Protecting genomic sequence anonymity with generalization lattices.

PubMed

Malin, B A

2005-01-01

Current genomic privacy technologies assume the identity of genomic sequence data is protected if personal information, such as demographics, are obscured, removed, or encrypted. While demographic features can directly compromise an individual's identity, recent research demonstrates such protections are insufficient because sequence data itself is susceptible to re-identification. To counteract this problem, we introduce an algorithm for anonymizing a collection of person-specific DNA sequences. The technique is termed DNA lattice anonymization (DNALA), and is based upon the formal privacy protection schema of k -anonymity. Under this model, it is impossible to observe or learn features that distinguish one genetic sequence from k-1 other entries in a collection. To maximize information retained in protected sequences, we incorporate a concept generalization lattice to learn the distance between two residues in a single nucleotide region. The lattice provides the most similar generalized concept for two residues (e.g. adenine and guanine are both purines). The method is tested and evaluated with several publicly available human population datasets ranging in size from 30 to 400 sequences. Our findings imply the anonymization schema is feasible for the protection of sequences privacy. The DNALA method is the first computational disclosure control technique for general DNA sequences. Given the computational nature of the method, guarantees of anonymity can be formally proven. There is room for improvement and validation, though this research provides the groundwork from which future researchers can construct genomics anonymization schemas tailored to specific datasharing scenarios.

Cation and anion sequences in dark-adapted Balanus photoreceptor

PubMed Central

1977-01-01

Anion and cation permeabilities in dark-adapted Balanus photoreceptors were determined by comparing changes in the membrane potential in response to replacement of the dominant anion (Cl-) or cation (Na+) by test anions or cations in the superfusing solution. The anion permeability sequence obtained was PI greater than PSO4 greater than PBr greater than PCl greater than Pisethionate greater than Pmethanesulfonate. Gluconate, glucuronate, and glutamate generally appeared more permeable and propionate less permeable than Cl-. The alkali-metal cation permeability sequence obtained was PK greater than PRb greater than PCx greater than PNa approximately PLi. This corresponds to Eisenman's IV which is the same sequencethat has been obtained for other classes of nerve cells in the resting state. The values obtained for the permeability ratios of the alkali-metal cations are considered to be minimal. The membrane conductance measured by passing inward current pulses in the different test cations followed the sequence, GK greater than GRb greater than GCs greater than GNa greater than GLi. The conductance ratios obtained for a full substitution of the test cation agreed quite well with permeability ratios for all the alkali-metal cations except K+ which was generally higher. PMID:199688

Detailed Test Plan Redundant Sensor Strapdown IMU Evaluation Program

NASA Technical Reports Server (NTRS)

Hartwell, T.; Miyatake, Y.; Wedekind, D. E.

1971-01-01

The test plan for a redundant sensor strapdown inertial measuring unit evaluation program is presented. The subjects discussed are: (1) test philosophy and limitations, (2) test sequence, (3) equipment specifications, (4) general operating procedures, (5) calibration procedures, (6) alignment test phase, and (7) navigation test phase. The data and analysis requirements are analyzed.

75 FR 58329 - Federal Travel Regulation (FTR); Relocation Expenses Test Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

...; Docket 2010-0016; Sequence 1] RIN 3090-ZA01 Federal Travel Regulation (FTR); Relocation Expenses Test... extended the authority for relocation expenses test programs for Federal employees, made by the passage of..., permits the Administrator of General Services to authorize Federal agencies to test new and innovative...

40 CFR 86.1430 - Certification Short Test sequence; general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... test procedure. Fuel tank drain and fill is performed or a transient test procedure is performed, as... sets of test conditions identified in this subpart are based on the test fuel type present in the vehicle fuel tank and the ambient temperature during the test. Tables O-96-1 and O-96-2 outline the...

40 CFR 86.1430 - Certification Short Test sequence; general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... test procedure. Fuel tank drain and fill is performed or a transient test procedure is performed, as... sets of test conditions identified in this subpart are based on the test fuel type present in the vehicle fuel tank and the ambient temperature during the test. Tables O-96-1 and O-96-2 outline the...

40 CFR 86.1430 - Certification Short Test sequence; general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... test procedure. Fuel tank drain and fill is performed or a transient test procedure is performed, as... sets of test conditions identified in this subpart are based on the test fuel type present in the vehicle fuel tank and the ambient temperature during the test. Tables O-96-1 and O-96-2 outline the...

40 CFR 86.1430 - Certification Short Test sequence; general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... test procedure. Fuel tank drain and fill is performed or a transient test procedure is performed, as... sets of test conditions identified in this subpart are based on the test fuel type present in the vehicle fuel tank and the ambient temperature during the test. Tables O-96-1 and O-96-2 outline the...

Learning of Grammar-Like Visual Sequences by Adults with and without Language-Learning Disabilities

ERIC Educational Resources Information Center

Aguilar, Jessica M.; Plante, Elena

2014-01-01

Purpose: Two studies examined learning of grammar-like visual sequences to determine whether a general deficit in statistical learning characterizes this population. Furthermore, we tested the hypothesis that difficulty in sustaining attention during the learning task might account for differences in statistical learning. Method: In Study 1,…

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

Discounting of reward sequences: a test of competing formal models of hyperbolic discounting

PubMed Central

Zarr, Noah; Alexander, William H.; Brown, Joshua W.

2014-01-01

Humans are known to discount future rewards hyperbolically in time. Nevertheless, a formal recursive model of hyperbolic discounting has been elusive until recently, with the introduction of the hyperbolically discounted temporal difference (HDTD) model. Prior to that, models of learning (especially reinforcement learning) have relied on exponential discounting, which generally provides poorer fits to behavioral data. Recently, it has been shown that hyperbolic discounting can also be approximated by a summed distribution of exponentially discounted values, instantiated in the μAgents model. The HDTD model and the μAgents model differ in one key respect, namely how they treat sequences of rewards. The μAgents model is a particular implementation of a Parallel discounting model, which values sequences based on the summed value of the individual rewards whereas the HDTD model contains a non-linear interaction. To discriminate among these models, we observed how subjects discounted a sequence of three rewards, and then we tested how well each candidate model fit the subject data. The results show that the Parallel model generally provides a better fit to the human data. PMID:24639662

Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing.

PubMed

Lo, Y M Dennis

2013-12-01

The discovery of cell-free fetal DNA in maternal plasma in 1997 has stimulated a rapid development of non-invasive prenatal testing. The recent advent of massively parallel sequencing has allowed the analysis of circulating cell-free fetal DNA to be performed with unprecedented sensitivity and precision. Fetal trisomies 21, 18 and 13 are now robustly detectable in maternal plasma and such analyses have been available clinically since 2011. Fetal genome-wide molecular karyotyping and whole-genome sequencing have now been demonstrated in a number of proof-of-concept studies. Genome-wide and targeted sequencing of maternal plasma has been shown to allow the non-invasive prenatal testing of β-thalassaemia and can potentially be generalized to other monogenic diseases. It is thus expected that plasma DNA-based non-invasive prenatal testing will play an increasingly important role in future obstetric care. It is thus timely and important that the ethical, social and legal issues of non-invasive prenatal testing be discussed actively by all parties involved in prenatal care. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Performance comparison of the Prophecy (forecasting) Algorithm in FFT form for unseen feature and time-series prediction

NASA Astrophysics Data System (ADS)

Jaenisch, Holger; Handley, James

2013-06-01

We introduce a generalized numerical prediction and forecasting algorithm. We have previously published it for malware byte sequence feature prediction and generalized distribution modeling for disparate test article analysis. We show how non-trivial non-periodic extrapolation of a numerical sequence (forecast and backcast) from the starting data is possible. Our ancestor-progeny prediction can yield new options for evolutionary programming. Our equations enable analytical integrals and derivatives to any order. Interpolation is controllable from smooth continuous to fractal structure estimation. We show how our generalized trigonometric polynomial can be derived using a Fourier transform.

Cumulative Axial and Torsional Fatigue: An Investigation of Load-Type Sequencing Effects

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh; Bonacuse, Peter J.

2000-01-01

Cumulative fatigue behavior of a wrought cobalt-base superalloy, Haynes 188 was investigated at 538 C under various single-step sequences of axial and torsional loading conditions. Initially, fully-reversed, axial and torsional fatigue tests were conducted under strain control at 538 C on thin-walled tubular specimens to establish baseline fatigue life relationships. Subsequently, four sequences (axial/axial, torsional/torsional, axial/torsional, and torsional/axial) of two load-level fatigue tests were conducted to characterize both the load-order (high/low) and load-type sequencing effects. For the two load-level tests, summations of life fractions and the remaining fatigue lives at the second load-level were computed by the Miner's Linear Damage Rule (LDR) and a nonlinear Damage Curve Approach (DCA). In general, for all four cases predictions by LDR were unconservative. Predictions by the DCA were within a factor of two of the experimentally observed fatigue lives for a majority of the cumulative axial and torsional fatigue tests.

Enhanced timing abilities in percussionists generalize to rhythms without a musical beat.

PubMed

Cameron, Daniel J; Grahn, Jessica A

2014-01-01

The ability to entrain movements to music is arguably universal, but it is unclear how specialized training may influence this. Previous research suggests that percussionists have superior temporal precision in perception and production tasks. Such superiority may be limited to temporal sequences that resemble real music or, alternatively, may generalize to musically implausible sequences. To test this, percussionists and nonpercussionists completed two tasks that used rhythmic sequences varying in musical plausibility. In the beat tapping task, participants tapped with the beat of a rhythmic sequence over 3 stages: finding the beat (as an initial sequence played), continuation of the beat (as a second sequence was introduced and played simultaneously), and switching to a second beat (the initial sequence finished, leaving only the second). The meters of the two sequences were either congruent or incongruent, as were their tempi (minimum inter-onset intervals). In the rhythm reproduction task, participants reproduced rhythms of four types, ranging from high to low musical plausibility: Metric simple rhythms induced a strong sense of the beat, metric complex rhythms induced a weaker sense of the beat, nonmetric rhythms had no beat, and jittered nonmetric rhythms also had no beat as well as low temporal predictability. For both tasks, percussionists performed more accurately than nonpercussionists. In addition, both groups were better with musically plausible than implausible conditions. Overall, the percussionists' superior abilities to entrain to, and reproduce, rhythms generalized to musically implausible sequences.

Learning of grammar-like visual sequences by adults with and without language-learning disabilities.

PubMed

Aguilar, Jessica M; Plante, Elena

2014-08-01

Two studies examined learning of grammar-like visual sequences to determine whether a general deficit in statistical learning characterizes this population. Furthermore, we tested the hypothesis that difficulty in sustaining attention during the learning task might account for differences in statistical learning. In Study 1, adults with normal language (NL) or language-learning disability (LLD) were familiarized with the visual artificial grammar and then tested using items that conformed or deviated from the grammar. In Study 2, a 2nd sample of adults with NL and LLD were presented auditory word pairs with weak semantic associations (e.g., groom + clean) along with the visual learning task. Participants were instructed to attend to visual sequences and to ignore the auditory stimuli. Incidental encoding of these words would indicate reduced attention to the primary task. In Studies 1 and 2, both groups demonstrated learning and generalization of the artificial grammar. In Study 2, neither the NL nor the LLD group appeared to encode the words presented during the learning phase. The results argue against a general deficit in statistical learning for individuals with LLD and demonstrate that both NL and LLD learners can ignore extraneous auditory stimuli during visual learning.

40 CFR 86.1773-99 - Test sequence; general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... test simulation procedures, AC1 and AC2, for the 2001 to 2003 model years only. If a manufacturer desires to conduct an alternative SC03 test simulation other than AC1 and AC2, or the AC1 and AC2 simulations for the 2004 and subsequent model years, the simulation test procedure must be approved in advance...

40 CFR 86.1773-99 - Test sequence; general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... test simulation procedures, AC1 and AC2, for the 2001 to 2003 model years only. If a manufacturer desires to conduct an alternative SC03 test simulation other than AC1 and AC2, or the AC1 and AC2 simulations for the 2004 and subsequent model years, the simulation test procedure must be approved in advance...

40 CFR 86.1773-99 - Test sequence; general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... test simulation procedures, AC1 and AC2, for the 2001 to 2003 model years only. If a manufacturer desires to conduct an alternative SC03 test simulation other than AC1 and AC2, or the AC1 and AC2 simulations for the 2004 and subsequent model years, the simulation test procedure must be approved in advance...

Detection of generalized synchronization using echo state networks

NASA Astrophysics Data System (ADS)

Ibáñez-Soria, D.; Garcia-Ojalvo, J.; Soria-Frisch, A.; Ruffini, G.

2018-03-01

Generalized synchronization between coupled dynamical systems is a phenomenon of relevance in applications that range from secure communications to physiological modelling. Here, we test the capabilities of reservoir computing and, in particular, echo state networks for the detection of generalized synchronization. A nonlinear dynamical system consisting of two coupled Rössler chaotic attractors is used to generate temporal series consisting of time-locked generalized synchronized sequences interleaved with unsynchronized ones. Correctly tuned, echo state networks are able to efficiently discriminate between unsynchronized and synchronized sequences even in the presence of relatively high levels of noise. Compared to other state-of-the-art techniques of synchronization detection, the online capabilities of the proposed Echo State Network based methodology make it a promising choice for real-time applications aiming to monitor dynamical synchronization changes in continuous signals.

The Consolidation of Implicit Sequence Memory in Obstructive Sleep Apnea

PubMed Central

Malecek, Nick

2014-01-01

Obstructive Sleep Apnea (OSA) Syndrome is a relatively frequent sleep disorder characterized by disrupted sleep patterns. It is a well-established fact that sleep has beneficial effect on memory consolidation by enhancing neural plasticity. Implicit sequence learning is a prominent component of skill learning. However, the formation and consolidation of this fundamental learning mechanism remains poorly understood in OSA. In the present study we examined the consolidation of different aspects of implicit sequence learning in patients with OSA. We used the Alternating Serial Reaction Time task to measure general skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 10-hour offline period with sleep. Our data showed differences in offline changes of general skill learning between the OSA and control group. The control group demonstrated offline improvement from evening to morning, while the OSA group did not. In contrast, we did not observe differences between the groups in offline changes in sequence-specific learning. Our findings suggest that disrupted sleep in OSA differently affects neural circuits involved in the consolidation of sequence learning. PMID:25329462

Auditory sequence analysis and phonological skill

PubMed Central

Grube, Manon; Kumar, Sukhbinder; Cooper, Freya E.; Turton, Stuart; Griffiths, Timothy D.

2012-01-01

This work tests the relationship between auditory and phonological skill in a non-selected cohort of 238 school students (age 11) with the specific hypothesis that sound-sequence analysis would be more relevant to phonological skill than the analysis of basic, single sounds. Auditory processing was assessed across the domains of pitch, time and timbre; a combination of six standard tests of literacy and language ability was used to assess phonological skill. A significant correlation between general auditory and phonological skill was demonstrated, plus a significant, specific correlation between measures of phonological skill and the auditory analysis of short sequences in pitch and time. The data support a limited but significant link between auditory and phonological ability with a specific role for sound-sequence analysis, and provide a possible new focus for auditory training strategies to aid language development in early adolescence. PMID:22951739

Study of exhaust emissions from 1978-1980 model year three way catalyst vehicles in Los Angeles. Final report

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

Moore, L.L.; Jones, A.D.

This report presents and summarizes exhaust emission data and other information obtained as a result of the testing and inspection of 350 in-use passenger cars. The test fleet was made up of 1978, 1979 and 1980 automobiles manufactured by Ford, General Motors, Mazda, Saab, Toyota, Volkswagen/Audi and Volvo. Each vehicle was equipped with a three way catalyst control system. They were obtained randomly from private owners in the Los Angeles and Orange County areas. The testing was completed December, 1979. Each vehicle was tested only in as-received condition. The test sequence consisted of the 1975 Federal Test Procedure (exhaust emissionsmore » only), a Highway Fuel Economy test, a Two-Speed Idle test, a Federal Three Mode test, and a Loaded Two Mode test. After the initial test sequence, each vehicle was subjected to a thorough underhood inspection.« less

Testing Based on Understanding: Implications from Studies of Spatial Ability.

ERIC Educational Resources Information Center

Egan, Dennis E.

1979-01-01

The information-processing approach and results of research on spatial ability are analyzed. Performance consists of a sequence of distinct mental operations that seem general across subjects, and can be individually measured. New interpretations for some classical concepts in psychological testing and procedures for abilities are suggested.…

40 CFR 86.130-00 - Test sequence; general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... measurements supersede previous values. [61 FR 54893, Oct. 22, 1996] ... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission... (US06) and air conditioning (SC03) use are conducted as stand-alone tests as described in §§ 86.158-00...

40 CFR 86.1530 - Test sequence; general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Emission Regulations for Otto-Cycle Heavy-Duty Engines, New Methanol-Fueled Natural Gas-Fueled, and... Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Light-Duty Trucks; Idle...

Prediction of protein tertiary structure from sequences using a very large back-propagation neural network

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

Liu, X.; Wilcox, G.L.

1993-12-31

We have implemented large scale back-propagation neural networks on a 544 node Connection Machine, CM-5, using the C language in MIMD mode. The program running on 512 processors performs backpropagation learning at 0.53 Gflops, which provides 76 million connection updates per second. We have applied the network to the prediction of protein tertiary structure from sequence information alone. A neural network with one hidden layer and 40 million connections is trained to learn the relationship between sequence and tertiary structure. The trained network yields predicted structures of some proteins on which it has not been trained given only their sequences.more » Presentation of the Fourier transform of the sequences accentuates periodicity in the sequence and yields good generalization with greatly increased training efficiency. Training simulations with a large, heterologous set of protein structures (111 proteins from CM-5 time) to solutions with under 2% RMS residual error within the training set (random responses give an RMS error of about 20%). Presentation of 15 sequences of related proteins in a testing set of 24 proteins yields predicted structures with less than 8% RMS residual error, indicating good apparent generalization.« less

Novel Degenerate PCR Method for Whole-Genome Amplification Applied to Peru Margin (ODP Leg 201) Subsurface Samples

PubMed Central

Martino, Amanda J.; Rhodes, Matthew E.; Biddle, Jennifer F.; Brandt, Leah D.; Tomsho, Lynn P.; House, Christopher H.

2011-01-01

A degenerate polymerase chain reaction (PCR)-based method of whole-genome amplification, designed to work fluidly with 454 sequencing technology, was developed and tested for use on deep marine subsurface DNA samples. While optimized here for use with Roche 454 technology, the general framework presented may be applicable to other next generation sequencing systems as well (e.g., Illumina, Ion Torrent). The method, which we have called random amplification metagenomic PCR (RAMP), involves the use of specific primers from Roche 454 amplicon sequencing, modified by the addition of a degenerate region at the 3′ end. It utilizes a PCR reaction, which resulted in no amplification from blanks, even after 50 cycles of PCR. After efforts to optimize experimental conditions, the method was tested with DNA extracted from cultured E. coli cells, and genome coverage was estimated after sequencing on three different occasions. Coverage did not vary greatly with the different experimental conditions tested, and was around 62% with a sequencing effort equivalent to a theoretical genome coverage of 14.10×. The GC content of the sequenced amplification product was within 2% of the predicted values for this strain of E. coli. The method was also applied to DNA extracted from marine subsurface samples from ODP Leg 201 site 1229 (Peru Margin), and results of a taxonomic analysis revealed microbial communities dominated by Proteobacteria, Chloroflexi, Firmicutes, Euryarchaeota, and Crenarchaeota, among others. These results were similar to those obtained previously for those samples; however, variations in the proportions of taxa identified illustrates well the generally accepted view that community analysis is sensitive to both the amplification technique used and the method of assigning sequences to taxonomic groups. Overall, we find that RAMP represents a valid methodology for amplifying metagenomes from low-biomass samples. PMID:22319519

Sequence specific motor performance gains after memory consolidation in children and adolescents.

PubMed

Dorfberger, Shoshi; Adi-Japha, Esther; Karni, Avi

2012-01-01

Memory consolidation for a trained sequence of finger opposition movements, in 9- and 12-year-old children, was recently found to be significantly less susceptible to interference by a subsequent training experience, compared to that of 17-year-olds. It was suggested that, in children, the experience of training on any sequence of finger movements may affect the performance of the sequence elements, component movements, rather than the sequence as a unit; the latter has been implicated in the learning of the task by adults. This hypothesis implied a possible childhood advantage in the ability to transfer the gains from a trained to the reversed, untrained, sequence of movements. Here we report the results of transfer tests undertaken to test this proposal in 9-, 12-, and 17-year-olds after training in the finger-to-thumb opposition sequence (FOS) learning task. Our results show that the performance gains in the trained sequence partially transferred from the left, trained hand, to the untrained hand at 48-hours after a single training session in the three age-groups tested. However, there was very little transfer of the gains from the trained to the untrained, reversed, sequence performed by either hand. The results indicate sequence specific post-training gains in FOS performance, as opposed to a general improvement in performance of the individual, component, movements that comprised both the trained and untrained sequences. These results do not support the proposal that the reduced susceptibility to interference, in children before adolescence, reflects a difference in movement syntax representation after training.

Current and future molecular approaches in the diagnosis of cystic fibrosis.

PubMed

Bergougnoux, Anne; Taulan-Cadars, Magali; Claustres, Mireille; Raynal, Caroline

2018-05-01

Cystic Fibrosis is among the first diseases to have general population genetic screening tests and one of the most common indications of prenatal and preimplantation genetic diagnosis for single gene disorders. During the past twenty years, thanks to the evolution of diagnostic techniques, our knowledge of CFTR genetics and pathophysiological mechanisms involved in cystic fibrosis has significantly improved. Areas covered: Sanger sequencing and quantitative methods greatly contributed to the identification of more than 2,000 sequence variations reported worldwide in the CFTR gene. We are now entering a new technological age with the generalization of high throughput approaches such as Next Generation Sequencing and Droplet Digital PCR technologies in diagnostics laboratories. These powerful technologies open up new perspectives for scanning the entire CFTR locus, exploring modifier factors that possibly influence the clinical evolution of patients, and for preimplantation and prenatal diagnosis. Expert commentary: Such breakthroughs would, however, require powerful bioinformatics tools and relevant functional tests of variants for analysis and interpretation of the resulting data. Ultimately, an optimal use of all those resources may improve patient care and therapeutic decision-making.

Learning to learn: From within-modality to cross-modality transfer during infancy.

PubMed

Hupp, Julie M; Sloutsky, Vladimir M

2011-11-01

One critical aspect of learning is the ability to apply learned knowledge to new situations. This ability to transfer is often limited, and its development is not well understood. The current research investigated the development of transfer between 8 and 16 months of age. In Experiment 1, 8- and 16-month-olds (who were established to have a preference to the beginning of a visual sequence) were trained to attend to the end of a sequence. They were then tested on novel visual sequences. Results indicated transfer of learning, with both groups changing baseline preferences as a result of training. In Experiment 2, participants were trained to attend to the end of a visual sequence and were then tested on an auditory sequence. Unlike Experiment 1, only older participants exhibited transfer of learning by changing baseline preferences. These findings suggest that the generalization of learning becomes broader with development, with transfer across modalities developing later than transfer within a modality. Copyright © 2011 Elsevier Inc. All rights reserved.

Learning to Learn: From Within-Modality to Cross-Modality Transfer in Infancy

PubMed Central

Hupp, Julie M.; Sloutsky, Vladimir M.

2011-01-01

One critical aspect of learning is the ability to apply learned knowledge to new situations. This ability to transfer is often limited, and its development is not well understood. The current research investigated the development of transfer between 8- and 16-months of age. In Experiment 1, 8- and 16-month-olds (who were established to have a preference to the beginning of a visual sequence) were trained to attend to the end of a sequence. They were then tested on novel visual sequences. Results indicated transfer of learning, as both groups changed baseline preferences as a result of training. In Experiment 2, participants were trained to attend to the end of a visual sequence and then tested on an auditory sequence. Unlike Experiment 1, only older participants exhibited transfer of learning by changing baseline preferences. These findings suggest that the generalization of learning becomes broader with development, with transfer across modalities developing later than transfer within a modality. PMID:21663920

40 CFR 86.230-11 - Test sequence: general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... vehicle interior climate control system shall be operated with the interior heating system on and the air... changes (e.g., engine-off logic, idle speed operation, spark advance changes) and engine control features...) Prior to the first acceleration of the test at T=20 seconds the climate control settings shall be set as...

40 CFR 86.230-11 - Test sequence: general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... vehicle interior climate control system shall be operated with the interior heating system on and the air... changes (e.g., engine-off logic, idle speed operation, spark advance changes) and engine control features...) Prior to the first acceleration of the test at T=20 seconds the climate control settings shall be set as...

40 CFR 86.230-11 - Test sequence: general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... vehicle interior climate control system shall be operated with the interior heating system on and the air... changes (e.g., engine-off logic, idle speed operation, spark advance changes) and engine control features...) Prior to the first acceleration of the test at T=20 seconds the climate control settings shall be set as...

40 CFR 86.230-11 - Test sequence: general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... vehicle interior climate control system shall be operated with the interior heating system on and the air... changes (e.g., engine-off logic, idle speed operation, spark advance changes) and engine control features...) Prior to the first acceleration of the test at T=20 seconds the climate control settings shall be set as...

Interagency Depainting Study Status

NASA Technical Reports Server (NTRS)

Clark-Ingram, Marceia; Cook, Beth

1999-01-01

This document discusses coating removal in general. Sections of this presentation include: regulatory background, the initial parameters of the study, the current parameters of the study, stages in each sequence, preparation of the test specimen, material evaluation testing, chemical stripping, CO2 blasting, Flashjet coating removal, plastic media blasting, sodium bicarbonate wet stripping, water stripping, and wheat starch stripping.

Retention of Implicit Sequence Learning in Persons who Stutter and Persons with Parkinson's Disease

PubMed Central

Smits-Bandstra, Sarah; Gracco, Vincent

2014-01-01

This study investigated the retention of implicit sequence learning in 14 persons with Parkinson's disease (PPD), 14 persons who stutter (PWS) and 14 control participants. Participants completed a nonsense syllable serial reaction time task in a 120-minute session. Participants named aloud four syllables in response to four visual stimuli. The syllables formed a repeating 8-item sequence not made known to participants. After one week, participants completed a 60-minute retention session that included an explicit learning questionnaire and a sequence generation task. PPD showed retention of general learning equivalent to controls but PWS's reaction times were significantly slower on early trials of the retention test relative to other groups. Controls showed implicit learning during the initial session that was retained on the retention test. In contrast, PPD and PWS did not demonstrate significant implicit learning until the retention test suggesting intact, but delayed, learning and retention of implicit sequencing skills. All groups demonstrated similar limited explicit sequence knowledge. Performance differences between PWS and PPD relative to controls during the initial session and on early retention trials indicated possible dysfunction of the cortico-striato-thalamo-cortical loop. The etiological implications for stuttering, and clinical implications for both populations, of this dysfunction are discussed. PMID:23844763

Parents' interest in whole-genome sequencing of newborns.

PubMed

Goldenberg, Aaron J; Dodson, Daniel S; Davis, Matthew M; Tarini, Beth A

2014-01-01

The aim of this study was to assess parents' interest in whole-genome sequencing for newborns. We conducted a survey of a nationally representative sample of 1,539 parents about their interest in whole-genome sequencing of newborns. Participants were randomly presented with one of two scenarios that differed in the venue of testing: one offered whole-genome sequencing through a state newborn screening program, whereas the other offered whole-genome sequencing in a pediatrician's office. Overall interest in having future newborns undergo whole-genome sequencing was generally high among parents. If whole-genome sequencing were offered through a state's newborn-screening program, 74% of parents were either definitely or somewhat interested in utilizing this technology. If offered in a pediatrician's office, 70% of parents were either definitely or somewhat interested. Parents in both groups most frequently identified test accuracy and the ability to prevent a child from developing a disease as "very important" in making a decision to have a newborn's whole genome sequenced. These data may help health departments and children's health-care providers anticipate parents' level of interest in genomic screening for newborns. As whole-genome sequencing is integrated into clinical and public health services, these findings may inform the development of educational strategies and outreach messages for parents.

General Framework for Meta-analysis of Rare Variants in Sequencing Association Studies

PubMed Central

Lee, Seunggeun; Teslovich, Tanya M.; Boehnke, Michael; Lin, Xihong

2013-01-01

We propose a general statistical framework for meta-analysis of gene- or region-based multimarker rare variant association tests in sequencing association studies. In genome-wide association studies, single-marker meta-analysis has been widely used to increase statistical power by combining results via regression coefficients and standard errors from different studies. In analysis of rare variants in sequencing studies, region-based multimarker tests are often used to increase power. We propose meta-analysis methods for commonly used gene- or region-based rare variants tests, such as burden tests and variance component tests. Because estimation of regression coefficients of individual rare variants is often unstable or not feasible, the proposed method avoids this difficulty by calculating score statistics instead that only require fitting the null model for each study and then aggregating these score statistics across studies. Our proposed meta-analysis rare variant association tests are conducted based on study-specific summary statistics, specifically score statistics for each variant and between-variant covariance-type (linkage disequilibrium) relationship statistics for each gene or region. The proposed methods are able to incorporate different levels of heterogeneity of genetic effects across studies and are applicable to meta-analysis of multiple ancestry groups. We show that the proposed methods are essentially as powerful as joint analysis by directly pooling individual level genotype data. We conduct extensive simulations to evaluate the performance of our methods by varying levels of heterogeneity across studies, and we apply the proposed methods to meta-analysis of rare variant effects in a multicohort study of the genetics of blood lipid levels. PMID:23768515

Analysis of genomic sequences by Chaos Game Representation.

PubMed

Almeida, J S; Carriço, J A; Maretzek, A; Noble, P A; Fletcher, M

2001-05-01

Chaos Game Representation (CGR) is an iterative mapping technique that processes sequences of units, such as nucleotides in a DNA sequence or amino acids in a protein, in order to find the coordinates for their position in a continuous space. This distribution of positions has two properties: it is unique, and the source sequence can be recovered from the coordinates such that distance between positions measures similarity between the corresponding sequences. The possibility of using the latter property to identify succession schemes have been entirely overlooked in previous studies which raises the possibility that CGR may be upgraded from a mere representation technique to a sequence modeling tool. The distribution of positions in the CGR plane were shown to be a generalization of Markov chain probability tables that accommodates non-integer orders. Therefore, Markov models are particular cases of CGR models rather than the reverse, as currently accepted. In addition, the CGR generalization has both practical (computational efficiency) and fundamental (scale independence) advantages. These results are illustrated by using Escherichia coli K-12 as a test data-set, in particular, the genes thrA, thrB and thrC of the threonine operon.

Generalization of Learning from Picture Books to Novel Test Conditions by 18- and 24-Month-Old Children

ERIC Educational Resources Information Center

Simcock, Gabrielle; Dooley, Megan

2007-01-01

Researchers know little about whether very young children can recognize objects originally introduced to them in a picture book when they encounter similar looking objects in various real-world contexts. The present studies used an imitation procedure to explore young children's ability to generalize a novel action sequence from a picture book to…

Toward a General Approach for RNA-Templated Hierarchical Assembly of Split-Proteins

PubMed Central

Furman, Jennifer L.; Badran, Ahmed H.; Ajulo, Oluyomi; Porter, Jason R.; Stains, Cliff I.; Segal, David J.; Ghosh, Indraneel

2010-01-01

The ability to conditionally turn on a signal or induce a function in the presence of a user-defined RNA target has potential applications in medicine and synthetic biology. Although sequence-specific pumilio repeat proteins can target a limited set of ssRNA sequences, there are no general methods for targeting ssRNA with designed proteins. As a first step toward RNA recognition, we utilized the RNA binding domain of argonaute, implicated in RNA interference, for specifically targeting generic 2-nucleotide, 3' overhangs of any dsRNA. We tested the reassembly of a split-luciferase enzyme guided by argonaute-mediated recognition of newly generated nucleotide overhangs when ssRNA is targeted by a designed complementary guide sequence. This approach was successful when argonaute was utilized in conjunction with a pumilio repeat and expanded the scope of potential ssRNA targets. However, targeting any desired ssRNA remained elusive as two argonaute domains provided minimal reassembled split-luciferase. We next designed and tested a second hierarchical assembly, wherein ssDNA guides are appended to DNA hairpins that serve as a scaffold for high affinity zinc fingers attached to split-luciferase. In the presence of a ssRNA target containing adjacent sequences complementary to the guides, the hairpins are brought into proximity, allowing for zinc finger binding and concomitant reassembly of the fragmented luciferase. The scope of this new approach was validated by specifically targeting RNA encoding VEGF, hDM2, and HER2. These approaches provide potentially general design paradigms for the conditional reassembly of fragmented proteins in the presence of any desired ssRNA target. PMID:20681585

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL.

PubMed

Deans, Zandra C; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjö, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn Jl; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A

2017-01-01

The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services.

Improving Grasp Skills Using Schema Structured Learning

NASA Technical Reports Server (NTRS)

Platt, Robert; Grupen, ROderic A.; Fagg, Andrew H.

2006-01-01

Abstract In the control-based approach to robotics, complex behavior is created by sequencing and combining control primitives. While it is desirable for the robot to autonomously learn the correct control sequence, searching through the large number of potential solutions can be time consuming. This paper constrains this search to variations of a generalized solution encoded in a framework known as an action schema. A new algorithm, SCHEMA STRUCTURED LEARNING, is proposed that repeatedly executes variations of the generalized solution in search of instantiations that satisfy action schema objectives. This approach is tested in a grasping task where Dexter, the UMass humanoid robot, learns which reaching and grasping controllers maximize the probability of grasp success.

Musicians' working memory for tones, words, and pseudowords.

PubMed

Benassi-Werke, Mariana E; Queiroz, Marcelo; Araújo, Rúben S; Bueno, Orlando F A; Oliveira, Maria Gabriela M

2012-01-01

Studies investigating factors that influence tone recognition generally use recognition tests, whereas the majority of the studies on verbal material use self-generated responses in the form of serial recall tests. In the present study we intended to investigate whether tonal and verbal materials share the same cognitive mechanisms, by presenting an experimental instrument that evaluates short-term and working memories for tones, using self-generated sung responses that may be compared to verbal tests. This paradigm was designed according to the same structure of the forward and backward digit span tests, but using digits, pseudowords, and tones as stimuli. The profile of amateur singers and professional singers in these tests was compared in forward and backward digit, pseudoword, tone, and contour spans. In addition, an absolute pitch experimental group was included, in order to observe the possible use of verbal labels in tone memorization tasks. In general, we observed that musical schooling has a slight positive influence on the recall of tones, as opposed to verbal material, which is not influenced by musical schooling. Furthermore, the ability to reproduce melodic contours (up and down patterns) is generally higher than the ability to reproduce exact tone sequences. However, backward spans were lower than forward spans for all stimuli (digits, pseudowords, tones, contour). Curiously, backward spans were disproportionately lower for tones than for verbal material-that is, the requirement to recall sequences in backward rather than forward order seems to differentially affect tonal stimuli. This difference does not vary according to musical expertise.

Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results

PubMed Central

Plon, Sharon E.; Eccles, Diana M.; Easton, Douglas; Foulkes, William D.; Genuardi, Maurizio; Greenblatt, Marc S.; Hogervorst, Frans B.L.; Hoogerbrugge, Nicoline; Spurdle, Amanda B.; Tavtigian, Sean

2011-01-01

Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genetic testing may detect changes that are clearly pathogenic, clearly neutral or variants of unclear clinical significance. Such variants present a considerable challenge to the diagnostic laboratory and the receiving clinician in terms of interpretation and clear presentation of the implications of the result to the patient. There does not appear to be a consistent approach to interpreting and reporting the clinical significance of variants either among genes or among laboratories. The potential for confusion among clinicians and patients is considerable and misinterpretation may lead to inappropriate clinical consequences. In this article we review the current state of sequence-based genetic testing, describe other standardized reporting systems used in oncology and propose a standardized classification system for application to sequence based results for cancer predisposition genes. We suggest a system of five classes of variants based on the degree of likelihood of pathogenicity. Each class is associated with specific recommendations for clinical management of at-risk relatives that will depend on the syndrome. We propose that panels of experts on each cancer predisposition syndrome facilitate the classification scheme and designate appropriate surveillance and cancer management guidelines. The international adoption of a standardized reporting system should improve the clinical utility of sequence-based genetic tests to predict cancer risk. PMID:18951446

Developing Understanding of Twentieth Century Composition in Junior High School General Music. Final Report.

ERIC Educational Resources Information Center

Adler, Marvin Stanley

To develop an understanding of major 20th century musical styles and compositional techniques in junior high school general music classes, and to utilize rather than ignore student interest in current music, a sequence for units-of-study was developed and tested over a 2-year period in urban junior high schools. The initial units dealt with what…

STAT1:DNA sequence-dependent binding modulation by phosphorylation, protein:protein interactions and small-molecule inhibition

PubMed Central

Bonham, Andrew J.; Wenta, Nikola; Osslund, Leah M.; Prussin, Aaron J.; Vinkemeier, Uwe; Reich, Norbert O.

2013-01-01

The DNA-binding specificity and affinity of the dimeric human transcription factor (TF) STAT1, were assessed by total internal reflectance fluorescence protein-binding microarrays (TIRF-PBM) to evaluate the effects of protein phosphorylation, higher-order polymerization and small-molecule inhibition. Active, phosphorylated STAT1 showed binding preferences consistent with prior characterization, whereas unphosphorylated STAT1 showed a weak-binding preference for one-half of the GAS consensus site, consistent with recent models of STAT1 structure and function in response to phosphorylation. This altered-binding preference was further tested by use of the inhibitor LLL3, which we show to disrupt STAT1 binding in a sequence-dependent fashion. To determine if this sequence-dependence is specific to STAT1 and not a general feature of human TF biology, the TF Myc/Max was analysed and tested with the inhibitor Mycro3. Myc/Max inhibition by Mycro3 is sequence independent, suggesting that the sequence-dependent inhibition of STAT1 may be specific to this system and a useful target for future inhibitor design. PMID:23180800

Sequence-specific procedural learning deficits in children with specific language impairment.

PubMed

Hsu, Hsinjen Julie; Bishop, Dorothy V M

2014-05-01

This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children's performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger typically developing children matched for receptive grammar (n = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-matched controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e. pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (the Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Sim3C: simulation of Hi-C and Meta3C proximity ligation sequencing technologies.

PubMed

DeMaere, Matthew Z; Darling, Aaron E

2018-02-01

Chromosome conformation capture (3C) and Hi-C DNA sequencing methods have rapidly advanced our understanding of the spatial organization of genomes and metagenomes. Many variants of these protocols have been developed, each with their own strengths. Currently there is no systematic means for simulating sequence data from this family of sequencing protocols, potentially hindering the advancement of algorithms to exploit this new datatype. We describe a computational simulator that, given simple parameters and reference genome sequences, will simulate Hi-C sequencing on those sequences. The simulator models the basic spatial structure in genomes that is commonly observed in Hi-C and 3C datasets, including the distance-decay relationship in proximity ligation, differences in the frequency of interaction within and across chromosomes, and the structure imposed by cells. A means to model the 3D structure of randomly generated topologically associating domains is provided. The simulator considers several sources of error common to 3C and Hi-C library preparation and sequencing methods, including spurious proximity ligation events and sequencing error. We have introduced the first comprehensive simulator for 3C and Hi-C sequencing protocols. We expect the simulator to have use in testing of Hi-C data analysis algorithms, as well as more general value for experimental design, where questions such as the required depth of sequencing, enzyme choice, and other decisions can be made in advance in order to ensure adequate statistical power with respect to experimental hypothesis testing.

A powerful and flexible approach to the analysis of RNA sequence count data.

PubMed

Zhou, Yi-Hui; Xia, Kai; Wright, Fred A

2011-10-01

A number of penalization and shrinkage approaches have been proposed for the analysis of microarray gene expression data. Similar techniques are now routinely applied to RNA sequence transcriptional count data, although the value of such shrinkage has not been conclusively established. If penalization is desired, the explicit modeling of mean-variance relationships provides a flexible testing regimen that 'borrows' information across genes, while easily incorporating design effects and additional covariates. We describe BBSeq, which incorporates two approaches: (i) a simple beta-binomial generalized linear model, which has not been extensively tested for RNA-Seq data and (ii) an extension of an expression mean-variance modeling approach to RNA-Seq data, involving modeling of the overdispersion as a function of the mean. Our approaches are flexible, allowing for general handling of discrete experimental factors and continuous covariates. We report comparisons with other alternate methods to handle RNA-Seq data. Although penalized methods have advantages for very small sample sizes, the beta-binomial generalized linear model, combined with simple outlier detection and testing approaches, appears to have favorable characteristics in power and flexibility. An R package containing examples and sample datasets is available at http://www.bios.unc.edu/research/genomic_software/BBSeq yzhou@bios.unc.edu; fwright@bios.unc.edu Supplementary data are available at Bioinformatics online.

Development and application of a general plasmid reference material for GMO screening.

PubMed

Wu, Yuhua; Li, Jun; Wang, Yulei; Li, Xiaofei; Li, Yunjing; Zhu, Li; Li, Jun; Wu, Gang

The use of analytical controls is essential when performing GMO detection through screening tests. Additionally, the presence of taxon-specific sequences is analyzed mostly for quality control during GMO detection. In this study, 11 commonly used genetic elements involving three promoters (P-35S, P-FMV35S and P-NOS), four marker genes (Bar, NPTII, HPT and Pmi), and four terminators (T-NOS, T-35S, T-g7 and T-e9), together with the reference gene fragments from six major crops of maize, soybean, rapeseed, rice, cotton and wheat, were co-integrated into the same single plasmid to construct a general reference plasmid pBI121-Screening. The suitability test of pBI121-Screening plasmid as reference material indicated that the non-target sequence on the pBI121-Screening plasmid did not affect the PCR amplification efficiencies of screening methods and taxon-specific methods. The sensitivity of screening and taxon-specific assays ranged from 5 to 10 copies of pBI121-Screening plasmid, meeting the sensitivity requirement of GMO detection. The construction of pBI121-Screening solves the lack of a general positive control for screening tests, thereby reducing the workload and cost of preparing a plurality of the positive control. Copyright © 2016 Elsevier B.V. All rights reserved.

Phylum- and Class-Specific PCR Primers for General Microbial Community Analysis

PubMed Central

Blackwood, Christopher B.; Oaks, Adam; Buyer, Jeffrey S.

2005-01-01

Amplification of a particular DNA fragment from a mixture of organisms by PCR is a common first step in methods of examining microbial community structure. The use of group-specific primers in community DNA profiling applications can provide enhanced sensitivity and phylogenetic detail compared to domain-specific primers. Other uses for group-specific primers include quantitative PCR and library screening. The purpose of the present study was to develop several primer sets targeting commonly occurring and important groups. Primers specific for the 16S ribosomal sequences of Alphaproteobacteria, Betaproteobacteria, Bacilli, Actinobacteria, and Planctomycetes and for parts of both the 18S ribosomal sequence and the internal transcribed spacer region of Basidiomycota were examined. Primers were tested by comparison to sequences in the ARB 2003 database, and chosen primers were further tested by cloning and sequencing from soil community DNA. Eighty-five to 100% of the sequences obtained from clone libraries were found to be placed with the groups intended as targets, demonstrating the specificity of the primers under field conditions. It will be important to reevaluate primers over time because of the continual growth of sequence databases and revision of microbial taxonomy. PMID:16204538

Apollo 7 - Press Kit

NASA Technical Reports Server (NTRS)

1968-01-01

Contents include the following: General release. Mission objectives. Mission description. Flight plan. Alternate missions. Experiments. Abort model. Spacecraft structure system. The Saturn 1B launch vehicle. Flight sequence. Launch preparations. Mission control center-Houston. Manned space flight network. Photographic equipment. Apollo 7 crew. Apollo 7 test program.

Searching for evidence of selection in avian DNA barcodes.

PubMed

Kerr, Kevin C R

2011-11-01

The barcode of life project has assembled a tremendous number of mitochondrial cytochrome c oxidase I (COI) sequences. Although these sequences were gathered to develop a DNA-based system for species identification, it has been suggested that further biological inferences may also be derived from this wealth of data. Recurrent selective sweeps have been invoked as an evolutionary mechanism to explain limited intraspecific COI diversity, particularly in birds, but this hypothesis has not been formally tested. In this study, I collated COI sequences from previous barcoding studies on birds and tested them for evidence of selection. Using this expanded data set, I re-examined the relationships between intraspecific diversity and interspecific divergence and sampling effort, respectively. I employed the McDonald-Kreitman test to test for neutrality in sequence evolution between closely related pairs of species. Because amino acid sequences were generally constrained between closely related pairs, I also included broader intra-order comparisons to quantify patterns of protein variation in avian COI sequences. Lastly, using 22 published whole mitochondrial genomes, I compared the evolutionary rate of COI against the other 12 protein-coding mitochondrial genes to assess intragenomic variability. I found no conclusive evidence of selective sweeps. Most evidence pointed to an overall trend of strong purifying selection and functional constraint. The COI protein did vary across the class Aves, but to a very limited extent. COI was the least variable gene in the mitochondrial genome, suggesting that other genes might be more informative for probing factors constraining mitochondrial variation within species. © 2011 Blackwell Publishing Ltd.

Healthy older adults demonstrate generalized postural motor learning in response to variable amplitude oscillations of the support surface

PubMed Central

Van Ooteghem, Karen; Frank, James S.; Allard, Fran; Horak, Fay B

2011-01-01

Postural motor learning for dynamic balance tasks has been demonstrated in healthy older adults (Van Ooteghem et al. 2009). The purpose of this study was to investigate the type of knowledge (general or specific) obtained with balance training in this age group and to examine whether embedding perturbation regularities within a balance task masks specific learning. Two groups of older adults maintained balance on a constant frequency-variable amplitude oscillating platform. One group was trained using an embedded sequence (ES) protocol which contained the same 15-s sequence of variable amplitude oscillations in the middle of each trial. A second group was trained using a looped sequence (LS) protocol which contained a 15-s sequence repeated three times to form each trial. All trials were 45-s. Participants were not informed of any repetition. To examine learning, participants performed a retention test following a 24-h delay. LS participants also completed a transfer task. Specificity of learning was examined by comparing performance for repeated versus random sequences (ES) and training versus transfer sequences (LS). Performance was measured by deriving spatial and temporal measures of whole body centre of mass (COM), and trunk orientation. Both groups improved performance with practice as characterized by reduced COM displacement, improved COM-platform phase relationships, and decreased angular trunk motion. Improvements were also characterized by general rather than specific postural motor learning. These findings are similar to young adults (Van Ooteghem et al. 2008) and indicate that age does not influence the type of learning which occurs for balance control. PMID:20544184

Pitch chroma discrimination, generalization, and transfer tests of octave equivalence in humans.

PubMed

Hoeschele, Marisa; Weisman, Ronald G; Sturdy, Christopher B

2012-11-01

Octave equivalence occurs when notes separated by an octave (a doubling in frequency) are judged as being perceptually similar. Considerable evidence points to the importance of the octave in music and speech. Yet, experimental demonstration of octave equivalence has been problematic. Using go/no-go operant discrimination and generalization, we studied octave equivalence in humans. In Experiment 1, we found that a procedure that failed to show octave equivalence in European starlings also failed in humans. In Experiment 2, we modified the procedure to control for the effects of pitch height perception by training participants in Octave 4 and testing in Octave 5. We found that the pattern of responding developed by discrimination training in Octave 4 generalized to Octave 5. We replicated and extended our findings in Experiment 3 by adding a transfer phase: Participants were trained with either the same or a reversed pattern of rewards in Octave 5. Participants transferred easily to the same pattern of reward in Octave 5 but struggled to learn the reversed pattern. We provided minimal instruction, presented no ordered sequences of notes, and used only sine-wave tones, but participants nonetheless constructed pitch chroma information from randomly ordered sequences of notes. Training in music weakly hindered octave generalization but moderately facilitated both positive and negative transfer.

Information-Theoretic Uncertainty of SCFG-Modeled Folding Space of The Non-coding RNA

PubMed Central

Manzourolajdad, Amirhossein; Wang, Yingfeng; Shaw, Timothy I.; Malmberg, Russell L.

2012-01-01

RNA secondary structure ensembles define probability distributions for alternative equilibrium secondary structures of an RNA sequence. Shannon’s Entropy is a measure for the amount of diversity present in any ensemble. In this work, Shannon’s entropy of the SCFG ensemble on an RNA sequence is derived and implemented in polynomial time for both structurally ambiguous and unambiguous grammars. Micro RNA sequences generally have low folding entropy, as previously discovered. Surprisingly, signs of significantly high folding entropy were observed in certain ncRNA families. More effective models coupled with targeted randomization tests can lead to a better insight into folding features of these families. PMID:23160142

Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study.

PubMed

Ream, Margie A; Mikati, Mohamad A

2014-08-01

The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined. To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center. We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES). We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29). We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing. Copyright © 2014. Published by Elsevier Inc.

Genetic Misdiagnoses and the Potential for Health Disparities.

PubMed

Manrai, Arjun K; Funke, Birgit H; Rehm, Heidi L; Olesen, Morten S; Maron, Bradley A; Szolovits, Peter; Margulies, David M; Loscalzo, Joseph; Kohane, Isaac S

2016-08-18

For more than a decade, risk stratification for hypertrophic cardiomyopathy has been enhanced by targeted genetic testing. Using sequencing results, clinicians routinely assess the risk of hypertrophic cardiomyopathy in a patient's relatives and diagnose the condition in patients who have ambiguous clinical presentations. However, the benefits of genetic testing come with the risk that variants may be misclassified. Using publicly accessible exome data, we identified variants that have previously been considered causal in hypertrophic cardiomyopathy and that are overrepresented in the general population. We studied these variants in diverse populations and reevaluated their initial ascertainments in the medical literature. We reviewed patient records at a leading genetic-testing laboratory for occurrences of these variants during the near-decade-long history of the laboratory. Multiple patients, all of whom were of African or unspecified ancestry, received positive reports, with variants misclassified as pathogenic on the basis of the understanding at the time of testing. Subsequently, all reported variants were recategorized as benign. The mutations that were most common in the general population were significantly more common among black Americans than among white Americans (P<0.001). Simulations showed that the inclusion of even small numbers of black Americans in control cohorts probably would have prevented these misclassifications. We identified methodologic shortcomings that contributed to these errors in the medical literature. The misclassification of benign variants as pathogenic that we found in our study shows the need for sequencing the genomes of diverse populations, both in asymptomatic controls and the tested patient population. These results expand on current guidelines, which recommend the use of ancestry-matched controls to interpret variants. As additional populations of different ancestry backgrounds are sequenced, we expect variant reclassifications to increase, particularly for ancestry groups that have historically been less well studied. (Funded by the National Institutes of Health.).

Shuttle/Agena study. Volume 2, part 3: Preliminary test plans

NASA Technical Reports Server (NTRS)

1972-01-01

Proposed testing for the Agena tug program is based upon best estimates of shuttle and Agena tug requirements and upon the Agena configuration currently envisioned to meet these requirements. The proposed tests are presented in development, qualification, system, and launch base test plans. These plans are based upon generalized requirements and assumed situations. The limitations of this study precluded all but minimal consideration of related shuttle orbiter and shuttle ground systems. The test plans include provisions for all testing from major component to systems level, identified as necessary to aid in confirmation of the modified Agena configuration for the space tug; considerations that crew safety requirements and new environmental conditions from shuttle interface effects do impose some new Agena testing requirements; considerations that many existing Agena flight-qualified components will be utilized and qualification testing will be minimal; testing not only for the Agena tug but also for new or modified items of handling or servicing equipment for supporting the Agena factory-to-launch sequence; and the assembly of required testing into a sequence-ordered series of events.

Cerebellar activation during motor sequence learning is associated with subsequent transfer to new sequences.

PubMed

Shimizu, Renee E; Wu, Allan D; Knowlton, Barbara J

2016-12-01

Effective learning results not only in improved performance on a practiced task, but also in the ability to transfer the acquired knowledge to novel, similar tasks. Using a modified serial reaction time (RT) task, the authors examined the ability to transfer to novel sequences after practicing sequences in a repetitive order versus a nonrepeating interleaved order. Interleaved practice resulted in better performance on new sequences than repetitive practice. In a second study, participants practiced interleaved sequences in a functional MRI (fMRI) scanner and received a transfer test of novel sequences. Transfer ability was positively correlated with cerebellar blood oxygen level dependent activity during practice, indicating that greater cerebellar engagement during training resulted in better subsequent transfer performance. Interleaved practice may thus result in a more generalized representation that is robust to interference, and the degree of activation in the cerebellum may be a reflection of the instantiation and engagement of internal models. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Naked-eye fingerprinting of single nucleotide polymorphisms on psoriasis patients

NASA Astrophysics Data System (ADS)

Valentini, Paola; Marsella, Alessandra; Tarantino, Paolo; Mauro, Salvatore; Baglietto, Silvia; Congedo, Maurizio; Paolo Pompa, Pier

2016-05-01

We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics.We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02200f

NIH Toolbox Cognition Battery (NIHTB-CB): list sorting test to measure working memory.

PubMed

Tulsky, David S; Carlozzi, Noelle; Chiaravalloti, Nancy D; Beaumont, Jennifer L; Kisala, Pamela A; Mungas, Dan; Conway, Kevin; Gershon, Richard

2014-07-01

The List Sorting Working Memory Test was designed to assess working memory (WM) as part of the NIH Toolbox Cognition Battery. List Sorting is a sequencing task requiring children and adults to sort and sequence stimuli that are presented visually and auditorily. Validation data are presented for 268 participants ages 20 to 85 years. A subset of participants (N=89) was retested 7 to 21 days later. As expected, the List Sorting Test had moderately high correlations with other measures of working memory and executive functioning (convergent validity) but a low correlation with a test of receptive vocabulary (discriminant validity). Furthermore, List Sorting demonstrates expected changes over the age span and has excellent test-retest reliability. Collectively, these results provide initial support for the construct validity of the List Sorting Working Memory Measure as a measure of working memory. However, the relationship between the List Sorting Test and general executive function has yet to be determined.

NIH Toolbox Cognition Battery (NIHTB-CB): The List Sorting Test to Measure Working Memory

PubMed Central

Tulsky, David S.; Carlozzi, Noelle; Chiaravalloti, Nancy D.; Beaumont, Jennifer L.; Kisala, Pamela A.; Mungas, Dan; Conway, Kevin; Gershon, Richard

2015-01-01

The List Sorting Working Memory Test was designed to assess working memory (WM) as part of the NIH Toolbox Cognition Battery. List Sorting is a sequencing task requiring children and adults to sort and sequence stimuli that are presented visually and auditorily. Validation data are presented for 268 participants ages 20 to 85 years. A subset of participants (N=89) was retested 7 to 21 days later. As expected, the List Sorting Test had moderately high correlations with other measures of working memory and executive functioning (convergent validity) but a low correlation with a test of receptive vocabulary (discriminant validity). Furthermore, List Sorting demonstrates expected changes over the age span and has excellent test-retest reliability. Collectively, these results provide initial support the construct validity of the List Sorting Working Memory Measure as a measure of working memory. However, the relation between the List Sorting Test and general executive function has yet to be determined. PMID:24959983

40 CFR 92.105 - General equipment specifications.

Code of Federal Regulations, 2012 CFR

2012-07-01

... measurements is 1 cm per minute. (Higher chart speeds are required for smoke measurements during the acceleration phases of the test sequence.) (2) All chart recorders (analyzers, torque, rpm, etc.) shall be... which indicate 1 second intervals are required for smoke measurements during the acceleration phases of...

40 CFR 92.105 - General equipment specifications.

Code of Federal Regulations, 2013 CFR

2013-07-01

... measurements is 1 cm per minute. (Higher chart speeds are required for smoke measurements during the acceleration phases of the test sequence.) (2) All chart recorders (analyzers, torque, rpm, etc.) shall be... which indicate 1 second intervals are required for smoke measurements during the acceleration phases of...

40 CFR 92.105 - General equipment specifications.

Code of Federal Regulations, 2014 CFR

2014-07-01

... measurements is 1 cm per minute. (Higher chart speeds are required for smoke measurements during the acceleration phases of the test sequence.) (2) All chart recorders (analyzers, torque, rpm, etc.) shall be... which indicate 1 second intervals are required for smoke measurements during the acceleration phases of...

Virulence Studies of Different Sequence Types and Geographical Origins of Streptococcus suis Serotype 2 in a Mouse Model of Infection

PubMed Central

Auger, Jean-Philippe; Fittipaldi, Nahuel; Benoit-Biancamano, Marie-Odile; Segura, Mariela; Gottschalk, Marcelo

2016-01-01

Multilocus sequence typing previously identified three predominant sequence types (STs) of Streptococcus suis serotype 2: ST1 strains predominate in Eurasia while North American (NA) strains are generally ST25 and ST28. However, ST25/ST28 and ST1 strains have also been isolated in Asia and NA, respectively. Using a well-standardized mouse model of infection, the virulence of strains belonging to different STs and different geographical origins was evaluated. Results demonstrated that although a certain tendency may be observed, S. suis serotype 2 virulence is difficult to predict based on ST and geographical origin alone; strains belonging to the same ST presented important differences of virulence and did not always correlate with origin. The only exception appears to be NA ST28 strains, which were generally less virulent in both systemic and central nervous system (CNS) infection models. Persistent and high levels of bacteremia accompanied by elevated CNS inflammation are required to cause meningitis. Although widely used, in vitro tests such as phagocytosis and killing assays require further standardization in order to be used as predictive tests for evaluating virulence of strains. The use of strains other than archetypal strains has increased our knowledge and understanding of the S. suis serotype 2 population dynamics. PMID:27409640

A powerful and flexible approach to the analysis of RNA sequence count data

PubMed Central

Zhou, Yi-Hui; Xia, Kai; Wright, Fred A.

2011-01-01

Motivation: A number of penalization and shrinkage approaches have been proposed for the analysis of microarray gene expression data. Similar techniques are now routinely applied to RNA sequence transcriptional count data, although the value of such shrinkage has not been conclusively established. If penalization is desired, the explicit modeling of mean–variance relationships provides a flexible testing regimen that ‘borrows’ information across genes, while easily incorporating design effects and additional covariates. Results: We describe BBSeq, which incorporates two approaches: (i) a simple beta-binomial generalized linear model, which has not been extensively tested for RNA-Seq data and (ii) an extension of an expression mean–variance modeling approach to RNA-Seq data, involving modeling of the overdispersion as a function of the mean. Our approaches are flexible, allowing for general handling of discrete experimental factors and continuous covariates. We report comparisons with other alternate methods to handle RNA-Seq data. Although penalized methods have advantages for very small sample sizes, the beta-binomial generalized linear model, combined with simple outlier detection and testing approaches, appears to have favorable characteristics in power and flexibility. Availability: An R package containing examples and sample datasets is available at http://www.bios.unc.edu/research/genomic_software/BBSeq Contact: yzhou@bios.unc.edu; fwright@bios.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21810900

Spread Spectrum Receiver Electromagnetic Interference (EMI) Test Guide

NASA Technical Reports Server (NTRS)

Wheeler, Mark L.

1998-01-01

This program consisted of: (1) a study to define appropriate EMI test guidelines and test methods for direct sequence (DS) spread spectrum receivers; and (2) preparation of a written test guide to document the recommended test methods. The scope of this test guide includes: (1) a discussion of generic DS receiver performance characteristics; (2) a summary of S-band TDRSS receiver operation; (3) a discussion of DS receiver EMI susceptibility mechanisms and characteristics; (4) a summary of military standard test guidelines; (5) recommended test approach and methods; and (6) general conclusions and recommendations for future studies in the area of spread spectrum receiver testing.

Livestock-associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 in Humans, Canada

PubMed Central

Golding, George R.; Bryden, Louis; Levett, Paul N.; McDonald, Ryan R.; Wong, Alice; Wylie, John; Graham, Morag R.; Tyler, Shaun; Van Domselaar, Gary; Simor, Andrew E.; Gravel, Denise

2010-01-01

Rates of colonization with livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) sequence type 398 have been high for pigs and pig farmers in Canada, but prevalence rates for the general human population are unknown. In this study, 5 LA-MRSA isolates, 4 of which were obtained from skin and soft tissue infections, were identified from 3,687 tested MRSA isolates from persons in Manitoba and Saskatchewan, Canada. Further molecular characterization determined that these isolates all contained staphylococcal cassette chromosome (SCC) mecV, were negative for Panton-Valentine leukocidin, and were closely related by macrorestriction analysis with the restriction enzyme Cfr91. The complete DNA sequence of the SCCmec region from the isolate showed a novel subtype of SCCmecV harboring clustered regularly interspaced short palindromic repeats and associated genes. Although prevalence of livestock-associated MRSA seems to be low for the general population in Canada, recent emergence of infections resulting from this strain is of public health concern. PMID:20350371

Aging does not affect generalized postural motor learning in response to variable amplitude oscillations of the support surface.

PubMed

Van Ooteghem, Karen; Frank, James S; Allard, Fran; Horak, Fay B

2010-08-01

Postural motor learning for dynamic balance tasks has been demonstrated in healthy older adults (Van Ooteghem et al. in Exp Brain Res 199(2):185-193, 2009). The purpose of this study was to investigate the type of knowledge (general or specific) obtained with balance training in this age group and to examine whether embedding perturbation regularities within a balance task masks specific learning. Two groups of older adults maintained balance on a translating platform that oscillated with variable amplitude and constant frequency. One group was trained using an embedded-sequence (ES) protocol which contained the same 15-s sequence of variable amplitude oscillations in the middle of each trial. A second group was trained using a looped-sequence (LS) protocol which contained a 15-s sequence repeated three times to form each trial. All trials were 45 s. Participants were not informed of any repetition. To examine learning, participants performed a retention test following a 24-h delay. LS participants also completed a transfer task. Specificity of learning was examined by comparing performance for repeated versus random sequences (ES) and training versus transfer sequences (LS). Performance was measured by deriving spatial and temporal measures of whole body center of mass (COM) and trunk orientation. Both groups improved performance with practice as characterized by reduced COM displacement, improved COM-platform phase relationships, and decreased angular trunk motion. Furthermore, improvements reflected general rather than specific postural motor learning regardless of training protocol (ES or LS). This finding is similar to young adults (Van Ooteghem et al. in Exp Brain Res 187(4):603-611, 2008) and indicates that age does not influence the type of learning which occurs for balance control.

HIV-1 tropism testing in subjects achieving undetectable HIV-1 RNA: diagnostic accuracy, viral evolution and compartmentalization.

PubMed

Pou, Christian; Codoñer, Francisco M; Thielen, Alexander; Bellido, Rocío; Pérez-Álvarez, Susana; Cabrera, Cecilia; Dalmau, Judith; Curriu, Marta; Lie, Yolanda; Noguera-Julian, Marc; Puig, Jordi; Martínez-Picado, Javier; Blanco, Julià; Coakley, Eoin; Däumer, Martin; Clotet, Bonaventura; Paredes, Roger

2013-01-01

Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs). However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA <50 copies/mL during at least 2 years after first-line ART initiation. First, we determined the diagnostic accuracy of 454 and population sequencing of gp120 V3-loops in plasma and PBMCs, as well as of MT-2 assays before ART initiation. The Enhanced Sensitivity Trofile Assay (ESTA) was used as the technical reference standard. 454 sequencing of plasma viruses provided the highest agreement with ESTA. The accuracy of 454 sequencing decreased in PBMCs due to reduced specificity. Population sequencing in plasma and PBMCs was slightly less accurate than plasma 454 sequencing, being less sensitive but more specific. MT-2 assays had low sensitivity but 100% specificity. Then, we used optimized 454 sequence data to investigate viral evolution in PBMCs during viremia suppression and only found evolution of R5 viruses in one subject. No de novo CXCR4-using HIV-1 production was observed over time. Finally, Slatkin-Maddison tests suggested that plasma and cell-associated V3 forms were sometimes compartmentalized. The absence of tropism shifts during viremia suppression suggests that, when available, testing of stored plasma samples is generally safe and informative, provided that HIV-1 suppression is maintained. Tropism testing in PBMCs may not necessarily produce equivalent biological results to plasma, because the structure of viral populations and the diagnostic performance of tropism assays may sometimes vary between compartments. Thereby, proviral DNA tropism testing should be specifically validated in clinical trials before it can be applied to routine clinical decision-making.

Nonneutral mitochondrial DNA variation in humans and chimpanzees

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

Nachman, M.W.; Aquadro, C.F.; Brown, W.M.

1996-03-01

We sequenced the NADH dehydrogenase subunit 3 (ND3) gene from a sample of 61 humans, five common chimpanzees, and one gorilla to test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution. Within humans and within chimpanzees, the ratio of replacement to silent nucleotide substitutions was higher than observed in comparisons between species, contrary to neutral expectations. To test the generality of this result, we reanalyzed published human RFLP data from the entire mitochondrial genome. Gains of restriction sites relative to a known human mtDNA sequence were used to infer unambiguous nucleotide substitutions.more » We also compared the complete mtDNA sequences of three humans. Both the RFLP data and the sequence data reveal a higher ratio of replacement to silent nucleotide substitutions within humans than is seen between species. This pattern is observed at most or all human mitochondrial genes and is inconsistent with a strictly neutral model. These data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases. 59 refs., 2 figs., 8 tabs.« less

Measuring episodic memory across the lifespan: NIH Toolbox Picture Sequence Memory Test.

PubMed

Dikmen, Sureyya S; Bauer, Patricia J; Weintraub, Sandra; Mungas, Dan; Slotkin, Jerry; Beaumont, Jennifer L; Gershon, Richard; Temkin, Nancy R; Heaton, Robert K

2014-07-01

Episodic memory is one of the most important cognitive domains that involves acquiring, storing and recalling new information. In this article, we describe a new measure developed for the NIH Toolbox, called the Picture Sequence Memory Test (PSMT) that is the first to examine episodic memory across the age range from 3 to 85. We describe the development of the measure and present validation data for ages 20 to 85. The PSMT involves presentation of sequences of pictured objects and activities in a fixed order on a computer screen and simultaneously verbally described, that the participant must remember and then reproduce over three learning trials. The results indicate good test-retest reliability and construct validity. Performance is strongly related to well-established "gold standard" measures of episodic memory and, as expected, much less well correlated with those of a measure of vocabulary. It shows clear decline with aging in parallel with a gold standard summary measure and relates to several other demographic factors and to self-reported general health status. The PSMT appears to be a reliable and valid test of episodic memory for adults, a finding similar to those found for the same measure with children.

A Molecular-Based Approach for Examining Responses of Eukaryotes in Microcosms to Contaminant-Spiked Estuarine Sediments

EPA Science Inventory

Ecotoxicological information for most contaminants is limited to a small number of taxa, and these are generally restricted to comparatively hardy organisms that are readily extractable from test media and easily identifiable. Advances in DNA sequencing can now provide a comprehe...

40 CFR 86.1773-99 - Test sequence; general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... paragraph (c) of this section shall apply. For all hybrid electric vehicles and all 1995 and subsequent... required for fuel-flexible and dual-fuel vehicles when operating on gasoline. Natural gas, hybrid electric...) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES...

40 CFR 86.1530 - Test sequence; general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Emission Regulations for Otto-Cycle Heavy-Duty Engines, New Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Heavy-Duty Engines, New Otto-Cycle Light-Duty Trucks, and New Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Light-Duty Trucks; Idle...

A Next Generation Sequencing custom gene panel as first line diagnostic tool for atypical cases of syndromic obesity: Application in a case of Alström syndrome.

PubMed

Maltese, Paolo E; Iarossi, Giancarlo; Ziccardi, Lucia; Colombo, Leonardo; Buzzonetti, Luca; Crinò, Antonino; Tezzele, Silvia; Bertelli, Matteo

2018-02-01

Obesity phenotype can be manifested as an isolated trait or accompanied by multisystem disorders as part of a syndromic picture. In both situations, same molecular pathways may be involved to different degrees. This evidence is stronger in syndromic obesity, in which phenotypes of different syndromes may overlap. In these cases, genetic testing can unequivocally provide a final diagnosis. Here we describe a patient who met the diagnostic criteria for Alström syndrome only during adolescence. Genetic testing was requested at 25 years of age for a final confirmation of the diagnosis. The genetic diagnosis of Alström syndrome was obtained through a Next Generation Sequencing genetic test approach using a custom-designed gene panel of 47 genes associated with syndromic and non-syndromic obesity. Genetic analysis revealed a novel homozygous frameshift variant p.(Arg1550Lysfs*10) on exon 8 of the ALMS1 gene. This case shows the need for a revision of the diagnostic criteria guidelines, as a consequence of the recent advent of massive parallel sequencing technology. Indications for genetic testing reported in these currently accepted diagnostic criteria for Alström syndrome, were drafted when sequencing was expensive and time consuming. Nowadays, Next Generation Sequencing testing could be considered as first line diagnostic tool not only for Alström syndrome but, more generally, for all those atypical or not clearly distinguishable cases of syndromic obesity, thus avoiding delayed diagnosis and treatments. Early diagnosis permits a better follow-up and pre-symptomatic interventions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Local tests of gravitation with Gaia observations of Solar System Objects

NASA Astrophysics Data System (ADS)

Hees, Aurélien; Le Poncin-Lafitte, Christophe; Hestroffer, Daniel; David, Pedro

2018-04-01

In this proceeding, we show how observations of Solar System Objects with Gaia can be used to test General Relativity and to constrain modified gravitational theories. The high number of Solar System objects observed and the variety of their orbital parameters associated with the impressive astrometric accuracy will allow us to perform local tests of General Relativity. In this communication, we present a preliminary sensitivity study of the Gaia observations on dynamical parameters such as the Sun quadrupolar moment and on various extensions to general relativity such as the parametrized post-Newtonian parameters, the fifth force formalism and a violation of Lorentz symmetry parametrized by the Standard-Model extension framework. We take into account the time sequences and the geometry of the observations that are particular to Gaia for its nominal mission (5 years) and for an extended mission (10 years).

DNA Barcoding analysis of seafood accuracy in Washington, D.C. restaurants

PubMed Central

Stern, David B.; Castro Nallar, Eduardo; Rathod, Jason

2017-01-01

In Washington D.C., recent legislation authorizes citizens to test if products are properly represented and, if they are not, to bring a lawsuit for the benefit of the general public. Recent studies revealing the widespread phenomenon of seafood substitution across the United States make it a fertile area for consumer protection testing. DNA barcoding provides an accurate and cost-effective way to perform these tests, especially when tissue alone is available making species identification based on morphology impossible. In this study, we sequenced the 5′ barcoding region of the Cytochrome Oxidase I gene for 12 samples of vertebrate and invertebrate food items across six restaurants in Washington, D.C. and used multiple analytical methods to make identifications. These samples included several ambiguous menu listings, sequences with little genetic variation among closely related species and one sequence with no available reference sequence. Despite these challenges, we were able to make identifications for all samples and found that 33% were potentially mislabeled. While we found a high degree of mislabeling, the errors involved closely related species and we did not identify egregious substitutions as have been found in other cities. This study highlights the efficacy of DNA barcoding and robust analyses in identifying seafood items for consumer protection. PMID:28462038

Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing

PubMed Central

Walsh, Tom; Lee, Ming K.; Casadei, Silvia; Thornton, Anne M.; Stray, Sunday M.; Pennil, Christopher; Nord, Alex S.; Mandell, Jessica B.; Swisher, Elizabeth M.; King, Mary-Claire

2010-01-01

Inherited loss-of-function mutations in the tumor suppressor genes BRCA1, BRCA2, and multiple other genes predispose to high risks of breast and/or ovarian cancer. Cancer-associated inherited mutations in these genes are collectively quite common, but individually rare or even private. Genetic testing for BRCA1 and BRCA2 mutations has become an integral part of clinical practice, but testing is generally limited to these two genes and to women with severe family histories of breast or ovarian cancer. To determine whether massively parallel, “next-generation” sequencing would enable accurate, thorough, and cost-effective identification of inherited mutations for breast and ovarian cancer, we developed a genomic assay to capture, sequence, and detect all mutations in 21 genes, including BRCA1 and BRCA2, with inherited mutations that predispose to breast or ovarian cancer. Constitutional genomic DNA from subjects with known inherited mutations, ranging in size from 1 to >100,000 bp, was hybridized to custom oligonucleotides and then sequenced using a genome analyzer. Analysis was carried out blind to the mutation in each sample. Average coverage was >1200 reads per base pair. After filtering sequences for quality and number of reads, all single-nucleotide substitutions, small insertion and deletion mutations, and large genomic duplications and deletions were detected. There were zero false-positive calls of nonsense mutations, frameshift mutations, or genomic rearrangements for any gene in any of the test samples. This approach enables widespread genetic testing and personalized risk assessment for breast and ovarian cancer. PMID:20616022

Flexible, fast and accurate sequence alignment profiling on GPGPU with PaSWAS.

PubMed

Warris, Sven; Yalcin, Feyruz; Jackson, Katherine J L; Nap, Jan Peter

2015-01-01

To obtain large-scale sequence alignments in a fast and flexible way is an important step in the analyses of next generation sequencing data. Applications based on the Smith-Waterman (SW) algorithm are often either not fast enough, limited to dedicated tasks or not sufficiently accurate due to statistical issues. Current SW implementations that run on graphics hardware do not report the alignment details necessary for further analysis. With the Parallel SW Alignment Software (PaSWAS) it is possible (a) to have easy access to the computational power of NVIDIA-based general purpose graphics processing units (GPGPUs) to perform high-speed sequence alignments, and (b) retrieve relevant information such as score, number of gaps and mismatches. The software reports multiple hits per alignment. The added value of the new SW implementation is demonstrated with two test cases: (1) tag recovery in next generation sequence data and (2) isotype assignment within an immunoglobulin 454 sequence data set. Both cases show the usability and versatility of the new parallel Smith-Waterman implementation.

Using variable rate models to identify genes under selection in sequence pairs: their validity and limitations for EST sequences.

PubMed

Church, Sheri A; Livingstone, Kevin; Lai, Zhao; Kozik, Alexander; Knapp, Steven J; Michelmore, Richard W; Rieseberg, Loren H

2007-02-01

Using likelihood-based variable selection models, we determined if positive selection was acting on 523 EST sequence pairs from two lineages of sunflower and lettuce. Variable rate models are generally not used for comparisons of sequence pairs due to the limited information and the inaccuracy of estimates of specific substitution rates. However, previous studies have shown that the likelihood ratio test (LRT) is reliable for detecting positive selection, even with low numbers of sequences. These analyses identified 56 genes that show a signature of selection, of which 75% were not identified by simpler models that average selection across codons. Subsequent mapping studies in sunflower show four of five of the positively selected genes identified by these methods mapped to domestication QTLs. We discuss the validity and limitations of using variable rate models for comparisons of sequence pairs, as well as the limitations of using ESTs for identification of positively selected genes.

A generalized global alignment algorithm.

PubMed

Huang, Xiaoqiu; Chao, Kun-Mao

2003-01-22

Homologous sequences are sometimes similar over some regions but different over other regions. Homologous sequences have a much lower global similarity if the different regions are much longer than the similar regions. We present a generalized global alignment algorithm for comparing sequences with intermittent similarities, an ordered list of similar regions separated by different regions. A generalized global alignment model is defined to handle sequences with intermittent similarities. A dynamic programming algorithm is designed to compute an optimal general alignment in time proportional to the product of sequence lengths and in space proportional to the sum of sequence lengths. The algorithm is implemented as a computer program named GAP3 (Global Alignment Program Version 3). The generalized global alignment model is validated by experimental results produced with GAP3 on both DNA and protein sequences. The GAP3 program extends the ability of standard global alignment programs to recognize homologous sequences of lower similarity. The GAP3 program is freely available for academic use at http://bioinformatics.iastate.edu/aat/align/align.html.

A functional U-statistic method for association analysis of sequencing data.

PubMed

Jadhav, Sneha; Tong, Xiaoran; Lu, Qing

2017-11-01

Although sequencing studies hold great promise for uncovering novel variants predisposing to human diseases, the high dimensionality of the sequencing data brings tremendous challenges to data analysis. Moreover, for many complex diseases (e.g., psychiatric disorders) multiple related phenotypes are collected. These phenotypes can be different measurements of an underlying disease, or measurements characterizing multiple related diseases for studying common genetic mechanism. Although jointly analyzing these phenotypes could potentially increase the power of identifying disease-associated genes, the different types of phenotypes pose challenges for association analysis. To address these challenges, we propose a nonparametric method, functional U-statistic method (FU), for multivariate analysis of sequencing data. It first constructs smooth functions from individuals' sequencing data, and then tests the association of these functions with multiple phenotypes by using a U-statistic. The method provides a general framework for analyzing various types of phenotypes (e.g., binary and continuous phenotypes) with unknown distributions. Fitting the genetic variants within a gene using a smoothing function also allows us to capture complexities of gene structure (e.g., linkage disequilibrium, LD), which could potentially increase the power of association analysis. Through simulations, we compared our method to the multivariate outcome score test (MOST), and found that our test attained better performance than MOST. In a real data application, we apply our method to the sequencing data from Minnesota Twin Study (MTS) and found potential associations of several nicotine receptor subunit (CHRN) genes, including CHRNB3, associated with nicotine dependence and/or alcohol dependence. © 2017 WILEY PERIODICALS, INC.

DIFFERENCES IN THE STRUCTURE AND FUNCTION OF FATHEAD MINNOW AND HUMAN ERA: IMPLICATIONS FOR IN VITRO TESTING OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Mammalian receptors and assay systems are generally used for in vitro analysis of endocrine disrupting chemicals (EDC) with the assumption that minor differences in amino acid sequences among species do not translate into significant differences in receptor function. We have fou...

[Hydrophidae identification through analysis on Cyt b gene barcode].

PubMed

Liao, Li-xi; Zeng, Ke-wu; Tu, Peng-fei

2015-08-01

Hydrophidae, one of the precious traditional Chinese medicines, is generally drily preserved to prevent corruption, but it is hard to identify the species of Hydrophidae through the appearance because of the change due to the drying process. The identification through analysis on gene barcode, a new technique in species identification, can avoid the problem. The gene barcodes of the 6 species of Hydrophidae like Lapemis hardwickii were aquired through DNA extraction and gene sequencing. These barcodes were then in sequence alignment and test the identification efficency by BLAST. Our results revealed that the barcode sequences performed high identification efficiency, and had obvious difference between intra- and inter-species. These all indicated that Cyt b DNA barcoding can confirm the Hydrophidae identification.

Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder.

PubMed

Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

2015-01-01

Healthy sleep is essential in children's cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain.

Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder

PubMed Central

Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

2016-01-01

Healthy sleep is essential in children’s cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain. PMID:26793090

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

PubMed

Yu, Stephanie C Y; Chan, K C Allen; Zheng, Yama W L; Jiang, Peiyong; Liao, Gary J W; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y; Go, Attie T J I; van Vugt, John M G; Minekawa, Ryoko; Oudejans, Cees B M; Nicolaides, Kypros H; Chiu, Rossa W K; Lo, Y M Dennis

2014-06-10

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing

PubMed Central

Yu, Stephanie C. Y.; Chan, K. C. Allen; Zheng, Yama W. L.; Jiang, Peiyong; Liao, Gary J. W.; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y.; Go, Attie T. J. I.; van Vugt, John M. G.; Minekawa, Ryoko; Oudejans, Cees B. M.; Nicolaides, Kypros H.; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2014-01-01

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring. PMID:24843150

A proteomic approach for studying insect phylogeny: CAPA peptides of ancient insect taxa (Dictyoptera, Blattoptera) as a test case

PubMed Central

Roth, Steffen; Fromm, Bastian; Gäde, Gerd; Predel, Reinhard

2009-01-01

Background Neuropeptide ligands have to fit exactly into their respective receptors and thus the evolution of the coding regions of their genes is constrained and may be strongly conserved. As such, they may be suitable for the reconstruction of phylogenetic relationships within higher taxa. CAPA peptides of major lineages of cockroaches (Blaberidae, Blattellidae, Blattidae, Polyphagidae, Cryptocercidae) and of the termite Mastotermes darwiniensis were chosen to test the above hypothesis. The phylogenetic relationships within various groups of the taxon Dictyoptera (praying mantids, termites and cockroaches) are still highly disputed. Results Tandem mass spectrometry of neuropeptides from perisympathetic organs was used to obtain sequence data of CAPA peptides from single specimens; the data were analysed by Maximum Parsimony and Bayesian Interference. The resulting cladograms, taking 61 species into account, show a topology which is in general agreement with recent molecular and morphological phylogenetic analyses, including the recent phylogenetic arrangement placing termites within the cockroaches. When sequence data sets from other neuropeptides, viz. adipokinetic hormones and sulfakinins, were included, the general topology of the cladogram did not change but bootstrap values increased considerably. Conclusion This study represents the first comprehensive survey of neuropeptides of insects for solely phylogenetic purposes and concludes that sequences of short neuropeptides are suitable to complement molecular biological and morphological data for the reconstruction of phylogenetic relationships. PMID:19257902

Development of a general method for detection and quantification of the P35S promoter based on assessment of existing methods

PubMed Central

Wu, Yuhua; Wang, Yulei; Li, Jun; Li, Wei; Zhang, Li; Li, Yunjing; Li, Xiaofei; Li, Jun; Zhu, Li; Wu, Gang

2014-01-01

The Cauliflower mosaic virus (CaMV) 35S promoter (P35S) is a commonly used target for detection of genetically modified organisms (GMOs). There are currently 24 reported detection methods, targeting different regions of the P35S promoter. Initial assessment revealed that due to the absence of primer binding sites in the P35S sequence, 19 of the 24 reported methods failed to detect P35S in MON88913 cotton, and the other two methods could only be applied to certain GMOs. The rest three reported methods were not suitable for measurement of P35S in some testing events, because SNPs in binding sites of the primer/probe would result in abnormal amplification plots and poor linear regression parameters. In this study, we discovered a conserved region in the P35S sequence through sequencing of P35S promoters from multiple transgenic events, and developed new qualitative and quantitative detection systems targeting this conserved region. The qualitative PCR could detect the P35S promoter in 23 unique GMO events with high specificity and sensitivity. The quantitative method was suitable for measurement of P35S promoter, exhibiting good agreement between the amount of template and Ct values for each testing event. This study provides a general P35S screening method, with greater coverage than existing methods. PMID:25483893

Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.

PubMed

Smith, Colin A; Kortemme, Tanja

2011-01-01

Predicting the set of sequences that are tolerated by a protein or protein interface, while maintaining a desired function, is useful for characterizing protein interaction specificity and for computationally designing sequence libraries to engineer proteins with new functions. Here we provide a general method, a detailed set of protocols, and several benchmarks and analyses for estimating tolerated sequences using flexible backbone protein design implemented in the Rosetta molecular modeling software suite. The input to the method is at least one experimentally determined three-dimensional protein structure or high-quality model. The starting structure(s) are expanded or refined into a conformational ensemble using Monte Carlo simulations consisting of backrub backbone and side chain moves in Rosetta. The method then uses a combination of simulated annealing and genetic algorithm optimization methods to enrich for low-energy sequences for the individual members of the ensemble. To emphasize certain functional requirements (e.g. forming a binding interface), interactions between and within parts of the structure (e.g. domains) can be reweighted in the scoring function. Results from each backbone structure are merged together to create a single estimate for the tolerated sequence space. We provide an extensive description of the protocol and its parameters, all source code, example analysis scripts and three tests applying this method to finding sequences predicted to stabilize proteins or protein interfaces. The generality of this method makes many other applications possible, for example stabilizing interactions with small molecules, DNA, or RNA. Through the use of within-domain reweighting and/or multistate design, it may also be possible to use this method to find sequences that stabilize particular protein conformations or binding interactions over others.

On the sum of generalized Fibonacci sequence

NASA Astrophysics Data System (ADS)

Chong, Chin-Yoon; Ho, C. K.

2014-06-01

We consider the generalized Fibonacci sequence {Un defined by U0 = 0, U1 = 1, and Un+2 = pUn+1+qUn for all n∈Z0+ and p, q∈Z+. In this paper, we derived various sums of the generalized Fibonacci sequence from their recursive relations.

Apollo experience report: Launch escape propulsion subsystem

NASA Technical Reports Server (NTRS)

Townsend, N. A.

1973-01-01

The Apollo launch escape propulsion subsystem contained three solid rocket motors. The general design, development, and qualification of the solid-propellant pitch-control, tower-jettison, and launch-escape motors of the Apollo launch escape propulsion subsystem were completed during years 1961 to 1966. The launch escape system components are described in general terms, and the sequence of events through the ground-based test programs and flight-test programs is discussed. The initial ground rules established for this system were that it should use existing technology and designs as much as possible. The practicality of this decision is proved by the minimum number of problems that were encountered during the development and qualification program.

Using structure to explore the sequence alignment space of remote homologs.

PubMed

Kuziemko, Andrew; Honig, Barry; Petrey, Donald

2011-10-01

Protein structure modeling by homology requires an accurate sequence alignment between the query protein and its structural template. However, sequence alignment methods based on dynamic programming (DP) are typically unable to generate accurate alignments for remote sequence homologs, thus limiting the applicability of modeling methods. A central problem is that the alignment that is "optimal" in terms of the DP score does not necessarily correspond to the alignment that produces the most accurate structural model. That is, the correct alignment based on structural superposition will generally have a lower score than the optimal alignment obtained from sequence. Variations of the DP algorithm have been developed that generate alternative alignments that are "suboptimal" in terms of the DP score, but these still encounter difficulties in detecting the correct structural alignment. We present here a new alternative sequence alignment method that relies heavily on the structure of the template. By initially aligning the query sequence to individual fragments in secondary structure elements and combining high-scoring fragments that pass basic tests for "modelability", we can generate accurate alignments within a small ensemble. Our results suggest that the set of sequences that can currently be modeled by homology can be greatly extended.

Oncogenic Human Papillomavirus (HPV) Type Distribution and HPV Type 16 E6 Variants in Two Spanish Population Groups with Different Levels of HPV Infection Risk

PubMed Central

Ortiz, M.; Torres, M.; Muñoz, L.; Fernández-García, E.; Canals, J.; Cabornero, A. I.; Aguilar, E.; Ballesteros, J.; del Amo, J.; García-Sáiz, A.

2006-01-01

The aim of this study is to determine oncogenic human papillomavirus (HPV) types and HPV type 16 (HPV16) variant distribution in two Spanish population groups, commercial sex workers and imprisoned women (CSW/IPW) and the general population. A multicenter cross-sectional study of 1,889 women from five clinical settings in two Spanish cities was conducted from May to November 2004. Oncogenic HPV infection was tested by an Hybrid Capture II (HC2) test, and positive samples were genotyped by direct sequencing using three different primer sets in L1 (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was the most frequent type. Distinct profiles of oncogenic HPV type prevalence were observed across the two populations. In order of decreasing frequency, HPV types 16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31, 52, 68, 51, and 53 were most frequent in the general population. We analyzed HPV16 intratype variants, and a large majority (78.7%) belonged to the European lineage. AA variants were detected in 16.0% of cases. African variants belonging to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16 intratype variants are involved in oncogenic HPV infections in our population. These results suggest that HPV type distribution differs in CSW/IPW women and in the general population, although further analysis is necessary. PMID:16597872

Oncogenic human papillomavirus (HPV) type distribution and HPV type 16 E6 variants in two Spanish population groups with different levels of HPV infection risk.

PubMed

Ortiz, M; Torres, M; Muñoz, L; Fernández-García, E; Canals, J; Cabornero, A I; Aguilar, E; Ballesteros, J; Del Amo, J; García-Sáiz, A

2006-04-01

The aim of this study is to determine oncogenic human papillomavirus (HPV) types and HPV type 16 (HPV16) variant distribution in two Spanish population groups, commercial sex workers and imprisoned women (CSW/IPW) and the general population. A multicenter cross-sectional study of 1,889 women from five clinical settings in two Spanish cities was conducted from May to November 2004. Oncogenic HPV infection was tested by an Hybrid Capture II (HC2) test, and positive samples were genotyped by direct sequencing using three different primer sets in L1 (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was the most frequent type. Distinct profiles of oncogenic HPV type prevalence were observed across the two populations. In order of decreasing frequency, HPV types 16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31, 52, 68, 51, and 53 were most frequent in the general population. We analyzed HPV16 intratype variants, and a large majority (78.7%) belonged to the European lineage. AA variants were detected in 16.0% of cases. African variants belonging to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16 intratype variants are involved in oncogenic HPV infections in our population. These results suggest that HPV type distribution differs in CSW/IPW women and in the general population, although further analysis is necessary.

Correcting for sequencing error in maximum likelihood phylogeny inference.

PubMed

Kuhner, Mary K; McGill, James

2014-11-04

Accurate phylogenies are critical to taxonomy as well as studies of speciation processes and other evolutionary patterns. Accurate branch lengths in phylogenies are critical for dating and rate measurements. Such accuracy may be jeopardized by unacknowledged sequencing error. We use simulated data to test a correction for DNA sequencing error in maximum likelihood phylogeny inference. Over a wide range of data polymorphism and true error rate, we found that correcting for sequencing error improves recovery of the branch lengths, even if the assumed error rate is up to twice the true error rate. Low error rates have little effect on recovery of the topology. When error is high, correction improves topological inference; however, when error is extremely high, using an assumed error rate greater than the true error rate leads to poor recovery of both topology and branch lengths. The error correction approach tested here was proposed in 2004 but has not been widely used, perhaps because researchers do not want to commit to an estimate of the error rate. This study shows that correction with an approximate error rate is generally preferable to ignoring the issue. Copyright © 2014 Kuhner and McGill.

Music and language perception: expectations, structural integration, and cognitive sequencing.

PubMed

Tillmann, Barbara

2012-10-01

Music can be described as sequences of events that are structured in pitch and time. Studying music processing provides insight into how complex event sequences are learned, perceived, and represented by the brain. Given the temporal nature of sound, expectations, structural integration, and cognitive sequencing are central in music perception (i.e., which sounds are most likely to come next and at what moment should they occur?). This paper focuses on similarities in music and language cognition research, showing that music cognition research provides insight into the understanding of not only music processing but also language processing and the processing of other structured stimuli. The hypothesis of shared resources between music and language processing and of domain-general dynamic attention has motivated the development of research to test music as a means to stimulate sensory, cognitive, and motor processes. Copyright © 2012 Cognitive Science Society, Inc.

Genome-wide mapping of autonomous promoter activity in human cells

PubMed Central

van Arensbergen, Joris; FitzPatrick, Vincent D.; de Haas, Marcel; Pagie, Ludo; Sluimer, Jasper; Bussemaker, Harmen J.; van Steensel, Bas

2017-01-01

Previous methods to systematically characterize sequence-intrinsic activity of promoters have been limited by relatively low throughput and the length of sequences that could be tested. Here we present Survey of Regulatory Elements (SuRE), a method to assay more than 108 DNA fragments, each 0.2–2kb in size, for their ability to drive transcription autonomously. In SuRE, a plasmid library is constructed of random genomic fragments upstream of a 20bp barcode and decoded by paired-end sequencing. This library is then transfected into cells and transcribed barcodes are quantified in the RNA by high throughput sequencing. When applied to the human genome, we achieved a 55-fold genome coverage, allowing us to map autonomous promoter activity genome-wide. By computational modeling we delineated subregions within promoters that are relevant for their activity. For instance, we show that antisense promoter transcription is generally dependent on the sense core promoter sequences, and that most enhancers and several families of repetitive elements act as autonomous transcription initiation sites. PMID:28024146

The role of consolidation in learning context-dependent phonotactic patterns in speech and digital sequence production.

PubMed

Anderson, Nathaniel D; Dell, Gary S

2018-04-03

Speakers implicitly learn novel phonotactic patterns by producing strings of syllables. The learning is revealed in their speech errors. First-order patterns, such as "/f/ must be a syllable onset," can be distinguished from contingent, or second-order, patterns, such as "/f/ must be an onset if the vowel is /a/, but a coda if the vowel is /o/." A metaanalysis of 19 experiments clearly demonstrated that first-order patterns affect speech errors to a very great extent in a single experimental session, but second-order vowel-contingent patterns only affect errors on the second day of testing, suggesting the need for a consolidation period. Two experiments tested an analogue to these studies involving sequences of button pushes, with fingers as "consonants" and thumbs as "vowels." The button-push errors revealed two of the key speech-error findings: first-order patterns are learned quickly, but second-order thumb-contingent patterns are only strongly revealed in the errors on the second day of testing. The influence of computational complexity on the implicit learning of phonotactic patterns in speech production may be a general feature of sequence production.

Correlation between MCAT Biology Content Specifications and Topic Scope and Sequence of General Education College Biology Textbooks

ERIC Educational Resources Information Center

Rissing, Steven W.

2013-01-01

Most American colleges and universities offer gateway biology courses to meet the needs of three undergraduate audiences: biology and related science majors, many of whom will become biomedical researchers; premedical students meeting medical school requirements and preparing for the Medical College Admissions Test (MCAT); and students completing…

Contribution of Implicit Sequence Learning to Spoken Language Processing: Some Preliminary Findings with Hearing Adults

ERIC Educational Resources Information Center

Conway, Christopher M.; Karpicke, Jennifer; Pisoni, David B.

2007-01-01

Spoken language consists of a complex, sequentially arrayed signal that contains patterns that can be described in terms of statistical relations among language units. Previous research has suggested that a domain-general ability to learn structured sequential patterns may underlie language acquisition. To test this prediction, we examined the…

Anomaly Detection in Large Sets of High-Dimensional Symbol Sequences

NASA Technical Reports Server (NTRS)

Budalakoti, Suratna; Srivastava, Ashok N.; Akella, Ram; Turkov, Eugene

2006-01-01

This paper addresses the problem of detecting and describing anomalies in large sets of high-dimensional symbol sequences. The approach taken uses unsupervised clustering of sequences using the normalized longest common subsequence (LCS) as a similarity measure, followed by detailed analysis of outliers to detect anomalies. As the LCS measure is expensive to compute, the first part of the paper discusses existing algorithms, such as the Hunt-Szymanski algorithm, that have low time-complexity. We then discuss why these algorithms often do not work well in practice and present a new hybrid algorithm for computing the LCS that, in our tests, outperforms the Hunt-Szymanski algorithm by a factor of five. The second part of the paper presents new algorithms for outlier analysis that provide comprehensible indicators as to why a particular sequence was deemed to be an outlier. The algorithms provide a coherent description to an analyst of the anomalies in the sequence, compared to more normal sequences. The algorithms we present are general and domain-independent, so we discuss applications in related areas such as anomaly detection.

Identifying functionally informative evolutionary sequence profiles.

PubMed

Gil, Nelson; Fiser, Andras

2018-04-15

Multiple sequence alignments (MSAs) can provide essential input to many bioinformatics applications, including protein structure prediction and functional annotation. However, the optimal selection of sequences to obtain biologically informative MSAs for such purposes is poorly explored, and has traditionally been performed manually. We present Selection of Alignment by Maximal Mutual Information (SAMMI), an automated, sequence-based approach to objectively select an optimal MSA from a large set of alternatives sampled from a general sequence database search. The hypothesis of this approach is that the mutual information among MSA columns will be maximal for those MSAs that contain the most diverse set possible of the most structurally and functionally homogeneous protein sequences. SAMMI was tested to select MSAs for functional site residue prediction by analysis of conservation patterns on a set of 435 proteins obtained from protein-ligand (peptides, nucleic acids and small substrates) and protein-protein interaction databases. Availability and implementation: A freely accessible program, including source code, implementing SAMMI is available at https://github.com/nelsongil92/SAMMI.git. andras.fiser@einstein.yu.edu. Supplementary data are available at Bioinformatics online.

Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies

PubMed Central

2010-01-01

Background All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences. Results The average accuracy based on leave-one-out (LOO) cross validation of a Bayesian classifier generated from 143 amyloidogenic sequences is 60.84%. This is consistent with the average accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non-amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08% when the training set is augmented by the holdout test set. In comparison, the average classification accuracy for the holdout test set obtained using a decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian classifier, depending on the training set size. The accuracy for the holdout test set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is 75.00%. Conclusions This exploratory study indicates that both classification methods may be promising in providing straightforward predictions on the amyloidogenicity of a sequence. Nevertheless, the number of available sequences that satisfy the premises of this study are limited, and are consequently smaller than the ideal training set size. Increasing the size of the training set clearly increases the accuracy, and the expansion of the training set to include not only more derivatives, but more alignments, would make the method more sound. The accuracy of the classifiers may also be improved when additional factors, such as structural and physico-chemical data, are considered. The development of this type of classifier has significant applications in evaluating engineered antibodies, and may be adapted for evaluating engineered proteins in general. PMID:20144194

Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies.

PubMed

David, Maria Pamela C; Concepcion, Gisela P; Padlan, Eduardo A

2010-02-08

All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences. The average accuracy based on leave-one-out (LOO) cross validation of a Bayesian classifier generated from 143 amyloidogenic sequences is 60.84%. This is consistent with the average accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non-amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08% when the training set is augmented by the holdout test set. In comparison, the average classification accuracy for the holdout test set obtained using a decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian classifier, depending on the training set size. The accuracy for the holdout test set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is 75.00%. This exploratory study indicates that both classification methods may be promising in providing straightforward predictions on the amyloidogenicity of a sequence. Nevertheless, the number of available sequences that satisfy the premises of this study are limited, and are consequently smaller than the ideal training set size. Increasing the size of the training set clearly increases the accuracy, and the expansion of the training set to include not only more derivatives, but more alignments, would make the method more sound. The accuracy of the classifiers may also be improved when additional factors, such as structural and physico-chemical data, are considered. The development of this type of classifier has significant applications in evaluating engineered antibodies, and may be adapted for evaluating engineered proteins in general.

Sequence Factorial and Its Applications

ERIC Educational Resources Information Center

Asiru, Muniru A.

2012-01-01

In this note, we introduce sequence factorial and use this to study generalized M-bonomial coefficients. For the sequence of natural numbers, the twin concepts of sequence factorial and generalized M-bonomial coefficients, respectively, extend the corresponding concepts of factorial of an integer and binomial coefficients. Some latent properties…

Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics.

PubMed

Dutheil, Julien; Gaillard, Sylvain; Bazin, Eric; Glémin, Sylvain; Ranwez, Vincent; Galtier, Nicolas; Belkhir, Khalid

2006-04-04

A large number of bioinformatics applications in the fields of bio-sequence analysis, molecular evolution and population genetics typically share input/output methods, data storage requirements and data analysis algorithms. Such common features may be conveniently bundled into re-usable libraries, which enable the rapid development of new methods and robust applications. We present Bio++, a set of Object Oriented libraries written in C++. Available components include classes for data storage and handling (nucleotide/amino-acid/codon sequences, trees, distance matrices, population genetics datasets), various input/output formats, basic sequence manipulation (concatenation, transcription, translation, etc.), phylogenetic analysis (maximum parsimony, markov models, distance methods, likelihood computation and maximization), population genetics/genomics (diversity statistics, neutrality tests, various multi-locus analyses) and various algorithms for numerical calculus. Implementation of methods aims at being both efficient and user-friendly. A special concern was given to the library design to enable easy extension and new methods development. We defined a general hierarchy of classes that allow the developer to implement its own algorithms while remaining compatible with the rest of the libraries. Bio++ source code is distributed free of charge under the CeCILL general public licence from its website http://kimura.univ-montp2.fr/BioPP.

Accelerated probabilistic inference of RNA structure evolution

PubMed Central

Holmes, Ian

2005-01-01

Background Pairwise stochastic context-free grammars (Pair SCFGs) are powerful tools for evolutionary analysis of RNA, including simultaneous RNA sequence alignment and secondary structure prediction, but the associated algorithms are intensive in both CPU and memory usage. The same problem is faced by other RNA alignment-and-folding algorithms based on Sankoff's 1985 algorithm. It is therefore desirable to constrain such algorithms, by pre-processing the sequences and using this first pass to limit the range of structures and/or alignments that can be considered. Results We demonstrate how flexible classes of constraint can be imposed, greatly reducing the computational costs while maintaining a high quality of structural homology prediction. Any score-attributed context-free grammar (e.g. energy-based scoring schemes, or conditionally normalized Pair SCFGs) is amenable to this treatment. It is now possible to combine independent structural and alignment constraints of unprecedented general flexibility in Pair SCFG alignment algorithms. We outline several applications to the bioinformatics of RNA sequence and structure, including Waterman-Eggert N-best alignments and progressive multiple alignment. We evaluate the performance of the algorithm on test examples from the RFAM database. Conclusion A program, Stemloc, that implements these algorithms for efficient RNA sequence alignment and structure prediction is available under the GNU General Public License. PMID:15790387

Tests of selection in pooled case-control data: an empirical study.

PubMed

Udpa, Nitin; Zhou, Dan; Haddad, Gabriel G; Bafna, Vineet

2011-01-01

For smaller organisms with faster breeding cycles, artificial selection can be used to create sub-populations with different phenotypic traits. Genetic tests can be employed to identify the causal markers for the phenotypes, as a precursor to engineering strains with a combination of traits. Traditional approaches involve analyzing crosses of inbred strains to test for co-segregation with genetic markers. Here we take advantage of cheaper next generation sequencing techniques to identify genetic signatures of adaptation to the selection constraints. Obtaining individual sequencing data is often unrealistic due to cost and sample issues, so we focus on pooled genomic data. We explore a series of statistical tests for selection using pooled case (under selection) and control populations. The tests generally capture skews in the scaled frequency spectrum of alleles in a region, which are indicative of a selective sweep. Extensive simulations are used to show that these approaches work well for a wide range of population divergence times and strong selective pressures. Control vs control simulations are used to determine an empirical False Positive Rate, and regions under selection are determined using a 1% FPR level. We show that pooling does not have a significant impact on statistical power. The tests are also robust to reasonable variations in several different parameters, including window size, base-calling error rate, and sequencing coverage. We then demonstrate the viability (and the challenges) of one of these methods in two independent Drosophila populations (Drosophila melanogaster) bred under selection for hypoxia and accelerated development, respectively. Testing for extreme hypoxia tolerance showed clear signals of selection, pointing to loci that are important for hypoxia adaptation. Overall, we outline a strategy for finding regions under selection using pooled sequences, then devise optimal tests for that strategy. The approaches show promise for detecting selection, even several generations after fixation of the beneficial allele has occurred.

Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants

PubMed Central

Danziger, Samuel A.; Swamidass, S. Joshua; Zeng, Jue; Dearth, Lawrence R.; Lu, Qiang; Chen, Jonathan H.; Cheng, Jainlin; Hoang, Vinh P.; Saigo, Hiroto; Luo, Ray; Baldi, Pierre; Brachmann, Rainer K.; Lathrop, Richard H.

2009-01-01

Many biomedical problems relate to mutant functional properties across a sequence space of interest, e.g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 rescue. We devised a general methodology for conducting a functional census of a mutation sequence space, and conducted a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of 3. Double-blind predictive accuracy (15-point moving window) rose from 47% to 86% over the trial (r = 0.74). Code and data are available upon request1. PMID:17048398

Use of tuf Sequences for Genus-Specific PCR Detection and Phylogenetic Analysis of 28 Streptococcal Species

PubMed Central

Picard, François J.; Ke, Danbing; Boudreau, Dominique K.; Boissinot, Maurice; Huletsky, Ann; Richard, Dave; Ouellette, Marc; Roy, Paul H.; Bergeron, Michel G.

2004-01-01

A 761-bp portion of the tuf gene (encoding the elongation factor Tu) from 28 clinically relevant streptococcal species was obtained by sequencing amplicons generated using broad-range PCR primers. These tuf sequences were used to select Streptococcus-specific PCR primers and to perform phylogenetic analysis. The specificity of the PCR assay was verified using 102 different bacterial species, including the 28 streptococcal species. Genomic DNA purified from all streptococcal species was efficiently detected, whereas there was no amplification with DNA from 72 of the 74 nonstreptococcal bacterial species tested. There was cross-amplification with DNAs from Enterococcus durans and Lactococcus lactis. However, the 15 to 31% nucleotide sequence divergence in the 761-bp tuf portion of these two species compared to any streptococcal tuf sequence provides ample sequence divergence to allow the development of internal probes specific to streptococci. The Streptococcus-specific assay was highly sensitive for all 28 streptococcal species tested (i.e., detection limit of 1 to 10 genome copies per PCR). The tuf sequence data was also used to perform extensive phylogenetic analysis, which was generally in agreement with phylogeny determined on the basis of 16S rRNA gene data. However, the tuf gene provided a better discrimination at the streptococcal species level that should be particularly useful for the identification of very closely related species. In conclusion, tuf appears more suitable than the 16S ribosomal RNA gene for the development of diagnostic assays for the detection and identification of streptococcal species because of its higher level of species-specific genetic divergence. PMID:15297518

To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

PubMed Central

Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Przekoracka-Krawczyk, Anna; Jaśkowski, Wojciech; van der Lubbe, Rob

2016-01-01

Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and motor imagery trials. Additionally, learning effects were compared between participants with an explicit motor imagery instruction and a control group. A Go/NoGo discrete sequence production (DSP) task was employed, wherein a five-stimulus sequence presented on each trial indicated the required sequence of finger movements after a Go signal. In the case of a NoGo signal, participants either had to imagine carrying out the response sequence (the motor imagery group), or the response sequence had to be withheld (the control group). Two practice days were followed by a final test day on which all sequences had to be executed. Learning effects were assessed by computing response times (RTs) and the percentages of correct responses (PCs). The electroencephalogram (EEG ) was additionally measured on this test day to examine whether motor preparation and the involvement of visual short term memory (VST M) depended on the amount of physical/mental practice. Accuracy data indicated strong learning effects. However, a substantial amount of physical practice was required to reach an optimal speed. EEG results suggest the involvement of VST M for sequences that had less or no physical practice in both groups. The absence of differences between the motor imagery and the control group underlines the possibility that motor preparation may actually resemble motor imagery. PMID:28154614

To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

PubMed

Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Przekoracka-Krawczyk, Anna; Jaśkowski, Wojciech; van der Lubbe, Rob

2016-01-01

Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and motor imagery trials. Additionally, learning effects were compared between participants with an explicit motor imagery instruction and a control group. A Go/NoGo discrete sequence production (DSP) task was employed, wherein a five-stimulus sequence presented on each trial indicated the required sequence of finger movements after a Go signal. In the case of a NoGo signal, participants either had to imagine carrying out the response sequence (the motor imagery group), or the response sequence had to be withheld (the control group). Two practice days were followed by a final test day on which all sequences had to be executed. Learning effects were assessed by computing response times (RTs) and the percentages of correct responses (PCs). The electroencephalogram (EEG ) was additionally measured on this test day to examine whether motor preparation and the involvement of visual short term memory (VST M) depended on the amount of physical/mental practice. Accuracy data indicated strong learning effects. However, a substantial amount of physical practice was required to reach an optimal speed. EEG results suggest the involvement of VST M for sequences that had less or no physical practice in both groups. The absence of differences between the motor imagery and the control group underlines the possibility that motor preparation may actually resemble motor imagery.

Simrank: Rapid and sensitive general-purpose k-mer search tool

PubMed Central

2011-01-01

Background Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project http://nihroadmap.nih.gov/hmp. Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available. Results Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset. Conclusions Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity. PMID:21524302

PhyloTreePruner: A Phylogenetic Tree-Based Approach for Selection of Orthologous Sequences for Phylogenomics.

PubMed

Kocot, Kevin M; Citarella, Mathew R; Moroz, Leonid L; Halanych, Kenneth M

2013-01-01

Molecular phylogenetics relies on accurate identification of orthologous sequences among the taxa of interest. Most orthology inference programs available for use in phylogenomics rely on small sets of pre-defined orthologs from model organisms or phenetic approaches such as all-versus-all sequence comparisons followed by Markov graph-based clustering. Such approaches have high sensitivity but may erroneously include paralogous sequences. We developed PhyloTreePruner, a software utility that uses a phylogenetic approach to refine orthology inferences made using phenetic methods. PhyloTreePruner checks single-gene trees for evidence of paralogy and generates a new alignment for each group containing only sequences inferred to be orthologs. Importantly, PhyloTreePruner takes into account support values on the tree and avoids unnecessarily deleting sequences in cases where a weakly supported tree topology incorrectly indicates paralogy. A test of PhyloTreePruner on a dataset generated from 11 completely sequenced arthropod genomes identified 2,027 orthologous groups sampled for all taxa. Phylogenetic analysis of the concatenated supermatrix yielded a generally well-supported topology that was consistent with the current understanding of arthropod phylogeny. PhyloTreePruner is freely available from http://sourceforge.net/projects/phylotreepruner/.

Genetic Architecture of the Delis-Kaplan Executive Function System Trail Making Test: Evidence for Distinct Genetic Influences on Executive Function

PubMed Central

Vasilopoulos, Terrie; Franz, Carol E.; Panizzon, Matthew S.; Xian, Hong; Grant, Michael D.; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C.; Kremen, William S.

2012-01-01

Objective To examine how genes and environments contribute to relationships among Trail Making test conditions and the extent to which these conditions have unique genetic and environmental influences. Method Participants included 1237 middle-aged male twins from the Vietnam-Era Twin Study of Aging (VESTA). The Delis-Kaplan Executive Function System Trail Making test included visual searching, number and letter sequencing, and set-shifting components. Results Phenotypic correlations among Trails conditions ranged from 0.29 – 0.60, and genes accounted for the majority (58–84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set-shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. Conclusions A common genetic factor, most likely representing a combination of speed and sequencing accounted for most of the correlation among Trails 1–4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set-shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in non-patient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes. PMID:22201299

A novel model for DNA sequence similarity analysis based on graph theory.

PubMed

Qi, Xingqin; Wu, Qin; Zhang, Yusen; Fuller, Eddie; Zhang, Cun-Quan

2011-01-01

Determination of sequence similarity is one of the major steps in computational phylogenetic studies. As we know, during evolutionary history, not only DNA mutations for individual nucleotide but also subsequent rearrangements occurred. It has been one of major tasks of computational biologists to develop novel mathematical descriptors for similarity analysis such that various mutation phenomena information would be involved simultaneously. In this paper, different from traditional methods (eg, nucleotide frequency, geometric representations) as bases for construction of mathematical descriptors, we construct novel mathematical descriptors based on graph theory. In particular, for each DNA sequence, we will set up a weighted directed graph. The adjacency matrix of the directed graph will be used to induce a representative vector for DNA sequence. This new approach measures similarity based on both ordering and frequency of nucleotides so that much more information is involved. As an application, the method is tested on a set of 0.9-kb mtDNA sequences of twelve different primate species. All output phylogenetic trees with various distance estimations have the same topology, and are generally consistent with the reported results from early studies, which proves the new method's efficiency; we also test the new method on a simulated data set, which shows our new method performs better than traditional global alignment method when subsequent rearrangements happen frequently during evolutionary history.

The effect of curriculum changes and instructional techniques on science-reasoning skills among high school students

NASA Astrophysics Data System (ADS)

Newman, Joan T.

Any change, particularly on a large scale like a sequence change in a district with 75,000 students, is difficult. However, with the advent of the new TAKS science test and the new requirements for high school graduation in the state of Texas, educators and students alike are engaged in innovative educational approaches to meet these requirements. This study investigated a different, non-traditional science sequence to investigate relationships among secondary core-science course sequencing, student science-reasoning performance, and classroom pedagogy. The methodology adopted in the study led to a deeper understanding of the successes and challenges faced by teachers in teaching conceptual physics and chemistry to 8 th and 9th grade students. The qualitative analysis suggested a difference in pedagogy employed by middle and high school science teachers and a need for secondary science teachers to enhance their content knowledge and pedagogical skills, as well as change their underlying attitudes and beliefs about the abilities of students. The study examined scores of 495 randomly chosen students following three different matriculation patterns within one large independent school district. The study indicated that students who follow a sequence with 9th grade IPC generally increase their science-reasoning skills as demonstrated on the 10th grade TAKS science test when these scores are compared with those of students who do not have 9th grade IPC in the science sequence.

Tissue-Specific Transcriptomics in the Field Cricket Teleogryllus oceanicus

PubMed Central

Bailey, Nathan W.; Veltsos, Paris; Tan, Yew-Foon; Millar, A. Harvey; Ritchie, Michael G.; Simmons, Leigh W.

2013-01-01

Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection—testis and accessory gland—would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection. PMID:23390599

Tissue-specific transcriptomics in the field cricket Teleogryllus oceanicus.

PubMed

Bailey, Nathan W; Veltsos, Paris; Tan, Yew-Foon; Millar, A Harvey; Ritchie, Michael G; Simmons, Leigh W

2013-02-01

Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection--testis and accessory gland--would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection.

A Study of the Comparative Effectiveness of Zoology Prerequisites at Slippery Rock State College.

ERIC Educational Resources Information Center

Morrison, William Sechler

This study compared the effectiveness of three sequences of prerequisite courses required before taking zoology. Sequence 1 prerequisite courses consisted of general biology and human biology; Sequence 2 consisted of general biology; and Sequence 3 required cell biology. Zoology students in the spring of 1972 were pretest and a posttest. The mean…

Pitfalls in genetic testing: a case of a SNP in primer-annealing region leading to allele dropout in BRCA1.

PubMed

Silva, Felipe Carneiro; Torrezan, Giovana Tardin; Brianese, Rafael Canfield; Stabellini, Raquel; Carraro, Dirce Maria

2017-07-01

Hereditary breast and ovarian cancer is characterized by mutations in BRCA1 or BRCA2 genes and PCR-based screening techniques, such as capillary sequencing and next-generation sequencing (NGS), are considered gold standard methods for detection of pathogenic mutations in these genes. Single-nucleotide polymorphisms (SNPs) constitute a vast source of variation in the human genome and represent a risk for misdiagnosis in genetic testing, since the presence of a SNP in primer-annealing sites may cause false negative results due to allele dropout. However, few reports are available and the frequency of this phenomenon in diagnostic assays remains unknown. In this article, we investigated the causes of a false negative capillary sequencing result in BRCA1 involving a mother-daughter dyad. Using several molecular strategies, including different DNA polymerases, primer redesign, allele-specific PCR and NGS, we established that the initial misdiagnosis was caused by a SNP located in the primer-annealing region, leading to allele dropout of the mutated allele. Assuming that this problem can also occur in any PCR-based method that are widely used in diagnostic settings, the clinical report presented here draws attention for one of the limitations of genetic testing in general, for which medical and laboratory communities need to be aware.

Genetic variability in E6, E7 and L1 genes of Human Papillomavirus 62 and its prevalence in Mexico.

PubMed

Artaza-Irigaray, Cristina; Flores-Miramontes, María Guadalupe; Olszewski, Dominik; Magaña-Torres, María Teresa; López-Cardona, María Guadalupe; Leal-Herrera, Yelda Aurora; Piña-Sánchez, Patricia; Jave-Suárez, Luis Felipe; Aguilar-Lemarroy, Adriana

2017-01-01

Human papillomavirus (HPV) is the main etiological agent of cervical cancer, the third most common cancer among women globally and the second most frequent in Mexico. Persistent infection with high-risk HPV genotypes is associated with premalignant lesions and cervical cancer development. HPVs considered as low risk or not yet classified, are often found in coinfection with different HPV genotypes. Indeed, HPV62 is one of the most prevalent HPV detected in some countries, but there is limited information about its prevalence in other regions and there are no HPV62 variants currently described. The aim of this study was to determine the prevalence of HPV62 in cervical samples from Mexican women and to identify mutations in the L1, E6 and E7 genes, which have never been reported in our population. HPV screening was performed by Cobas HPV Test in women who attended prevention health programs and dysplasia clinics. All HPV positive samples ( n  = 491) and 87 additional cervical cancer samples were then genotyped with Linear Array HPV Genotyping test. Some samples were selected to corroborate genotyping by Next-Generation sequencing. On the other hand, nucleotide changes in L1, E6 and E7 genes were determined using PCR, Sanger sequencing and analysis with the CLC-MainWorkbench 7.6.1 software. L1 protein structure was predicted with the I-TASSER server. Using Linear Array, HPV62 prevalence was 7.6% in general population, 8% in Cervical Intraepithelial Neoplasia grade 1 (CIN1) samples and 4.6% in cervical samples. The presence of HPV62 was confirmed with Next-Generation sequencing. Regarding L1 gene, novel sequence variations were detected, but they did not alter the tertiary structure of the protein. Moreover, several nucleotide substitutions were found in E6 and E7 genes compared to reference HPV62 genomic sequence. Specifically, three non-synonymous sequence variations were detected, two in E6 and one in E7. HPV62 is a frequent HPV genotype found mainly in general population and in women with CIN1, and in 90.5% of the cases it was found in coinfection with other HPVs. Novel nucleotide changes in its L1, E6 and E7 genes were detected, some of them lead to changes in the protein sequence.

Classification of video sequences into chosen generalized use classes of target size and lighting level.

PubMed

Leszczuk, Mikołaj; Dudek, Łukasz; Witkowski, Marcin

The VQiPS (Video Quality in Public Safety) Working Group, supported by the U.S. Department of Homeland Security, has been developing a user guide for public safety video applications. According to VQiPS, five parameters have particular importance influencing the ability to achieve a recognition task. They are: usage time-frame, discrimination level, target size, lighting level, and level of motion. These parameters form what are referred to as Generalized Use Classes (GUCs). The aim of our research was to develop algorithms that would automatically assist classification of input sequences into one of the GUCs. Target size and lighting level parameters were approached. The experiment described reveals the experts' ambiguity and hesitation during the manual target size determination process. However, the automatic methods developed for target size classification make it possible to determine GUC parameters with 70 % compliance to the end-users' opinion. Lighting levels of the entire sequence can be classified with an efficiency reaching 93 %. To make the algorithms available for use, a test application has been developed. It is able to process video files and display classification results, the user interface being very simple and requiring only minimal user interaction.

Math anxiety differentially affects WAIS-IV arithmetic performance in undergraduates.

PubMed

Buelow, Melissa T; Frakey, Laura L

2013-06-01

Previous research has shown that math anxiety can influence the math performance level; however, to date, it is unknown whether math anxiety influences performance on working memory tasks during neuropsychological evaluation. In the present study, 172 undergraduate students completed measures of math achievement (the Math Computation subtest from the Wide Range Achievement Test-IV), math anxiety (the Math Anxiety Rating Scale-Revised), general test anxiety (from the Adult Manifest Anxiety Scale-College version), and the three Working Memory Index tasks from the Wechsler Adult Intelligence Scale-IV Edition (WAIS-IV; Digit Span [DS], Arithmetic, Letter-Number Sequencing [LNS]). Results indicated that math anxiety predicted performance on Arithmetic, but not DS or LNS, above and beyond the effects of gender, general test anxiety, and math performance level. Our findings suggest that math anxiety can negatively influence WAIS-IV working memory subtest scores. Implications for clinical practice include the utilization of LNS in individuals expressing high math anxiety.

New metric for optimizing Continuous Loop Averaging Deconvolution (CLAD) sequences under the 1/f noise model

PubMed Central

Peng, Xian; Yuan, Han; Chen, Wufan; Ding, Lei

2017-01-01

Continuous loop averaging deconvolution (CLAD) is one of the proven methods for recovering transient auditory evoked potentials (AEPs) in rapid stimulation paradigms, which requires an elaborated stimulus sequence design to attenuate impacts from noise in data. The present study aimed to develop a new metric in gauging a CLAD sequence in terms of noise gain factor (NGF), which has been proposed previously but with less effectiveness in the presence of pink (1/f) noise. We derived the new metric by explicitly introducing the 1/f model into the proposed time-continuous sequence. We selected several representative CLAD sequences to test their noise property on typical EEG recordings, as well as on five real CLAD electroencephalogram (EEG) recordings to retrieve the middle latency responses. We also demonstrated the merit of the new metric in generating and quantifying optimized sequences using a classic genetic algorithm. The new metric shows evident improvements in measuring actual noise gains at different frequencies, and better performance than the original NGF in various aspects. The new metric is a generalized NGF measurement that can better quantify the performance of a CLAD sequence, and provide a more efficient mean of generating CLAD sequences via the incorporation with optimization algorithms. The present study can facilitate the specific application of CLAD paradigm with desired sequences in the clinic. PMID:28414803

Automated DNA mutation detection using universal conditions direct sequencing: application to ten muscular dystrophy genes

PubMed Central

2009-01-01

Background One of the most common and efficient methods for detecting mutations in genes is PCR amplification followed by direct sequencing. Until recently, the process of designing PCR assays has been to focus on individual assay parameters rather than concentrating on matching conditions for a set of assays. Primers for each individual assay were selected based on location and sequence concerns. The two primer sequences were then iteratively adjusted to make the individual assays work properly. This generally resulted in groups of assays with different annealing temperatures that required the use of multiple thermal cyclers or multiple passes in a single thermal cycler making diagnostic testing time-consuming, laborious and expensive. These factors have severely hampered diagnostic testing services, leaving many families without an answer for the exact cause of a familial genetic disease. A search of GeneTests for sequencing analysis of the entire coding sequence for genes that are known to cause muscular dystrophies returns only a small list of laboratories that perform comprehensive gene panels. The hypothesis for the study was that a complete set of universal assays can be designed to amplify and sequence any gene or family of genes using computer aided design tools. If true, this would allow automation and optimization of the mutation detection process resulting in reduced cost and increased throughput. Results An automated process has been developed for the detection of deletions, duplications/insertions and point mutations in any gene or family of genes and has been applied to ten genes known to bear mutations that cause muscular dystrophy: DMD; CAV3; CAPN3; FKRP; TRIM32; LMNA; SGCA; SGCB; SGCG; SGCD. Using this process, mutations have been found in five DMD patients and four LGMD patients (one in the FKRP gene, one in the CAV3 gene, and two likely causative heterozygous pairs of variations in the CAPN3 gene of two other patients). Methods and assay sequences are reported in this paper. Conclusion This automated process allows laboratories to discover DNA variations in a short time and at low cost. PMID:19835634

Automated DNA mutation detection using universal conditions direct sequencing: application to ten muscular dystrophy genes.

PubMed

Bennett, Richard R; Schneider, Hal E; Estrella, Elicia; Burgess, Stephanie; Cheng, Andrew S; Barrett, Caitlin; Lip, Va; Lai, Poh San; Shen, Yiping; Wu, Bai-Lin; Darras, Basil T; Beggs, Alan H; Kunkel, Louis M

2009-10-18

One of the most common and efficient methods for detecting mutations in genes is PCR amplification followed by direct sequencing. Until recently, the process of designing PCR assays has been to focus on individual assay parameters rather than concentrating on matching conditions for a set of assays. Primers for each individual assay were selected based on location and sequence concerns. The two primer sequences were then iteratively adjusted to make the individual assays work properly. This generally resulted in groups of assays with different annealing temperatures that required the use of multiple thermal cyclers or multiple passes in a single thermal cycler making diagnostic testing time-consuming, laborious and expensive.These factors have severely hampered diagnostic testing services, leaving many families without an answer for the exact cause of a familial genetic disease. A search of GeneTests for sequencing analysis of the entire coding sequence for genes that are known to cause muscular dystrophies returns only a small list of laboratories that perform comprehensive gene panels.The hypothesis for the study was that a complete set of universal assays can be designed to amplify and sequence any gene or family of genes using computer aided design tools. If true, this would allow automation and optimization of the mutation detection process resulting in reduced cost and increased throughput. An automated process has been developed for the detection of deletions, duplications/insertions and point mutations in any gene or family of genes and has been applied to ten genes known to bear mutations that cause muscular dystrophy: DMD; CAV3; CAPN3; FKRP; TRIM32; LMNA; SGCA; SGCB; SGCG; SGCD. Using this process, mutations have been found in five DMD patients and four LGMD patients (one in the FKRP gene, one in the CAV3 gene, and two likely causative heterozygous pairs of variations in the CAPN3 gene of two other patients). Methods and assay sequences are reported in this paper. This automated process allows laboratories to discover DNA variations in a short time and at low cost.

Correcting for Sample Contamination in Genotype Calling of DNA Sequence Data

PubMed Central

Flickinger, Matthew; Jun, Goo; Abecasis, Gonçalo R.; Boehnke, Michael; Kang, Hyun Min

2015-01-01

DNA sample contamination is a frequent problem in DNA sequencing studies and can result in genotyping errors and reduced power for association testing. We recently described methods to identify within-species DNA sample contamination based on sequencing read data, showed that our methods can reliably detect and estimate contamination levels as low as 1%, and suggested strategies to identify and remove contaminated samples from sequencing studies. Here we propose methods to model contamination during genotype calling as an alternative to removal of contaminated samples from further analyses. We compare our contamination-adjusted calls to calls that ignore contamination and to calls based on uncontaminated data. We demonstrate that, for moderate contamination levels (5%–20%), contamination-adjusted calls eliminate 48%–77% of the genotyping errors. For lower levels of contamination, our contamination correction methods produce genotypes nearly as accurate as those based on uncontaminated data. Our contamination correction methods are useful generally, but are particularly helpful for sample contamination levels from 2% to 20%. PMID:26235984

Investigation of the contextual interference effect in the manipulation of the motor parameter of over-all force.

PubMed

Goodwin, J E; Meeuwsen, H J

1996-12-01

This investigation examined the contextual interference effect when manipulating over-all force in a golf-putting task. Undergraduate women (N = 30) were randomly assigned to a Random, Blocked-Random, or Blocked practice condition and practiced golf putting from distances of 2.43 m, 3.95 m, and 5.47 m during acquisition. Subjects in the Random condition practiced trials in a quasirandom sequence and those in the Blocked-Random condition practiced trials initially in a blocked sequence with the remainder of the trials practiced in a quasirandom sequence. In the Blocked condition subjects practiced trials in a blocked sequence. A 24-hr. transfer test consisted of 30 trials with 10 trials each from 1.67 m, 3.19 m, and 6.23 m. Transfer scores supported the Magill and Hall (1990) hypothesis that, when task variations involve learning parameters of a generalized motor program, the benefit of random practice over blocked practice would not be found.

Sequence co-evolution gives 3D contacts and structures of protein complexes

PubMed Central

Hopf, Thomas A; Schärfe, Charlotta P I; Rodrigues, João P G L M; Green, Anna G; Kohlbacher, Oliver; Sander, Chris; Bonvin, Alexandre M J J; Marks, Debora S

2014-01-01

Protein–protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions, and structural biology has provided detailed functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins identifies residues that are close in space with sufficient accuracy to determine the three-dimensional structure of the protein complexes. We evaluate prediction performance in blinded tests on 76 complexes of known 3D structure, predict protein–protein contacts in 32 complexes of unknown structure, and demonstrate how evolutionary couplings can be used to distinguish between interacting and non-interacting protein pairs in a large complex. With the current growth of sequences, we expect that the method can be generalized to genome-wide elucidation of protein–protein interaction networks and used for interaction predictions at residue resolution. DOI: http://dx.doi.org/10.7554/eLife.03430.001 PMID:25255213

Characterization of an endogenous retrovirus class in elephants and their relatives

PubMed Central

Greenwood, Alex D; Englbrecht, Claudia C; MacPhee, Ross DE

2004-01-01

Background Endogenous retrovirus-like elements (ERV-Ls, primed with tRNA leucine) are a diverse group of reiterated sequences related to foamy viruses and widely distributed among mammals. As shown in previous investigations, in many primates and rodents this class of elements has remained transpositionally active, as reflected by increased copy number and high sequence diversity within and among taxa. Results Here we examine whether proviral-like sequences may be suitable molecular probes for investigating the phylogeny of groups known to have high element diversity. As a test we characterized ERV-Ls occurring in a sample of extant members of superorder Uranotheria (Asian and African elephants, manatees, and hyraxes). The ERV-L complement in this group is even more diverse than previously suspected, and there is sequence evidence for active expansion, particularly in elephantids. Many of the elements characterized have protein coding potential suggestive of activity. Conclusions In general, the evidence supports the hypothesis that the complement had a single origin within basal Uranotheria. PMID:15476555

Synthesis and monitored selection of nucleotide surrogates for binding T:A base pairs in homopurine-homopyrimidine DNA triple helices.

PubMed

Mokhir, A A; Connors, W H; Richert, C

2001-09-01

A total of 16 oligodeoxyribonucleotides of general sequence 5'-TCTTCTZTCTTTCT-3', where Z denotes an N-acyl-N-(2-hydroxyethyl)glycine residue, were prepared via solid phase synthesis. The ability of these oligonucleotides to form triplexes with the duplex 5'-AGAAGATAGAAAGA-HEG-TCTTTCTATCTTCT-3', where HEG is a hexaethylene glycol linker, was tested. In these triplexes, an 'interrupting' T:A base pair faces the Z residue in the third strand. Among the acyl moieties of Z tested, an anthraquinone carboxylic acid residue linked via a glycinyl group gave the most stable triplex, whose UV melting point was 8.4 degrees C higher than that of the triplex with 5'-TCTTCTGTCTTTCT-3' as the third strand. The results from exploratory nuclease selection experiments suggest that a combinatorial search for strands capable of recognizing mixed sequences by triple helix formation is feasible.

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

Burkholderia pseudomallei Isolates from Sarawak, Malaysian Borneo, Are Predominantly Susceptible to Aminoglycosides and Macrolides

PubMed Central

Podin, Yuwana; Sarovich, Derek S.; Price, Erin P.; Kaestli, Mirjam; Mayo, Mark; Hii, KingChing; Ngian, HieUng; Wong, SeeChang; Wong, IngTien; Wong, JinShyan; Mohan, Anand; Ooi, MongHow; Fam, TemLom; Wong, Jack; Tuanyok, Apichai; Keim, Paul; Giffard, Philip M.

2014-01-01

Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity. PMID:24145517

Burkholderia pseudomallei isolates from Sarawak, Malaysian Borneo, are predominantly susceptible to aminoglycosides and macrolides.

PubMed

Podin, Yuwana; Sarovich, Derek S; Price, Erin P; Kaestli, Mirjam; Mayo, Mark; Hii, KingChing; Ngian, Hieung; Wong, SeeChang; Wong, IngTien; Wong, JinShyan; Mohan, Anand; Ooi, MongHow; Fam, TemLom; Wong, Jack; Tuanyok, Apichai; Keim, Paul; Giffard, Philip M; Currie, Bart J

2014-01-01

Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.

Some identities of generalized Fibonacci sequence

NASA Astrophysics Data System (ADS)

Chong, Chin-Yoon; Cheah, C. L.; Ho, C. K.

2014-07-01

We introduced the generalized Fibonacci sequence {Un} defined by U0 = 0, U1 = 1, and Un+2 = pUn+1+qUn for all p, q∈Z+ and for all non-negative integers n. In this paper, we obtained some recursive formulas of the sequence.

Comparison of taxon-specific versus general locus sets for targeted sequence capture in plant phylogenomics.

PubMed

Chau, John H; Rahfeldt, Wolfgang A; Olmstead, Richard G

2018-03-01

Targeted sequence capture can be used to efficiently gather sequence data for large numbers of loci, such as single-copy nuclear loci. Most published studies in plants have used taxon-specific locus sets developed individually for a clade using multiple genomic and transcriptomic resources. General locus sets can also be developed from loci that have been identified as single-copy and have orthologs in large clades of plants. We identify and compare a taxon-specific locus set and three general locus sets (conserved ortholog set [COSII], shared single-copy nuclear [APVO SSC] genes, and pentatricopeptide repeat [PPR] genes) for targeted sequence capture in Buddleja (Scrophulariaceae) and outgroups. We evaluate their performance in terms of assembly success, sequence variability, and resolution and support of inferred phylogenetic trees. The taxon-specific locus set had the most target loci. Assembly success was high for all locus sets in Buddleja samples. For outgroups, general locus sets had greater assembly success. Taxon-specific and PPR loci had the highest average variability. The taxon-specific data set produced the best-supported tree, but all data sets showed improved resolution over previous non-sequence capture data sets. General locus sets can be a useful source of sequence capture targets, especially if multiple genomic resources are not available for a taxon.

Conditional Monte Carlo randomization tests for regression models.

PubMed

Parhat, Parwen; Rosenberger, William F; Diao, Guoqing

2014-08-15

We discuss the computation of randomization tests for clinical trials of two treatments when the primary outcome is based on a regression model. We begin by revisiting the seminal paper of Gail, Tan, and Piantadosi (1988), and then describe a method based on Monte Carlo generation of randomization sequences. The tests based on this Monte Carlo procedure are design based, in that they incorporate the particular randomization procedure used. We discuss permuted block designs, complete randomization, and biased coin designs. We also use a new technique by Plamadeala and Rosenberger (2012) for simple computation of conditional randomization tests. Like Gail, Tan, and Piantadosi, we focus on residuals from generalized linear models and martingale residuals from survival models. Such techniques do not apply to longitudinal data analysis, and we introduce a method for computation of randomization tests based on the predicted rate of change from a generalized linear mixed model when outcomes are longitudinal. We show, by simulation, that these randomization tests preserve the size and power well under model misspecification. Copyright © 2014 John Wiley & Sons, Ltd.

[Affective behavioural responses by dogs to tactile human-dog interactions].

PubMed

Kuhne, Franziska; Hössler, Johanna C; Struwe, Rainer

2012-01-01

The communication of dogs is based on complex, subtle body postures and facial expressions. Some social interaction between dogs includes physical contact. Humans generally use both verbal and tactile signals to communicate with dogs. Hence, interaction between humans and dogs might lead to conflicts because the behavioural responses of dogs to human-dog interaction may be misinterpreted and wrongly assessed. The behavioural responses of dogs to tactile human-dog interactions and human gestures are the focus of this study. The participating dogs (n = 47) were privately owned pets.They were of varying breed and gender.The test consisted of nine randomised test sequences (e. g. petting the dog's head or chest). A test sequence was performed for a period of 30 seconds. The inter-trial interval was set at 60 seconds and the test-retest interval was set at 10 minutes. The frequency and duration of the dogs'behavioural responses were recorded using INTERACT. To examine the behavioural responses of the dogs, a two-way analysis of variance within the linear mixed models procedure of IBM SPSS Statistics 19 was conducted. A significant influence of the test-sequenc order on the dogs' behaviour could be analysed for appeasement gestures (F8,137 = 2.42; p = 0.018), redirected behaviour (F8,161 = 6.31; p = 0.012) and socio-positive behaviour (F8,148 = 6.28; p = 0.012). The behavioural responses of the dogs, which were considered as displacement activities (F8,109 = 2.5; p = 0.014) differed significantly among the test sequences. The response of the dogs, measured as gestures of appeasement, redirected behaviours, and displacement activities, was most obvious during petting around the head and near the paws.The results of this study conspicuously indicate that dogs respond to tactile human-dog interactions with gestures of appeasement and displacement activities. Redirected behaviours, socio-positive behaviours as well displacement activities are behavioural responses which dogs mainly show after a human-dog interaction.

How to Choose the Suitable Template for Homology Modelling of GPCRs: 5-HT7 Receptor as a Test Case.

PubMed

Shahaf, Nir; Pappalardo, Matteo; Basile, Livia; Guccione, Salvatore; Rayan, Anwar

2016-09-01

G protein-coupled receptors (GPCRs) are a super-family of membrane proteins that attract great pharmaceutical interest due to their involvement in almost every physiological activity, including extracellular stimuli, neurotransmission, and hormone regulation. Currently, structural information on many GPCRs is mainly obtained by the techniques of computer modelling in general and by homology modelling in particular. Based on a quantitative analysis of eighteen antagonist-bound, resolved structures of rhodopsin family "A" receptors - also used as templates to build 153 homology models - it was concluded that a higher sequence identity between two receptors does not guarantee a lower RMSD between their structures, especially when their pair-wise sequence identity (within trans-membrane domain and/or in binding pocket) lies between 25 % and 40 %. This study suggests that we should consider all template receptors having a sequence identity ≤50 % with the query receptor. In fact, most of the GPCRs, compared to the currently available resolved structures of GPCRs, fall within this range and lack a correlation between structure and sequence. When testing suitability for structure-based drug design, it was found that choosing as a template the most similar resolved protein, based on sequence resemblance only, led to unsound results in many cases. Molecular docking analyses were carried out, and enrichment factors as well as attrition rates were utilized as criteria for assessing suitability for structure-based drug design. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sequence-Stratigraphic Analysis of the Regional Observation Monitoring Program (ROMP) 29A Test Corehole and Its Relation to Carbonate Porosity and Regional Transmissivity in the Floridan Aquifer System, Highlands County, Florida

USGS Publications Warehouse

Ward, W. C.; Cunningham, K.J.; Renken, R.A.; Wacker, M.A.; Carlson, J.I.

2003-01-01

An analysis was made to describe and interpret the lithology of a part of the Upper Floridan aquifer penetrated by the Regional Observation Monitoring Program (ROMP) 29A test corehole in Highlands County, Florida. This information was integrated into a one-dimensional hydrostratigraphic model that delineates candidate flow zones and confining units in the context of sequence stratigraphy. Results from this test corehole will serve as a starting point to build a robust three-dimensional sequence-stratigraphic framework of the Floridan aquifer system. The ROMP 29A test corehole penetrated the Avon Park Formation, Ocala Limestone, Suwannee Limestone, and Hawthorn Group of middle Eocene to Pliocene age. The part of the Avon Park Formation penetrated in the ROMP 29A test corehole contains two composite depositional sequences. A transgressive systems tract and a highstand systems tract were interpreted for the upper composite sequence; however, only a highstand systems tract was interpreted for the lower composite sequence of the deeper Avon Park stratigraphic section. The composite depositional sequences are composed of at least five high-frequency depositional sequences. These sequences contain high-frequency cycle sets that are an amalgamation of vertically stacked high-frequency cycles. Three types of high-frequency cycles have been identified in the Avon Park Formation: peritidal, shallow subtidal, and deeper subtidal high-frequency cycles. The vertical distribution of carbonate-rock diffuse flow zones within the Avon Park Formation is heterogeneous. Porous vuggy intervals are less than 10 feet, and most are much thinner. The volumetric arrangement of the diffuse flow zones shows that most occur in the highstand systems tract of the lower composite sequence of the Avon Park Formation as compared to the upper composite sequence, which contains both a backstepping transgressive systems tract and a prograding highstand systems tract. Although the porous and permeable layers are not thick, some intervals may exhibit lateral continuity because of their deposition on a broad low-relief ramp. A thick interval of thin vuggy zones and open faults forms thin conduit flow zones mixed with relatively thicker carbonate-rock diffuse flow zones between a depth of 1,070 and 1,244 feet below land surface (bottom of the test corehole). This interval is the most transmissive part of the Avon Park Formation penetrated in the ROMP 29A test corehole and is included in the highstand systems tract of the lower composite sequence. The Ocala Limestone is considered to be a semiconfining unit and contains three depositional sequences penetrated by the ROMP 29A test corehole. Deposited within deeper subtidal depositional cycles, no zones of enhanced porosity and permeability are expected in the Ocala Limestone. A thin erosional remnant of the shallow marine Suwannee Limestone overlies the Ocala Limestone, and permeability seems to be comparatively low because moldic porosity is poorly connected. Rocks that comprise the lower Hawthorn Group, Suwannee Limestone, and Ocala Limestone form a permeable upper zone of the Upper Floridan aquifer, and rocks of the lower Ocala Limestone and Avon Park Formation form a permeable lower zone of the Upper Floridan aquifer. On the basis of a preliminary analysis of transmissivity estimates for wells located north of Lake Okeechobee, spatial relations among groups of relatively high and low transmissivity values within the upper zone are evident. Upper zone transmissivity is generally less than 10,000 feet squared per day in areas located south of a line that extends through Charlotte, Sarasota, DeSoto, Highlands, Polk, Osceola, Okeechobee, and St. Lucie Counties. Transmissivity patterns within the lower zone of the Avon Park Formation cannot be regionally assessed because insufficient data over a wide areal extent have not been compiled.

A Novel Genome-Information Content-Based Statistic for Genome-Wide Association Analysis Designed for Next-Generation Sequencing Data

PubMed Central

Luo, Li; Zhu, Yun

2012-01-01

Abstract The genome-wide association studies (GWAS) designed for next-generation sequencing data involve testing association of genomic variants, including common, low frequency, and rare variants. The current strategies for association studies are well developed for identifying association of common variants with the common diseases, but may be ill-suited when large amounts of allelic heterogeneity are present in sequence data. Recently, group tests that analyze their collective frequency differences between cases and controls shift the current variant-by-variant analysis paradigm for GWAS of common variants to the collective test of multiple variants in the association analysis of rare variants. However, group tests ignore differences in genetic effects among SNPs at different genomic locations. As an alternative to group tests, we developed a novel genome-information content-based statistics for testing association of the entire allele frequency spectrum of genomic variation with the diseases. To evaluate the performance of the proposed statistics, we use large-scale simulations based on whole genome low coverage pilot data in the 1000 Genomes Project to calculate the type 1 error rates and power of seven alternative statistics: a genome-information content-based statistic, the generalized T2, collapsing method, multivariate and collapsing (CMC) method, individual χ2 test, weighted-sum statistic, and variable threshold statistic. Finally, we apply the seven statistics to published resequencing dataset from ANGPTL3, ANGPTL4, ANGPTL5, and ANGPTL6 genes in the Dallas Heart Study. We report that the genome-information content-based statistic has significantly improved type 1 error rates and higher power than the other six statistics in both simulated and empirical datasets. PMID:22651812

A novel genome-information content-based statistic for genome-wide association analysis designed for next-generation sequencing data.

PubMed

Luo, Li; Zhu, Yun; Xiong, Momiao

2012-06-01

The genome-wide association studies (GWAS) designed for next-generation sequencing data involve testing association of genomic variants, including common, low frequency, and rare variants. The current strategies for association studies are well developed for identifying association of common variants with the common diseases, but may be ill-suited when large amounts of allelic heterogeneity are present in sequence data. Recently, group tests that analyze their collective frequency differences between cases and controls shift the current variant-by-variant analysis paradigm for GWAS of common variants to the collective test of multiple variants in the association analysis of rare variants. However, group tests ignore differences in genetic effects among SNPs at different genomic locations. As an alternative to group tests, we developed a novel genome-information content-based statistics for testing association of the entire allele frequency spectrum of genomic variation with the diseases. To evaluate the performance of the proposed statistics, we use large-scale simulations based on whole genome low coverage pilot data in the 1000 Genomes Project to calculate the type 1 error rates and power of seven alternative statistics: a genome-information content-based statistic, the generalized T(2), collapsing method, multivariate and collapsing (CMC) method, individual χ(2) test, weighted-sum statistic, and variable threshold statistic. Finally, we apply the seven statistics to published resequencing dataset from ANGPTL3, ANGPTL4, ANGPTL5, and ANGPTL6 genes in the Dallas Heart Study. We report that the genome-information content-based statistic has significantly improved type 1 error rates and higher power than the other six statistics in both simulated and empirical datasets.

Generalization of Entropy Based Divergence Measures for Symbolic Sequence Analysis

PubMed Central

Ré, Miguel A.; Azad, Rajeev K.

2014-01-01

Entropy based measures have been frequently used in symbolic sequence analysis. A symmetrized and smoothed form of Kullback-Leibler divergence or relative entropy, the Jensen-Shannon divergence (JSD), is of particular interest because of its sharing properties with families of other divergence measures and its interpretability in different domains including statistical physics, information theory and mathematical statistics. The uniqueness and versatility of this measure arise because of a number of attributes including generalization to any number of probability distributions and association of weights to the distributions. Furthermore, its entropic formulation allows its generalization in different statistical frameworks, such as, non-extensive Tsallis statistics and higher order Markovian statistics. We revisit these generalizations and propose a new generalization of JSD in the integrated Tsallis and Markovian statistical framework. We show that this generalization can be interpreted in terms of mutual information. We also investigate the performance of different JSD generalizations in deconstructing chimeric DNA sequences assembled from bacterial genomes including that of E. coli, S. enterica typhi, Y. pestis and H. influenzae. Our results show that the JSD generalizations bring in more pronounced improvements when the sequences being compared are from phylogenetically proximal organisms, which are often difficult to distinguish because of their compositional similarity. While small but noticeable improvements were observed with the Tsallis statistical JSD generalization, relatively large improvements were observed with the Markovian generalization. In contrast, the proposed Tsallis-Markovian generalization yielded more pronounced improvements relative to the Tsallis and Markovian generalizations, specifically when the sequences being compared arose from phylogenetically proximal organisms. PMID:24728338

Generalization of entropy based divergence measures for symbolic sequence analysis.

PubMed

Ré, Miguel A; Azad, Rajeev K

2014-01-01

Entropy based measures have been frequently used in symbolic sequence analysis. A symmetrized and smoothed form of Kullback-Leibler divergence or relative entropy, the Jensen-Shannon divergence (JSD), is of particular interest because of its sharing properties with families of other divergence measures and its interpretability in different domains including statistical physics, information theory and mathematical statistics. The uniqueness and versatility of this measure arise because of a number of attributes including generalization to any number of probability distributions and association of weights to the distributions. Furthermore, its entropic formulation allows its generalization in different statistical frameworks, such as, non-extensive Tsallis statistics and higher order Markovian statistics. We revisit these generalizations and propose a new generalization of JSD in the integrated Tsallis and Markovian statistical framework. We show that this generalization can be interpreted in terms of mutual information. We also investigate the performance of different JSD generalizations in deconstructing chimeric DNA sequences assembled from bacterial genomes including that of E. coli, S. enterica typhi, Y. pestis and H. influenzae. Our results show that the JSD generalizations bring in more pronounced improvements when the sequences being compared are from phylogenetically proximal organisms, which are often difficult to distinguish because of their compositional similarity. While small but noticeable improvements were observed with the Tsallis statistical JSD generalization, relatively large improvements were observed with the Markovian generalization. In contrast, the proposed Tsallis-Markovian generalization yielded more pronounced improvements relative to the Tsallis and Markovian generalizations, specifically when the sequences being compared arose from phylogenetically proximal organisms.

A Statistical Test of Walrasian Equilibrium by Means of Complex Networks Theory

NASA Astrophysics Data System (ADS)

Bargigli, Leonardo; Viaggiu, Stefano; Lionetto, Andrea

2016-10-01

We represent an exchange economy in terms of statistical ensembles for complex networks by introducing the concept of market configuration. This is defined as a sequence of nonnegative discrete random variables {w_{ij}} describing the flow of a given commodity from agent i to agent j. This sequence can be arranged in a nonnegative matrix W which we can regard as the representation of a weighted and directed network or digraph G. Our main result consists in showing that general equilibrium theory imposes highly restrictive conditions upon market configurations, which are in most cases not fulfilled by real markets. An explicit example with reference to the e-MID interbank credit market is provided.

Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

PubMed

Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

2012-03-01

To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

Spread Spectrum Receiver Electromagnetic Interference (EMI) Test Guide

NASA Technical Reports Server (NTRS)

Wheeler, M. L.

1998-01-01

The objective of this test guide is to document appropriate unit level test methods and techniques for the performance of EMI testing of Direct Sequence (DS) spread spectrum receivers. Consideration of EMI test methods tailored for spread spectrum receivers utilizing frequency spreading, techniques other than direct sequence (such as frequency hopping, frequency chirping, and various hybrid methods) is beyond the scope of this test guide development program and is not addressed as part of this document EMI test requirements for NASA programs are primarily developed based on the requirements contained in MIL-STD-46 1 D (or earlier revisions of MIL-STD-46 1). The corresponding test method guidelines for the MIL-STD-461 D tests are provided in MIL-STD-462D. These test methods are well documented with the exception of the receiver antenna port susceptibility tests (intermodulation, cross modulation, and rejection of undesired signals) which must be tailored to the specific type of receiver that is being tested. Thus, test methods addressed in this guide consist only of antenna port tests designed to evaluate receiver susceptibility characteristics. MIL-STD-462D should be referred for guidance pertaining to test methods for EMI tests other than the antenna port tests. The scope of this test guide includes: (1) a discussion of generic DS receiver performance characteristics; (2) a summary of S-band TDRSS receiver operation; (3) a discussion of DS receiver EMI susceptibility mechanisms and characteristics; (4) a summary of military standard test guidelines; (5) recommended test approach and methods; and (6) general conclusions and recommendations for future studies in the area of spread spectrum receiver testing.

Barcode extension for analysis and reconstruction of structures

NASA Astrophysics Data System (ADS)

Myhrvold, Cameron; Baym, Michael; Hanikel, Nikita; Ong, Luvena L.; Gootenberg, Jonathan S.; Yin, Peng

2017-03-01

Collections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures.

Barcode extension for analysis and reconstruction of structures.

PubMed

Myhrvold, Cameron; Baym, Michael; Hanikel, Nikita; Ong, Luvena L; Gootenberg, Jonathan S; Yin, Peng

2017-03-13

Collections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures.

MILP model for integrated balancing and sequencing mixed-model two-sided assembly line with variable launching interval and assignment restrictions

NASA Astrophysics Data System (ADS)

Azmi, N. I. L. Mohd; Ahmad, R.; Zainuddin, Z. M.

2017-09-01

This research explores the Mixed-Model Two-Sided Assembly Line (MMTSAL). There are two interrelated problems in MMTSAL which are line balancing and model sequencing. In previous studies, many researchers considered these problems separately and only few studied them simultaneously for one-sided line. However in this study, these two problems are solved simultaneously to obtain more efficient solution. The Mixed Integer Linear Programming (MILP) model with objectives of minimizing total utility work and idle time is generated by considering variable launching interval and assignment restriction constraint. The problem is analysed using small-size test cases to validate the integrated model. Throughout this paper, numerical experiment was conducted by using General Algebraic Modelling System (GAMS) with the solver CPLEX. Experimental results indicate that integrating the problems of model sequencing and line balancing help to minimise the proposed objectives function.

Automated design of genetic toggle switches with predetermined bistability.

PubMed

Chen, Shuobing; Zhang, Haoqian; Shi, Handuo; Ji, Weiyue; Feng, Jingchen; Gong, Yan; Yang, Zhenglin; Ouyang, Qi

2012-07-20

Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment are therefore highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links ribosome binding site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parametrize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistabilities were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology.

Barcode extension for analysis and reconstruction of structures

PubMed Central

Myhrvold, Cameron; Baym, Michael; Hanikel, Nikita; Ong, Luvena L; Gootenberg, Jonathan S; Yin, Peng

2017-01-01

Collections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures. PMID:28287117

Recombinative Generalization: An Exploratory Study in Musical Reading

PubMed Central

Perez, William Ferreira; de Rose, Julio C

2010-01-01

The present study aimed to extend the findings of recombinative generalization research in alphabetical reading and spelling to the context of musical reading. One participant was taught to respond discriminatively to six two-note sequences, choosing the corresponding notation on the staff in the presence of each sequence. When novel three- and four-note sequences were presented, she selected the corresponding notation. These results suggest the generality of previous research to the context of musical teaching. PMID:22477462

DRUMS: Disk Repository with Update Management and Select option for high throughput sequencing data.

PubMed

Nettling, Martin; Thieme, Nils; Both, Andreas; Grosse, Ivo

2014-02-04

New technologies for analyzing biological samples, like next generation sequencing, are producing a growing amount of data together with quality scores. Moreover, software tools (e.g., for mapping sequence reads), calculating transcription factor binding probabilities, estimating epigenetic modification enriched regions or determining single nucleotide polymorphism increase this amount of position-specific DNA-related data even further. Hence, requesting data becomes challenging and expensive and is often implemented using specialised hardware. In addition, picking specific data as fast as possible becomes increasingly important in many fields of science. The general problem of handling big data sets was addressed by developing specialized databases like HBase, HyperTable or Cassandra. However, these database solutions require also specialized or distributed hardware leading to expensive investments. To the best of our knowledge, there is no database capable of (i) storing billions of position-specific DNA-related records, (ii) performing fast and resource saving requests, and (iii) running on a single standard computer hardware. Here, we present DRUMS (Disk Repository with Update Management and Select option), satisfying demands (i)-(iii). It tackles the weaknesses of traditional databases while handling position-specific DNA-related data in an efficient manner. DRUMS is capable of storing up to billions of records. Moreover, it focuses on optimizing relating single lookups as range request, which are needed permanently for computations in bioinformatics. To validate the power of DRUMS, we compare it to the widely used MySQL database. The test setting considers two biological data sets. We use standard desktop hardware as test environment. DRUMS outperforms MySQL in writing and reading records by a factor of two up to a factor of 10000. Furthermore, it can work with significantly larger data sets. Our work focuses on mid-sized data sets up to several billion records without requiring cluster technology. Storing position-specific data is a general problem and the concept we present here is a generalized approach. Hence, it can be easily applied to other fields of bioinformatics.

Phylogenetic relationships of South American lizards of the genus Stenocercus (Squamata: Iguania): A new approach using a general mixture model for gene sequence data.

PubMed

Torres-Carvajal, Omar; Schulte, James A; Cadle, John E

2006-04-01

The South American iguanian lizard genus Stenocercus includes 54 species occurring mostly in the Andes and adjacent lowland areas from northern Venezuela and Colombia to central Argentina at elevations of 0-4000m. Small taxon or character sampling has characterized all phylogenetic analyses of Stenocercus, which has long been recognized as sister taxon to the Tropidurus Group. In this study, we use mtDNA sequence data to perform phylogenetic analyses that include 32 species of Stenocercus and 12 outgroup taxa. Monophyly of this genus is strongly supported by maximum parsimony and Bayesian analyses. Evolutionary relationships within Stenocercus are further analyzed with a Bayesian implementation of a general mixture model, which accommodates variability in the pattern of evolution across sites. These analyses indicate a basal split of Stenocercus into two clades, one of which receives very strong statistical support. In addition, we test previous hypotheses using non-parametric and parametric statistical methods, and provide a phylogenetic classification for Stenocercus.

Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

PubMed Central

Pfundt, Rolph; del Rosario, Marisol; Vissers, Lisenka E.L.M.; Kwint, Michael P.; Janssen, Irene M.; de Leeuw, Nicole; Yntema, Helger G.; Nelen, Marcel R.; Lugtenberg, Dorien; Kamsteeg, Erik-Jan; Wieskamp, Nienke; Stegmann, Alexander P.A.; Stevens, Servi J.C.; Rodenburg, Richard J.T.; Simons, Annet; Mensenkamp, Arjen R.; Rinne, Tuula; Gilissen, Christian; Scheffer, Hans; Veltman, Joris A.; Hehir-Kwa, Jayne Y.

2017-01-01

Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10–20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test. Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting. Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to –5.8% per disorder). Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics. Genet Med advance online publication 27 October 2016 PMID:28574513

Golden Proportions for the Generalized Tribonacci Numbers

ERIC Educational Resources Information Center

Shah, Devbhadra V.; Mehta, Darshana A.

2009-01-01

It is known that the ratios of consecutive terms of Fibonacci and Tribonacci sequences converge to the fixed ratio. In this article, we consider the generalized form of Tribonacci numbers and derive the "golden proportion" for the whole family of this generalized sequence. (Contains 2 tables.)

Sequence Factorial of "g"-Gonal Numbers

ERIC Educational Resources Information Center

Asiru, Muniru A.

2013-01-01

The gamma function, which has the property to interpolate the factorial whenever the argument is an integer, is a special case (the case "g"?=?2) of the general term of the sequence factorial of "g"-gonal numbers. In relation to this special case, a formula for calculating the general term of the sequence factorial of any…

Verifying Digital Components of Physical Systems: Experimental Evaluation of Test Quality

NASA Astrophysics Data System (ADS)

Laputenko, A. V.; López, J. E.; Yevtushenko, N. V.

2018-03-01

This paper continues the study of high quality test derivation for verifying digital components which are used in various physical systems; those are sensors, data transfer components, etc. We have used logic circuits b01-b010 of the package of ITC'99 benchmarks (Second Release) for experimental evaluation which as stated before, describe digital components of physical systems designed for various applications. Test sequences are derived for detecting the most known faults of the reference logic circuit using three different approaches to test derivation. Three widely used fault types such as stuck-at-faults, bridges, and faults which slightly modify the behavior of one gate are considered as possible faults of the reference behavior. The most interesting test sequences are short test sequences that can provide appropriate guarantees after testing, and thus, we experimentally study various approaches to the derivation of the so-called complete test suites which detect all fault types. In the first series of experiments, we compare two approaches for deriving complete test suites. In the first approach, a shortest test sequence is derived for testing each fault. In the second approach, a test sequence is pseudo-randomly generated by the use of an appropriate software for logic synthesis and verification (ABC system in our study) and thus, can be longer. However, after deleting sequences detecting the same set of faults, a test suite returned by the second approach is shorter. The latter underlines the fact that in many cases it is useless to spend `time and efforts' for deriving a shortest distinguishing sequence; it is better to use the test minimization afterwards. The performed experiments also show that the use of only randomly generated test sequences is not very efficient since such sequences do not detect all the faults of any type. After reaching the fault coverage around 70%, saturation is observed, and the fault coverage cannot be increased anymore. For deriving high quality short test suites, the approach that is the combination of randomly generated sequences together with sequences which are aimed to detect faults not detected by random tests, allows to reach the good fault coverage using shortest test sequences.

Design of Sensors for Control of Closed Loop Life Support Systems

NASA Technical Reports Server (NTRS)

1990-01-01

A brief summary is presented of a Engineering Design sequence, a cooperation between NASA-Kennedy and the University of Florida on the Controlled Environmental Life Support System (CELSS) program. Part of the class was devoted to learning general principles and techniques of design. The next portion of the class was devoted to learning to design, actually fabricating and testing small components and subsystems of a CELSS.

Development of Integrated Programs for Aerospace-vehicle design (IPAD): Reference design process

NASA Technical Reports Server (NTRS)

Meyer, D. D.

1979-01-01

The airplane design process and its interfaces with manufacturing and customer operations are documented to be used as criteria for the development of integrated programs for the analysis, design, and testing of aerospace vehicles. Topics cover: design process management, general purpose support requirements, design networks, and technical program elements. Design activity sequences are given for both supersonic and subsonic commercial transports, naval hydrofoils, and military aircraft.

MDR/Omni-band Reconfigurable Terminal: Design Concept

DTIC Science & Technology

1998-09-01

tasks, data bases and major communications flows. Global issues relevant to most of the blocks are then covered. Finally the planned sequence of...and event logger that are detailed in later paragraphs. The BITE(built-in test equipment)/Debugger detail can be found separately in the Global Issues paragraphs...conditions. Every part of the simulator has a BITE/Debugger component, the general description of which is given in Global Issues . Simulator control

Phonological and Semantic Cues to Learning from Word-Types

PubMed Central

Richtsmeier, Peter

2017-01-01

Word-types represent the primary form of data for many models of phonological learning, and they often predict performance in psycholinguistic tasks. Word-types are often tacitly defined as phonologically unique words. Yet, an explicit test of this definition is lacking, and natural language patterning suggests that word meaning could also act as a cue to word-type status. This possibility was tested in a statistical phonotactic learning experiment in which phonological and semantic properties of word-types varied. During familiarization, the learning targets—word-medial consonant sequences—were instantiated either by four related word-types or by just one word-type (the experimental frequency factor). The expectation was that more word-types would lead participants to generalize the target sequences. Regarding semantic cues, related word-types were either associated with different referents or all with a single referent. Regarding phonological cues, related word-types differed from each other by one, two, or more phonemes. At test, participants rated novel wordforms for their similarity to the familiarization words. When participants heard four related word-types, they gave higher ratings to test words with the same consonant sequences, irrespective of the phonological and semantic manipulations. The results support the existing phonological definition of word-types. PMID:29187914

Predicting membrane protein types by incorporating protein topology, domains, signal peptides, and physicochemical properties into the general form of Chou's pseudo amino acid composition.

PubMed

Chen, Yen-Kuang; Li, Kuo-Bin

2013-02-07

The type information of un-annotated membrane proteins provides an important hint for their biological functions. The experimental determination of membrane protein types, despite being more accurate and reliable, is not always feasible due to the costly laboratory procedures, thereby creating a need for the development of bioinformatics methods. This article describes a novel computational classifier for the prediction of membrane protein types using proteins' sequences. The classifier, comprising a collection of one-versus-one support vector machines, makes use of the following sequence attributes: (1) the cationic patch sizes, the orientation, and the topology of transmembrane segments; (2) the amino acid physicochemical properties; (3) the presence of signal peptides or anchors; and (4) the specific protein motifs. A new voting scheme was implemented to cope with the multi-class prediction. Both the training and the testing sequences were collected from SwissProt. Homologous proteins were removed such that there is no pair of sequences left in the datasets with a sequence identity higher than 40%. The performance of the classifier was evaluated by a Jackknife cross-validation and an independent testing experiments. Results show that the proposed classifier outperforms earlier predictors in prediction accuracy in seven of the eight membrane protein types. The overall accuracy was increased from 78.3% to 88.2%. Unlike earlier approaches which largely depend on position-specific substitution matrices and amino acid compositions, most of the sequence attributes implemented in the proposed classifier have supported literature evidences. The classifier has been deployed as a web server and can be accessed at http://bsaltools.ym.edu.tw/predmpt. Copyright © 2012 Elsevier Ltd. All rights reserved.

Breaking the computational barriers of pairwise genome comparison.

PubMed

Torreno, Oscar; Trelles, Oswaldo

2015-08-11

Conventional pairwise sequence comparison software algorithms are being used to process much larger datasets than they were originally designed for. This can result in processing bottlenecks that limit software capabilities or prevent full use of the available hardware resources. Overcoming the barriers that limit the efficient computational analysis of large biological sequence datasets by retrofitting existing algorithms or by creating new applications represents a major challenge for the bioinformatics community. We have developed C libraries for pairwise sequence comparison within diverse architectures, ranging from commodity systems to high performance and cloud computing environments. Exhaustive tests were performed using different datasets of closely- and distantly-related sequences that span from small viral genomes to large mammalian chromosomes. The tests demonstrated that our solution is capable of generating high quality results with a linear-time response and controlled memory consumption, being comparable or faster than the current state-of-the-art methods. We have addressed the problem of pairwise and all-versus-all comparison of large sequences in general, greatly increasing the limits on input data size. The approach described here is based on a modular out-of-core strategy that uses secondary storage to avoid reaching memory limits during the identification of High-scoring Segment Pairs (HSPs) between the sequences under comparison. Software engineering concepts were applied to avoid intermediate result re-calculation, to minimise the performance impact of input/output (I/O) operations and to modularise the process, thus enhancing application flexibility and extendibility. Our computationally-efficient approach allows tasks such as the massive comparison of complete genomes, evolutionary event detection, the identification of conserved synteny blocks and inter-genome distance calculations to be performed more effectively.

Enzymatic repair of selected cross-linked homoduplex molecules enhances nuclear gene rescue from Pompeii and Herculaneum remains.

PubMed

Di Bernardo, Giovanni; Del Gaudio, Stefania; Cammarota, Marcella; Galderisi, Umberto; Cascino, Antonino; Cipollaro, Marilena

2002-02-15

Ancient DNA (aDNA) samples extracted from the bone remains of six equids buried by the Vesuvius eruption in 79 AD were investigated to test pre-amplification and enzymatic repair procedures designed to enhance the rescue of nuclear genes. The extracts, which proved all positive for Equidae mtDNA amplification, proved positive only four times out of 18 when tested for single-copy Equidae nuclear genes (epsilon globin, p53 and gamma interferon). Pre-amplification did not change the number of retrieved aDNA sequences but 10 times out of 14 enzymatic repair restored the amplifiability of the genes analysed, proving that repair increases the rate of successful rescue from 22 to alpha(lambda)mu(omicron)sigma(tau) 80%. These findings support the hypothesis that some of these cross-linked aDNA molecules, which are not completely separated when DNA is extracted under denaturing conditions, become homoduplex substrates for Pol I and/or T4 ligase action upon renaturation. aDNA authenticity is proved by the homology of the nucleotide sequences of loci tested to the corresponding modern Equidae sequences. Data also indicate that cross-linked homoduplex molecules selected by denaturation of the extract are repaired without any chimera formation. The general features of aDNA amplification with and without denaturation and enzymatic repair are discussed.

Enzymatic repair of selected cross-linked homoduplex molecules enhances nuclear gene rescue from Pompeii and Herculaneum remains

PubMed Central

Di Bernardo, Giovanni; Del Gaudio, Stefania; Cammarota, Marcella; Galderisi, Umberto; Cascino, Antonino; Cipollaro, Marilena

2002-01-01

Ancient DNA (aDNA) samples extracted from the bone remains of six equids buried by the Vesuvius eruption in 79 AD were investigated to test pre-amplification and enzymatic repair procedures designed to enhance the rescue of nuclear genes. The extracts, which proved all positive for Equidae mtDNA amplification, proved positive only four times out of 18 when tested for single-copy Equidae nuclear genes (ɛ globin, p53 and γ interferon). Pre-amplification did not change the number of retrieved aDNA sequences but 10 times out of 14 enzymatic repair restored the amplifiability of the genes analysed, proving that repair increases the rate of successful rescue from 22 to αλµοστ 80%. These findings support the hypothesis that some of these cross-linked aDNA molecules, which are not completely separated when DNA is extracted under denaturing conditions, become homoduplex substrates for Pol I and/or T4 ligase action upon renaturation. aDNA authenticity is proved by the homology of the nucleotide sequences of loci tested to the corresponding modern Equidae sequences. Data also indicate that cross-linked homoduplex molecules selected by denaturation of the extract are repaired without any chimera formation. The general features of aDNA amplification with and without denaturation and enzymatic repair are discussed. PMID:11842122

iHyd-PseCp: Identify hydroxyproline and hydroxylysine in proteins by incorporating sequence-coupled effects into general PseAAC.

PubMed

Qiu, Wang-Ren; Sun, Bi-Qian; Xiao, Xuan; Xu, Zhao-Chun; Chou, Kuo-Chen

2016-07-12

Protein hydroxylation is a posttranslational modification (PTM), in which a CH group in Pro (P) or Lys (K) residue has been converted into a COH group, or a hydroxyl group (-OH) is converted into an organic compound. Closely associated with cellular signaling activities, this type of PTM is also involved in some major diseases, such as stomach cancer and lung cancer. Therefore, from the angles of both basic research and drug development, we are facing a challenging problem: for an uncharacterized protein sequence containing many residues of P or K, which ones can be hydroxylated, and which ones cannot? With the explosive growth of protein sequences in the post-genomic age, the problem has become even more urgent. To address such a problem, we have developed a predictor called iHyd-PseCp by incorporating the sequence-coupled information into the general pseudo amino acid composition (PseAAC) and introducing the "Random Forest" algorithm to operate the calculation. Rigorous jackknife tests indicated that the new predictor remarkably outperformed the existing state-of-the-art prediction method for the same purpose. For the convenience of most experimental scientists, a user-friendly web-server for iHyd-PseCp has been established at http://www.jci-bioinfo.cn/iHyd-PseCp, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved.

Maximizing lipocalin prediction through balanced and diversified training set and decision fusion.

PubMed

Nath, Abhigyan; Subbiah, Karthikeyan

2015-12-01

Lipocalins are short in sequence length and perform several important biological functions. These proteins are having less than 20% sequence similarity among paralogs. Experimentally identifying them is an expensive and time consuming process. The computational methods based on the sequence similarity for allocating putative members to this family are also far elusive due to the low sequence similarity existing among the members of this family. Consequently, the machine learning methods become a viable alternative for their prediction by using the underlying sequence/structurally derived features as the input. Ideally, any machine learning based prediction method must be trained with all possible variations in the input feature vector (all the sub-class input patterns) to achieve perfect learning. A near perfect learning can be achieved by training the model with diverse types of input instances belonging to the different regions of the entire input space. Furthermore, the prediction performance can be improved through balancing the training set as the imbalanced data sets will tend to produce the prediction bias towards majority class and its sub-classes. This paper is aimed to achieve (i) the high generalization ability without any classification bias through the diversified and balanced training sets as well as (ii) enhanced the prediction accuracy by combining the results of individual classifiers with an appropriate fusion scheme. Instead of creating the training set randomly, we have first used the unsupervised Kmeans clustering algorithm to create diversified clusters of input patterns and created the diversified and balanced training set by selecting an equal number of patterns from each of these clusters. Finally, probability based classifier fusion scheme was applied on boosted random forest algorithm (which produced greater sensitivity) and K nearest neighbour algorithm (which produced greater specificity) to achieve the enhanced predictive performance than that of individual base classifiers. The performance of the learned models trained on Kmeans preprocessed training set is far better than the randomly generated training sets. The proposed method achieved a sensitivity of 90.6%, specificity of 91.4% and accuracy of 91.0% on the first test set and sensitivity of 92.9%, specificity of 96.2% and accuracy of 94.7% on the second blind test set. These results have established that diversifying training set improves the performance of predictive models through superior generalization ability and balancing the training set improves prediction accuracy. For smaller data sets, unsupervised Kmeans based sampling can be an effective technique to increase generalization than that of the usual random splitting method. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tribonacci-Like Sequences and Generalized Pascal's Pyramids

ERIC Educational Resources Information Center

Anatriello, Giuseppina; Vincenzi, Giovanni

2014-01-01

A well-known result of Feinberg and Shannon states that the tribonacci sequence can be detected by the so-called "Pascal's pyramid." Here we will show that any tribonacci-like sequence can be obtained by the diagonals of the "Feinberg's triangle" associated to a suitable "generalized Pascal's pyramid."…

From Environmental Sequences to Morphology: Observation and Characterisation of a Paulinellid Testate Amoeba (Micropyxidiella edaphonis gen. nov. sp. nov. Euglyphida, Paulinellidae) from Soil using Fluorescent in situ Hybridization.

PubMed

Tarnawski, Sonia-Estelle; Lara, Enrique

2015-05-01

High microbial diversity is revealed by environmental DNA surveys. However, nothing is known about the morphology and function of these potentially new organisms. In the course of an environmental soil diversity study, we found for the first time environmental sequences that reveal the presence of Paulinellidae (a mostly marine and marginally freshwater family of euglyphid testate amoebae) in samples of forest litter from different geographic origins. The new sequences form a basal, robust clade in the family. We used fluorescent in situ hybridization (FISH) to detect the organisms from which these sequences derived. We isolated the cells and documented them with light and scanning electron microscopy. Based on these observations, we described these organisms as Micropyxidiella edaphonis gen. nov. sp. nov. The organisms were very small testate amoebae (generally less than 10μm) with an irregular proteinaceous test. This suggests an unknown diversity in testate amoebae, and calls for extending this type of investigations to other protist groups which are known only as environmental DNA sequences. Copyright © 2015 Elsevier GmbH. All rights reserved.

Correlation between MCAT biology content specifications and topic scope and sequence of general education college biology textbooks.

PubMed

Rissing, Steven W

2013-01-01

Most American colleges and universities offer gateway biology courses to meet the needs of three undergraduate audiences: biology and related science majors, many of whom will become biomedical researchers; premedical students meeting medical school requirements and preparing for the Medical College Admissions Test (MCAT); and students completing general education (GE) graduation requirements. Biology textbooks for these three audiences present a topic scope and sequence that correlates with the topic scope and importance ratings of the biology content specifications for the MCAT regardless of the intended audience. Texts for "nonmajors," GE courses appear derived directly from their publisher's majors text. Topic scope and sequence of GE texts reflect those of "their" majors text and, indirectly, the MCAT. MCAT term density of GE texts equals or exceeds that of their corresponding majors text. Most American universities require a GE curriculum to promote a core level of academic understanding among their graduates. This includes civic scientific literacy, recognized as an essential competence for the development of public policies in an increasingly scientific and technological world. Deriving GE biology and related science texts from majors texts designed to meet very different learning objectives may defeat the scientific literacy goals of most schools' GE curricula.

Correlation between MCAT Biology Content Specifications and Topic Scope and Sequence of General Education College Biology Textbooks

PubMed Central

Rissing, Steven W.

2013-01-01

Most American colleges and universities offer gateway biology courses to meet the needs of three undergraduate audiences: biology and related science majors, many of whom will become biomedical researchers; premedical students meeting medical school requirements and preparing for the Medical College Admissions Test (MCAT); and students completing general education (GE) graduation requirements. Biology textbooks for these three audiences present a topic scope and sequence that correlates with the topic scope and importance ratings of the biology content specifications for the MCAT regardless of the intended audience. Texts for “nonmajors,” GE courses appear derived directly from their publisher's majors text. Topic scope and sequence of GE texts reflect those of “their” majors text and, indirectly, the MCAT. MCAT term density of GE texts equals or exceeds that of their corresponding majors text. Most American universities require a GE curriculum to promote a core level of academic understanding among their graduates. This includes civic scientific literacy, recognized as an essential competence for the development of public policies in an increasingly scientific and technological world. Deriving GE biology and related science texts from majors texts designed to meet very different learning objectives may defeat the scientific literacy goals of most schools’ GE curricula. PMID:24006392

Changes in behavior and salivary cortisol after targeted cognitive training in typical 12-month-old infants.

PubMed

Wass, Sam V; Cook, Clare; Clackson, Kaili

2017-05-01

Previous research has suggested that early development may be an optimal period to implement cognitive training interventions, particularly those relating to attention control, a basic ability that is essential for the development of other cognitive skills. In the present study, we administered gaze-contingent training (95 min across 2 weeks) targeted at voluntary attention control to a cohort of typical 12-month-old children (N = 24) and sham training to a control group (N = 24). We assessed training effects on (a) tasks involving nontrained aspects of attention control: visual sustained attention, habituation speed, visual recognition memory, sequence learning, and reversal learning; (b) general attentiveness (on-task behaviors during testing); and (c) salivary cortisol levels. Assessments were administered immediately after the cessation of training and at a 6-week follow-up. On the immediate posttest infants showed significantly more sustained visual attention, faster habituation, and improved sequence learning. Significant effects were also found for increased general attentiveness and decreased salivary cortisol. Some of these effects were still evident at the 6-week follow-up (significantly improved sequence learning and marginally improved sustained attention). These findings extend the emerging literature showing that attention training is possible in infancy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Three closely related herpesviruses are associated with fibropapillomatosis in marine turtles

USGS Publications Warehouse

Quackenbush, S.L.; Work, Thierry M.; Balazs, George H.; Casey, Rufina N.; Rovnak, J.; Chaves, A.; duToit, L.; Baines, J.D.; Parrish, C.R.; Bowser, Paul R.; Casey, James W.

1998-01-01

Green turtle fibropapillomatosis is a neoplastic disease of increasingly significant threat to the survivability of this species. Degenerate PCR primers that target highly conserved regions of genes encoding herpesvirus DNA polymerases were used to amplify a DNA sequence from fibropapillomas and fibromas from Hawaiian and Florida green turtles. All of the tumors tested (n= 23) were found to harbor viral DNA, whereas no viral DNA was detected in skin biopsies from tumor-negative turtles. The tissue distribution of the green turtle herpesvirus appears to be generally limited to tumors where viral DNA was found to accumulate at approximately two to five copies per cell and is occasionally detected, only by PCR, in some tissues normally associated with tumor development. In addition, herpesviral DNA was detected in fibropapillomas from two loggerhead and four olive ridley turtles. Nucleotide sequencing of a 483-bp fragment of the turtle herpesvirus DNA polymerase gene determined that the Florida green turtle and loggerhead turtle sequences are identical and differ from the Hawaiian green turtle sequence by five nucleotide changes, which results in two amino acid substitutions. The olive ridley sequence differs from the Florida and Hawaiian green turtle sequences by 15 and 16 nucleotide changes, respectively, resulting in four amino acid substitutions, three of which are unique to the olive ridley sequence. Our data suggest that these closely related turtle herpesviruses are intimately involved in the genesis of fibropapillomatosis.

Enhanced spatio-temporal alignment of plantar pressure image sequences using B-splines.

PubMed

Oliveira, Francisco P M; Tavares, João Manuel R S

2013-03-01

This article presents an enhanced methodology to align plantar pressure image sequences simultaneously in time and space. The temporal alignment of the sequences is accomplished using B-splines in the time modeling, and the spatial alignment can be attained using several geometric transformation models. The methodology was tested on a dataset of 156 real plantar pressure image sequences (3 sequences for each foot of the 26 subjects) that was acquired using a common commercial plate during barefoot walking. In the alignment of image sequences that were synthetically deformed both in time and space, an outstanding accuracy was achieved with the cubic B-splines. This accuracy was significantly better (p < 0.001) than the one obtained using the best solution proposed in our previous work. When applied to align real image sequences with unknown transformation involved, the alignment based on cubic B-splines also achieved superior results than our previous methodology (p < 0.001). The consequences of the temporal alignment on the dynamic center of pressure (COP) displacement was also assessed by computing the intraclass correlation coefficients (ICC) before and after the temporal alignment of the three image sequence trials of each foot of the associated subject at six time instants. The results showed that, generally, the ICCs related to the medio-lateral COP displacement were greater when the sequences were temporally aligned than the ICCs of the original sequences. Based on the experimental findings, one can conclude that the cubic B-splines are a remarkable solution for the temporal alignment of plantar pressure image sequences. These findings also show that the temporal alignment can increase the consistency of the COP displacement on related acquired plantar pressure image sequences.

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.

PubMed

Vissers, Lisenka E L M; van Nimwegen, Kirsten J M; Schieving, Jolanda H; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A; Willemsen, Michèl A A P

2017-09-01

Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously. Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017.

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

PubMed Central

Vissers, Lisenka E.L.M.; van Nimwegen, Kirsten J.M.; Schieving, Jolanda H.; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G.; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G.; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A.; Willemsen, Michèl A.A.P.

2017-01-01

Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene–based testing) and WES simultaneously. Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin. Genet Med advance online publication 23 March 2017 PMID:28333917

Test versus analysis: A discussion of methods

NASA Technical Reports Server (NTRS)

Butler, T. G.

1986-01-01

Some techniques for comparing structural vibration data determined from test and analysis are discussed. Orthogonality is a general category of one group, correlation is a second, synthesis is a third and matrix improvement is a fourth. Advantages and short-comings of the methods are explored with suggestions as to how they can complement one another. The purpose for comparing vibration data from test and analysis for a given structure is to find out whether each is representing the dynamic properties of the structure in the same way. Specifically, whether: mode shapes are alike; the frequencies of the modes are alike; modes appear in the same frequency sequence; and if they are not alike, how to judge which to believe.

A Window Into Clinical Next-Generation Sequencing-Based Oncology Testing Practices.

PubMed

Nagarajan, Rakesh; Bartley, Angela N; Bridge, Julia A; Jennings, Lawrence J; Kamel-Reid, Suzanne; Kim, Annette; Lazar, Alexander J; Lindeman, Neal I; Moncur, Joel; Rai, Alex J; Routbort, Mark J; Vasalos, Patricia; Merker, Jason D

2017-12-01

- Detection of acquired variants in cancer is a paradigm of precision medicine, yet little has been reported about clinical laboratory practices across a broad range of laboratories. - To use College of American Pathologists proficiency testing survey results to report on the results from surveys on next-generation sequencing-based oncology testing practices. - College of American Pathologists proficiency testing survey results from more than 250 laboratories currently performing molecular oncology testing were used to determine laboratory trends in next-generation sequencing-based oncology testing. - These presented data provide key information about the number of laboratories that currently offer or are planning to offer next-generation sequencing-based oncology testing. Furthermore, we present data from 60 laboratories performing next-generation sequencing-based oncology testing regarding specimen requirements and assay characteristics. The findings indicate that most laboratories are performing tumor-only targeted sequencing to detect single-nucleotide variants and small insertions and deletions, using desktop sequencers and predesigned commercial kits. Despite these trends, a diversity of approaches to testing exists. - This information should be useful to further inform a variety of topics, including national discussions involving clinical laboratory quality systems, regulation and oversight of next-generation sequencing-based oncology testing, and precision oncology efforts in a data-driven manner.

StrBioLib: a Java library for development of custom computational structural biology applications.

PubMed

Chandonia, John-Marc

2007-08-01

StrBioLib is a library of Java classes useful for developing software for computational structural biology research. StrBioLib contains classes to represent and manipulate protein structures, biopolymer sequences, sets of biopolymer sequences, and alignments between biopolymers based on either sequence or structure. Interfaces are provided to interact with commonly used bioinformatics applications, including (psi)-blast, modeller, muscle and Primer3, and tools are provided to read and write many file formats used to represent bioinformatic data. The library includes a general-purpose neural network object with multiple training algorithms, the Hooke and Jeeves non-linear optimization algorithm, and tools for efficient C-style string parsing and formatting. StrBioLib is the basis for the Pred2ary secondary structure prediction program, is used to build the astral compendium for sequence and structure analysis, and has been extensively tested through use in many smaller projects. Examples and documentation are available at the site below. StrBioLib may be obtained under the terms of the GNU LGPL license from http://strbio.sourceforge.net/

Whole genome sequencing data and de novo draft assemblies for 66 teleost species

PubMed Central

Malmstrøm, Martin; Matschiner, Michael; Tørresen, Ole K.; Jakobsen, Kjetill S.; Jentoft, Sissel

2017-01-01

Teleost fishes comprise more than half of all vertebrate species, yet genomic data are only available for 0.2% of their diversity. Here, we present whole genome sequencing data for 66 new species of teleosts, vastly expanding the availability of genomic data for this important vertebrate group. We report on de novo assemblies based on low-coverage (9–39×) sequencing and present detailed methodology for all analyses. To facilitate further utilization of this data set, we present statistical analyses of the gene space completeness and verify the expected phylogenetic position of the sequenced genomes in a large mitogenomic context. We further present a nuclear marker set used for phylogenetic inference and evaluate each gene tree in relation to the species tree to test for homogeneity in the phylogenetic signal. Collectively, these analyses illustrate the robustness of this highly diverse data set and enable extensive reuse of the selected phylogenetic markers and the genomic data in general. This data set covers all major teleost lineages and provides unprecedented opportunities for comparative studies of teleosts. PMID:28094797

Youth in crisis: dimensions of self-destructive conduct among adolescent prisoners.

PubMed

Johnson, R

1978-01-01

Self-mutilation and attempted suidcide among adolescent prisoners are explored in relation to concrete coping tests posed in prison and to self-esteem problems posed by failure of external (family) and internal (peer) support systems. Crisis sequences are traced using verbatim excerpts from interviews with self-destructive prisoners and conceptualized in terms of enduring adolescent needs and concerns. Some general observations regarding strategies of intervention with crisisprone prisoners are included.

Department of Defense Fiscal Year (FY) 2005 Budget Estimates. Research, Development, Test and Evaluation, Defense-Wide. Volume 1 - Defense Advanced Research Projects Agency

DTIC Science & Technology

2004-02-01

UNCLASSIFIED − Conducted experiments to determine the usability of general-purpose anomaly detection algorithms to monitor a large, complex military...reaction and detection modules to perform tailored analysis sequences to monitor environmental conditions, health hazards and physiological states...scalability of lab proven anomaly detection techniques for intrusion detection in real world high volume environments. Narrative Title FY 2003

Decreased Load on General Motor Preparation and Visual-Working Memory while Preparing Familiar as Compared to Unfamiliar Movement Sequences

ERIC Educational Resources Information Center

De Kleine, Elian; Van der Lubbe, Rob H. J.

2011-01-01

Learning movement sequences is thought to develop from an initial controlled attentive phase to a more automatic inattentive phase. Furthermore, execution of sequences becomes faster with practice, which may result from changes at a general motor processing level rather than at an effector specific motor processing level. In the current study, we…

General distribution of the nitrogen control gene ntcA in cyanobacteria.

PubMed Central

Frías, J E; Mérida, A; Herrero, A; Martín-Nieto, J; Flores, E

1993-01-01

The ntcA gene from Synechococcus sp. strain PCC 7942 encodes a regulatory protein which is required for the expression of all of the genes known to be subject to repression by ammonium in that cyanobacterium. Homologs to ntcA have now been cloned by hybridization from the cyanobacteria Synechocystis sp. strain PCC 6803 and Anabaena sp. strain PCC 7120. Sequence analysis has shown that these ntcA genes would encode polypeptides strongly similar (77 to 79% identity) to the Synechococcus NtcA protein. Sequences hybridizing to ntcA have been detected in the genomes of nine other cyanobacteria that were tested, including strains of the genera Anabaena, Calothrix, Fischerella, Nostoc, Pseudoanabaena, Synechococcus, and Synechocystis. Images PMID:8366058

Statistical tests for detecting associations with groups of genetic variants: generalization, evaluation, and implementation

PubMed Central

Ferguson, John; Wheeler, William; Fu, YiPing; Prokunina-Olsson, Ludmila; Zhao, Hongyu; Sampson, Joshua

2013-01-01

With recent advances in sequencing, genotyping arrays, and imputation, GWAS now aim to identify associations with rare and uncommon genetic variants. Here, we describe and evaluate a class of statistics, generalized score statistics (GSS), that can test for an association between a group of genetic variants and a phenotype. GSS are a simple weighted sum of single-variant statistics and their cross-products. We show that the majority of statistics currently used to detect associations with rare variants are equivalent to choosing a specific set of weights within this framework. We then evaluate the power of various weighting schemes as a function of variant characteristics, such as MAF, the proportion associated with the phenotype, and the direction of effect. Ultimately, we find that two classical tests are robust and powerful, but details are provided as to when other GSS may perform favorably. The software package CRaVe is available at our website (http://dceg.cancer.gov/bb/tools/crave). PMID:23092956

Posttest analysis of MIST Test 320201 using TRAC-PF1/MOD1

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

Siebe, D.A.; Steiner, J.L.; Boyack, B.E.

A posttest calculation and analysis of Multi-Loop Integral System Test 320201, a small-break loss-of-coolant accident (SBLOCA) test with a scaled 50-cm{sup 2} cold-leg pump discharge leak, has been completed and is reported herein. It was one in a series of tests, with leak size varied parametrically. Scaled leak sizes included 5, 10, (the nominal, Test 3109AA), and 50 cm{sub 2}. The test exhibited the major post-SBLOCA phenomena, as expected, including depressurization to saturation, interruption of loop flow, boiler-condenser mode cooling, refill, and postrefill cooldown. Full high-pressure injection and auxiliary feedwater were available, reactor coolant pumps were not available, and reactor-vesselmore » vent valves and guard heaters were automatically controlled. Constant level control in the steam-generator (SG) secondaries was used after SG-secondary refill; and symmetric SG pressure control was also used. The sequence of events seen in this test was similar to the sequence of events for much of the nominal test except that events occurred in a shorter time frame as the system inventory was reduced and the system depressurized at a faster rate. The calculation was performed using TRAC-PFL/MOD 1. Agreement between test data and the calculation was generally reasonable. All major trends and phenomena were correctly predicted. We believe that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications.« less

Posttest analysis of MIST Test 320201 using TRAC-PF1/MOD1

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

Siebe, D.A.; Steiner, J.L.; Boyack, B.E.

A posttest calculation and analysis of Multi-Loop Integral System Test 320201, a small-break loss-of-coolant accident (SBLOCA) test with a scaled 50-cm[sup 2] cold-leg pump discharge leak, has been completed and is reported herein. It was one in a series of tests, with leak size varied parametrically. Scaled leak sizes included 5, 10, (the nominal, Test 3109AA), and 50 cm[sub 2]. The test exhibited the major post-SBLOCA phenomena, as expected, including depressurization to saturation, interruption of loop flow, boiler-condenser mode cooling, refill, and postrefill cooldown. Full high-pressure injection and auxiliary feedwater were available, reactor coolant pumps were not available, and reactor-vesselmore » vent valves and guard heaters were automatically controlled. Constant level control in the steam-generator (SG) secondaries was used after SG-secondary refill; and symmetric SG pressure control was also used. The sequence of events seen in this test was similar to the sequence of events for much of the nominal test except that events occurred in a shorter time frame as the system inventory was reduced and the system depressurized at a faster rate. The calculation was performed using TRAC-PFL/MOD 1. Agreement between test data and the calculation was generally reasonable. All major trends and phenomena were correctly predicted. We believe that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications.« less

A Unified Mixed-Effects Model for Rare-Variant Association in Sequencing Studies

PubMed Central

Sun, Jianping; Zheng, Yingye; Hsu, Li

2013-01-01

For rare-variant association analysis, due to extreme low frequencies of these variants, it is necessary to aggregate them by a prior set (e.g., genes and pathways) in order to achieve adequate power. In this paper, we consider hierarchical models to relate a set of rare variants to phenotype by modeling the effects of variants as a function of variant characteristics while allowing for variant-specific effect (heterogeneity). We derive a set of two score statistics, testing the group effect by variant characteristics and the heterogeneity effect. We make a novel modification to these score statistics so that they are independent under the null hypothesis and their asymptotic distributions can be derived. As a result, the computational burden is greatly reduced compared with permutation-based tests. Our approach provides a general testing framework for rare variants association, which includes many commonly used tests, such as the burden test [Li and Leal, 2008] and the sequence kernel association test [Wu et al., 2011], as special cases. Furthermore, in contrast to these tests, our proposed test has an added capacity to identify which components of variant characteristics and heterogeneity contribute to the association. Simulations under a wide range of scenarios show that the proposed test is valid, robust and powerful. An application to the Dallas Heart Study illustrates that apart from identifying genes with significant associations, the new method also provides additional information regarding the source of the association. Such information may be useful for generating hypothesis in future studies. PMID:23483651

Decision Tree Algorithm-Generated Single-Nucleotide Polymorphism Barcodes of rbcL Genes for 38 Brassicaceae Species Tagging.

PubMed

Yang, Cheng-Hong; Wu, Kuo-Chuan; Chuang, Li-Yeh; Chang, Hsueh-Wei

2018-01-01

DNA barcode sequences are accumulating in large data sets. A barcode is generally a sequence larger than 1000 base pairs and generates a computational burden. Although the DNA barcode was originally envisioned as straightforward species tags, the identification usage of barcode sequences is rarely emphasized currently. Single-nucleotide polymorphism (SNP) association studies provide us an idea that the SNPs may be the ideal target of feature selection to discriminate between different species. We hypothesize that SNP-based barcodes may be more effective than the full length of DNA barcode sequences for species discrimination. To address this issue, we tested a r ibulose diphosphate carboxylase ( rbcL ) S NP b arcoding (RSB) strategy using a decision tree algorithm. After alignment and trimming, 31 SNPs were discovered in the rbcL sequences from 38 Brassicaceae plant species. In the decision tree construction, these SNPs were computed to set up the decision rule to assign the sequences into 2 groups level by level. After algorithm processing, 37 nodes and 31 loci were required for discriminating 38 species. Finally, the sequence tags consisting of 31 rbcL SNP barcodes were identified for discriminating 38 Brassicaceae species based on the decision tree-selected SNP pattern using RSB method. Taken together, this study provides the rational that the SNP aspect of DNA barcode for rbcL gene is a useful and effective sequence for tagging 38 Brassicaceae species.

The Rare-Variant Generalized Disequilibrium Test for Association Analysis of Nuclear and Extended Pedigrees with Application to Alzheimer Disease WGS Data.

PubMed

He, Zongxiao; Zhang, Di; Renton, Alan E; Li, Biao; Zhao, Linhai; Wang, Gao T; Goate, Alison M; Mayeux, Richard; Leal, Suzanne M

2017-02-02

Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population-based designs. Moreover, some family-based designs are robust to confounding due to population admixture or substructure. We developed a RV extension of the generalized disequilibrium test (GDT) to analyze sequence data obtained from nuclear and extended families. The GDT utilizes genotype differences of all discordant relative pairs to assess associations within a family, and the RV extension combines the single-variant GDT statistic over a genomic region of interest. The RV-GDT has increased power by efficiently incorporating information beyond first-degree relatives and allows for the inclusion of covariates. Using simulated genetic data, we demonstrated that the RV-GDT method has well-controlled type I error rates, even when applied to admixed populations and populations with substructure. It is more powerful than existing family-based RV association methods, particularly for the analysis of extended pedigrees and pedigrees with missing data. We analyzed whole-genome sequence data from families affected by Alzheimer disease to illustrate the application of the RV-GDT. Given the capability of the RV-GDT to adequately control for population admixture or substructure and analyze pedigrees with missing genotype data and its superior power over other family-based methods, it is an effective tool for elucidating the involvement of RVs in the etiology of complex traits. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Necessary Sequencing Depth and Clustering Method to Obtain Relatively Stable Diversity Patterns in Studying Fish Gut Microbiota.

PubMed

Xiao, Fanshu; Yu, Yuhe; Li, Jinjin; Juneau, Philippe; Yan, Qingyun

2018-05-25

The 16S rRNA gene is one of the most commonly used molecular markers for estimating bacterial diversity during the past decades. However, there is no consistency about the sequencing depth (from thousand to millions of sequences per sample), and the clustering methods used to generate OTUs may also be different among studies. These inconsistent premises make effective comparisons among studies difficult or unreliable. This study aims to examine the necessary sequencing depth and clustering method that would be needed to ensure a stable diversity patterns for studying fish gut microbiota. A total number of 42 samples dataset of Siniperca chuatsi (carnivorous fish) gut microbiota were used to test how the sequencing depth and clustering may affect the alpha and beta diversity patterns of fish intestinal microbiota. Interestingly, we found that the sequencing depth (resampling 1000-11,000 per sample) and the clustering methods (UPARSE and UCLUST) did not bias the estimates of the diversity patterns during the fish development from larva to adult. Although we should acknowledge that a suitable sequencing depth may differ case by case, our finding indicates that a shallow sequencing such as 1000 sequences per sample may be also enough to reflect the general diversity patterns of fish gut microbiota. However, we have shown in the present study that strict pre-processing of the original sequences is required to ensure reliable results. This study provides evidences to help making a strong scientific choice of the sequencing depth and clustering method for future studies on fish gut microbiota patterns, but at the same time reducing as much as possible the costs related to the analysis.

Program for Editing Spacecraft Command Sequences

NASA Technical Reports Server (NTRS)

Gladden, Roy; Waggoner, Bruce; Kordon, Mark; Hashemi, Mahnaz; Hanks, David; Salcedo, Jose

2006-01-01

Sequence Translator, Editor, and Expander Resource (STEER) is a computer program that facilitates construction of sequences and blocks of sequences (hereafter denoted generally as sequence products) for commanding a spacecraft. STEER also provides mechanisms for translating among various sequence product types and quickly expanding activities of a given sequence in chronological order for review and analysis of the sequence. To date, construction of sequence products has generally been done by use of such clumsy mechanisms as text-editor programs, translating among sequence product types has been challenging, and expanding sequences to time-ordered lists has involved arduous processes of converting sequence products to "real" sequences and running them through Class-A software (defined, loosely, as flight and ground software critical to a spacecraft mission). Also, heretofore, generating sequence products in standard formats has been troublesome because precise formatting and syntax are required. STEER alleviates these issues by providing a graphical user interface containing intuitive fields in which the user can enter the necessary information. The STEER expansion function provides a "quick and dirty" means of seeing how a sequence and sequence block would expand into a chronological list, without need to use of Class-A software.

Rapidly rotating polytropes in general relativity

NASA Technical Reports Server (NTRS)

Cook, Gregory B.; Shapiro, Stuart L.; Teukolsky, Saul A.

1994-01-01

We construct an extensive set of equilibrium sequences of rotating polytropes in general relativity. We determine a number of important physical parameters of such stars, including maximum mass and maximum spin rate. The stability of the configurations against quasi-radial perturbations is diagnosed. Two classes of evolutionary sequences of fixed rest mass and entropy are explored: normal sequences which behave very much like Newtonian evolutionary sequences, and supramassive sequences which exist solely because of relativistic effects. Dissipation leading to loss of angular momentum causes a star to evolve in a quasi-stationary fashion along an evolutionary sequence. Supramassive sequences evolve towards eventual catastrophic collapse to a black hole. Prior to collapse, the star must spin up as it loses angular momentum, an effect which may provide an observational precursor to gravitational collapse to a black hole.

Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer.

PubMed

Kurian, Allison W; Ward, Kevin C; Hamilton, Ann S; Deapen, Dennis M; Abrahamse, Paul; Bondarenko, Irina; Li, Yun; Hawley, Sarah T; Morrow, Monica; Jagsi, Reshma; Katz, Steven J

2018-05-10

Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice. To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories. Type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines. Among 5026 patients (mean [SD] age, 59.9 [10.7]), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%;in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 (BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%). Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.

Infectious pancreatic necrosis virus in Atlantic salmon, Salmo salar L., post-smolts in the Shetland Isles, Scotland: virus identification, histopathology, immunohistochemistry and genetic comparison with Scottish mainland isolates.

PubMed

Smail, D A; Bain, N; Bruno, D W; King, J A; Thompson, F; Pendrey, D J; Morrice, S; Cunningham, C O

2006-01-01

During mid-June 1999 peak mortalities of 11% of the total stock per week were seen at a sea cage site of Atlantic salmon, Salmo salar L., post-smolts in the Shetland Isles, Scotland. Virus was isolated on chinook salmon embryo (CHSE) cells in a standard diagnostic test and infectious pancreatic necrosis virus (IPNV) identified by enzyme-linked immunosorbent assay. IPNV was confirmed as serogroup A by a cell immunofluorescent antibody test using the cross-reactive monoclonal antibody AS-1. Four weeks after the main outbreak, virus titres in surviving moribund fish were assayed at >10(10) TCID50 g(-1) kidney. Histopathology of moribund fish was characterized by pancreatic acinar cell necrosis and a marked catarrhal enteritis of the intestinal mucosa. In the liver, necrosis, leucocytic infiltration and a generalized cell vacuolation were noted. IPNV-specific immunostaining was demonstrated in pancreas, liver, heart, gill and kidney tissue. The nucleotide sequence of the coding region of segment A was determined from the Shetland isolate. A 1180 bp fragment of the VP2 gene of this isolate was compared with a 1979 reference isolate from mainland Scottish Atlantic salmon, La/79 and another more recent mainland isolate, 432/00. Both A2 isolates were derived from carrier fish without signs of IPN and serotyped by a plaque neutralization test. The Shetland isolate shows a different nucleotide and amino acid sequence compared with the two isolates from carrier fish. These latter isolates showed identical amino acid sequences in the fragment examined, despite the 21 years separating the isolations. Sequence comparisons with other A2 (Sp) isolates on the database confirm all three Scottish isolates are A2 (Sp).

Diagnosis - Using automatic test equipment and artificial intelligence expert systems

NASA Astrophysics Data System (ADS)

Ramsey, J. E., Jr.

Three expert systems (ATEOPS, ATEFEXPERS, and ATEFATLAS), which were created to direct automatic test equipment (ATE), are reviewed. The purpose of the project was to develop an expert system to troubleshoot the converter-programmer power supply card for the F-15 aircraft and have that expert system direct the automatic test equipment. Each expert system uses a different knowledge base or inference engine, basing the testing on the circuit schematic, test requirements document, or ATLAS code. Implementing generalized modules allows the expert systems to be used for any different unit under test. Using converted ATLAS to LISP code allows the expert system to direct any ATE using ATLAS. The constraint propagated frame system allows for the expansion of control by creating the ATLAS code, checking the code for good software engineering techniques, directing the ATE, and changing the test sequence as needed (planning).

All APAPs Are Not Equivalent for the Treatment of Sleep Disordered Breathing: A Bench Evaluation of Eleven Commercially Available Devices.

PubMed

Zhu, Kaixian; Roisman, Gabriel; Aouf, Sami; Escourrou, Pierre

2015-07-15

This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports. Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle. In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports. Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study. © 2015 American Academy of Sleep Medicine.

Push it to the limit: Characterizing the convergence of common sequences of basis sets for intermolecular interactions as described by density functional theory

NASA Astrophysics Data System (ADS)

Witte, Jonathon; Neaton, Jeffrey B.; Head-Gordon, Martin

2016-05-01

With the aim of systematically characterizing the convergence of common families of basis sets such that general recommendations for basis sets can be made, we have tested a wide variety of basis sets against complete-basis binding energies across the S22 set of intermolecular interactions—noncovalent interactions of small and medium-sized molecules consisting of first- and second-row atoms—with three distinct density functional approximations: SPW92, a form of local-density approximation; B3LYP, a global hybrid generalized gradient approximation; and B97M-V, a meta-generalized gradient approximation with nonlocal correlation. We have found that it is remarkably difficult to reach the basis set limit; for the methods and systems examined, the most complete basis is Jensen's pc-4. The Dunning correlation-consistent sequence of basis sets converges slowly relative to the Jensen sequence. The Karlsruhe basis sets are quite cost effective, particularly when a correction for basis set superposition error is applied: counterpoise-corrected def2-SVPD binding energies are better than corresponding energies computed in comparably sized Dunning and Jensen bases, and on par with uncorrected results in basis sets 3-4 times larger. These trends are exhibited regardless of the level of density functional approximation employed. A sense of the magnitude of the intrinsic incompleteness error of each basis set not only provides a foundation for guiding basis set choice in future studies but also facilitates quantitative comparison of existing studies on similar types of systems.

KRAS Mutation Test in Korean Patients with Colorectal Carcinomas: A Methodological Comparison between Sanger Sequencing and a Real-Time PCR-Based Assay.

PubMed

Lee, Sung Hak; Chung, Arthur Minwoo; Lee, Ahwon; Oh, Woo Jin; Choi, Yeong Jin; Lee, Youn-Soo; Jung, Eun Sun

2017-01-01

Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti-epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing-454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. The cobas test is an accurate and sensitive test for detecting KRAS -activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.

A variational Bayes discrete mixture test for rare variant association

PubMed Central

Logsdon, Benjamin A.; Dai, James Y.; Auer, Paul L.; Johnsen, Jill M.; Ganesh, Santhi K.; Smith, Nicholas L.; Wilson, James G.; Tracy, Russell P.; Lange, Leslie A.; Jiao, Shuo; Rich, Stephen S.; Lettre, Guillaume; Carlson, Christopher S.; Jackson, Rebecca D.; O’Donnell, Christopher J.; Wurfel, Mark M.; Nickerson, Deborah A.; Tang, Hua; Reiner, Alexander P.; Kooperberg, Charles

2014-01-01

Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that “aggregate” tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute’s Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans. PMID:24482836

A variational Bayes discrete mixture test for rare variant association.

PubMed

Logsdon, Benjamin A; Dai, James Y; Auer, Paul L; Johnsen, Jill M; Ganesh, Santhi K; Smith, Nicholas L; Wilson, James G; Tracy, Russell P; Lange, Leslie A; Jiao, Shuo; Rich, Stephen S; Lettre, Guillaume; Carlson, Christopher S; Jackson, Rebecca D; O'Donnell, Christopher J; Wurfel, Mark M; Nickerson, Deborah A; Tang, Hua; Reiner, Alexander P; Kooperberg, Charles

2014-01-01

Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that "aggregate" tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.

Secondary structural entropy in RNA switch (Riboswitch) identification.

PubMed

Manzourolajdad, Amirhossein; Arnold, Jonathan

2015-04-28

RNA regulatory elements play a significant role in gene regulation. Riboswitches, a widespread group of regulatory RNAs, are vital components of many bacterial genomes. These regulatory elements generally function by forming a ligand-induced alternative fold that controls access to ribosome binding sites or other regulatory sites in RNA. Riboswitch-mediated mechanisms are ubiquitous across bacterial genomes. A typical class of riboswitch has its own unique structural and biological complexity, making de novo riboswitch identification a formidable task. Traditionally, riboswitches have been identified through comparative genomics based on sequence and structural homology. The limitations of structural-homology-based approaches, coupled with the assumption that there is a great diversity of undiscovered riboswitches, suggests the need for alternative methods for riboswitch identification, possibly based on features intrinsic to their structure. As of yet, no such reliable method has been proposed. We used structural entropy of riboswitch sequences as a measure of their secondary structural dynamics. Entropy values of a diverse set of riboswitches were compared to that of their mutants, their dinucleotide shuffles, and their reverse complement sequences under different stochastic context-free grammar folding models. Significance of our results was evaluated by comparison to other approaches, such as the base-pairing entropy and energy landscapes dynamics. Classifiers based on structural entropy optimized via sequence and structural features were devised as riboswitch identifiers and tested on Bacillus subtilis, Escherichia coli, and Synechococcus elongatus as an exploration of structural entropy based approaches. The unusually long untranslated region of the cotH in Bacillus subtilis, as well as upstream regions of certain genes, such as the sucC genes were associated with significant structural entropy values in genome-wide examinations. Various tests show that there is in fact a relationship between higher structural entropy and the potential for the RNA sequence to have alternative structures, within the limitations of our methodology. This relationship, though modest, is consistent across various tests. Understanding the behavior of structural entropy as a fairly new feature for RNA conformational dynamics, however, may require extensive exploratory investigation both across RNA sequences and folding models.

Association between the genetic similarity of the open reading frame 5 sequence of Porcine reproductive and respiratory syndrome virus and the similarity in clinical signs of Porcine reproductive and respiratory syndrome in Ontario swine herds.

PubMed

Rosendal, Thomas; Dewey, Cate; Friendship, Robert; Wootton, Sarah; Young, Beth; Poljak, Zvonimir

2014-10-01

A study of Ontario swine farms positive for Porcine reproductive and respiratory syndrome virus (PRRSV) tested the association between genetic similarity of the virus and similarity of clinical signs reported by the herd owner. Herds were included if a positive result of polymerase chain reaction for PRRSV at the Animal Health Laboratory at the University of Guelph, Guelph, Ontario, was found between September 2004 and August 2007. Nucleotide-sequence similarity and clinical similarity, as determined from a telephone survey, were calculated for all pairs of herds. The Mantel test indicated that clinical similarity and sequence similarity were weakly correlated for most clinical signs. The generalized additive model indicated that virus homology with 2 vaccine viruses affected the association between sequence similarity and clinical similarity. When the data for herds with vaccine-like virus were removed from the dataset there was a significant association between virus similarity and similarity of the reported presence of abortion, stillbirth, preweaning mortality, and sow/boar mortality. Ownership similarity was also found to be associated with virus similarity and with similarity of the reported presence of sows being off-feed, nursery respiratory disease, nursery mortality, finisher respiratory disease, and finisher mortality. These results indicate that clinical signs of PRRS are associated with PRRSV genotype and that herd ownership is associated with both of these.

Association between the genetic similarity of the open reading frame 5 sequence of Porcine reproductive and respiratory syndrome virus and the similarity in clinical signs of Porcine reproductive and respiratory syndrome in Ontario swine herds

PubMed Central

Rosendal, Thomas; Dewey, Cate; Friendship, Robert; Wootton, Sarah; Young, Beth; Poljak, Zvonimir

2014-01-01

A study of Ontario swine farms positive for Porcine reproductive and respiratory syndrome virus (PRRSV) tested the association between genetic similarity of the virus and similarity of clinical signs reported by the herd owner. Herds were included if a positive result of polymerase chain reaction for PRRSV at the Animal Health Laboratory at the University of Guelph, Guelph, Ontario, was found between September 2004 and August 2007. Nucleotide-sequence similarity and clinical similarity, as determined from a telephone survey, were calculated for all pairs of herds. The Mantel test indicated that clinical similarity and sequence similarity were weakly correlated for most clinical signs. The generalized additive model indicated that virus homology with 2 vaccine viruses affected the association between sequence similarity and clinical similarity. When the data for herds with vaccine-like virus were removed from the dataset there was a significant association between virus similarity and similarity of the reported presence of abortion, stillbirth, preweaning mortality, and sow/boar mortality. Ownership similarity was also found to be associated with virus similarity and with similarity of the reported presence of sows being off-feed, nursery respiratory disease, nursery mortality, finisher respiratory disease, and finisher mortality. These results indicate that clinical signs of PRRS are associated with PRRSV genotype and that herd ownership is associated with both of these. PMID:25355993

Phenotypic and genotypic discrepancy of Streptococcus pneumoniae strains isolated from Asian countries.

PubMed

Ko, Kwan Soo; Oh, Won Sup; Peck, Kyong Ran; Lee, Jang Ho; Lee, Nam Yong; Song, Jae-Hoon

2005-07-01

Non-typeable isolates of Streptococcus pneumoniae collected from Asian countries were characterized by optochin susceptibility test, bile solubility test, multilocus sequence typing of housekeeping genes, amplification of virulence-related genes, 16S rDNA-RsaI digestion, and 16S rDNA sequencing. Six of 54 non-typeable pneumococcal isolates showed divergence of gene sequences of recP and xpt from typical pneumococcal strains. Of these six atypical pneumococcal strains, two showed different results in optochin susceptibility or bile solubility test from typical pneumococcal strains. All six isolates showed high sequence dissimilarities of multilocus sequence typing, 16S rDNA sequences, and lytA sequences from typical S. pneumoniae strains. Data from this study suggest that classic tests such as optochin susceptibility and bile solubility tests may lead to incorrect identification of S. pneumoniae. These atypical strains may belong to different bacterial species from S. pneumoniae.

Impaired sequential and partially compensated probabilistic skill learning in Parkinson's disease.

PubMed

Kemény, Ferenc; Demeter, Gyula; Racsmány, Mihály; Valálik, István; Lukács, Ágnes

2018-06-08

The striatal dopaminergic dysfunction in Parkinson's disease (PD) has been associated with deficits in skill learning in numerous studies, but some of the findings remain controversial. Our aim was to explore the generality of the learning deficit using two widely reported skill learning tasks in the same group of Parkinson's patients. Thirty-four patients with PD (mean age: 62.83 years, SD: 7.67) were compared to age-matched healthy adults. Two tasks were employed: the Serial Reaction Time Task (SRT), testing the learning of motor sequences, and the Weather Prediction (WP) task, testing non-sequential probabilistic category learning. On the SRT task, patients with PD showed no significant evidence for sequence learning. These results support and also extend previous findings, suggesting that motor skill learning is vulnerable in PD. On the WP task, the PD group showed the same amount of learning as controls, but they exploited qualitatively different strategies in predicting the target categories. While controls typically combined probabilities from multiple predicting cues, patients with PD instead focused on individual cues. We also found moderate to high correlations between the different measures of skill learning. These findings support our hypothesis that skill learning is generally impaired in PD, and can in some cases be compensated by relying on alternative learning strategies. © 2018 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Aftershock occurrence rate decay for individual sequences and catalogs

NASA Astrophysics Data System (ADS)

Nyffenegger, Paul A.

One of the earliest observations of the Earth's seismicity is that the rate of aftershock occurrence decays with time according to a power law commonly known as modified Omori-law (MOL) decay. However, the physical reasons for aftershock occurrence and the empirical decay in rate remain unclear despite numerous models that yield similar rate decay behavior. Key problems in relating the observed empirical relationship to the physical conditions of the mainshock and fault are the lack of studies including small magnitude mainshocks and the lack of uniformity between studies. We use simulated aftershock sequences to investigate the factors which influence the maximum likelihood (ML) estimate of the Omori-law p value, the parameter describing aftershock occurrence rate decay, for both individual aftershock sequences and "stacked" or superposed sequences. Generally the ML estimate of p is accurate, but since the ML estimated uncertainty is unaffected by whether the sequence resembles an MOL model, a goodness-of-fit test such as the Anderson-Darling statistic is necessary. While stacking aftershock sequences permits the study of entire catalogs and sequences with small aftershock populations, stacking introduces artifacts. The p value for stacked sequences is approximately equal to the mean of the individual sequence p values. We apply single-link cluster analysis to identify all aftershock sequences from eleven regional seismicity catalogs. We observe two new mathematically predictable empirical relationships for the distribution of aftershock sequence populations. The average properties of aftershock sequences are not correlated with tectonic environment, but aftershock populations and p values do show a depth dependence. The p values show great variability with time, and large values or changes in p sometimes precedes major earthquakes. Studies of teleseismic earthquake catalogs over the last twenty years have led seismologists to question seismicity models and aftershock sequence decay for deep sequences. For seven exceptional deep sequences, we conclude that MOL decay adequately describes these sequences, and little difference exists compared to shallow sequences. However, they do include larger aftershock populations compared to most deep sequences. These results imply that p values for deep sequences are larger than those for intermediate depth sequences.

An algorithm for extraction of periodic signals from sparse, irregularly sampled data

NASA Technical Reports Server (NTRS)

Wilcox, J. Z.

1994-01-01

Temporal gaps in discrete sampling sequences produce spurious Fourier components at the intermodulation frequencies of an oscillatory signal and the temporal gaps, thus significantly complicating spectral analysis of such sparsely sampled data. A new fast Fourier transform (FFT)-based algorithm has been developed, suitable for spectral analysis of sparsely sampled data with a relatively small number of oscillatory components buried in background noise. The algorithm's principal idea has its origin in the so-called 'clean' algorithm used to sharpen images of scenes corrupted by atmospheric and sensor aperture effects. It identifies as the signal's 'true' frequency that oscillatory component which, when passed through the same sampling sequence as the original data, produces a Fourier image that is the best match to the original Fourier space. The algorithm has generally met with succession trials with simulated data with a low signal-to-noise ratio, including those of a type similar to hourly residuals for Earth orientation parameters extracted from VLBI data. For eight oscillatory components in the diurnal and semidiurnal bands, all components with an amplitude-noise ratio greater than 0.2 were successfully extracted for all sequences and duty cycles (greater than 0.1) tested; the amplitude-noise ratios of the extracted signals were as low as 0.05 for high duty cycles and long sampling sequences. When, in addition to these high frequencies, strong low-frequency components are present in the data, the low-frequency components are generally eliminated first, by employing a version of the algorithm that searches for non-integer multiples of the discrete FET minimum frequency.

Detection of nonauthorized genetically modified organisms using differential quantitative polymerase chain reaction: application to 35S in maize.

PubMed

Cankar, Katarina; Chauvensy-Ancel, Valérie; Fortabat, Marie-Noelle; Gruden, Kristina; Kobilinsky, André; Zel, Jana; Bertheau, Yves

2008-05-15

Detection of nonauthorized genetically modified organisms (GMOs) has always presented an analytical challenge because the complete sequence data needed to detect them are generally unavailable although sequence similarity to known GMOs can be expected. A new approach, differential quantitative polymerase chain reaction (PCR), for detection of nonauthorized GMOs is presented here. This method is based on the presence of several common elements (e.g., promoter, genes of interest) in different GMOs. A statistical model was developed to study the difference between the number of molecules of such a common sequence and the number of molecules identifying the approved GMO (as determined by border-fragment-based PCR) and the donor organism of the common sequence. When this difference differs statistically from zero, the presence of a nonauthorized GMO can be inferred. The interest and scope of such an approach were tested on a case study of different proportions of genetically modified maize events, with the P35S promoter as the Cauliflower Mosaic Virus common sequence. The presence of a nonauthorized GMO was successfully detected in the mixtures analyzed and in the presence of (donor organism of P35S promoter). This method could be easily transposed to other common GMO sequences and other species and is applicable to other detection areas such as microbiology.

A Glimpse into the Satellite DNA Library in Characidae Fish (Teleostei, Characiformes)

PubMed Central

Utsunomia, Ricardo; Ruiz-Ruano, Francisco J.; Silva, Duílio M. Z. A.; Serrano, Érica A.; Rosa, Ivana F.; Scudeler, Patrícia E. S.; Hashimoto, Diogo T.; Oliveira, Claudio; Camacho, Juan Pedro M.; Foresti, Fausto

2017-01-01

Satellite DNA (satDNA) is an abundant fraction of repetitive DNA in eukaryotic genomes and plays an important role in genome organization and evolution. In general, satDNA sequences follow a concerted evolutionary pattern through the intragenomic homogenization of different repeat units. In addition, the satDNA library hypothesis predicts that related species share a series of satDNA variants descended from a common ancestor species, with differential amplification of different satDNA variants. The finding of a same satDNA family in species belonging to different genera within Characidae fish provided the opportunity to test both concerted evolution and library hypotheses. For this purpose, we analyzed here sequence variation and abundance of this satDNA family in ten species, by a combination of next generation sequencing (NGS), PCR and Sanger sequencing, and fluorescence in situ hybridization (FISH). We found extensive between-species variation for the number and size of pericentromeric FISH signals. At genomic level, the analysis of 1000s of DNA sequences obtained by Illumina sequencing and PCR amplification allowed defining 150 haplotypes which were linked in a common minimum spanning tree, where different patterns of concerted evolution were apparent. This also provided a glimpse into the satDNA library of this group of species. In consistency with the library hypothesis, different variants for this satDNA showed high differences in abundance between species, from highly abundant to simply relictual variants. PMID:28855916

The role of RT carry-over for congruence sequence effects in masked priming.

PubMed

Huber-Huber, Christoph; Ansorge, Ulrich

2017-05-01

The present study disentangles 2 sources of the congruence sequence effect with masked primes: congruence and response time of the previous trial (reaction time [RT] carry-over). Using arrows as primes and targets and a metacontrast masking procedure we found congruence as well as congruence sequence effects. In addition, congruence sequence effects decreased when RT carry-over was accounted for in a mixed model analysis, suggesting that RT carry-over contributes to congruence sequence effects in masked priming. Crucially, effects of previous trial congruence were not cancelled out completely indicating that RT carry-over and previous trial congruence are 2 sources feeding into the congruence sequence effect. A secondary task requiring response speed judgments demonstrated general awareness of response speed (Experiments 1), but removing this secondary task (Experiment 2) showed that RT carry-over effects were also present in single-task conditions. During (dual-task) prime-awareness test parts of both experiments, however, RT carry-over failed to modulate congruence effects, suggesting that some task sets of the participants can prevent the effect. The basic RT carry-over effects are consistent with the conflict adaptation account, with the adaptation to the statistics of the environment (ASE) model, and possibly with the temporal learning explanation. Additionally considering the task-dependence of RT carry-over, the results are most compatible with the conflict adaptation account. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Muscle MR Imaging in Tubular Aggregate Myopathy

PubMed Central

Beltrame, Valeria; Ortolan, Paolo; Coran, Alessandro; Zanato, Riccardo; Gazzola, Matteo; Frigo, Annachiara; Bello, Luca; Pegoraro, Elena; Stramare, Roberto

2014-01-01

Purpose To evaluate with Magnetic Resonance (MR) the degree of fatty replacement and edematous involvement in skeletal muscles in patients with Tubular Aggregate Myopathy (TAM). To asses the inter-observer agreement in evaluating muscle involvement and the symmetry index of fatty replacement. Materials and Methods 13 patients were evaluated by MR to ascertain the degree of fatty replacement (T1W sequences) according to Mercuri's scale, and edema score (STIR sequences) according to extent and site. Results Fatty replacement mainly affects the posterior superficial compartment of the leg; the anterior compartment is generally spared. Edema was generally poor and almost only in the superficial compartment of the leg. The inter-observer agreement is very good with a Krippendorff's coefficient >0.9. Data show a total symmetry in the muscular replacement (McNemar-Bowker test with p = 1). Conclusions MR reveals characteristic muscular involvement, and is a reproducible technique for evaluation of TAM. There may also be a characteristic involvement of the long and short heads of the biceps femoris. It is useful for aimed biopsies, diagnostic hypotheses and evaluation of disease progression. PMID:24722334

PRED-CLASS: cascading neural networks for generalized protein classification and genome-wide applications.

PubMed

Pasquier, C; Promponas, V J; Hamodrakas, S J

2001-08-15

A cascading system of hierarchical, artificial neural networks (named PRED-CLASS) is presented for the generalized classification of proteins into four distinct classes-transmembrane, fibrous, globular, and mixed-from information solely encoded in their amino acid sequences. The architecture of the individual component networks is kept very simple, reducing the number of free parameters (network synaptic weights) for faster training, improved generalization, and the avoidance of data overfitting. Capturing information from as few as 50 protein sequences spread among the four target classes (6 transmembrane, 10 fibrous, 13 globular, and 17 mixed), PRED-CLASS was able to obtain 371 correct predictions out of a set of 387 proteins (success rate approximately 96%) unambiguously assigned into one of the target classes. The application of PRED-CLASS to several test sets and complete proteomes of several organisms demonstrates that such a method could serve as a valuable tool in the annotation of genomic open reading frames with no functional assignment or as a preliminary step in fold recognition and ab initio structure prediction methods. Detailed results obtained for various data sets and completed genomes, along with a web sever running the PRED-CLASS algorithm, can be accessed over the World Wide Web at http://o2.biol.uoa.gr/PRED-CLASS.

Rapidly rotating neutron stars in general relativity: Realistic equations of state

NASA Technical Reports Server (NTRS)

Cook, Gregory B.; Shapiro, Stuart L.; Teukolsky, Saul A.

1994-01-01

We construct equilibrium sequences of rotating neutron stars in general relativity. We compare results for 14 nuclear matter equations of state. We determine a number of important physical parameters for such stars, including the maximum mass and maximum spin rate. The stability of the configurations to quasi-radial perturbations is assessed. We employ a numerical scheme particularly well suited to handle rapid rotation and large departures from spherical symmetry. We provide an extensive tabulation of models for future reference. Two classes of evolutionary sequences of fixed baryon rest mass and entropy are explored: normal sequences, which behave very much like Newtonian sequences, and supramassive sequences, which exist for neutron stars solely because of general relativistic effects. Adiabatic dissipation of energy and angular momentum causes a star to evolve in quasi-stationary fashion along an evolutionary sequence. Supramassive sequences have masses exceeding the maximum mass of a nonrotating neutron star. A supramassive star evolves toward eventual catastrophic collapse to a black hole. Prior to collapse, the star actually spins up as it loses angular momentum, an effect that may provide an observable precursor to gravitational collapse to a black hole.

Whole exome or genome sequencing: nurses need to prepare families for the possibilities.

PubMed

Prows, Cynthia A; Tran, Grace; Blosser, Beverly

2014-12-01

A discussion of whole exome sequencing and the type of possible results patients and families should be aware of before samples are obtained. To find the genetic cause of a rare disorder, whole exome sequencing analyses all known and suspected human genes from a single sample. Over 20,000 detected DNA variants in each individual exome must be considered as possibly causing disease or disregarded as not relevant to the person's disease. In the process, unexpected gene variants associated with known diseases unrelated to the primary purpose of the test may be incidentally discovered. Because family members' DNA samples are often needed, gene variants associated with known genetic diseases or predispositions for diseases can also be discovered in their samples. Discussion paper. PubMed 2009-2013, list of references in retrieved articles, Google Scholar. Nurses need a general understanding of the scope of potential genomic information that may be revealed with whole exome sequencing to provide support and guidance to individuals and families during their decision-making process, while waiting for results and after disclosure. Nurse scientists who want to use whole exome sequencing in their study design and methods must decide early in study development if they will return primary whole exome sequencing research results and if they will give research participants choices about learning incidental research results. It is critical that nurses translate their knowledge about whole exome sequencing into their patient education and patient advocacy roles and relevant programmes of research. © 2014 John Wiley & Sons Ltd.

The Winds of Main Sequence B Stars in NGC 6231, Evidence for Shocks in Weak Winds.

NASA Astrophysics Data System (ADS)

Massa, Derck

1996-07-01

Because the main sequence B stars in NGC 6231 have abnormallystrong C iv wind lines, they are the only main sequence Bstars with distinct edge velocities. Although the underlyingcause for the strong lines remains unknown, these stars doprovide an opportunity to test two important ideas concerningB star winds: 1) that the driving ions in the winds of starswith low mass loss rates decouple from the general flow, and;2) that shocks deep in the winds of main sequence B stars areresponsible for their observed X-rays. In both of thesemodels, the wind accelerates toward a terminal velocity,v_infty, far greater than the observed value, shocking ordecoupling well before it can attain the high v_infty. As aresult, the observable wind accelerates very rapidly, leadingto wind flushing times less than 30 minutes. If theseconjectures are correct, then the winds of main sequence Bstars should be highly variable on time scales of minutes.Model fitting of available IUE data are consistant with thegeneral notion of a rapidly accelerating wind, shocking wellbefore its actual v_infty. However, these are 5 hourexposures, so the fits are to ill-defined mean wind flows.The new GHRS observations will provide adequate spectral andtemporal resolution to observe the expected variability and,thereby, verify the existance of two important astrophysicalprocesses.

Relationships between palaeogeography and opal occurrence in Australia: A data-mining approach

NASA Astrophysics Data System (ADS)

Landgrebe, T. C. W.; Merdith, A.; Dutkiewicz, A.; Müller, R. D.

2013-07-01

Age-coded multi-layered geological datasets are becoming increasingly prevalent with the surge in open-access geodata, yet there are few methodologies for extracting geological information and knowledge from these data. We present a novel methodology, based on the open-source GPlates software in which age-coded digital palaeogeographic maps are used to “data-mine” spatio-temporal patterns related to the occurrence of Australian opal. Our aim is to test the concept that only a particular sequence of depositional/erosional environments may lead to conditions suitable for the formation of gem quality sedimentary opal. Time-varying geographic environment properties are extracted from a digital palaeogeographic dataset of the eastern Australian Great Artesian Basin (GAB) at 1036 opal localities. We obtain a total of 52 independent ordinal sequences sampling 19 time slices from the Early Cretaceous to the present-day. We find that 95% of the known opal deposits are tied to only 27 sequences all comprising fluvial and shallow marine depositional sequences followed by a prolonged phase of erosion. We then map the total area of the GAB that matches these 27 opal-specific sequences, resulting in an opal-prospective region of only about 10% of the total area of the basin. The key patterns underlying this association involve only a small number of key environmental transitions. We demonstrate that these key associations are generally absent at arbitrary locations in the basin. This new methodology allows for the simplification of a complex time-varying geological dataset into a single map view, enabling straightforward application for opal exploration and for future co-assessment with other datasets/geological criteria. This approach may help unravel the poorly understood opal formation process using an empirical spatio-temporal data-mining methodology and readily available datasets to aid hypothesis testing.

Predicting membrane protein types by fusing composite protein sequence features into pseudo amino acid composition.

PubMed

Hayat, Maqsood; Khan, Asifullah

2011-02-21

Membrane proteins are vital type of proteins that serve as channels, receptors, and energy transducers in a cell. Prediction of membrane protein types is an important research area in bioinformatics. Knowledge of membrane protein types provides some valuable information for predicting novel example of the membrane protein types. However, classification of membrane protein types can be both time consuming and susceptible to errors due to the inherent similarity of membrane protein types. In this paper, neural networks based membrane protein type prediction system is proposed. Composite protein sequence representation (CPSR) is used to extract the features of a protein sequence, which includes seven feature sets; amino acid composition, sequence length, 2 gram exchange group frequency, hydrophobic group, electronic group, sum of hydrophobicity, and R-group. Principal component analysis is then employed to reduce the dimensionality of the feature vector. The probabilistic neural network (PNN), generalized regression neural network, and support vector machine (SVM) are used as classifiers. A high success rate of 86.01% is obtained using SVM for the jackknife test. In case of independent dataset test, PNN yields the highest accuracy of 95.73%. These classifiers exhibit improved performance using other performance measures such as sensitivity, specificity, Mathew's correlation coefficient, and F-measure. The experimental results show that the prediction performance of the proposed scheme for classifying membrane protein types is the best reported, so far. This performance improvement may largely be credited to the learning capabilities of neural networks and the composite feature extraction strategy, which exploits seven different properties of protein sequences. The proposed Mem-Predictor can be accessed at http://111.68.99.218/Mem-Predictor. Copyright © 2010 Elsevier Ltd. All rights reserved.

Fatigue of graphite/epoxy /0/90/45/-45/s laminates under dual stress levels

NASA Technical Reports Server (NTRS)

Yang, J. N.; Jones, D. L.

1982-01-01

A model for the prediction of loading sequence effects on the statistical distribution of fatigue life and residual strength in composite materials is generalized and applied to (0/90/45/-45)s graphite/epoxy laminates. Load sequence effects are found to be caused by both the difference in residual strength when failure occurs (boundary effect) and the effect of previously applied loads (memory effect). The model allows the isolation of these two effects, and the estimation of memory effect magnitudes under dual fatigue loading levels. It is shown that the material memory effect is insignificant, and that correlations between predictions of the number of early failures agree with the verification tests, as do predictions of fatigue life and residual strength degradation under dual stress levels.

AST: an automated sequence-sampling method for improving the taxonomic diversity of gene phylogenetic trees.

PubMed

Zhou, Chan; Mao, Fenglou; Yin, Yanbin; Huang, Jinling; Gogarten, Johann Peter; Xu, Ying

2014-01-01

A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php.

AST: An Automated Sequence-Sampling Method for Improving the Taxonomic Diversity of Gene Phylogenetic Trees

PubMed Central

Zhou, Chan; Mao, Fenglou; Yin, Yanbin; Huang, Jinling; Gogarten, Johann Peter; Xu, Ying

2014-01-01

A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php. PMID:24892935

Implementation of personalized medicine in Central-Eastern Europe: pitfalls and potentials based on citizen's attitude.

PubMed

Balicza, Peter; Terebessy, Andras; Grosz, Zoltan; Varga, Noemi Agnes; Gal, Aniko; Fekete, Balint Andras; Molnar, Maria Judit

2018-03-01

Next-generation sequencing is increasingly utilized worldwide as a research and diagnostic tool and is anticipated to be implemented into everyday clinical practice. Since Central-Eastern European attitude toward genetic testing, especially broad genetic testing, is not well known, we performed a survey on this issue among Hungarian participants. A self-administered questionnaire was distributed among patients and patient relatives at our neurogenetic outpatient clinic. Members of the general population were also recruited via public media. We used chi-square testing and binary logistic regression to examine factors influencing attitude. We identified a mixed attitude toward genetic testing. Access to physician consultation positively influenced attitude. A higher self-determined genetic familiarity score associated with higher perceived genetic influence score, which in turn associated with greater willingness to participate in genetic testing. Medical professionals constituted a skeptical group. We think that given the controversies and complexities of the next-generation sequencing field, the optimal clinical translation of NGS data should be performed in institutions which have the unique capability to provide interprofessional health education, transformative biomedical research, and crucial patient care. With optimization of the clinical translational process, improvement of genetic literacy may increase patient engagement and empowerment. The paper highlights that in countries with relatively low-genetic literacy, a special strategy is needed to enhance the implementation of personalized medicine.

AUDIOME: a tiered exome sequencing-based comprehensive gene panel for the diagnosis of heterogeneous nonsyndromic sensorineural hearing loss.

PubMed

Guan, Qiaoning; Balciuniene, Jorune; Cao, Kajia; Fan, Zhiqian; Biswas, Sawona; Wilkens, Alisha; Gallo, Daniel J; Bedoukian, Emma; Tarpinian, Jennifer; Jayaraman, Pushkala; Sarmady, Mahdi; Dulik, Matthew; Santani, Avni; Spinner, Nancy; Abou Tayoun, Ahmad N; Krantz, Ian D; Conlin, Laura K; Luo, Minjie

2018-03-29

PurposeHereditary hearing loss is highly heterogeneous. To keep up with rapidly emerging disease-causing genes, we developed the AUDIOME test for nonsyndromic hearing loss (NSHL) using an exome sequencing (ES) platform and targeted analysis for the curated genes.MethodsA tiered strategy was implemented for this test. Tier 1 includes combined Sanger and targeted deletion analyses of the two most common NSHL genes and two mitochondrial genes. Nondiagnostic tier 1 cases are subjected to ES and array followed by targeted analysis of the remaining AUDIOME genes.ResultsES resulted in good coverage of the selected genes with 98.24% of targeted bases at >15 ×. A fill-in strategy was developed for the poorly covered regions, which generally fell within GC-rich or highly homologous regions. Prospective testing of 33 patients with NSHL revealed a diagnosis in 11 (33%) and a possible diagnosis in 8 cases (24.2%). Among those, 10 individuals had variants in tier 1 genes. The ES data in the remaining nondiagnostic cases are readily available for further analysis.ConclusionThe tiered and ES-based test provides an efficient and cost-effective diagnostic strategy for NSHL, with the potential to reflex to full exome to identify causal changes outside of the AUDIOME test.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.48.

DRUMS: Disk Repository with Update Management and Select option for high throughput sequencing data

PubMed Central

2014-01-01

Background New technologies for analyzing biological samples, like next generation sequencing, are producing a growing amount of data together with quality scores. Moreover, software tools (e.g., for mapping sequence reads), calculating transcription factor binding probabilities, estimating epigenetic modification enriched regions or determining single nucleotide polymorphism increase this amount of position-specific DNA-related data even further. Hence, requesting data becomes challenging and expensive and is often implemented using specialised hardware. In addition, picking specific data as fast as possible becomes increasingly important in many fields of science. The general problem of handling big data sets was addressed by developing specialized databases like HBase, HyperTable or Cassandra. However, these database solutions require also specialized or distributed hardware leading to expensive investments. To the best of our knowledge, there is no database capable of (i) storing billions of position-specific DNA-related records, (ii) performing fast and resource saving requests, and (iii) running on a single standard computer hardware. Results Here, we present DRUMS (Disk Repository with Update Management and Select option), satisfying demands (i)-(iii). It tackles the weaknesses of traditional databases while handling position-specific DNA-related data in an efficient manner. DRUMS is capable of storing up to billions of records. Moreover, it focuses on optimizing relating single lookups as range request, which are needed permanently for computations in bioinformatics. To validate the power of DRUMS, we compare it to the widely used MySQL database. The test setting considers two biological data sets. We use standard desktop hardware as test environment. Conclusions DRUMS outperforms MySQL in writing and reading records by a factor of two up to a factor of 10000. Furthermore, it can work with significantly larger data sets. Our work focuses on mid-sized data sets up to several billion records without requiring cluster technology. Storing position-specific data is a general problem and the concept we present here is a generalized approach. Hence, it can be easily applied to other fields of bioinformatics. PMID:24495746

Discriminative prediction of mammalian enhancers from DNA sequence

PubMed Central

Lee, Dongwon; Karchin, Rachel; Beer, Michael A.

2011-01-01

Accurately predicting regulatory sequences and enhancers in entire genomes is an important but difficult problem, especially in large vertebrate genomes. With the advent of ChIP-seq technology, experimental detection of genome-wide EP300/CREBBP bound regions provides a powerful platform to develop predictive tools for regulatory sequences and to study their sequence properties. Here, we develop a support vector machine (SVM) framework which can accurately identify EP300-bound enhancers using only genomic sequence and an unbiased set of general sequence features. Moreover, we find that the predictive sequence features identified by the SVM classifier reveal biologically relevant sequence elements enriched in the enhancers, but we also identify other features that are significantly depleted in enhancers. The predictive sequence features are evolutionarily conserved and spatially clustered, providing further support of their functional significance. Although our SVM is trained on experimental data, we also predict novel enhancers and show that these putative enhancers are significantly enriched in both ChIP-seq signal and DNase I hypersensitivity signal in the mouse brain and are located near relevant genes. Finally, we present results of comparisons between other EP300/CREBBP data sets using our SVM and uncover sequence elements enriched and/or depleted in the different classes of enhancers. Many of these sequence features play a role in specifying tissue-specific or developmental-stage-specific enhancer activity, but our results indicate that some features operate in a general or tissue-independent manner. In addition to providing a high confidence list of enhancer targets for subsequent experimental investigation, these results contribute to our understanding of the general sequence structure of vertebrate enhancers. PMID:21875935

Approximating the Basset force by optimizing the method of van Hinsberg et al.

NASA Astrophysics Data System (ADS)

Casas, G.; Ferrer, A.; Oñate, E.

2018-01-01

In this work we put the method proposed by van Hinsberg et al. [29] to the test, highlighting its accuracy and efficiency in a sequence of benchmarks of increasing complexity. Furthermore, we explore the possibility of systematizing the way in which the method's free parameters are determined by generalizing the optimization problem that was considered originally. Finally, we provide a list of worked-out values, ready for implementation in large-scale particle-laden flow simulations.

Development of Overarm Throwing Technique Reflects Throwing Ability during Childhood

PubMed Central

KASUYAMA, Tatsuya; MUTOU, Ikuo; SASAMOTO, Hitoshi

2016-01-01

Background: It is important to acquire fundamental movement skills during childhood. Throwing is a representative manipulative skill required for various intrinsic factors. However, the relationship between intrinsic factors and throwing ability in childhood is unclear. The purpose of this study was to investigate intrinsic factors related to the ball throwing distance of Japanese elementary school children. Methods: Japanese elementary school children from grades 1-6 (aged 6-12 years; n=112) participated in this study. The main outcome was throwing ability, which was measured as the ball throwing distance. We measured five general anthropometric parameters, seven physical fitness parameters, and the Roberton's developmental sequence for all subjects. The relationships between the throwing ability and the 13 parameters were analysed. Results: The Roberton's developmental sequence was the best predictor of ball throwing distance (r=0.80, p≤0.01). The best multiple regression model, which included sex, handgrip strength, shuttle run test, and the Roberton's developmental sequence, accounted for 81% of the total variance. Conclusions: The development of correct throwing technique reflects throwing abilities in childhood. In addition to the throwing sequence, enhancement of grip strength and aerobic capacity are also required for children's throwing ability. PMID:28289578

A New Primer to Amplify pmoA Gene From NC10 Bacteria in the Sediments of Dongchang Lake and Dongping Lake.

PubMed

Wang, Shenghui; Liu, Yanjun; Liu, Guofu; Huang, Yaru; Zhou, Yu

2017-08-01

Nitrite-dependent anaerobic methane oxidation (n-damo) is catalyzed by the NC10 phylum bacterium "Candidatus Methylomirabilis oxyfera" (M. oxyfera). Generally, the pmoA gene is applied as a functional marker to test and identify NC10-like bacteria. However, it is difficult to detect the NC10 bacteria from sediments of freshwater lake (Dongchang Lake and Dongping Lake) with the previous pmoA gene primer sets. In this work, a new primer cmo208 was designed and used to amplify pmoA gene of NC10-like bacteria. A newly nested PCR approach was performed using the new primer cmo208 and the previous primers cmo182, cmo682, and cmo568 to detect the NC10 bacteria. The obtained pmoA gene sequences exhibited 85-92% nucleotide identity and 95-97% amino acid sequence identity to pmoA gene of M. oxyfera. The obtained diversity of pmoA gene sequences coincided well with the diversity of 16S rRNA sequences. These results indicated that the newly designed pmoA primer cmo208 could give one more option to detect NC10 bacteria from different environmental samples.

Wind data mining by Kohonen Neural Networks.

PubMed

Fayos, José; Fayos, Carolina

2007-02-14

Time series of Circulation Weather Type (CWT), including daily averaged wind direction and vorticity, are self-classified by similarity using Kohonen Neural Networks (KNN). It is shown that KNN is able to map by similarity all 7300 five-day CWT sequences during the period of 1975-94, in London, United Kingdom. It gives, as a first result, the most probable wind sequences preceding each one of the 27 CWT Lamb classes in that period. Inversely, as a second result, the observed diffuse correlation between both five-day CWT sequences and the CWT of the 6(th) day, in the long 20-year period, can be generalized to predict the last from the previous CWT sequence in a different test period, like 1995, as both time series are similar. Although the average prediction error is comparable to that obtained by forecasting standard methods, the KNN approach gives complementary results, as they depend only on an objective classification of observed CWT data, without any model assumption. The 27 CWT of the Lamb Catalogue were coded with binary three-dimensional vectors, pointing to faces, edges and vertex of a "wind-cube," so that similar CWT vectors were close.

Illustrative case studies in the return of exome and genome sequencing results

PubMed Central

Amendola, Laura M; Lautenbach, Denise; Scollon, Sarah; Bernhardt, Barbara; Biswas, Sawona; East, Kelly; Everett, Jessica; Gilmore, Marian J; Himes, Patricia; Raymond, Victoria M; Wynn, Julia; Hart, Ragan; Jarvik, Gail P

2015-01-01

Whole genome and exome sequencing tests are increasingly being ordered in clinical practice, creating a need for research exploring the return of results from these tests. A goal of the Clinical Sequencing and Exploratory Research (CSER) consortium is to gain experience with this process to develop best practice recommendations for offering exome and genome testing and returning results. Genetic counselors in the CSER consortium have an integral role in the return of results from these genomic sequencing tests and have gained valuable insight. We present seven emerging themes related to return of exome and genome sequencing results accompanied by case descriptions illustrating important lessons learned, counseling challenges specific to these tests and considerations for future research and practice. PMID:26478737

Measurements for liquid rocket engine performance code verification

NASA Technical Reports Server (NTRS)

Praharaj, Sarat C.; Palko, Richard L.

1986-01-01

The goal of the rocket engine performance code verification tests is to obtain the I sub sp with an accuracy of 0.25% or less. This needs to be done during the sequence of four related tests (two reactive and two hot gas simulation) to best utilize the loss separation technique recommended in this study. In addition to I sub sp, the measurements of the input and output parameters for the codes are needed. This study has shown two things in regard to obtaining the I sub sp uncertainty within the 0.25% target. First, this target is generally not being realized at the present time, and second, the instrumentation and testing technology does exist to obtain this 0.25% uncertainty goal. However, to achieve this goal will require carefully planned, designed, and conducted testing. In addition, the test-stand (or system) dynamics must be evaluated in the pre-test and post-test phases of the design of the experiment and data analysis, respectively always keeping in mind that a .25% overall uncertainty in I sub sp is targeted. A table gives the maximum allowable uncertainty required for obtaining I sub sp with 0.25% uncertainty, the currently-quoted instrument specification, and present test uncertainty for the parameters. In general, it appears that measurement of the mass flow parameter within the required uncertainty may be the most difficult.

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients

PubMed Central

2014-01-01

Background Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. Methods We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Results Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients’ clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Conclusions Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology. PMID:24885126

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients.

PubMed

Chang, Lixian; Yuan, Weiping; Zeng, Huimin; Zhou, Quanquan; Wei, Wei; Zhou, Jianfeng; Li, Miaomiao; Wang, Xiaomin; Xu, Mingjiang; Yang, Fengchun; Yang, Yungui; Cheng, Tao; Zhu, Xiaofan

2014-05-15

Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients' clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology.

Fission products and nuclear fuel behaviour under severe accident conditions part 1: Main lessons learnt from the first VERDON test

NASA Astrophysics Data System (ADS)

Pontillon, Y.; Geiger, E.; Le Gall, C.; Bernard, S.; Gallais-During, A.; Malgouyres, P. P.; Hanus, E.; Ducros, G.

2017-11-01

This paper describes the first VERDON test performed at the end of September 2011 with special emphasis on the behaviour of fission products (FP) and actinides during the accidental sequence itself. Two other papers discuss in detail the post-test examination results (SEM, EPMA and SIMS) of the VERDON-1 sample. The first VERDON test was devoted to studying UO2 fuel behaviour and fission product releases under reducing conditions at very high temperature (∼2883 K), which was able to confirm the very good performance of the VERDON loop. The fuel sample did not lose its integrity during this test. According to the FP behaviour measured by the online gamma station (fuel sight), the general classification of the FP in relation to their released fraction is very accurate, and the burn-up effect on the release rate is clearly highlighted.

All APAPs Are Not Equivalent for the Treatment of Sleep Disordered Breathing: A Bench Evaluation of Eleven Commercially Available Devices

PubMed Central

Zhu, Kaixian; Roisman, Gabriel; Aouf, Sami; Escourrou, Pierre

2015-01-01

Study Objectives: This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports. Methods: Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle. Results: In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports. Conclusion: Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study. Citation: Zhu K, Roisman G, Aouf S, Escourrou P. All APAPs are not equivalent for the treatment of sleep disordered breathing: a bench evaluation of eleven commercially available devices. J Clin Sleep Med 2015;11(7):725–734. PMID:25766708

An approach for Ewing test selection to support the clinical assessment of cardiac autonomic neuropathy.

PubMed

Stranieri, Andrew; Abawajy, Jemal; Kelarev, Andrei; Huda, Shamsul; Chowdhury, Morshed; Jelinek, Herbert F

2013-07-01

This article addresses the problem of determining optimal sequences of tests for the clinical assessment of cardiac autonomic neuropathy (CAN). We investigate the accuracy of using only one of the recommended Ewing tests to classify CAN and the additional accuracy obtained by adding the remaining tests of the Ewing battery. This is important as not all five Ewing tests can always be applied in each situation in practice. We used new and unique database of the diabetes screening research initiative project, which is more than ten times larger than the data set used by Ewing in his original investigation of CAN. We utilized decision trees and the optimal decision path finder (ODPF) procedure for identifying optimal sequences of tests. We present experimental results on the accuracy of using each one of the recommended Ewing tests to classify CAN and the additional accuracy that can be achieved by adding the remaining tests of the Ewing battery. We found the best sequences of tests for cost-function equal to the number of tests. The accuracies achieved by the initial segments of the optimal sequences for 2, 3 and 4 categories of CAN are 80.80, 91.33, 93.97 and 94.14, and respectively, 79.86, 89.29, 91.16 and 91.76, and 78.90, 86.21, 88.15 and 88.93. They show significant improvement compared to the sequence considered previously in the literature and the mathematical expectations of the accuracies of a random sequence of tests. The complete outcomes obtained for all subsets of the Ewing features are required for determining optimal sequences of tests for any cost-function with the use of the ODPF procedure. We have also found two most significant additional features that can increase the accuracy when some of the Ewing attributes cannot be obtained. The outcomes obtained can be used to determine the optimal sequences of tests for each individual cost-function by following the ODPF procedure. The results show that the best single Ewing test for diagnosing CAN is the deep breathing heart rate variation test. Optimal sequences found for the cost-function equal to the number of tests guarantee that the best accuracy is achieved after any number of tests and provide an improvement in comparison with the previous ordering of tests or a random sequence. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimal digital dynamical decoupling for general decoherence via Walsh modulation

NASA Astrophysics Data System (ADS)

Qi, Haoyu; Dowling, Jonathan P.; Viola, Lorenza

2017-11-01

We provide a general framework for constructing digital dynamical decoupling sequences based on Walsh modulation—applicable to arbitrary qubit decoherence scenarios. By establishing equivalence between decoupling design based on Walsh functions and on concatenated projections, we identify a family of optimal Walsh sequences, which can be exponentially more efficient, in terms of the required total pulse number, for fixed cancellation order, than known digital sequences based on concatenated design. Optimal sequences for a given cancellation order are highly non-unique—their performance depending sensitively on the control path. We provide an analytic upper bound to the achievable decoupling error and show how sequences within the optimal Walsh family can substantially outperform concatenated decoupling in principle, while respecting realistic timing constraints.

Toward a Theory of Sequencing: Study 1-7: An Exploration of the Effect of Instructional Sequences Involving Enactive and Iconic Embodiments on the Ability to Generalize.

ERIC Educational Resources Information Center

Beardslee, Edward Clarke

The purpose of the study was to examine the effect of instruction using Dienes' perceptual variability principles on primitive generalization and mathematical generalization. The following was studied: the effect of achievement-to-criterion on one, two, or three non-symbolic embodiments of an objective using a selected class of variables on the…

Assessment of the generalization of learned image reconstruction and the potential for transfer learning.

PubMed

Knoll, Florian; Hammernik, Kerstin; Kobler, Erich; Pock, Thomas; Recht, Michael P; Sodickson, Daniel K

2018-05-17

Although deep learning has shown great promise for MR image reconstruction, an open question regarding the success of this approach is the robustness in the case of deviations between training and test data. The goal of this study is to assess the influence of image contrast, SNR, and image content on the generalization of learned image reconstruction, and to demonstrate the potential for transfer learning. Reconstructions were trained from undersampled data using data sets with varying SNR, sampling pattern, image contrast, and synthetic data generated from a public image database. The performance of the trained reconstructions was evaluated on 10 in vivo patient knee MRI acquisitions from 2 different pulse sequences that were not used during training. Transfer learning was evaluated by fine-tuning baseline trainings from synthetic data with a small subset of in vivo MR training data. Deviations in SNR between training and testing led to substantial decreases in reconstruction image quality, whereas image contrast was less relevant. Trainings from heterogeneous training data generalized well toward the test data with a range of acquisition parameters. Trainings from synthetic, non-MR image data showed residual aliasing artifacts, which could be removed by transfer learning-inspired fine-tuning. This study presents insights into the generalization ability of learned image reconstruction with respect to deviations in the acquisition settings between training and testing. It also provides an outlook for the potential of transfer learning to fine-tune trainings to a particular target application using only a small number of training cases. © 2018 International Society for Magnetic Resonance in Medicine.

Statistical method evaluation for differentially methylated CpGs in base resolution next-generation DNA sequencing data.

PubMed

Zhang, Yun; Baheti, Saurabh; Sun, Zhifu

2018-05-01

High-throughput bisulfite methylation sequencing such as reduced representation bisulfite sequencing (RRBS), Agilent SureSelect Human Methyl-Seq (Methyl-seq) or whole-genome bisulfite sequencing is commonly used for base resolution methylome research. These data are represented either by the ratio of methylated cytosine versus total coverage at a CpG site or numbers of methylated and unmethylated cytosines. Multiple statistical methods can be used to detect differentially methylated CpGs (DMCs) between conditions, and these methods are often the base for the next step of differentially methylated region identification. The ratio data have a flexibility of fitting to many linear models, but the raw count data take consideration of coverage information. There is an array of options in each datatype for DMC detection; however, it is not clear which is an optimal statistical method. In this study, we systematically evaluated four statistic methods on methylation ratio data and four methods on count-based data and compared their performances with regard to type I error control, sensitivity and specificity of DMC detection and computational resource demands using real RRBS data along with simulation. Our results show that the ratio-based tests are generally more conservative (less sensitive) than the count-based tests. However, some count-based methods have high false-positive rates and should be avoided. The beta-binomial model gives a good balance between sensitivity and specificity and is preferred method. Selection of methods in different settings, signal versus noise and sample size estimation are also discussed.

Comparison of 16S rRNA sequencing with biochemical testing for species-level identification of clinical isolates of Neisseria spp.

PubMed

Mechergui, Arij; Achour, Wafa; Ben Hassen, Assia

2014-08-01

We aimed to compare accuracy of genus and species level identification of Neisseria spp. using biochemical testing and 16S rRNA sequence analysis. These methods were evaluated using 85 Neisseria spp. clinical isolates initially identified to the genus level by conventional biochemical tests and API NH system (Bio-Mérieux(®)). In 34 % (29/85), more than one possibility was given by 16S rRNA sequence analysis. In 6 % (5/85), one of the possibilities offered by 16S rRNA gene sequencing, agreed with the result given by biochemical testing. In 4 % (3/85), the same species was given by both methods. 16S rRNA gene sequencing results did not correlate well with biochemical tests.

Generalized lessons about sequence learning from the study of the serial reaction time task

PubMed Central

Schwarb, Hillary; Schumacher, Eric H.

2012-01-01

Over the last 20 years researchers have used the serial reaction time (SRT) task to investigate the nature of spatial sequence learning. They have used the task to identify the locus of spatial sequence learning, identify situations that enhance and those that impair learning, and identify the important cognitive processes that facilitate this type of learning. Although controversies remain, the SRT task has been integral in enhancing our understanding of implicit sequence learning. It is important, however, to ask what, if anything, the discoveries made using the SRT task tell us about implicit learning more generally. This review analyzes the state of the current spatial SRT sequence learning literature highlighting the stimulus-response rule hypothesis of sequence learning which we believe provides a unifying account of discrepant SRT data. It also challenges researchers to use the vast body of knowledge acquired with the SRT task to understand other implicit learning literatures too often ignored in the context of this particular task. This broad perspective will make it possible to identify congruences among data acquired using various different tasks that will allow us to generalize about the nature of implicit learning. PMID:22723815

Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

PubMed

Majiduddin, Fahd K; Palzkill, Timothy

2003-03-01

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

Amino Acid Sequence Requirements at Residues 69 and 238 for the SME-1 β-Lactamase To Confer Resistance to β-Lactam Antibiotics

PubMed Central

Majiduddin, Fahd K.; Palzkill, Timothy

2003-01-01

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring β-lactamases and extended-spectrum β-lactamases. Four enzymes from the class A group of β-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these β-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of β-lactam antibiotics. PMID:12604542

Evaluation of electrical test conditions in MIL-M-38510 slash sheets

NASA Astrophysics Data System (ADS)

Sandgren, K.

1980-08-01

Adequacy of MIL-M-38510 slash sheet requirements for electrical test conditions in an automated test environment were evaluated. Military temperature range commercial devices of 13 types from 6 manufacturers were purchased. Software for testing these devices and for varying the test conditions was written for the Tektronix S-3260 test system. The devices were tested to evaluate the effects of pin-condition settling time, measurement sequence of the same and different D-C parameters, temperature sequence, differently defined temperature ambients, variable measurement conditions, sequence of time measurements, pin-application sequence, and undesignated pin condition ambiguity. An alternative to current tri-state enable and disable time measurements is proposed; S-3260 'open' and 'ground' conditions are characterized; and suggestions for changes in MIL-M-38510 slash sheet specifications and MIL-STD-883 test methods are proposed, both to correct errors and ambiguities and to facilitate the gathering of repeatable data on automated test equipment. Data obtained showed no sensitivity to measurement or temperature sequence nor to temperature ambient, provided that test times were not excessive. V sub ICP tests and some low current measurements required allowance for a pin condition settling time because of the test system speed. Some pin condition application sequences yielded incorrect measurements. Undefined terminal conditions of output pins were found to affect I sub OS and propagation delay time measurements. Truth table test results varied with test frequency and V sub IL for low-power Schottky devices.

Subcellular location prediction of proteins using support vector machines with alignment of block sequences utilizing amino acid composition.

PubMed

Tamura, Takeyuki; Akutsu, Tatsuya

2007-11-30

Subcellular location prediction of proteins is an important and well-studied problem in bioinformatics. This is a problem of predicting which part in a cell a given protein is transported to, where an amino acid sequence of the protein is given as an input. This problem is becoming more important since information on subcellular location is helpful for annotation of proteins and genes and the number of complete genomes is rapidly increasing. Since existing predictors are based on various heuristics, it is important to develop a simple method with high prediction accuracies. In this paper, we propose a novel and general predicting method by combining techniques for sequence alignment and feature vectors based on amino acid composition. We implemented this method with support vector machines on plant data sets extracted from the TargetP database. Through fivefold cross validation tests, the obtained overall accuracies and average MCC were 0.9096 and 0.8655 respectively. We also applied our method to other datasets including that of WoLF PSORT. Although there is a predictor which uses the information of gene ontology and yields higher accuracy than ours, our accuracies are higher than existing predictors which use only sequence information. Since such information as gene ontology can be obtained only for known proteins, our predictor is considered to be useful for subcellular location prediction of newly-discovered proteins. Furthermore, the idea of combination of alignment and amino acid frequency is novel and general so that it may be applied to other problems in bioinformatics. Our method for plant is also implemented as a web-system and available on http://sunflower.kuicr.kyoto-u.ac.jp/~tamura/slpfa.html.

Experimental investigation of an RNA sequence space

NASA Technical Reports Server (NTRS)

Lee, Youn-Hyung; Dsouza, Lisa; Fox, George E.

1993-01-01

Modern rRNAs are the historic consequence of an ongoing evolutionary exploration of a sequence space. These extant sequences belong to a special subset of the sequence space that is comprised only of those primary sequences that can validly perform the biological function(s) required of the particular RNA. If it were possible to readily identify all such valid sequences, stochastic predictions could be made about the relative likelihood of various evolutionary pathways available to an RNA. Herein an experimental system which can assess whether a particular sequence is likely to have validity as a eubacterial 5S rRNA is described. A total of ten naturally occurring, and hence known to be valid, sequences and two point mutants of unknown validity were used to test the usefulness of the approach. Nine of the ten valid sequences tested positive whereas both mutants tested as clearly defective. The tenth valid sequence gave results that would be interpreted as reflecting a borderline status were the answer not known. These results demonstrate that it is possible to experimentally determine which sequences in local regions of the sequence space are potentially valid 5S rRNAs.

Concept of a programmable maintenance processor applicable to multiprocessing systems

NASA Technical Reports Server (NTRS)

Glover, Richard D.

1988-01-01

A programmable maintenance processor concept applicable to multiprocessing systems has been developed at the NASA Ames Research Center's Dryden Flight Research Facility. This stand-alone-processor is intended to provide support for system and application software testing as well as hardware diagnostics. An initial machanization has been incorporated into the extended aircraft interrogation and display system (XAIDS) which is multiprocessing general-purpose ground support equipment. The XAIDS maintenance processor has independent terminal and printer interfaces and a dedicated magnetic bubble memory that stores system test sequences entered from the terminal. This report describes the hardware and software embodied in this processor and shows a typical application in the check-out of a new XAIDS.

Successful Recovery of Nuclear Protein-Coding Genes from Small Insects in Museums Using Illumina Sequencing.

PubMed

Kanda, Kojun; Pflug, James M; Sproul, John S; Dasenko, Mark A; Maddison, David R

2015-01-01

In this paper we explore high-throughput Illumina sequencing of nuclear protein-coding, ribosomal, and mitochondrial genes in small, dried insects stored in natural history collections. We sequenced one tenebrionid beetle and 12 carabid beetles ranging in size from 3.7 to 9.7 mm in length that have been stored in various museums for 4 to 84 years. Although we chose a number of old, small specimens for which we expected low sequence recovery, we successfully recovered at least some low-copy nuclear protein-coding genes from all specimens. For example, in one 56-year-old beetle, 4.4 mm in length, our de novo assembly recovered about 63% of approximately 41,900 nucleotides in a target suite of 67 nuclear protein-coding gene fragments, and 70% using a reference-based assembly. Even in the least successfully sequenced carabid specimen, reference-based assembly yielded fragments that were at least 50% of the target length for 34 of 67 nuclear protein-coding gene fragments. Exploration of alternative references for reference-based assembly revealed few signs of bias created by the reference. For all specimens we recovered almost complete copies of ribosomal and mitochondrial genes. We verified the general accuracy of the sequences through comparisons with sequences obtained from PCR and Sanger sequencing, including of conspecific, fresh specimens, and through phylogenetic analysis that tested the placement of sequences in predicted regions. A few possible inaccuracies in the sequences were detected, but these rarely affected the phylogenetic placement of the samples. Although our sample sizes are low, an exploratory regression study suggests that the dominant factor in predicting success at recovering nuclear protein-coding genes is a high number of Illumina reads, with success at PCR of COI and killing by immersion in ethanol being secondary factors; in analyses of only high-read samples, the primary significant explanatory variable was body length, with small beetles being more successfully sequenced.

Successful Recovery of Nuclear Protein-Coding Genes from Small Insects in Museums Using Illumina Sequencing

PubMed Central

Dasenko, Mark A.

2015-01-01

In this paper we explore high-throughput Illumina sequencing of nuclear protein-coding, ribosomal, and mitochondrial genes in small, dried insects stored in natural history collections. We sequenced one tenebrionid beetle and 12 carabid beetles ranging in size from 3.7 to 9.7 mm in length that have been stored in various museums for 4 to 84 years. Although we chose a number of old, small specimens for which we expected low sequence recovery, we successfully recovered at least some low-copy nuclear protein-coding genes from all specimens. For example, in one 56-year-old beetle, 4.4 mm in length, our de novo assembly recovered about 63% of approximately 41,900 nucleotides in a target suite of 67 nuclear protein-coding gene fragments, and 70% using a reference-based assembly. Even in the least successfully sequenced carabid specimen, reference-based assembly yielded fragments that were at least 50% of the target length for 34 of 67 nuclear protein-coding gene fragments. Exploration of alternative references for reference-based assembly revealed few signs of bias created by the reference. For all specimens we recovered almost complete copies of ribosomal and mitochondrial genes. We verified the general accuracy of the sequences through comparisons with sequences obtained from PCR and Sanger sequencing, including of conspecific, fresh specimens, and through phylogenetic analysis that tested the placement of sequences in predicted regions. A few possible inaccuracies in the sequences were detected, but these rarely affected the phylogenetic placement of the samples. Although our sample sizes are low, an exploratory regression study suggests that the dominant factor in predicting success at recovering nuclear protein-coding genes is a high number of Illumina reads, with success at PCR of COI and killing by immersion in ethanol being secondary factors; in analyses of only high-read samples, the primary significant explanatory variable was body length, with small beetles being more successfully sequenced. PMID:26716693

Ego depletion impairs implicit learning.

PubMed

Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

2014-01-01

Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

Ego Depletion Impairs Implicit Learning

PubMed Central

Thompson, Kelsey R.; Sanchez, Daniel J.; Wesley, Abigail H.; Reber, Paul J.

2014-01-01

Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent. PMID:25275517

Personality and cognitive profiles of a general synesthetic trait.

PubMed

Rouw, Romke; Scholte, H Steven

2016-07-29

The recent sharp increase in studies on synesthesia has taught us a lot about this fascinating condition. Still, while we define synesthesia as 'the mixing of senses', the great majority of synesthesia studies focus on only one synesthesia type (in particular grapheme-color synesthesia). In this study, a large group of subjects are tested on the presence or absence of different types of synesthesia. Efforts to recruit a representative sample of the Dutch population, not related to or aware of synesthesia as a research topic, helped counter a selection bias or a self-report bias in our subject group. A sharp increase in synesthesia prevalence was found, at least partially due to including many different types of synesthesia in the synesthesia 'diagnoses'. The five synesthesia types reported in the Novich et al (2011) study were obtained; Colored Sequences, Colored Music, Colored Sensations, Spatial Sequences, Non-Visual Sequelae, as well as an additional synesthesia type, Sequence-Personality. No differences were found between synesthetes and non-synesthetes in education level, handedness, age, and sex. The synesthetes showed increased intelligence as compared with matched non-synesthetes. This was a general effect rather than bound to a specific cognitive domain or to a specific (synesthesia-type to stimulus-material) relationship. The expected effect of increased "Openness" in synesthetes was obtained, as well as two unexpected effects in personality traits (increased "Neuroticism" and decreased "Conscientiousness"). We also found increased "Emotionality" (experiencing emotions) and increased "Fantasizing", but synesthetes did not differ in cognitive appraisal of emotions (identifying/analyzing/verbalizing of emotions). The personality and cognitive characteristics were found related to having synesthesia (in general) rather then to particular synesthesia subtypes. This supports the existence of a general synesthetic 'trait', over the notion of relatively independent 'types' of synesthesia. In further support, exploratory analyses showed that a measurement of synesthetic strength (number of subtypes of synesthesia) correlates with stronger findings (increased "Openness", "Fantasizing", and "Emotionality", and decreased "Conscientiousness"). In conclusion, results are in line with the notion of a general synesthetic 'trait', and this synesthetic trait is associated with particular personality traits and cognitive characteristics. Copyright © 2016. Published by Elsevier Ltd.

A generalization of Cesàro sequence spaces in the Orlicz space

NASA Astrophysics Data System (ADS)

Haryadi; Supama; Zulijanto, A.

2018-04-01

In this paper, we generalize the Cesàro sequence spaces in the classic Banach space Lp to the generalized Orlicz space Lφ . We construct the space by replacing the norm {\\Vert \\cdot \\Vert }p in Lp with modular ρφ in Lφ . This generalization has lead to the use of the Luxemburg norm to discuss some topological properties of the spaces. We prove results regarding to modular and norm convergence. We also describe some properties of the spaces and a closed subspaces of the space.

Music Program of Study: Educational Program Definition.

ERIC Educational Resources Information Center

West Virginia State Dept. of Education, Charleston.

The West Virginia music study program is a public school K-12 curriculum sequence. This program is divided into the four principal areas of: (1) general classroom music; (2) string instrumental music; (3) wind and percussion instrumental music; and (4) choral music. The general classroom music program is an early and middle childhood sequence of…

The Bivariate (Complex) Fibonacci and Lucas Polynomials: An Historical Investigation with the Maple's Help

ERIC Educational Resources Information Center

Alves, Francisco Regis Vieira; Catarino, Paula Maria Machado Cruz

2016-01-01

The current research around the Fibonacci's and Lucas' sequence evidences the scientific vigor of both mathematical models that continue to inspire and provide numerous specializations and generalizations, especially from the sixties. One of the current of research and investigations around the Generalized Sequence of Lucas, involves it's…

Student Mental Models of the Greenhouse Effect: Retention Months After Interventions

NASA Astrophysics Data System (ADS)

Harris, S. E.; Gold, A. U.

2013-12-01

Individual understanding of climate science, and the greenhouse effect in particular, is one factor important for societal decision-making. Ideally, learning opportunities about the greenhouse effect will not only move people toward expert-like ideas but will also have long-lasting effects for those individuals. We assessed university students' mental models of the greenhouse effect before and after specific learning experiences, on a final exam, then again a few months later. Our aim was to measure retention after students had not necessarily been thinking about, nor studying, the greenhouse effect recently. How sticky were the ideas learned? 164 students in an introductory science course participated in a sequence of two learning activities and assessments regarding the greenhouse effect. The first lesson involved the full class, then, for the second lesson, half the students completed a simulation-based activity and the other half completed a data-driven activity. We assessed student thinking through concept sketches, multiple choice and short answer questions. All students generated concept sketches four times, and completed a set of multiple choice (MCQs) and short answer questions twice. Later, 3-4 months after the course ended, 27 students ('retention students') completed an additional concept sketch and answered the questions again, as a retention assessment. These 27 students were nearly evenly split between the two contrasting second lessons in the sequence and included both high and low-achieving students. We then compared student sketches and scores to 'expert' answers. The general pattern over time showed a significant increase in student scores from before the lesson sequence to after, both on concept sketches and MCQs, then an additional increase in concept sketch score on the final exam (MCQs were not asked on the final exam). The scores for the retention students were not significantly different from the full class. Within the retention group, there was also no difference in scores based on which contrasting lesson a student did. Students in both of the contrasting lessons scored significantly higher on the retention test than on the initial pre-test. Their concept sketch scores on the retention test were slightly lower than their scores on the final exam (not significantly), but matched their post-lesson-sequence scores. Their MCQ scores were slightly higher on the retention test than on the post-lesson-sequence test (also not significantly). These results imply that students both learned and retained new ideas about the greenhouse effect for at least a few months after the end of the course and did not regress to their pre-lesson ideas. Further analysis should show which particular aspects of student mental models changed over the full temporal sequence.

Detecting Coevolution in and among Protein Domains

PubMed Central

Yeang, Chen-Hsiang; Haussler, David

2007-01-01

Correlated changes of nucleic or amino acids have provided strong information about the structures and interactions of molecules. Despite the rich literature in coevolutionary sequence analysis, previous methods often have to trade off between generality, simplicity, phylogenetic information, and specific knowledge about interactions. Furthermore, despite the evidence of coevolution in selected protein families, a comprehensive screening of coevolution among all protein domains is still lacking. We propose an augmented continuous-time Markov process model for sequence coevolution. The model can handle different types of interactions, incorporate phylogenetic information and sequence substitution, has only one extra free parameter, and requires no knowledge about interaction rules. We employ this model to large-scale screenings on the entire protein domain database (Pfam). Strikingly, with 0.1 trillion tests executed, the majority of the inferred coevolving protein domains are functionally related, and the coevolving amino acid residues are spatially coupled. Moreover, many of the coevolving positions are located at functionally important sites of proteins/protein complexes, such as the subunit linkers of superoxide dismutase, the tRNA binding sites of ribosomes, the DNA binding region of RNA polymerase, and the active and ligand binding sites of various enzymes. The results suggest sequence coevolution manifests structural and functional constraints of proteins. The intricate relations between sequence coevolution and various selective constraints are worth pursuing at a deeper level. PMID:17983264

Gibbs motif sampling: detection of bacterial outer membrane protein repeats.

PubMed Central

Neuwald, A. F.; Liu, J. S.; Lawrence, C. E.

1995-01-01

The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane-spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID:8520488

Disease Suppressive Soils: New Insights from the Soil Microbiome.

PubMed

Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

2017-11-01

Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

Supplementary motor area as key structure for domain-general sequence processing: A unified account.

PubMed

Cona, Giorgia; Semenza, Carlo

2017-01-01

The Supplementary Motor Area (SMA) is considered as an anatomically and functionally heterogeneous region and is implicated in several functions. We propose that SMA plays a crucial role in domain-general sequence processes, contributing to the integration of sequential elements into higher-order representations regardless of the nature of such elements (e.g., motor, temporal, spatial, numerical, linguistic, etc.). This review emphasizes the domain-general involvement of the SMA, as this region has been found to support sequence operations in a variety of cognitive domains that, albeit different, share an inherent sequence processing. These include action, time and spatial processing, numerical cognition, music and language processing, and working memory. In this light, we reviewed and synthesized recent neuroimaging, stimulation and electrophysiological studies in order to compare and reconcile the distinct sources of data by proposing a unifying account for the role of the SMA. We also discussed the differential contribution of the pre-SMA and SMA-proper in sequence operations, and possible neural mechanisms by which such operations are executed. Copyright © 2016 Elsevier Ltd. All rights reserved.

A generalized theoretical framework for the description of spin decoupling in solid-state MAS NMR: Offset effect on decoupling performance

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

Tan, Kong Ooi; Meier, Beat H., E-mail: beme@ethz.ch, E-mail: maer@ethz.ch; Ernst, Matthias, E-mail: beme@ethz.ch, E-mail: maer@ethz.ch

2016-09-07

We present a generalized theoretical framework that allows the approximate but rapid analysis of residual couplings of arbitrary decoupling sequences in solid-state NMR under magic-angle spinning conditions. It is a generalization of the tri-modal Floquet analysis of TPPM decoupling [Scholz et al., J. Chem. Phys. 130, 114510 (2009)] where three characteristic frequencies are used to describe the pulse sequence. Such an approach can be used to describe arbitrary periodic decoupling sequences that differ only in the magnitude of the Fourier coefficients of the interaction-frame transformation. It allows a ∼100 times faster calculation of second-order residual couplings as a function ofmore » pulse sequence parameters than full spin-dynamics simulations. By comparing the theoretical calculations with full numerical simulations, we show the potential of the new approach to examine the performance of decoupling sequences. We exemplify the usefulness of this framework by analyzing the performance of commonly used high-power decoupling sequences and low-power decoupling sequences such as amplitude-modulated XiX (AM-XiX) and its super-cycled variant SC-AM-XiX. In addition, the effect of chemical-shift offset is examined for both high- and low-power decoupling sequences. The results show that the cross-terms between the dipolar couplings are the main contributions to the line broadening when offset is present. We also show that the SC-AM-XIX shows a better offset compensation.« less

A generalized theoretical framework for the description of spin decoupling in solid-state MAS NMR: Offset effect on decoupling performance.

PubMed

Tan, Kong Ooi; Agarwal, Vipin; Meier, Beat H; Ernst, Matthias

2016-09-07

We present a generalized theoretical framework that allows the approximate but rapid analysis of residual couplings of arbitrary decoupling sequences in solid-state NMR under magic-angle spinning conditions. It is a generalization of the tri-modal Floquet analysis of TPPM decoupling [Scholz et al., J. Chem. Phys. 130, 114510 (2009)] where three characteristic frequencies are used to describe the pulse sequence. Such an approach can be used to describe arbitrary periodic decoupling sequences that differ only in the magnitude of the Fourier coefficients of the interaction-frame transformation. It allows a ∼100 times faster calculation of second-order residual couplings as a function of pulse sequence parameters than full spin-dynamics simulations. By comparing the theoretical calculations with full numerical simulations, we show the potential of the new approach to examine the performance of decoupling sequences. We exemplify the usefulness of this framework by analyzing the performance of commonly used high-power decoupling sequences and low-power decoupling sequences such as amplitude-modulated XiX (AM-XiX) and its super-cycled variant SC-AM-XiX. In addition, the effect of chemical-shift offset is examined for both high- and low-power decoupling sequences. The results show that the cross-terms between the dipolar couplings are the main contributions to the line broadening when offset is present. We also show that the SC-AM-XIX shows a better offset compensation.

A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?

PubMed Central

Alekseyev, Yuriy O.; Fazeli, Roghayeh; Yang, Shi; Basran, Raveen; Miller, Nancy S.

2018-01-01

Next-generation sequencing refers to a high-throughput technology that determines the nucleic acid sequences and identifies variants in a sample. The technology has been introduced into clinical laboratory testing and produces test results for precision medicine. Since next-generation sequencing is relatively new, graduate students, medical students, pathology residents, and other physicians may benefit from a primer to provide a foundation about basic next-generation sequencing methods and applications, as well as specific examples where it has had diagnostic and prognostic utility. Next-generation sequencing technology grew out of advances in multiple fields to produce a sophisticated laboratory test with tremendous potential. Next-generation sequencing may be used in the clinical setting to look for specific genetic alterations in patients with cancer, diagnose inherited conditions such as cystic fibrosis, and detect and profile microbial organisms. This primer will review DNA sequencing technology, the commercialization of next-generation sequencing, and clinical uses of next-generation sequencing. Specific applications where next-generation sequencing has demonstrated utility in oncology are provided. PMID:29761157

Apollo 13 post-flight Service Module tests to determine reason for explosion

NASA Technical Reports Server (NTRS)

1970-01-01

Sequence photo from 16mm motion picture film of test at Langley Research Center which seeks to determine mechanism by which Apollo 13 panel was separated from Service Module. The test used a 1/2 scale model with a honeycomb sandwich panel and was conducted in a vacuum (41982); Second photograph in sequence of three of panel separation test at Langley Research Center (41983); Full-scale propogation test at the NASA Manned Spacecraft Center of fire inside the Apollo Service Module oxygen tank. The photograph from a motion picture sequence taken from outside the vessel shows failure of tank conduit with abrupt loss of oxygen pressure (41984); Third photograph in sequence of three showing panel separation test at Langley Research Center (41985).

Frontal dynamic aphasia in progressive supranuclear palsy: Distinguishing between generation and fluent sequencing of novel thoughts.

PubMed

Robinson, Gail A; Spooner, Donna; Harrison, William J

2015-10-01

Frontal dynamic aphasia is characterised by a profound reduction in spontaneous speech despite well-preserved naming, repetition and comprehension. Since Luria (1966, 1970) designated this term, two main forms of dynamic aphasia have been identified: one, a language-specific selection deficit at the level of word/sentence generation, associated with left inferior frontal lesions; and two, a domain-general impairment in generating multiple responses or connected speech, associated with more extensive bilateral frontal and/or frontostriatal damage. Both forms of dynamic aphasia have been interpreted as arising due to disturbances in early prelinguistic conceptual preparation mechanisms that are critical for language production. We investigate language-specific and domain-general accounts of dynamic aphasia and address two issues: one, whether deficits in multiple conceptual preparation mechanisms can co-occur; and two, the contribution of broader cognitive processes such as energization, the ability to initiate and sustain response generation over time, to language generation failure. Thus, we report patient WAL who presented with frontal dynamic aphasia in the context of progressive supranuclear palsy (PSP). WAL was given a series of experimental tests that showed that his dynamic aphasia was not underpinned by a language-specific deficit in selection or in microplanning. By contrast, WAL presented with a domain-general deficit in fluent sequencing of novel thoughts. The latter replicated the pattern documented in a previous PSP patient (Robinson, et al., 2006); however, unique to WAL, generating novel thoughts was impaired but there was no evidence of a sequencing deficit because perseveration was absent. Thus, WAL is the first unequivocal case to show a distinction between novel thought generation and subsequent fluent sequencing. Moreover, WAL's generation deficit encompassed verbal and non-verbal responses, showing a similar (but more profoundly reduced) pattern of performance to frontal patients with an energization deficit. In addition to impaired generation of novel thoughts, WAL presented with a concurrent strategy generation deficit, both falling within the second form of dynamic aphasia comprised of domain-general conceptual preparation mechanisms. Thus, within this second form of dynamic aphasia, concurrent deficits can co-occur. Overall, WAL presented with the second form of dynamic aphasia and was impaired in the generation of novel thoughts and internally-generated strategies, in the context of PSP and bilateral frontostriatal damage. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Statistical tests to compare motif count exceptionalities

PubMed Central

Robin, Stéphane; Schbath, Sophie; Vandewalle, Vincent

2007-01-01

Background Finding over- or under-represented motifs in biological sequences is now a common task in genomics. Thanks to p-value calculation for motif counts, exceptional motifs are identified and represent candidate functional motifs. The present work addresses the related question of comparing the exceptionality of one motif in two different sequences. Just comparing the motif count p-values in each sequence is indeed not sufficient to decide if this motif is significantly more exceptional in one sequence compared to the other one. A statistical test is required. Results We develop and analyze two statistical tests, an exact binomial one and an asymptotic likelihood ratio test, to decide whether the exceptionality of a given motif is equivalent or significantly different in two sequences of interest. For that purpose, motif occurrences are modeled by Poisson processes, with a special care for overlapping motifs. Both tests can take the sequence compositions into account. As an illustration, we compare the octamer exceptionalities in the Escherichia coli K-12 backbone versus variable strain-specific loops. Conclusion The exact binomial test is particularly adapted for small counts. For large counts, we advise to use the likelihood ratio test which is asymptotic but strongly correlated with the exact binomial test and very simple to use. PMID:17346349

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

PubMed Central

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-01-01

Purpose Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. Methods We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. Results WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. Conclusion WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort. PMID:28771251

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.

PubMed

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-04-01

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Folate bioavailability from foods rich in folates assessed in a short term human study using stable isotope dilution assays.

PubMed

Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

2015-01-01

Different sources of folate may have different bioavailability and hence may impact the standard definition of folate equivalents. In order to examine this, a short term human study was undertaken to evaluate the relative native folate bioavailabilities from spinach, Camembert cheese and wheat germs compared to pteroylmonoglutamic acid as the reference dose. The study had a single-centre, randomised, four-treatment, four-period, four-sequence, cross-over design, i.e. the four (food) items to be tested (referred to as treatments) were administered in sequences according to the Latin square, so that each experimental treatment occurred only once within each sequence and once within each study period. Each of the 24 subjects received the four experimental items separated by a 14-day equilibrium phase and received a pteroylmonoglutamic acid supplement for 14 days before the first testing and between the testings for saturation of body pools. Folates in test foods, plasma and urine samples were determined by stable isotope dilution assays, and in urine and plasma, the concentrations of 5-methyltetrahydrofolate were evaluated. Standard non-compartmental methods were applied to determine the biokinetic parameters C(max), t(max) and AUC from baseline corrected 5-methyltetrahydrofolate concentrations within the interval from 0 to 12 hours. The variability of AUC and C(max) was moderate for spinach and oral solution of pteroylmonoglutamic acid but high for Camembert cheese and very high for wheat germs. The median t(max) was lowest for spinach, though t(max) showed a high variability among all treatments. When comparing the ratio estimates of AUC and C(max) for the different test foods, highest bioavailability was found for spinach followed by that for wheat germs and Camembert cheese. The results underline the dependence of folate bioavailability on the type of food ingested. Therefore, the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents has to be questioned and requires further investigation.

Accurate clinical genetic testing for autoinflammatory diseases using the next-generation sequencing platform MiSeq.

PubMed

Nakayama, Manabu; Oda, Hirotsugu; Nakagawa, Kenji; Yasumi, Takahiro; Kawai, Tomoki; Izawa, Kazushi; Nishikomori, Ryuta; Heike, Toshio; Ohara, Osamu

2017-03-01

Autoinflammatory diseases occupy one of a group of primary immunodeficiency diseases that are generally thought to be caused by mutation of genes responsible for innate immunity, rather than by acquired immunity. Mutations related to autoinflammatory diseases occur in 12 genes. For example, low-level somatic mosaic NLRP3 mutations underlie chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID). In current clinical practice, clinical genetic testing plays an important role in providing patients with quick, definite diagnoses. To increase the availability of such testing, low-cost high-throughput gene-analysis systems are required, ones that not only have the sensitivity to detect even low-level somatic mosaic mutations, but also can operate simply in a clinical setting. To this end, we developed a simple method that employs two-step tailed PCR and an NGS system, MiSeq platform, to detect mutations in all coding exons of the 12 genes responsible for autoinflammatory diseases. Using this amplicon sequencing system, we amplified a total of 234 amplicons derived from the 12 genes with multiplex PCR. This was done simultaneously and in one test tube. Each sample was distinguished by an index sequence of second PCR primers following PCR amplification. With our procedure and tips for reducing PCR amplification bias, we were able to analyze 12 genes from 25 clinical samples in one MiSeq run. Moreover, with the certified primers designed by our short program-which detects and avoids common SNPs in gene-specific PCR primers-we used this system for routine genetic testing. Our optimized procedure uses a simple protocol, which can easily be followed by virtually any office medical staff. Because of the small PCR amplification bias, we can analyze simultaneously several clinical DNA samples with low cost and can obtain sufficient read numbers to detect a low level of somatic mosaic mutations.

Characterisation of nasal Staphylococcus delphini and Staphylococcus pseudintermedius isolates from healthy donkeys in Tunisia.

PubMed

Gharsa, H; Slama, K Ben; Gómez-Sanz, E; Gómez, P; Klibi, N; Zarazaga, M; Boudabous, A; Torres, C

2015-07-01

Staphylococcus intermedius group (SIG) bacteria can colonise the nares of some animals but are also emerging pathogens in humans and animals. To analyse SIG nasal carriage in healthy donkeys destined for food consumption in Tunisia and to characterise recovered isolates. Nasal swabs from 100 healthy donkeys were tested for SIG recovery, and isolates were identified by biochemical and molecular methods. Antimicrobial susceptibility of isolates was tested and detection of antimicrobial resistance and virulence genes was performed. Isolates were typed at the clonal level by multilocus sequence typing and SmaI pulsed-field gel electrophoresis. Staphylococcus delphini and Staphylococcus pseudintermedius (included in SIG) were obtained in 19% and 2% of the tested samples, respectively, and one isolate per sample was characterised. All isolates were meticillin susceptible and mecA negative. Most S. delphini and S. pseudintermedius isolates showed susceptibility to all antimicrobials tested, with the exception of 2 isolates resistant to tetracycline (tet(M) gene) or fusidic acid. The following toxin genes were identified (percentage of isolates): lukS-I (100%), lukF-I (9.5%), siet (100%), se-int (90%), seccanine (19%) and expA (9.5%). Thirteen different pulsed-field gel electrophoresis profiles were identified among the 21 SIG isolates. Additionally, the following 9 different sequence types (STs) were detected by multilocus sequence typing, 6 of them new: ST219 (6 isolates), ST12 (5 isolates), ST220 (3 isolates), ST13, ST50, ST193, ST196, ST218 and ST221 (one isolate each). Staphylococcus delphini and S. pseudintermedius are common nasal colonisers of donkeys, generally susceptible to the antimicrobials tested; nevertheless, these SIG isolates contain virulence genes, including the recently described exfoliative gene (expA) and several enterotoxin genes, with potential implications for public health. This is the first description of S. delphini in Tunisia. The Summary is available in Chinese - see Supporting information. © 2014 EVJ Ltd.

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

Hachisu, Izumi; Kato, Mariko, E-mail: hachisu@ea.c.u-tokyo.ac.jp, E-mail: mariko@educ.cc.keio.ac.jp

We identified a general course of classical nova outbursts in the B – V versus U – B color-color diagram. It is reported that novae show spectra similar to those of A-F supergiants near optical light maximum. However, they do not follow the supergiant sequence in the color-color diagram, neither the blackbody nor the main-sequence sequence. Instead, we found that novae evolve along a new sequence in the pre-maximum and near-maximum phases, which we call 'the nova-giant sequence'. This sequence is parallel to but Δ(U – B) ≈ –0.2 mag bluer than the supergiant sequence. This is because the massmore » of a nova envelope is much (∼10{sup –4} times) less than that of a normal supergiant. After optical maximum, its color quickly evolves back blueward along the same nova-giant sequence and reaches the point of free-free emission (B – V = –0.03, U – B = –0.97), which coincides with the intersection of the blackbody sequence and the nova-giant sequence, and remains there for a while. Then the color evolves leftward (blueward in B – V but almost constant in U – B), owing mainly to the development of strong emission lines. This is the general course of nova outbursts in the color-color diagram, which was deduced from eight well-observed novae in various speed classes. For a nova with unknown extinction, we can determine a reliable value of the color excess by matching the observed track of the target nova with this general course. This is a new and convenient method for obtaining the color excesses of classical novae. Using this method, we redetermined the color excesses of 20 well-observed novae. The obtained color excesses are in reasonable agreement with the previous results, which in turn support the idea of our general track of nova outbursts. Additionally, we estimated the absolute V magnitudes of about 30 novae using a method for time-stretching nova light curves to analyze the distance-reddening relations of the novae.« less

StrBioLib: a Java library for development of custom computationalstructural biology applications

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

Chandonia, John-Marc

2007-05-14

Summary: StrBioLib is a library of Java classes useful fordeveloping software for computational structural biology research.StrBioLib contains classes to represent and manipulate proteinstructures, biopolymer sequences, sets of biopolymer sequences, andalignments between biopolymers based on either sequence or structure.Interfaces are provided to interact with commonly used bioinformaticsapplications, including (PSI)-BLAST, MODELLER, MUSCLE, and Primer3, andtools are provided to read and write many file formats used to representbioinformatic data. The library includes a general-purpose neural networkobject with multiple training algorithms, the Hooke and Jeeves nonlinearoptimization algorithm, and tools for efficient C-style string parsingand formatting. StrBioLib is the basis for the Pred2ary secondarystructure predictionmore » program, is used to build the ASTRAL compendium forsequence and structure analysis, and has been extensively tested throughuse in many smaller projects. Examples and documentation are available atthe site below.Availability: StrBioLib may be obtained under the terms ofthe GNU LGPL license from http://strbio.sourceforge.net/Contact:JMChandonia@lbl.gov« less

An improved immune algorithm for optimizing the pulse width modulation control sequence of inverters

NASA Astrophysics Data System (ADS)

Sheng, L.; Qian, S. Q.; Ye, Y. Q.; Wu, Y. H.

2017-09-01

In this article, an improved immune algorithm (IIA), based on the fundamental principles of the biological immune system, is proposed for optimizing the pulse width modulation (PWM) control sequence of a single-phase full-bridge inverter. The IIA takes advantage of the receptor editing and adaptive mutation mechanisms of the immune system to develop two operations that enhance the population diversity and convergence of the proposed algorithm. To verify the effectiveness and examine the performance of the IIA, 17 cases are considered, including fixed and disturbed resistances. Simulation results show that the IIA is able to obtain an effective PWM control sequence. Furthermore, when compared with existing immune algorithms (IAs), genetic algorithms (GAs), a non-traditional GA, simplified simulated annealing, and a generalized Hopfield neural network method, the IIA can achieve small total harmonic distortion (THD) and large magnitude. Meanwhile, a non-parametric test indicates that the IIA is significantly better than most comparison algorithms. Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/0305215X.2016.1250894.

454 Pyrosequencing to Describe Microbial Eukaryotic Community Composition, Diversity and Relative Abundance: A Test for Marine Haptophytes

PubMed Central

Egge, Elianne; Bittner, Lucie; Andersen, Tom; Audic, Stéphane; de Vargas, Colomban; Edvardsen, Bente

2013-01-01

Next generation sequencing of ribosomal DNA is increasingly used to assess the diversity and structure of microbial communities. Here we test the ability of 454 pyrosequencing to detect the number of species present, and assess the relative abundance in terms of cell numbers and biomass of protists in the phylum Haptophyta. We used a mock community consisting of equal number of cells of 11 haptophyte species and compared targeting DNA and RNA/cDNA, and two different V4 SSU rDNA haptophyte-biased primer pairs. Further, we tested four different bioinformatic filtering methods to reduce errors in the resulting sequence dataset. With sequencing depth of 11000–20000 reads and targeting cDNA with Haptophyta specific primers Hap454 we detected all 11 species. A rarefaction analysis of expected number of species recovered as a function of sampling depth suggested that minimum 1400 reads were required here to recover all species in the mock community. Relative read abundance did not correlate to relative cell numbers. Although the species represented with the largest biomass was also proportionally most abundant among the reads, there was generally a weak correlation between proportional read abundance and proportional biomass of the different species, both with DNA and cDNA as template. The 454 sequencing generated considerable spurious diversity, and more with cDNA than DNA as template. With initial filtering based only on match with barcode and primer we observed 100-fold more operational taxonomic units (OTUs) at 99% similarity than the number of species present in the mock community. Filtering based on quality scores, or denoising with PyroNoise resulted in ten times more OTU99% than the number of species. Denoising with AmpliconNoise reduced the number of OTU99% to match the number of species present in the mock community. Based on our analyses, we propose a strategy to more accurately depict haptophyte diversity using 454 pyrosequencing. PMID:24069303

Modeling Explosion Induced Aftershocks

NASA Astrophysics Data System (ADS)

Kroll, K.; Ford, S. R.; Pitarka, A.; Walter, W. R.; Richards-Dinger, K. B.

2017-12-01

Many traditional earthquake-explosion discrimination tools are based on properties of the seismic waveform or their spectral components. Common discrimination methods include estimates of body wave amplitude ratios, surface wave magnitude scaling, moment tensor characteristics, and depth. Such methods are limited by station coverage and noise. Ford and Walter (2010) proposed an alternate discrimination method based on using properties of aftershock sequences as a means of earthquakeexplosion differentiation. Previous studies have shown that explosion sources produce fewer aftershocks that are generally smaller in magnitude compared to aftershocks of similarly sized earthquake sources (Jarpe et al., 1994, Ford and Walter, 2010). It has also been suggested that the explosion-induced aftershocks have smaller Gutenberg- Richter b-values (Ryall and Savage, 1969) and that their rates decay faster than a typical Omori-like sequence (Gross, 1996). To discern whether these observations are generally true of explosions or are related to specific site conditions (e.g. explosion proximity to active faults, tectonic setting, crustal stress magnitudes) would require a thorough global analysis. Such a study, however, is hindered both by lack of evenly distributed explosion-sources and the availability of global seismicity data. Here, we employ two methods to test the efficacy of explosions at triggering aftershocks under a variety of physical conditions. First, we use the earthquake rate equations from Dieterich (1994) to compute the rate of aftershocks related to an explosion source assuming a simple spring-slider model. We compare seismicity rates computed with these analytical solutions to those produced by the 3D, multi-cycle earthquake simulator, RSQSim. We explore the relationship between geological conditions and the characteristics of the resulting explosion-induced aftershock sequence. We also test hypothesis that aftershock generation is dependent upon the frequency content of the passing dynamic seismic waves as suggested by Parsons and Velasco (2009). Lastly, we compare all results of explosion-induced aftershocks with aftershocks generated by similarly sized earthquake sources. Prepared by LLNL under Contract DE-AC52-07NA27344.

Fatigue-test acceleration with flight-by-flight loading and heating to simulate supersonic-transport operation

NASA Technical Reports Server (NTRS)

Imig, L. A.; Garrett, L. E.

1973-01-01

Possibilities for reducing fatigue-test time for supersonic-transport materials and structures were studied in tests with simulated flight-by-flight loading. In order to determine whether short-time tests were feasible, the results of accelerated tests (2 sec per flight) were compared with the results of real-time tests (96 min per flight). The effects of design mean stress, the stress range for ground-air-ground cycles, simulated thermal stress, the number of stress cycles in each flight, and salt corrosion were studied. The flight-by-flight stress sequences were applied to notched sheet specimens of Ti-8Al-1Mo-1V and Ti-6Al-4V titanium alloys. A linear cumulative-damage analysis accounted for large changes in stress range of the simulated flights but did not account for the differences between real-time and accelerated tests. The fatigue lives from accelerated tests were generally within a factor of two of the lives from real-time tests; thus, within the scope of the investigation, accelerated testing seems feasible.

Genomic treasure troves: complete genome sequencing of herbarium and insect museum specimens.

PubMed

Staats, Martijn; Erkens, Roy H J; van de Vossenberg, Bart; Wieringa, Jan J; Kraaijeveld, Ken; Stielow, Benjamin; Geml, József; Richardson, James E; Bakker, Freek T

2013-01-01

Unlocking the vast genomic diversity stored in natural history collections would create unprecedented opportunities for genome-scale evolutionary, phylogenetic, domestication and population genomic studies. Many researchers have been discouraged from using historical specimens in molecular studies because of both generally limited success of DNA extraction and the challenges associated with PCR-amplifying highly degraded DNA. In today's next-generation sequencing (NGS) world, opportunities and prospects for historical DNA have changed dramatically, as most NGS methods are actually designed for taking short fragmented DNA molecules as templates. Here we show that using a standard multiplex and paired-end Illumina sequencing approach, genome-scale sequence data can be generated reliably from dry-preserved plant, fungal and insect specimens collected up to 115 years ago, and with minimal destructive sampling. Using a reference-based assembly approach, we were able to produce the entire nuclear genome of a 43-year-old Arabidopsis thaliana (Brassicaceae) herbarium specimen with high and uniform sequence coverage. Nuclear genome sequences of three fungal specimens of 22-82 years of age (Agaricus bisporus, Laccaria bicolor, Pleurotus ostreatus) were generated with 81.4-97.9% exome coverage. Complete organellar genome sequences were assembled for all specimens. Using de novo assembly we retrieved between 16.2-71.0% of coding sequence regions, and hence remain somewhat cautious about prospects for de novo genome assembly from historical specimens. Non-target sequence contaminations were observed in 2 of our insect museum specimens. We anticipate that future museum genomics projects will perhaps not generate entire genome sequences in all cases (our specimens contained relatively small and low-complexity genomes), but at least generating vital comparative genomic data for testing (phylo)genetic, demographic and genetic hypotheses, that become increasingly more horizontal. Furthermore, NGS of historical DNA enables recovering crucial genetic information from old type specimens that to date have remained mostly unutilized and, thus, opens up a new frontier for taxonomic research as well.

Unlinking the methylome pattern from nucleotide sequence, revealed by large-scale in vivo genome engineering and methylome editing in medaka fish

PubMed Central

Nakamura, Ryohei; Uno, Ayako; Kumagai, Masahiko; Fukushima, Hiroto S.; Morishita, Shinichi; Takeda, Hiroyuki

2017-01-01

The heavily methylated vertebrate genomes are punctuated by stretches of poorly methylated DNA sequences that usually mark gene regulatory regions. It is known that the methylation state of these regions confers transcriptional control over their associated genes. Given its governance on the transcriptome, cellular functions and identity, genome-wide DNA methylation pattern is tightly regulated and evidently predefined. However, how is the methylation pattern determined in vivo remains enigmatic. Based on in silico and in vitro evidence, recent studies proposed that the regional hypomethylated state is primarily determined by local DNA sequence, e.g., high CpG density and presence of specific transcription factor binding sites. Nonetheless, the dependency of DNA methylation on nucleotide sequence has not been carefully validated in vertebrates in vivo. Herein, with the use of medaka (Oryzias latipes) as a model, the sequence dependency of DNA methylation was intensively tested in vivo. Our statistical modeling confirmed the strong statistical association between nucleotide sequence pattern and methylation state in the medaka genome. However, by manipulating the methylation state of a number of genomic sequences and reintegrating them into medaka embryos, we demonstrated that artificially conferred DNA methylation states were predominantly and robustly maintained in vivo, regardless of their sequences and endogenous states. This feature was also observed in the medaka transgene that had passed across generations. Thus, despite the observed statistical association, nucleotide sequence was unable to autonomously determine its own methylation state in medaka in vivo. Our results apparently argue against the notion of the governance on the DNA methylation by nucleotide sequence, but instead suggest the involvement of other epigenetic factors in defining and maintaining the DNA methylation landscape. Further investigation in other vertebrate models in vivo will be needed for the generalization of our observations made in medaka. PMID:29267279

Regular Pentagons and the Fibonacci Sequence.

ERIC Educational Resources Information Center

French, Doug

1989-01-01

Illustrates how to draw a regular pentagon. Shows the sequence of a succession of regular pentagons formed by extending the sides. Calculates the general formula of the Lucas and Fibonacci sequences. Presents a regular icosahedron as an example of the golden ratio. (YP)

State of Iowa Scope and Sequence for Vocational Home Economics.

ERIC Educational Resources Information Center

Iowa State Dept. of Public Instruction, Des Moines. Div. of Career Education.

This scope and sequence guide for vocational home economics programs in Iowa discusses the most important dimensions of the program and describes the general purposes of programs along with factors that affect them, both in general and for Iowa specifically. The introductory chapter of the guide sets the context and the mission and also includes a…

Use of low frequency repetitive transcranial magnetic stimulation to reduce context-dependent learning in people with Parkinson's disease.

PubMed

Lee, Ya-Yun; Fisher, Beth E

2017-05-22

Compared with age-matched non-disabled adults, people with Parkinson's disease (PD) demonstrated greater context-dependent learning, a phenomenon in which an individual shows inferior motor performance when the testing environmental context is different from the original practice context. Additionally, enhanced context- dependency has been shown to be associated with an increased activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine whether context-dependent learning in people with PD could be reduced by decreasing DLPFC activation with low frequency repetitive transcranial magnetic stimulation (rTMS). Quasi-experimental pre-post test controlled study. University laboratory. Twenty-seven participants (18 individuals with PD and 9 age-matched non- disabled adults) were recruited into the PD, PD_rTMS (PD participants who received low frequency rTMS), and Control groups. All participants practiced a finger sequence task containing 3 sequences embedded within specific contexts (colored circles and spatial location on a computer screen) on the first day. On day 2, the participants were tested under the SWITCH and SAME conditions. In the SWITCH condition, the sequence-context association changed from that of practice; in the SAME condition, the sequence-context association remained the same as practice. The PD_rTMS group received 1 Hz rTMS applied over the left DLPFC on the second day before the testing conditions. Switch cost, the performance difference between the SWITCH and SAME conditions, was calculated to indicate context-dependency. All participants improved throughout practice on the first day. Analysis of the switch cost revealed a significant group main effect (p = 0.050). Post-hoc analysis revealed that the PD_rTMS group had significantly smaller switch cost than the PD group (p = 0.031) but not the Control group. Low frequency rTMS applied over DLPFC reduced context-dependency in people with PD. The findings provide a preliminary evidence of using low frequency rTMS as an adjuvant intervention approach to facilitate individuals with PD to generalize a learned motor task from one environmental context to another.

Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis.

PubMed

Nolan, Danielle; Carlson, Martha

2016-06-01

Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations. © The Author(s) 2016.

Care delivery considerations for widespread and equitable implementation of inherited cancer predisposition testing

PubMed Central

Cragun, Deborah; Kinney, Anita Y; Pal, Tuya

2017-01-01

Introduction DNA sequencing advances through next-generation sequencing (NGS) and several practice changing events, have led to shifting paradigms for inherited cancer predisposition testing. These changes necessitated a means by which to maximize health benefits without unnecessarily inflating healthcare costs and exacerbating health disparities. Areas covered NGS-based tests encompass multi-gene panel tests, whole exome sequencing, and whole genome sequencing, all of which test for multiple genes simultaneously, compared to prior sequencing practices through which testing was performed sequentially for one or two genes. Taking an ecological approach, this article synthesizes the current literature to consider the broad impact of these advances from the individual patient-, interpersonal-, organizational-, community- and policy-levels. Furthermore, the authors describe how multi-level factors that impact genetic testing and follow-up care reveal great potential to widen existing health disparities if these issues are not addressed. Expert Commentary As we consider ways to maximize patient benefit from testing in a cost effective manner, it is important to consider perspectives from multiple levels. This information is needed to guide the development of interventions such that the promise of genomic testing may be realized by all populations, regardless of race, ethnicity and ability to pay. PMID:27910721

Some observations on mesh refinement schemes applied to shock wave phenomena

NASA Technical Reports Server (NTRS)

Quirk, James J.

1995-01-01

This workshop's double-wedge test problem is taken from one of a sequence of experiments which were performed in order to classify the various canonical interactions between a planar shock wave and a double wedge. Therefore to build up a reasonably broad picture of the performance of our mesh refinement algorithm we have simulated three of these experiments and not just the workshop case. Here, using the results from these simulations together with their experimental counterparts, we make some general observations concerning the development of mesh refinement schemes for shock wave phenomena.

Multiclass Bayes error estimation by a feature space sampling technique

NASA Technical Reports Server (NTRS)

Mobasseri, B. G.; Mcgillem, C. D.

1979-01-01

A general Gaussian M-class N-feature classification problem is defined. An algorithm is developed that requires the class statistics as its only input and computes the minimum probability of error through use of a combined analytical and numerical integration over a sequence simplifying transformations of the feature space. The results are compared with those obtained by conventional techniques applied to a 2-class 4-feature discrimination problem with results previously reported and 4-class 4-feature multispectral scanner Landsat data classified by training and testing of the available data.

A flexible motif search technique based on generalized profiles.

PubMed

Bucher, P; Karplus, K; Moeri, N; Hofmann, K

1996-03-01

A flexible motif search technique is presented which has two major components: (1) a generalized profile syntax serving as a motif definition language; and (2) a motif search method specifically adapted to the problem of finding multiple instances of a motif in the same sequence. The new profile structure, which is the core of the generalized profile syntax, combines the functions of a variety of motif descriptors implemented in other methods, including regular expression-like patterns, weight matrices, previously used profiles, and certain types of hidden Markov models (HMMs). The relationship between generalized profiles and other biomolecular motif descriptors is analyzed in detail, with special attention to HMMs. Generalized profiles are shown to be equivalent to a particular class of HMMs, and conversion procedures in both directions are given. The conversion procedures provide an interpretation for local alignment in the framework of stochastic models, allowing for clear, simple significance tests. A mathematical statement of the motif search problem defines the new method exactly without linking it to a specific algorithmic solution. Part of the definition includes a new definition of disjointness of alignments.

Communicating the Benefits of a Full Sequence of High School Science Courses

ERIC Educational Resources Information Center

Nicholas, Catherine Marie

2014-01-01

High school students are generally uninformed about the benefits of enrolling in a full sequence of science courses, therefore only about a third of our nation's high school graduates have completed the science sequence of Biology, Chemistry and Physics. The lack of students completing a full sequence of science courses contributes to the deficit…

Characterization of Bleomycin-Mediated Cleavage of a Hairpin DNA Library

PubMed Central

Segerman, Zachary J.; Roy, Basab; Hecht, Sidney M.

2013-01-01

A study of BLM A5 was conducted using a previously isolated library of hairpin DNAs found to bind strongly to metal free BLM. The ability of Fe(II)•BLM to effect cleavage on both the 3' and 5'-arms of the hairpin DNAs was characterized. The strongly bound DNAs were found to be efficient substrates for Fe•BLM A5-mediated hairpin DNA cleavage. Surprisingly, the most prevalent site of BLM-mediated cleavage was found to be the 5′-AT-3′ dinucleotide sequence. This dinucleotide sequence, and other sequences generally not cleaved well by BLM when examined using arbitrarily chosen DNA substrates, were apparent when examining the library of ten hairpin DNAs. In total, 132 sites of DNA cleavage were produced by exposure of the hairpin DNA library to Fe•BLM A5. The existence of multiple sites of cleavage on both the 3′- and 5′-arms of the hairpin DNAs suggested that some of these might be double-strand cleavage events. Accordingly, an assay was developed with which to test the propensity of the hairpin DNAs to undergo double-strand DNA damage. One hairpin DNA was characterized using this method, and gave results consistent with earlier reports of double-strand DNA cleavage, but with a sequence selectivity different from those reported previously. PMID:23834496

Nucleic acid arrays and methods of synthesis

DOEpatents

Sabanayagam, Chandran R.; Sano, Takeshi; Misasi, John; Hatch, Anson; Cantor, Charles

2001-01-01

The present invention generally relates to high density nucleic acid arrays and methods of synthesizing nucleic acid sequences on a solid surface. Specifically, the present invention contemplates the use of stabilized nucleic acid primer sequences immobilized on solid surfaces, and circular nucleic acid sequence templates combined with the use of isothermal rolling circle amplification to thereby increase nucleic acid sequence concentrations in a sample or on an array of nucleic acid sequences.

Updates in the genetic evaluation of the child with global developmental delay or intellectual disability.

PubMed

Flore, Leigh Anne; Milunsky, Jeff M

2012-12-01

Global developmental delay (GDD) and intellectual disability (ID) occur in up to 3% of the general population and are even more commonly encountered in the setting of the pediatric neurology clinic. New advances in technology and in the understanding of genetic disorders have led to changes in the diagnostic approach to a child with unexplained GDD or ID. Chromosomal microarray has become a first-line test for evaluation of patients in this population and has both significantly increased diagnostic yield and introduced new challenges in the interpretation of copy number variants of uncertain significance. The G-banded karyotype is now frequently utilized as an adjunct to the microarray rather than as a first-line test in individuals with GDD or ID. Fragile X DNA testing continues to be recommended in the initial evaluation of the child with GDD or ID. The presence or absence of certain cardinal features (such as microcephaly or macrocephaly, seizures, autism, abnormal neurologic examination, and facial dysmorphism) can be utilized to direct single-gene molecular testing. The availability of next-generation and massively parallel sequencing technologies has enabled the use of genetic testing panels, in which dozens of genes associated with GDD or ID may be rapidly analyzed. Most recently, the clinical availability of whole-genome and whole-exome sequencing has opened new possibilities for the evaluation of individuals with GDD or ID who have previously eluded a genetic diagnosis. Consultation with a medical geneticist is recommended when progressing beyond first-tier analyses to most efficiently prioritize testing. Copyright © 2012 Elsevier Inc. All rights reserved.

Hemispheric asymmetries of a motor memory in a recognition test after learning a movement sequence.

PubMed

Leinen, Peter; Panzer, Stefan; Shea, Charles H

2016-11-01

Two experiments utilizing a spatial-temporal movement sequence were designed to determine if the memory of the sequence is lateralized in the left or right hemisphere. In Experiment 1, dominant right-handers were randomly assigned to one of two acquisition groups: a left-hand starter and a right-hand starter group. After an acquisition phase, reaction time (RT) was measured in a recognition test by providing the learned sequential pattern in the left or right visual half-field for 150ms. In a retention test and two transfer tests the dominant coordinate system for sequence production was evaluated. In Experiment 2 dominant left-handers and dominant right-handers had to acquire the sequence with their dominant limb. The results of Experiment 1 indicated that RT was significantly shorter when the acquired sequence was provided in the right visual field during the recognition test. The same results occurred in Experiment 2 for dominant right-handers and left-handers. These results indicated a right visual field left hemisphere advantage in the recognition test for the practiced stimulus for dominant left and right-handers, when the task was practiced with the dominant limb. Copyright © 2016 Elsevier B.V. All rights reserved.

Equilibrium figures inside the dark-matter ring and the shapes of elliptical galaxies

NASA Astrophysics Data System (ADS)

Kondratyev, B. P.; Trubitsyna, N. G.; Kireeva, E. N.

We solve the general problem of the theory of equilibrium figures and analyze two classes of liquid rotating gravitating figures residing inside a gravitating ring or torus. These figures form families of sequences of generalized oblate spheroids and triaxial ellipsoids, which at the lower limit of the tidal parameter α = 0 have the form of the Maclaurin spheroids and the Jacobi ellipsoids. In intermediate cases 0 < α ≤ αmax each new sequence of axisymmetric equilibrium figures has two non-rotating boundary spheroids. At the upper limit αmax/(π Gρ ) = 0.1867 the sequence degenerates into a single non-rotating spheroid with the eccentricity {e cr} ≈ 0.96 corresponding to the flattening limit of elliptical galaxies (E7). We also perform a detailed study of the sequences of generalized triaxial ellipsoids and find bifurcation points of triaxial ellipsoids in the sequences of generalized spheroids. We use this method to explain the shapes of E-galaxies. According to observations, very slowly rotating oblate E-type galaxies are known that have the shapes, which, because of instability, cannot be supported by velocity dispersion anisotropy exclusively. The hypothesis of a massive dark-matter outer ring requires no extreme anisotropy of pressure; it not only explains the shape of these elliptical galaxies, but also sheds new light on the riddle of the ellipticity limit (E7) of elliptical galaxies.

Validation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection.

PubMed

Schlaberg, Robert; Chiu, Charles Y; Miller, Steve; Procop, Gary W; Weinstock, George

2017-06-01

- Metagenomic sequencing can be used for detection of any pathogens using unbiased, shotgun next-generation sequencing (NGS), without the need for sequence-specific amplification. Proof-of-concept has been demonstrated in infectious disease outbreaks of unknown causes and in patients with suspected infections but negative results for conventional tests. Metagenomic NGS tests hold great promise to improve infectious disease diagnostics, especially in immunocompromised and critically ill patients. - To discuss challenges and provide example solutions for validating metagenomic pathogen detection tests in clinical laboratories. A summary of current regulatory requirements, largely based on prior guidance for NGS testing in constitutional genetics and oncology, is provided. - Examples from 2 separate validation studies are provided for steps from assay design, and validation of wet bench and bioinformatics protocols, to quality control and assurance. - Although laboratory and data analysis workflows are still complex, metagenomic NGS tests for infectious diseases are increasingly being validated in clinical laboratories. Many parallels exist to NGS tests in other fields. Nevertheless, specimen preparation, rapidly evolving data analysis algorithms, and incomplete reference sequence databases are idiosyncratic to the field of microbiology and often overlooked.

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

Poyer, D.A.

In this report, tests of statistical significance of five sets of variables with household energy consumption (at the point of end-use) are described. Five models, in sequence, were empirically estimated and tested for statistical significance by using the Residential Energy Consumption Survey of the US Department of Energy, Energy Information Administration. Each model incorporated additional information, embodied in a set of variables not previously specified in the energy demand system. The variable sets were generally labeled as economic variables, weather variables, household-structure variables, end-use variables, and housing-type variables. The tests of statistical significance showed each of the variable sets tomore » be highly significant in explaining the overall variance in energy consumption. The findings imply that the contemporaneous interaction of different types of variables, and not just one exclusive set of variables, determines the level of household energy consumption.« less

Parameter Estimation in Atmospheric Data Sets

NASA Technical Reports Server (NTRS)

Wenig, Mark; Colarco, Peter

2004-01-01

In this study the structure tensor technique is used to estimate dynamical parameters in atmospheric data sets. The structure tensor is a common tool for estimating motion in image sequences. This technique can be extended to estimate other dynamical parameters such as diffusion constants or exponential decay rates. A general mathematical framework was developed for the direct estimation of the physical parameters that govern the underlying processes from image sequences. This estimation technique can be adapted to the specific physical problem under investigation, so it can be used in a variety of applications in trace gas, aerosol, and cloud remote sensing. As a test scenario this technique will be applied to modeled dust data. In this case vertically integrated dust concentrations were used to derive wind information. Those results can be compared to the wind vector fields which served as input to the model. Based on this analysis, a method to compute atmospheric data parameter fields will be presented. .

Riverine effects on mitochondrial structure of Bornean orangutans (Pongo pygmaeus) at two spatial scales.

PubMed

Jalil, M F; Cable, J; Sinyor, J; Lackman-Ancrenaz, I; Ancrenaz, M; Bruford, M W; Goossens, B

2008-06-01

We examined mitochondrial DNA control region sequences of 73 Kinabatangan orangutans to test the hypothesis that the phylogeographical structure of the Bornean orangutan is influenced by riverine barriers. The Lower Kinabatangan Wildlife Sanctuary contains one of the most northern populations of orangutans (Pongo pygmaeus) on Borneo and is bisected by the Kinabatangan River, the longest river in Sabah. Orang-utan samples on either side of the river were strongly differentiated with a high Phi(ST) value of 0.404 (P < 0.001). Results also suggest an east-west gradient of genetic diversity and evidence for population expansion along the river, possibly reflecting a postglacial colonization of the Kinabatangan floodplain. We compared our data with previously published sequences of Bornean orangutans in the context of river catchment structure on the island and evaluated the general relevance of rivers as barriers to gene flow in this long-lived, solitary arboreal ape.

Theory of mind and executive function in Chinese preschool children.

PubMed

Duh, Shinchieh; Paik, Jae H; Miller, Patricia H; Gluck, Stephanie C; Li, Hui; Himelfarb, Igor

2016-04-01

Cross-cultural research on children's theory of mind (ToM) understanding has raised questions about its developmental sequence and relationship with executive function (EF). The current study examined how ToM develops (using the tasks from Wellman & Liu, 2004) in relation to 2 EF skills (conflict inhibition, working memory) in 997 Chinese preschoolers (ages 3, 4, 5) in Chengdu, China. Compared with prior research with other Chinese and non-Chinese children, some general patterns in development were replicated in this sample. However, the children showed culture-specific reversals in the developmental sequence of ToM. For example, Chengdu children performed differently on the 2 false-belief tasks that were thought to be equivalent. Furthermore, conflict inhibition as well as working memory uniquely predicted ToM performance. We discuss the issues of ToM development as they relate to test items and cross-cultural--and subcultural--differences. (c) 2016 APA, all rights reserved).

Spatial methods for deriving crop rotation history

NASA Astrophysics Data System (ADS)

Mueller-Warrant, George W.; Trippe, Kristin M.; Whittaker, Gerald W.; Anderson, Nicole P.; Sullivan, Clare S.

2017-08-01

Benefits of converting 11 years of remote sensing classification data into cropping history of agricultural fields included measuring lengths of rotation cycles and identifying specific sequences of intervening crops grown between final years of old grass seed stands and establishment of new ones. Spatial and non-spatial methods were complementary. Individual-year classification errors were often correctable in spreadsheet-based non-spatial analysis, whereas their presence in spatial data generally led to exclusion of fields from further analysis. Markov-model testing of non-spatial data revealed that year-to-year cropping sequences did not match average frequencies for transitions among crops grown in western Oregon, implying that rotations into new grass seed stands were influenced by growers' desires to achieve specific objectives. Moran's I spatial analysis of length of time between consecutive grass seed stands revealed that clustering of fields was relatively uncommon, with high and low value clusters only accounting for 7.1 and 6.2% of fields.

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2013 CFR

2013-07-01

... temperature continuously to verify that it remains within the pre-test temperature range as specified in... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2012 CFR

2012-07-01

... temperature continuously to verify that it remains within the pre-test temperature range as specified in... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2014 CFR

2014-07-01

... temperature continuously to verify that it remains within the pre-test temperature range as specified in... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

Investigating the genetic diversity of Echinococcus granulosus sensu stricto with new microsatellites.

PubMed

Umhang, Gérald; Grenouillet, Frédéric; Bastid, Vanessa; M'Rad, Selim; Valot, Benoît; Oudni-M'Rad, Myriam; Babba, Hamouda; Boué, Franck

2018-06-18

Cystic echinococcosis is a zoonotic disease with worldwide distribution caused by the larval stage of the Cestode parasite Echinococcus granulosus sensu lato. Due to the predominance or even the exclusive presence of E. granulosus sensu stricto (s.s.) among E. granulosus species in many areas, the genetic diversity needs to be further investigated at the species level to better understand the inter- and intra-focus epidemiological features. Short sequences of mitochondrial or nuclear genes generally lack or have limited discriminatory power, hindering the detection of polymorphisms to reflect geographically based peculiarities and/or any history of infection. A high discriminatory power can only be reached by sequencing complete or near complete mitogenomes or relatively long nuclear sequences, which is time-consuming and onerous. To overcome this issue, a systematic research for single-locus microsatellites was performed on the nuclear genome of E. granulosus s.s. in order to investigate its intra-species genetic diversity. Two microsatellites, EgSca6 and EgSca11, were selected and characterized. The test of a panel of 75 cystic echinococcosis samples revealed a very high discrimination index of 0.824 for EgSca6, 0.987 for EgSca11, and 0.994 when multiplexing both microsatellites. Testing cystic echinococcosis samples from both liver and lungs in five sheep revealed that these two microsatellites appear to be of particular interest for investigating genetic diversity at the intra-individual host level. As this method has many advantages compared to classical sequencing, the availability of other targets means that it is potentially possible to constitute a panel facilitating large-scale molecular epidemiology studies for E. granulosus s.l.

Evidence of automatic processing in sequence learning using process-dissociation

PubMed Central

Mong, Heather M.; McCabe, David P.; Clegg, Benjamin A.

2012-01-01

This paper proposes a way to apply process-dissociation to sequence learning in addition and extension to the approach used by Destrebecqz and Cleeremans (2001). Participants were trained on two sequences separated from each other by a short break. Following training, participants self-reported their knowledge of the sequences. A recognition test was then performed which required discrimination of two trained sequences, either under the instructions to call any sequence encountered in the experiment “old” (the inclusion condition), or only sequence fragments from one half of the experiment “old” (the exclusion condition). The recognition test elicited automatic and controlled process estimates using the process dissociation procedure, and suggested both processes were involved. Examining the underlying processes supporting performance may provide more information on the fundamental aspects of the implicit and explicit constructs than has been attainable through awareness testing. PMID:22679465

Examining the Effectiveness of a Semi-Self-Paced Flipped Learning Format in a College General Chemistry Sequence

ERIC Educational Resources Information Center

Hibbard, Lisa; Sung, Shannon; Wells, Breche´

2016-01-01

Flipped learning has come to the forefront in education. It maximizes learning by moving content delivery online, where learning can be self-paced, allowing for class time to focus on student-centered active learning. This five-year cross-sectional study assessed student performance in a college general chemistry for majors sequence taught by a…

dictyExpress: a web-based platform for sequence data management and analytics in Dictyostelium and beyond.

PubMed

Stajdohar, Miha; Rosengarten, Rafael D; Kokosar, Janez; Jeran, Luka; Blenkus, Domen; Shaulsky, Gad; Zupan, Blaz

2017-06-02

Dictyostelium discoideum, a soil-dwelling social amoeba, is a model for the study of numerous biological processes. Research in the field has benefited mightily from the adoption of next-generation sequencing for genomics and transcriptomics. Dictyostelium biologists now face the widespread challenges of analyzing and exploring high dimensional data sets to generate hypotheses and discovering novel insights. We present dictyExpress (2.0), a web application designed for exploratory analysis of gene expression data, as well as data from related experiments such as Chromatin Immunoprecipitation sequencing (ChIP-Seq). The application features visualization modules that include time course expression profiles, clustering, gene ontology enrichment analysis, differential expression analysis and comparison of experiments. All visualizations are interactive and interconnected, such that the selection of genes in one module propagates instantly to visualizations in other modules. dictyExpress currently stores the data from over 800 Dictyostelium experiments and is embedded within a general-purpose software framework for management of next-generation sequencing data. dictyExpress allows users to explore their data in a broader context by reciprocal linking with dictyBase-a repository of Dictyostelium genomic data. In addition, we introduce a companion application called GenBoard, an intuitive graphic user interface for data management and bioinformatics analysis. dictyExpress and GenBoard enable broad adoption of next generation sequencing based inquiries by the Dictyostelium research community. Labs without the means to undertake deep sequencing projects can mine the data available to the public. The entire information flow, from raw sequence data to hypothesis testing, can be accomplished in an efficient workspace. The software framework is generalizable and represents a useful approach for any research community. To encourage more wide usage, the backend is open-source, available for extension and further development by bioinformaticians and data scientists.

The study of human Y chromosome variation through ancient DNA.

PubMed

Kivisild, Toomas

2017-05-01

High throughput sequencing methods have completely transformed the study of human Y chromosome variation by offering a genome-scale view on genetic variation retrieved from ancient human remains in context of a growing number of high coverage whole Y chromosome sequence data from living populations from across the world. The ancient Y chromosome sequences are providing us the first exciting glimpses into the past variation of male-specific compartment of the genome and the opportunity to evaluate models based on previously made inferences from patterns of genetic variation in living populations. Analyses of the ancient Y chromosome sequences are challenging not only because of issues generally related to ancient DNA work, such as DNA damage-induced mutations and low content of endogenous DNA in most human remains, but also because of specific properties of the Y chromosome, such as its highly repetitive nature and high homology with the X chromosome. Shotgun sequencing of uniquely mapping regions of the Y chromosomes to sufficiently high coverage is still challenging and costly in poorly preserved samples. To increase the coverage of specific target SNPs capture-based methods have been developed and used in recent years to generate Y chromosome sequence data from hundreds of prehistoric skeletal remains. Besides the prospects of testing directly as how much genetic change in a given time period has accompanied changes in material culture the sequencing of ancient Y chromosomes allows us also to better understand the rate at which mutations accumulate and get fixed over time. This review considers genome-scale evidence on ancient Y chromosome diversity that has recently started to accumulate in geographic areas favourable to DNA preservation. More specifically the review focuses on examples of regional continuity and change of the Y chromosome haplogroups in North Eurasia and in the New World.

Genetic variability of Echinococcus granulosus complex in various geographical populations of Iran inferred by mitochondrial DNA sequences.

PubMed

Spotin, Adel; Mahami-Oskouei, Mahmoud; Harandi, Majid Fasihi; Baratchian, Mehdi; Bordbar, Ali; Ahmadpour, Ehsan; Ebrahimi, Sahar

2017-01-01

To investigate the genetic variability and population structure of Echinococcus granulosus complex, 79 isolates were sequenced from different host species covering human, dog, camel, goat, sheep and cattle as of various geographical sub-populations of Iran (Northwestern, Northern, and Southeastern). In addition, 36 sequences of other geographical populations (Western, Southeastern and Central Iran), were directly retrieved from GenBank database for the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. The confirmed isolates were grouped as G1 genotype (n=92), G6 genotype (n=14), G3 genotype (n=8) and G2 genotype (n=1). 50 unique haplotypes were identified based on the analyzed sequences of cox1. A parsimonious network of the sequence haplotypes displayed star-like features in the overall population containing IR23 (22: 19.1%) as the most common haplotype. According to the analysis of molecular variance (AMOVA) test, the high value of haplotype diversity of E. granulosus complex was shown the total genetic variability within populations while nucleotide diversity was low in all populations. Neutrality indices of the cox1 (Tajima's D and Fu's Fs tests) were shown negative values in Western-Northwestern, Northern and Southeastern populations which indicating significant divergence from neutrality and positive but not significant in Central isolates. A pairwise fixation index (Fst) as a degree of gene flow was generally low value for all populations (0.00647-0.15198). The statistically Fst values indicate that Echinococcus sensu stricto (genotype G1-G3) populations are not genetically well differentiated in various geographical regions of Iran. To appraise the hypothetical evolutionary scenario, further study is needed to analyze concatenated mitogenomes and as well a panel of single locus nuclear markers should be considered in wider areas of Iran and neighboring countries. Copyright © 2016 Elsevier B.V. All rights reserved.

[Development of laboratory sequence analysis software based on WWW and UNIX].

PubMed

Huang, Y; Gu, J R

2001-01-01

Sequence analysis tools based on WWW and UNIX were developed in our laboratory to meet the needs of molecular genetics research in our laboratory. General principles of computer analysis of DNA and protein sequences were also briefly discussed in this paper.

47 CFR 32.21 - Sequence of accounts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Sequence of accounts. 32.21 Section 32.21 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.21 Sequence of accounts. The order in which...

47 CFR 32.21 - Sequence of accounts.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Sequence of accounts. 32.21 Section 32.21 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.21 Sequence of accounts. The order in which...

47 CFR 32.21 - Sequence of accounts.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Sequence of accounts. 32.21 Section 32.21 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.21 Sequence of accounts. The order in which...

Strong-field gravitational-wave emission in Schwarzschild and Kerr geometries: some general considerations

NASA Astrophysics Data System (ADS)

Rodríguez, J. F.; Rueda, J. A.; Ruffini, R.

2018-01-01

We have used the perturbations of the exact solutions of the Einstein equations to estimate the relativistic wave emission of a test particle orbiting around a black hole. We show how the hamiltonian equations of motion of a test particle augmented with the radiation-reaction force can establish a priori constraints on the possible phenomena occurring in the merger of compact objects. The dynamical evolution consists of a helicoidal sequence of quasi-circular orbits, induced by the radiation-reaction and the background spacetime. Near the innermost stable circular orbit the evolution is followed by a smooth transition and finally plunges geodesically into the black hole horizon. This analysis gives physical insight of the merger of two equal masses objects.

A model of the human observer and decision maker

NASA Technical Reports Server (NTRS)

Wewerinke, P. H.

1981-01-01

The decision process is described in terms of classical sequential decision theory by considering the hypothesis that an abnormal condition has occurred by means of a generalized likelihood ratio test. For this, a sufficient statistic is provided by the innovation sequence which is the result of the perception an information processing submodel of the human observer. On the basis of only two model parameters, the model predicts the decision speed/accuracy trade-off and various attentional characteristics. A preliminary test of the model for single variable failure detection tasks resulted in a very good fit of the experimental data. In a formal validation program, a variety of multivariable failure detection tasks was investigated and the predictive capability of the model was demonstrated.

Random and externally controlled occurrences of Dansgaard-Oeschger events

NASA Astrophysics Data System (ADS)

Lohmann, Johannes; Ditlevsen, Peter D.

2018-05-01

Dansgaard-Oeschger (DO) events constitute the most pronounced mode of centennial to millennial climate variability of the last glacial period. Since their discovery, many decades of research have been devoted to understand the origin and nature of these rapid climate shifts. In recent years, a number of studies have appeared that report emergence of DO-type variability in fully coupled general circulation models via different mechanisms. These mechanisms result in the occurrence of DO events at varying degrees of regularity, ranging from periodic to random. When examining the full sequence of DO events as captured in the North Greenland Ice Core Project (NGRIP) ice core record, one can observe high irregularity in the timing of individual events at any stage within the last glacial period. In addition to the prevailing irregularity, certain properties of the DO event sequence, such as the average event frequency or the relative distribution of cold versus warm periods, appear to be changing throughout the glacial. By using statistical hypothesis tests on simple event models, we investigate whether the observed event sequence may have been generated by stationary random processes or rather was strongly modulated by external factors. We find that the sequence of DO warming events is consistent with a stationary random process, whereas dividing the event sequence into warming and cooling events leads to inconsistency with two independent event processes. As we include external forcing, we find a particularly good fit to the observed DO sequence in a model where the average residence time in warm periods are controlled by global ice volume and cold periods by boreal summer insolation.

FANSe2: a robust and cost-efficient alignment tool for quantitative next-generation sequencing applications.

PubMed

Xiao, Chuan-Le; Mai, Zhi-Biao; Lian, Xin-Lei; Zhong, Jia-Yong; Jin, Jing-Jie; He, Qing-Yu; Zhang, Gong

2014-01-01

Correct and bias-free interpretation of the deep sequencing data is inevitably dependent on the complete mapping of all mappable reads to the reference sequence, especially for quantitative RNA-seq applications. Seed-based algorithms are generally slow but robust, while Burrows-Wheeler Transform (BWT) based algorithms are fast but less robust. To have both advantages, we developed an algorithm FANSe2 with iterative mapping strategy based on the statistics of real-world sequencing error distribution to substantially accelerate the mapping without compromising the accuracy. Its sensitivity and accuracy are higher than the BWT-based algorithms in the tests using both prokaryotic and eukaryotic sequencing datasets. The gene identification results of FANSe2 is experimentally validated, while the previous algorithms have false positives and false negatives. FANSe2 showed remarkably better consistency to the microarray than most other algorithms in terms of gene expression quantifications. We implemented a scalable and almost maintenance-free parallelization method that can utilize the computational power of multiple office computers, a novel feature not present in any other mainstream algorithm. With three normal office computers, we demonstrated that FANSe2 mapped an RNA-seq dataset generated from an entire Illunima HiSeq 2000 flowcell (8 lanes, 608 M reads) to masked human genome within 4.1 hours with higher sensitivity than Bowtie/Bowtie2. FANSe2 thus provides robust accuracy, full indel sensitivity, fast speed, versatile compatibility and economical computational utilization, making it a useful and practical tool for deep sequencing applications. FANSe2 is freely available at http://bioinformatics.jnu.edu.cn/software/fanse2/.

Newborn Screening in the Era of Precision Medicine.

PubMed

Yang, Lan; Chen, Jiajia; Shen, Bairong

2017-01-01

As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Besides, we can develop novel interventions directed at the molecular characteristics of genetic diseases in newborns. The implementation of genomics in NBS programs would provide an effective premise for the identification of the majority of genetic aberrations and primarily help in accurate guidance in treatment and better prediction. However, there are some debate correlated with the widespread application of genome sequencing in NBS due to some major concerns such as clinical analysis, result interpretation, storage of sequencing data, and communication of clinically relevant mutations to pediatricians and parents, along with the ethical, legal, and social implications (so-called ELSI). This review is focused on these critical issues and concerns about the expanding role of genomics in NBS for precision medicine. If WGS or WES is to be incorporated into NBS practice, considerations about these challenges should be carefully regarded and tackled properly to adapt the requirement of genome sequencing in the era of precision medicine.

A Varifold Approach to Surface Approximation

NASA Astrophysics Data System (ADS)

Buet, Blanche; Leonardi, Gian Paolo; Masnou, Simon

2017-11-01

We show that the theory of varifolds can be suitably enriched to open the way to applications in the field of discrete and computational geometry. Using appropriate regularizations of the mass and of the first variation of a varifold we introduce the notion of approximate mean curvature and show various convergence results that hold, in particular, for sequences of discrete varifolds associated with point clouds or pixel/voxel-type discretizations of d-surfaces in the Euclidean n-space, without restrictions on dimension and codimension. The variational nature of the approach also allows us to consider surfaces with singularities, and in that case the approximate mean curvature is consistent with the generalized mean curvature of the limit surface. A series of numerical tests are provided in order to illustrate the effectiveness and generality of the method.

Applications of a Sequence of Points in Teaching Linear Algebra, Numerical Methods and Discrete Mathematics

ERIC Educational Resources Information Center

Shi, Yixun

2009-01-01

Based on a sequence of points and a particular linear transformation generalized from this sequence, two recent papers (E. Mauch and Y. Shi, "Using a sequence of number pairs as an example in teaching mathematics". Math. Comput. Educ., 39 (2005), pp. 198-205; Y. Shi, "Case study projects for college mathematics courses based on a particular…

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to verify that it remains within the pre-test temperature range as specified in § 1065.520(b): (1... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2011 CFR

2011-07-01

... to verify that it remains within the pre-test temperature range as specified in § 1065.520(b): (1... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

Noninvasive Prenatal Paternity Testing (NIPAT) through Maternal Plasma DNA Sequencing: A Pilot Study.

PubMed

Jiang, Haojun; Xie, Yifan; Li, Xuchao; Ge, Huijuan; Deng, Yongqiang; Mu, Haofang; Feng, Xiaoli; Yin, Lu; Du, Zhou; Chen, Fang; He, Nongyue

2016-01-01

Short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) have been already used to perform noninvasive prenatal paternity testing from maternal plasma DNA. The frequently used technologies were PCR followed by capillary electrophoresis and SNP typing array, respectively. Here, we developed a noninvasive prenatal paternity testing (NIPAT) based on SNP typing with maternal plasma DNA sequencing. We evaluated the influence factors (minor allele frequency (MAF), the number of total SNP, fetal fraction and effective sequencing depth) and designed three different selective SNP panels in order to verify the performance in clinical cases. Combining targeted deep sequencing of selective SNP and informative bioinformatics pipeline, we calculated the combined paternity index (CPI) of 17 cases to determine paternity. Sequencing-based NIPAT results fully agreed with invasive prenatal paternity test using STR multiplex system. Our study here proved that the maternal plasma DNA sequencing-based technology is feasible and accurate in determining paternity, which may provide an alternative in forensic application in the future.

Inferring Short-Range Linkage Information from Sequencing Chromatograms

PubMed Central

Beggel, Bastian; Neumann-Fraune, Maria; Kaiser, Rolf; Verheyen, Jens; Lengauer, Thomas

2013-01-01

Direct Sanger sequencing of viral genome populations yields multiple ambiguous sequence positions. It is not straightforward to derive linkage information from sequencing chromatograms, which in turn hampers the correct interpretation of the sequence data. We present a method for determining the variants existing in a viral quasispecies in the case of two nearby ambiguous sequence positions by exploiting the effect of sequence context-dependent incorporation of dideoxynucleotides. The computational model was trained on data from sequencing chromatograms of clonal variants and was evaluated on two test sets of in vitro mixtures. The approach achieved high accuracies in identifying the mixture components of 97.4% on a test set in which the positions to be analyzed are only one base apart from each other, and of 84.5% on a test set in which the ambiguous positions are separated by three bases. In silico experiments suggest two major limitations of our approach in terms of accuracy. First, due to a basic limitation of Sanger sequencing, it is not possible to reliably detect minor variants with a relative frequency of no more than 10%. Second, the model cannot distinguish between mixtures of two or four clonal variants, if one of two sets of linear constraints is fulfilled. Furthermore, the approach requires repetitive sequencing of all variants that might be present in the mixture to be analyzed. Nevertheless, the effectiveness of our method on the two in vitro test sets shows that short-range linkage information of two ambiguous sequence positions can be inferred from Sanger sequencing chromatograms without any further assumptions on the mixture composition. Additionally, our model provides new insights into the established and widely used Sanger sequencing technology. The source code of our method is made available at http://bioinf.mpi-inf.mpg.de/publications/beggel/linkageinformation.zip. PMID:24376502

Learning multiple variable-speed sequences in striatum via cortical tutoring.

PubMed

Murray, James M; Escola, G Sean

2017-05-08

Sparse, sequential patterns of neural activity have been observed in numerous brain areas during timekeeping and motor sequence tasks. Inspired by such observations, we construct a model of the striatum, an all-inhibitory circuit where sequential activity patterns are prominent, addressing the following key challenges: (i) obtaining control over temporal rescaling of the sequence speed, with the ability to generalize to new speeds; (ii) facilitating flexible expression of distinct sequences via selective activation, concatenation, and recycling of specific subsequences; and (iii) enabling the biologically plausible learning of sequences, consistent with the decoupling of learning and execution suggested by lesion studies showing that cortical circuits are necessary for learning, but that subcortical circuits are sufficient to drive learned behaviors. The same mechanisms that we describe can also be applied to circuits with both excitatory and inhibitory populations, and hence may underlie general features of sequential neural activity pattern generation in the brain.

Social cognition dysfunction in adolescents with 22q11.2 deletion syndrome (velo-cardio-facial syndrome): relationship with executive functioning and social competence/functioning.

PubMed

Campbell, L E; McCabe, K L; Melville, J L; Strutt, P A; Schall, U

2015-09-01

Social difficulties are often noted among people with intellectual disabilities. Children and adults with 22q.11.2 deletion syndrome (22q11DS) often have poorer social competence as well as poorer performance on measures of executive and social-cognitive skills compared with typically developing young people. However, the relationship between social functioning and more basic processes of social cognition and executive functioning are not well understood in 22q11DS. The present study examined the relationship between social-cognitive measures of emotion attribution and theory of mind with executive functioning and their contribution to social competence in 22q11DS. The present cross-sectional study measured social cognition and executive performance of 24 adolescents with 22q11DS compared with 27 age-matched typically developing controls. Social cognition was tested using the emotion attribution task (EAT) and a picture sequencing task (PST), which tested mentalising (false-belief), sequencing, cause and effect, and inhibition. Executive functioning was assessed using computerised versions of the Tower of London task and working memory measures of spatial and non-spatial ability. Social competence was also assessed using the parent-reported Strengths and Difficulties Questionnaire. Adolescents with 22q11DS showed impaired false-belief, emotion attribution and executive functioning compared with typically developing control participants. Poorer performance was reported on all story types in the PST, although, patterns of errors and response times across story types were similar in both groups. General sequencing ability was the strongest predictor of false-belief, and performance on the false-belief task predicted emotion attribution accuracy. Intellectual functioning, rather than theory of mind or executive functioning, predicted social competence in 22q11DS. Performance on social-cognitive tasks of theory of mind indicate evidence of a general underlying dysfunction in 22q11DS that includes executive ability to understand cause and effect, to logically reason about social scenarios and also to inhibit responses to salient, but misleading cues. However, general intellectual ability is closely related to actual social competence suggesting that a generalised intellectual deficit coupled with more specific executive impairments may best explain poor social cognition in 22q11DS. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Testing genotyping strategies for ultra-deep sequencing of a co-amplifying gene family: MHC class I in a passerine bird.

PubMed

Biedrzycka, Aleksandra; Sebastian, Alvaro; Migalska, Magdalena; Westerdahl, Helena; Radwan, Jacek

2017-07-01

Characterization of highly duplicated genes, such as genes of the major histocompatibility complex (MHC), where multiple loci often co-amplify, has until recently been hindered by insufficient read depths per amplicon. Here, we used ultra-deep Illumina sequencing to resolve genotypes at exon 3 of MHC class I genes in the sedge warbler (Acrocephalus schoenobaenus). We sequenced 24 individuals in two replicates and used this data, as well as a simulated data set, to test the effect of amplicon coverage (range: 500-20 000 reads per amplicon) on the repeatability of genotyping using four different genotyping approaches. A third replicate employed unique barcoding to assess the extent of tag jumping, that is swapping of individual tag identifiers, which may confound genotyping. The reliability of MHC genotyping increased with coverage and approached or exceeded 90% within-method repeatability of allele calling at coverages of >5000 reads per amplicon. We found generally high agreement between genotyping methods, especially at high coverages. High reliability of the tested genotyping approaches was further supported by our analysis of the simulated data set, although the genotyping approach relying primarily on replication of variants in independent amplicons proved sensitive to repeatable errors. According to the most repeatable genotyping method, the number of co-amplifying variants per individual ranged from 19 to 42. Tag jumping was detectable, but at such low frequencies that it did not affect the reliability of genotyping. We thus demonstrate that gene families with many co-amplifying genes can be reliably genotyped using HTS, provided that there is sufficient per amplicon coverage. © 2016 John Wiley & Sons Ltd.

Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/D3 antagonist sulpiride.

PubMed

Santangelo, Andrea; Provensi, Gustavo; Costa, Alessia; Blandina, Patrizio; Ricca, Valdo; Crescimanno, Giuseppe; Casarrubea, Maurizio; Passani, M Beatrice

2017-02-01

Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found 42 patterns of different composition occurring, on average, 520.90 ± 50.23 times per mouse in the histamine depleted (HD) group, whereas controls showed 12 different patterns occurring on average 223.30 ± 20.64 times. Exploratory and grooming behaviours clustered separately, and the increased pattern complexity involved exclusively exploratory patterns. To test the hypothesis of a histamine-dopamine interplay on behavioural pattern phenotype, non-sedative doses of the D2/D3 antagonist sulpiride (12.5-25-50 mg/kg) were additionally administered to different groups of HD mice. Sulpiride counterbalanced the enhancement of exploratory patterns of different composition, but it did not affect the mean number of patterns at none of the doses used. Our results provide new insights on the role of histamine on repetitive behavioural sequences of freely moving mice. Histamine deficiency is correlated with a general enhancement of pattern complexity. This study supports a putative involvement of histamine in the pathophysiology of tics and related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of new spectral bands for multi-spectral imaging: SMIRR aircraft test results

USGS Publications Warehouse

Goetz, Alexander F.H.; Rowan, Lawrence C.; Barringer, Anthony R.

1980-01-01

A 10-channel radiometer called the Shuttle Multispectral Infrared Radiometer (SMIRR) is scheduled to take data from orbit on the second shuttle orbital light test. As part of the instrument test sequence, a series of aircraft flights was carried out over 10 test areas in Utah and Nevada. Apart from vegetation, the materials exposed at the surface were volcanic sequences ranging from tuffs to basalts, areas of hydrothermally altered volcanic rocks, sedimentary sequences of sandstone and carbonate rocks, and alluvial cover.

The genetics of Charcot–Marie–Tooth disease: current trends and future implications for diagnosis and management

PubMed Central

Hoyle, J Chad; Isfort, Michael C; Roggenbuck, Jennifer; Arnold, W David

2015-01-01

Charcot–Marie–Tooth (CMT) disease is the most common hereditary polyneuropathy and is classically associated with an insidious onset of distal predominant motor and sensory loss, muscle wasting, and pes cavus. Other forms of hereditary neuropathy, including sensory predominant or motor predominant forms, are sometimes included in the general classification of CMT, but for the purpose of this review, we will focus primarily on the forms associated with both sensory and motor deficits. CMT has a great deal of genetic heterogeneity, leading to diagnostic considerations that are still rapidly evolving for this disorder. Clinical features, inheritance pattern, gene mutation frequencies, and electrodiagnostic features all are helpful in formulating targeted testing algorithms in practical clinical settings, but these still have shortcomings. Next-generation sequencing (NGS), combined with multigene testing panels, is increasing the sensitivity and efficiency of genetic testing and is quickly overtaking targeted testing strategies. Currently, multigene panel testing and NGS can be considered first-line in many circumstances, although obtaining initial targeted testing for the PMP22 duplication in CMT patients with demyelinating conduction velocities is still a reasonable strategy. As technology improves and cost continues to fall, targeted testing will be completely replaced by multigene NGS panels that can detect the full spectrum of CMT mutations. Nevertheless, clinical acumen is still necessary given the variants of uncertain significance encountered with NGS. Despite the current limitations, the genetic diagnosis of CMT is critical for accurate prognostication, genetic counseling, and in the future, specific targeted therapies. Although whole exome and whole genome sequencing strategies have the power to further elucidate the genetics of CMT, continued technological advances are needed. PMID:26527893

Biodegradation of hydrocarbon mixtures in surface waters at environmentally relevant levels - Effect of inoculum origin on kinetics and sequence of degradation.

PubMed

Birch, Heidi; Hammershøj, Rikke; Comber, Mike; Mayer, Philipp

2017-10-01

Biodegradation is a dominant removal process for many organic pollutants, and biodegradation tests serve as tools for assessing their environmental fate within regulatory risk assessment. In simulation tests, the inoculum is not standardized, varying in microbial quantity and quality, thereby potentially impacting the observed biodegradation kinetics. In this study we investigated the effect of inoculum origin on the biodegradation kinetics of hydrocarbons for five inocula from surface waters varying in urbanization and thus expected pre-exposure to petroleum hydrocarbons. A new biodegradation method for testing mixtures of hydrophobic chemicals at trace concentrations was demonstrated: Aqueous solutions containing 9 hydrocarbons were generated by passive dosing and diluted with surface water resulting in test systems containing native microorganisms exposed to test substances at ng-μg/L levels. Automated Headspace Solid Phase Microextraction coupled to GC-MS was applied directly to these test systems to determine substrate depletion relative to abiotic controls. Lag phases were generally less than 8 days. First order rate constants were within one order of magnitude for each hydrocarbon in four of the five waters but lower in water from a rural lake. The sequence of degradation between the 9 hydrocarbons showed similar patterns in the five waters indicating the potential for using selected hydrocarbons for benchmarking between biodegradation tests. Degradation half-times were shorter than or within one order of magnitude of BioHCwin predictions for 8 of 9 hydrocarbons. These results showed that location choice is important for biodegradation kinetics and can provide a relevant input to aquatic exposure and fate models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Update on HER2 testing for breast and upper gastrointestinal tract cancers.

PubMed

Ross, Jeffrey S

2011-06-01

With the regulatory approvals in Europe and the USA of trastuzumab-based anti-HER2 targeted therapy for upper gastrointestinal cancers in 2010, HER2 testing has now become universal for newly diagnosed cases of both breast cancer and adenocarcinomas of esophagus, stomach and gastroesophageal origin. In the 12 years or more since the approval of trastuzumab for breast cancer, general refinements in approaches to HER2 testing, including a greater understanding of the implications of preanalytic factors impacting the test results and the application of standardization of reporting of HER2 test results, have taken place. There has also been continuing development in breast cancer with the introduction of new HER2 tests, including non-FISH tests, dimerization assays, phosphorylated HER2 receptor tests, mRNA-based tests, HER2 gene sequencing tests and the application of HER2 testing to circulating tumor cells. Most recently, the introduction of HER2 testing for upper gastrointentinal malignancies has emphasized the need for performing and interpreting slide-based assays in a manner unique to these specimens and not to apply the breast cancer testing protocols to esophageal and gastric adenocarcinomas.

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

PubMed

Punetha, Jaya; Kesari, Akanchha; Uapinyoying, Prech; Giri, Mamta; Clarke, Nigel F; Waddell, Leigh B; North, Kathryn N; Ghaoui, Roula; O'Grady, Gina L; Oates, Emily C; Sandaradura, Sarah A; Bönnemann, Carsten G; Donkervoort, Sandra; Plotz, Paul H; Smith, Edward C; Tesi-Rocha, Carolina; Bertorini, Tulio E; Tarnopolsky, Mark A; Reitter, Bernd; Hausmanowa-Petrusewicz, Irena; Hoffman, Eric P

2016-05-27

Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies. To evaluate efficiency of next-generation sequencing technologies to provide molecular diagnostics for patients with previously undiagnosed myopathies. We tested a targeted re-sequencing approach, using a 45 gene emulsion PCR myopathy panel, with subsequent sequencing on the Illumina platform in 94 undiagnosed patients. We compared the targeted re-sequencing approach to exome sequencing for 10 of these patients studied. We detected likely pathogenic mutations in 33 out of 94 patients with a molecular diagnostic rate of approximately 35%. The remaining patients showed variants of unknown significance (35/94 patients) or no mutations detected in the 45 genes tested (26/94 patients). Mutation detection rates for targeted re-sequencing vs. whole exome were similar in both methods; however exome sequencing showed better distribution of reads and fewer exon dropouts. Given that costs of highly parallel re-sequencing and whole exome sequencing are similar, and that exome sequencing now takes considerably less laboratory processing time than targeted re-sequencing, we recommend exome sequencing as the standard approach for molecular diagnostics of myopathies.

Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.

PubMed

Shi, Lei; Lin, Qiang; Su, Bing

2015-06-30

Sexual dimorphism in brain size is common among primates, including humans, apes and some Old World monkeys. In these species, the brain size of males is generally larger than that of females. Curiously, this dimorphism has persisted over the course of primate evolution and human origin, but there is no explanation for the underlying genetic controls that have maintained this disparity in brain size. In the present study, we tested the effect of the female hormone (estradiol) on seven genes known to be related to brain size in both humans and nonhuman primates, and we identified half estrogen responsive elements (half EREs) in the promoter regions of four genes (MCPH1, ASPM, CDK5RAP2 and WDR62). Likewise, at sequence level, it appears that these half EREs are generally conserved across primates. Later testing via a reporter gene assay and cell-based endogenous expression measurement revealed that estradiol could significantly suppress the expression of the four affected genes involved in brain size. More intriguingly, when the half EREs were deleted from the promoters, the suppression effect disappeared, suggesting that the half EREs mediate the regulation of estradiol on the brain size genes. We next replicated these experiments using promoter sequences from chimpanzees and rhesus macaques, and observed a similar suppressive effect of estradiol on gene expression, suggesting that this mechanism is conserved among primate species that exhibit brain size dimorphism. Brain size dimorphism among certain primates, including humans, is likely regulated by estrogen through its sex-dependent suppression of brain size genes during development.

A comparative study of working memory: immediate serial spatial recall in baboons (Papio papio) and humans.

PubMed

Fagot, Joël; De Lillo, Carlo

2011-12-01

Two experiments assessed if non-human primates can be meaningfully compared to humans in a non-verbal test of serial recall. A procedure was used that was derived from variations of the Corsi test, designed to test the effects of sequence structure and movement path length in humans. Two baboons were tested in Experiment 1. The monkeys showed several attributes of human serial recall. These included an easier recall of sequences with a shorter number of items and of sequences characterized by a shorter path length when the number of items was kept constant. However, the accuracy and speed of processing did not indicate that the monkeys were able to benefit from the spatiotemporal structure of sequences. Humans tested in Experiment 2 showed a quantitatively longer memory span, and, in contrast with monkeys, benefitted from sequence structure. The results are discussed in relation to differences in how human and non-human primates segment complex visual patterns. Copyright © 2011 Elsevier Ltd. All rights reserved.

40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

Code of Federal Regulations, 2012 CFR

2012-07-01

... concentration of CO plus CO2 falls below 6 percent or the vehicle's engine stalls at any time during the test... the overall maximum test time. (b) Test sequence. (1) The test sequence consists of a first-chance... indicator or road-load controller. (ii) The vehicle is tested in as-received condition with all accessories...

40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

Code of Federal Regulations, 2013 CFR

2013-07-01

... concentration of CO plus CO2 falls below 6 percent or the vehicle's engine stalls at any time during the test... the overall maximum test time. (b) Test sequence. (1) The test sequence consists of a first-chance... indicator or road-load controller. (ii) The vehicle is tested in as-received condition with all accessories...

Codon-Anticodon Recognition in the Bacillus subtilis glyQS T Box Riboswitch

PubMed Central

Caserta, Enrico; Liu, Liang-Chun; Grundy, Frank J.; Henkin, Tina M.

2015-01-01

Many amino acid-related genes in Gram-positive bacteria are regulated by the T box riboswitch. The leader RNA of genes in the T box family controls the expression of downstream genes by monitoring the aminoacylation status of the cognate tRNA. Previous studies identified a three-nucleotide codon, termed the “Specifier Sequence,” in the riboswitch that corresponds to the amino acid identity of the downstream genes. Pairing of the Specifier Sequence with the anticodon of the cognate tRNA is the primary determinant of specific tRNA recognition. This interaction mimics codon-anticodon pairing in translation but occurs in the absence of the ribosome. The goal of the current study was to determine the effect of a full range of mismatches for comparison with codon recognition in translation. Mutations were individually introduced into the Specifier Sequence of the glyQS leader RNA and tRNAGly anticodon to test the effect of all possible pairing combinations on tRNA binding affinity and antitermination efficiency. The functional role of the conserved purine 3′ of the Specifier Sequence was also verifiedin this study. We found that substitutions at the Specifier Sequence resulted in reduced binding, the magnitude of which correlates well with the predicted stability of the RNA-RNA pairing. However, the tolerance for specific mismatches in antitermination was generally different from that during decoding, which reveals a unique tRNA recognition pattern in the T box antitermination system. PMID:26229106

N-terminal segments modulate the α-helical propensities of the intrinsically disordered basic regions of bZIP proteins.

PubMed

Das, Rahul K; Crick, Scott L; Pappu, Rohit V

2012-02-17

Basic region leucine zippers (bZIPs) are modular transcription factors that play key roles in eukaryotic gene regulation. The basic regions of bZIPs (bZIP-bRs) are necessary and sufficient for DNA binding and specificity. Bioinformatic predictions and spectroscopic studies suggest that unbound monomeric bZIP-bRs are uniformly disordered as isolated domains. Here, we test this assumption through a comparative characterization of conformational ensembles for 15 different bZIP-bRs using a combination of atomistic simulations and circular dichroism measurements. We find that bZIP-bRs have quantifiable preferences for α-helical conformations in their unbound monomeric forms. This helicity varies from one bZIP-bR to another despite a significant sequence similarity of the DNA binding motifs (DBMs). Our analysis reveals that intramolecular interactions between DBMs and eight-residue segments directly N-terminal to DBMs are the primary modulators of bZIP-bR helicities. We test the accuracy of this inference by designing chimeras of bZIP-bRs to have either increased or decreased overall helicities. Our results yield quantitative insights regarding the relationship between sequence and the degree of intrinsic disorder within bZIP-bRs, and might have general implications for other intrinsically disordered proteins. Understanding how natural sequence variations lead to modulation of disorder is likely to be important for understanding the evolution of specificity in molecular recognition through intrinsically disordered regions (IDRs). Copyright © 2011 Elsevier Ltd. All rights reserved.

Discovering [superscript 13]C NMR, [superscript 1]H NMR, and IR Spectroscopy in the General Chemistry Laboratory through a Sequence of Guided-Inquiry Exercises

ERIC Educational Resources Information Center

Iler, H. Darrell; Justice, David; Brauer, Shari; Landis, Amanda

2012-01-01

This sequence of three guided-inquiry labs is designed for a second-semester general chemistry course and challenges students to discover basic theoretical principles associated with [superscript 13]C NMR, [superscript 1]H NMR, and IR spectroscopy. Students learn to identify and explain basic concepts of magnetic resonance and vibrational…

Stresses and deformations in angle-ply composite tubes

NASA Technical Reports Server (NTRS)

Rousseau, Carl Q.; Hyer, Michael W.; Tompkins, Stephen S.

1987-01-01

The stress and deformations in angle-ply composite tubes subjected to axisymmetric thermal loading were investigated both experimentally and analytically. For the theoretical portion a generalized plane strain elasticity analysis was developed. The analysis included mechanical and thermal loading, and temperature-dependent material properties. The elasticity analysis was also used to study the effect of including a thin metallic coating on a graphite-epoxy tube. The stresses in the coatings were found to be quite high, exceeding the yield stress of aluminum. An important finding in the analytical studies was the fact that even tubes with a balanced-symmetric lamination sequence exhibit shear deformation, or twist. For the experimental portion an apparatus was developed to measure torsional and axial response in the temperature range of 140 to 360 K. Eighteen specimens were tested, combining three material systems, eight lamination sequences, and three off-axis ply orientation angles. For the twist response, agreement between analysis and experiment was found to be good. The axial response of the tubes tested was found to be greater than predicted by a factor of three. As a result, it is recommended that the thermally induced axial deformations be investigated, both experimentally and analytically.

A test for correction made to spin systematics for coupled band in doubly-odd nuclei

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

Kumar, Vinod, E-mail: vinod2.k2@gmail.com

2015-12-15

Systematic Spin Assignments were generally made by using the argument that the energy of levels is a function of neutron number. In the present systematics, the excitation energy of the levels incorporated the effect of nuclear deformation and signature splitting. The nuclear deformation changes toward the mid-shell, therefore a smooth variation in the excitation energy of the levels is observed towards the mid-shell, that intended to make systematics as a function of neutron number towards the mid-shell. Another term “signature splitting” that push the energy of levels for odd- and even-spin sequences up and down, caused the different energy variationmore » pattern for odd- and even-spin sequences. The corrections made in the spin systematics were tested for the known spins of various isotopic chain. In addition, the inconsistency in spin assignments made by the spin systematics and other methods of the configuration πh{sub 11/2} ⊗ νh{sub 11/2} band belonging to {sup 112,114,116}Cs, {sup 126}Pr, and {sup 138}Pr, as an example, was resolved by the correctionmade in the present spin systematics.« less

Normal sensory and range of motion (ROM) responses during Thoracic Slump Test (ST) in asymptomatic subjects.

PubMed

Joshi, Ketaki C; Eapen, Charu; Kumar, Senthil P

2013-02-01

The purpose of the study was to determine the normal sensory and range of motion (ROM) responses during the movement components of Thoracic Slump Test (Thoracic ST) in asymptomatic subjects. Sixty asymptomatic subjects were included in the study. Thoracic ST was performed in two sequences, proximal initiation, which was proximal to distal and distal initiation, which was distal to proximal. Subjects were randomized into four groups depending on the order of sequences and sides. Outcome measures of sensory responses (intensity, type, and location) and ROM responses were recorded after each sequence. Friedman's test was done to compare between sensory responses of the subjects. Between-component comparison for prevalence of sensory responses within each sequence was done using Kruskal-Wallis test and Wilcoxonsigned ranks test was used for between-component comparisons of intensity of symptoms within each sequence of testing. Independent t test was used to assess the ROM responses. Results show the prevalence of sensory responses, its nature, area and intensity. These sensory and ROM responses may be considered as normal response of Thoracic ST. The intensity of the symptoms of proximal initiation sequence (1.09±1.35 cm) was significant (P<0.05) when compared to distal initiation sequence (0.08±1.26 cm). The change in the ROM was significant (P<0.05) for distal initiation (7.55±4.51 degrees) when compared to proximal initiation (4.96±3.76 degrees). These normal responses may be used as a reference when using the Thoracic ST as an assessment technique.

Normal sensory and range of motion (ROM) responses during Thoracic Slump Test (ST) in asymptomatic subjects

PubMed Central

Joshi, Ketaki C; Eapen, Charu; Kumar, Senthil P

2013-01-01

The purpose of the study was to determine the normal sensory and range of motion (ROM) responses during the movement components of Thoracic Slump Test (Thoracic ST) in asymptomatic subjects. Sixty asymptomatic subjects were included in the study. Thoracic ST was performed in two sequences, proximal initiation, which was proximal to distal and distal initiation, which was distal to proximal. Subjects were randomized into four groups depending on the order of sequences and sides. Outcome measures of sensory responses (intensity, type, and location) and ROM responses were recorded after each sequence. Friedman’s test was done to compare between sensory responses of the subjects. Between-component comparison for prevalence of sensory responses within each sequence was done using Kruskal–Wallis test and Wilcoxonsigned ranks test was used for between-component comparisons of intensity of symptoms within each sequence of testing. Independent t test was used to assess the ROM responses. Results show the prevalence of sensory responses, its nature, area and intensity. These sensory and ROM responses may be considered as normal response of Thoracic ST. The intensity of the symptoms of proximal initiation sequence (1.09±1.35 cm) was significant (P<0.05) when compared to distal initiation sequence (0.08±1.26 cm). The change in the ROM was significant (P<0.05) for distal initiation (7.55±4.51 degrees) when compared to proximal initiation (4.96±3.76 degrees). These normal responses may be used as a reference when using the Thoracic ST as an assessment technique. PMID:24421610

Segmentation and Recognition of Continuous Human Activity

DTIC Science & Technology

2001-01-01

This paper presents a methodology for automatic segmentation and recognition of continuous human activity . We segment a continuous human activity into...commencement or termination. We use single action sequences for the training data set. The test sequences, on the other hand, are continuous sequences of human ... activity that consist of three or more actions in succession. The system has been tested on continuous activity sequences containing actions such as

Health Occupations: Scope and Sequence.

ERIC Educational Resources Information Center

Nashville - Davidson County Metropolitan Public Schools, TN.

This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 3-year program in health occupations. The guide consists of a course description; general course…

VOE Computer Programming: Scope and Sequence.

ERIC Educational Resources Information Center

Nashville - Davidson County Metropolitan Public Schools, TN.

This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 3-year program in computer programming. The guide consists of a course description; general course…

A Sequence for Sentence-Combining Instruction.

ERIC Educational Resources Information Center

Lawlor, Joseph

Although sentence combining practice has been shown to be an effective instructional technique for improving students' writing, scant attention has been paid to the appropriate sequence for such instruction. Studies of the natural development of oral and written language point out two general trends that should be considered in sequencing sentence…

Scalable Kernel Methods and Algorithms for General Sequence Analysis

ERIC Educational Resources Information Center

Kuksa, Pavel

2011-01-01

Analysis of large-scale sequential data has become an important task in machine learning and pattern recognition, inspired in part by numerous scientific and technological applications such as the document and text classification or the analysis of biological sequences. However, current computational methods for sequence comparison still lack…

Dynamic assessment of microbial ecology (DAME): A shiny app for analysis and visualization of microbial sequencing data

USDA-ARS?s Scientific Manuscript database

A new renaissance in knowledge about the role of commensal microbiota in health and disease is well underway facilitated by culture-independent sequencing technologies; however, microbial sequencing data poses new challenges (e.g., taxonomic hierarchy, overdispersion) not generally seen in more trad...

Urban Horticulture: Scope and Sequence.

ERIC Educational Resources Information Center

Nashville - Davidson County Metropolitan Public Schools, TN.

This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 4-year program in urban horticulture. The guide consists of a course description; general course…

VOE Accounting: Scope and Sequence.

ERIC Educational Resources Information Center

Nashville - Davidson County Metropolitan Public Schools, TN.

This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 2-year program in accounting. The guide consists of a course description; general course objectives;…

Agriculture: Scope and Sequence.

ERIC Educational Resources Information Center

Nashville - Davidson County Metropolitan Public Schools, TN.

This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 3-year program in agriculture. The guide consists of a course description; general course objectives;…

Test Input Generation for Red-Black Trees using Abstraction

NASA Technical Reports Server (NTRS)

Visser, Willem; Pasareanu, Corina S.; Pelanek, Radek

2005-01-01

We consider the problem of test input generation for code that manipulates complex data structures. Test inputs are sequences of method calls from the data structure interface. We describe test input generation techniques that rely on state matching to avoid generation of redundant tests. Exhaustive techniques use explicit state model checking to explore all the possible test sequences up to predefined input sizes. Lossy techniques rely on abstraction mappings to compute and store abstract versions of the concrete states; they explore under-approximations of all the possible test sequences. We have implemented the techniques on top of the Java PathFinder model checker and we evaluate them using a Java implementation of red-black trees.

Sequence modelling and an extensible data model for genomic database

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

Li, Peter Wei-Der

1992-01-01

The Human Genome Project (HGP) plans to sequence the human genome by the beginning of the next century. It will generate DNA sequences of more than 10 billion bases and complex marker sequences (maps) of more than 100 million markers. All of these information will be stored in database management systems (DBMSs). However, existing data models do not have the abstraction mechanism for modelling sequences and existing DBMS's do not have operations for complex sequences. This work addresses the problem of sequence modelling in the context of the HGP and the more general problem of an extensible object data modelmore » that can incorporate the sequence model as well as existing and future data constructs and operators. First, we proposed a general sequence model that is application and implementation independent. This model is used to capture the sequence information found in the HGP at the conceptual level. In addition, abstract and biological sequence operators are defined for manipulating the modelled sequences. Second, we combined many features of semantic and object oriented data models into an extensible framework, which we called the Extensible Object Model'', to address the need of a modelling framework for incorporating the sequence data model with other types of data constructs and operators. This framework is based on the conceptual separation between constructors and constraints. We then used this modelling framework to integrate the constructs for the conceptual sequence model. The Extensible Object Model is also defined with a graphical representation, which is useful as a tool for database designers. Finally, we defined a query language to support this model and implement the query processor to demonstrate the feasibility of the extensible framework and the usefulness of the conceptual sequence model.« less

Sequence modelling and an extensible data model for genomic database

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

Li, Peter Wei-Der

1992-01-01

The Human Genome Project (HGP) plans to sequence the human genome by the beginning of the next century. It will generate DNA sequences of more than 10 billion bases and complex marker sequences (maps) of more than 100 million markers. All of these information will be stored in database management systems (DBMSs). However, existing data models do not have the abstraction mechanism for modelling sequences and existing DBMS`s do not have operations for complex sequences. This work addresses the problem of sequence modelling in the context of the HGP and the more general problem of an extensible object data modelmore » that can incorporate the sequence model as well as existing and future data constructs and operators. First, we proposed a general sequence model that is application and implementation independent. This model is used to capture the sequence information found in the HGP at the conceptual level. In addition, abstract and biological sequence operators are defined for manipulating the modelled sequences. Second, we combined many features of semantic and object oriented data models into an extensible framework, which we called the ``Extensible Object Model``, to address the need of a modelling framework for incorporating the sequence data model with other types of data constructs and operators. This framework is based on the conceptual separation between constructors and constraints. We then used this modelling framework to integrate the constructs for the conceptual sequence model. The Extensible Object Model is also defined with a graphical representation, which is useful as a tool for database designers. Finally, we defined a query language to support this model and implement the query processor to demonstrate the feasibility of the extensible framework and the usefulness of the conceptual sequence model.« less

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks.

PubMed

Zhang, Haitao; Wu, Chenxue; Chen, Zewei; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive rules variation ratios with the traditional spatial-temporal k-anonymity method. Furthermore, we also found the performance variation tendency from the parameter K value, which can help achieve the goal of hiding the maximum number of original sensitive rules while generating a minimum of new sensitive rules and affecting a minimum number of non-sensitive rules.

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks

PubMed Central

Wu, Chenxue; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive rules variation ratios with the traditional spatial-temporal k-anonymity method. Furthermore, we also found the performance variation tendency from the parameter K value, which can help achieve the goal of hiding the maximum number of original sensitive rules while generating a minimum of new sensitive rules and affecting a minimum number of non-sensitive rules. PMID:28767687

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

Witte, Jonathon; Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720; Neaton, Jeffrey B.

With the aim of systematically characterizing the convergence of common families of basis sets such that general recommendations for basis sets can be made, we have tested a wide variety of basis sets against complete-basis binding energies across the S22 set of intermolecular interactions—noncovalent interactions of small and medium-sized molecules consisting of first- and second-row atoms—with three distinct density functional approximations: SPW92, a form of local-density approximation; B3LYP, a global hybrid generalized gradient approximation; and B97M-V, a meta-generalized gradient approximation with nonlocal correlation. We have found that it is remarkably difficult to reach the basis set limit; for the methodsmore » and systems examined, the most complete basis is Jensen’s pc-4. The Dunning correlation-consistent sequence of basis sets converges slowly relative to the Jensen sequence. The Karlsruhe basis sets are quite cost effective, particularly when a correction for basis set superposition error is applied: counterpoise-corrected def2-SVPD binding energies are better than corresponding energies computed in comparably sized Dunning and Jensen bases, and on par with uncorrected results in basis sets 3-4 times larger. These trends are exhibited regardless of the level of density functional approximation employed. A sense of the magnitude of the intrinsic incompleteness error of each basis set not only provides a foundation for guiding basis set choice in future studies but also facilitates quantitative comparison of existing studies on similar types of systems.« less

Human Chromosome Y and Haplogroups; introducing YDHS Database.

PubMed

Tiirikka, Timo; Moilanen, Jukka S

2015-12-01

As the high throughput sequencing efforts generate more biological information, scientists from different disciplines are interpreting the polymorphisms that make us unique. In addition, there is an increasing trend in general public to research their own genealogy, find distant relatives and to know more about their biological background. Commercial vendors are providing analyses of mitochondrial and Y-chromosomal markers for such purposes. Clearly, an easy-to-use free interface to the existing data on the identified variants would be in the interest of general public and professionals less familiar with the field. Here we introduce a novel metadatabase YDHS that aims to provide such an interface for Y-chromosomal DNA (Y-DNA) haplogroups and sequence variants. The database uses ISOGG Y-DNA tree as the source of mutations and haplogroups and by using genomic positions of the mutations the database links them to genes and other biological entities. YDHS contains analysis tools for deeper Y-SNP analysis. YDHS addresses the shortage of Y-DNA related databases. We have tested our database using a set of different cases from literature ranging from infertility to autism. The database is at http://www.semanticgen.net/ydhs Y-chromosomal DNA (Y-DNA) haplogroups and sequence variants have not been in the scientific limelight, excluding certain specialized fields like forensics, mainly because there is not much freely available information or it is scattered in different sources. However, as we have demonstrated Y-SNPs do play a role in various cases on the haplogroup level and it is possible to create a free Y-DNA dedicated bioinformatics resource.

Software for pre-processing Illumina next-generation sequencing short read sequences

PubMed Central

2014-01-01

Background When compared to Sanger sequencing technology, next-generation sequencing (NGS) technologies are hindered by shorter sequence read length, higher base-call error rate, non-uniform coverage, and platform-specific sequencing artifacts. These characteristics lower the quality of their downstream analyses, e.g. de novo and reference-based assembly, by introducing sequencing artifacts and errors that may contribute to incorrect interpretation of data. Although many tools have been developed for quality control and pre-processing of NGS data, none of them provide flexible and comprehensive trimming options in conjunction with parallel processing to expedite pre-processing of large NGS datasets. Methods We developed ngsShoRT (next-generation sequencing Short Reads Trimmer), a flexible and comprehensive open-source software package written in Perl that provides a set of algorithms commonly used for pre-processing NGS short read sequences. We compared the features and performance of ngsShoRT with existing tools: CutAdapt, NGS QC Toolkit and Trimmomatic. We also compared the effects of using pre-processed short read sequences generated by different algorithms on de novo and reference-based assembly for three different genomes: Caenorhabditis elegans, Saccharomyces cerevisiae S288c, and Escherichia coli O157 H7. Results Several combinations of ngsShoRT algorithms were tested on publicly available Illumina GA II, HiSeq 2000, and MiSeq eukaryotic and bacteria genomic short read sequences with the focus on removing sequencing artifacts and low-quality reads and/or bases. Our results show that across three organisms and three sequencing platforms, trimming improved the mean quality scores of trimmed sequences. Using trimmed sequences for de novo and reference-based assembly improved assembly quality as well as assembler performance. In general, ngsShoRT outperformed comparable trimming tools in terms of trimming speed and improvement of de novo and reference-based assembly as measured by assembly contiguity and correctness. Conclusions Trimming of short read sequences can improve the quality of de novo and reference-based assembly and assembler performance. The parallel processing capability of ngsShoRT reduces trimming time and improves the memory efficiency when dealing with large datasets. We recommend combining sequencing artifacts removal, and quality score based read filtering and base trimming as the most consistent method for improving sequence quality and downstream assemblies. ngsShoRT source code, user guide and tutorial are available at http://research.bioinformatics.udel.edu/genomics/ngsShoRT/. ngsShoRT can be incorporated as a pre-processing step in genome and transcriptome assembly projects. PMID:24955109

The detection error of thermal test low-frequency cable based on M sequence correlation algorithm

NASA Astrophysics Data System (ADS)

Wu, Dongliang; Ge, Zheyang; Tong, Xin; Du, Chunlin

2018-04-01

The problem of low accuracy and low efficiency of off-line detecting on thermal test low-frequency cable faults could be solved by designing a cable fault detection system, based on FPGA export M sequence code(Linear feedback shift register sequence) as pulse signal source. The design principle of SSTDR (Spread spectrum time-domain reflectometry) reflection method and hardware on-line monitoring setup figure is discussed in this paper. Testing data show that, this detection error increases with fault location of thermal test low-frequency cable.

Abstracting Sequences: Reasoning That Is a Key to Academic Achievement.

PubMed

Pasnak, Robert; Kidd, Julie K; Gadzichowski, K Marinka; Gallington, Debbie A; Schmerold, Katrina Lea; West, Heather

2015-01-01

The ability to understand sequences of items may be an important cognitive ability. To test this proposition, 8 first-grade children from each of 36 classes were randomly assigned to four conditions. Some were taught sequences that represented increasing or decreasing values, or were symmetrical, or were rotations of an object through 6 or 8 positions. Control children received equal numbers of sessions on mathematics, reading, or social studies. Instruction was conducted three times weekly in 15-min sessions for seven months. In May, the children taught sequences applied their understanding to novel sequences, and scored as well or better on three standardized reading tests as the control children. They outscored all children on tests of mathematics concepts, and scored better than control children on some mathematics scales. These findings indicate that developing an understanding of sequences is a form of abstraction, probably involving fluid reasoning, that provides a foundation for academic achievement in early education.

An Experimental Analysis of Memory Processing

PubMed Central

Wright, Anthony A

2007-01-01

Rhesus monkeys were trained and tested in visual and auditory list-memory tasks with sequences of four travel pictures or four natural/environmental sounds followed by single test items. Acquisitions of the visual list-memory task are presented. Visual recency (last item) memory diminished with retention delay, and primacy (first item) memory strengthened. Capuchin monkeys, pigeons, and humans showed similar visual-memory changes. Rhesus learned an auditory memory task and showed octave generalization for some lists of notes—tonal, but not atonal, musical passages. In contrast with visual list memory, auditory primacy memory diminished with delay and auditory recency memory strengthened. Manipulations of interitem intervals, list length, and item presentation frequency revealed proactive and retroactive inhibition among items of individual auditory lists. Repeating visual items from prior lists produced interference (on nonmatching tests) revealing how far back memory extended. The possibility of using the interference function to separate familiarity vs. recollective memory processing is discussed. PMID:18047230

Meta-analysis of quantitative pleiotropic traits for next-generation sequencing with multivariate functional linear models

PubMed Central

Chiu, Chi-yang; Jung, Jeesun; Chen, Wei; Weeks, Daniel E; Ren, Haobo; Boehnke, Michael; Amos, Christopher I; Liu, Aiyi; Mills, James L; Ting Lee, Mei-ling; Xiong, Momiao; Fan, Ruzong

2017-01-01

To analyze next-generation sequencing data, multivariate functional linear models are developed for a meta-analysis of multiple studies to connect genetic variant data to multiple quantitative traits adjusting for covariates. The goal is to take the advantage of both meta-analysis and pleiotropic analysis in order to improve power and to carry out a unified association analysis of multiple studies and multiple traits of complex disorders. Three types of approximate F -distributions based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants. Simulation analysis is performed to evaluate false-positive rates and power of the proposed tests. The proposed methods are applied to analyze lipid traits in eight European cohorts. It is shown that it is more advantageous to perform multivariate analysis than univariate analysis in general, and it is more advantageous to perform meta-analysis of multiple studies instead of analyzing the individual studies separately. The proposed models require individual observations. The value of the current paper can be seen at least for two reasons: (a) the proposed methods can be applied to studies that have individual genotype data; (b) the proposed methods can be used as a criterion for future work that uses summary statistics to build test statistics to meta-analyze the data. PMID:28000696

Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice.

PubMed

Kalueff, A V; Fox, M A; Gallagher, P S; Murphy, D L

2007-06-01

Although mice with a targeted disruption of the serotonin transporter (SERT) have been studied extensively using various tests, their complex behavioral phenotype is not yet fully understood. Here we assess in detail the behavior of adult female SERT wild type (+/+), heterozygous (+/-) and knockout (-/-) mice on an isogenic C57BL/6J background subjected to a battery of behavioral paradigms. Overall, there were no differences in the ability to find food or a novel object, nest-building, self-grooming and its sequencing, and horizontal rod balancing, indicating unimpaired sensory functions, motor co-ordination and behavioral sequencing. In contrast, there were striking reductions in exploration and activity in novelty-based tests (novel object, sticky label and open field tests), accompanied by pronounced thigmotaxis, suggesting that combined hypolocomotion and anxiety (rather than purely anxiety) influence the SERT -/- behavioral phenotype. Social interaction behaviors were also markedly reduced. In addition, SERT -/- mice tended to move close to the ground, frequently displayed spontaneous Straub tail, tics, tremor and backward gait - a phenotype generally consistent with 'serotonin syndrome'-like behavior. In line with replicated evidence of much enhanced serotonin availability in SERT -/- mice, this serotonin syndrome-like state may represent a third factor contributing to their behavioral profile. An understanding of the emerging complexity of SERT -/- mouse behavior is crucial for a detailed dissection of their phenotype and for developing further neurobehavioral models using these mice.

Detection of Chlamydiaceae and Chlamydia-like organisms on the ocular surface of children and adults from a trachoma-endemic region.

PubMed

Ghasemian, Ehsan; Inic-Kanada, Aleksandra; Collingro, Astrid; Tagini, Florian; Stein, Elisabeth; Alchalabi, Hadeel; Schuerer, Nadine; Keše, Darja; Babiker, Balgesa Elkheir; Borel, Nicole; Greub, Gilbert; Barisani-Asenbauer, Talin

2018-05-09

Trachoma, the leading infectious cause of blindness, is caused by Chlamydia trachomatis (Ct), a bacterium of the phylum Chlamydiae. Recent investigations revealed the existence of additional families within the phylum Chlamydiae, also termed Chlamydia-like organisms (CLOs). In this study, the frequency of Ct and CLOs was examined in the eyes of healthy Sudanese (control) participants and those with trachoma (case). We tested 96 children (54 cases and 42 controls) and 93 adults (51 cases and 42 controls) using broad-range Chlamydiae and Ct-specific (omcB) real-time PCR. Samples positive by broad-range Chlamydiae testing were subjected to DNA sequencing. Overall Chlamydiae prevalence was 36%. Sequences corresponded to unclassified and classified Chlamydiae. Ct infection rate was significantly higher in children (31.5%) compared to adults (0%) with trachoma (p < 0.0001). In general, 21.5% of adults and 4.2% of children tested positive for CLOs (p = 0.0003). Our findings are consistent with previous investigations describing the central role of Ct in trachoma among children. This is the first study examining human eyes for the presence of CLOs. We found an age-dependent distribution of CLO DNA in human eyes with significantly higher positivity in adults. Further studies are needed to understand the impact of CLOs in trachoma pathogenicity and/or protection.

Meta-analysis of quantitative pleiotropic traits for next-generation sequencing with multivariate functional linear models.

PubMed

Chiu, Chi-Yang; Jung, Jeesun; Chen, Wei; Weeks, Daniel E; Ren, Haobo; Boehnke, Michael; Amos, Christopher I; Liu, Aiyi; Mills, James L; Ting Lee, Mei-Ling; Xiong, Momiao; Fan, Ruzong

2017-02-01

To analyze next-generation sequencing data, multivariate functional linear models are developed for a meta-analysis of multiple studies to connect genetic variant data to multiple quantitative traits adjusting for covariates. The goal is to take the advantage of both meta-analysis and pleiotropic analysis in order to improve power and to carry out a unified association analysis of multiple studies and multiple traits of complex disorders. Three types of approximate F -distributions based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants. Simulation analysis is performed to evaluate false-positive rates and power of the proposed tests. The proposed methods are applied to analyze lipid traits in eight European cohorts. It is shown that it is more advantageous to perform multivariate analysis than univariate analysis in general, and it is more advantageous to perform meta-analysis of multiple studies instead of analyzing the individual studies separately. The proposed models require individual observations. The value of the current paper can be seen at least for two reasons: (a) the proposed methods can be applied to studies that have individual genotype data; (b) the proposed methods can be used as a criterion for future work that uses summary statistics to build test statistics to meta-analyze the data.

Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.

PubMed

Lee, Cha Gon; Lee, Jeehun; Lee, Munhyang

2018-01-01

Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.

Optimization of parameter values for complex pulse sequences by simulated annealing: application to 3D MP-RAGE imaging of the brain.

PubMed

Epstein, F H; Mugler, J P; Brookeman, J R

1994-02-01

A number of pulse sequence techniques, including magnetization-prepared gradient echo (MP-GRE), segmented GRE, and hybrid RARE, employ a relatively large number of variable pulse sequence parameters and acquire the image data during a transient signal evolution. These sequences have recently been proposed and/or used for clinical applications in the brain, spine, liver, and coronary arteries. Thus, the need for a method of deriving optimal pulse sequence parameter values for this class of sequences now exists. Due to the complexity of these sequences, conventional optimization approaches, such as applying differential calculus to signal difference equations, are inadequate. We have developed a general framework for adapting the simulated annealing algorithm to pulse sequence parameter value optimization, and applied this framework to the specific case of optimizing the white matter-gray matter signal difference for a T1-weighted variable flip angle 3D MP-RAGE sequence. Using our algorithm, the values of 35 sequence parameters, including the magnetization-preparation RF pulse flip angle and delay time, 32 flip angles in the variable flip angle gradient-echo acquisition sequence, and the magnetization recovery time, were derived. Optimized 3D MP-RAGE achieved up to a 130% increase in white matter-gray matter signal difference compared with optimized 3D RF-spoiled FLASH with the same total acquisition time. The simulated annealing approach was effective at deriving optimal parameter values for a specific 3D MP-RAGE imaging objective, and may be useful for other imaging objectives and sequences in this general class.

CLUSTOM-CLOUD: In-Memory Data Grid-Based Software for Clustering 16S rRNA Sequence Data in the Cloud Environment.

PubMed

Oh, Jeongsu; Choi, Chi-Hwan; Park, Min-Kyu; Kim, Byung Kwon; Hwang, Kyuin; Lee, Sang-Heon; Hong, Soon Gyu; Nasir, Arshan; Cho, Wan-Sup; Kim, Kyung Mo

2016-01-01

High-throughput sequencing can produce hundreds of thousands of 16S rRNA sequence reads corresponding to different organisms present in the environmental samples. Typically, analysis of microbial diversity in bioinformatics starts from pre-processing followed by clustering 16S rRNA reads into relatively fewer operational taxonomic units (OTUs). The OTUs are reliable indicators of microbial diversity and greatly accelerate the downstream analysis time. However, existing hierarchical clustering algorithms that are generally more accurate than greedy heuristic algorithms struggle with large sequence datasets. To keep pace with the rapid rise in sequencing data, we present CLUSTOM-CLOUD, which is the first distributed sequence clustering program based on In-Memory Data Grid (IMDG) technology-a distributed data structure to store all data in the main memory of multiple computing nodes. The IMDG technology helps CLUSTOM-CLOUD to enhance both its capability of handling larger datasets and its computational scalability better than its ancestor, CLUSTOM, while maintaining high accuracy. Clustering speed of CLUSTOM-CLOUD was evaluated on published 16S rRNA human microbiome sequence datasets using the small laboratory cluster (10 nodes) and under the Amazon EC2 cloud-computing environments. Under the laboratory environment, it required only ~3 hours to process dataset of size 200 K reads regardless of the complexity of the human microbiome data. In turn, one million reads were processed in approximately 20, 14, and 11 hours when utilizing 20, 30, and 40 nodes on the Amazon EC2 cloud-computing environment. The running time evaluation indicates that CLUSTOM-CLOUD can handle much larger sequence datasets than CLUSTOM and is also a scalable distributed processing system. The comparative accuracy test using 16S rRNA pyrosequences of a mock community shows that CLUSTOM-CLOUD achieves higher accuracy than DOTUR, mothur, ESPRIT-Tree, UCLUST and Swarm. CLUSTOM-CLOUD is written in JAVA and is freely available at http://clustomcloud.kopri.re.kr.

A Phylogenomic Approach Based on PCR Target Enrichment and High Throughput Sequencing: Resolving the Diversity within the South American Species of Bartsia L. (Orobanchaceae)

PubMed Central

Tank, David C.

2016-01-01

Advances in high-throughput sequencing (HTS) have allowed researchers to obtain large amounts of biological sequence information at speeds and costs unimaginable only a decade ago. Phylogenetics, and the study of evolution in general, is quickly migrating towards using HTS to generate larger and more complex molecular datasets. In this paper, we present a method that utilizes microfluidic PCR and HTS to generate large amounts of sequence data suitable for phylogenetic analyses. The approach uses the Fluidigm Access Array System (Fluidigm, San Francisco, CA, USA) and two sets of PCR primers to simultaneously amplify 48 target regions across 48 samples, incorporating sample-specific barcodes and HTS adapters (2,304 unique amplicons per Access Array). The final product is a pooled set of amplicons ready to be sequenced, and thus, there is no need to construct separate, costly genomic libraries for each sample. Further, we present a bioinformatics pipeline to process the raw HTS reads to either generate consensus sequences (with or without ambiguities) for every locus in every sample or—more importantly—recover the separate alleles from heterozygous target regions in each sample. This is important because it adds allelic information that is well suited for coalescent-based phylogenetic analyses that are becoming very common in conservation and evolutionary biology. To test our approach and bioinformatics pipeline, we sequenced 576 samples across 96 target regions belonging to the South American clade of the genus Bartsia L. in the plant family Orobanchaceae. After sequencing cleanup and alignment, the experiment resulted in ~25,300bp across 486 samples for a set of 48 primer pairs targeting the plastome, and ~13,500bp for 363 samples for a set of primers targeting regions in the nuclear genome. Finally, we constructed a combined concatenated matrix from all 96 primer combinations, resulting in a combined aligned length of ~40,500bp for 349 samples. PMID:26828929

CLUSTOM-CLOUD: In-Memory Data Grid-Based Software for Clustering 16S rRNA Sequence Data in the Cloud Environment

PubMed Central

Park, Min-Kyu; Kim, Byung Kwon; Hwang, Kyuin; Lee, Sang-Heon; Hong, Soon Gyu; Nasir, Arshan; Cho, Wan-Sup; Kim, Kyung Mo

2016-01-01

High-throughput sequencing can produce hundreds of thousands of 16S rRNA sequence reads corresponding to different organisms present in the environmental samples. Typically, analysis of microbial diversity in bioinformatics starts from pre-processing followed by clustering 16S rRNA reads into relatively fewer operational taxonomic units (OTUs). The OTUs are reliable indicators of microbial diversity and greatly accelerate the downstream analysis time. However, existing hierarchical clustering algorithms that are generally more accurate than greedy heuristic algorithms struggle with large sequence datasets. To keep pace with the rapid rise in sequencing data, we present CLUSTOM-CLOUD, which is the first distributed sequence clustering program based on In-Memory Data Grid (IMDG) technology–a distributed data structure to store all data in the main memory of multiple computing nodes. The IMDG technology helps CLUSTOM-CLOUD to enhance both its capability of handling larger datasets and its computational scalability better than its ancestor, CLUSTOM, while maintaining high accuracy. Clustering speed of CLUSTOM-CLOUD was evaluated on published 16S rRNA human microbiome sequence datasets using the small laboratory cluster (10 nodes) and under the Amazon EC2 cloud-computing environments. Under the laboratory environment, it required only ~3 hours to process dataset of size 200 K reads regardless of the complexity of the human microbiome data. In turn, one million reads were processed in approximately 20, 14, and 11 hours when utilizing 20, 30, and 40 nodes on the Amazon EC2 cloud-computing environment. The running time evaluation indicates that CLUSTOM-CLOUD can handle much larger sequence datasets than CLUSTOM and is also a scalable distributed processing system. The comparative accuracy test using 16S rRNA pyrosequences of a mock community shows that CLUSTOM-CLOUD achieves higher accuracy than DOTUR, mothur, ESPRIT-Tree, UCLUST and Swarm. CLUSTOM-CLOUD is written in JAVA and is freely available at http://clustomcloud.kopri.re.kr. PMID:26954507

Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.

PubMed

Saunders, Christopher T; Wong, Wendy S W; Swamy, Sajani; Becq, Jennifer; Murray, Lisa J; Cheetham, R Keira

2012-07-15

Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity. We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. We demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests. The Strelka workflow source code is available at ftp://strelka@ftp.illumina.com/. csaunders@illumina.com

Visual Sequence Learning in Infancy: Domain-General and Domain-Specific Associations with Language

ERIC Educational Resources Information Center

Shafto, Carissa L.; Conway, Christopher M.; Field, Suzanne L.; Houston, Derek M.

2012-01-01

Research suggests that nonlinguistic sequence learning abilities are an important contributor to language development (Conway, Bauernschmidt, Huang, & Pisoni, 2010). The current study investigated visual sequence learning (VSL) as a possible predictor of vocabulary development in infants. Fifty-eight 8.5-month-old infants were presented with a…

Teaching Inquiry with Linked Classes and Learning Communities

ERIC Educational Resources Information Center

Piercey, Victor; Cullen, Roxanne

2017-01-01

In order to improve problem-solving dispositions, a section of an inquiry-based math sequence for first-year business students was linked with a section of our general education English sequence. We describe how the linked classes worked and compare some preliminary results from linked and unlinked sections of the math sequence.

Comparison of simple sequence repeats in 19 Archaea.

PubMed

Trivedi, S

2006-12-05

All organisms that have been studied until now have been found to have differential distribution of simple sequence repeats (SSRs), with more SSRs in intergenic than in coding sequences. SSR distribution was investigated in Archaea genomes where complete chromosome sequences of 19 Archaea were analyzed with the program SPUTNIK to find di- to penta-nucleotide repeats. The number of repeats was determined for the complete chromosome sequences and for the coding and non-coding sequences. Different from what has been found for other groups of organisms, there is an abundance of SSRs in coding regions of the genome of some Archaea. Dinucleotide repeats were rare and CG repeats were found in only two Archaea. In general, trinucleotide repeats are the most abundant SSR motifs; however, pentanucleotide repeats are abundant in some Archaea. Some of the tetranucleotide and pentanucleotide repeat motifs are organism specific. In general, repeats are short and CG-rich repeats are present in Archaea having a CG-rich genome. Among the 19 Archaea, SSR density was not correlated with genome size or with optimum growth temperature. Pentanucleotide density had an inverse correlation with the CG content of the genome.

Genetic and Physical Structure of Salmonella-coli Phage Hybrids and Development of New Generalized Transducing Hybrid Phages for E. Coli.

DTIC Science & Technology

1984-05-01

YAHANOTO KAY 84 UNLSIID DM1-4C45 / /3 N EMhEEhEhEMEE I.’.’.MMMMN II.l I MI2 MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS 1963 A 1.0 w o...antigenic peptide sequences. Since antibodies against various parts (not limited to adsorption binding or its adjacent sites) of tail fiber contribute to...10 fold reduced rate of P2 neutralization.-This observation suggests that anti-P2 serum contains antibodies which cross-react with the G(-) products

Impact of cultivation on characterisation of species composition of soil bacterial communities.

PubMed

McCaig, A E.; Grayston, S J.; Prosser, J I.; Glover, L A.

2001-03-01

The species composition of culturable bacteria in Scottish grassland soils was investigated using a combination of Biolog and 16S rDNA analysis for characterisation of isolates. The inclusion of a molecular approach allowed direct comparison of sequences from culturable bacteria with sequences obtained during analysis of DNA extracted directly from the same soil samples. Bacterial strains were isolated on Pseudomonas isolation agar (PIA), a selective medium, and on tryptone soya agar (TSA), a general laboratory medium. In total, 12 and 21 morphologically different bacterial cultures were isolated on PIA and TSA, respectively. Biolog and sequencing placed PIA isolates in the same taxonomic groups, the majority of cultures belonging to the Pseudomonas (sensu stricto) group. However, analysis of 16S rDNA sequences proved more efficient than Biolog for characterising TSA isolates due to limitations of the Microlog database for identifying environmental bacteria. In general, 16S rDNA sequences from TSA isolates showed high similarities to cultured species represented in sequence databases, although TSA-8 showed only 92.5% similarity to the nearest relative, Bacillus insolitus. In general, there was very little overlap between the culturable and uncultured bacterial communities, although two sequences, PIA-2 and TSA-13, showed >99% similarity to soil clones. A cloning step was included prior to sequence analysis of two isolates, TSA-5 and TSA-14, and analysis of several clones confirmed that these cultures comprised at least four and three sequence types, respectively. All isolate clones were most closely related to uncultured bacteria, with clone TSA-5.1 showing 99.8% similarity to a sequence amplified directly from the same soil sample. Interestingly, one clone, TSA-5.4, clustered within a novel group comprising only uncultured sequences. This group, which is associated with the novel, deep-branching Acidobacterium capsulatum lineage, also included clones isolated during direct analysis of the same soil and from a wide range of other sample types studied elsewhere. The study demonstrates the value of fine-scale molecular analysis for identification of laboratory isolates and indicates the culturability of approximately 1% of the total population but under a restricted range of media and cultivation conditions.

Robot Tracking of Human Subjects in Field Environments

NASA Technical Reports Server (NTRS)

Graham, Jeffrey; Shillcutt, Kimberly

2003-01-01

Future planetary exploration will involve both humans and robots. Understanding and improving their interaction is a main focus of research in the Intelligent Systems Branch at NASA's Johnson Space Center. By teaming intelligent robots with astronauts on surface extra-vehicular activities (EVAs), safety and productivity can be improved. The EVA Robotic Assistant (ERA) project was established to study the issues of human-robot teams, to develop a testbed robot to assist space-suited humans in exploration tasks, and to experimentally determine the effectiveness of an EVA assistant robot. A companion paper discusses the ERA project in general, its history starting with ASRO (Astronaut-Rover project), and the results of recent field tests in Arizona. This paper focuses on one aspect of the research, robot tracking, in greater detail: the software architecture and algorithms. The ERA robot is capable of moving towards and/or continuously following mobile or stationary targets or sequences of targets. The contributions made by this research include how the low-level pose data is assembled, normalized and communicated, how the tracking algorithm was generalized and implemented, and qualitative performance reports from recent field tests.

Use of Competitive PCR to Detect and Quantify Haplosporidium nelsoni Infection (MSX disease) in the Eastern Oyster (Crassostrea virginica).

PubMed

Day, J Michael; Franklin, Dean E.; Brown, Bonnie L.

2000-09-01

This study was undertaken to develop a quantitative polymerase chain reaction assay that would improve the utility of PCR for detecting Haplosporidium nelsoni (MSX), a serious parasite of the eastern oyster Crassostrea virginica. A competitive PCR sequence was generated from the H. nelsoni small subunit ribosomal DNA fragment, originally described by Stokes and colleagues, that was amplified by the same PCR primers and had similar amplification performance. Assays performed using competitor dilutions ranging from 0.05 to 500 pg/µl DNA were used to test oyster samples designated using histological techniques as having "light" or "heavy" MSX infections. Visual diagnoses were confirmed equally well with three methods: densitometry of ethidium-bromide-stained agarose, densitometry of SYBRGreen-stained polyacrylamide gels, and analysis by GeneScan 3.0 of fluorescent products detected in ultrathin gels. Oysters diagnosed as negative for MSX tested as negative or light by PCR. Oysters with light MSX infections generally had less than 5 pg/µl infectious DNA. Oysters with heavy infections generally corresponded to 5 pg/µl or greater competitor dilutions.

Application of next generation sequencing in clinical microbiology and infection prevention.

PubMed

Deurenberg, Ruud H; Bathoorn, Erik; Chlebowicz, Monika A; Couto, Natacha; Ferdous, Mithila; García-Cobos, Silvia; Kooistra-Smid, Anna M D; Raangs, Erwin C; Rosema, Sigrid; Veloo, Alida C M; Zhou, Kai; Friedrich, Alexander W; Rossen, John W A

2017-02-10

Current molecular diagnostics of human pathogens provide limited information that is often not sufficient for outbreak and transmission investigation. Next generation sequencing (NGS) determines the DNA sequence of a complete bacterial genome in a single sequence run, and from these data, information on resistance and virulence, as well as information for typing is obtained, useful for outbreak investigation. The obtained genome data can be further used for the development of an outbreak-specific screening test. In this review, a general introduction to NGS is presented, including the library preparation and the major characteristics of the most common NGS platforms, such as the MiSeq (Illumina) and the Ion PGM™ (ThermoFisher). An overview of the software used for NGS data analyses used at the medical microbiology diagnostic laboratory in the University Medical Center Groningen in The Netherlands is given. Furthermore, applications of NGS in the clinical setting are described, such as outbreak management, molecular case finding, characterization and surveillance of pathogens, rapid identification of bacteria using the 16S-23S rRNA region, taxonomy, metagenomics approaches on clinical samples, and the determination of the transmission of zoonotic micro-organisms from animals to humans. Finally, we share our vision on the use of NGS in personalised microbiology in the near future, pointing out specific requirements. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Molecular determinants of origin discrimination by Orc1 initiators in archaea.

PubMed

Dueber, Erin C; Costa, Alessandro; Corn, Jacob E; Bell, Stephen D; Berger, James M

2011-05-01

Unlike bacteria, many eukaryotes initiate DNA replication from genomic sites that lack apparent sequence conservation. These loci are identified and bound by the origin recognition complex (ORC), and subsequently activated by a cascade of events that includes recruitment of an additional factor, Cdc6. Archaeal organisms generally possess one or more Orc1/Cdc6 homologs, belonging to the Initiator clade of ATPases associated with various cellular activities (AAA(+)) superfamily; however, these proteins recognize specific sequences within replication origins. Atomic resolution studies have shown that archaeal Orc1 proteins contact double-stranded DNA through an N-terminal AAA(+) domain and a C-terminal winged-helix domain (WHD), but use remarkably few base-specific contacts. To investigate the biochemical effects of these associations, we mutated the DNA-interacting elements of the Orc1-1 and Orc1-3 paralogs from the archaeon Sulfolobus solfataricus, and tested their effect on origin binding and deformation. We find that the AAA(+) domain has an unpredicted role in controlling the sequence selectivity of DNA binding, despite an absence of base-specific contacts to this region. Our results show that both the WHD and ATPase region influence origin recognition by Orc1/Cdc6, and suggest that not only DNA sequence, but also local DNA structure help define archaeal initiator binding sites. © The Author(s) 2011. Published by Oxford University Press.

Genetic dissection of the consensus sequence for the class 2 and class 3 flagellar promoters

PubMed Central

Wozniak, Christopher E.; Hughes, Kelly T.

2008-01-01

Summary Computational searches for DNA binding sites often utilize consensus sequences. These search models make assumptions that the frequency of a base pair in an alignment relates to the base pair’s importance in binding and presume that base pairs contribute independently to the overall interaction with the DNA binding protein. These two assumptions have generally been found to be accurate for DNA binding sites. However, these assumptions are often not satisfied for promoters, which are involved in additional steps in transcription initiation after RNA polymerase has bound to the DNA. To test these assumptions for the flagellar regulatory hierarchy, class 2 and class 3 flagellar promoters were randomly mutagenized in Salmonella. Important positions were then saturated for mutagenesis and compared to scores calculated from the consensus sequence. Double mutants were constructed to determine how mutations combined for each promoter type. Mutations in the binding site for FlhD4C2, the activator of class 2 promoters, better satisfied the assumptions for the binding model than did mutations in the class 3 promoter, which is recognized by the σ28 transcription factor. These in vivo results indicate that the activator sites within flagellar promoters can be modeled using simple assumptions but that the DNA sequences recognized by the flagellar sigma factor require more complex models. PMID:18486950

Reprint of "Application of next generation sequencing in clinical microbiology and infection prevention".

PubMed

Deurenberg, Ruud H; Bathoorn, Erik; Chlebowicz, Monika A; Couto, Natacha; Ferdous, Mithila; García-Cobos, Silvia; Kooistra-Smid, Anna M D; Raangs, Erwin C; Rosema, Sigrid; Veloo, Alida C M; Zhou, Kai; Friedrich, Alexander W; Rossen, John W A

2017-05-20

Current molecular diagnostics of human pathogens provide limited information that is often not sufficient for outbreak and transmission investigation. Next generation sequencing (NGS) determines the DNA sequence of a complete bacterial genome in a single sequence run, and from these data, information on resistance and virulence, as well as information for typing is obtained, useful for outbreak investigation. The obtained genome data can be further used for the development of an outbreak-specific screening test. In this review, a general introduction to NGS is presented, including the library preparation and the major characteristics of the most common NGS platforms, such as the MiSeq (Illumina) and the Ion PGM™ (ThermoFisher). An overview of the software used for NGS data analyses used at the medical microbiology diagnostic laboratory in the University Medical Center Groningen in The Netherlands is given. Furthermore, applications of NGS in the clinical setting are described, such as outbreak management, molecular case finding, characterization and surveillance of pathogens, rapid identification of bacteria using the 16S-23S rRNA region, taxonomy, metagenomics approaches on clinical samples, and the determination of the transmission of zoonotic micro-organisms from animals to humans. Finally, we share our vision on the use of NGS in personalised microbiology in the near future, pointing out specific requirements. Copyright © 2017. Published by Elsevier B.V.

AlexSys: a knowledge-based expert system for multiple sequence alignment construction and analysis

PubMed Central

Aniba, Mohamed Radhouene; Poch, Olivier; Marchler-Bauer, Aron; Thompson, Julie Dawn

2010-01-01

Multiple sequence alignment (MSA) is a cornerstone of modern molecular biology and represents a unique means of investigating the patterns of conservation and diversity in complex biological systems. Many different algorithms have been developed to construct MSAs, but previous studies have shown that no single aligner consistently outperforms the rest. This has led to the development of a number of ‘meta-methods’ that systematically run several aligners and merge the output into one single solution. Although these methods generally produce more accurate alignments, they are inefficient because all the aligners need to be run first and the choice of the best solution is made a posteriori. Here, we describe the development of a new expert system, AlexSys, for the multiple alignment of protein sequences. AlexSys incorporates an intelligent inference engine to automatically select an appropriate aligner a priori, depending only on the nature of the input sequences. The inference engine was trained on a large set of reference multiple alignments, using a novel machine learning approach. Applying AlexSys to a test set of 178 alignments, we show that the expert system represents a good compromise between alignment quality and running time, making it suitable for high throughput projects. AlexSys is freely available from http://alnitak.u-strasbg.fr/∼aniba/alexsys. PMID:20530533

Democratization of genetic data: connecting government approval of clinical tests with data sharing

PubMed Central

Ross, Theodora S.

2015-01-01

Abstract When a doctor orders a genetic test, patients assume that the test will yield a useful result to guide how their physicians take care of them. That assumption is frequently correct, but not always. Until recently, a genetic test only interrogated the sequence of one or two genes. Now, DNA-sequencing technologies are so fast and cheap that they have enabled clinicians to sequence panels of genes that may or may not be relevant to the patient's condition. The technology has outpaced our ability to interpret the results. Connecting approval of clinical tests to data sharing could help close this gap. PMID:27148568

Democratization of genetic data: connecting government approval of clinical tests with data sharing.

PubMed

Ross, Theodora S

2015-10-01

When a doctor orders a genetic test, patients assume that the test will yield a useful result to guide how their physicians take care of them. That assumption is frequently correct, but not always. Until recently, a genetic test only interrogated the sequence of one or two genes. Now, DNA-sequencing technologies are so fast and cheap that they have enabled clinicians to sequence panels of genes that may or may not be relevant to the patient's condition. The technology has outpaced our ability to interpret the results. Connecting approval of clinical tests to data sharing could help close this gap.

Identification of a novel nonsense mutation and a missense substitution in the AGPAT2 gene causing congenital generalized lipodystrophy type 1

PubMed Central

Haghighi, Amirreza; Razzaghy-Azar, Maryam; Talea, Ali; Sadeghian, Mahnaz; Ellard, Sian; Haghighi, Alireza

2012-01-01

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disease characterized by the generalized scant of adipose tissue. CGL type 1 is caused by mutations in gene encoding 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2). A clinical and molecular genetic investigation was performed in affected and unaffected members of two families with CGL type 1. The AGPAT2 coding region was sequenced in index cases of the two families. The presence of the identified mutations in relevant parents was tested. We identified a novel nonsense mutation (c.685G>T, p.Glu229*) and a missense substitution (c.514G>A, p.Glu172Lys). The unaffected parents in both families were heterozygous carrier of the relevant mutation. The results expand genotype–phenotype spectrum in CGL1 and will have applications in prenatal and early diagnosis of the disease. This is the first report of Persian families identified with AGPAT2 mutations. PMID:22902344

GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.

PubMed

Brittnacher, Mitchell J; Heltshe, Sonya L; Hayden, Hillary S; Radey, Matthew C; Weiss, Eli J; Damman, Christopher J; Zisman, Timothy L; Suskind, David L; Miller, Samuel I

2016-01-01

Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome.

Shuttle avionics and the goal language including the impact of error detection and redundancy management

NASA Technical Reports Server (NTRS)

Flanders, J. H.; Helmers, C. T.; Stanten, S. F.

1973-01-01

The relationship is examined between the space shuttle onboard avionics and the ground test computer language GOAL when used in the onboard computers. The study is aimed at providing system analysis support to the feasibility analysis of a GOAL to HAL translator, where HAL is the language used to program the onboard computers for flight. The subject is dealt with in three aspects. First, the system configuration at checkout, the general checkout and launch sequences, and the inventory of subsystems are described. Secondly, the hierarchic organization of onboard software and different ways of introducing GOAL-derived software onboard are described. Also the flow of commands and test data during checkout is diagrammed. Finally, possible impact of error detection and redundancy management on the GOAL language is discussed.

Reliability and validity of the Spanish Language Wechsler Adult Intelligence Scale (3rd Edition) in a sample of American, urban, Spanish-speaking Hispanics.

PubMed

Renteria, Laura; Li, Susan Tinsley; Pliskin, Neil H

2008-05-01

The utility of the Spanish WAIS-III was investigated by examining its reliability and validity among 100 Spanish-speaking participants. Results indicated that the internal consistency of the subtests was satisfactory, but inadequate for Letter Number Sequencing. Criterion validity was adequate. Convergent and discriminant validity results were generally similar to the North American normative sample. Paired sample t-tests suggested that the WAIS-III may underestimate ability when compared to the criterion measures that were utilized to assess validity. This study provides support for the use of the Spanish WAIS-III in urban Hispanic populations, but also suggests that caution be used when administering specific subtests, due to the nature of the Latin America alphabet and potential test bias.

Spiking of contemporary human template DNA with ancient DNA extracts induces mutations under PCR and generates nonauthentic mitochondrial sequences.

PubMed

Pusch, Carsten M; Bachmann, Lutz

2004-05-01

Proof of authenticity is the greatest challenge in palaeogenetic research, and many safeguards have become standard routine in laboratories specialized on ancient DNA research. Here we describe an as-yet unknown source of artifacts that will require special attention in the future. We show that ancient DNA extracts on their own can have an inhibitory and mutagenic effect under PCR. We have spiked PCR reactions including known human test DNA with 14 selected ancient DNA extracts from human and nonhuman sources. We find that the ancient DNA extracts inhibit the amplification of large fragments to different degrees, suggesting that the usual control against contaminations, i.e., the absence of long amplifiable fragments, is not sufficient. But even more important, we find that the extracts induce mutations in a nonrandom fashion. We have amplified a 148-bp stretch of the mitochondrial HVRI from contemporary human template DNA in spiked PCR reactions. Subsequent analysis of 547 sequences from cloned amplicons revealed that the vast majority (76.97%) differed from the correct sequence by single nucleotide substitutions and/or indels. In total, 34 positions of a 103-bp alignment are affected, and most mutations occur repeatedly in independent PCR amplifications. Several of the induced mutations occur at positions that have previously been detected in studies of ancient hominid sequences, including the Neandertal sequences. Our data imply that PCR-induced mutations are likely to be an intrinsic and general problem of PCR amplifications of ancient templates. Therefore, ancient DNA sequences should be considered with caution, at least as long as the molecular basis for the extract-induced mutations is not understood.

Computational design of enzyme-ligand binding using a combined energy function and deterministic sequence optimization algorithm.

PubMed

Tian, Ye; Huang, Xiaoqiang; Zhu, Yushan

2015-08-01

Enzyme amino-acid sequences at ligand-binding interfaces are evolutionarily optimized for reactions, and the natural conformation of an enzyme-ligand complex must have a low free energy relative to alternative conformations in native-like or non-native sequences. Based on this assumption, a combined energy function was developed for enzyme design and then evaluated by recapitulating native enzyme sequences at ligand-binding interfaces for 10 enzyme-ligand complexes. In this energy function, the electrostatic interaction between polar or charged atoms at buried interfaces is described by an explicitly orientation-dependent hydrogen-bonding potential and a pairwise-decomposable generalized Born model based on the general side chain in the protein design framework. The energy function is augmented with a pairwise surface-area based hydrophobic contribution for nonpolar atom burial. Using this function, on average, 78% of the amino acids at ligand-binding sites were predicted correctly in the minimum-energy sequences, whereas 84% were predicted correctly in the most-similar sequences, which were selected from the top 20 sequences for each enzyme-ligand complex. Hydrogen bonds at the enzyme-ligand binding interfaces in the 10 complexes were usually recovered with the correct geometries. The binding energies calculated using the combined energy function helped to discriminate the active sequences from a pool of alternative sequences that were generated by repeatedly solving a series of mixed-integer linear programming problems for sequence selection with increasing integer cuts.

Statistical learning of music- and language-like sequences and tolerance for spectral shifts.

PubMed

Daikoku, Tatsuya; Yatomi, Yutaka; Yumoto, Masato

2015-02-01

In our previous study (Daikoku, Yatomi, & Yumoto, 2014), we demonstrated that the N1m response could be a marker for the statistical learning process of pitch sequence, in which each tone was ordered by a Markov stochastic model. The aim of the present study was to investigate how the statistical learning of music- and language-like auditory sequences is reflected in the N1m responses based on the assumption that both language and music share domain generality. By using vowel sounds generated by a formant synthesizer, we devised music- and language-like auditory sequences in which higher-ordered transitional rules were embedded according to a Markov stochastic model by controlling fundamental (F0) and/or formant frequencies (F1-F2). In each sequence, F0 and/or F1-F2 were spectrally shifted in the last one-third of the tone sequence. Neuromagnetic responses to the tone sequences were recorded from 14 right-handed normal volunteers. In the music- and language-like sequences with pitch change, the N1m responses to the tones that appeared with higher transitional probability were significantly decreased compared with the responses to the tones that appeared with lower transitional probability within the first two-thirds of each sequence. Moreover, the amplitude difference was even retained within the last one-third of the sequence after the spectral shifts. However, in the language-like sequence without pitch change, no significant difference could be detected. The pitch change may facilitate the statistical learning in language and music. Statistically acquired knowledge may be appropriated to process altered auditory sequences with spectral shifts. The relative processing of spectral sequences may be a domain-general auditory mechanism that is innate to humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Verbal implicit sequence learning in persons who stutter and persons with Parkinson's disease.

PubMed

Smits-Bandstra, Sarah; Gracco, Vincent

2013-01-01

The authors investigated the integrity of implicit learning systems in 14 persons with Parkinson's disease (PPD), 14 persons who stutter (PWS), and 14 control participants. In a 120-min session participants completed a verbal serial reaction time task, naming aloud 4 syllables in response to 4 visual stimuli. Unbeknownst to participants, the syllables formed a repeating 8-item sequence. PWS and PPD demonstrated slower reaction times for early but not late learning trials relative to controls reflecting delays but not deficiencies in general learning. PPD also demonstrated less accuracy in general learning relative to controls. All groups demonstrated similar limited explicit sequence knowledge. Both PWS and PPD demonstrated significantly less implicit sequence learning relative to controls, suggesting that stuttering may be associated with compromised functional integrity of the cortico-striato-thalamo-cortical loop.

Nucleic acid-based diagnostics for infectious diseases in public health affairs.

PubMed

Yu, Albert Cheung-Hoi; Vatcher, Greg; Yue, Xin; Dong, Yan; Li, Mao Hua; Tam, Patrick H K; Tsang, Parker Y L; Wong, April K Y; Hui, Michael H K; Yang, Bin; Tang, Hao; Lau, Lok-Ting

2012-06-01

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

A selective egocentric topographical working memory deficit in the early stages of Alzheimer's disease: a preliminary study.

PubMed

Bianchini, F; Di Vita, A; Palermo, L; Piccardi, L; Blundo, C; Guariglia, C

2014-12-01

The aim of this study was to determine whether an egocentric topographical working memory (WM) deficit is present in the early stages of Alzheimer's disease (AD) with respect to other forms of visuospatial WM. Further, we would investigate whether this deficit could be present in patients having AD without topographical disorientation (TD) signs in everyday life assessed through an informal interview to caregivers. Seven patients with AD and 20 healthy participants performed the Walking Corsi Test and the Corsi Block-Tapping Test. The former test requires memorizing a sequence of places by following a path and the latter is a well-known visuospatial memory task. Patients with AD also performed a verbal WM test to exclude the presence of general WM impairments. Preliminary results suggest that egocentric topographical WM is selectively impaired, with respect to visuospatial and verbal WM, even without TD suggesting an important role of this memory in the early stages of AD. © The Author(s) 2014.

Use of Contemporary Genetics in Cardiovascular Diagnosis

PubMed Central

George, Alfred L.

2015-01-01

An explosion of knowledge regarding the genetic and genomic basis for rare and common diseases has provided a framework for revolutionizing the practice of medicine. Achieving the reality of a genomic medicine era requires that basic discoveries are effectively translated into clinical practice through implementation of genetic and genomic testing. Clinical genetic tests have become routine for many inherited disorders and can be regarded as the standard-of-care in many circumstances including disorders affecting the cardiovascular system. New, high-throughput methods for determining the DNA sequence of all coding exons or complete genomes are being adopted for clinical use to expand the speed and breadth of genetic testing. Along with these extraordinary advances have emerged new challenges to practicing physicians for understanding when and how to use genetic testing along with how to appropriately interpret test results. This review will acquaint readers with general principles of genetic testing including newer technologies, test interpretation and pitfalls. The focus will be on testing genes responsible for monogenic disorders and on other emerging applications such as pharmacogenomic profiling. The discussion will be extended to the new paradigm of direct-to-consumer genetic testing and the value of assessing genomic risk for common diseases. PMID:25421045

Assembling in Sequence: A Saleable Work Skill. Occupation Simulation Packet. Grades 3rd-4th.

ERIC Educational Resources Information Center

Hueston, Jean

This teacher's guide for grades 3 and 4 contains simulated work experiences for students using the isolated skill concept - assembling in sequence. Teacher instructions include objectives, evaluation, and sequence of activities. The guide contains pre-tests and post-tests with instructions and answer keys. Three pre-skill activities are suggested,…

An evaluation of computerized adaptive testing for general psychological distress: combining GHQ-12 and Affectometer-2 in an item bank for public mental health research.

PubMed

Stochl, Jan; Böhnke, Jan R; Pickett, Kate E; Croudace, Tim J

2016-05-20

Recent developments in psychometric modeling and technology allow pooling well-validated items from existing instruments into larger item banks and their deployment through methods of computerized adaptive testing (CAT). Use of item response theory-based bifactor methods and integrative data analysis overcomes barriers in cross-instrument comparison. This paper presents the joint calibration of an item bank for researchers keen to investigate population variations in general psychological distress (GPD). Multidimensional item response theory was used on existing health survey data from the Scottish Health Education Population Survey (n = 766) to calibrate an item bank consisting of pooled items from the short common mental disorder screen (GHQ-12) and the Affectometer-2 (a measure of "general happiness"). Computer simulation was used to evaluate usefulness and efficacy of its adaptive administration. A bifactor model capturing variation across a continuum of population distress (while controlling for artefacts due to item wording) was supported. The numbers of items for different required reliabilities in adaptive administration demonstrated promising efficacy of the proposed item bank. Psychometric modeling of the common dimension captured by more than one instrument offers the potential of adaptive testing for GPD using individually sequenced combinations of existing survey items. The potential for linking other item sets with alternative candidate measures of positive mental health is discussed since an optimal item bank may require even more items than these.

Effects of neostriatal 6-OHDA lesion on performance in a rat sequential reaction time task.

PubMed

Domenger, D; Schwarting, R K W

2008-10-31

Work in humans and monkeys has provided evidence that the basal ganglia, and the neurotransmitter dopamine therein, play an important role for sequential learning and performance. Compared to primates, experimental work in rodents is rather sparse, largely due to the fact that tasks comparable to the human ones, especially serial reaction time tasks (SRTT), had been lacking until recently. We have developed a rat model of the SRTT, which allows to study neural correlates of sequential performance and motor sequence execution. Here, we report the effects of dopaminergic neostriatal lesions, performed using bilateral 6-hydroxydopamine injections, on performance of well-trained rats tested in our SRTT. Sequential behavior was measured in two ways: for one, the effects of small violations of otherwise well trained sequences were examined as a measure of attention and automation. Secondly, sequential versus random performance was compared as a measure of sequential learning. Neurochemically, the lesions led to sub-total dopamine depletions in the neostriatum, which ranged around 60% in the lateral, and around 40% in the medial neostriatum. These lesions led to a general instrumental impairment in terms of reduced speed (response latencies) and response rate, and these deficits were correlated with the degree of striatal dopamine loss. Furthermore, the violation test indicated that the lesion group conducted less automated responses. The comparison of random versus sequential responding showed that the lesion group did not retain its superior sequential performance in terms of speed, whereas they did in terms of accuracy. Also, rats with lesions did not improve further in overall performance as compared to pre-lesion values, whereas controls did. These results support previous results that neostriatal dopamine is involved in instrumental behaviour in general. Also, these lesions are not sufficient to completely abolish sequential performance, at least when acquired before lesion as tested here.

How much detail and accuracy is required in plant growth sub-models to address questions about optimal management strategies in agricultural systems?

PubMed Central

Renton, Michael

2011-01-01

Background and aims Simulations that integrate sub-models of important biological processes can be used to ask questions about optimal management strategies in agricultural and ecological systems. Building sub-models with more detail and aiming for greater accuracy and realism may seem attractive, but is likely to be more expensive and time-consuming and result in more complicated models that lack transparency. This paper illustrates a general integrated approach for constructing models of agricultural and ecological systems that is based on the principle of starting simple and then directly testing for the need to add additional detail and complexity. Methodology The approach is demonstrated using LUSO (Land Use Sequence Optimizer), an agricultural system analysis framework based on simulation and optimization. A simple sensitivity analysis and functional perturbation analysis is used to test to what extent LUSO's crop–weed competition sub-model affects the answers to a number of questions at the scale of the whole farming system regarding optimal land-use sequencing strategies and resulting profitability. Principal results The need for accuracy in the crop–weed competition sub-model within LUSO depended to a small extent on the parameter being varied, but more importantly and interestingly on the type of question being addressed with the model. Only a small part of the crop–weed competition model actually affects the answers to these questions. Conclusions This study illustrates an example application of the proposed integrated approach for constructing models of agricultural and ecological systems based on testing whether complexity needs to be added to address particular questions of interest. We conclude that this example clearly demonstrates the potential value of the general approach. Advantages of this approach include minimizing costs and resources required for model construction, keeping models transparent and easy to analyse, and ensuring the model is well suited to address the question of interest. PMID:22476477

Domain-specific and domain-general constraints on word and sequence learning.

PubMed

Archibald, Lisa M D; Joanisse, Marc F

2013-02-01

The relative influences of language-related and memory-related constraints on the learning of novel words and sequences were examined by comparing individual differences in performance of children with and without specific deficits in either language or working memory. Children recalled lists of words in a Hebbian learning protocol in which occasional lists repeated, yielding improved recall over the course of the task on the repeated lists. The task involved presentation of pictures of common nouns followed immediately by equivalent presentations of the spoken names. The same participants also completed a paired-associate learning task involving word-picture and nonword-picture pairs. Hebbian learning was observed for all groups. Domain-general working memory constrained immediate recall, whereas language abilities impacted recall in the auditory modality only. In addition, working memory constrained paired-associate learning generally, whereas language abilities disproportionately impacted novel word learning. Overall, all of the learning tasks were highly correlated with domain-general working memory. The learning of nonwords was additionally related to general intelligence, phonological short-term memory, language abilities, and implicit learning. The results suggest that distinct associations between language- and memory-related mechanisms support learning of familiar and unfamiliar phonological forms and sequences.

A long PCR–based approach for DNA enrichment prior to next-generation sequencing for systematic studies1

PubMed Central

Uribe-Convers, Simon; Duke, Justin R.; Moore, Michael J.; Tank, David C.

2014-01-01

• Premise of the study: We present an alternative approach for molecular systematic studies that combines long PCR and next-generation sequencing. Our approach can be used to generate templates from any DNA source for next-generation sequencing. Here we test our approach by amplifying complete chloroplast genomes, and we present a set of 58 potentially universal primers for angiosperms to do so. Additionally, this approach is likely to be particularly useful for nuclear and mitochondrial regions. • Methods and Results: Chloroplast genomes of 30 species across angiosperms were amplified to test our approach. Amplification success varied depending on whether PCR conditions were optimized for a given taxon. To further test our approach, some amplicons were sequenced on an Illumina HiSeq 2000. • Conclusions: Although here we tested this approach by sequencing plastomes, long PCR amplicons could be generated using DNA from any genome, expanding the possibilities of this approach for molecular systematic studies. PMID:25202592

Fatigue testing of weldable high strength steels under simulated service conditions

NASA Astrophysics Data System (ADS)

Tantbirojn, Natee

There have been concerns over the effect of Cathodic Protection (CP) on weldable high strength steels employed in Jack-up production platform. The guidance provided by the Department of Energy HSE on higher strength steels, based on previous work, was to avoid overprotection as this could cause hydrogen embrittlement. However, the tests conducted so far at UCL for the SE702 type high strength steels (yields strength around 690 MPa) have shown that the effect of over protection on high strength steels may not be as severe as previously thought. For this thesis, SE702 high strength steels have been investigated in more detail. Thick (85mm) parent and ground welded plates were tested under constant amplitude in air and seawater with CP. Tests were also conducted on Thick (40mm) T-butt welded plates under variable amplitude loading in air and seawater with two CP levels (-800mV and -1050mV). Different backing materials (ceramic and metallic) for the welding process of the T-butt plates were also investigated. The variable amplitude sequences employed were generated using the Jack-up Offshore Standard load History (JOSH). The fatigue results are presented as crack growth and S/N curves. They were compared to the conventional offshore steel (BS 4360 50D). The results suggested that the fatigue life of the high strength steels was comparable to the BS 4360 50D steels. The effect of increasing the CP was found to be detrimental to the fatigue life but the effect was not large. The effect of CP was less noticeable in T-butt welded plates. However, in general, the effect of overprotection is not as detrimental to the Jack-up steels as previously thought. The load histories generated by JOSH were found to have some unfavourable characteristics. The framework is based on Markov Chain method and pseudo-random number generator for selecting sea-states. A study was carried out on the sequence generated by JOSH. The generated sequences were analysed for their validity for fatigue testing. This has resulted in recommendations on the methods for generating standard load histories.

Multigene panel next generation sequencing in a patient with cherry red macular spot: Identification of two novel mutations in NEU1 gene causing sialidosis type I associated with mild to unspecific biochemical and enzymatic findings.

PubMed

Mütze, Ulrike; Bürger, Friederike; Hoffmann, Jessica; Tegetmeyer, Helmut; Heichel, Jens; Nickel, Petra; Lemke, Johannes R; Syrbe, Steffen; Beblo, Skadi

2017-03-01

Lysosomal storage diseases (LSD) often manifest with cherry red macular spots. Diagnosis is based on clinical features and specific biochemical and enzymatic patterns. In uncertain cases, genetic testing with next generation sequencing can establish a diagnosis, especially in milder or atypical phenotypes. We report on the diagnostic work-up in a boy with sialidosis type I, presenting initially with marked cherry red macular spots but non-specific urinary oligosaccharide patterns and unusually mild excretion of bound sialic acid. Biochemical, enzymatic and genetic tests were performed in the patient. The clinical and electrophysiological data was reviewed and a genotype-phenotype analysis was performed. In addition a systematic literature review was carried out. Cherry red macular spots were first noted at 6 years of age after routine screening myopia. Physical examination, psychometric testing, laboratory investigations as well as cerebral MRI were unremarkable at 9 years of age. So far no clinical myoclonic seizures occurred, but EEG displays generalized epileptic discharges and visual evoked potentials are prolonged bilaterally. Urine thin layer chromatography showed an oligosaccharide pattern compatible with different LSD including sialidosis, galactosialidosis, GM1 gangliosidosis or mucopolysaccharidosis type IV B. Urinary bound sialic acid excretion was mildly elevated in spontaneous and 24 h urine samples. In cultured fibroblasts, α-sialidase activity was markedly decreased to < 1%; however, bound and free sialic acid were within normal range. Diagnosis was eventually established by multigene panel next generation sequencing of genes associated to LSD, identifying two novel, compound heterozygous variants in NEU1 gene (c.699C > A, p.S233R in exon 4 and c.803A > G; p.Y268C in Exon 5 in NEU1 transcript NM_000434.3), leading to amino acid changes predicted to impair protein function. Sialidosis should be suspected in patients with cherry red macular spots, even with non-significant urinary sialic acid excretion. Multigene panel next generation sequencing can establish a definite diagnosis, allowing for counseling of the patient and family.

Comparative analysis of Campylobacter isolates from wild birds and chickens using MALDI-TOF MS, biochemical testing, and DNA sequencing.

PubMed

Lawton, Samantha J; Weis, Allison M; Byrne, Barbara A; Fritz, Heather; Taff, Conor C; Townsend, Andrea K; Weimer, Bart C; Mete, Aslı; Wheeler, Sarah; Boyce, Walter M

2018-05-01

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was compared to conventional biochemical testing methods and nucleic acid analyses (16S rDNA sequencing, hippurate hydrolysis gene testing, whole genome sequencing [WGS]) for species identification of Campylobacter isolates obtained from chickens ( Gallus gallus domesticus, n = 8), American crows ( Corvus brachyrhynchos, n = 17), a mallard duck ( Anas platyrhynchos, n = 1), and a western scrub-jay ( Aphelocoma californica, n = 1). The test results for all 27 isolates were in 100% agreement between MALDI-TOF MS, the combined results of 16S rDNA sequencing, and the hippurate hydrolysis gene PCR ( p = 0.0027, kappa = 1). Likewise, the identifications derived from WGS from a subset of 14 isolates were in 100% agreement with the MALDI-TOF MS identification. In contrast, biochemical testing misclassified 5 isolates of C. jejuni as C. coli, and 16S rDNA sequencing alone was not able to differentiate between C. coli and C. jejuni for 11 sequences ( p = 0.1573, kappa = 0.0857) when compared to MALDI-TOF MS and WGS. No agreement was observed between MALDI-TOF MS dendrograms and the phylogenetic relationships revealed by rDNA sequencing or WGS. Our results confirm that MALDI-TOF MS is a fast and reliable method for identifying Campylobacter isolates to the species level from wild birds and chickens, but not for elucidating phylogenetic relationships among Campylobacter isolates.

Statistical learning of movement.

PubMed

Ongchoco, Joan Danielle Khonghun; Uddenberg, Stefan; Chun, Marvin M

2016-12-01

The environment is dynamic, but objects move in predictable and characteristic ways, whether they are a dancer in motion, or a bee buzzing around in flight. Sequences of movement are comprised of simpler motion trajectory elements chained together. But how do we know where one trajectory element ends and another begins, much like we parse words from continuous streams of speech? As a novel test of statistical learning, we explored the ability to parse continuous movement sequences into simpler element trajectories. Across four experiments, we showed that people can robustly parse such sequences from a continuous stream of trajectories under increasingly stringent tests of segmentation ability and statistical learning. Observers viewed a single dot as it moved along simple sequences of paths, and were later able to discriminate these sequences from novel and partial ones shown at test. Observers demonstrated this ability when there were potentially helpful trajectory-segmentation cues such as a common origin for all movements (Experiment 1); when the dot's motions were entirely continuous and unconstrained (Experiment 2); when sequences were tested against partial sequences as a more stringent test of statistical learning (Experiment 3); and finally, even when the element trajectories were in fact pairs of trajectories, so that abrupt directional changes in the dot's motion could no longer signal inter-trajectory boundaries (Experiment 4). These results suggest that observers can automatically extract regularities in movement - an ability that may underpin our capacity to learn more complex biological motions, as in sport or dance.

Content, Structure, and Sequence of the Detailing Discipline at Kendall College of Art and Design.

ERIC Educational Resources Information Center

Mulder, Bruce E.

A study identified the appropriate general content, structure, and sequence for a detailing discipline that promoted student achievement to professional levels. Its focus was the detailing discipline, a sequence of studio courses within the furniture design program at Kendall College of Art and Design, Grand Rapids, Michigan. (Detailing, an…

Chronology of Eocene-Miocene sequences on the New Jersey shallow shelf: implications for regional, interregional, and global correlations

USGS Publications Warehouse

Browning, James V.; Miller, Kenneth G.; Sugarman, Peter J.; Barron, John; McCarthy, Francine M.G.; Kulhanek, Denise K.; Katz, Miriam E.; Feigenson, Mark D.

2013-01-01

Integrated Ocean Drilling Program Expedition 313 continuously cored and logged latest Eocene to early-middle Miocene sequences at three sites (M27, M28, and M29) on the inner-middle continental shelf offshore New Jersey, providing an opportunity to evaluate the ages, global correlations, and significance of sequence boundaries. We provide a chronology for these sequences using integrated strontium isotopic stratigraphy and biostratigraphy (primarily calcareous nannoplankton, diatoms, and dinocysts [dinoflagellate cysts]). Despite challenges posed by shallow-water sediments, age resolution is typically ±0.5 m.y. and in many sequences is as good as ±0.25 m.y. Three Oligocene sequences were sampled at Site M27 on sequence bottomsets. Fifteen early to early-middle Miocene sequences were dated at Sites M27, M28, and M29 across clinothems in topsets, foresets (where the sequences are thickest), and bottomsets. A few sequences have coarse (∼1 m.y.) or little age constraint due to barren zones; we constrain the age estimates of these less well dated sequences by applying the principle of superposition, i.e., sediments above sequence boundaries in any site are younger than the sediments below the sequence boundaries at other sites. Our age control provides constraints on the timing of deposition in the clinothem; sequences on the topsets are generally the youngest in the clinothem, whereas the bottomsets generally are the oldest. The greatest amount of time is represented on foresets, although we have no evidence for a correlative conformity. Our chronology provides a baseline for regional and interregional correlations and sea-level reconstructions: (1) we correlate a major increase in sedimentation rate precisely with the timing of the middle Miocene climate changes associated with the development of a permanent East Antarctic Ice Sheet; and (2) the timing of sequence boundaries matches the deep-sea oxygen isotopic record, implicating glacioeustasy as a major driver for forming sequence boundaries.

Evaluation of nearest-neighbor methods for detection of chimeric small-subunit rRNA sequences

NASA Technical Reports Server (NTRS)

Robison-Cox, J. F.; Bateson, M. M.; Ward, D. M.

1995-01-01

Detection of chimeric artifacts formed when PCR is used to retrieve naturally occurring small-subunit (SSU) rRNA sequences may rely on demonstrating that different sequence domains have different phylogenetic affiliations. We evaluated the CHECK_CHIMERA method of the Ribosomal Database Project and another method which we developed, both based on determining nearest neighbors of different sequence domains, for their ability to discern artificially generated SSU rRNA chimeras from authentic Ribosomal Database Project sequences. The reliability of both methods decreases when the parental sequences which contribute to chimera formation are more than 82 to 84% similar. Detection is also complicated by the occurrence of authentic SSU rRNA sequences that behave like chimeras. We developed a naive statistical test based on CHECK_CHIMERA output and used it to evaluate previously reported SSU rRNA chimeras. Application of this test also suggests that chimeras might be formed by retrieving SSU rRNAs as cDNA. The amount of uncertainty associated with nearest-neighbor analyses indicates that such tests alone are insufficient and that better methods are needed.

A fault injection experiment using the AIRLAB Diagnostic Emulation Facility

NASA Technical Reports Server (NTRS)

Baker, Robert; Mangum, Scott; Scheper, Charlotte

1988-01-01

The preparation for, conduct of, and results of a simulation based fault injection experiment conducted using the AIRLAB Diagnostic Emulation facilities is described. An objective of this experiment was to determine the effectiveness of the diagnostic self-test sequences used to uncover latent faults in a logic network providing the key fault tolerance features for a flight control computer. Another objective was to develop methods, tools, and techniques for conducting the experiment. More than 1600 faults were injected into a logic gate level model of the Data Communicator/Interstage (C/I). For each fault injected, diagnostic self-test sequences consisting of over 300 test vectors were supplied to the C/I model as inputs. For each test vector within a test sequence, the outputs from the C/I model were compared to the outputs of a fault free C/I. If the outputs differed, the fault was considered detectable for the given test vector. These results were then analyzed to determine the effectiveness of some test sequences. The results established coverage of selt-test diagnostics, identified areas in the C/I logic where the tests did not locate faults, and suggest fault latency reduction opportunities.

Some Effects of Changes in Question Structure and Sequence on Performance in a Multiple Choice Chemistry Test.

ERIC Educational Resources Information Center

Hodson, D.

1984-01-01

Investigated the effect on student performance of changes in question structure and sequence on a GCE 0-level multiple-choice chemistry test. One finding noted is that there was virtually no change in test reliability on reducing the number of options (from five to per test item). (JN)

Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Performance Verification Report: Initial Comprehensive Performance Test Report, P/N 1331200-2-IT, S/N 105/A2

NASA Technical Reports Server (NTRS)

Platt, R.

1999-01-01

This is the Performance Verification Report, Initial Comprehensive Performance Test Report, P/N 1331200-2-IT, S/N 105/A2, for the Integrated Advanced Microwave Sounding Unit-A (AMSU-A). The specification establishes the requirements for the Comprehensive Performance Test (CPT) and Limited Performance Test (LPT) of the Advanced Microwave Sounding, Unit-A2 (AMSU-A2), referred to herein as the unit. The unit is defined on Drawing 1331200. 1.2 Test procedure sequence. The sequence in which the several phases of this test procedure shall take place is shown in Figure 1, but the sequence can be in any order.

Generalized functional linear models for gene-based case-control association studies.

PubMed

Fan, Ruzong; Wang, Yifan; Mills, James L; Carter, Tonia C; Lobach, Iryna; Wilson, Alexander F; Bailey-Wilson, Joan E; Weeks, Daniel E; Xiong, Momiao

2014-11-01

By using functional data analysis techniques, we developed generalized functional linear models for testing association between a dichotomous trait and multiple genetic variants in a genetic region while adjusting for covariates. Both fixed and mixed effect models are developed and compared. Extensive simulations show that Rao's efficient score tests of the fixed effect models are very conservative since they generate lower type I errors than nominal levels, and global tests of the mixed effect models generate accurate type I errors. Furthermore, we found that the Rao's efficient score test statistics of the fixed effect models have higher power than the sequence kernel association test (SKAT) and its optimal unified version (SKAT-O) in most cases when the causal variants are both rare and common. When the causal variants are all rare (i.e., minor allele frequencies less than 0.03), the Rao's efficient score test statistics and the global tests have similar or slightly lower power than SKAT and SKAT-O. In practice, it is not known whether rare variants or common variants in a gene region are disease related. All we can assume is that a combination of rare and common variants influences disease susceptibility. Thus, the improved performance of our models when the causal variants are both rare and common shows that the proposed models can be very useful in dissecting complex traits. We compare the performance of our methods with SKAT and SKAT-O on real neural tube defects and Hirschsprung's disease datasets. The Rao's efficient score test statistics and the global tests are more sensitive than SKAT and SKAT-O in the real data analysis. Our methods can be used in either gene-disease genome-wide/exome-wide association studies or candidate gene analyses. © 2014 WILEY PERIODICALS, INC.

Generalized Functional Linear Models for Gene-based Case-Control Association Studies

PubMed Central

Mills, James L.; Carter, Tonia C.; Lobach, Iryna; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Weeks, Daniel E.; Xiong, Momiao

2014-01-01

By using functional data analysis techniques, we developed generalized functional linear models for testing association between a dichotomous trait and multiple genetic variants in a genetic region while adjusting for covariates. Both fixed and mixed effect models are developed and compared. Extensive simulations show that Rao's efficient score tests of the fixed effect models are very conservative since they generate lower type I errors than nominal levels, and global tests of the mixed effect models generate accurate type I errors. Furthermore, we found that the Rao's efficient score test statistics of the fixed effect models have higher power than the sequence kernel association test (SKAT) and its optimal unified version (SKAT-O) in most cases when the causal variants are both rare and common. When the causal variants are all rare (i.e., minor allele frequencies less than 0.03), the Rao's efficient score test statistics and the global tests have similar or slightly lower power than SKAT and SKAT-O. In practice, it is not known whether rare variants or common variants in a gene are disease-related. All we can assume is that a combination of rare and common variants influences disease susceptibility. Thus, the improved performance of our models when the causal variants are both rare and common shows that the proposed models can be very useful in dissecting complex traits. We compare the performance of our methods with SKAT and SKAT-O on real neural tube defects and Hirschsprung's disease data sets. The Rao's efficient score test statistics and the global tests are more sensitive than SKAT and SKAT-O in the real data analysis. Our methods can be used in either gene-disease genome-wide/exome-wide association studies or candidate gene analyses. PMID:25203683

40 CFR 86.099-9 - Emission standards for 1999 and later model year light-duty trucks.

Code of Federal Regulations, 2012 CFR

2012-07-01

... § 86.130-96, diurnal plus hot soak measurements: 2.5 grams per test. (2) For the supplemental two-diurnal test sequence described in § 86.130-96, diurnal plus hot soak measurements: 3.0 grams per test. (B..., diurnal plus hot soak measurements: 2.0 grams per test. (2) For the supplemental two-diurnal test sequence...

40 CFR 86.099-9 - Emission standards for 1999 and later model year light-duty trucks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... § 86.130-96, diurnal plus hot soak measurements: 2.5 grams per test. (2) For the supplemental two-diurnal test sequence described in § 86.130-96, diurnal plus hot soak measurements: 3.0 grams per test. (B..., diurnal plus hot soak measurements: 2.0 grams per test. (2) For the supplemental two-diurnal test sequence...

Contrast-enhanced T1-weighted fluid-attenuated inversion-recovery BLADE magnetic resonance imaging of the brain: an alternative to spin-echo technique for detection of brain lesions in the unsedated pediatric patient?

PubMed

Alibek, Sedat; Adamietz, Boris; Cavallaro, Alexander; Stemmer, Alto; Anders, Katharina; Kramer, Manuel; Bautz, Werner; Staatz, Gundula

2008-08-01

We compared contrast-enhanced T1-weighted magnetic resonance (MR) imaging of the brain using different types of data acquisition techniques: periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER, BLADE) imaging versus standard k-space sampling (conventional spin-echo pulse sequence) in the unsedated pediatric patient with focus on artifact reduction, overall image quality, and lesion detectability. Forty-eight pediatric patients (aged 3 months to 18 years) were scanned with a clinical 1.5-T whole body MR scanner. Cross-sectional contrast-enhanced T1-weighted spin-echo sequence was compared to a T1-weighted dark-fluid fluid-attenuated inversion-recovery (FLAIR) BLADE sequence for qualitative and quantitative criteria (image artifacts, image quality, lesion detectability) by two experienced radiologists. Imaging protocols were matched for imaging parameters. Reader agreement was assessed using the exact Bowker test. BLADE images showed significantly less pulsation and motion artifacts than the standard T1-weighted spin-echo sequence scan. BLADE images showed statistically significant lower signal-to-noise ratio but higher contrast-to-noise ratios with superior gray-white matter contrast. All lesions were demonstrated on FLAIR BLADE imaging, and one false-positive lesion was visible in spin-echo sequence images. BLADE MR imaging at 1.5 T is applicable for central nervous system imaging of the unsedated pediatric patient, reduces motion and pulsation artifacts, and minimizes the need for sedation or general anesthesia without loss of relevant diagnostic information.

Hepatitis C infection among intravenous drug users attending therapy programs in Cyprus.

PubMed

Demetriou, Victoria L; van de Vijver, David A M C; Hezka, Johana; Kostrikis, Leondios G; Kostrikis, Leondios G

2010-02-01

The most high-risk population for HCV transmission worldwide today are intravenous drug users. HCV genotypes in the general population in Cyprus demonstrate a polyphyletic infection and include subtypes associated with intravenous drug users. The prevalence of HCV, HBV, and HIV infection, HCV genotypes and risk factors among intravenous drug users in Cyprus were investigated here for the first time. Blood samples and interviews were obtained from 40 consenting users in treatment centers, and were tested for HCV, HBV, and HIV antibodies. On the HCV-positive samples, viral RNA extraction, RT-PCR and sequencing were performed. Phylogenetic analysis determined subtype and any relationships with database sequences and statistical analysis determined any correlation of risk factors with HCV infection. The prevalence of HCV infection was 50%, but no HBV or HIV infections were found. Of the PCR-positive samples, eight (57%) were genotype 3a, and six (43%) were 1b. No other subtypes, recombinant strains or mixed infections were observed. The phylogenetic analysis of the injecting drug users' strains against database sequences observed no clustering, which does not allow determination of transmission route, possibly due to a limitation of sequences in the database. However, three clusters were discovered among the drug users' sequences, revealing small groups who possibly share injecting equipment. Statistical analysis showed the risk factor associated with HCV infection is drug use duration. Overall, the polyphyletic nature of HCV infection in Cyprus is confirmed, but the transmission route remains unknown. These findings highlight the need for harm-reduction strategies to reduce HCV transmission. (c) 2009 Wiley-Liss, Inc.

Preliminary Stratigraphic Basis for Geologic Mapping of Venus

NASA Technical Reports Server (NTRS)

Basilevsky, A. T.; Head, J. W.

1993-01-01

The age relations between geologic formations have been studied at 36 1000x1000 km areas centered at the dark paraboloid craters. The geologic setting in all these sites could be characterized using only 16 types of features and terrains (units). These units form a basic stratigraphic sequence (from older to younger: (1) Tessera (Tt); (2-3) Densely fractured terrains associated with coronae (COdf) and in the form of remnants among plains (Pdf); (4) Fractured and ridged plains (Pfr); (5) Plains with wrinkle ridges (Pwr); (6-7) Smooth and lobate plains (Ps/Pl); and (8) Rift-associated fractures (Fra). The stratigraphic position of the other units is determined by their relation with the units of the basic sequence: (9) Ridge bells (RB), contemporary with Pfr; (10-11) Ridges of coronae and arachnoids annuli (COar/Aar), contemporary with wrinkle ridges of Pwr; (12) Fractures of coronae annuli (COaf) disrupt Pwr and Ps/Pl; (13) Fractures (F) disrupt Pwr or younger units; (14) Craters with associated dark paraboloids (Cdp), which are on top of all volcanic and tectonic units except the youngest episodes of rift-associated fracturing and volcanism; (15-16) Surficial streaks (Ss) and surficial patches (Sp) are approximately contemporary with Cdp. These units may be used as a tentative basis for the geologic mapping of Venus including VMAP. This mapping should test the stratigraphy and answer the question of whether this stratigraphic sequence corresponds to geologic events which were generally synchronous all around the planet or whether the sequence is simply a typical sequence of events which occurred in different places at diffferent times.

Distribution of endogenous type B and type D sheep retrovirus sequences in ungulates and other mammals.

PubMed Central

Hecht, S J; Stedman, K E; Carlson, J O; DeMartini, J C

1996-01-01

The jaagsiekte sheep retrovirus (JSRV), which appears to be a type B/D retrovirus chimera, has been incriminated as the cause of ovine pulmonary carcinoma. Recent studies suggest that the sequences related to this virus are found in the genomes of normal sheep and goats. To learn whether there are breeds of sheep that lack the endogenous viral sequences and to study their distribution among other groups of mammals, we surveyed several domestic sheep and goat breeds, other ungulates, and various mammal groups for sequences related to JSRV. Probes prepared from the envelope (SU) region of JSRV and the capsid (CA) region of a Peruvian type D virus related to JSRV were used in Southern blot hybridization with genomic DNA followed by low- and high-stringency washes. Fifteen to 20 CA and SU bands were found in all members of the 13 breeds of domestic sheep and 6 breeds of goats tested. There were similar findings in 6 wild Ovis and Capra genera. Within 22 other genera of Bovidae including domestic cattle, and 7 other families of Artiodactyla including Cervidae, there were usually a few CA or SU bands at low stringency and rare bands at high stringency. Among 16 phylogenetically distant genera, there were generally fewer bands hybridizing with either probe. These results reveal wide-spread phylogenetic distribution of endogenous type B and type D retroviral sequences related to JSRV among mammals and argue for further investigation of their potential role in disease. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8622932

Evolution of Mhc-DRB introns: implications for the origin of primates.

PubMed

Kupfermann, H; Satta, Y; Takahata, N; Tichy, H; Klein, J

1999-06-01

Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions. Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian orders-Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my) of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta superorder, and to confirm the monophyly of the Chiroptera.

Whole transcriptome analysis of the poultry red mite Dermanyssus gallinae (De Geer, 1778).

PubMed

Schicht, Sabine; Qi, Weihong; Poveda, Lucy; Strube, Christina

2014-03-01

SUMMARY Although the poultry red mite Dermanyssus gallinae (De Geer, 1778) is the major parasitic pest in poultry farming causing substantial economic losses every year, nucleotide data are rare in the public databases. Therefore, de novo sequencing covering the transcriptome of D. gallinae was carried out resulting in a dataset of 232 097 singletons and 42 130 contiguous sequences (contigs) which were subsequently clustered into 24 140 isogroups consisting of 35 788 isotigs. After removal of sequences possibly originating from bacteria or the chicken host, 267 464 sequences (231 657 singletons, 56 contigs and 35 751 isotigs) remained, of which 10·3% showed homology to proteins derived from other organisms. The most significant Blast top-hit species was the mite Metaseiulus occidentalis followed by the tick Ixodes scapularis. To gain functional knowledge of D. gallinae transcripts, sequences were mapped to Gene Ontology terms, Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways and parsed to InterProScan. The transcriptome dataset provides new insights in general mite genetics and lays a foundation for future studies on stage-specific transcriptomics as well as genomic, proteomic, and metabolomic explorations and might provide new perspectives to control this parasitic mite by identifying possible drug targets or vaccine candidates. It is also worth noting that in different tested species of the class Arachnida no 28S rRNA was detectable in the rRNA profile, indicating that 28S rRNA might consists of two separate, hydrogen-bonded fragments, whose (heat-induced) disruption may led to co-migration with 18S rRNA.

Development and Verification of an RNA Sequencing (RNA-Seq) Assay for the Detection of Gene Fusions in Tumors.

PubMed

Winters, Jennifer L; Davila, Jaime I; McDonald, Amber M; Nair, Asha A; Fadra, Numrah; Wehrs, Rebecca N; Thomas, Brittany C; Balcom, Jessica R; Jin, Long; Wu, Xianglin; Voss, Jesse S; Klee, Eric W; Oliver, Gavin R; Graham, Rondell P; Neff, Jadee L; Rumilla, Kandelaria M; Aypar, Umut; Kipp, Benjamin R; Jenkins, Robert B; Jen, Jin; Halling, Kevin C

2018-06-13

We assessed the performance characteristics of an RNA sequencing (RNA-Seq) assay designed to detect gene fusions in 571 genes to help manage patients with cancer. Polyadenylated RNA was converted to cDNA, which was then used to prepare next-generation sequencing libraries that were sequenced on an Illumina HiSeq 2500 instrument and analyzed with an in-house developed bioinformatic pipeline. The assay identified 38 of 41 gene fusions detected by another method, such as fluorescence in situ hybridization or RT-PCR, for a sensitivity of 93%. No false-positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA sequencing or Mate Pair NGS (100% specificity). The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods. Eighteen of the 22 fusions had not previously been described. Good intra-assay and interassay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion-positive cases with fusion-negative RNA. Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. This assay can help identify fusions in patients with cancer; these patients may in turn benefit from both US Food and Drug Administration-approved and investigational targeted therapies. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Species classifier choice is a key consideration when analysing low-complexity food microbiome data.

PubMed

Walsh, Aaron M; Crispie, Fiona; O'Sullivan, Orla; Finnegan, Laura; Claesson, Marcus J; Cotter, Paul D

2018-03-20

The use of shotgun metagenomics to analyse low-complexity microbial communities in foods has the potential to be of considerable fundamental and applied value. However, there is currently no consensus with respect to choice of species classification tool, platform, or sequencing depth. Here, we benchmarked the performances of three high-throughput short-read sequencing platforms, the Illumina MiSeq, NextSeq 500, and Ion Proton, for shotgun metagenomics of food microbiota. Briefly, we sequenced six kefir DNA samples and a mock community DNA sample, the latter constructed by evenly mixing genomic DNA from 13 food-related bacterial species. A variety of bioinformatic tools were used to analyse the data generated, and the effects of sequencing depth on these analyses were tested by randomly subsampling reads. Compositional analysis results were consistent between the platforms at divergent sequencing depths. However, we observed pronounced differences in the predictions from species classification tools. Indeed, PERMANOVA indicated that there was no significant differences between the compositional results generated by the different sequencers (p = 0.693, R 2  = 0.011), but there was a significant difference between the results predicted by the species classifiers (p = 0.01, R 2  = 0.127). The relative abundances predicted by the classifiers, apart from MetaPhlAn2, were apparently biased by reference genome sizes. Additionally, we observed varying false-positive rates among the classifiers. MetaPhlAn2 had the lowest false-positive rate, whereas SLIMM had the greatest false-positive rate. Strain-level analysis results were also similar across platforms. Each platform correctly identified the strains present in the mock community, but accuracy was improved slightly with greater sequencing depth. Notably, PanPhlAn detected the dominant strains in each kefir sample above 500,000 reads per sample. Again, the outputs from functional profiling analysis using SUPER-FOCUS were generally accordant between the platforms at different sequencing depths. Finally, and expectedly, metagenome assembly completeness was significantly lower on the MiSeq than either on the NextSeq (p = 0.03) or the Proton (p = 0.011), and it improved with increased sequencing depth. Our results demonstrate a remarkable similarity in the results generated by the three sequencing platforms at different sequencing depths, and, in fact, the choice of bioinformatics methodology had a more evident impact on results than the choice of sequencer did.

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RATIONAL APPROXIMATIONS TO GENERALIZED HYPERGEOMETRIC FUNCTIONS.

DTIC Science & Technology

Under weak restrictions on the various free parameters, general theorems for rational representations of the generalized hypergeometric functions...and certain Meijer G-functions are developed. Upon specialization, these theorems yield a sequency of rational approximations which converge to the

Delay test generation for synchronous sequential circuits

NASA Astrophysics Data System (ADS)

Devadas, Srinivas

1989-05-01

We address the problem of generating tests for delay faults in non-scan synchronous sequential circuits. Delay test generation for sequential circuits is a considerably more difficult problem than delay testing of combinational circuits and has received much less attention. In this paper, we present a method for generating test sequences to detect delay faults in sequential circuits using the stuck-at fault sequential test generator STALLION. The method is complete in that it will generate a delay test sequence for a targeted fault given sufficient CPU time, if such a sequence exists. We term faults for which no delay test sequence exists, under out test methodology, sequentially delay redundant. We describe means of eliminating sequential delay redundancies in logic circuits. We present a partial-scan methodology for enhancing the testability of difficult-to-test of untestable sequential circuits, wherein a small number of flip-flops are selected and made controllable/observable. The selection process guarantees the elimination of all sequential delay redundancies. We show that an intimate relationship exists between state assignment and delay testability of a sequential machine. We describe a state assignment algorithm for the synthesis of sequential machines with maximal delay fault testability. Preliminary experimental results using the test generation, partial-scan and synthesis algorithm are presented.

Is maternal plasma DNA testing impacting serum-based screening for aneuploidy in the United States?

PubMed

Palomaki, Glenn E; Ashwood, Edward R; Best, Robert G; Lambert-Messerlian, Geralyn; Knight, George J

2015-11-01

We sought to determine whether tests for fetal aneuploidy based on next-generation sequencing of cell-free DNA in maternal circulation have had an impact on routine serum-based screening in the general pregnant population. We compared results from laboratory surveys in 2011 and 2014 that reported types of prenatal serum screening tests and numbers of tests performed. Testing records from two prenatal serum screening laboratories examined temporal trends in the proportion of screened women 35 years of age and older from 2008 (or 2009) to 2014. The 82 laboratory survey results available for comparison showed that 1.7 million women were screened in 2014, a 5% increase over 2011. In the two screening laboratories, the proportion of screened women age 35 and older increased for several years but then experienced reductions of 8 and 18% by mid-2014 when compared with the highest rates observed. As of 2014, maternal plasma DNA testing appears to have had only a minor impact on serum screening rates in the United States. Ongoing surveillance has the potential to determine if, and when, DNA testing begins to replace serum testing as a primary screen for Down syndrome in the United States.

Buckling Test Results from the 8-Foot-Diameter Orthogrid-Stiffened Cylinder Test Article TA01. [Test Dates: 19-21 November 2008

NASA Technical Reports Server (NTRS)

Hilburger, Mark W.; Waters, W. Allen, Jr.; Haynie, Waddy T.

2015-01-01

Results from the testing of cylinder test article SBKF-P2-CYLTA01 (referred to herein as TA01) are presented. The testing was conducted at the Marshall Space Flight Center (MSFC), November 19?21, 2008, in support of the Shell Buckling Knockdown Factor (SBKF) Project.i The test was used to verify the performance of a newly constructed buckling test facility at MSFC and to verify the test article design and analysis approach used by the SBKF project researchers. TA01 is an 8-foot-diameter (96-inches), 78.0-inch long, aluminum-lithium (Al-Li), orthogrid-stiffened cylindrical shell similar to those used in current state-of-the-art launch vehicle structures and was designed to exhibit global buckling when subjected to compression loads. Five different load sequences were applied to TA01 during testing and included four sub-critical load sequences, i.e., loading conditions that did not cause buckling or material failure, and one final load sequence to buckling and collapse. The sub-critical load sequences consisted of either uniform axial compression loading or combined axial compression and bending and the final load sequence subjected TA01 to uniform axial compression. Traditional displacement transducers and strain gages were used to monitor the test article response at nearly 300 locations and an advanced digital image correlation system was used to obtain low-speed and high-speed full-field displacement measurements of the outer surface of the test article. Overall, the test facility and test article performed as designed. In particular, the test facility successfully applied all desired load combinations to the test article and was able to test safely into the postbuckling range of loading, and the test article failed by global buckling. In addition, the test results correlated well with initial pretest predictions.

Alignment-free sequence comparison (II): theoretical power of comparison statistics.

PubMed

Wan, Lin; Reinert, Gesine; Sun, Fengzhu; Waterman, Michael S

2010-11-01

Rapid methods for alignment-free sequence comparison make large-scale comparisons between sequences increasingly feasible. Here we study the power of the statistic D2, which counts the number of matching k-tuples between two sequences, as well as D2*, which uses centralized counts, and D2S, which is a self-standardized version, both from a theoretical viewpoint and numerically, providing an easy to use program. The power is assessed under two alternative hidden Markov models; the first one assumes that the two sequences share a common motif, whereas the second model is a pattern transfer model; the null model is that the two sequences are composed of independent and identically distributed letters and they are independent. Under the first alternative model, the means of the tuple counts in the individual sequences change, whereas under the second alternative model, the marginal means are the same as under the null model. Using the limit distributions of the count statistics under the null and the alternative models, we find that generally, asymptotically D2S has the largest power, followed by D2*, whereas the power of D2 can even be zero in some cases. In contrast, even for sequences of length 140,000 bp, in simulations D2* generally has the largest power. Under the first alternative model of a shared motif, the power of D2*approaches 100% when sufficiently many motifs are shared, and we recommend the use of D2* for such practical applications. Under the second alternative model of pattern transfer,the power for all three count statistics does not increase with sequence length when the sequence is sufficiently long, and hence none of the three statistics under consideration canbe recommended in such a situation. We illustrate the approach on 323 transcription factor binding motifs with length at most 10 from JASPAR CORE (October 12, 2009 version),verifying that D2* is generally more powerful than D2. The program to calculate the power of D2, D2* and D2S can be downloaded from http://meta.cmb.usc.edu/d2. Supplementary Material is available at www.liebertonline.com/cmb.

Novel Rickettsia raoultii strain isolated and propagated from Austrian Dermacentor reticulatus ticks.

PubMed

Wijnveld, Michiel; Schötta, Anna-Margarita; Pintér, Adriano; Stockinger, Hannes; Stanek, Gerold

2016-11-03

Continuous culture of tick cell lines has proven a valuable asset in isolating and propagating several different vector-borne pathogens, making it possible to study these microorganisms under laboratory conditions and develop serological tests to benefit public health. We describe a method for effective, cost- and labor-efficient isolation and propagation of Rickettsia raoultii using generally available laboratory equipment and Rhipicephalus microplus cells, further demonstrating the usefulness of continuous tick cell lines. R. raoultii is one of the causative agents of tick-borne lymphadenopathy (TIBOLA) and is, together with its vector Dermacentor reticulatus, emerging in novel regions of Europe, giving rise to an increased threat to general public health. Dermacentor reticulatus ticks were collected in the Donau-Auen (Lobau) national park in Vienna, Austria. The hemolymph of ten collected ticks was screened by PCR-reverse line blot for the presence of rickettsial DNA. A single tick tested positive for R. raoultii DNA and was used to infect Rhipicephalus microplus BME/CTVM2 cells. Sixty-five days after infection of the tick-cell line with an extract from a R. raoultii-infected tick, we observed intracellular bacteria in the cultured cells. On the basis of microscopy we suspected that the intracellular bacteria were a species of Rickettsia; this was confirmed by several PCRs targeting different genes. Subsequent sequencing showed 99-100 % identity with R. raoultii. Cryopreservation and resuscitation of R. raoultii was successful. After 28 days identical intracellular bacteria were microscopically observed. R. raoultii was successfully isolated and propagated from D. reticulatus ticks using R. microplus BME/CTVM2 cells. The isolated strain shows significant molecular variation compared to currently known sequences. Furthermore we show for the first time the successful cryopreservation and resuscitation of R. raoultii.

Benchmarking protein classification algorithms via supervised cross-validation.

PubMed

Kertész-Farkas, Attila; Dhir, Somdutta; Sonego, Paolo; Pacurar, Mircea; Netoteia, Sergiu; Nijveen, Harm; Kuzniar, Arnold; Leunissen, Jack A M; Kocsor, András; Pongor, Sándor

2008-04-24

Development and testing of protein classification algorithms are hampered by the fact that the protein universe is characterized by groups vastly different in the number of members, in average protein size, similarity within group, etc. Datasets based on traditional cross-validation (k-fold, leave-one-out, etc.) may not give reliable estimates on how an algorithm will generalize to novel, distantly related subtypes of the known protein classes. Supervised cross-validation, i.e., selection of test and train sets according to the known subtypes within a database has been successfully used earlier in conjunction with the SCOP database. Our goal was to extend this principle to other databases and to design standardized benchmark datasets for protein classification. Hierarchical classification trees of protein categories provide a simple and general framework for designing supervised cross-validation strategies for protein classification. Benchmark datasets can be designed at various levels of the concept hierarchy using a simple graph-theoretic distance. A combination of supervised and random sampling was selected to construct reduced size model datasets, suitable for algorithm comparison. Over 3000 new classification tasks were added to our recently established protein classification benchmark collection that currently includes protein sequence (including protein domains and entire proteins), protein structure and reading frame DNA sequence data. We carried out an extensive evaluation based on various machine-learning algorithms such as nearest neighbor, support vector machines, artificial neural networks, random forests and logistic regression, used in conjunction with comparison algorithms, BLAST, Smith-Waterman, Needleman-Wunsch, as well as 3D comparison methods DALI and PRIDE. The resulting datasets provide lower, and in our opinion more realistic estimates of the classifier performance than do random cross-validation schemes. A combination of supervised and random sampling was used to construct model datasets, suitable for algorithm comparison.

Setting up a probe based, closed tube real-time PCR assay for focused detection of variable sequence alterations.

PubMed

Becságh, Péter; Szakács, Orsolya

2014-10-01

During diagnostic workflow when detecting sequence alterations, sometimes it is important to design an algorithm that includes screening and direct tests in combination. Normally the use of direct test, which is mainly sequencing, is limited. There is an increased need for effective screening tests, with "closed tube" during the whole process and therefore decreasing the risk of PCR product contamination. The aim of this study was to design such a closed tube, detection probe based screening assay to detect different kind of sequence alterations in the exon 11 of the human c-kit gene region. Inside this region there are variable possible deletions and single nucleotide changes. During assay setup, more probe chemistry formats were screened and tested. After some optimization steps the taqman probe format was selected.

Short- and Long-Term Earthquake Forecasts Based on Statistical Models

NASA Astrophysics Data System (ADS)

Console, Rodolfo; Taroni, Matteo; Murru, Maura; Falcone, Giuseppe; Marzocchi, Warner

2017-04-01

The epidemic-type aftershock sequences (ETAS) models have been experimentally used to forecast the space-time earthquake occurrence rate during the sequence that followed the 2009 L'Aquila earthquake and for the 2012 Emilia earthquake sequence. These forecasts represented the two first pioneering attempts to check the feasibility of providing operational earthquake forecasting (OEF) in Italy. After the 2009 L'Aquila earthquake the Italian Department of Civil Protection nominated an International Commission on Earthquake Forecasting (ICEF) for the development of the first official OEF in Italy that was implemented for testing purposes by the newly established "Centro di Pericolosità Sismica" (CPS, the seismic Hazard Center) at the Istituto Nazionale di Geofisica e Vulcanologia (INGV). According to the ICEF guidelines, the system is open, transparent, reproducible and testable. The scientific information delivered by OEF-Italy is shaped in different formats according to the interested stakeholders, such as scientists, national and regional authorities, and the general public. The communication to people is certainly the most challenging issue, and careful pilot tests are necessary to check the effectiveness of the communication strategy, before opening the information to the public. With regard to long-term time-dependent earthquake forecast, the application of a newly developed simulation algorithm to Calabria region provided typical features in time, space and magnitude behaviour of the seismicity, which can be compared with those of the real observations. These features include long-term pseudo-periodicity and clustering of strong earthquakes, and a realistic earthquake magnitude distribution departing from the Gutenberg-Richter distribution in the moderate and higher magnitude range.

Effect of multimedia information sequencing on educational outcome in orthodontic training.

PubMed

Aly, Medhat; Willems, Guy; Van Den Noortgate, Wim; Elen, Jan

2012-08-01

The aim of this research was to compare the effectiveness of hierarchical sequencing (HS) versus elaboration sequencing (ES) models in improving educational outcome of clinical knowledge when using instructional multimedia programs in postgraduate orthodontic training. Twenty-four postgraduate and 24 undergraduate dental students participated in this study. The postgraduates were following an orthodontic speciality training programme. The undergraduates were fourth- and fifth-year dental students. Twelve instructional multimedia modules were developed, six logically sequenced (LS) discussing six different orthodontic topics. Another six modules on identical topics were sequenced according to one macro-sequencing (MS) model. The implemented MS model was either HS or ES. The only difference between LS and MS modules was the adopted sequencing model. All participants were assigned into consistent pairs of students and were randomly divided into a test and a control group. In each pair, one student studied the LS module (control group) while the other studied the MS version (test group). Pre- and post-evaluation tests of each pair of participants were performed to measure knowledge, understanding and application of each participant with regard to the discussed topic. A multilevel analysis was conducted to assess the estimated effect of the different sequencing models. The level of significance was set at 0.05. At baseline, no significant differences (P > 0.05) were found in pre-test scores between groups. The HS model showed a significant effect on the scores achieved (P = 0.05). The test group showed a significantly higher estimated probability of correct answers to the questions (P = 0.003) when applying the HS model. The HS model may improve educational outcome when using instructional multimedia programs in postgraduate orthodontic training.

The impact of cerebellar transcranial direct current stimulation (tDCS) on learning fine-motor sequences

PubMed Central

Wu, Allan D.; Samra, Jasmine K.

2017-01-01

The cerebellum has been shown to be important for skill learning, including the learning of motor sequences. We investigated whether cerebellar transcranial direct current stimulation (tDCS) would enhance learning of fine motor sequences. Because the ability to generalize or transfer to novel task variations or circumstances is a crucial goal of real world training, we also examined the effect of tDCS on performance of novel sequences after training. In Study 1, participants received either anodal, cathodal or sham stimulation while simultaneously practising three eight-element key press sequences in a non-repeating, interleaved order. Immediately after sequence practice with concurrent tDCS, a transfer session was given in which participants practised three interleaved novel sequences. No stimulation was given during transfer. An inhibitory effect of cathodal tDCS was found during practice, such that the rate of learning was slowed in comparison to the anodal and sham groups. In Study 2, participants received anodal or sham stimulation and a 24 h delay was added between the practice and transfer sessions to reduce mental fatigue. Although this consolidation period benefitted subsequent transfer for both tDCS groups, anodal tDCS enhanced transfer performance. Together, these studies demonstrate polarity-specific effects on fine motor sequence learning and generalization. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’. PMID:27872369

The impact of cerebellar transcranial direct current stimulation (tDCS) on learning fine-motor sequences.

PubMed

Shimizu, Renee E; Wu, Allan D; Samra, Jasmine K; Knowlton, Barbara J

2017-01-05

The cerebellum has been shown to be important for skill learning, including the learning of motor sequences. We investigated whether cerebellar transcranial direct current stimulation (tDCS) would enhance learning of fine motor sequences. Because the ability to generalize or transfer to novel task variations or circumstances is a crucial goal of real world training, we also examined the effect of tDCS on performance of novel sequences after training. In Study 1, participants received either anodal, cathodal or sham stimulation while simultaneously practising three eight-element key press sequences in a non-repeating, interleaved order. Immediately after sequence practice with concurrent tDCS, a transfer session was given in which participants practised three interleaved novel sequences. No stimulation was given during transfer. An inhibitory effect of cathodal tDCS was found during practice, such that the rate of learning was slowed in comparison to the anodal and sham groups. In Study 2, participants received anodal or sham stimulation and a 24 h delay was added between the practice and transfer sessions to reduce mental fatigue. Although this consolidation period benefitted subsequent transfer for both tDCS groups, anodal tDCS enhanced transfer performance. Together, these studies demonstrate polarity-specific effects on fine motor sequence learning and generalization.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

77 FR 10665 - General Services Administration Acquisition Regulation; Acquisition-Related Thresholds

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... GENERAL SERVICES ADMINISTRATION 48 CFR Parts 519 and 552 [GSAR Amendment 2012-02; GSAR Case 2011-G502; (Change 54) Docket 2012- 0003, Sequence 1] RIN 3090-AJ24 General Services Administration Acquisition Regulation; Acquisition-Related Thresholds AGENCIES: Office of Acquisition Policy, General...

76 FR 5375 - Public Availability of General Services Administration FY 2010 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-31

... GENERAL SERVICES ADMINISTRATION [2011-MV-1; Docket No. 2011-0006; Sequence 4] Public Availability of General Services Administration FY 2010 Service Contract Inventory AGENCY: Office of Acquisition Policy; General Services Administration (GSA). ACTION: Notice. SUMMARY: This notice announces that GSA is...

77 FR 5253 - Public Availability of General Services Administration FY 2011 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-02

... GENERAL SERVICES ADMINISTRATION [Notice-MV-2012-01; Docket 2012-0002; Sequence 3] Public Availability of General Services Administration FY 2011 Service Contract Inventory AGENCY: Office of Acquisition Policy (MV); General Services Administration (GSA). ACTION: Notice of public availability of FY...

77 FR 54917 - Public Availability of General Services Administration FY 2012 Federal Activities Inventory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... GENERAL SERVICES ADMINISTRATION [Notice-MV-2012-02; Docket No. 2012-0002; Sequence 14] Public Availability of General Services Administration FY 2012 Federal Activities Inventory Reform (FAIR) Act Inventory AGENCY: General Services Administration (GSA). ACTION: Notice of Public Availability of Fiscal...

Bioinformatic Analysis of the Contribution of Primer Sequences to Aptamer Structures

PubMed Central

Ellington, Andrew D.

2009-01-01

Aptamers are nucleic acid molecules selected in vitro to bind a particular ligand. While numerous experimental studies have examined the sequences, structures, and functions of individual aptamers, considerably fewer studies have applied bioinformatics approaches to try to infer more general principles from these individual studies. We have used a large Aptamer Database to parse the contributions of both random and constant regions to the secondary structures of more than 2000 aptamers. We find that the constant, primer-binding regions do not, in general, contribute significantly to aptamer structures. These results suggest that (a) binding function is not contributed to nor constrained by constant regions; (b) in consequence, the landscape of functional binding sequences is sparse but robust, favoring scenarios for short, functional nucleic acid sequences near origins; and (c) many pool designs for the selection of aptamers are likely to prove robust. PMID:18594898

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.

Direct sequencing of hepatitis A virus and norovirus RT-PCR products from environmentally contaminated oyster using M13-tailed primers.

PubMed

Williams-Woods, Jacquelina; González-Escalona, Narjol; Burkhardt, William

2011-12-01

Human norovirus (HuNoV) and hepatitis A (HAV) are recognized as leading causes of non-bacterial foodborne associated illnesses in the United States. DNA sequencing is generally considered the standard for accurate viral genotyping in support of epidemiological investigations. Due to the genetic diversity of noroviruses (NoV), degenerate primer sets are often used in conventional reverse transcription (RT) PCR and real-time RT-quantitative PCR (RT-qPCR) for the detection of these viruses and cDNA fragments are generally cloned prior to sequencing. HAV detection methods that are sensitive and specific for real-time RT-qPCR yields small fragments sizes of 89-150bp, which can be difficult to sequence. In order to overcome these obstacles, norovirus and HAV primers were tailed with M13 forward and reverse primers. This modification increases the sequenced product size and allows for direct sequencing of the amplicons utilizing complementary M13 primers. HuNoV and HAV cDNA products from environmentally contaminated oysters were analyzed using this method. Alignments of the sequenced samples revealed ≥95% nucleotide identities. Tailing NoV and HAV primers with M13 sequence increases the cDNA product size, offers an alternative to cloning, and allows for rapid, accurate and direct sequencing of cDNA products produced by conventional or real time RT-qPCR assays. Published by Elsevier B.V.

Visualizing and Clustering Protein Similarity Networks: Sequences, Structures, and Functions.

PubMed

Mai, Te-Lun; Hu, Geng-Ming; Chen, Chi-Ming

2016-07-01

Research in the recent decade has demonstrated the usefulness of protein network knowledge in furthering the study of molecular evolution of proteins, understanding the robustness of cells to perturbation, and annotating new protein functions. In this study, we aimed to provide a general clustering approach to visualize the sequence-structure-function relationship of protein networks, and investigate possible causes for inconsistency in the protein classifications based on sequences, structures, and functions. Such visualization of protein networks could facilitate our understanding of the overall relationship among proteins and help researchers comprehend various protein databases. As a demonstration, we clustered 1437 enzymes by their sequences and structures using the minimum span clustering (MSC) method. The general structure of this protein network was delineated at two clustering resolutions, and the second level MSC clustering was found to be highly similar to existing enzyme classifications. The clustering of these enzymes based on sequence, structure, and function information is consistent with each other. For proteases, the Jaccard's similarity coefficient is 0.86 between sequence and function classifications, 0.82 between sequence and structure classifications, and 0.78 between structure and function classifications. From our clustering results, we discussed possible examples of divergent evolution and convergent evolution of enzymes. Our clustering approach provides a panoramic view of the sequence-structure-function network of proteins, helps visualize the relation between related proteins intuitively, and is useful in predicting the structure and function of newly determined protein sequences.

Mojibake - The rehearsal of word fragments in verbal recall.

PubMed

Lange-Küttner, Christiane; Sykorova, Eva

2015-01-01

Theories of verbal rehearsal usually assume that whole words are being rehearsed. However, words consist of letter sequences, or syllables, or word onset-vowel-coda, amongst many other conceptualizations of word structure. A more general term is the 'grain size' of word units (Ziegler and Goswami, 2005). In the current study, a new method measured the quantitative percentage of correctly remembered word structure. The amount of letters in the correct letter sequence as per cent of word length was calculated, disregarding missing or added letters. A forced rehearsal was tested by repeating each memory list four times. We tested low frequency (LF) English words versus geographical (UK) town names to control for content. We also tested unfamiliar international (INT) non-words and names of international (INT) European towns to control for familiarity. An immediate versus distributed repetition was tested with a between-subject design. Participants responded with word fragments in their written recall especially when they had to remember unfamiliar words. While memory of whole words was sensitive to content, presentation distribution and individual sex and language differences, recall of word fragments was not. There was no trade-off between memory of word fragments with whole word recall during the repetition, instead also word fragments significantly increased. Moreover, while whole word responses correlated with each other during repetition, and word fragment responses correlated with each other during repetition, these two types of word recall responses were not correlated with each other. Thus there may be a lower layer consisting of free, sparse word fragments and an upper layer that consists of language-specific, orthographically and semantically constrained words.

Model for calculation of electrostatic contribution into protein stability

NASA Astrophysics Data System (ADS)

Kundrotas, Petras; Karshikoff, Andrey

2003-03-01

Existing models of the denatured state of proteins consider only one possible spatial distribution of protein charges and therefore are applicable to a limited number of cases. In this presentation a more general framework for the modeling of the denatured state is proposed. It is based on the assumption that the titratable groups of an unfolded protein can adopt a quasi-random distribution, restricted by the protein sequence. The model was tested on two proteins, barnase and N-terminal domain of the ribosomal protein L9. The calculated free energy of denaturation, Δ G( pH), reproduces the experimental data essentially better than the commonly used null approximation (NA). It was demonstrated that the seemingly good agreement with experimental data obtained by NA originates from the compensatory effect between the pair-wise electrostatic interactions and the desolvation energy of the individual sites. It was also found that the ionization properties of denatured proteins are influenced by the protein sequence.

Individual differences in adult foreign language learning: the mediating effect of metalinguistic awareness.

PubMed

Brooks, Patricia J; Kempe, Vera

2013-02-01

In this study, we sought to identify cognitive predictors of individual differences in adult foreign-language learning and to test whether metalinguistic awareness mediated the observed relationships. Using a miniature language-learning paradigm, adults (N = 77) learned Russian vocabulary and grammar (gender agreement and case marking) over six 1-h sessions, completing tasks that encouraged attention to phrases without explicitly teaching grammatical rules. The participants' ability to describe the Russian gender and case-marking patterns mediated the effects of nonverbal intelligence and auditory sequence learning on grammar learning and generalization. Hence, even under implicit-learning conditions, individual differences stemmed from explicit metalinguistic awareness of the underlying grammar, which, in turn, was linked to nonverbal intelligence and auditory sequence learning. Prior knowledge of languages with grammatical gender (predominantly Spanish) predicted learning of gender agreement. Transfer of knowledge of gender from other languages to Russian was not mediated by awareness, which suggests that transfer operates through an implicit process akin to structural priming.

Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields.

PubMed

Wang, Sheng; Peng, Jian; Ma, Jianzhu; Xu, Jinbo

2016-01-11

Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.

Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields

NASA Astrophysics Data System (ADS)

Wang, Sheng; Peng, Jian; Ma, Jianzhu; Xu, Jinbo

2016-01-01

Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.

Energy efficiency trade-offs drive nucleotide usage in transcribed regions

PubMed Central

Chen, Wei-Hua; Lu, Guanting; Bork, Peer; Hu, Songnian; Lercher, Martin J.

2016-01-01

Efficient nutrient usage is a trait under universal selection. A substantial part of cellular resources is spent on making nucleotides. We thus expect preferential use of cheaper nucleotides especially in transcribed sequences, which are often amplified thousand-fold compared with genomic sequences. To test this hypothesis, we derive a mutation-selection-drift equilibrium model for nucleotide skews (strand-specific usage of ‘A' versus ‘T' and ‘G' versus ‘C'), which explains nucleotide skews across 1,550 prokaryotic genomes as a consequence of selection on efficient resource usage. Transcription-related selection generally favours the cheaper nucleotides ‘U' and ‘C' at synonymous sites. However, the information encoded in mRNA is further amplified through translation. Due to unexpected trade-offs in the codon table, cheaper nucleotides encode on average energetically more expensive amino acids. These trade-offs apply to both strand-specific nucleotide usage and GC content, causing a universal bias towards the more expensive nucleotides ‘A' and ‘G' at non-synonymous coding sites. PMID:27098217

Dual gait generative models for human motion estimation from a single camera.

PubMed

Zhang, Xin; Fan, Guoliang

2010-08-01

This paper presents a general gait representation framework for video-based human motion estimation. Specifically, we want to estimate the kinematics of an unknown gait from image sequences taken by a single camera. This approach involves two generative models, called the kinematic gait generative model (KGGM) and the visual gait generative model (VGGM), which represent the kinematics and appearances of a gait by a few latent variables, respectively. The concept of gait manifold is proposed to capture the gait variability among different individuals by which KGGM and VGGM can be integrated together, so that a new gait with unknown kinematics can be inferred from gait appearances via KGGM and VGGM. Moreover, a new particle-filtering algorithm is proposed for dynamic gait estimation, which is embedded with a segmental jump-diffusion Markov Chain Monte Carlo scheme to accommodate the gait variability in a long observed sequence. The proposed algorithm is trained from the Carnegie Mellon University (CMU) Mocap data and tested on the Brown University HumanEva data with promising results.

Diving into marine genomics with CRISPR/Cas9 systems.

PubMed

Momose, Tsuyoshi; Concordet, Jean-Paul

2016-12-01

More and more genomes are sequenced and a great range of biological questions can be examined at the genomic level in a growing number of organisms. Testing the function of genome features, from gene networks, genome organization, conserved non-coding sequences to microRNAs, and, more generally, experimentally addressing the genotype-phenotype relationship is now possible owing to the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 revolution of genome editing. In the present review, we give a brief overview of the CRISPR/Cas9 toolbox and different strategies for genome editing currently available. We list the first examples of applications to marine organisms and also draw from studies in more common laboratory models to suggest both guidelines for design of genome editing experiments as well as discuss challenges specific to marine organisms. In addition, we discuss future perspectives, including applications of CRISPR/Cas9 to base editing and targeted reprogramming of gene transcription. Copyright © 2016 Elsevier B.V. All rights reserved.

Isolation, antimicrobial activities, and primary structures of hamster neutrophil defensins.

PubMed Central

Mak, P; Wójcik, K; Thogersen, I B; Dubin, A

1996-01-01

Hamster (Mesocricetus auratus) neutrophil granules contain at least four microbicidal peptides belonging to the defensin family. These compounds were purified from granule acid extracts by reverse-phase chromatography and termed HaNP-1 to -4 (hamster neutrophil peptide). HaNP-1 and HaNP-3 revealed the most bactericidal activity, with a 50% inhibitory concentration of 0.3 to 0.8 microg/ml for Staphylococcus aureus and Streptococcus pyogenes strains. The HaNP-4 was always isolated in concentrations exceeding about 10 times the concentrations of other hamster peptides, but its antibacterial activity as well as that of HaNP-2 was relatively lower, probably as a result of conserved Arg residue substitutions. Other microorganisms were also tested, and generally, hamster defensins exhibited less potency against gram-negative bacteria. The amino acid sequence of hamster defensins showed a high percentage of identity to the sequence of mouse enteric defensins, reaching about 60% identical residues in the case of HaNP-3 and cryptdin 3. PMID:8890190

Predicting nuclear gene coalescence from mitochondrial data: the three-times rule.

PubMed

Palumbi, S R; Cipriano, F; Hare, M P

2001-05-01

Coalescence theory predicts when genetic drift at nuclear loci will result in fixation of sequence differences to produce monophyletic gene trees. However, the theory is difficult to apply to particular taxa because it hinges on genetically effective population size, which is generally unknown. Neutral theory also predicts that evolution of monophyly will be four times slower in nuclear than in mitochondrial genes primarily because genetic drift is slower at nuclear loci. Variation in mitochondrial DNA (mtDNA) within and between species has been studied extensively, but can these mtDNA data be used to predict coalescence in nuclear loci? Comparison of neutral theories of coalescence of mitochondrial and nuclear loci suggests a simple rule of thumb. The "three-times rule" states that, on average, most nuclear loci will be monophyletic when the branch length leading to the mtDNA sequences of a species is three times longer than the average mtDNA sequence diversity observed within that species. A test using mitochondrial and nuclear intron data from seven species of whales and dolphins suggests general agreement with predictions of the three-times rule. We define the coalescence ratio as the mitochondrial branch length for a species divided by intraspecific mtDNA diversity. We show that species with high coalescence ratios show nuclear monophyly, whereas species with low ratios have polyphyletic nuclear gene trees. As expected, species with intermediate coalescence ratios show a variety of patterns. Especially at very high or low coalescence ratios, the three-times rule predicts nuclear gene patterns that can help detect the action of selection. The three-times rule may be useful as an empirical benchmark for evaluating evolutionary processes occurring at multiple loci.

Harnessing the sorghum genome sequence:development of a genome-wide microsattelite (SSR) resource for swift genetic mapping and map based cloning in sorghum

USDA-ARS?s Scientific Manuscript database

Sorghum is the second cereal crop to have a full genome completely sequenced (Nature (2009), 457:551). This achievement is widely recognized as a scientific milestone for grass genetics and genomics in general. However, the true worth of genetic information lies in translating the sequence informa...

Generalized statistical convergence of order β for sequences of fuzzy numbers

NASA Astrophysics Data System (ADS)

Altınok, Hıfsı; Karakaş, Abdulkadir; Altın, Yavuz

2018-01-01

In the present paper, we introduce the concepts of Δm-statistical convergence of order β for sequences of fuzzy numbers and strongly Δm-summable of order β for sequences of fuzzy numbers by using a modulus function f and taking supremum on metric d for 0 < β ≤ 1 and give some inclusion relations between them.

Armillaria phylogeny based on tef-1α sequences suggests ongoing divergent speciation within the boreal floristic kingdom

Treesearch

Ned B. Klopfenstein; John W. Hanna; Amy L. Ross-Davis; Jane E. Stewart; Yuko Ota; Rosario Medel-Ortiz; Miguel Armando Lopez-Ramirez; Ruben Damian Elias-Roman; Dionicio Alvarado-Rosales; Mee-Sook Kim

2013-01-01

Armillaria plays diverse ecological roles in forests worldwide, which has inspired interest in understanding phylogenetic relationships within and among species of this genus. Previous rDNA sequence-based phylogenetic analyses of Armillaria have shown general relationships among widely divergent taxa, but rDNA sequences were not reliable for separating closely related...

Application of Cydia pomonella expressed sequence tags: identification and expression of three general odorant binding proteins in codling moth

USDA-ARS?s Scientific Manuscript database

The codling moth, Cydia pomonella, is one of the most important pests of pome fruits in the world, yet the molecular genetics and physiology of this insect remains poorly understood. A combined assembly of 8340 expressed sequence tags (ESTs) was generated from Roche 454 GS-FLX sequencing of 8 tissu...

Evaluation and validation of de novo and hybrid assembly techniques to derive high quality genome sequences

DOE PAGES

Utturkar, Sagar M.; Klingeman, Dawn Marie; Land, Miriam L.; ...

2014-06-14

Our motivation with this work was to assess the potential of different types of sequence data combined with de novo and hybrid assembly approaches to improve existing draft genome sequences. Our results show Illumina, 454 and PacBio sequencing technologies were used to generate de novo and hybrid genome assemblies for four different bacteria, which were assessed for quality using summary statistics (e.g. number of contigs, N50) and in silico evaluation tools. Differences in predictions of multiple copies of rDNA operons for each respective bacterium were evaluated by PCR and Sanger sequencing, and then the validated results were applied as anmore » additional criterion to rank assemblies. In general, assemblies using longer PacBio reads were better able to resolve repetitive regions. In this study, the combination of Illumina and PacBio sequence data assembled through the ALLPATHS-LG algorithm gave the best summary statistics and most accurate rDNA operon number predictions. This study will aid others looking to improve existing draft genome assemblies. As to availability and implementation–all assembly tools except CLC Genomics Workbench are freely available under GNU General Public License.« less

Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.

PubMed

Yao, H; Jiang, F; Hu, H; Gao, Y; Zhu, Z; Zhang, H; Wang, Y; Guo, Y; Liu, L; Yuan, Y; Zhou, L; Wang, J; Du, B; Qu, N; Zhang, R; Dong, Y; Xu, H; Chen, F; Jiang, H; Liu, Y; Zhang, L; Tian, Z; Liu, Q; Zhang, C; Pan, X; Yang, S; Zhao, L; Wang, W; Liang, Z

2014-07-01

To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Evolutionary Dynamics of Microsatellite Distribution in Plants: Insight from the Comparison of Sequenced Brassica, Arabidopsis and Other Angiosperm Species

PubMed Central

Shi, Jiaqin; Huang, Shunmou; Fu, Donghui; Yu, Jinyin; Wang, Xinfa; Hua, Wei; Liu, Shengyi; Liu, Guihua; Wang, Hanzhong

2013-01-01

Despite their ubiquity and functional importance, microsatellites have been largely ignored in comparative genomics, mostly due to the lack of genomic information. In the current study, microsatellite distribution was characterized and compared in the whole genomes and both the coding and non-coding DNA sequences of the sequenced Brassica, Arabidopsis and other angiosperm species to investigate their evolutionary dynamics in plants. The variation in the microsatellite frequencies of these angiosperm species was much smaller than those for their microsatellite numbers and genome sizes, suggesting that microsatellite frequency may be relatively stable in plants. The microsatellite frequencies of these angiosperm species were significantly negatively correlated with both their genome sizes and transposable elements contents. The pattern of microsatellite distribution may differ according to the different genomic regions (such as coding and non-coding sequences). The observed differences in many important microsatellite characteristics (especially the distribution with respect to motif length, type and repeat number) of these angiosperm species were generally accordant with their phylogenetic distance, which suggested that the evolutionary dynamics of microsatellite distribution may be generally consistent with plant divergence/evolution. Importantly, by comparing these microsatellite characteristics (especially the distribution with respect to motif type) the angiosperm species (aside from a few species) all clustered into two obviously different groups that were largely represented by monocots and dicots, suggesting a complex and generally dichotomous evolutionary pattern of microsatellite distribution in angiosperms. Polyploidy may lead to a slight increase in microsatellite frequency in the coding sequences and a significant decrease in microsatellite frequency in the whole genome/non-coding sequences, but have little effect on the microsatellite distribution with respect to motif length, type and repeat number. Interestingly, several microsatellite characteristics seemed to be constant in plant evolution, which can be well explained by the general biological rules. PMID:23555856

A regulatory sequence from the retinoid X receptor γ gene directs expression to horizontal cells and photoreceptors in the embryonic chicken retina.

PubMed

Blixt, Maria K E; Hallböök, Finn

2016-01-01

Combining techniques of episomal vector gene-specific Cre expression and genomic integration using the piggyBac transposon system enables studies of gene expression-specific cell lineage tracing in the chicken retina. In this work, we aimed to target the retinal horizontal cell progenitors. A 208 bp gene regulatory sequence from the chicken retinoid X receptor γ gene (RXRγ208) was used to drive Cre expression. RXRγ is expressed in progenitors and photoreceptors during development. The vector was combined with a piggyBac "donor" vector containing a floxed STOP sequence followed by enhanced green fluorescent protein (EGFP), as well as a piggyBac helper vector for efficient integration into the host cell genome. The vectors were introduced into the embryonic chicken retina with in ovo electroporation. Tissue electroporation targets specific developmental time points and in specific structures. Cells that drove Cre expression from the regulatory RXRγ208 sequence excised the floxed STOP-sequence and expressed GFP. The approach generated a stable lineage with robust expression of GFP in retinal cells that have activated transcription from the RXRγ208 sequence. Furthermore, GFP was expressed in cells that express horizontal or photoreceptor markers when electroporation was performed between developmental stages 22 and 28. Electroporation of a stage 12 optic cup gave multiple cell types in accordance with RXRγ gene expression in the early retina. In this study, we describe an easy, cost-effective, and time-efficient method for testing regulatory sequences in general. More specifically, our results open up the possibility for further studies of the RXRγ-gene regulatory network governing the formation of photoreceptor and horizontal cells. In addition, the method presents approaches to target the expression of effector genes, such as regulators of cell fate or cell cycle progression, to these cells and their progenitor.