic vulnerabilities and environmental factors is of critical importance for genetic research on health and behavior. In the previous work of Van Hulle et al. (Behavior Genetics, Vol. 43, 2013, pp. 71-84), we explored the operating characteristics for a set of biometric (e.g., twin) models of Rathouz et al. (Behavior Genetics, Vol. 38, 2008, pp. 301-315), for testing gene-by-measured environment interaction (GxM) in the presence of gene-by-measured environment correlation (rGM) where data followed the assumed distributional structure. Here we explore the effects that violating distributional assumptions have on the operating characteristics of these same models even when structural model assumptions are correct. We simulated N = 2,000 replicates of n = 1,000 twin pairs under a number of conditions. Non-normality was imposed on either the putative moderator or on the ultimate outcome by ordinalizing or censoring the data. We examined the empirical Type I error rates and compared Bayesian information criterion (BIC) values. In general, non-normality in the putative moderator had little impact on the Type I error rates or BIC comparisons. In contrast, non-normality in the outcome was often mistaken for or masked GxM, especially when the outcome data were censored.

The MAX Statistic is Less Powerful for Genome Wide Association Studies Under Most Alternative Hypotheses.

PubMed

Shifflett, Benjamin; Huang, Rong; Edland, Steven D

2017-01-01

Genotypic association studies are prone to inflated type I error rates if multiple hypothesis testing is performed, e.g., sequentially testing for recessive, multiplicative, and dominant risk. Alternatives to multiple hypothesis testing include the model independent genotypic χ 2 test, the efficiency robust MAX statistic, which corrects for multiple comparisons but with some loss of power, or a single Armitage test for multiplicative trend, which has optimal power when the multiplicative model holds but with some loss of power when dominant or recessive models underlie the genetic association. We used Monte Carlo simulations to describe the relative performance of these three approaches under a range of scenarios. All three approaches maintained their nominal type I error rates. The genotypic χ 2 and MAX statistics were more powerful when testing a strictly recessive genetic effect or when testing a dominant effect when the allele frequency was high. The Armitage test for multiplicative trend was most powerful for the broad range of scenarios where heterozygote risk is intermediate between recessive and dominant risk. Moreover, all tests had limited power to detect recessive genetic risk unless the sample size was large, and conversely all tests were relatively well powered to detect dominant risk. Taken together, these results suggest the general utility of the multiplicative trend test when the underlying genetic model is unknown.

Application of artificial neural networks and genetic algorithms to modeling molecular electronic spectra in solution

NASA Astrophysics Data System (ADS)

Lilichenko, Mark; Kelley, Anne Myers

2001-04-01

A novel approach is presented for finding the vibrational frequencies, Franck-Condon factors, and vibronic linewidths that best reproduce typical, poorly resolved electronic absorption (or fluorescence) spectra of molecules in condensed phases. While calculation of the theoretical spectrum from the molecular parameters is straightforward within the harmonic oscillator approximation for the vibrations, "inversion" of an experimental spectrum to deduce these parameters is not. Standard nonlinear least-squares fitting methods such as Levenberg-Marquardt are highly susceptible to becoming trapped in local minima in the error function unless very good initial guesses for the molecular parameters are made. Here we employ a genetic algorithm to force a broad search through parameter space and couple it with the Levenberg-Marquardt method to speed convergence to each local minimum. In addition, a neural network trained on a large set of synthetic spectra is used to provide an initial guess for the fitting parameters and to narrow the range searched by the genetic algorithm. The combined algorithm provides excellent fits to a variety of single-mode absorption spectra with experimentally negligible errors in the parameters. It converges more rapidly than the genetic algorithm alone and more reliably than the Levenberg-Marquardt method alone, and is robust in the presence of spectral noise. Extensions to multimode systems, and/or to include other spectroscopic data such as resonance Raman intensities, are straightforward.

Action errors, error management, and learning in organizations.

PubMed

Frese, Michael; Keith, Nina

2015-01-03

Every organization is confronted with errors. Most errors are corrected easily, but some may lead to negative consequences. Organizations often focus on error prevention as a single strategy for dealing with errors. Our review suggests that error prevention needs to be supplemented by error management--an approach directed at effectively dealing with errors after they have occurred, with the goal of minimizing negative and maximizing positive error consequences (examples of the latter are learning and innovations). After defining errors and related concepts, we review research on error-related processes affected by error management (error detection, damage control). Empirical evidence on positive effects of error management in individuals and organizations is then discussed, along with emotional, motivational, cognitive, and behavioral pathways of these effects. Learning from errors is central, but like other positive consequences, learning occurs under certain circumstances--one being the development of a mind-set of acceptance of human error.

Treatable newborn and infant seizures due to inborn errors of metabolism.

PubMed

Campistol, Jaume; Plecko, Barbara

2015-09-01

About 25% of seizures in the neonatal period have causes other than asphyxia, ischaemia or intracranial bleeding. Among these are primary genetic epileptic encephalopathies with sometimes poor prognosis and high mortality. In addition, some forms of neonatal infant seizures are due to inborn errors of metabolism that do not respond to common AEDs, but are amenable to specific treatment. In this situation, early recognition can allow seizure control and will prevent neurological deterioration and long-term sequelae. We review the group of inborn errors of metabolism that lead to newborn/infant seizures and epilepsy, of which the treatment with cofactors is very different to that used in typical epilepsy management.

"Apologies" from pathologists: why, when, and how to say "sorry" after committing a medical error.

PubMed

Dewar, Rajan; Parkash, Vinita; Forrow, Lachlan; Truog, Robert D

2014-05-01

How pathologists communicate an error is complicated by the absence of a direct physician-patient relationship. Using 2 examples, we elaborate on how other physician colleagues routinely play an intermediary role in our day-to-day transactions and in the communication of a pathologist error to the patient. The concept of a "dual-hybrid" mind-set in the intermediary physician and its role in representing the pathologists' viewpoint adequately is considered. In a dual-hybrid mind-set, the intermediary physician can align with the patients' philosophy and like the patient, consider the smallest deviation from norm to be an error. Alternatively, they might embrace the traditional physician philosophy and communicate only those errors that resulted in a clinically inappropriate outcome. Neither may effectively reflect the pathologists' interests. We propose that pathologists develop strategies to communicate errors that include considerations of meeting with the patients directly. Such interactions promote healing for the patient and are relieving to the well-intentioned pathologist.

Correction of a Technical Error in the Golf Swing: Error Amplification Versus Direct Instruction.

PubMed

Milanese, Chiara; Corte, Stefano; Salvetti, Luca; Cavedon, Valentina; Agostini, Tiziano

2016-01-01

Performance errors drive motor learning for many tasks. The authors' aim was to determine which of two strategies, method of amplification of error (MAE) or direct instruction (DI), would be more beneficial for error correction during a full golfing swing with a driver. Thirty-four golfers were randomly assigned to one of three training conditions (MAE, DI, and control). Participants were tested in a practice session in which each golfer performed 7 pretraining trials, 6 training-intervention trials, and 7 posttraining trials; and a retention test after 1 week. An optoeletronic motion capture system was used to measure the kinematic parameters of each golfer's performance. Results showed that MAE is an effective strategy for correcting the technical errors leading to a rapid improvement in performance. These findings could have practical implications for sport psychology and physical education because, while practice is obviously necessary for improving learning, the efficacy of the learning process is essential in enhancing learners' motivation and sport enjoyment.

Detecting Spatial Patterns in Biological Array Experiments

PubMed Central

ROOT, DAVID E.; KELLEY, BRIAN P.; STOCKWELL, BRENT R.

2005-01-01

Chemical genetic screening and DNA and protein microarrays are among a number of increasingly important and widely used biological research tools that involve large numbers of parallel experiments arranged in a spatial array. It is often difficult to ensure that uniform experimental conditions are present throughout the entire array, and as a result, one often observes systematic spatially correlated errors, especially when array experiments are performed using robots. Here, the authors apply techniques based on the discrete Fourier transform to identify and quantify spatially correlated errors superimposed on a spatially random background. They demonstrate that these techniques are effective in identifying common spatially systematic errors in high-throughput 384-well microplate assay data. In addition, the authors employ a statistical test to allow for automatic detection of such errors. Software tools for using this approach are provided. PMID:14567791

E-prescribing errors in community pharmacies: exploring consequences and contributing factors.

PubMed

Odukoya, Olufunmilola K; Stone, Jamie A; Chui, Michelle A

2014-06-01

To explore types of e-prescribing errors in community pharmacies and their potential consequences, as well as the factors that contribute to e-prescribing errors. Data collection involved performing 45 total hours of direct observations in five pharmacies. Follow-up interviews were conducted with 20 study participants. Transcripts from observations and interviews were subjected to content analysis using NVivo 10. Pharmacy staff detected 75 e-prescription errors during the 45 h observation in pharmacies. The most common e-prescribing errors were wrong drug quantity, wrong dosing directions, wrong duration of therapy, and wrong dosage formulation. Participants estimated that 5 in 100 e-prescriptions have errors. Drug classes that were implicated in e-prescribing errors were antiinfectives, inhalers, ophthalmic, and topical agents. The potential consequences of e-prescribing errors included increased likelihood of the patient receiving incorrect drug therapy, poor disease management for patients, additional work for pharmacy personnel, increased cost for pharmacies and patients, and frustrations for patients and pharmacy staff. Factors that contribute to errors included: technology incompatibility between pharmacy and clinic systems, technology design issues such as use of auto-populate features and dropdown menus, and inadvertently entering incorrect information. Study findings suggest that a wide range of e-prescribing errors is encountered in community pharmacies. Pharmacists and technicians perceive that causes of e-prescribing errors are multidisciplinary and multifactorial, that is to say e-prescribing errors can originate from technology used in prescriber offices and pharmacies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

E-Prescribing Errors in Community Pharmacies: Exploring Consequences and Contributing Factors

PubMed Central

Stone, Jamie A.; Chui, Michelle A.

2014-01-01

Objective To explore types of e-prescribing errors in community pharmacies and their potential consequences, as well as the factors that contribute to e-prescribing errors. Methods Data collection involved performing 45 total hours of direct observations in five pharmacies. Follow-up interviews were conducted with 20 study participants. Transcripts from observations and interviews were subjected to content analysis using NVivo 10. Results Pharmacy staff detected 75 e-prescription errors during the 45 hour observation in pharmacies. The most common e-prescribing errors were wrong drug quantity, wrong dosing directions, wrong duration of therapy, and wrong dosage formulation. Participants estimated that 5 in 100 e-prescriptions have errors. Drug classes that were implicated in e-prescribing errors were antiinfectives, inhalers, ophthalmic, and topical agents. The potential consequences of e-prescribing errors included increased likelihood of the patient receiving incorrect drug therapy, poor disease management for patients, additional work for pharmacy personnel, increased cost for pharmacies and patients, and frustrations for patients and pharmacy staff. Factors that contribute to errors included: technology incompatibility between pharmacy and clinic systems, technology design issues such as use of auto-populate features and dropdown menus, and inadvertently entering incorrect information. Conclusion Study findings suggest that a wide range of e-prescribing errors are encountered in community pharmacies. Pharmacists and technicians perceive that causes of e-prescribing errors are multidisciplinary and multifactorial, that is to say e-prescribing errors can originate from technology used in prescriber offices and pharmacies. PMID:24657055

Improvement in Patient Transfer Process From the Operating Room to the PICU Using a Lean and Six Sigma-Based Quality Improvement Project.

PubMed

Gleich, Stephen J; Nemergut, Michael E; Stans, Anthony A; Haile, Dawit T; Feigal, Scott A; Heinrich, Angela L; Bosley, Christopher L; Tripathi, Sandeep

2016-08-01

Ineffective and inefficient patient transfer processes can increase the chance of medical errors. Improvements in such processes are high-priority local institutional and national patient safety goals. At our institution, nonintubated postoperative pediatric patients are first admitted to the postanesthesia care unit before transfer to the PICU. This quality improvement project was designed to improve the patient transfer process from the operating room (OR) to the PICU. After direct observation of the baseline process, we introduced a structured, direct OR-PICU transfer process for orthopedic spinal fusion patients. We performed value stream mapping of the process to determine error-prone and inefficient areas. We evaluated primary outcome measures of handoff error reduction and the overall efficiency of patient transfer process time. Staff satisfaction was evaluated as a counterbalance measure. With the introduction of the new direct OR-PICU patient transfer process, the handoff communication error rate improved from 1.9 to 0.3 errors per patient handoff (P = .002). Inefficiency (patient wait time and non-value-creating activity) was reduced from 90 to 32 minutes. Handoff content was improved with fewer information omissions (P < .001). Staff satisfaction significantly improved among nearly all PICU providers. By using quality improvement methodology to design and implement a new direct OR-PICU transfer process with a structured multidisciplinary verbal handoff, we achieved sustained improvements in patient safety and efficiency. Handoff communication was enhanced, with fewer errors and content omissions. The new process improved efficiency, with high staff satisfaction. Copyright © 2016 by the American Academy of Pediatrics.

An Empirical State Error Covariance Matrix for Batch State Estimation

NASA Technical Reports Server (NTRS)

Frisbee, Joseph H., Jr.

2011-01-01

State estimation techniques serve effectively to provide mean state estimates. However, the state error covariance matrices provided as part of these techniques suffer from some degree of lack of confidence in their ability to adequately describe the uncertainty in the estimated states. A specific problem with the traditional form of state error covariance matrices is that they represent only a mapping of the assumed observation error characteristics into the state space. Any errors that arise from other sources (environment modeling, precision, etc.) are not directly represented in a traditional, theoretical state error covariance matrix. Consider that an actual observation contains only measurement error and that an estimated observation contains all other errors, known and unknown. It then follows that a measurement residual (the difference between expected and observed measurements) contains all errors for that measurement. Therefore, a direct and appropriate inclusion of the actual measurement residuals in the state error covariance matrix will result in an empirical state error covariance matrix. This empirical state error covariance matrix will fully account for the error in the state estimate. By way of a literal reinterpretation of the equations involved in the weighted least squares estimation algorithm, it is possible to arrive at an appropriate, and formally correct, empirical state error covariance matrix. The first specific step of the method is to use the average form of the weighted measurement residual variance performance index rather than its usual total weighted residual form. Next it is helpful to interpret the solution to the normal equations as the average of a collection of sample vectors drawn from a hypothetical parent population. From here, using a standard statistical analysis approach, it directly follows as to how to determine the standard empirical state error covariance matrix. This matrix will contain the total uncertainty in the state estimate, regardless as to the source of the uncertainty. Also, in its most straight forward form, the technique only requires supplemental calculations to be added to existing batch algorithms. The generation of this direct, empirical form of the state error covariance matrix is independent of the dimensionality of the observations. Mixed degrees of freedom for an observation set are allowed. As is the case with any simple, empirical sample variance problems, the presented approach offers an opportunity (at least in the case of weighted least squares) to investigate confidence interval estimates for the error covariance matrix elements. The diagonal or variance terms of the error covariance matrix have a particularly simple form to associate with either a multiple degree of freedom chi-square distribution (more approximate) or with a gamma distribution (less approximate). The off diagonal or covariance terms of the matrix are less clear in their statistical behavior. However, the off diagonal covariance matrix elements still lend themselves to standard confidence interval error analysis. The distributional forms associated with the off diagonal terms are more varied and, perhaps, more approximate than those associated with the diagonal terms. Using a simple weighted least squares sample problem, results obtained through use of the proposed technique are presented. The example consists of a simple, two observer, triangulation problem with range only measurements. Variations of this problem reflect an ideal case (perfect knowledge of the range errors) and a mismodeled case (incorrect knowledge of the range errors).

Inheritance of astigmatism: evidence for a major autosomal dominant locus.

PubMed Central

Clementi, M; Angi, M; Forabosco, P; Di Gianantonio, E; Tenconi, R

1998-01-01

Although astigmatism is a frequent refractive error, its mode of inheritance remains uncertain. Complex segregation analysis was performed, by the POINTER and COMDS programs, with data from a geographically well-defined sample of 125 nuclear families of individuals affected by astigmatism. POINTER could not distinguish between alternative genetic models, and only the hypothesis of no familial transmission could be rejected. After inclusion of the severity parameter, COMDS results defined a genetic model for corneal astigmatism and provided evidence for single-major-locus inheritance. These results suggest that genetic linkage studies could be implemented and that they should be limited to multiplex families with severely affected individuals. PMID:9718344

δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 (ALAD2) and Peptide Transporter 2*2 Haplotype (hPEPT2*2) Differently Influence Neurobehavior in Low-Level Lead Exposed Children

PubMed Central

Sobin, Christina; Gisel Flores-Montoya, Mayra; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2014-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1 to 11.8 years. Ninety-six percent of children had BLLs < 5.0 µg/dL. After adjusting for covariates (sex, age and mother’s level of education) and sibling exclusion (N = 252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. PMID:25514583

δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter 2*2 haplotype (hPEPT2*2) differently influence neurobehavior in low-level lead exposed children.

PubMed

Sobin, Christina; Flores-Montoya, Mayra Gisel; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2015-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1-11.8years. Ninety-six percent of children had BLLs<5.0μg/dl. After adjusting for covariates (sex, age and mother's level of education) and sibling exclusion (N=252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Space-Borne Laser Altimeter Geolocation Error Analysis

NASA Astrophysics Data System (ADS)

Wang, Y.; Fang, J.; Ai, Y.

2018-05-01

This paper reviews the development of space-borne laser altimetry technology over the past 40 years. Taking the ICESAT satellite as an example, a rigorous space-borne laser altimeter geolocation model is studied, and an error propagation equation is derived. The influence of the main error sources, such as the platform positioning error, attitude measurement error, pointing angle measurement error and range measurement error, on the geolocation accuracy of the laser spot are analysed by simulated experiments. The reasons for the different influences on geolocation accuracy in different directions are discussed, and to satisfy the accuracy of the laser control point, a design index for each error source is put forward.

Improving Brain Magnetic Resonance Image (MRI) Segmentation via a Novel Algorithm based on Genetic and Regional Growth

PubMed Central

A., Javadpour; A., Mohammadi

2016-01-01

Background Regarding the importance of right diagnosis in medical applications, various methods have been exploited for processing medical images solar. The method of segmentation is used to analyze anal to miscall structures in medical imaging. Objective This study describes a new method for brain Magnetic Resonance Image (MRI) segmentation via a novel algorithm based on genetic and regional growth. Methods Among medical imaging methods, brains MRI segmentation is important due to high contrast of non-intrusive soft tissue and high spatial resolution. Size variations of brain tissues are often accompanied by various diseases such as Alzheimer’s disease. As our knowledge about the relation between various brain diseases and deviation of brain anatomy increases, MRI segmentation is exploited as the first step in early diagnosis. In this paper, regional growth method and auto-mate selection of initial points by genetic algorithm is used to introduce a new method for MRI segmentation. Primary pixels and similarity criterion are automatically by genetic algorithms to maximize the accuracy and validity in image segmentation. Results By using genetic algorithms and defining the fixed function of image segmentation, the initial points for the algorithm were found. The proposed algorithms are applied to the images and results are manually selected by regional growth in which the initial points were compared. The results showed that the proposed algorithm could reduce segmentation error effectively. Conclusion The study concluded that the proposed algorithm could reduce segmentation error effectively and help us to diagnose brain diseases. PMID:27672629

Covariance analysis for evaluating head trackers

NASA Astrophysics Data System (ADS)

Kang, Donghoon

2017-10-01

Existing methods for evaluating the performance of head trackers usually rely on publicly available face databases, which contain facial images and the ground truths of their corresponding head orientations. However, most of the existing publicly available face databases are constructed by assuming that a frontal head orientation can be determined by compelling the person under examination to look straight ahead at the camera on the first video frame. Since nobody can accurately direct one's head toward the camera, this assumption may be unrealistic. Rather than obtaining estimation errors, we present a method for computing the covariance of estimation error rotations to evaluate the reliability of head trackers. As an uncertainty measure of estimators, the Schatten 2-norm of a square root of error covariance (or the algebraic average of relative error angles) can be used. The merit of the proposed method is that it does not disturb the person under examination by asking him to direct his head toward certain directions. Experimental results using real data validate the usefulness of our method.

Genetics Home Reference: Imerslund-Gräsbeck syndrome

MedlinePlus

... 1172-7-56. Citation on PubMed or Free article on PubMed Central Watkins D, Rosenblatt DS. Lessons in biology from patients with inborn errors of vitamin B12 metabolism. Biochimie. 2013 May;95(5):1019-22. doi: ...

Precision genome editing in the CRISPR era.

PubMed

Salsman, Jayme; Dellaire, Graham

2017-04-01

With the introduction of precision genome editing using CRISPR-Cas9 technology, we have entered a new era of genetic engineering and gene therapy. With RNA-guided endonucleases, such as Cas9, it is possible to engineer DNA double strand breaks (DSB) at specific genomic loci. DSB repair by the error-prone non-homologous end-joining (NHEJ) pathway can disrupt a target gene by generating insertions and deletions. Alternatively, Cas9-mediated DSBs can be repaired by homology-directed repair (HDR) using an homologous DNA repair template, thus allowing precise gene editing by incorporating genetic changes into the repair template. HDR can introduce gene sequences for protein epitope tags, delete genes, make point mutations, or alter enhancer and promoter activities. In anticipation of adapting this technology for gene therapy in human somatic cells, much focus has been placed on increasing the fidelity of CRISPR-Cas9 and increasing HDR efficiency to improve precision genome editing. In this review, we will discuss applications of CRISPR technology for gene inactivation and genome editing with a focus on approaches to enhancing CRISPR-Cas9-mediated HDR for the generation of cell and animal models, and conclude with a discussion of recent advances and challenges towards the application of this technology for gene therapy in humans.

Direct-to-Consumer Genetic Testing: Helping Patients Make Informed Choices
.

PubMed

Mahon, Suzanne M

2018-02-01

Using direct-to-consumer genetic testing (DTCGT), individuals can order a genetic test, collect and submit a saliva sample, and obtain results about their genetic risk for a variety of traits and health conditions without involving a healthcare provider. Potential benefits of DTCGT include personal control over genetic information and health management decisions, whereas potential risks include misinterpretation of results, psychosocial distress, and lack of informed consent. Oncology nurses can provide education, support, and advocacy to enable patients to truly understand the positives and negatives associated with DTCGT.
.

Effects of specimen preparation on the electromagnetic property measurements of solid materials with an automatic network analyzer

NASA Technical Reports Server (NTRS)

Long, E. R., Jr.

1986-01-01

Effects of specimen preparation on measured values of an acrylic's electomagnetic properties at X-band microwave frequencies, TE sub 1,0 mode, utilizing an automatic network analyzer have been studied. For 1 percent or less error, a gap between the specimen edge and the 0.901-in. wall of the specimen holder was the most significant parameter. The gap had to be less than 0.002 in. The thickness variation and alignment errors in the direction parallel to the 0.901-in. wall were equally second most significant and had to be less than 1 degree. Errors in the measurement f the thickness were third most significant. They had to be less than 3 percent. The following parameters caused errors of 1 percent or less: ratios of specimen-holder thicknesses of more than 15 percent, gaps between the specimen edge and the 0.401-in. wall less than 0.045 in., position errors less than 15 percent, surface roughness, hickness variation in the direction parallel to the 0.401-in. wall less than 35 percent, and specimen alignment in the direction parallel to the 0.401-in. wall mass than 5 degrees.

Evaluating software development characteristics: A comparison of software errors in different environments

NASA Technical Reports Server (NTRS)

Weiss, D. M.

1981-01-01

Error data obtained from two different software development environments are compared. To obtain data that was complete, accurate, and meaningful, a goal-directed data collection methodology was used. Changes made to software were monitored concurrently with its development. Similarities common to both environments are included: (1) the principal error was in the design and implementation of single routines; (2) few errors were the result of changes, required more than one attempt to correct, and resulted in other errors; (3) relatively few errors took more than a day to correct.

Pointing error analysis of Risley-prism-based beam steering system.

PubMed

Zhou, Yuan; Lu, Yafei; Hei, Mo; Liu, Guangcan; Fan, Dapeng

2014-09-01

Based on the vector form Snell's law, ray tracing is performed to quantify the pointing errors of Risley-prism-based beam steering systems, induced by component errors, prism orientation errors, and assembly errors. Case examples are given to elucidate the pointing error distributions in the field of regard and evaluate the allowances of the error sources for a given pointing accuracy. It is found that the assembly errors of the second prism will result in more remarkable pointing errors in contrast with the first one. The pointing errors induced by prism tilt depend on the tilt direction. The allowances of bearing tilt and prism tilt are almost identical if the same pointing accuracy is planned. All conclusions can provide a theoretical foundation for practical works.

Sources of uncertainty in the quantification of genetically modified oilseed rape contamination in seed lots.

PubMed

Begg, Graham S; Cullen, Danny W; Iannetta, Pietro P M; Squire, Geoff R

2007-02-01

Testing of seed and grain lots is essential in the enforcement of GM labelling legislation and needs reliable procedures for which associated errors have been identified and minimised. In this paper we consider the testing of oilseed rape seed lots obtained from the harvest of a non-GM crop known to be contaminated by volunteer plants from a GM herbicide tolerant variety. The objective was to identify and quantify the error associated with the testing of these lots from the initial sampling to completion of the real-time PCR assay with which the level of GM contamination was quantified. The results showed that, under the controlled conditions of a single laboratory, the error associated with the real-time PCR assay to be negligible in comparison with sampling error, which was exacerbated by heterogeneity in the distribution of GM seeds, most notably at a small scale, i.e. 25 cm3. Sampling error was reduced by one to two thirds on the application of appropriate homogenisation procedures.

TH-AB-202-02: Real-Time Verification and Error Detection for MLC Tracking Deliveries Using An Electronic Portal Imaging Device

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

J Zwan, B; Central Coast Cancer Centre, Gosford, NSW; Colvill, E

2016-06-15

Purpose: The added complexity of the real-time adaptive multi-leaf collimator (MLC) tracking increases the likelihood of undetected MLC delivery errors. In this work we develop and test a system for real-time delivery verification and error detection for MLC tracking radiotherapy using an electronic portal imaging device (EPID). Methods: The delivery verification system relies on acquisition and real-time analysis of transit EPID image frames acquired at 8.41 fps. In-house software was developed to extract the MLC positions from each image frame. Three comparison metrics were used to verify the MLC positions in real-time: (1) field size, (2) field location and, (3)more » field shape. The delivery verification system was tested for 8 VMAT MLC tracking deliveries (4 prostate and 4 lung) where real patient target motion was reproduced using a Hexamotion motion stage and a Calypso system. Sensitivity and detection delay was quantified for various types of MLC and system errors. Results: For both the prostate and lung test deliveries the MLC-defined field size was measured with an accuracy of 1.25 cm{sup 2} (1 SD). The field location was measured with an accuracy of 0.6 mm and 0.8 mm (1 SD) for lung and prostate respectively. Field location errors (i.e. tracking in wrong direction) with a magnitude of 3 mm were detected within 0.4 s of occurrence in the X direction and 0.8 s in the Y direction. Systematic MLC gap errors were detected as small as 3 mm. The method was not found to be sensitive to random MLC errors and individual MLC calibration errors up to 5 mm. Conclusion: EPID imaging may be used for independent real-time verification of MLC trajectories during MLC tracking deliveries. Thresholds have been determined for error detection and the system has been shown to be sensitive to a range of delivery errors.« less

Frequency-domain Green's functions for radar waves in heterogeneous 2.5D media

USGS Publications Warehouse

Ellefsen, K.J.; Croize, D.; Mazzella, A.T.; McKenna, J.R.

2009-01-01

Green's functions for radar waves propagating in heterogeneous 2.5D media might be calculated in the frequency domain using a hybrid method. The model is defined in the Cartesian coordinate system, and its electromagnetic properties might vary in the x- and z-directions, but not in the y-direction. Wave propagation in the x- and z-directions is simulated with the finite-difference method, and wave propagation in the y-direction is simulated with an analytic function. The absorbing boundaries on the finite-difference grid are perfectly matched layers that have been modified to make them compatible with the hybrid method. The accuracy of these numerical Greens functions is assessed by comparing them with independently calculated Green's functions. For a homogeneous model, the magnitude errors range from -4.16% through 0.44%, and the phase errors range from -0.06% through 4.86%. For a layered model, the magnitude errors range from -2.60% through 2.06%, and the phase errors range from -0.49% through 2.73%. These numerical Green's functions might be used for forward modeling and full waveform inversion. ?? 2009 Society of Exploration Geophysicists. All rights reserved.

Error Checking and Graphical Representation of Multiple–Complete–Digest (MCD) Restriction-Fragment Maps

PubMed Central

Thayer, Edward C.; Olson, Maynard V.; Karp, Richard M.

1999-01-01

Genetic and physical maps display the relative positions of objects or markers occurring within a target DNA molecule. In constructing maps, the primary objective is to determine the ordering of these objects. A further objective is to assign a coordinate to each object, indicating its distance from a reference end of the target molecule. This paper describes a computational method and a body of software for assigning coordinates to map objects, given a solution or partial solution to the ordering problem. We describe our method in the context of multiple–complete–digest (MCD) mapping, but it should be applicable to a variety of other mapping problems. Because of errors in the data or insufficient clone coverage to uniquely identify the true ordering of the map objects, a partial ordering is typically the best one can hope for. Once a partial ordering has been established, one often seeks to overlay a metric along the map to assess the distances between the map objects. This problem often proves intractable because of data errors such as erroneous local length measurements (e.g., large clone lengths on low-resolution physical maps). We present a solution to the coordinate assignment problem for MCD restriction-fragment mapping, in which a coordinated set of single-enzyme restriction maps are simultaneously constructed. We show that the coordinate assignment problem can be expressed as the solution of a system of linear constraints. If the linear system is free of inconsistencies, it can be solved using the standard Bellman–Ford algorithm. In the more typical case where the system is inconsistent, our program perturbs it to find a new consistent system of linear constraints, close to those of the given inconsistent system, using a modified Bellman–Ford algorithm. Examples are provided of simple map inconsistencies and the methods by which our program detects candidate data errors and directs the user to potential suspect regions of the map. PMID:9927487

Trends and Gaps in Awareness of Direct-to-Consumer Genetic Tests From 2007 to 2014.

PubMed

Apathy, Nate C; Menser, Terri; Keeran, Lindsay M; Ford, Eric W; Harle, Christopher A; Huerta, Timothy R

2018-06-01

Direct-to-consumer genetic tests for inherited disease risks have gained recent approvals from the Food and Drug Administration, and interest in these tests has continued to grow. Broad use of these tests coupled with planning and discussion with health providers regarding genetic risks and potential protective behavior changes have been proposed as preventive tools to reduce health disparities and improve equity in health outcomes. However, awareness of direct-to-consumer genetic testing has historically demonstrated differences by education, income, and race; these disparities could jeopardize potential benefits by limiting access and use. The national survey data from the Health Information National Trends Survey was analyzed to understand how overall awareness of direct-to-consumer genetic testing and disparities in awareness across sociodemographic groups have changed since 2007. The findings showed persistent disparities, as well as a widening gap in awareness between Hispanics and non-Hispanic whites (OR 2007 =1.52, OR 2014 =0.58, p change =0.0056), despite overall increases in awareness over time. Given these findings, policies regulating direct-to-consumer genetic tests should prioritize equitable distribution of benefits by including provisions that counteract prevailing disparities in awareness. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Automation and validation of DNA-banking systems.

PubMed

Thornton, Melissa; Gladwin, Amanda; Payne, Robin; Moore, Rachael; Cresswell, Carl; McKechnie, Douglas; Kelly, Steve; March, Ruth

2005-10-15

DNA banking is one of the central capabilities on which modern genetic research rests. The DNA-banking system plays an essential role in the flow of genetic data from patients and genetics researchers to the application of genetic research in the clinic. Until relatively recently, large collections of DNA samples were not common in human genetics. Now, collections of hundreds of thousands of samples are common in academic institutions and private companies. Automation of DNA banking can dramatically increase throughput, eliminate manual errors and improve the productivity of genetics research. An increased emphasis on pharmacogenetics and personalized medicine has highlighted the need for genetics laboratories to operate within the principles of a recognized quality system such as good laboratory practice (GLP). Automated systems are suitable for such laboratories but require a level of validation that might be unfamiliar to many genetics researchers. In this article, we use the AstraZeneca automated DNA archive and reformatting system (DART) as a case study of how such a system can be successfully developed and validated within the principles of GLP.

Maintaining Genetic Integrity Under Extreme Conditions: Novel DNA Damage Repair Biology in the Archaea

DTIC Science & Technology

2013-11-23

Genetic analysis of Nre DNA repair function A4 Conclusions B. Widening the net in the search for new DNA-directed enzyme activities C. New tools for H...Figure 1) were hypothesised to be novel DNA repair enzymes . The stated aims of the proposal were to use a combination of genetic, biochemical and...in E.coli Almost all proteins that interact directly with PCNA are enzymes possessing DNA-directed activities such as nucleases, glycosylases

Nutrigenomics and ethics interface: direct-to-consumer services and commercial aspects.

PubMed

Ries, Nola M; Castle, David

2008-12-01

A growing variety and number of genetic tests are advertised and sold directly to consumers (DTC) via the Internet, including nutrigenomic tests and associated products and services. Consumers have more access to genetic information about themselves, but access does not entail certainty about the implications of test results. Potential personal and public health harms and benefits are associated with DTC access to genetic testing services. Early policy responses to direct-to-consumer (DTC) genetic testing often involved calls for bans, and some jurisdictions prohibited DTC genetic tests. Recent policy responses by oversight bodies acknowledge expansion in the range of DTC tests available and suggest that a "one-size-fits-all" regulatory approach is not appropriate for all genetic tests. This review discusses ethical and regulatory aspects of DTC genetic testing, focusing particularly on nutrigenomic tests. We identify policy options for regulating DTC genetic tests, including full or partial prohibitions, enforcement of existing truth-in-advertising laws, and more comprehensive information disclosure about genetic tests. We advocate the latter option as an important means to improve transparency about current evidence on the strengths and limits of gene-disease associations and allow consumers to make informed purchasing decisions in the DTC marketplace.

Proximal Versus Distal Control of Two-Joint Planar Reaching Movements in the Presence of Neuromuscular Noise

PubMed Central

Nguyen, Hung P.; Dingwell, Jonathan B.

2012-01-01

Determining how the human nervous system contends with neuro-motor noise is vital to understanding how humans achieve accurate goal-directed movements. Experimentally, people learning skilled tasks tend to reduce variability in distal joint movements more than in proximal joint movements. This suggests that they might be imposing greater control over distal joints than proximal joints. However, the reasons for this remain unclear, largely because it is not experimentally possible to directly manipulate either the noise or the control at each joint independently. Therefore, this study used a 2 degree-of-freedom torque driven arm model to determine how different combinations of noise and/or control independently applied at each joint affected the reaching accuracy and the total work required to make the movement. Signal-dependent noise was simultaneously and independently added to the shoulder and elbow torques to induce endpoint errors during planar reaching. Feedback control was then applied, independently and jointly, at each joint to reduce endpoint error due to the added neuromuscular noise. Movement direction and the inertia distribution along the arm were varied to quantify how these biomechanical variations affected the system performance. Endpoint error and total net work were computed as dependent measures. When each joint was independently subjected to noise in the absence of control, endpoint errors were more sensitive to distal (elbow) noise than to proximal (shoulder) noise for nearly all combinations of reaching direction and inertia ratio. The effects of distal noise on endpoint errors were more pronounced when inertia was distributed more toward the forearm. In contrast, the total net work decreased as mass was shifted to the upper arm for reaching movements in all directions. When noise was present at both joints and joint control was implemented, controlling the distal joint alone reduced endpoint errors more than controlling the proximal joint alone for nearly all combinations of reaching direction and inertia ratio. Applying control only at the distal joint was more effective at reducing endpoint errors when more of the mass was more proximally distributed. Likewise, controlling the distal joint alone required less total net work than controlling the proximal joint alone for nearly all combinations of reaching distance and inertia ratio. It is more efficient to reduce endpoint error and energetic cost by selectively applying control to reduce variability in the distal joint than the proximal joint. The reasons for this arise from the biomechanical configuration of the arm itself. PMID:22757504

Proximal versus distal control of two-joint planar reaching movements in the presence of neuromuscular noise.

PubMed

Nguyen, Hung P; Dingwell, Jonathan B

2012-06-01

Determining how the human nervous system contends with neuro-motor noise is vital to understanding how humans achieve accurate goal-directed movements. Experimentally, people learning skilled tasks tend to reduce variability in distal joint movements more than in proximal joint movements. This suggests that they might be imposing greater control over distal joints than proximal joints. However, the reasons for this remain unclear, largely because it is not experimentally possible to directly manipulate either the noise or the control at each joint independently. Therefore, this study used a 2 degree-of-freedom torque driven arm model to determine how different combinations of noise and/or control independently applied at each joint affected the reaching accuracy and the total work required to make the movement. Signal-dependent noise was simultaneously and independently added to the shoulder and elbow torques to induce endpoint errors during planar reaching. Feedback control was then applied, independently and jointly, at each joint to reduce endpoint error due to the added neuromuscular noise. Movement direction and the inertia distribution along the arm were varied to quantify how these biomechanical variations affected the system performance. Endpoint error and total net work were computed as dependent measures. When each joint was independently subjected to noise in the absence of control, endpoint errors were more sensitive to distal (elbow) noise than to proximal (shoulder) noise for nearly all combinations of reaching direction and inertia ratio. The effects of distal noise on endpoint errors were more pronounced when inertia was distributed more toward the forearm. In contrast, the total net work decreased as mass was shifted to the upper arm for reaching movements in all directions. When noise was present at both joints and joint control was implemented, controlling the distal joint alone reduced endpoint errors more than controlling the proximal joint alone for nearly all combinations of reaching direction and inertia ratio. Applying control only at the distal joint was more effective at reducing endpoint errors when more of the mass was more proximally distributed. Likewise, controlling the distal joint alone required less total net work than controlling the proximal joint alone for nearly all combinations of reaching distance and inertia ratio. It is more efficient to reduce endpoint error and energetic cost by selectively applying control to reduce variability in the distal joint than the proximal joint. The reasons for this arise from the biomechanical configuration of the arm itself.

Clearing the Air: A Qualitative Investigation of Genetic Counselors' Experiences of Counselor-Focused Patient Anger.

PubMed

Schema, Lynn; McLaughlin, Michaela; Veach, Patricia McCarthy; LeRoy, Bonnie S

2015-10-01

Patient anger is challenging for healthcare professionals to manage, particularly when it is directed at them. This study comprises the first in-depth investigation of genetic counselors' experiences with patient anger. Using a brief survey and interview methods, this study explored prevalence and context of patient anger directed at the genetic counselor, how genetic counselors manage patient anger directed at them, and possible thematic differences due to genetic counseling experience. Individuals enrolled in the National Society of Genetic Counselors (NSGC) listserv were invited to participate in a study of their experiences with patient anger directed at them. A majority of survey respondents (95.7 %, 243/254) reported experiencing patient anger directed at them, and 19.4 % reported having feared for their safety because of patient anger. Twenty-two survey respondents were purposively selected to participate in individual interviews. Inductive and cross case analysis yielded prevalent themes concerning patient triggers for anger, including bad news, logistical mishaps, and perceived counselor characteristics. Interview results further suggest unaddressed patient anger negatively affected patient and counselor emotional well-being and hindered genetic counseling goals. Prevalent challenges included genetic counselor attempts to accurately recognize, understand, and effectively manage patient anger without taking it personally. Commonly recommended strategies for addressing anger were empathy (i.e., understanding origins of patient anger), anticipating and acknowledging anger, maintaining personal, professional and legal protection, and debriefing with colleagues. Themes were quite similar across counselor experience levels. The findings underscore the importance of training and continuing education regarding patient anger. Additional findings, practice implications, and research recommendations are presented.

Error detection and reduction in blood banking.

PubMed

Motschman, T L; Moore, S B

1996-12-01

Error management plays a major role in facility process improvement efforts. By detecting and reducing errors, quality and, therefore, patient care improve. It begins with a strong organizational foundation of management attitude with clear, consistent employee direction and appropriate physical facilities. Clearly defined critical processes, critical activities, and SOPs act as the framework for operations as well as active quality monitoring. To assure that personnel can detect an report errors they must be trained in both operational duties and error management practices. Use of simulated/intentional errors and incorporation of error detection into competency assessment keeps employees practiced, confident, and diminishes fear of the unknown. Personnel can clearly see that errors are indeed used as opportunities for process improvement and not for punishment. The facility must have a clearly defined and consistently used definition for reportable errors. Reportable errors should include those errors with potentially harmful outcomes as well as those errors that are "upstream," and thus further away from the outcome. A well-written error report consists of who, what, when, where, why/how, and follow-up to the error. Before correction can occur, an investigation to determine the underlying cause of the error should be undertaken. Obviously, the best corrective action is prevention. Correction can occur at five different levels; however, only three of these levels are directed at prevention. Prevention requires a method to collect and analyze data concerning errors. In the authors' facility a functional error classification method and a quality system-based classification have been useful. An active method to search for problems uncovers them further upstream, before they can have disastrous outcomes. In the continual quest for improving processes, an error management program is itself a process that needs improvement, and we must strive to always close the circle of quality assurance. Ultimately, the goal of better patient care will be the reward.

The genome architecture of the Collaborative Cross mouse genetic reference population.

PubMed

2012-02-01

The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multiparental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.

Genetic Code Analysis Toolkit: A novel tool to explore the coding properties of the genetic code and DNA sequences

NASA Astrophysics Data System (ADS)

Kraljić, K.; Strüngmann, L.; Fimmel, E.; Gumbel, M.

2018-01-01

The genetic code is degenerated and it is assumed that redundancy provides error detection and correction mechanisms in the translation process. However, the biological meaning of the code's structure is still under current research. This paper presents a Genetic Code Analysis Toolkit (GCAT) which provides workflows and algorithms for the analysis of the structure of nucleotide sequences. In particular, sets or sequences of codons can be transformed and tested for circularity, comma-freeness, dichotomic partitions and others. GCAT comes with a fertile editor custom-built to work with the genetic code and a batch mode for multi-sequence processing. With the ability to read FASTA files or load sequences from GenBank, the tool can be used for the mathematical and statistical analysis of existing sequence data. GCAT is Java-based and provides a plug-in concept for extensibility. Availability: Open source Homepage:http://www.gcat.bio/

Developments in Ocular Genetics: 2013 Annual Review

PubMed Central

Aboobakar, Inas F.; Allingham, R. Rand

2014-01-01

Purpose To highlight major advancements in ocular genetics from the year 2013. Design Literature review. Methods A literature search was conducted on PubMed to identify articles pertaining to genetic influences on human eye diseases. This review focuses on manuscripts published in print or online in the English language between January 1, 2013 and December 31, 2013. A total of 120 papers from 2013 were included in this review. Results Significant progress has been made in our understanding of the genetic basis of a broad group of ocular disorders, including glaucoma, age-related macular degeneration, cataract, diabetic retinopathy, keratoconus, Fuchs’ endothelial dystrophy, and refractive error. Conclusions The latest next-generation sequencing technologies have become extremely effective tools for identifying gene mutations associated with ocular disease. These technological advancements have also paved the way for utilization of genetic information in clinical practice, including disease diagnosis, prediction of treatment response and molecular interventions guided by gene-based knowledge. PMID:25097799

Neural system for heartbeats recognition using genetically integrated ensemble of classifiers.

PubMed

Osowski, Stanislaw; Siwek, Krzysztof; Siroic, Robert

2011-03-01

This paper presents the application of genetic algorithm for the integration of neural classifiers combined in the ensemble for the accurate recognition of heartbeat types on the basis of ECG registration. The idea presented in this paper is that using many classifiers arranged in the form of ensemble leads to the increased accuracy of the recognition. In such ensemble the important problem is the integration of all classifiers into one effective classification system. This paper proposes the use of genetic algorithm. It was shown that application of the genetic algorithm is very efficient and allows to reduce significantly the total error of heartbeat recognition. This was confirmed by the numerical experiments performed on the MIT BIH Arrhythmia Database. Copyright © 2011 Elsevier Ltd. All rights reserved.

New Genetics

MedlinePlus

... Century-Old Evolutionary Puzzle Computing Genetics Model Organisms RNA Interference The New Genetics is a science education ... the basics of DNA and its molecular cousin RNA, and new directions in genetic research. The New ...

Genetics Home Reference: TK2-related mitochondrial DNA depletion syndrome, myopathic form

MedlinePlus

... mtDNA. Specifically, this enzyme plays a role in recycling mtDNA building blocks (nucleotides) so that errors in ... kinase 2. A decrease in enzyme activity impairs recycling of mtDNA nucleotides, causing a shortage of nucleotides ...

Natural History Study of Children With Metachromatic Leukodystrophy

ClinicalTrials.gov

2016-04-19

Lipid Metabolism Disorders; Metachromatic Leukodystrophy (MLD); Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Sphingolipidoses; Hereditary Central Nervous System Demyelinating Diseases; Metabolic Inborn Brain Diseases; Lysosomal Storage Diseases; Metabolic Diseases; Sulfatidosis

Genetics Home Reference: neuroferritinopathy

MedlinePlus

... J. Neuroferritinopathy: a new inborn error of iron metabolism. Neurogenetics. 2012 Feb;13(1):93-6. doi: 10.1007/s10048-011-0310-9. Epub 2012 Jan 26. Citation on PubMed or Free article on PubMed Central Keogh MJ, Morris CM, Chinnery ...

Plumage condition in laying hens: genetic parameters for direct and indirect effects in two purebred layer lines.

PubMed

Brinker, Tessa; Bijma, Piter; Visscher, Jeroen; Rodenburg, T Bas; Ellen, Esther D

2014-05-29

Feather pecking is a major welfare issue in laying hen industry that leads to mortality. Due to a ban on conventional cages in the EU and on beak trimming in some countries of the EU, feather pecking will become an even bigger problem. Its severity depends both on the victim receiving pecking and on its group mates inflicting pecking (indirect effects), which together determine plumage condition of the victim. Plumage condition may depend, therefore, on both the direct genetic effect of an individual itself and on the indirect genetic effects of its group mates. Here, we present estimated genetic parameters for direct and indirect effects on plumage condition of different body regions in two purebred layer lines, and estimates of genetic correlations between body regions. Feather condition scores (FCS) were recorded at 40 weeks of age for neck, back, rump and belly and these four scores were added-up into a total FCS. A classical animal model and a direct-indirect effects model were used to estimate genetic parameters for FCS. In addition, a bivariate model with mortality (0/1) was used to account for mortality before recording FCS. Due to mortality during the first 23 weeks of laying, 5363 (for W1) and 5089 (for WB) FCS records were available. Total heritable variance for FCS ranged from 1.5% to 9.8% and from 9.8% to 53.6% when estimated respectively with the classical animal and the direct-indirect effects model. The direct-indirect effects model had a significantly higher likelihood. In both lines, 70% to 94% of the estimated total heritable variation in FCS was due to indirect effects. Using bivariate analysis of FCS and mortality did not affect estimates of genetic parameters. Genetic correlations were high between adjacent regions for FCS on neck, back, and rump but moderate to low for belly with other regions. Our results show that 70% to 94% of the heritable variation in FCS relates to indirect effects, indicating that methods of genetic selection that include indirect genetic effects offer perspectives to improve plumage condition in laying hens. This, in turn could reduce a major welfare problem.

Classification and conservation priority of five Deccani sheep ecotypes of Maharashtra, India

PubMed Central

Arora, Reena; Jain, Anand

2017-01-01

Characterization of Indian livestock breeds has mostly been limited to single breed/population focused on either physical description of traditionally recognized breeds/populations or to their genetic description. Usually, morphological and genetic characterization has taken place in isolation. A parallel morphological characterization of genetically identified breeds or genetic characterization of morphologically described breeds is mostly missing, and their conservation priorities have largely been based on solely considering degree of endangerment. This study uses parallel approach based on morphometric and genetic differentiation for classification of five sheep ecotypes of Maharashtra state, and sets their conservation priority using threat parameters, current utilities/merits and contribution to genetic diversity. A total of 1101 animals were described for 7 body measurements for morphometric characterization. From this sample set, 456 animals were genotyped for 25 microsatellite markers for genetic characterization. Conservation priorities were assessed combining genetic and non-genetic factors. All studied traits varied significantly among ecotypes (p<0.05). All morphometric traits exhibited substantial sexual dimorphism except ear length. Males were 42% heavier than females. Madgyal sheep were the largest amongst the five ecotypes. In the stepwise discriminant analysis, all measured traits were significant and were found to have potential discriminatory power. Tail length was the most discriminatory trait. The Mahalanobis distance of the morphological traits between Kolhapuri and Madgyal was maximum (12.07) while the least differentiation was observed between Madgyal and Solapuri (1.50). Discriminant analysis showed that 68.12% sheep were classified into their source population. The Sangamneri sheep showed least assignment error (22%) whilst Solapuri exhibited maximum error level (41%). A total of 407 alleles were observed, with an average of 16.28 alleles per locus. Sufficient levels of genetic diversity were observed in all the ecotypes with observed heterozygosity values exceeding 0.47 and gene diversity values exceeding 0.76. About 6% of the total genetic variation was explained by population differences (FST = 0.059). Pairwise FST values indicated least differentiation between Solapuri and Madgyal (0.025). In terms of genetic distances, Kolhapuri and Lonand were most closely related (Ds = 0.177). The most probable structure clustering of the five studied populations was at K = 5. The study showed a fair congruence between the dendrogram constructed on the basis of Mahalanobis distances and Nei’s as well as Reynolds genetic distances. The findings gave highest conservation priority to Lonand and least to Solapuri ecotype. PMID:28910329

Accounting for uncertainty in DNA sequencing data.

PubMed

O'Rawe, Jason A; Ferson, Scott; Lyon, Gholson J

2015-02-01

Science is defined in part by an honest exposition of the uncertainties that arise in measurements and propagate through calculations and inferences, so that the reliabilities of its conclusions are made apparent. The recent rapid development of high-throughput DNA sequencing technologies has dramatically increased the number of measurements made at the biochemical and molecular level. These data come from many different DNA-sequencing technologies, each with their own platform-specific errors and biases, which vary widely. Several statistical studies have tried to measure error rates for basic determinations, but there are no general schemes to project these uncertainties so as to assess the surety of the conclusions drawn about genetic, epigenetic, and more general biological questions. We review here the state of uncertainty quantification in DNA sequencing applications, describe sources of error, and propose methods that can be used for accounting and propagating these errors and their uncertainties through subsequent calculations. Copyright © 2014 Elsevier Ltd. All rights reserved.

What are incident reports telling us? A comparative study at two Australian hospitals of medication errors identified at audit, detected by staff and reported to an incident system

PubMed Central

Westbrook, Johanna I.; Li, Ling; Lehnbom, Elin C.; Baysari, Melissa T.; Braithwaite, Jeffrey; Burke, Rosemary; Conn, Chris; Day, Richard O.

2015-01-01

Objectives To (i) compare medication errors identified at audit and observation with medication incident reports; (ii) identify differences between two hospitals in incident report frequency and medication error rates; (iii) identify prescribing error detection rates by staff. Design Audit of 3291patient records at two hospitals to identify prescribing errors and evidence of their detection by staff. Medication administration errors were identified from a direct observational study of 180 nurses administering 7451 medications. Severity of errors was classified. Those likely to lead to patient harm were categorized as ‘clinically important’. Setting Two major academic teaching hospitals in Sydney, Australia. Main Outcome Measures Rates of medication errors identified from audit and from direct observation were compared with reported medication incident reports. Results A total of 12 567 prescribing errors were identified at audit. Of these 1.2/1000 errors (95% CI: 0.6–1.8) had incident reports. Clinically important prescribing errors (n = 539) were detected by staff at a rate of 218.9/1000 (95% CI: 184.0–253.8), but only 13.0/1000 (95% CI: 3.4–22.5) were reported. 78.1% (n = 421) of clinically important prescribing errors were not detected. A total of 2043 drug administrations (27.4%; 95% CI: 26.4–28.4%) contained ≥1 errors; none had an incident report. Hospital A had a higher frequency of incident reports than Hospital B, but a lower rate of errors at audit. Conclusions Prescribing errors with the potential to cause harm frequently go undetected. Reported incidents do not reflect the profile of medication errors which occur in hospitals or the underlying rates. This demonstrates the inaccuracy of using incident frequency to compare patient risk or quality performance within or across hospitals. New approaches including data mining of electronic clinical information systems are required to support more effective medication error detection and mitigation. PMID:25583702

What Is Direct-to-Consumer Genetic Testing?

MedlinePlus

... different: these genetic tests are marketed directly to customers via television, print advertisements, or the Internet, and ... tests can be bought online or in stores. Customers send the company a DNA sample and receive ...

Effect of Antenna Pointing Errors on SAR Imaging Considering the Change of the Point Target Location

NASA Astrophysics Data System (ADS)

Zhang, Xin; Liu, Shijie; Yu, Haifeng; Tong, Xiaohua; Huang, Guoman

2018-04-01

Towards spaceborne spotlight SAR, the antenna is regulated by the SAR system with specific regularity, so the shaking of the internal mechanism is inevitable. Moreover, external environment also has an effect on the stability of SAR platform. Both of them will cause the jitter of the SAR platform attitude. The platform attitude instability will introduce antenna pointing error on both the azimuth and range directions, and influence the acquisition of SAR original data and ultimate imaging quality. In this paper, the relations between the antenna pointing errors and the three-axis attitude errors are deduced, then the relations between spaceborne spotlight SAR imaging of the point target and antenna pointing errors are analysed based on the paired echo theory, meanwhile, the change of the azimuth antenna gain is considered as the spotlight SAR platform moves ahead. The simulation experiments manifest the effects on spotlight SAR imaging caused by antenna pointing errors are related to the target location, that is, the pointing errors of the antenna beam will severely influence the area far away from the scene centre of azimuth direction in the illuminated scene.

Sampling Errors of SSM/I and TRMM Rainfall Averages: Comparison with Error Estimates from Surface Data and a Sample Model

NASA Technical Reports Server (NTRS)

Bell, Thomas L.; Kundu, Prasun K.; Kummerow, Christian D.; Einaudi, Franco (Technical Monitor)

2000-01-01

Quantitative use of satellite-derived maps of monthly rainfall requires some measure of the accuracy of the satellite estimates. The rainfall estimate for a given map grid box is subject to both remote-sensing error and, in the case of low-orbiting satellites, sampling error due to the limited number of observations of the grid box provided by the satellite. A simple model of rain behavior predicts that Root-mean-square (RMS) random error in grid-box averages should depend in a simple way on the local average rain rate, and the predicted behavior has been seen in simulations using surface rain-gauge and radar data. This relationship was examined using satellite SSM/I data obtained over the western equatorial Pacific during TOGA COARE. RMS error inferred directly from SSM/I rainfall estimates was found to be larger than predicted from surface data, and to depend less on local rain rate than was predicted. Preliminary examination of TRMM microwave estimates shows better agreement with surface data. A simple method of estimating rms error in satellite rainfall estimates is suggested, based on quantities that can be directly computed from the satellite data.

Jumping to the wrong conclusions? An investigation of the mechanisms of reasoning errors in delusions

PubMed Central

Jolley, Suzanne; Thompson, Claire; Hurley, James; Medin, Evelina; Butler, Lucy; Bebbington, Paul; Dunn, Graham; Freeman, Daniel; Fowler, David; Kuipers, Elizabeth; Garety, Philippa

2014-01-01

Understanding how people with delusions arrive at false conclusions is central to the refinement of cognitive behavioural interventions. Making hasty decisions based on limited data (‘jumping to conclusions’, JTC) is one potential causal mechanism, but reasoning errors may also result from other processes. In this study, we investigated the correlates of reasoning errors under differing task conditions in 204 participants with schizophrenia spectrum psychosis who completed three probabilistic reasoning tasks. Psychotic symptoms, affect, and IQ were also evaluated. We found that hasty decision makers were more likely to draw false conclusions, but only 37% of their reasoning errors were consistent with the limited data they had gathered. The remainder directly contradicted all the presented evidence. Reasoning errors showed task-dependent associations with IQ, affect, and psychotic symptoms. We conclude that limited data-gathering contributes to false conclusions but is not the only mechanism involved. Delusions may also be maintained by a tendency to disregard evidence. Low IQ and emotional biases may contribute to reasoning errors in more complex situations. Cognitive strategies to reduce reasoning errors should therefore extend beyond encouragement to gather more data, and incorporate interventions focused directly on these difficulties. PMID:24958065

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project.

PubMed

Cutting, Elizabeth M; Overby, Casey L; Banchero, Meghan; Pollin, Toni; Kelemen, Mark; Shuldiner, Alan R; Beitelshees, Amber L

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease.

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project

PubMed Central

Cutting, Elizabeth M.; Overby, Casey L.; Banchero, Meghan; Pollin, Toni; Kelemen, Mark; Shuldiner, Alan R.; Beitelshees, Amber L.

2015-01-01

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease. PMID:26958179

Image guidance in prostate cancer - can offline corrections be an effective substitute for daily online imaging?

PubMed

Prasad, Devleena; Das, Pinaki; Saha, Niladri S; Chatterjee, Sanjoy; Achari, Rimpa; Mallick, Indranil

2014-01-01

This aim of this study was to determine if a less resource-intensive and established offline correction protocol - the No Action Level (NAL) protocol was as effective as daily online corrections of setup deviations in curative high-dose radiotherapy of prostate cancer. A total of 683 daily megavoltage CT (MVCT) or kilovoltage CT (kvCBCT) images of 30 patients with localized prostate cancer treated with intensity modulated radiotherapy were evaluated. Daily image-guidance was performed and setup errors in three translational axes recorded. The NAL protocol was simulated by using the mean shift calculated from the first five fractions and implemented on all subsequent treatments. Using the imaging data from the remaining fractions, the daily residual error (RE) was determined. The proportion of fractions where the RE was greater than 3,5 and 7 mm was calculated, and also the actual PTV margin that would be required if the offline protocol was followed. Using the NAL protocol reduced the systematic but not the random errors. Corrections made using the NAL protocol resulted in small and acceptable RE in the mediolateral (ML) and superoinferior (SI) directions with 46/533 (8.1%) and 48/533 (5%) residual shifts above 5 mm. However; residual errors greater than 5mm in the anteroposterior (AP) direction remained in 181/533 (34%) of fractions. The PTV margins calculated based on residual errors were 5mm, 5mm and 13 mm in the ML, SI and AP directions respectively. Offline correction using the NAL protocol resulted in unacceptably high residual errors in the AP direction, due to random uncertainties of rectal and bladder filling. Daily online imaging and corrections remain the standard image guidance policy for highly conformal radiotherapy of prostate cancer.

Large Uncertainty in Estimating pCO2 From Carbonate Equilibria in Lakes

NASA Astrophysics Data System (ADS)

Golub, Malgorzata; Desai, Ankur R.; McKinley, Galen A.; Remucal, Christina K.; Stanley, Emily H.

2017-11-01

Most estimates of carbon dioxide (CO2) evasion from freshwaters rely on calculating partial pressure of aquatic CO2 (pCO2) from two out of three CO2-related parameters using carbonate equilibria. However, the pCO2 uncertainty has not been systematically evaluated across multiple lake types and equilibria. We quantified random errors in pH, dissolved inorganic carbon, alkalinity, and temperature from the North Temperate Lakes Long-Term Ecological Research site in four lake groups across a broad gradient of chemical composition. These errors were propagated onto pCO2 calculated from three carbonate equilibria, and for overlapping observations, compared against uncertainties in directly measured pCO2. The empirical random errors in CO2-related parameters were mostly below 2% of their median values. Resulting random pCO2 errors ranged from ±3.7% to ±31.5% of the median depending on alkalinity group and choice of input parameter pairs. Temperature uncertainty had a negligible effect on pCO2. When compared with direct pCO2 measurements, all parameter combinations produced biased pCO2 estimates with less than one third of total uncertainty explained by random pCO2 errors, indicating that systematic uncertainty dominates over random error. Multidecadal trend of pCO2 was difficult to reconstruct from uncertain historical observations of CO2-related parameters. Given poor precision and accuracy of pCO2 estimates derived from virtually any combination of two CO2-related parameters, we recommend direct pCO2 measurements where possible. To achieve consistently robust estimates of CO2 emissions from freshwater components of terrestrial carbon balances, future efforts should focus on improving accuracy and precision of CO2-related parameters (including direct pCO2) measurements and associated pCO2 calculations.

Dominance genetic and maternal effects for genetic evaluation of egg production traits in dual-purpose chickens.

PubMed

Jasouri, M; Zamani, P; Alijani, S

2017-10-01

1. A study was conducted to study direct dominance genetic and maternal effects on genetic evaluation of production traits in dual-purpose chickens. The data set consisted of records of body weight and egg production of 49 749 Mazandaran fowls from 19 consecutive generations. Based on combinations of different random effects, including direct additive and dominance genetic and maternal additive genetic and environmental effects, 8 different models were compared. 2. Inclusion of a maternal genetic effect in the models noticeably improved goodness of fit for all traits. Direct dominance genetic effect did not have noticeable effects on goodness of fit but simultaneous inclusion of both direct dominance and maternal additive genetic effects improved fitting criteria and accuracies of genetic parameter estimates for hatching body weight and egg production traits. 3. Estimates of heritability (h 2 ) for body weights at hatch, 8 weeks and 12 weeks of age (BW0, BW8 and BW12, respectively), age at sexual maturity (ASM), average egg weights at 28-32 weeks of laying period (AEW), egg number (EN) and egg production intensity (EI) were 0.08, 0.21, 0.22, 0.22, 0.21, 0.09 and 0.10, respectively. For BW0, BW8, BW12, ASM, AEW, EN and EI, proportion of dominance genetic to total phenotypic variance (d 2 ) were 0.06, 0.08, 0.01, 0.06, 0.06, 0.08 and 0.07 and maternal heritability estimates (m 2 ) were 0.05, 0.04, 0.03, 0.13, 0.21, 0.07 and 0.03, respectively. Negligible coefficients of maternal environmental effect (c 2 ) from 0.01 to 0.08 were estimated for all traits, other than BW0, which had an estimate of 0.30. 4. Breeding values (BVs) estimated for body weights at early ages (BW0 and BW8) were considerably affected by components of the models, but almost similar BVs were estimated by different models for higher age body weight (BW12) and egg production traits (ASM, AEW, EN and EI). Generally, it could be concluded that inclusion of maternal effects (both genetic and environmental) and, to a lesser extent, direct dominance genetic effect would improve the accuracy of genetic evaluation for early age body weights in dual-purpose chickens.

The Differential Effect of Two Types of Direct Written Corrective Feedback on Noticing and Uptake: Reformulation vs. Error Correction

ERIC Educational Resources Information Center

Santos, Maria; Lopez-Serrano, Sonia; Manchon, Rosa M.

2010-01-01

Framed in a cognitively-oriented strand of research on corrective feedback (CF) in SLA, the controlled three-stage (composition/comparison-noticing/revision) study reported in this paper investigated the effects of two forms of direct CF (error correction and reformulation) on noticing and uptake, as evidenced in the written output produced by a…

SU-E-J-45: The Correlation Between CBCT Flat Panel Misalignment and 3D Image Guidance Accuracy

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

Kenton, O; Valdes, G; Yin, L

Purpose To simulate the impact of CBCT flat panel misalignment on the image quality, the calculated correction vectors in 3D image guided proton therapy and to determine if these calibration errors can be caught in our QA process. Methods The X-ray source and detector geometrical calibration (flexmap) file of the CBCT system in the AdaPTinsight software (IBA proton therapy) was edited to induce known changes in the rotational and translational calibrations of the imaging panel. Translations of up to ±10 mm in the x, y and z directions (see supplemental) and rotational errors of up to ±3° were induced. Themore » calibration files were then used to reconstruct the CBCT image of a pancreatic patient and CatPhan phantom. Correction vectors were calculated for the patient using the software’s auto match system and compared to baseline values. The CatPhan CBCT images were used for quantitative evaluation of image quality for each type of induced error. Results Translations of 1 to 3 mm in the x and y calibration resulted in corresponding correction vector errors of equal magnitude. Similar 10mm shifts were seen in the y-direction; however, in the x-direction, the image quality was too degraded for a match. These translational errors can be identified through differences in isocenter from orthogonal kV images taken during routine QA. Errors in the z-direction had no effect on the correction vector and image quality.Rotations of the imaging panel calibration resulted in corresponding correction vector rotations of the patient images. These rotations also resulted in degraded image quality which can be identified through quantitative image quality metrics. Conclusion Misalignment of CBCT geometry can lead to incorrect translational and rotational patient correction vectors. These errors can be identified through QA of the imaging isocenter as compared to orthogonal images combined with monitoring of CBCT image quality.« less

Color-motion feature-binding errors are mediated by a higher-order chromatic representation

PubMed Central

Shevell, Steven K.; Wang, Wei

2017-01-01

Peripheral and central moving objects of the same color may be perceived to move in the same direction even though peripheral objects have a different true direction of motion [Nature 429, 262 (2004)]. The perceived, illusory direction of peripheral motion is a color-motion feature-binding error. Recent work shows that such binding errors occur even without an exact color match between central and peripheral objects, and, moreover, the frequency of the binding errors in the periphery declines as the chromatic difference increases between the central and peripheral objects [J. Opt. Soc. Am. A 31, A60 (2014)]. This change in the frequency of binding errors with the chromatic difference raises the general question of the chromatic representation from which the difference is determined. Here, basic properties of the chromatic representation are tested to discover whether it depends on independent chromatic differences on the l and the s cardinal axes or, alternatively, on a more specific higher-order chromatic representation. Experimental tests compared the rate of feature-binding errors when the central and peripheral colors had the identical s chromaticity (so zero difference in s) and a fixed magnitude of l difference, while varying the identical s level in center and periphery (thus always keeping the s difference at zero). A chromatic representation based on independent l and s differences would result in the same frequency of color-motion binding errors at every s level. The results are contrary to this prediction, thus showing that the chromatic representation at the level of color-motion feature binding depends on a higherorder chromatic mechanism. PMID:26974945

Written Identification of Errors to Learn Professional Procedures in VET

ERIC Educational Resources Information Center

Boldrini, Elena; Cattaneo, Alberto

2013-01-01

Research has demonstrated that the use of worked-out examples to present errors has great potential for procedural knowledge acquirement. Nevertheless, the identification of errors alone does not directly enhance a deep learning process if it is not adequately scaffolded by written self-explanations. We hypothesised that in learning a professional…

Direct Measures of Character Mislocalizations with Masked/Unmasked Exposures.

ERIC Educational Resources Information Center

Chastain, Garvin; And Others

Butler (1980) compared errors representing intrusions and mislocalizations on 3x3 letter displays under pattern-mask versus no-mask conditions and found that pattern masking increased character mislocalization errors (naming a character in the display but not in the target position as being the target) over intrusion errors (naming a character not…

Bayesian analysis of input uncertainty in hydrological modeling: 2. Application

NASA Astrophysics Data System (ADS)

Kavetski, Dmitri; Kuczera, George; Franks, Stewart W.

2006-03-01

The Bayesian total error analysis (BATEA) methodology directly addresses both input and output errors in hydrological modeling, requiring the modeler to make explicit, rather than implicit, assumptions about the likely extent of data uncertainty. This study considers a BATEA assessment of two North American catchments: (1) French Broad River and (2) Potomac basins. It assesses the performance of the conceptual Variable Infiltration Capacity (VIC) model with and without accounting for input (precipitation) uncertainty. The results show the considerable effects of precipitation errors on the predicted hydrographs (especially the prediction limits) and on the calibrated parameters. In addition, the performance of BATEA in the presence of severe model errors is analyzed. While BATEA allows a very direct treatment of input uncertainty and yields some limited insight into model errors, it requires the specification of valid error models, which are currently poorly understood and require further work. Moreover, it leads to computationally challenging highly dimensional problems. For some types of models, including the VIC implemented using robust numerical methods, the computational cost of BATEA can be reduced using Newton-type methods.

Impact of automated dispensing cabinets on medication selection and preparation error rates in an emergency department: a prospective and direct observational before-and-after study.

PubMed

Fanning, Laura; Jones, Nick; Manias, Elizabeth

2016-04-01

The implementation of automated dispensing cabinets (ADCs) in healthcare facilities appears to be increasing, in particular within Australian hospital emergency departments (EDs). While the investment in ADCs is on the increase, no studies have specifically investigated the impacts of ADCs on medication selection and preparation error rates in EDs. Our aim was to assess the impact of ADCs on medication selection and preparation error rates in an ED of a tertiary teaching hospital. Pre intervention and post intervention study involving direct observations of nurses completing medication selection and preparation activities before and after the implementation of ADCs in the original and new emergency departments within a 377-bed tertiary teaching hospital in Australia. Medication selection and preparation error rates were calculated and compared between these two periods. Secondary end points included the impact on medication error type and severity. A total of 2087 medication selection and preparations were observed among 808 patients pre and post intervention. Implementation of ADCs in the new ED resulted in a 64.7% (1.96% versus 0.69%, respectively, P = 0.017) reduction in medication selection and preparation errors. All medication error types were reduced in the post intervention study period. There was an insignificant impact on medication error severity as all errors detected were categorised as minor. The implementation of ADCs could reduce medication selection and preparation errors and improve medication safety in an ED setting. © 2015 John Wiley & Sons, Ltd.

A new open-loop fiber optic gyro error compensation method based on angular velocity error modeling.

PubMed

Zhang, Yanshun; Guo, Yajing; Li, Chunyu; Wang, Yixin; Wang, Zhanqing

2015-02-27

With the open-loop fiber optic gyro (OFOG) model, output voltage and angular velocity can effectively compensate OFOG errors. However, the model cannot reflect the characteristics of OFOG errors well when it comes to pretty large dynamic angular velocities. This paper puts forward a modeling scheme with OFOG output voltage u and temperature T as the input variables and angular velocity error Δω as the output variable. Firstly, the angular velocity error Δω is extracted from OFOG output signals, and then the output voltage u, temperature T and angular velocity error Δω are used as the learning samples to train a Radial-Basis-Function (RBF) neural network model. Then the nonlinear mapping model over T, u and Δω is established and thus Δω can be calculated automatically to compensate OFOG errors according to T and u. The results of the experiments show that the established model can be used to compensate the nonlinear OFOG errors. The maximum, the minimum and the mean square error of OFOG angular velocity are decreased by 97.0%, 97.1% and 96.5% relative to their initial values, respectively. Compared with the direct modeling of gyro angular velocity, which we researched before, the experimental results of the compensating method proposed in this paper are further reduced by 1.6%, 1.4% and 1.42%, respectively, so the performance of this method is better than that of the direct modeling for gyro angular velocity.

A New Open-Loop Fiber Optic Gyro Error Compensation Method Based on Angular Velocity Error Modeling

PubMed Central

Zhang, Yanshun; Guo, Yajing; Li, Chunyu; Wang, Yixin; Wang, Zhanqing

2015-01-01

With the open-loop fiber optic gyro (OFOG) model, output voltage and angular velocity can effectively compensate OFOG errors. However, the model cannot reflect the characteristics of OFOG errors well when it comes to pretty large dynamic angular velocities. This paper puts forward a modeling scheme with OFOG output voltage u and temperature T as the input variables and angular velocity error Δω as the output variable. Firstly, the angular velocity error Δω is extracted from OFOG output signals, and then the output voltage u, temperature T and angular velocity error Δω are used as the learning samples to train a Radial-Basis-Function (RBF) neural network model. Then the nonlinear mapping model over T, u and Δω is established and thus Δω can be calculated automatically to compensate OFOG errors according to T and u. The results of the experiments show that the established model can be used to compensate the nonlinear OFOG errors. The maximum, the minimum and the mean square error of OFOG angular velocity are decreased by 97.0%, 97.1% and 96.5% relative to their initial values, respectively. Compared with the direct modeling of gyro angular velocity, which we researched before, the experimental results of the compensating method proposed in this paper are further reduced by 1.6%, 1.4% and 1.2%, respectively, so the performance of this method is better than that of the direct modeling for gyro angular velocity. PMID:25734642

Attitude-error compensation for airborne down-looking synthetic-aperture imaging lidar

NASA Astrophysics Data System (ADS)

Li, Guang-yuan; Sun, Jian-feng; Zhou, Yu; Lu, Zhi-yong; Zhang, Guo; Cai, Guang-yu; Liu, Li-ren

2017-11-01

Target-coordinate transformation in the lidar spot of the down-looking synthetic-aperture imaging lidar (SAIL) was performed, and the attitude errors were deduced in the process of imaging, according to the principle of the airborne down-looking SAIL. The influence of the attitude errors on the imaging quality was analyzed theoretically. A compensation method for the attitude errors was proposed and theoretically verified. An airborne down-looking SAIL experiment was performed and yielded the same results. A point-by-point error-compensation method for solving the azimuthal-direction space-dependent attitude errors was also proposed.

Design and scheduling for periodic concurrent error detection and recovery in processor arrays

NASA Technical Reports Server (NTRS)

Wang, Yi-Min; Chung, Pi-Yu; Fuchs, W. Kent

1992-01-01

Periodic application of time-redundant error checking provides the trade-off between error detection latency and performance degradation. The goal is to achieve high error coverage while satisfying performance requirements. We derive the optimal scheduling of checking patterns in order to uniformly distribute the available checking capability and maximize the error coverage. Synchronous buffering designs using data forwarding and dynamic reconfiguration are described. Efficient single-cycle diagnosis is implemented by error pattern analysis and direct-mapped recovery cache. A rollback recovery scheme using start-up control for local recovery is also presented.

[Issues on business of genetic testing in near future].

PubMed

Takada, Fumio

2009-06-01

Since 1990's, a business condition that company sells genetic testing services directly to consumers without through medical facility, so called "direct-to-consumers (DTC) genetic testing", has risen. They provide genetic testing for obesity, disease susceptibility or paternity, etc. There are serious problems in this kind of business. Most of the providers do not make sales with face-to-face selling, and do through internet instead. They do not provide genetic counseling by certified genetic counselor or clinical geneticist. Most DTC genetic testing services for disease susceptibility or predispositions including obesity, lack scientific validity, clinical validity and clinical utility. And also including paternity genetic testing, they all have risks of ethical legal and social issues (ELSI) in genetic discrimination and/or eugenics. The specific problem in Japan is that the healthcare section of the government still has not paid attention and not taken seriously the requirement to deploy safety net.

Genetic Testing Integration Panels (GTIPs): A novel approach for considering integration of direct-to-consumer and other new genetic tests into patient care

PubMed Central

Uhlmann, Wendy R.; Sharp, Richard R.

2014-01-01

There has been a dramatic increase in the number of genetic tests available but few tests have practice guidelines. In addition, many tests have become available outside of genetics clinics through direct-to-consumer (DTC) companies and several offer tests not considered standard of care. To address several practical challenges associated with the rapid introduction of clinical and DTC genetic tests, we propose that genetic counselors and geneticists organize expert panels in their institutions to discuss the integration of new tests into patient care. We propose the establishment of Genetic Testing Integration Panels (GTIPs) to bring together local experts in medical genetics, genetic counseling, bioethics and law, health communication and clinical laboratory genetics. We describe key features of this approach and consider some of the potential advantages and limitations of using a GTIP to address the many clinical challenges raised by rapidly emerging clinical and DTC genetic tests. PMID:22246561

Theoretical evaluation of errors in aerosol optical depth retrievals from ground-based direct-sun measurements due to circumsolar and related effects

NASA Astrophysics Data System (ADS)

Kocifaj, Miroslav; Gueymard, Christian A.

2011-02-01

Aerosol optical depth (AOD) has a crucial importance for estimating the optical properties of the atmosphere, and is constantly present in optical models of aerosol systems. Any error in aerosol optical depth (∂AOD) has direct and indirect consequences. On the one hand, such errors affect the accuracy of radiative transfer models (thus implying, e.g., potential errors in the evaluation of radiative forcing by aerosols). Additionally, any error in determining AOD is reflected in the retrieved microphysical properties of aerosol particles, which might therefore be inaccurate. Three distinct effects (circumsolar radiation, optical mass, and solar disk's brightness distribution) affecting ∂AOD are qualified and quantified in the present study. The contribution of circumsolar (CS) radiation to the measured flux density of direct solar radiation has received more attention than the two other effects in the literature. It varies rapidly with meteorological conditions and size distribution of the aerosol particles, but also with instrument field of view. Numerical simulations of the three effects just mentioned were conducted, assuming otherwise "perfect" experimental conditions. The results show that CS is responsible for the largest error in AOD, while the effect of brightness distribution (BD) has only a negligible impact. The optical mass (OM) effect yields negligible errors in AOD generally, but noticeable errors for low sun (within 10° of the horizon). In general, the OM and BD effects result in negative errors in AOD (i.e. the true AOD is smaller than that of the experimental determination), conversely to CS. Although the rapid increase in optical mass at large zenith angles can change the sign of ∂AOD, the CS contribution frequently plays the leading role in ∂AOD. To maximize the accuracy in AOD retrievals, the CS effect should not be ignored. In practice, however, this effect can be difficult to evaluate correctly unless the instantaneous aerosols size distribution is known from, e.g., inversion techniques.

Recursive Directional Ligation Approach for Cloning Recombinant Spider Silks.

PubMed

Dinjaski, Nina; Huang, Wenwen; Kaplan, David L

2018-01-01

Recent advances in genetic engineering have provided a route to produce various types of recombinant spider silks. Different cloning strategies have been applied to achieve this goal (e.g., concatemerization, step-by-step ligation, recursive directional ligation). Here we describe recursive directional ligation as an approach that allows for facile modularity and control over the size of the genetic cassettes. This approach is based on sequential ligation of genetic cassettes (monomers) where the junctions between them are formed without interrupting key gene sequences with additional base pairs.

From classical mutagenesis to nuclease-based breeding - directing natural DNA repair for a natural end-product.

PubMed

Pacher, Michael; Puchta, Holger

2017-05-01

Production of mutants of crop plants by the use of chemical or physical genotoxins has a long tradition. These factors induce the natural DNA repair machinery to repair damage in an error-prone way. In the case of radiation, multiple double-strand breaks (DSBs) are induced randomly in the genome, leading in very rare cases to a desirable phenotype. In recent years the use of synthetic, site-directed nucleases (SDNs) - also referred to as sequence-specific nucleases - like the CRISPR/Cas system has enabled scientists to use exactly the same naturally occurring DNA repair mechanisms for the controlled induction of genomic changes at pre-defined sites in plant genomes. As these changes are not necessarily associated with the permanent integration of foreign DNA, the obtained organisms per se cannot be regarded as genetically modified as there is no way to distinguish them from natural variants. This applies to changes induced by DSBs as well as single-strand breaks, and involves repair by non-homologous end-joining and homologous recombination. The recent development of SDN-based 'DNA-free' approaches makes mutagenesis strategies in classical breeding indistinguishable from SDN-derived targeted genome modifications, even in regard to current regulatory rules. With the advent of new SDN technologies, much faster and more precise genome editing becomes available at reasonable cost, and potentially without requiring time-consuming deregulation of newly created phenotypes. This review will focus on classical mutagenesis breeding and the application of newly developed SDNs in order to emphasize similarities in the context of the regulatory situation for genetically modified crop plants. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: is a new evolutionary paradigm necessary?

PubMed

Valenzuela, Carlos Y

2013-01-01

The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fixation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insufficient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coefficients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fixation by drift) untenable. Recurrent forward and backward mutation and random fluctuations of base frequencies alone in a site make life organization and fixations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coefficients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co-adapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift effect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.

Skeletal Mechanism Generation of Surrogate Jet Fuels for Aeropropulsion Modeling

NASA Astrophysics Data System (ADS)

Sung, Chih-Jen; Niemeyer, Kyle E.

2010-05-01

A novel implementation for the skeletal reduction of large detailed reaction mechanisms using the directed relation graph with error propagation and sensitivity analysis (DRGEPSA) is developed and presented with skeletal reductions of two important hydrocarbon components, n-heptane and n-decane, relevant to surrogate jet fuel development. DRGEPSA integrates two previously developed methods, directed relation graph-aided sensitivity analysis (DRGASA) and directed relation graph with error propagation (DRGEP), by first applying DRGEP to efficiently remove many unimportant species prior to sensitivity analysis to further remove unimportant species, producing an optimally small skeletal mechanism for a given error limit. It is illustrated that the combination of the DRGEP and DRGASA methods allows the DRGEPSA approach to overcome the weaknesses of each previous method, specifically that DRGEP cannot identify all unimportant species and that DRGASA shields unimportant species from removal.

Directional control-response relationships for mining equipment.

PubMed

Burgess-Limerick, R; Krupenia, V; Wallis, G; Pratim-Bannerjee, A; Steiner, L

2010-06-01

A variety of directional control-response relationships are currently found in mining equipment. Two experiments were conducted in a virtual environment to determine optimal direction control-response relationships in a wide variety of circumstances. Direction errors were measured as a function of control orientation (horizontal or vertical), location (left, front, right) and directional control-response relationships. The results confirm that the principles of consistent direction and visual field compatibility are applicable to the majority of situations. An exception is that fewer direction errors were observed when an upward movement of a horizontal lever or movement of a vertical lever away from the participants caused extension (lengthening) of the controlled device, regardless of whether the direction of movement of the control is consistent with the direction in which the extension occurs. Further, both the control of slew by horizontally oriented controls and the control of device movements in a frontal plane by the perpendicular movements of vertical levers were associated with relatively high rates of directional errors, regardless of the directional control-response relationship, and these situations should be avoided. STATEMENT OF RELEVANCE: The results are particularly applicable to the design of mining equipment such as drilling and bolting machines, and have been incorporated into MDG35.1 Guideline for bolting & drilling plant in mines (Industry & Investment NSW, 2010). The results are also relevant to the design of any equipment where vertical or horizontal levers are used to control the movement of equipment appendages, e.g. cranes mounted to mobile equipment and the like.

Benefits and Limitations of Prenatal Screening for Prader-Willi Syndrome

PubMed Central

Butler, Merlin G.

2016-01-01

This review the status of genetic laboratory testing in Prader-Willi syndrome (PWS) due to different genetic subtypes, most often a paternally derived 15q11-q13 deletion, with benefits and limitations related to prenatal screening. Medical literature was searched for prenatal screening and genetic laboratory testing methods in use or under development and discussed in relationship to PWS. Genetic testing includes six established laboratory diagnostic approaches for PWS with direct application to prenatal screening. Ultrasonographic, obstetric and cytogenetic reports were summarized in relationship to the cause of Prader-Willi syndrome and identification of specific genetic subtypes including maternal disomy 15. Advances in genetic technology were described for diagnosing PWS specifically DNA methylation and high-resolution chromosomal SNP microarrays as current tools for genetic screening and incorporating next generation DNA sequencing for noninvasive prenatal testing (NIPT) using cell-free fetal DNA. Positive experiences are reported with NIPT for detection of numerical chromosomal problems (aneuploidies) but not for structural problems (microdeletions). These reports will be discussed along with future directions for genetic screening of PWS. In summary, this review describes and discusses the status of established and ongoing genetic testing options for PWS applicable in prenatal screening including NIPT and future directions for early diagnosis in Prader-Willi syndrome. PMID:27537837

Benefits and limitations of prenatal screening for Prader-Willi syndrome.

PubMed

Butler, Merlin G

2017-01-01

This review summarizes the status of genetic laboratory testing in Prader-Willi syndrome (PWS) with different genetic subtypes, most often a paternally derived 15q11-q13 deletion and discusses benefits and limitations related to prenatal screening. Medical literature was searched for prenatal screening and genetic laboratory testing methods in use or under development and discussed in relationship to PWS. Genetic testing includes six established laboratory diagnostic approaches for PWS with direct application to prenatal screening. Ultrasonographic, obstetric and cytogenetic reports were summarized in relationship to the cause of PWS and identification of specific genetic subtypes including maternal disomy 15. Advances in genetic technology were described for diagnosing PWS specifically DNA methylation and high-resolution chromosomal SNP microarrays as current tools for genetic screening and incorporating next generation DNA sequencing for noninvasive prenatal testing (NIPT) using cell-free fetal DNA. Positive experiences are reported with NIPT for detection of numerical chromosomal problems (aneuploidies) but not for structural problems (microdeletions). These reports will be discussed along with future directions for genetic screening of PWS. In summary, this review describes and discusses the status of established and ongoing genetic testing options for PWS applicable in prenatal screening including NIPT and future directions for early diagnosis in PWS. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Challenges of primate embryonic stem cell research.

PubMed

Bavister, Barry D; Wolf, Don P; Brenner, Carol A

2005-01-01

Embryonic stem (ES) cells hold great promise for treating degenerative diseases, including diabetes, Parkinson's, Alzheimer's, neural degeneration, and cardiomyopathies. This research is controversial to some because producing ES cells requires destroying embryos, which generally means human embryos. However, some of the surplus human embryos available from in vitro fertilization (IVF) clinics may have a high rate of genetic errors and therefore would be unsuitable for ES cell research. Although gross chromosome errors can readily be detected in ES cells, other anomalies such as mitochondrial DNA defects may have gone unrecognized. An insurmountable problem is that there are no human ES cells derived from in vivo-produced embryos to provide normal comparative data. In contrast, some monkey ES cell lines have been produced using in vivo-generated, normal embryos obtained from fertile animals; these can represent a "gold standard" for primate ES cells. In this review, we argue a need for strong research programs using rhesus monkey ES cells, conducted in parallel with studies on human ES and adult stem cells, to derive the maximum information about the biology of normal stem cells and to produce technical protocols for their directed differentiation into safe and functional replacement cells, tissues, and organs. In contrast, ES cell research using only human cell lines is likely to be incomplete, which could hinder research progress, and delay or diminish the effective application of ES cell technology to the treatment of human diseases.

A novel method to correct for pitch and yaw patient setup errors in helical tomotherapy.

PubMed

Boswell, Sarah A; Jeraj, Robert; Ruchala, Kenneth J; Olivera, Gustavo H; Jaradat, Hazim A; James, Joshua A; Gutierrez, Alonso; Pearson, Dave; Frank, Gary; Mackie, T Rock

2005-06-01

An accurate means of determining and correcting for daily patient setup errors is important to the cancer outcome in radiotherapy. While many tools have been developed to detect setup errors, difficulty may arise in accurately adjusting the patient to account for the rotational error components. A novel, automated method to correct for rotational patient setup errors in helical tomotherapy is proposed for a treatment couch that is restricted to motion along translational axes. In tomotherapy, only a narrow superior/inferior section of the target receives a dose at any instant, thus rotations in the sagittal and coronal planes may be approximately corrected for by very slow continuous couch motion in a direction perpendicular to the scanning direction. Results from proof-of-principle tests indicate that the method improves the accuracy of treatment delivery, especially for long and narrow targets. Rotational corrections about an axis perpendicular to the transverse plane continue to be implemented easily in tomotherapy by adjustment of the initial gantry angle.

Impact of Spacecraft Shielding on Direct Ionization Soft Error Rates for sub-130 nm Technologies

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.; Xapsos, Michael A.; Stauffer, Craig A.; Jordan, Michael M.; Sanders, Anthony B.; Ladbury, Raymond L.; Oldham, Timothy R.; Marshall, Paul W.; Heidel, David F.; Rodbell, Kenneth P.

2010-01-01

We use ray tracing software to model various levels of spacecraft shielding complexity and energy deposition pulse height analysis to study how it affects the direct ionization soft error rate of microelectronic components in space. The analysis incorporates the galactic cosmic ray background, trapped proton, and solar heavy ion environments as well as the October 1989 and July 2000 solar particle events.

Impact of Spacecraft Shielding on Direct Ionization Soft Error Rates for Sub-130 nm Technologies

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.; Xapsos, Michael A.; Stauffer, Craig A.; Jordan, Thomas M.; Sanders, Anthony B.; Ladbury, Raymond L.; Oldham, Timothy R.; Marshall, Paul W.; Heidel, David F.; Rodbell, Kenneth P.

2010-01-01

We use ray tracing software to model various levels of spacecraft shielding complexity and energy deposition pulse height analysis to study how it affects the direct ionization soft error rate of microelectronic components in space. The analysis incorporates the galactic cosmic ray background, trapped proton, and solar heavy ion environments as well as the October 1989 and July 2000 solar particle events.

Invited review: Genetics and claw health: Opportunities to enhance claw health by genetic selection.

PubMed

Heringstad, B; Egger-Danner, C; Charfeddine, N; Pryce, J E; Stock, K F; Kofler, J; Sogstad, A M; Holzhauer, M; Fiedler, A; Müller, K; Nielsen, P; Thomas, G; Gengler, N; de Jong, G; Ødegård, C; Malchiodi, F; Miglior, F; Alsaaod, M; Cole, J B

2018-06-01

Routine recording of claw health status at claw trimming of dairy cattle has been established in several countries, providing valuable data for genetic evaluation. In this review, we examine issues related to genetic evaluation of claw health; discuss data sources, trait definitions, and data validation procedures; and present a review of genetic parameters, possible indicator traits, and status of genetic and genomic evaluations for claw disorders. Different sources of data and traits can be used to describe claw health. Severe cases of claw disorders can be identified by veterinary diagnoses. Data from lameness and locomotion scoring, activity information from sensors, and feet and leg conformation traits are used as auxiliary traits. The most reliable and comprehensive information is data from regular hoof trimming. In genetic evaluation, claw disorders are usually defined as binary traits, based on whether or not the claw disorder was present (recorded) at least once during a defined time period. The traits can be specific disorders, composite traits, or overall claw health. Data validation and editing criteria are needed to ensure reliable data at the trimmer, herd, animal, and record levels. Different strategies have been chosen, reflecting differences in herd sizes, data structures, management practices, and recording systems among countries. Heritabilities of the most commonly analyzed claw disorders based on data from routine claw trimming were generally low, with ranges of linear model estimates from 0.01 to 0.14, and threshold model estimates from 0.06 to 0.39. Estimated genetic correlations among claw disorders varied from -0.40 to 0.98. The strongest genetic correlations were found among sole hemorrhage (SH), sole ulcer (SU), and white line disease (WL), and between digital/interdigital dermatitis (DD/ID) and heel horn erosion (HHE). Genetic correlations between DD/ID and HHE on the one hand and SH, SU, or WL on the other hand were, in most cases, low. Although some of the studies were based on relatively few records and the estimated genetic parameters had large standard errors, there was, with some exceptions, consistency among studies. Various studies evaluate the potential of various data soureces for use in breeding. The use of hoof trimming data is recommended for maximization of genetic gain, although auxiliary traits, such as locomotion score and some conformation traits, may be valuable for increasing the reliability of genetic evaluations. Routine genetic evaluation of direct claw health has been implemented in the Netherlands (2010); Denmark, Finland, and Sweden (joint Nordic evaluation; 2011); and Norway (2014), and other countries plan to implement evaluations in the near future. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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

Aristophanous, M; Court, L

Purpose: Despite daily image guidance setup uncertainties can be high when treating large areas of the body. The aim of this study was to measure local uncertainties inside the PTV for patients receiving IMRT to the mediastinum region. Methods: Eleven lymphoma patients that received radiotherapy (breath-hold) to the mediastinum were included in this study. The treated region could range all the way from the neck to the diaphragm. Each patient had a CT scan with a CT-on-rails system prior to every treatment. The entire PTV region was matched to the planning CT using automatic rigid registration. The PTV was thenmore » split into 5 regions: neck, supraclavicular, superior mediastinum, upper heart, lower heart. Additional auto-registrations for each of the 5 local PTV regions were performed. The residual local setup errors were calculated as the difference between the final global PTV position and the individual final local PTV positions for the AP, SI and RL directions. For each patient 4 CT scans were analyzed (1 per week of treatment). Results: The residual mean group error (M) and standard deviation of the inter-patient (or systematic) error (Σ) were lowest in the RL direction of the superior mediastinum (0.0mm and 0.5mm) and highest in the RL direction of the lower heart (3.5mm and 2.9mm). The standard deviation of the inter-fraction (or random) error (σ) was lowest in the RL direction of the superior mediastinum (0.5mm) and highest in the SI direction of the lower heart (3.9mm) The directionality of local uncertainties is important; a superior residual error in the lower heart for example keeps it in the global PTV. Conclusion: There is a complex relationship between breath-holding and positioning uncertainties that needs further investigation. Residual setup uncertainties can be significant even under daily CT image guidance when treating large regions of the body.« less

Assessment and Calibration of Ultrasonic Measurement Errors in Estimating Weathering Index of Stone Cultural Heritage

NASA Astrophysics Data System (ADS)

Lee, Y.; Keehm, Y.

2011-12-01

Estimating the degree of weathering in stone cultural heritage, such as pagodas and statues is very important to plan conservation and restoration. The ultrasonic measurement is one of commonly-used techniques to evaluate weathering index of stone cultual properties, since it is easy to use and non-destructive. Typically we use a portable ultrasonic device, PUNDIT with exponential sensors. However, there are many factors to cause errors in measurements such as operators, sensor layouts or measurement directions. In this study, we carried out variety of measurements with different operators (male and female), different sensor layouts (direct and indirect), and sensor directions (anisotropy). For operators bias, we found that there were not significant differences by the operator's sex, while the pressure an operator exerts can create larger error in measurements. Calibrating with a standard sample for each operator is very essential in this case. For the sensor layout, we found that the indirect measurement (commonly used for cultural properties, since the direct measurement is difficult in most cases) gives lower velocity than the real one. We found that the correction coefficient is slightly different for different types of rocks: 1.50 for granite and sandstone and 1.46 for marble. From the sensor directions, we found that many rocks have slight anisotropy in their ultrasonic velocity measurement, though they are considered isotropic in macroscopic scale. Thus averaging four different directional measurement (0°, 45°, 90°, 135°) gives much less errors in measurements (the variance is 2-3 times smaller). In conclusion, we reported the error in ultrasonic meaurement of stone cultural properties by various sources quantitatively and suggested the amount of correction and procedures to calibrate the measurements. Acknowledgement: This study, which forms a part of the project, has been achieved with the support of national R&D project, which has been hosted by National Research Institute of Cultural Heritage of Cultural Heritage Administration(No. NRICH-1107-B01F).

Signal location using generalized linear constraints

NASA Astrophysics Data System (ADS)

Griffiths, Lloyd J.; Feldman, D. D.

1992-01-01

This report has presented a two-part method for estimating the directions of arrival of uncorrelated narrowband sources when there are arbitrary phase errors and angle independent gain errors. The signal steering vectors are estimated in the first part of the method; in the second part, the arrival directions are estimated. It should be noted that the second part of the method can be tailored to incorporate additional information about the nature of the phase errors. For example, if the phase errors are known to be caused solely by element misplacement, the element locations can be estimated concurrently with the DOA's by trying to match the theoretical steering vectors to the estimated ones. Simulation results suggest that, for general perturbation, the method can resolve closely spaced sources under conditions for which a standard high-resolution DOA method such as MUSIC fails.

Direct-to-consumer DNA testing and the GP.

PubMed

Trent, Ronald

2014-07-01

From early 2000 a new form of DNA genetic testing became available commercially. It bypasses the medical practitioner and can be ordered directly by the individual. To understand direct-to-consumer (DTC) DNA genetic testing and be able to respond appropriately if asked to be involved by a patient. Presently, all but one or two DTC DNA genetic testing laboratories are located outside Australia. The industry promotes itself as a means to better health through giving individuals complete control over their results. When communicating with patients about DTC DNA genetic testing, general practitioners will need to make a determination about the clinical utility of the test and the laboratory validity, both of which can be difficult in the current environment. Assistance may be available through public hospital clinical genetics services, although waiting times can be long. There is likely to be tighter regulation of these types of testing in the future, which may include involvement of medical practitioners.

Corrective Techniques and Future Directions for Treatment of Residual Refractive Error Following Cataract Surgery

PubMed Central

Moshirfar, Majid; McCaughey, Michael V; Santiago-Caban, Luis

2015-01-01

Postoperative residual refractive error following cataract surgery is not an uncommon occurrence for a large proportion of modern-day patients. Residual refractive errors can be broadly classified into 3 main categories: myopic, hyperopic, and astigmatic. The degree to which a residual refractive error adversely affects a patient is dependent on the magnitude of the error, as well as the specific type of intraocular lens the patient possesses. There are a variety of strategies for resolving residual refractive errors that must be individualized for each specific patient scenario. In this review, the authors discuss contemporary methods for rectification of residual refractive error, along with their respective indications/contraindications, and efficacies. PMID:25663845

Corrective Techniques and Future Directions for Treatment of Residual Refractive Error Following Cataract Surgery.

PubMed

Moshirfar, Majid; McCaughey, Michael V; Santiago-Caban, Luis

2014-12-01

Postoperative residual refractive error following cataract surgery is not an uncommon occurrence for a large proportion of modern-day patients. Residual refractive errors can be broadly classified into 3 main categories: myopic, hyperopic, and astigmatic. The degree to which a residual refractive error adversely affects a patient is dependent on the magnitude of the error, as well as the specific type of intraocular lens the patient possesses. There are a variety of strategies for resolving residual refractive errors that must be individualized for each specific patient scenario. In this review, the authors discuss contemporary methods for rectification of residual refractive error, along with their respective indications/contraindications, and efficacies.

Fault-tolerant quantum error detection.

PubMed

Linke, Norbert M; Gutierrez, Mauricio; Landsman, Kevin A; Figgatt, Caroline; Debnath, Shantanu; Brown, Kenneth R; Monroe, Christopher

2017-10-01

Quantum computers will eventually reach a size at which quantum error correction becomes imperative. Quantum information can be protected from qubit imperfections and flawed control operations by encoding a single logical qubit in multiple physical qubits. This redundancy allows the extraction of error syndromes and the subsequent detection or correction of errors without destroying the logical state itself through direct measurement. We show the encoding and syndrome measurement of a fault-tolerantly prepared logical qubit via an error detection protocol on four physical qubits, represented by trapped atomic ions. This demonstrates the robustness of a logical qubit to imperfections in the very operations used to encode it. The advantage persists in the face of large added error rates and experimental calibration errors.

Fisher classifier and its probability of error estimation

NASA Technical Reports Server (NTRS)

Chittineni, C. B.

1979-01-01

Computationally efficient expressions are derived for estimating the probability of error using the leave-one-out method. The optimal threshold for the classification of patterns projected onto Fisher's direction is derived. A simple generalization of the Fisher classifier to multiple classes is presented. Computational expressions are developed for estimating the probability of error of the multiclass Fisher classifier.

Genes, Culture and Conservatism-A Psychometric-Genetic Approach.

PubMed

Schwabe, Inga; Jonker, Wilfried; van den Berg, Stéphanie M

2016-07-01

The Wilson-Patterson conservatism scale was psychometrically evaluated using homogeneity analysis and item response theory models. Results showed that this scale actually measures two different aspects in people: on the one hand people vary in their agreement with either conservative or liberal catch-phrases and on the other hand people vary in their use of the "?" response category of the scale. A 9-item subscale was constructed, consisting of items that seemed to measure liberalism, and this subscale was subsequently used in a biometric analysis including genotype-environment interaction, correcting for non-homogeneous measurement error. Biometric results showed significant genetic and shared environmental influences, and significant genotype-environment interaction effects, suggesting that individuals with a genetic predisposition for conservatism show more non-shared variance but less shared variance than individuals with a genetic predisposition for liberalism.

Management of Newborn Infants with Phenylketonuria.

ERIC Educational Resources Information Center

Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

The booklet covers the identification, diagnosis, and clinical treatment of newborns with Phenylketonuria (PKU), an inborn error of metabolism, which, if untreated, can lead to mental retardation. An initial section considers biochemical and genetic factors of PKU including a diagram of aromatic amino acid hydroxylation systems. Screening…

Improving precision of forage yield trials: A case study

USDA-ARS?s Scientific Manuscript database

Field-based agronomic and genetic research relies heavily on the data generated from field evaluations. Therefore, it is imperative to optimize the precision of yield estimates in cultivar evaluation trials to make reliable selections. Experimental error in yield trials is sensitive to several facto...

Prader-Willi Syndrome (PWS): Condition Information

MedlinePlus

... with this disorder. Some can work in sheltered environments. Scientists do not know what increases the risk for Prader-Willi syndrome. The genetic error that leads to Prader-Willi syndrome occurs randomly, usually very early in fetal development. The syndrome is usually not hereditary. 3 Cassidy, S. ...

Elucidating an Adverse Outcome Pathway of Microcephaly for use in Computational Toxicology (SOT Annual Meeting)

EPA Science Inventory

While evidence now supports a causal link between maternal Zika viral infection and microcephaly, genetic errors and chemical stressors may also precipitate this malformation through disruption of neuroprogenitor cell (NPC) proliferation, migration and differentiation in the earl...

What's New with Newborn Screening

ERIC Educational Resources Information Center

Exceptional Parent, 2008

2008-01-01

Newborn screening is the process of testing and screening newborns shortly after birth for certain, potentially dangerous, conditions and/or impairments--conditions that include everything from inborn errors of metabolism and other genetic disorders to hearing impairment. Early detection through newborn screening is paramount, often allowing the…

Contrast improvement of continuous wave diffuse optical tomography reconstruction by hybrid approach using least square and genetic algorithm

NASA Astrophysics Data System (ADS)

Patra, Rusha; Dutta, Pranab K.

2015-07-01

Reconstruction of the absorption coefficient of tissue with good contrast is of key importance in functional diffuse optical imaging. A hybrid approach using model-based iterative image reconstruction and a genetic algorithm is proposed to enhance the contrast of the reconstructed image. The proposed method yields an observed contrast of 98.4%, mean square error of 0.638×10-3, and object centroid error of (0.001 to 0.22) mm. Experimental validation of the proposed method has also been provided with tissue-like phantoms which shows a significant improvement in image quality and thus establishes the potential of the method for functional diffuse optical tomography reconstruction with continuous wave setup. A case study of finger joint imaging is illustrated as well to show the prospect of the proposed method in clinical diagnosis. The method can also be applied to the concentration measurement of a region of interest in a turbid medium.

Ancient DNA sequence revealed by error-correcting codes.

PubMed

Brandão, Marcelo M; Spoladore, Larissa; Faria, Luzinete C B; Rocha, Andréa S L; Silva-Filho, Marcio C; Palazzo, Reginaldo

2015-07-10

A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code.

Ancient DNA sequence revealed by error-correcting codes

PubMed Central

Brandão, Marcelo M.; Spoladore, Larissa; Faria, Luzinete C. B.; Rocha, Andréa S. L.; Silva-Filho, Marcio C.; Palazzo, Reginaldo

2015-01-01

A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code. PMID:26159228

Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution

PubMed Central

Crawford, Forrest W.; Suchard, Marc A.

2011-01-01

A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with n current particles, a new particle is born with instantaneous rate λn and a particle dies with instantaneous rate μn. Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error-controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics. PMID:21984359

Identity-by-Descent-Based Phasing and Imputation in Founder Populations Using Graphical Models

PubMed Central

Palin, Kimmo; Campbell, Harry; Wright, Alan F; Wilson, James F; Durbin, Richard

2011-01-01

Accurate knowledge of haplotypes, the combination of alleles co-residing on a single copy of a chromosome, enables powerful gene mapping and sequence imputation methods. Since humans are diploid, haplotypes must be derived from genotypes by a phasing process. In this study, we present a new computational model for haplotype phasing based on pairwise sharing of haplotypes inferred to be Identical-By-Descent (IBD). We apply the Bayesian network based model in a new phasing algorithm, called systematic long-range phasing (SLRP), that can capitalize on the close genetic relationships in isolated founder populations, and show with simulated and real genome-wide genotype data that SLRP substantially reduces the rate of phasing errors compared to previous phasing algorithms. Furthermore, the method accurately identifies regions of IBD, enabling linkage-like studies without pedigrees, and can be used to impute most genotypes with very low error rate. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc.35:853-860, 2011 PMID:22006673

Phase Retrieval Using a Genetic Algorithm on the Systematic Image-Based Optical Alignment Testbed

NASA Technical Reports Server (NTRS)

Taylor, Jaime R.

2003-01-01

NASA s Marshall Space Flight Center s Systematic Image-Based Optical Alignment (SIBOA) Testbed was developed to test phase retrieval algorithms and hardware techniques. Individuals working with the facility developed the idea of implementing phase retrieval by breaking the determination of the tip/tilt of each mirror apart from the piston motion (or translation) of each mirror. Presented in this report is an algorithm that determines the optimal phase correction associated only with the piston motion of the mirrors. A description of the Phase Retrieval problem is first presented. The Systematic Image-Based Optical Alignment (SIBOA) Testbeb is then described. A Discrete Fourier Transform (DFT) is necessary to transfer the incoming wavefront (or estimate of phase error) into the spatial frequency domain to compare it with the image. A method for reducing the DFT to seven scalar/matrix multiplications is presented. A genetic algorithm is then used to search for the phase error. The results of this new algorithm on a test problem are presented.

Stochastic models for inferring genetic regulation from microarray gene expression data.

PubMed

Tian, Tianhai

2010-03-01

Microarray expression profiles are inherently noisy and many different sources of variation exist in microarray experiments. It is still a significant challenge to develop stochastic models to realize noise in microarray expression profiles, which has profound influence on the reverse engineering of genetic regulation. Using the target genes of the tumour suppressor gene p53 as the test problem, we developed stochastic differential equation models and established the relationship between the noise strength of stochastic models and parameters of an error model for describing the distribution of the microarray measurements. Numerical results indicate that the simulated variance from stochastic models with a stochastic degradation process can be represented by a monomial in terms of the hybridization intensity and the order of the monomial depends on the type of stochastic process. The developed stochastic models with multiple stochastic processes generated simulations whose variance is consistent with the prediction of the error model. This work also established a general method to develop stochastic models from experimental information. 2009 Elsevier Ireland Ltd. All rights reserved.

A Slowed Cell Cycle Stabilizes the Budding Yeast Genome.

PubMed

Vinton, Peter J; Weinert, Ted

2017-06-01

During cell division, aberrant DNA structures are detected by regulators called checkpoints that slow division to allow error correction. In addition to checkpoint-induced delay, it is widely assumed, though rarely shown, that merely slowing the cell cycle might allow more time for error detection and correction, thus resulting in a more stable genome. Fidelity by a slowed cell cycle might be independent of checkpoints. Here we tested the hypothesis that a slowed cell cycle stabilizes the genome, independent of checkpoints, in the budding yeast Saccharomyces cerevisiae We were led to this hypothesis when we identified a gene ( ERV14 , an ER cargo membrane protein) that when mutated, unexpectedly stabilized the genome, as measured by three different chromosome assays. After extensive studies of pathways rendered dysfunctional in erv14 mutant cells, we are led to the inference that no particular pathway is involved in stabilization, but rather the slowed cell cycle induced by erv14 stabilized the genome. We then demonstrated that, in genetic mutations and chemical treatments unrelated to ERV14 , a slowed cell cycle indeed correlates with a more stable genome, even in checkpoint-proficient cells. Data suggest a delay in G2/M may commonly stabilize the genome. We conclude that chromosome errors are more rarely made or are more readily corrected when the cell cycle is slowed (even ∼15 min longer in an ∼100-min cell cycle). And, some chromosome errors may not signal checkpoint-mediated responses, or do not sufficiently signal to allow correction, and their correction benefits from this "time checkpoint." Copyright © 2017 by the Genetics Society of America.

Caries: Review of Human Genetics Research

PubMed Central

Vieira, Alexandre R.; Modesto, Adriana; Marazita, Mary L.

2014-01-01

The NIH Consensus Development Program released a statement in 2001 (NIH Consensus Statement, 2001) and listed six major clinical caries research directions. One of these directions was the need for genetic studies to identify genes and genetic markers of diagnostic, prognostic, and therapeutic value. This last decade has seen a steep increase in studies investigating the presence of genetic factors influencing individual susceptibility to caries. This review revisits recent caries human genetic studies and provides a perspective for future studies in order to fulfill their promise of revolutionizing our understanding of and the standard of care for the most prevalent bacteria-mediated non-contagious disease in the world. PMID:24853115

Genetic Association Study of KCNQ5 Polymorphisms with High Myopia.

PubMed

Liao, Xuan; Yap, Maurice K H; Leung, Kim Hung; Kao, Patrick Y P; Liu, Long Qian; Yip, Shea Ping

2017-01-01

Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5) polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls). Five tag single-nucleotide polymorphisms (SNPs) of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give P asym values, and multiple comparisons were corrected by permutation test to give P emp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63-0.90; P emp = 0.0058) for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64-0.89; P emp = 0.0045) for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.

Prediction of body lipid change in pregnancy and lactation.

PubMed

Friggens, N C; Ingvartsen, K L; Emmans, G C

2004-04-01

A simple method to predict the genetically driven pattern of body lipid change through pregnancy and lactation in dairy cattle is proposed. The rationale and evidence for genetically driven body lipid change have their basis in evolutionary considerations and in the homeorhetic changes in lipid metabolism through the reproductive cycle. The inputs required to predict body lipid change are body lipid mass at calving (kg) and the date of conception (days in milk). Body lipid mass can be derived from body condition score and live weight. A key assumption is that there is a linear rate of change of the rate of body lipid change (dL/dt) between calving and a genetically determined time in lactation (T') at which a particular level of body lipid (L') is sought. A second assumption is that there is a linear rate of change of the rate of body lipid change (dL/dt) between T' and the next calving. The resulting model was evaluated using 2 sets of data. The first was from Holstein cows with 3 different levels of body fatness at calving. The second was from Jersey cows in first, second, and third parity. The model was found to reproduce the observed patterns of change in body lipid reserves through lactation in both data sets. The average error of prediction was low, less than the variation normally associated with the recording of condition score, and was similar for the 2 data sets. When the model was applied using the initially suggested parameter values derived from the literature the average error of prediction was 0.185 units of condition score (+/- 0.086 SD). After minor adjustments to the parameter values, the average error of prediction was 0.118 units of condition score (+/- 0.070 SD). The assumptions on which the model is based were sufficient to predict the changes in body lipid of both Holstein and Jersey cows under different nutritional conditions and parities. Thus, the model presented here shows that it is possible to predict genetically driven curves of body lipid change through lactation in a simple way that requires few parameters and inputs that can be derived in practice. It is expected that prediction of the cow's energy requirements can be substantially improved, particularly in early lactation, by incorporating a genetically driven body energy mobilization.

Detection of gene-environment interactions in the presence of linkage disequilibrium and noise by using genetic risk scores with internal weights from elastic net regression.

PubMed

Hüls, Anke; Ickstadt, Katja; Schikowski, Tamara; Krämer, Ursula

2017-06-12

For the analysis of gene-environment (GxE) interactions commonly single nucleotide polymorphisms (SNPs) are used to characterize genetic susceptibility, an approach that mostly lacks power and has poor reproducibility. One promising approach to overcome this problem might be the use of weighted genetic risk scores (GRS), which are defined as weighted sums of risk alleles of gene variants. The gold-standard is to use external weights from published meta-analyses. In this study, we used internal weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression and thereby provided a method that can be used if there are no external weights available. We conducted a simulation study for the detection of GxE interactions and compared power and type I error of single SNPs analyses with Bonferroni correction and corresponding analysis with unweighted and our weighted GRS approach in scenarios with six risk SNPs and an increasing number of highly correlated (up to 210) and noise SNPs (up to 840). Applying weighted GRS increased the power enormously in comparison to the common single SNPs approach (e.g. 94.2% vs. 35.4%, respectively, to detect a weak interaction with an OR ≈ 1.04 for six uncorrelated risk SNPs and n = 700 with a well-controlled type I error). Furthermore, weighted GRS outperformed the unweighted GRS, in particular in the presence of SNPs without any effect on the phenotype (e.g. 90.1% vs. 43.9%, respectively, when 20 noise SNPs were added to the six risk SNPs). This outperforming of the weighted GRS was confirmed in a real data application on lung inflammation in the SALIA cohort (n = 402). However, in scenarios with a high number of noise SNPs (>200 vs. 6 risk SNPs), larger sample sizes are needed to avoid an increased type I error, whereas a high number of correlated SNPs can be handled even in small samples (e.g. n = 400). In conclusion, weighted GRS with weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression were shown to be a powerful tool to detect gene-environment interactions in scenarios of high Linkage disequilibrium and noise.

How important are direct fitness benefits of sexual selection?

NASA Astrophysics Data System (ADS)

Møller, A. P.; Jennions, M. D.

2001-10-01

Females may choose mates based on the expression of secondary sexual characters that signal direct, material fitness benefits or indirect, genetic fitness benefits. Genetic benefits are acquired in the generation subsequent to that in which mate choice is performed, and the maintenance of genetic variation in viability has been considered a theoretical problem. Consequently, the magnitude of indirect benefits has traditionally been considered to be small. Direct fitness benefits can be maintained without consideration of mechanisms sustaining genetic variability, and they have thus been equated with the default benefits acquired by choosy females. There is, however, still debate as to whether or not males should honestly advertise direct benefits such as their willingness to invest in parental care. We use meta-analysis to estimate the magnitude of direct fitness benefits in terms of fertility, fecundity and two measures of paternal care (feeding rate in birds, hatching rate in male guarding ectotherms) based on an extensive literature survey. The mean coefficients of determination weighted by sample size were 6.3%, 2.3%, 1.3% and 23.6%, respectively. This compares to a mean weighted coefficient of determination of 1.5% for genetic viability benefits in studies of sexual selection. Thus, for several fitness components, direct benefits are only slightly more important than indirect ones arising from female choice. Hatching rate in male guarding ectotherms was by far the most important direct fitness component, explaining almost a quarter of the variance. Our analysis also shows that male sexual advertisements do not always reliably signal direct fitness benefits.

Incorporating gene-environment interaction in testing for association with rare genetic variants.

PubMed

Chen, Han; Meigs, James B; Dupuis, Josée

2014-01-01

The incorporation of gene-environment interactions could improve the ability to detect genetic associations with complex traits. For common genetic variants, single-marker interaction tests and joint tests of genetic main effects and gene-environment interaction have been well-established and used to identify novel association loci for complex diseases and continuous traits. For rare genetic variants, however, single-marker tests are severely underpowered due to the low minor allele frequency, and only a few gene-environment interaction tests have been developed. We aimed at developing powerful and computationally efficient tests for gene-environment interaction with rare variants. In this paper, we propose interaction and joint tests for testing gene-environment interaction of rare genetic variants. Our approach is a generalization of existing gene-environment interaction tests for multiple genetic variants under certain conditions. We show in our simulation studies that our interaction and joint tests have correct type I errors, and that the joint test is a powerful approach for testing genetic association, allowing for gene-environment interaction. We also illustrate our approach in a real data example from the Framingham Heart Study. Our approach can be applied to both binary and continuous traits, it is powerful and computationally efficient.

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

Analysis of uncertainties and convergence of the statistical quantities in turbulent wall-bounded flows by means of a physically based criterion

NASA Astrophysics Data System (ADS)

Andrade, João Rodrigo; Martins, Ramon Silva; Thompson, Roney Leon; Mompean, Gilmar; da Silveira Neto, Aristeu

2018-04-01

The present paper provides an analysis of the statistical uncertainties associated with direct numerical simulation (DNS) results and experimental data for turbulent channel and pipe flows, showing a new physically based quantification of these errors, to improve the determination of the statistical deviations between DNSs and experiments. The analysis is carried out using a recently proposed criterion by Thompson et al. ["A methodology to evaluate statistical errors in DNS data of plane channel flows," Comput. Fluids 130, 1-7 (2016)] for fully turbulent plane channel flows, where the mean velocity error is estimated by considering the Reynolds stress tensor, and using the balance of the mean force equation. It also presents how the residual error evolves in time for a DNS of a plane channel flow, and the influence of the Reynolds number on its convergence rate. The root mean square of the residual error is shown in order to capture a single quantitative value of the error associated with the dimensionless averaging time. The evolution in time of the error norm is compared with the final error provided by DNS data of similar Reynolds numbers available in the literature. A direct consequence of this approach is that it was possible to compare different numerical results and experimental data, providing an improved understanding of the convergence of the statistical quantities in turbulent wall-bounded flows.

Type I error rates of rare single nucleotide variants are inflated in tests of association with non-normally distributed traits using simple linear regression methods.

PubMed

Schwantes-An, Tae-Hwi; Sung, Heejong; Sabourin, Jeremy A; Justice, Cristina M; Sorant, Alexa J M; Wilson, Alexander F

2016-01-01

In this study, the effects of (a) the minor allele frequency of the single nucleotide variant (SNV), (b) the degree of departure from normality of the trait, and (c) the position of the SNVs on type I error rates were investigated in the Genetic Analysis Workshop (GAW) 19 whole exome sequence data. To test the distribution of the type I error rate, 5 simulated traits were considered: standard normal and gamma distributed traits; 2 transformed versions of the gamma trait (log 10 and rank-based inverse normal transformations); and trait Q1 provided by GAW 19. Each trait was tested with 313,340 SNVs. Tests of association were performed with simple linear regression and average type I error rates were determined for minor allele frequency classes. Rare SNVs (minor allele frequency < 0.05) showed inflated type I error rates for non-normally distributed traits that increased as the minor allele frequency decreased. The inflation of average type I error rates increased as the significance threshold decreased. Normally distributed traits did not show inflated type I error rates with respect to the minor allele frequency for rare SNVs. There was no consistent effect of transformation on the uniformity of the distribution of the location of SNVs with a type I error.

Evaluation of causes and frequency of medication errors during information technology downtime.

PubMed

Hanuscak, Tara L; Szeinbach, Sheryl L; Seoane-Vazquez, Enrique; Reichert, Brendan J; McCluskey, Charles F

2009-06-15

The causes and frequency of medication errors occurring during information technology downtime were evaluated. Individuals from a convenience sample of 78 hospitals who were directly responsible for supporting and maintaining clinical information systems (CISs) and automated dispensing systems (ADSs) were surveyed using an online tool between February 2007 and May 2007 to determine if medication errors were reported during periods of system downtime. The errors were classified using the National Coordinating Council for Medication Error Reporting and Prevention severity scoring index. The percentage of respondents reporting downtime was estimated. Of the 78 eligible hospitals, 32 respondents with CIS and ADS responsibilities completed the online survey for a response rate of 41%. For computerized prescriber order entry, patch installations and system upgrades caused an average downtime of 57% over a 12-month period. Lost interface and interface malfunction were reported for centralized and decentralized ADSs, with an average downtime response of 34% and 29%, respectively. The average downtime response was 31% for software malfunctions linked to clinical decision-support systems. Although patient harm did not result from 30 (54%) medication errors, the potential for harm was present for 9 (16%) of these errors. Medication errors occurred during CIS and ADS downtime despite the availability of backup systems and standard protocols to handle periods of system downtime. Efforts should be directed to reduce the frequency and length of down-time in order to minimize medication errors during such downtime.

An Empirical State Error Covariance Matrix for the Weighted Least Squares Estimation Method

NASA Technical Reports Server (NTRS)

Frisbee, Joseph H., Jr.

2011-01-01

State estimation techniques effectively provide mean state estimates. However, the theoretical state error covariance matrices provided as part of these techniques often suffer from a lack of confidence in their ability to describe the un-certainty in the estimated states. By a reinterpretation of the equations involved in the weighted least squares algorithm, it is possible to directly arrive at an empirical state error covariance matrix. This proposed empirical state error covariance matrix will contain the effect of all error sources, known or not. Results based on the proposed technique will be presented for a simple, two observer, measurement error only problem.

Color-motion feature-binding errors are mediated by a higher-order chromatic representation.

PubMed

Shevell, Steven K; Wang, Wei

2016-03-01

Peripheral and central moving objects of the same color may be perceived to move in the same direction even though peripheral objects have a different true direction of motion [Nature429, 262 (2004)10.1038/429262a]. The perceived, illusory direction of peripheral motion is a color-motion feature-binding error. Recent work shows that such binding errors occur even without an exact color match between central and peripheral objects, and, moreover, the frequency of the binding errors in the periphery declines as the chromatic difference increases between the central and peripheral objects [J. Opt. Soc. Am. A31, A60 (2014)JOAOD60740-323210.1364/JOSAA.31.000A60]. This change in the frequency of binding errors with the chromatic difference raises the general question of the chromatic representation from which the difference is determined. Here, basic properties of the chromatic representation are tested to discover whether it depends on independent chromatic differences on the l and the s cardinal axes or, alternatively, on a more specific higher-order chromatic representation. Experimental tests compared the rate of feature-binding errors when the central and peripheral colors had the identical s chromaticity (so zero difference in s) and a fixed magnitude of l difference, while varying the identical s level in center and periphery (thus always keeping the s difference at zero). A chromatic representation based on independent l and s differences would result in the same frequency of color-motion binding errors at everyslevel. The results are contrary to this prediction, thus showing that the chromatic representation at the level of color-motion feature binding depends on a higher-order chromatic mechanism.

Darwinism, not mutationism, explains the design of organisms.

PubMed

Gardner, Andy

2013-04-01

Shapiro claims that advances in molecular genetics have undermined Darwinism, leading him to advocate mutationism. However, this extreme view is bourne out of conceptual error. He has misunderstood the distinction between gradualism and saltationism, which do not concern the rate of genetic change, but rather the emergence of complex design. And he has misunderstood the relationship between the dynamics of natural selection and the agency of individual organisms: these are not competing hypotheses, but rather alternative conceptualizations of the same phenomenon. Copyright © 2012 Elsevier Ltd. All rights reserved.

Jumping to the wrong conclusions? An investigation of the mechanisms of reasoning errors in delusions.

PubMed

Jolley, Suzanne; Thompson, Claire; Hurley, James; Medin, Evelina; Butler, Lucy; Bebbington, Paul; Dunn, Graham; Freeman, Daniel; Fowler, David; Kuipers, Elizabeth; Garety, Philippa

2014-10-30

Understanding how people with delusions arrive at false conclusions is central to the refinement of cognitive behavioural interventions. Making hasty decisions based on limited data ('jumping to conclusions', JTC) is one potential causal mechanism, but reasoning errors may also result from other processes. In this study, we investigated the correlates of reasoning errors under differing task conditions in 204 participants with schizophrenia spectrum psychosis who completed three probabilistic reasoning tasks. Psychotic symptoms, affect, and IQ were also evaluated. We found that hasty decision makers were more likely to draw false conclusions, but only 37% of their reasoning errors were consistent with the limited data they had gathered. The remainder directly contradicted all the presented evidence. Reasoning errors showed task-dependent associations with IQ, affect, and psychotic symptoms. We conclude that limited data-gathering contributes to false conclusions but is not the only mechanism involved. Delusions may also be maintained by a tendency to disregard evidence. Low IQ and emotional biases may contribute to reasoning errors in more complex situations. Cognitive strategies to reduce reasoning errors should therefore extend beyond encouragement to gather more data, and incorporate interventions focused directly on these difficulties. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Nature or nurture: effects of parental ametropia on children's refractive errors].

PubMed

Landmann, A; Bechrakis, E

2013-12-01

The aim of this study was to quantify the degree of association between juvenile refraction errors and parental refraction status. Using a simple questionnaire we conducted a cross-sectional study to determine the prevalence and magnitudes of refractive errors and of parental refraction status in a sample (n=728) of 10- to 18-year-old Austrian grammar school students. Students with myopia or hyperopia were more likely to have ametropic parents and refraction was more myopic in juveniles with one or two parents being ametropic. The prevalence of myopia in children with 2 ametropic parents was 54%, decreasing to 35% in pupils with 1 and to 13% in children with no ametropic parents. The odds ratio for 1 and 2 compared with no ametropic parents was 8.3 and 3.7 for myopia and 1.3 and 1.6 for hyperopia, respectively. Furthermore, the data indicate a stronger influence of the maternal ametropia on children's refractive errors than paternal ametropia. Genetic factors play a significant role in refractive error and may be of dominant influence for school myopia under conditions of low environmental variation.

Pollen flow in the wildservice tree, Sorbus torminalis (L.) Crantz. I. Evaluating the paternity analysis procedure in continuous populations.

PubMed

Oddou-Muratorio, S; Houot, M-L; Demesure-Musch, B; Austerlitz, F

2003-12-01

The joint development of polymorphic molecular markers and paternity analysis methods provides new approaches to investigate ongoing patterns of pollen flow in natural plant populations. However, paternity studies are hindered by false paternity assignment and the nondetection of true fathers. To gauge the risk of these two types of errors, we performed a simulation study to investigate the impact on paternity analysis of: (i) the assumed values for the size of the breeding male population (NBMP), and (ii) the rate of scoring error in genotype assessment. Our simulations were based on microsatellite data obtained from a natural population of the entomophilous wild service tree, Sorbus torminalis (L.) Crantz. We show that an accurate estimate of NBMP is required to minimize both types of errors, and we assess the reliability of a technique used to estimate NBMP based on parent-offspring genetic data. We then show that scoring errors in genotype assessment only slightly affect the assessment of paternity relationships, and conclude that it is generally better to neglect the scoring error rate in paternity analyses within a nonisolated population.

Real-time catheter tracking for high-dose-rate prostate brachytherapy using an electromagnetic 3D-guidance device: A preliminary performance study

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

Zhou Jun; Sebastian, Evelyn; Mangona, Victor

2013-02-15

Purpose: In order to increase the accuracy and speed of catheter reconstruction in a high-dose-rate (HDR) prostate implant procedure, an automatic tracking system has been developed using an electromagnetic (EM) device (trakSTAR, Ascension Technology, VT). The performance of the system, including the accuracy and noise level with various tracking parameters and conditions, were investigated. Methods: A direct current (dc) EM transmitter (midrange model) and a sensor with diameter of 1.3 mm (Model 130) were used in the trakSTAR system for tracking catheter position during HDR prostate brachytherapy. Localization accuracy was assessed under both static and dynamic analyses conditions. For themore » static analysis, a calibration phantom was used to investigate error dependency on operating room (OR) table height (bottom vs midposition vs top), sensor position (distal tip of catheter vs connector end of catheter), direction [left-right (LR) vs anterior-posterior (AP) vs superior-inferior (SI)], sampling frequency (40 vs 80 vs 120 Hz), and interference from OR equipment (present vs absent). The mean and standard deviation of the localization offset in each direction and the corresponding error vectors were calculated. For dynamic analysis, the paths of five straight catheters were tracked to study the effects of directions, sampling frequency, and interference of EM field. Statistical analysis was conducted to compare the results in different configurations. Results: When interference was present in the static analysis, the error vectors were significantly higher at the top table position (3.3 {+-} 1.3 vs 1.8 {+-} 0.9 mm at bottom and 1.7 {+-} 1.0 mm at middle, p < 0.001), at catheter end position (3.1 {+-} 1.1 vs 1.4 {+-} 0.7 mm at the tip position, p < 0.001), and at 40 Hz sampling frequency (2.6 {+-} 1.1 vs 2.4 {+-} 1.5 mm at 80 Hz and 1.8 {+-} 1.1 at 160 Hz, p < 0.001). So did the mean offset errors in the LR direction (-1.7 {+-} 1.4 vs 0.4 {+-} 0.5 mm in AP and 0.8 {+-} 0.8 mm in SI directions, p < 0.001). The error vectors were significantly higher with surrounding interference (2.2 {+-} 1.3 mm) vs without interference (1.0 {+-} 0.7 mm, p < 0.001). An accuracy of 1.6 {+-} 0.2 mm can be reached when using optimum configuration (160 Hz at middle table position). When interference was present in the dynamic tracking, the mean tracking errors in LR direction (1.4 {+-} 0.5 mm) was significantly higher than that in AP direction (0.3 {+-} 0.2 mm, p < 0.001). So did the mean vector errors at 40 Hz (2.1 {+-} 0.2 mm vs 1.3 {+-} 0.2 mm at 80 Hz and 0.9 {+-} 0.2 mm at 160 Hz, p < 0.05). However, when interference was absent, they were comparable in the both directions and at all sampling frequencies. An accuracy of 0.9 {+-} 0.2 mm was obtained for the dynamic tracking when using optimum configuration. Conclusions: The performance of an EM tracking system depends highly on the system configuration and surrounding environment. The accuracy of EM tracking for catheter reconstruction in a prostate HDR brachytherapy procedure can be improved by reducing interference from surrounding equipment, decreasing distance from transmitter to tracking area, and choosing appropriated sampling frequency. A calibration scheme is needed to further reduce the tracking error when the interference is high.« less

Direct and maternal genetic relationships between calving ease, gestation length, milk production, fertility, type, and lifespan of Holstein-Friesian primiparous cows.

PubMed

Eaglen, S A E; Coffey, M P; Woolliams, J A; Wall, E

2013-06-01

As the emphasis in cattle breeding is shifting from traits that increase income toward traits that reduce costs, national breeding indices are expanding to include functional traits such as calving ease (CE). However, one issue is the lack of knowledge of genetic relationships between CE and other dairy traits. The same can be said about gestation length (GL), a potential novel selection trait with considerable heritabilities and possible genetic relationships with the calving process. This study aimed to estimate the genetic relationships between CE, GL, and other dairy traits of interest using a national data set of 31,053 primiparous cow performance records, as well as to separate direct and maternal genetic effects. Chosen dairy traits included fertility (calving interval, days to first service, nonreturn rate after 56 d, number of inseminations per conception), milk production (milk yield at d 110 in milk, accumulated 305-d milk yield, accumulated 305-d fat yield, accumulated 305-d protein yield), type (udder depth, chest width, rump width, rump angle, mammary composition, stature, body depth), and lifespan traits (functional days of productive life). To allow the separation of direct and maternal genetic effects, a random sire of the calf effect was included in the multi-trait linear trivariate sire models fitted using ASReml. Significant results showed that easily born individuals were genetically prone to high milk yield and reduced fertility in first lactation. Difficult calving primiparous cows were likely associated with being high-producing, wide and deep animals, with a reduced ability to subsequently conceive. Individuals that were born relatively early were associated with good genetic merit for milk production. Finally, individuals carrying their offspring longer were genetically associated with being wide and large animals that were themselves born relatively early. The study shows that it is feasible and valuable to separate direct and maternal effects when estimating genetic correlations between calving and other dairy traits. Furthermore, gestation length is best used as an indicator trait for lowly heritable calving traits, rather than as a novel selection trait. As estimated direct and maternal genetic correlations differ, we can conclude that genetic relationships between CE, GL, and traits of interest are present, but caution is required if these traits are implemented in national breeding indices. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Direct to consumer genetic testing-law and policy concerns in Ireland.

PubMed

de Paor, Aisling

2017-11-25

With rapid scientific and technological advances, the past few years has witnessed the emergence of a new genetic era and a growing understanding of the genetic make-up of human beings. These advances have propelled the introduction of companies offering direct to consumer (DTC) genetic testing, which facilitates the direct provision of such tests to consumers, (for example, via the internet). Although DTC genetic testing offers benefits by enhancing consumer accessibility to such technology, promoting proactive healthcare and increasing genetic awareness, it presents a myriad of challenges, from an ethical, legal and regulatory perspective. As DTC genetic testing usually eliminates the need for a medical professional in accessing genetic tests, this lack of professional guidance and counselling may result in misinterpretation and confusion regarding results. In addition, an evident concern relates to the scientific validity and quality of these tests. A further problem arising is the lack or inadequacy of regulation in this field. Despite the increasing accessibility of DTC genetic testing, this legislative vacuum is apparent in Ireland, where there is no concrete legislation. This article explores the main ethical, legal and regulatory issues arising with the advent of rapid advances in DTC genetic testing in Ireland. Further, with inevitable future advances in genetic science, as well as increasing internet accessibility, the challenges presented are likely to become more amplified. In consideration of the ethical and legal challenges, this paper highlights the regulation of DTC genetic testing as a growing concern in Ireland, recognising its importance to both the scientific community as well as in respect of enhancing consumer confidence in such technologies.

Overlay improvement by exposure map based mask registration optimization

NASA Astrophysics Data System (ADS)

Shi, Irene; Guo, Eric; Chen, Ming; Lu, Max; Li, Gordon; Li, Rivan; Tian, Eric

2015-03-01

Along with the increased miniaturization of semiconductor electronic devices, the design rules of advanced semiconductor devices shrink dramatically. [1] One of the main challenges of lithography step is the layer-to-layer overlay control. Furthermore, DPT (Double Patterning Technology) has been adapted for the advanced technology node like 28nm and 14nm, corresponding overlay budget becomes even tighter. [2][3] After the in-die mask registration (pattern placement) measurement is introduced, with the model analysis of a KLA SOV (sources of variation) tool, it's observed that registration difference between masks is a significant error source of wafer layer-to-layer overlay at 28nm process. [4][5] Mask registration optimization would highly improve wafer overlay performance accordingly. It was reported that a laser based registration control (RegC) process could be applied after the pattern generation or after pellicle mounting and allowed fine tuning of the mask registration. [6] In this paper we propose a novel method of mask registration correction, which can be applied before mask writing based on mask exposure map, considering the factors of mask chip layout, writing sequence, and pattern density distribution. Our experiment data show if pattern density on the mask keeps at a low level, in-die mask registration residue error in 3sigma could be always under 5nm whatever blank type and related writer POSCOR (position correction) file was applied; it proves random error induced by material or equipment would occupy relatively fixed error budget as an error source of mask registration. On the real production, comparing the mask registration difference through critical production layers, it could be revealed that registration residue error of line space layers with higher pattern density is always much larger than the one of contact hole layers with lower pattern density. Additionally, the mask registration difference between layers with similar pattern density could also achieve under 5nm performance. We assume mask registration excluding random error is mostly induced by charge accumulation during mask writing, which may be calculated from surrounding exposed pattern density. Multi-loading test mask registration result shows that with x direction writing sequence, mask registration behavior in x direction is mainly related to sequence direction, but mask registration in y direction would be highly impacted by pattern density distribution map. It proves part of mask registration error is due to charge issue from nearby environment. If exposure sequence is chip by chip for normal multi chip layout case, mask registration of both x and y direction would be impacted analogously, which has also been proved by real data. Therefore, we try to set up a simple model to predict the mask registration error based on mask exposure map, and correct it with the given POSCOR (position correction) file for advanced mask writing if needed.

Intelligence/Electronic Warfare (IEW) direction-finding and fix estimation analysis report. Volume 2: Trailblazer

NASA Technical Reports Server (NTRS)

Gardner, Robert; Gillis, James W.; Griesel, Ann; Pardo, Bruce

1985-01-01

An analysis of the direction finding (DF) and fix estimation algorithms in TRAILBLAZER is presented. The TRAILBLAZER software analyzed is old and not currently used in the field. However, the algorithms analyzed are used in other current IEW systems. The underlying algorithm assumptions (including unmodeled errors) are examined along with their appropriateness for TRAILBLAZER. Coding and documentation problems are then discussed. A detailed error budget is presented.

DEPRESSION AND INTERNALLY DIRECTED AGGRESSION: GENETIC AND ENVIRONMENTAL CONTRIBUTIONS

PubMed Central

Haddad, Suzanne K.; Neiderhiser, Jenae M.; Spotts, Erica L.; Ganiban, Jody; Lichtenstein, Paul; Reiss, David

2013-01-01

This study uses behavior genetic (BG) methodology to investigate Freud’s theory of depression as aggression directed toward the self (1930) and the extent to which genetically and environmentally influenced aggressive tendencies contribute to depressive symptoms. Data from the Twin and Offspring Study in Sweden (TOSS) is used to demonstrate how, in estimating shared and unique environmental influences, BG methods can inform psychoanalytic theory and practice, particularly because of their shared emphasis on the importance of individual experience in development. The TOSS sample consists of 909 pairs of adult twins, their partners, and one adolescent child per couple. The Center for Epidemiologic Studies Depression Scale (Radloff 1977) was used to measure depressive symptoms and the Karolinska Scales of Personality (Schalling and Edman 1993) to measure internally directed aggression. Genetic analyses indicated that for both men and women, their unique experiences as well as genetic factors contributed equally to the association between internally directed aggression and depressive symptoms. These findings support Freud’s theory that constitutionally based differences in aggression, along with individual experiences, contribute to a person’s depressive symptoms. Establishing that an individual’s unique, not shared, experiences and perceptions contribute to depressive symptoms and internally directed aggression reinforces the use of patient-specific treatment approaches implemented in psychoanalytic psychotherapy or psychoanalysis. PMID:18515705

SU-F-J-42: Comparison of Varian TrueBeam Cone-Beam CT and BrainLab ExacTrac X-Ray for Cranial Radiotherapy

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

Li, J; Shi, W; Andrews, D

2016-06-15

Purpose: To compare online image registrations of TrueBeam cone-beam CT (CBCT) and BrainLab ExacTrac x-ray imaging systems for cranial radiotherapy. Method: Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (Version 2.5), which is integrated with a BrainLab ExacTrac imaging system (Version 6.1.1). The phantom study was based on a Rando head phantom, which was designed to evaluate isocenter-location dependence of the image registrations. Ten isocenters were selected at various locations in the phantom, which represented clinical treatment sites. CBCT and ExacTrac x-ray images were taken when the phantom was located at each isocenter. The patientmore » study included thirteen patients. CBCT and ExacTrac x-ray images were taken at each patient’s treatment position. Six-dimensional image registrations were performed on CBCT and ExacTrac, and residual errors calculated from CBCT and ExacTrac were compared. Results: In the phantom study, the average residual-error differences between CBCT and ExacTrac image registrations were: 0.16±0.10 mm, 0.35±0.20 mm, and 0.21±0.15 mm, in the vertical, longitudinal, and lateral directions, respectively. The average residual-error differences in the rotation, roll, and pitch were: 0.36±0.11 degree, 0.14±0.10 degree, and 0.12±0.10 degree, respectively. In the patient study, the average residual-error differences in the vertical, longitudinal, and lateral directions were: 0.13±0.13 mm, 0.37±0.21 mm, 0.22±0.17 mm, respectively. The average residual-error differences in the rotation, roll, and pitch were: 0.30±0.10 degree, 0.18±0.11 degree, and 0.22±0.13 degree, respectively. Larger residual-error differences (up to 0.79 mm) were observed in the longitudinal direction in the phantom and patient studies where isocenters were located in or close to frontal lobes, i.e., located superficially. Conclusion: Overall, the average residual-error differences were within 0.4 mm in the translational directions and were within 0.4 degree in the rotational directions.« less

Field design factors affecting the precision of ryegrass forage yield estimation

USDA-ARS?s Scientific Manuscript database

Field-based agronomic and genetic research relies heavily on the data generated from field evaluations. Therefore, it is imperative to optimize the precision and accuracy of yield estimates in cultivar evaluation trials to make reliable selections. Experimental error in yield trials is sensitive to ...

What are incident reports telling us? A comparative study at two Australian hospitals of medication errors identified at audit, detected by staff and reported to an incident system.

PubMed

Westbrook, Johanna I; Li, Ling; Lehnbom, Elin C; Baysari, Melissa T; Braithwaite, Jeffrey; Burke, Rosemary; Conn, Chris; Day, Richard O

2015-02-01

To (i) compare medication errors identified at audit and observation with medication incident reports; (ii) identify differences between two hospitals in incident report frequency and medication error rates; (iii) identify prescribing error detection rates by staff. Audit of 3291 patient records at two hospitals to identify prescribing errors and evidence of their detection by staff. Medication administration errors were identified from a direct observational study of 180 nurses administering 7451 medications. Severity of errors was classified. Those likely to lead to patient harm were categorized as 'clinically important'. Two major academic teaching hospitals in Sydney, Australia. Rates of medication errors identified from audit and from direct observation were compared with reported medication incident reports. A total of 12 567 prescribing errors were identified at audit. Of these 1.2/1000 errors (95% CI: 0.6-1.8) had incident reports. Clinically important prescribing errors (n = 539) were detected by staff at a rate of 218.9/1000 (95% CI: 184.0-253.8), but only 13.0/1000 (95% CI: 3.4-22.5) were reported. 78.1% (n = 421) of clinically important prescribing errors were not detected. A total of 2043 drug administrations (27.4%; 95% CI: 26.4-28.4%) contained ≥ 1 errors; none had an incident report. Hospital A had a higher frequency of incident reports than Hospital B, but a lower rate of errors at audit. Prescribing errors with the potential to cause harm frequently go undetected. Reported incidents do not reflect the profile of medication errors which occur in hospitals or the underlying rates. This demonstrates the inaccuracy of using incident frequency to compare patient risk or quality performance within or across hospitals. New approaches including data mining of electronic clinical information systems are required to support more effective medication error detection and mitigation. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care.

Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries.

PubMed

Lee, Yi-Ying; Hsu, Chih-Yuan; Lin, Ling-Jiun; Chang, Chih-Chun; Cheng, Hsiao-Chun; Yeh, Tsung-Hsien; Hu, Rei-Hsing; Lin, Che; Xie, Zhen; Chen, Bor-Sen

2013-10-27

Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications. Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components.According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor. This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching.

Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries

PubMed Central

2013-01-01

Background Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications. Results Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components. According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor. Conclusion This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching. PMID:24160305

[Direct genetic manipulation and criminal code in Venezuela: absolute criminal law void?].

PubMed

Cermeño Zambrano, Fernando G De J

2002-01-01

The judicial regulation of genetic biotechnology applied to the human genome is of big relevance currently in Venezuela due to the drafting of an innovative bioethical law in the country's parliament. This article will highlight the constitutional normative of Venezuela's 1999 Constitution regarding this subject, as it establishes the framework from which this matter will be legally regulated. The approach this article makes towards the genetic biotechnology applied to the human genome is made taking into account the Venezuelan penal law and by highlighting the violent genetic manipulations that have criminal relevance. The genetic biotechnology applied to the human genome has another important relevance as a consequence of the reformulation of the Venezuelan Penal Code discussed by the country's National Assembly. Therefore, a concise study of the country's penal code will be made in this article to better understand what judicial-penal properties have been protected by the Venezuelan penal legislation. This last step will enable us to identify the penal tools Venezuela counts on to face direct genetic manipulations. We will equally indicate the existing punitive loophole and that should be covered by the penal legislator. In conclusion, this essay concerns criminal policy, referred to the direct genetic manipulations on the human genome that haven't been typified in Venezuelan law, thus discovering a genetic biotechnology paradise.

Errors in radiation oncology: A study in pathways and dosimetric impact

PubMed Central

Drzymala, Robert E.; Purdy, James A.; Michalski, Jeff

2005-01-01

As complexity for treating patients increases, so does the risk of error. Some publications have suggested that record and verify (R&V) systems may contribute in propagating errors. Direct data transfer has the potential to eliminate most, but not all, errors. And although the dosimetric consequences may be obvious in some cases, a detailed study does not exist. In this effort, we examined potential errors in terms of scenarios, pathways of occurrence, and dosimetry. Our goal was to prioritize error prevention according to likelihood of event and dosimetric impact. For conventional photon treatments, we investigated errors of incorrect source‐to‐surface distance (SSD), energy, omitted wedge (physical, dynamic, or universal) or compensating filter, incorrect wedge or compensating filter orientation, improper rotational rate for arc therapy, and geometrical misses due to incorrect gantry, collimator or table angle, reversed field settings, and setup errors. For electron beam therapy, errors investigated included incorrect energy, incorrect SSD, along with geometric misses. For special procedures we examined errors for total body irradiation (TBI, incorrect field size, dose rate, treatment distance) and LINAC radiosurgery (incorrect collimation setting, incorrect rotational parameters). Likelihood of error was determined and subsequently rated according to our history of detecting such errors. Dosimetric evaluation was conducted by using dosimetric data, treatment plans, or measurements. We found geometric misses to have the highest error probability. They most often occurred due to improper setup via coordinate shift errors or incorrect field shaping. The dosimetric impact is unique for each case and depends on the proportion of fields in error and volume mistreated. These errors were short‐lived due to rapid detection via port films. The most significant dosimetric error was related to a reversed wedge direction. This may occur due to incorrect collimator angle or wedge orientation. For parallel‐opposed 60° wedge fields, this error could be as high as 80% to a point off‐axis. Other examples of dosimetric impact included the following: SSD, ~2%/cm for photons or electrons; photon energy (6 MV vs. 18 MV), on average 16% depending on depth, electron energy, ~0.5cm of depth coverage per MeV (mega‐electron volt). Of these examples, incorrect distances were most likely but rapidly detected by in vivo dosimetry. Errors were categorized by occurrence rate, methods and timing of detection, longevity, and dosimetric impact. Solutions were devised according to these criteria. To date, no one has studied the dosimetric impact of global errors in radiation oncology. Although there is heightened awareness that with increased use of ancillary devices and automation, there must be a parallel increase in quality check systems and processes, errors do and will continue to occur. This study has helped us identify and prioritize potential errors in our clinic according to frequency and dosimetric impact. For example, to reduce the use of an incorrect wedge direction, our clinic employs off‐axis in vivo dosimetry. To avoid a treatment distance setup error, we use both vertical table settings and optical distance indicator (ODI) values to properly set up fields. As R&V systems become more automated, more accurate and efficient data transfer will occur. This will require further analysis. Finally, we have begun examining potential intensity‐modulated radiation therapy (IMRT) errors according to the same criteria. PACS numbers: 87.53.Xd, 87.53.St PMID:16143793

Is my study system good enough? A case study for identifying maternal effects.

PubMed

Holand, Anna Marie; Steinsland, Ingelin

2016-06-01

In this paper, we demonstrate how simulation studies can be used to answer questions about identifiability and consequences of omitting effects from a model. The methodology is presented through a case study where identifiability of genetic and/or individual (environmental) maternal effects is explored. Our study system is a wild house sparrow ( Passer domesticus ) population with known pedigree. We fit pedigree-based (generalized) linear mixed models (animal models), with and without additive genetic and individual maternal effects, and use deviance information criterion (DIC) for choosing between these models. Pedigree and R-code for simulations are available. For this study system, the simulation studies show that only large maternal effects can be identified. The genetic maternal effect (and similar for individual maternal effect) has to be at least half of the total genetic variance to be identified. The consequences of omitting a maternal effect when it is present are explored. Our results indicate that the total (genetic and individual) variance are accounted for. When an individual (environmental) maternal effect is omitted from the model, this only influences the estimated (direct) individual (environmental) variance. When a genetic maternal effect is omitted from the model, both (direct) genetic and (direct) individual variance estimates are overestimated.

Error Types and Error Positions in Neglect Dyslexia: Comparative Analyses in Neglect Patients and Healthy Controls

ERIC Educational Resources Information Center

Weinzierl, Christiane; Kerkhoff, Georg; van Eimeren, Lucia; Keller, Ingo; Stenneken, Prisca

2012-01-01

Unilateral spatial neglect frequently involves a lateralised reading disorder, neglect dyslexia (ND). Reading of single words in ND is characterised by left-sided omissions and substitutions of letters. However, it is unclear whether the distribution of error types and positions within a word shows a unique pattern of ND when directly compared to…

Incorporating approximation error in surrogate based Bayesian inversion

NASA Astrophysics Data System (ADS)

Zhang, J.; Zeng, L.; Li, W.; Wu, L.

2015-12-01

There are increasing interests in applying surrogates for inverse Bayesian modeling to reduce repetitive evaluations of original model. In this way, the computational cost is expected to be saved. However, the approximation error of surrogate model is usually overlooked. This is partly because that it is difficult to evaluate the approximation error for many surrogates. Previous studies have shown that, the direct combination of surrogates and Bayesian methods (e.g., Markov Chain Monte Carlo, MCMC) may lead to biased estimations when the surrogate cannot emulate the highly nonlinear original system. This problem can be alleviated by implementing MCMC in a two-stage manner. However, the computational cost is still high since a relatively large number of original model simulations are required. In this study, we illustrate the importance of incorporating approximation error in inverse Bayesian modeling. Gaussian process (GP) is chosen to construct the surrogate for its convenience in approximation error evaluation. Numerical cases of Bayesian experimental design and parameter estimation for contaminant source identification are used to illustrate this idea. It is shown that, once the surrogate approximation error is well incorporated into Bayesian framework, promising results can be obtained even when the surrogate is directly used, and no further original model simulations are required.

Spatial Representativeness Error in the Ground-Level Observation Networks for Black Carbon Radiation Absorption

NASA Astrophysics Data System (ADS)

Wang, Rong; Andrews, Elisabeth; Balkanski, Yves; Boucher, Olivier; Myhre, Gunnar; Samset, Bjørn Hallvard; Schulz, Michael; Schuster, Gregory L.; Valari, Myrto; Tao, Shu

2018-02-01

There is high uncertainty in the direct radiative forcing of black carbon (BC), an aerosol that strongly absorbs solar radiation. The observation-constrained estimate, which is several times larger than the bottom-up estimate, is influenced by the spatial representativeness error due to the mesoscale inhomogeneity of the aerosol fields and the relatively low resolution of global chemistry-transport models. Here we evaluated the spatial representativeness error for two widely used observational networks (AErosol RObotic NETwork and Global Atmosphere Watch) by downscaling the geospatial grid in a global model of BC aerosol absorption optical depth to 0.1° × 0.1°. Comparing the models at a spatial resolution of 2° × 2° with BC aerosol absorption at AErosol RObotic NETwork sites (which are commonly located near emission hot spots) tends to cause a global spatial representativeness error of 30%, as a positive bias for the current top-down estimate of global BC direct radiative forcing. By contrast, the global spatial representativeness error will be 7% for the Global Atmosphere Watch network, because the sites are located in such a way that there are almost an equal number of sites with positive or negative representativeness error.

A geometric model for initial orientation errors in pigeon navigation.

PubMed

Postlethwaite, Claire M; Walker, Michael M

2011-01-21

All mobile animals respond to gradients in signals in their environment, such as light, sound, odours and magnetic and electric fields, but it remains controversial how they might use these signals to navigate over long distances. The Earth's surface is essentially two-dimensional, so two stimuli are needed to act as coordinates for navigation. However, no environmental fields are known to be simple enough to act as perpendicular coordinates on a two-dimensional grid. Here, we propose a model for navigation in which we assume that an animal has a simplified 'cognitive map' in which environmental stimuli act as perpendicular coordinates. We then investigate how systematic deviation of the contour lines of the environmental signals from a simple orthogonal arrangement can cause errors in position determination and lead to systematic patterns of directional errors in initial homing directions taken by pigeons. The model reproduces patterns of initial orientation errors seen in previously collected data from homing pigeons, predicts that errors should increase with distance from the loft, and provides a basis for efforts to identify further sources of orientation errors made by homing pigeons. Copyright © 2010 Elsevier Ltd. All rights reserved.

Design of an all-attitude flight control system to execute commanded bank angles and angles of attack

NASA Technical Reports Server (NTRS)

Burgin, G. H.; Eggleston, D. M.

1976-01-01

A flight control system for use in air-to-air combat simulation was designed. The input to the flight control system are commanded bank angle and angle of attack, the output are commands to the control surface actuators such that the commanded values will be achieved in near minimum time and sideslip is controlled to remain small. For the longitudinal direction, a conventional linear control system with gains scheduled as a function of dynamic pressure is employed. For the lateral direction, a novel control system, consisting of a linear portion for small bank angle errors and a bang-bang control system for large errors and error rates is employed.

Directional variance adjustment: bias reduction in covariance matrices based on factor analysis with an application to portfolio optimization.

PubMed

Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W; Müller, Klaus-Robert; Lemm, Steven

2013-01-01

Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation.

Directional Variance Adjustment: Bias Reduction in Covariance Matrices Based on Factor Analysis with an Application to Portfolio Optimization

PubMed Central

Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W.; Müller, Klaus-Robert; Lemm, Steven

2013-01-01

Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation. PMID:23844016

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics

PubMed Central

Lee, Sandra Soo-Jin; Vernez, Simone L.; Ormond, K.E.; Granovetter, Mark

2013-01-01

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Methods: Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. Results: 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Conclusion: Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities. PMID:25562728

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics.

PubMed

Lee, Sandra Soo-Jin; Vernez, Simone L; Ormond, K E; Granovetter, Mark

2013-10-14

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities.

The prospects of selection for social genetic effects to improve welfare and productivity in livestock

PubMed Central

Ellen, Esther D.; Rodenburg, T. Bas; Albers, Gerard A. A.; Bolhuis, J. Elizabeth; Camerlink, Irene; Duijvesteijn, Naomi; Knol, Egbert F.; Muir, William M.; Peeters, Katrijn; Reimert, Inonge; Sell-Kubiak, Ewa; van Arendonk, Johan A. M.; Visscher, Jeroen; Bijma, Piter

2014-01-01

Social interactions between individuals living in a group can have both positive and negative effects on welfare, productivity, and health of these individuals. Negative effects of social interactions in livestock are easier to observe than positive effects. For example, laying hens may develop feather pecking, which can cause mortality due to cannibalism, and pigs may develop tail biting or excessive aggression. Several studies have shown that social interactions affect the genetic variation in a trait. Genetic improvement of socially-affected traits, however, has proven to be difficult until relatively recently. The use of classical selection methods, like individual selection, may result in selection responses opposite to expected, because these methods neglect the effect of an individual on its group mates (social genetic effects). It has become clear that improvement of socially-affected traits requires selection methods that take into account not only the direct effect of an individual on its own phenotype but also the social genetic effects, also known as indirect genetic effects, of an individual on the phenotypes of its group mates. Here, we review the theoretical and empirical work on social genetic effects, with a focus on livestock. First, we present the theory of social genetic effects. Subsequently, we evaluate the evidence for social genetic effects in livestock and other species, by reviewing estimates of genetic parameters for direct and social genetic effects. Then we describe the results of different selection experiments. Finally, we discuss issues concerning the implementation of social genetic effects in livestock breeding programs. This review demonstrates that selection for socially-affected traits, using methods that target both the direct and social genetic effects, is a promising, but sometimes difficult to use in practice, tool to simultaneously improve production and welfare in livestock. PMID:25426136

Familial transmission of depression and antisocial behavior symptoms: disentangling the contribution of inherited and environmental factors and testing the mediating role of parenting.

PubMed

Harold, G T; Rice, F; Hay, D F; Boivin, J; van den Bree, M; Thapar, A

2011-06-01

Genetic and environmental influences on child psychopathology have been studied extensively through twin and adoption designs. We offer a novel methodology to examine genetic and environmental influences on the intergenerational transmission of psychopathology using a sample of parents and children conceived through in vitro fertilization (IVF). The sample included families with children born through IVF methods, who varied as to whether the child was genetically related or unrelated to the rearing mother and father (mother genetically related, n=434; mother genetically unrelated, n=127; father genetically related, n=403; father genetically unrelated, n=156). Using standardized questionnaires, mothers and fathers respectively reported on their own psychopathology (depression, aggression), their parenting behavior toward their child (warmth, hostility) and their child's psychopathology (depression, aggression). A cross-rater approach was used, where opposite parents reported on child symptoms (i.e. fathers reported on symptoms for the mother-child dyad, and vice versa). For mother-child dyads, a direct association between mother depression and child depression was observed among genetically unrelated dyads, whereas a fully mediated path was observed among genetically related dyads through mother-to-child hostility and warmth. For father-child dyads, direct and mediated pathways were observed for genetically related father-child dyads. For aggression, the direct association between parent aggression and child aggression was fully mediated by parent-to-child hostility for both groups, indicating the role of parent-to-child hostility as a risk mechanism for transmission. A differential pattern of genetic and environmental mediation underlying the intergenerational transmission of psychopathology was observed among genetically related and genetically unrelated father-child and mother-child dyads.

The prospects of selection for social genetic effects to improve welfare and productivity in livestock.

PubMed

Ellen, Esther D; Rodenburg, T Bas; Albers, Gerard A A; Bolhuis, J Elizabeth; Camerlink, Irene; Duijvesteijn, Naomi; Knol, Egbert F; Muir, William M; Peeters, Katrijn; Reimert, Inonge; Sell-Kubiak, Ewa; van Arendonk, Johan A M; Visscher, Jeroen; Bijma, Piter

2014-01-01

Social interactions between individuals living in a group can have both positive and negative effects on welfare, productivity, and health of these individuals. Negative effects of social interactions in livestock are easier to observe than positive effects. For example, laying hens may develop feather pecking, which can cause mortality due to cannibalism, and pigs may develop tail biting or excessive aggression. Several studies have shown that social interactions affect the genetic variation in a trait. Genetic improvement of socially-affected traits, however, has proven to be difficult until relatively recently. The use of classical selection methods, like individual selection, may result in selection responses opposite to expected, because these methods neglect the effect of an individual on its group mates (social genetic effects). It has become clear that improvement of socially-affected traits requires selection methods that take into account not only the direct effect of an individual on its own phenotype but also the social genetic effects, also known as indirect genetic effects, of an individual on the phenotypes of its group mates. Here, we review the theoretical and empirical work on social genetic effects, with a focus on livestock. First, we present the theory of social genetic effects. Subsequently, we evaluate the evidence for social genetic effects in livestock and other species, by reviewing estimates of genetic parameters for direct and social genetic effects. Then we describe the results of different selection experiments. Finally, we discuss issues concerning the implementation of social genetic effects in livestock breeding programs. This review demonstrates that selection for socially-affected traits, using methods that target both the direct and social genetic effects, is a promising, but sometimes difficult to use in practice, tool to simultaneously improve production and welfare in livestock.

Non-additive genetic variation in growth, carcass and fertility traits of beef cattle.

PubMed

Bolormaa, Sunduimijid; Pryce, Jennie E; Zhang, Yuandan; Reverter, Antonio; Barendse, William; Hayes, Ben J; Goddard, Michael E

2015-04-02

A better understanding of non-additive variance could lead to increased knowledge on the genetic control and physiology of quantitative traits, and to improved prediction of the genetic value and phenotype of individuals. Genome-wide panels of single nucleotide polymorphisms (SNPs) have been mainly used to map additive effects for quantitative traits, but they can also be used to investigate non-additive effects. We estimated dominance and epistatic effects of SNPs on various traits in beef cattle and the variance explained by dominance, and quantified the increase in accuracy of phenotype prediction by including dominance deviations in its estimation. Genotype data (729 068 real or imputed SNPs) and phenotypes on up to 16 traits of 10 191 individuals from Bos taurus, Bos indicus and composite breeds were used. A genome-wide association study was performed by fitting the additive and dominance effects of single SNPs. The dominance variance was estimated by fitting a dominance relationship matrix constructed from the 729 068 SNPs. The accuracy of predicted phenotypic values was evaluated by best linear unbiased prediction using the additive and dominance relationship matrices. Epistatic interactions (additive × additive) were tested between each of the 28 SNPs that are known to have additive effects on multiple traits, and each of the other remaining 729 067 SNPs. The number of significant dominance effects was greater than expected by chance and most of them were in the direction that is presumed to increase fitness and in the opposite direction to inbreeding depression. Estimates of dominance variance explained by SNPs varied widely between traits, but had large standard errors. The median dominance variance across the 16 traits was equal to 5% of the phenotypic variance. Including a dominance deviation in the prediction did not significantly increase its accuracy for any of the phenotypes. The number of additive × additive epistatic effects that were statistically significant was greater than expected by chance. Significant dominance and epistatic effects occur for growth, carcass and fertility traits in beef cattle but they are difficult to estimate precisely and including them in phenotype prediction does not increase its accuracy.

Motor skills under varied gravitoinertial force in parabolic flight

NASA Astrophysics Data System (ADS)

Ross, Helen E.

Parabolic flight produces brief alternating periods of high and low gravitoinertial force. Subjects were tested on various paper-and-pencil aiming and tapping tasks during both normal and varied gravity in flight. It was found that changes in g level caused directional errors in the z body axis (the gravity axis), the arm aiming too high under 0g and too low under 2g. The standard deviation also increased for both vertical and lateral movements in the mid-frontal plane. Both variable and directional errors were greater under 0g than 2g. In an unpaced reciprocal tapping task subjects tended to increase their error rate rather than their movement time, but showed a non-significant trend towards slower speeds under 0g for all movement orientations. Larger variable errors or slower speeds were probably due to the difficulty of re-organising a motor skill in an unfamiliar force environment, combined with anchorage difficulties under 0g.

Empirical State Error Covariance Matrix for Batch Estimation

NASA Technical Reports Server (NTRS)

Frisbee, Joe

2015-01-01

State estimation techniques effectively provide mean state estimates. However, the theoretical state error covariance matrices provided as part of these techniques often suffer from a lack of confidence in their ability to describe the uncertainty in the estimated states. By a reinterpretation of the equations involved in the weighted batch least squares algorithm, it is possible to directly arrive at an empirical state error covariance matrix. The proposed empirical state error covariance matrix will contain the effect of all error sources, known or not. This empirical error covariance matrix may be calculated as a side computation for each unique batch solution. Results based on the proposed technique will be presented for a simple, two observer and measurement error only problem.