Public health and precision medicine share a goal.

PubMed

Vaithinathan, Asokan G; Asokan, Vanitha

2017-05-01

The advances made in genomics and molecular tools aid public health programs in the investigation of outbreaks and control of diseases by taking advantage of the precision medicine. Precision medicine means "segregating the individuals into subpopulations who vary in their disease susceptibility and response to a precise treatment" and not merely designing of drugs or creation of medical devices. By 2017, the United Kingdom 100,000 Genomes Project is expected to sequence 100,000 genomes from 70,000 patients. Similarly, the Precision Medicine Initiative of the United States plans to increase population-based genome sequencing and link it with clinical data. A national cohort of around 1 million people is to be established in the long term, to investigate the genetic and environmental determinants of health and disease, and further integrated to their electronic health records that are optional. Precision public health can be seen as administering the right intervention to the needy population at an appropriate time. Precision medicine originates from a wet-lab while evidence-based medicine is nurtured in a clinic. Linking the quintessential basic science research and clinical practice is necessary. In addition, new technologies to employ and analyze data in an integrated and dynamic way are essential for public health and precision medicine. The transition from evidence-based approach in public health to genomic approach to individuals with a paradigm shift of a "reactive" medicine to a more "proactive" and personalized health care may sound exceptional. However, a population perspective is needed for the precision medicine to succeed. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

A comprehensive molecular cytogenetic analysis of chromosome rearrangements in gibbons

PubMed Central

Capozzi, Oronzo; Carbone, Lucia; Stanyon, Roscoe R.; Marra, Annamaria; Yang, Fengtang; Whelan, Christopher W.; de Jong, Pieter J.; Rocchi, Mariano; Archidiacono, Nicoletta

2012-01-01

Chromosome rearrangements in small apes are up to 20 times more frequent than in most mammals. Because of their complexity, the full extent of chromosome evolution in these hominoids is not yet fully documented. However, previous work with array painting, BAC-FISH, and selective sequencing in two of the four karyomorphs has shown that high-resolution methods can precisely define chromosome breakpoints and map the complex flow of evolutionary chromosome rearrangements. Here we use these tools to precisely define the rearrangements that have occurred in the remaining two karyomorphs, genera Symphalangus (2n = 50) and Hoolock (2n = 38). This research provides the most comprehensive insight into the evolutionary origins of chromosome rearrangements involved in transforming small apes genome. Bioinformatics analyses of the human–gibbon synteny breakpoints revealed association with transposable elements and segmental duplications, providing some insight into the mechanisms that might have promoted rearrangements in small apes. In the near future, the comparison of gibbon genome sequences will provide novel insights to test hypotheses concerning the mechanisms of chromosome evolution. The precise definition of synteny block boundaries and orientation, chromosomal fusions, and centromere repositioning events presented here will facilitate genome sequence assembly for these close relatives of humans. PMID:22892276

Precision Medicine: Functional Advancements.

PubMed

Caskey, Thomas

2018-01-29

Precision medicine was conceptualized on the strength of genomic sequence analysis. High-throughput functional metrics have enhanced sequence interpretation and clinical precision. These technologies include metabolomics, magnetic resonance imaging, and I rhythm (cardiac monitoring), among others. These technologies are discussed and placed in clinical context for the medical specialties of internal medicine, pediatrics, obstetrics, and gynecology. Publications in these fields support the concept of a higher level of precision in identifying disease risk. Precise disease risk identification has the potential to enable intervention with greater specificity, resulting in disease prevention-an important goal of precision medicine.

[Prospects for applications in human health of nanopore-based sequencing].

PubMed

Audebert, Christophe; Hot, David; Caboche, Ségolène

2018-04-01

High throughput sequencing has opened up new clinical opportunities moving towards a medicine of precision. Oncology, infectious diseases or human genomics, many applications have been developed in recent years. The introduction of a third generation of nanopore-based sequencing technology, addressing some of the weaknesses of the previous generation, heralds a new revolution. Portability, real time, long reads and marginal investment costs, these promising new technologies point to a new shift of paradigm. What are the perspectives opened up by nanopores for clinical applications? © 2018 médecine/sciences – Inserm.

Estimating time of HIV-1 infection from next-generation sequence diversity

PubMed Central

2017-01-01

Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection. The results were validated on a second dataset from 31 patients. Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing that diversity in NGS data yields superior estimates to the number of ambiguous sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of deep NGS was utilized with continuous diversity measures such as average pairwise distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene were used. For these data, TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 years at 6 years. Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection many years after the infection, in contrast to most alternative biomarkers. We provide the regression coefficients as well as web tool for TI estimation. PMID:28968389

HIITE: HIV-1 incidence and infection time estimator.

PubMed

Park, Sung Yong; Love, Tanzy M T; Kapoor, Shivankur; Lee, Ha Youn

2018-06-15

Around 2.1 million new HIV-1 infections were reported in 2015, alerting that the HIV-1 epidemic remains a significant global health challenge. Precise incidence assessment strengthens epidemic monitoring efforts and guides strategy optimization for prevention programs. Estimating the onset time of HIV-1 infection can facilitate optimal clinical management and identify key populations largely responsible for epidemic spread and thereby infer HIV-1 transmission chains. Our goal is to develop a genomic assay estimating the incidence and infection time in a single cross-sectional survey setting. We created a web-based platform, HIV-1 incidence and infection time estimator (HIITE), which processes envelope gene sequences using hierarchical clustering algorithms and informs the stage of infection, along with time since infection for incident cases. HIITE's performance was evaluated using 585 incident and 305 chronic specimens' envelope gene sequences collected from global cohorts including HIV-1 vaccine trial participants. HIITE precisely identified chronically infected individuals as being chronic with an error less than 1% and correctly classified 94% of recently infected individuals as being incident. Using a mixed-effect model, an incident specimen's time since infection was estimated from its single lineage diversity, showing 14% prediction error for time since infection. HIITE is the first algorithm to inform two key metrics from a single time point sequence sample. HIITE has the capacity for assessing not only population-level epidemic spread but also individual-level transmission events from a single survey, advancing HIV prevention and intervention programs. Web-based HIITE and source code of HIITE are available at http://www.hayounlee.org/software.html. Supplementary data are available at Bioinformatics online.

SSAW: A new sequence similarity analysis method based on the stationary discrete wavelet transform.

PubMed

Lin, Jie; Wei, Jing; Adjeroh, Donald; Jiang, Bing-Hua; Jiang, Yue

2018-05-02

Alignment-free sequence similarity analysis methods often lead to significant savings in computational time over alignment-based counterparts. A new alignment-free sequence similarity analysis method, called SSAW is proposed. SSAW stands for Sequence Similarity Analysis using the Stationary Discrete Wavelet Transform (SDWT). It extracts k-mers from a sequence, then maps each k-mer to a complex number field. Then, the series of complex numbers formed are transformed into feature vectors using the stationary discrete wavelet transform. After these steps, the original sequence is turned into a feature vector with numeric values, which can then be used for clustering and/or classification. Using two different types of applications, namely, clustering and classification, we compared SSAW against the the-state-of-the-art alignment free sequence analysis methods. SSAW demonstrates competitive or superior performance in terms of standard indicators, such as accuracy, F-score, precision, and recall. The running time was significantly better in most cases. These make SSAW a suitable method for sequence analysis, especially, given the rapidly increasing volumes of sequence data required by most modern applications.

Neural correlates of skill acquisition: decreased cortical activity during a serial interception sequence learning task.

PubMed

Gobel, Eric W; Parrish, Todd B; Reber, Paul J

2011-10-15

Learning of complex motor skills requires learning of component movements as well as the sequential structure of their order and timing. Using a Serial Interception Sequence Learning (SISL) task, participants learned a sequence of precisely timed interception responses through training with a repeating sequence. Following initial implicit learning of the repeating sequence, functional MRI data were collected during performance of that known sequence and compared with activity evoked during novel sequences of actions, novel timing patterns, or both. Reduced activity was observed during the practiced sequence in a distributed bilateral network including extrastriate occipital, parietal, and premotor cortical regions. These reductions in evoked activity likely reflect improved efficiency in visuospatial processing, spatio-motor integration, motor planning, and motor execution for the trained sequence, which is likely supported by nondeclarative skill learning. In addition, the practiced sequence evoked increased activity in the left ventral striatum and medial prefrontal cortex, while the posterior cingulate was more active during periods of better performance. Many prior studies of perceptual-motor skill learning have found increased activity in motor areas of the frontal cortex (e.g., motor and premotor cortex, SMA) and striatal areas (e.g., the putamen). The change in activity observed here (i.e., decreased activity across a cortical network) may reflect skill learning that is predominantly expressed through more accurate performance rather than decreased reaction time. Copyright © 2011 Elsevier Inc. All rights reserved.

Neural Correlates of Skill Acquisition: Decreased Cortical Activity During a Serial Interception Sequence Learning Task

PubMed Central

Gobel, Eric W.; Parrish, Todd B.; Reber, Paul J.

2011-01-01

Learning of complex motor skills requires learning of component movements as well as the sequential structure of their order and timing. Using a Serial Interception Sequence Learning (SISL) task, participants learned a sequence of precisely timed interception responses through training with a repeating sequence. Following initial implicit learning of the repeating sequence, functional MRI data were collected during performance of that known sequence and compared with activity evoked during novel sequences of actions, novel timing patterns, or both. Reduced activity was observed during the practiced sequence in a distributed bilateral network including extrastriate occipital, parietal, and premotor cortical regions. These reductions in evoked activity likely reflect improved efficiency in visuospatial processing, spatio-motor integration, motor planning, and motor execution for the trained sequence, which is likely supported by nondeclarative skill learning. In addition, the practiced sequence evoked increased activity in the left ventral striatum and medial prefrontal cortex, while the posterior cingulate was more active during periods of better performance. Many prior studies of perceptual-motor skill learning have found increased activity in motor areas of frontal cortex (e.g., motor and premotor cortex, SMA) and striatal areas (e.g., the putamen). The change in activity observed here (i.e., decreased activity across a cortical network) may reflect skill learning that is predominantly expressed through more accurate performance rather than decreased reaction time. PMID:21771663

Triphasic spike-timing-dependent plasticity organizes networks to produce robust sequences of neural activity

PubMed Central

Waddington, Amelia; Appleby, Peter A.; De Kamps, Marc; Cohen, Netta

2012-01-01

Synfire chains have long been proposed to generate precisely timed sequences of neural activity. Such activity has been linked to numerous neural functions including sensory encoding, cognitive and motor responses. In particular, it has been argued that synfire chains underlie the precise spatiotemporal firing patterns that control song production in a variety of songbirds. Previous studies have suggested that the development of synfire chains requires either initial sparse connectivity or strong topological constraints, in addition to any synaptic learning rules. Here, we show that this necessity can be removed by using a previously reported but hitherto unconsidered spike-timing-dependent plasticity (STDP) rule and activity-dependent excitability. Under this rule the network develops stable synfire chains that possess a non-trivial, scalable multi-layer structure, in which relative layer sizes appear to follow a universal function. Using computational modeling and a coarse grained random walk model, we demonstrate the role of the STDP rule in growing, molding and stabilizing the chain, and link model parameters to the resulting structure. PMID:23162457

Quantification of the ciliary muscle and crystalline lens interaction during accommodation with synchronous OCT imaging

PubMed Central

Ruggeri, Marco; de Freitas, Carolina; Williams, Siobhan; Hernandez, Victor M.; Cabot, Florence; Yesilirmak, Nilufer; Alawa, Karam; Chang, Yu-Cherng; Yoo, Sonia H.; Gregori, Giovanni; Parel, Jean-Marie; Manns, Fabrice

2016-01-01

Abstract: Two SD-OCT systems and a dual channel accommodation target were combined and precisely synchronized to simultaneously image the anterior segment and the ciliary muscle during dynamic accommodation. The imaging system simultaneously generates two synchronized OCT image sequences of the anterior segment and ciliary muscle with an imaging speed of 13 frames per second. The system was used to acquire OCT image sequences of a non-presbyopic and a pre-presbyopic subject accommodating in response to step changes in vergence. The image sequences were processed to extract dynamic morphological data from the crystalline lens and the ciliary muscle. The synchronization between the OCT systems allowed the precise correlation of anatomical changes occurring in the crystalline lens and ciliary muscle at identical time points during accommodation. To describe the dynamic interaction between the crystalline lens and ciliary muscle, we introduce accommodation state diagrams that display the relation between anatomical changes occurring in the accommodating crystalline lens and ciliary muscle. PMID:27446660

Quantification of the ciliary muscle and crystalline lens interaction during accommodation with synchronous OCT imaging.

PubMed

Ruggeri, Marco; de Freitas, Carolina; Williams, Siobhan; Hernandez, Victor M; Cabot, Florence; Yesilirmak, Nilufer; Alawa, Karam; Chang, Yu-Cherng; Yoo, Sonia H; Gregori, Giovanni; Parel, Jean-Marie; Manns, Fabrice

2016-04-01

Two SD-OCT systems and a dual channel accommodation target were combined and precisely synchronized to simultaneously image the anterior segment and the ciliary muscle during dynamic accommodation. The imaging system simultaneously generates two synchronized OCT image sequences of the anterior segment and ciliary muscle with an imaging speed of 13 frames per second. The system was used to acquire OCT image sequences of a non-presbyopic and a pre-presbyopic subject accommodating in response to step changes in vergence. The image sequences were processed to extract dynamic morphological data from the crystalline lens and the ciliary muscle. The synchronization between the OCT systems allowed the precise correlation of anatomical changes occurring in the crystalline lens and ciliary muscle at identical time points during accommodation. To describe the dynamic interaction between the crystalline lens and ciliary muscle, we introduce accommodation state diagrams that display the relation between anatomical changes occurring in the accommodating crystalline lens and ciliary muscle.

Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals

PubMed Central

Baker, Christa A.; Ma, Lisa; Casareale, Chelsea R.

2016-01-01

In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8–12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. SIGNIFICANCE STATEMENT The timing patterns of action potentials, or spikes, play important roles in representing information in the nervous system. However, how these temporal patterns are recognized by downstream neurons is not well understood. Here we use the electrosensory system of mormyrid weakly electric fish to investigate how a population of neurons with diverse temporal filtering properties encodes behaviorally relevant input timing patterns, and how this relates to behavioral sensitivity. We show that fish are behaviorally sensitive to millisecond variations in natural, temporally patterned communication signals, and that the responses of individual midbrain neurons are also sensitive to variation in these patterns. In fact, the output of single neurons contains enough information to discriminate stereotyped communication signals produced by different individuals. PMID:27559179

Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals.

PubMed

Baker, Christa A; Ma, Lisa; Casareale, Chelsea R; Carlson, Bruce A

2016-08-24

In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8-12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. The timing patterns of action potentials, or spikes, play important roles in representing information in the nervous system. However, how these temporal patterns are recognized by downstream neurons is not well understood. Here we use the electrosensory system of mormyrid weakly electric fish to investigate how a population of neurons with diverse temporal filtering properties encodes behaviorally relevant input timing patterns, and how this relates to behavioral sensitivity. We show that fish are behaviorally sensitive to millisecond variations in natural, temporally patterned communication signals, and that the responses of individual midbrain neurons are also sensitive to variation in these patterns. In fact, the output of single neurons contains enough information to discriminate stereotyped communication signals produced by different individuals. Copyright © 2016 the authors 0270-6474/16/368985-16$15.00/0.

Analysing playing using the note-time playing path.

PubMed

de Graaff, Deborah L E; Schubert, Emery

2011-03-01

This article introduces a new method of data analysis that represents the playing of written music as a graph. The method, inspired by Miklaszewski, charts low-level note timings from a sound recording of a single-line instrument using high-precision audio-to-MIDI conversion software. Note onset times of pitch sequences are then plotted against the score-predicted timings to produce a Note-Time Playing Path (NTPP). The score-predicted onset time of each sequentially performed note (horizontal axis) unfolds in performed time down the page (vertical axis). NTPPs provide a visualisation that shows (1) tempo variations, (2) repetitive practice behaviours, (3) segmenting of material, (4) precise note time positions, and (5) time spent on playing or not playing. The NTPP can provide significant new insights into behaviour and cognition of music performance and may also be used to complement established traditional approaches such as think-alouds, interviews, and video coding.

Distribution and Characteristics of Repeating Earthquakes in Northern California

NASA Astrophysics Data System (ADS)

Waldhauser, F.; Schaff, D. P.; Zechar, J. D.; Shaw, B. E.

2012-12-01

Repeating earthquakes are playing an increasingly important role in the study of fault processes and behavior, and have the potential to improve hazard assessment, earthquake forecast, and seismic monitoring capabilities. These events rupture the same fault patch repeatedly, generating virtually identical seismograms. In California, repeating earthquakes have been found predominately along the creeping section of the central San Andreas Fault, where they are believed to represent failing asperities on an otherwise creeping fault. Here, we use the northern California double-difference catalog of 450,000 precisely located events (1984-2009) and associated database of 2 billion waveform cross-correlation measurements to systematically search for repeating earthquakes across various tectonic regions. An initial search for pairs of earthquakes with high-correlation coefficients and similar magnitudes resulted in 4,610 clusters including a total of over 26,000 earthquakes. A subsequent double-difference re-analysis of these clusters resulted in 1,879 sequences (8,640 events) where a common rupture area can be resolved to the precision of a few tens of meters or less. These repeating earthquake sequences (RES) include between 3 and 24 events with magnitudes up to ML=4. We compute precise relative magnitudes between events in each sequence from differential amplitude measurements. Differences between these and standard coda-duration magnitudes have a standard deviation of 0.09. The RES occur throughout northern California, but RES with 10 or more events (6%) only occur along the central San Andreas and Calaveras faults. We are establishing baseline characteristics for each sequence, such as recurrence intervals and their coefficient of variation (CV), in order to compare them across tectonic regions. CVs for these clusters range from 0.002 to 2.6, indicating a range of behavior between periodic occurrence (CV~0), random occurrence, and temporal clustering. 10% of the RES show burst-like behavior with mean recurrence times smaller than one month. 5% of the RES have mean recurrence times greater than one year and include more than 10 earthquakes. Earthquakes in the 50 most periodic sequences (CV<0.2) do not appear to be predictable by either time- or slip-predictable models, consistent with previous findings. We demonstrate that changes in recurrence intervals of repeating earthquakes can be routinely monitored. This is especially important for sequences with CV~0, as they may indicate changes in the loading rate. We also present results from retrospective forecast experiments based on near-real time hazard functions.

Web Apollo: a web-based genomic annotation editing platform.

PubMed

Lee, Eduardo; Helt, Gregg A; Reese, Justin T; Munoz-Torres, Monica C; Childers, Chris P; Buels, Robert M; Stein, Lincoln; Holmes, Ian H; Elsik, Christine G; Lewis, Suzanna E

2013-08-30

Web Apollo is the first instantaneous, collaborative genomic annotation editor available on the web. One of the natural consequences following from current advances in sequencing technology is that there are more and more researchers sequencing new genomes. These researchers require tools to describe the functional features of their newly sequenced genomes. With Web Apollo researchers can use any of the common browsers (for example, Chrome or Firefox) to jointly analyze and precisely describe the features of a genome in real time, whether they are in the same room or working from opposite sides of the world.

Web Apollo: a web-based genomic annotation editing platform

PubMed Central

2013-01-01

Web Apollo is the first instantaneous, collaborative genomic annotation editor available on the web. One of the natural consequences following from current advances in sequencing technology is that there are more and more researchers sequencing new genomes. These researchers require tools to describe the functional features of their newly sequenced genomes. With Web Apollo researchers can use any of the common browsers (for example, Chrome or Firefox) to jointly analyze and precisely describe the features of a genome in real time, whether they are in the same room or working from opposite sides of the world. PMID:24000942

High precision in protein contact prediction using fully convolutional neural networks and minimal sequence features.

PubMed

Jones, David T; Kandathil, Shaun M

2018-04-26

In addition to substitution frequency data from protein sequence alignments, many state-of-the-art methods for contact prediction rely on additional sources of information, or features, of protein sequences in order to predict residue-residue contacts, such as solvent accessibility, predicted secondary structure, and scores from other contact prediction methods. It is unclear how much of this information is needed to achieve state-of-the-art results. Here, we show that using deep neural network models, simple alignment statistics contain sufficient information to achieve state-of-the-art precision. Our prediction method, DeepCov, uses fully convolutional neural networks operating on amino-acid pair frequency or covariance data derived directly from sequence alignments, without using global statistical methods such as sparse inverse covariance or pseudolikelihood estimation. Comparisons against CCMpred and MetaPSICOV2 show that using pairwise covariance data calculated from raw alignments as input allows us to match or exceed the performance of both of these methods. Almost all of the achieved precision is obtained when considering relatively local windows (around 15 residues) around any member of a given residue pairing; larger window sizes have comparable performance. Assessment on a set of shallow sequence alignments (fewer than 160 effective sequences) indicates that the new method is substantially more precise than CCMpred and MetaPSICOV2 in this regime, suggesting that improved precision is attainable on smaller sequence families. Overall, the performance of DeepCov is competitive with the state of the art, and our results demonstrate that global models, which employ features from all parts of the input alignment when predicting individual contacts, are not strictly needed in order to attain precise contact predictions. DeepCov is freely available at https://github.com/psipred/DeepCov. d.t.jones@ucl.ac.uk.

Object detection in cinematographic video sequences for automatic indexing

NASA Astrophysics Data System (ADS)

Stauder, Jurgen; Chupeau, Bertrand; Oisel, Lionel

2003-06-01

This paper presents an object detection framework applied to cinematographic post-processing of video sequences. Post-processing is done after production and before editing. At the beginning of each shot of a video, a slate (also called clapperboard) is shown. The slate contains notably an electronic audio timecode that is necessary for audio-visual synchronization. This paper presents an object detection framework to detect slates in video sequences for automatic indexing and post-processing. It is based on five steps. The first two steps aim to reduce drastically the video data to be analyzed. They ensure high recall rate but have low precision. The first step detects images at the beginning of a shot possibly showing up a slate while the second step searches in these images for candidates regions with color distribution similar to slates. The objective is to not miss any slate while eliminating long parts of video without slate appearance. The third and fourth steps are statistical classification and pattern matching to detected and precisely locate slates in candidate regions. These steps ensure high recall rate and high precision. The objective is to detect slates with very little false alarms to minimize interactive corrections. In a last step, electronic timecodes are read from slates to automize audio-visual synchronization. The presented slate detector has a recall rate of 89% and a precision of 97,5%. By temporal integration, much more than 89% of shots in dailies are detected. By timecode coherence analysis, the precision can be raised too. Issues for future work are to accelerate the system to be faster than real-time and to extend the framework for several slate types.

What can neuromorphic event-driven precise timing add to spike-based pattern recognition?

PubMed

Akolkar, Himanshu; Meyer, Cedric; Clady, Zavier; Marre, Olivier; Bartolozzi, Chiara; Panzeri, Stefano; Benosman, Ryad

2015-03-01

This letter introduces a study to precisely measure what an increase in spike timing precision can add to spike-driven pattern recognition algorithms. The concept of generating spikes from images by converting gray levels into spike timings is currently at the basis of almost every spike-based modeling of biological visual systems. The use of images naturally leads to generating incorrect artificial and redundant spike timings and, more important, also contradicts biological findings indicating that visual processing is massively parallel, asynchronous with high temporal resolution. A new concept for acquiring visual information through pixel-individual asynchronous level-crossing sampling has been proposed in a recent generation of asynchronous neuromorphic visual sensors. Unlike conventional cameras, these sensors acquire data not at fixed points in time for the entire array but at fixed amplitude changes of their input, resulting optimally sparse in space and time-pixel individually and precisely timed only if new, (previously unknown) information is available (event based). This letter uses the high temporal resolution spiking output of neuromorphic event-based visual sensors to show that lowering time precision degrades performance on several recognition tasks specifically when reaching the conventional range of machine vision acquisition frequencies (30-60 Hz). The use of information theory to characterize separability between classes for each temporal resolution shows that high temporal acquisition provides up to 70% more information that conventional spikes generated from frame-based acquisition as used in standard artificial vision, thus drastically increasing the separability between classes of objects. Experiments on real data show that the amount of information loss is correlated with temporal precision. Our information-theoretic study highlights the potentials of neuromorphic asynchronous visual sensors for both practical applications and theoretical investigations. Moreover, it suggests that representing visual information as a precise sequence of spike times as reported in the retina offers considerable advantages for neuro-inspired visual computations.

Droplet Digital™ PCR Next-Generation Sequencing Library QC Assay.

PubMed

Heredia, Nicholas J

2018-01-01

Digital PCR is a valuable tool to quantify next-generation sequencing (NGS) libraries precisely and accurately. Accurately quantifying NGS libraries enable accurate loading of the libraries on to the sequencer and thus improve sequencing performance by reducing under and overloading error. Accurate quantification also benefits users by enabling uniform loading of indexed/barcoded libraries which in turn greatly improves sequencing uniformity of the indexed/barcoded samples. The advantages gained by employing the Droplet Digital PCR (ddPCR™) library QC assay includes the precise and accurate quantification in addition to size quality assessment, enabling users to QC their sequencing libraries with confidence.

A distributed, graphical user interface based, computer control system for atomic physics experiments

NASA Astrophysics Data System (ADS)

Keshet, Aviv; Ketterle, Wolfgang

2013-01-01

Atomic physics experiments often require a complex sequence of precisely timed computer controlled events. This paper describes a distributed graphical user interface-based control system designed with such experiments in mind, which makes use of off-the-shelf output hardware from National Instruments. The software makes use of a client-server separation between a user interface for sequence design and a set of output hardware servers. Output hardware servers are designed to use standard National Instruments output cards, but the client-server nature should allow this to be extended to other output hardware. Output sequences running on multiple servers and output cards can be synchronized using a shared clock. By using a field programmable gate array-generated variable frequency clock, redundant buffers can be dramatically shortened, and a time resolution of 100 ns achieved over effectively arbitrary sequence lengths.

A distributed, graphical user interface based, computer control system for atomic physics experiments.

PubMed

Keshet, Aviv; Ketterle, Wolfgang

2013-01-01

Atomic physics experiments often require a complex sequence of precisely timed computer controlled events. This paper describes a distributed graphical user interface-based control system designed with such experiments in mind, which makes use of off-the-shelf output hardware from National Instruments. The software makes use of a client-server separation between a user interface for sequence design and a set of output hardware servers. Output hardware servers are designed to use standard National Instruments output cards, but the client-server nature should allow this to be extended to other output hardware. Output sequences running on multiple servers and output cards can be synchronized using a shared clock. By using a field programmable gate array-generated variable frequency clock, redundant buffers can be dramatically shortened, and a time resolution of 100 ns achieved over effectively arbitrary sequence lengths.

A Tool for Multiple Targeted Genome Deletions that Is Precise, Scar-Free, and Suitable for Automation.

PubMed

Aubrey, Wayne; Riley, Michael C; Young, Michael; King, Ross D; Oliver, Stephen G; Clare, Amanda

2015-01-01

Many advances in synthetic biology require the removal of a large number of genomic elements from a genome. Most existing deletion methods leave behind markers, and as there are a limited number of markers, such methods can only be applied a fixed number of times. Deletion methods that recycle markers generally are either imprecise (remove untargeted sequences), or leave scar sequences which can cause genome instability and rearrangements. No existing marker recycling method is automation-friendly. We have developed a novel openly available deletion tool that consists of: 1) a method for deleting genomic elements that can be repeatedly used without limit, is precise, scar-free, and suitable for automation; and 2) software to design the method's primers. Our tool is sequence agnostic and could be used to delete large numbers of coding sequences, promoter regions, transcription factor binding sites, terminators, etc in a single genome. We have validated our tool on the deletion of non-essential open reading frames (ORFs) from S. cerevisiae. The tool is applicable to arbitrary genomes, and we provide primer sequences for the deletion of: 90% of the ORFs from the S. cerevisiae genome, 88% of the ORFs from S. pombe genome, and 85% of the ORFs from the L. lactis genome.

A Tool for Multiple Targeted Genome Deletions that Is Precise, Scar-Free, and Suitable for Automation

PubMed Central

Aubrey, Wayne; Riley, Michael C.; Young, Michael; King, Ross D.; Oliver, Stephen G.; Clare, Amanda

2015-01-01

Many advances in synthetic biology require the removal of a large number of genomic elements from a genome. Most existing deletion methods leave behind markers, and as there are a limited number of markers, such methods can only be applied a fixed number of times. Deletion methods that recycle markers generally are either imprecise (remove untargeted sequences), or leave scar sequences which can cause genome instability and rearrangements. No existing marker recycling method is automation-friendly. We have developed a novel openly available deletion tool that consists of: 1) a method for deleting genomic elements that can be repeatedly used without limit, is precise, scar-free, and suitable for automation; and 2) software to design the method’s primers. Our tool is sequence agnostic and could be used to delete large numbers of coding sequences, promoter regions, transcription factor binding sites, terminators, etc in a single genome. We have validated our tool on the deletion of non-essential open reading frames (ORFs) from S. cerevisiae. The tool is applicable to arbitrary genomes, and we provide primer sequences for the deletion of: 90% of the ORFs from the S. cerevisiae genome, 88% of the ORFs from S. pombe genome, and 85% of the ORFs from the L. lactis genome. PMID:26630677

An early illness recognition framework using a temporal Smith Waterman algorithm and NLP.

PubMed

Hajihashemi, Zahra; Popescu, Mihail

2013-01-01

In this paper we propose a framework for detecting health patterns based on non-wearable sensor sequence similarity and natural language processing (NLP). In TigerPlace, an aging in place facility from Columbia, MO, we deployed 47 sensor networks together with a nursing electronic health record (EHR) system to provide early illness recognition. The proposed framework utilizes sensor sequence similarity and NLP on EHR nursing comments to automatically notify the physician when health problems are detected. The reported methodology is inspired by genomic sequence annotation using similarity algorithms such as Smith Waterman (SW). Similarly, for each sensor sequence, we associate health concepts extracted from the nursing notes using Metamap, a NLP tool provided by Unified Medical Language System (UMLS). Since sensor sequences, unlike genomics ones, have an associated time dimension we propose a temporal variant of SW (TSW) to account for time. The main challenges presented by our framework are finding the most suitable time sequence similarity and aggregation of the retrieved UMLS concepts. On a pilot dataset from three Tiger Place residents, with a total of 1685 sensor days and 626 nursing records, we obtained an average precision of 0.64 and a recall of 0.37.

Data precision of X-ray fluorescence (XRF) scanning of discrete samples with the ITRAX XRF core-scanner exemplified on loess-paleosol samples

NASA Astrophysics Data System (ADS)

Profe, Jörn; Ohlendorf, Christian

2017-04-01

XRF-scanning is the state-of-the-art technique for geochemical analyses in marine and lacustrine sedimentology for more than a decade. However, little attention has been paid to data precision and technical limitations so far. Using homogenized, dried and powdered samples (certified geochemical reference standards and samples from a lithologically-contrasting loess-paleosol sequence) minimizes many adverse effects that influence the XRF-signal when analyzing wet sediment cores. This allows the investigation of data precision under ideal conditions and documents a new application of the XRF core-scanner technology at the same time. Reliable interpretations of XRF results require data precision evaluation of single elements as a function of X-ray tube, measurement time, sample compaction and quality of peak fitting. Ten-fold measurement of each sample constitutes data precision. Data precision of XRF measurements theoretically obeys Poisson statistics. Fe and Ca exhibit largest deviations from Poisson statistics. The same elements show the least mean relative standard deviations in the range from 0.5% to 1%. This represents the technical limit of data precision achievable by the installed detector. Measurement times ≥ 30 s reveal mean relative standard deviations below 4% for most elements. The quality of peak fitting is only relevant for elements with overlapping fluorescence lines such as Ba, Ti and Mn or for elements with low concentrations such as Y, for example. Differences in sample compaction are marginal and do not change mean relative standard deviation considerably. Data precision is in the range reported for geochemical reference standards measured by conventional techniques. Therefore, XRF scanning of discrete samples provide a cost- and time-efficient alternative to conventional multi-element analyses. As best trade-off between economical operation and data quality, we recommend a measurement time of 30 s resulting in a total scan time of 30 minutes for 30 samples.

Precision of working memory for visual motion sequences and transparent motion surfaces

PubMed Central

Zokaei, Nahid; Gorgoraptis, Nikos; Bahrami, Bahador; Bays, Paul M; Husain, Masud

2012-01-01

Recent studies investigating working memory for location, colour and orientation support a dynamic resource model. We examined whether this might also apply to motion, using random dot kinematograms (RDKs) presented sequentially or simultaneously. Mean precision for motion direction declined as sequence length increased, with precision being lower for earlier RDKs. Two alternative models of working memory were compared specifically to distinguish between the contributions of different sources of error that corrupt memory (Zhang & Luck (2008) vs. Bays et al (2009)). The latter provided a significantly better fit for the data, revealing that decrease in memory precision for earlier items is explained by an increase in interference from other items in a sequence, rather than random guessing or a temporal decay of information. Misbinding feature attributes is an important source of error in working memory. Precision of memory for motion direction decreased when two RDKs were presented simultaneously as transparent surfaces, compared to sequential RDKs. However, precision was enhanced when one motion surface was prioritized, demonstrating that selective attention can improve recall precision. These results are consistent with a resource model that can be used as a general conceptual framework for understanding working memory across a range of visual features. PMID:22135378

Sensorimotor synchronization with tempo-changing auditory sequences: Modeling temporal adaptation and anticipation.

PubMed

van der Steen, M C Marieke; Jacoby, Nori; Fairhurst, Merle T; Keller, Peter E

2015-11-11

The current study investigated the human ability to synchronize movements with event sequences containing continuous tempo changes. This capacity is evident, for example, in ensemble musicians who maintain precise interpersonal coordination while modulating the performance tempo for expressive purposes. Here we tested an ADaptation and Anticipation Model (ADAM) that was developed to account for such behavior by combining error correction processes (adaptation) with a predictive temporal extrapolation process (anticipation). While previous computational models of synchronization incorporate error correction, they do not account for prediction during tempo-changing behavior. The fit between behavioral data and computer simulations based on four versions of ADAM was assessed. These versions included a model with adaptation only, one in which adaptation and anticipation act in combination (error correction is applied on the basis of predicted tempo changes), and two models in which adaptation and anticipation were linked in a joint module that corrects for predicted discrepancies between the outcomes of adaptive and anticipatory processes. The behavioral experiment required participants to tap their finger in time with three auditory pacing sequences containing tempo changes that differed in the rate of change and the number of turning points. Behavioral results indicated that sensorimotor synchronization accuracy and precision, while generally high, decreased with increases in the rate of tempo change and number of turning points. Simulations and model-based parameter estimates showed that adaptation mechanisms alone could not fully explain the observed precision of sensorimotor synchronization. Including anticipation in the model increased the precision of simulated sensorimotor synchronization and improved the fit of model to behavioral data, especially when adaptation and anticipation mechanisms were linked via a joint module based on the notion of joint internal models. Overall results suggest that adaptation and anticipation mechanisms both play an important role during sensorimotor synchronization with tempo-changing sequences. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2015 Elsevier B.V. All rights reserved.

MRI of bone marrow in the distal radius: in vivo precision of effective transverse relaxation times

NASA Technical Reports Server (NTRS)

Grampp, S.; Majumdar, S.; Jergas, M.; Lang, P.; Gies, A.; Genant, H. K.

1995-01-01

The effective transverse relaxation time T2* is influenced by the presence of trabecular bone, and can potentially provide a measure of bone density as well as bone structure. We determined the in vivo precision of T2* in repeated bone marrow measurements. The T2* measurements of the bone marrow of the distal radius were performed twice within 2 weeks in six healthy young volunteers using a modified water-presaturated 3D Gradient-Recalled Acquisition at Steady State (GRASS) sequence with TE 7, 10, 12, 20, and 30; TR 67; flip angle (FA) 90 degrees. An axial volume covering a length of 5.6 cm in the distal radius was measured. Regions of interest (ROIs) were determined manually and consisted of the entire trabecular bone cross-section extending proximally from the radial subchondral endplate. Reproducibility of T2* and area measurements was expressed as the absolute precision error (standard deviation [SD] in ms or mm2) or as the relative precision error (SD/mean x 100, or coefficient of variation [CV] in %) between the two-point measurements. Short-term precision of T2* and area measurements varied depending on section thickness and location of the ROI in the distal radius. Absolute precision errors for T2* times were between 1.3 and 2.9 ms (relative precision errors 3.8-9.5 %) and for area measurements between 20 and 55 mm2 (relative precision errors 5.1-16.4%). This MR technique for quantitative assessment of trabecular bone density showed reasonable reproducibility in vivo and is a promising future tool for the assessment of osteoporosis.

Precision Medicine: From Science to Value

PubMed Central

Ginsburg, Geoffrey S; Phillips, Kathryn A

2018-01-01

Precision medicine is poised to have an impact on patients, health care delivery systems and research participants in ways that were only imagined 15 years ago when the human genome was first sequenced. While discovery using genome-based technologies has accelerated, these have only begun to be adopted into clinical medicine. Here we define precision medicine and the stakeholder ecosystem required to enable its integration into research and health care. We explore the intersection of data science, analytics and precision medicine in creating a learning health system that carries out research in the context of clinical care and at the same time optimizes the tools and information used to delivery improved patient outcomes. We provide examples of real world impact, and conclude with a policy and economic agenda that will be necessary for the adoption of this new paradigm of health care both in the United States and globally. PMID:29733705

Light beam range finder

DOEpatents

McEwan, Thomas E.

1998-01-01

A "laser tape measure" for measuring distance which includes a transmitter such as a laser diode which transmits a sequence of electromagnetic pulses in response to a transmit timing signal. A receiver samples reflections from objects within the field of the sequence of visible electromagnetic pulses with controlled timing, in response to a receive timing signal. The receiver generates a sample signal in response to the samples which indicates distance to the object causing the reflections. The timing circuit supplies the transmit timing signal to the transmitter and supplies the receive timing signal to the receiver. The receive timing signal causes the receiver to sample the reflection such that the time between transmission of pulses in the sequence in sampling by the receiver sweeps over a range of delays. The transmit timing signal causes the transmitter to transmit the sequence of electromagnetic pulses at a pulse repetition rate, and the received timing signal sweeps over the range of delays in a sweep cycle such that reflections are sampled at the pulse repetition rate and with different delays in the range of delays, such that the sample signal represents received reflections in equivalent time. The receiver according to one aspect of the invention includes an avalanche photodiode and a sampling gate coupled to the photodiode which is responsive to the received timing signal. The transmitter includes a laser diode which supplies a sequence of visible electromagnetic pulses. A bright spot projected on to the target clearly indicates the point that is being measured, and the user can read the range to that point with precision of better than 0.1%.

Light beam range finder

DOEpatents

McEwan, T.E.

1998-06-16

A ``laser tape measure`` for measuring distance is disclosed which includes a transmitter such as a laser diode which transmits a sequence of electromagnetic pulses in response to a transmit timing signal. A receiver samples reflections from objects within the field of the sequence of visible electromagnetic pulses with controlled timing, in response to a receive timing signal. The receiver generates a sample signal in response to the samples which indicates distance to the object causing the reflections. The timing circuit supplies the transmit timing signal to the transmitter and supplies the receive timing signal to the receiver. The receive timing signal causes the receiver to sample the reflection such that the time between transmission of pulses in the sequence in sampling by the receiver sweeps over a range of delays. The transmit timing signal causes the transmitter to transmit the sequence of electromagnetic pulses at a pulse repetition rate, and the received timing signal sweeps over the range of delays in a sweep cycle such that reflections are sampled at the pulse repetition rate and with different delays in the range of delays, such that the sample signal represents received reflections in equivalent time. The receiver according to one aspect of the invention includes an avalanche photodiode and a sampling gate coupled to the photodiode which is responsive to the received timing signal. The transmitter includes a laser diode which supplies a sequence of visible electromagnetic pulses. A bright spot projected on to the target clearly indicates the point that is being measured, and the user can read the range to that point with precision of better than 0.1%. 7 figs.

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.

An Adaptive Method for Switching between Pedestrian/Car Indoor Positioning Algorithms based on Multilayer Time Sequences

PubMed Central

Gu, Zhining; Guo, Wei; Li, Chaoyang; Zhu, Xinyan; Guo, Tao

2018-01-01

Pedestrian dead reckoning (PDR) positioning algorithms can be used to obtain a target’s location only for movement with step features and not for driving, for which the trilateral Bluetooth indoor positioning method can be used. In this study, to obtain the precise locations of different states (pedestrian/car) using the corresponding positioning algorithms, we propose an adaptive method for switching between the PDR and car indoor positioning algorithms based on multilayer time sequences (MTSs). MTSs, which consider the behavior context, comprise two main aspects: filtering of noisy data in small-scale time sequences and using a state chain to reduce the time delay of algorithm switching in large-scale time sequences. The proposed method can be expected to realize the recognition of stationary, walking, driving, or other states; switch to the correct indoor positioning algorithm; and improve the accuracy of localization compared to using a single positioning algorithm. Our experiments show that the recognition of static, walking, driving, and other states improves by 5.5%, 45.47%, 26.23%, and 21% on average, respectively, compared with convolutional neural network (CNN) method. The time delay decreases by approximately 0.5–8.5 s for the transition between states and by approximately 24 s for the entire process. PMID:29495503

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.

Quantifying and Mitigating the Effect of Preferential Sampling on Phylodynamic Inference

PubMed Central

Karcher, Michael D.; Palacios, Julia A.; Bedford, Trevor; Suchard, Marc A.; Minin, Vladimir N.

2016-01-01

Phylodynamics seeks to estimate effective population size fluctuations from molecular sequences of individuals sampled from a population of interest. One way to accomplish this task formulates an observed sequence data likelihood exploiting a coalescent model for the sampled individuals’ genealogy and then integrating over all possible genealogies via Monte Carlo or, less efficiently, by conditioning on one genealogy estimated from the sequence data. However, when analyzing sequences sampled serially through time, current methods implicitly assume either that sampling times are fixed deterministically by the data collection protocol or that their distribution does not depend on the size of the population. Through simulation, we first show that, when sampling times do probabilistically depend on effective population size, estimation methods may be systematically biased. To correct for this deficiency, we propose a new model that explicitly accounts for preferential sampling by modeling the sampling times as an inhomogeneous Poisson process dependent on effective population size. We demonstrate that in the presence of preferential sampling our new model not only reduces bias, but also improves estimation precision. Finally, we compare the performance of the currently used phylodynamic methods with our proposed model through clinically-relevant, seasonal human influenza examples. PMID:26938243

DB2: a probabilistic approach for accurate detection of tandem duplication breakpoints using paired-end reads.

PubMed

Yavaş, Gökhan; Koyutürk, Mehmet; Gould, Meetha P; McMahon, Sarah; LaFramboise, Thomas

2014-03-05

With the advent of paired-end high throughput sequencing, it is now possible to identify various types of structural variation on a genome-wide scale. Although many methods have been proposed for structural variation detection, most do not provide precise boundaries for identified variants. In this paper, we propose a new method, Distribution Based detection of Duplication Boundaries (DB2), for accurate detection of tandem duplication breakpoints, an important class of structural variation, with high precision and recall. Our computational experiments on simulated data show that DB2 outperforms state-of-the-art methods in terms of finding breakpoints of tandem duplications, with a higher positive predictive value (precision) in calling the duplications' presence. In particular, DB2's prediction of tandem duplications is correct 99% of the time even for very noisy data, while narrowing down the space of possible breakpoints within a margin of 15 to 20 bps on the average. Most of the existing methods provide boundaries in ranges that extend to hundreds of bases with lower precision values. Our method is also highly robust to varying properties of the sequencing library and to the sizes of the tandem duplications, as shown by its stable precision, recall and mean boundary mismatch performance. We demonstrate our method's efficacy using both simulated paired-end reads, and those generated from a melanoma sample and two ovarian cancer samples. Newly discovered tandem duplications are validated using PCR and Sanger sequencing. Our method, DB2, uses discordantly aligned reads, taking into account the distribution of fragment length to predict tandem duplications along with their breakpoints on a donor genome. The proposed method fine tunes the breakpoint calls by applying a novel probabilistic framework that incorporates the empirical fragment length distribution to score each feasible breakpoint. DB2 is implemented in Java programming language and is freely available at http://mendel.gene.cwru.edu/laframboiselab/software.php.

Precision of working memory for visual motion sequences and transparent motion surfaces.

PubMed

Zokaei, Nahid; Gorgoraptis, Nikos; Bahrami, Bahador; Bays, Paul M; Husain, Masud

2011-12-01

Recent studies investigating working memory for location, color, and orientation support a dynamic resource model. We examined whether this might also apply to motion, using random dot kinematograms (RDKs) presented sequentially or simultaneously. Mean precision for motion direction declined as sequence length increased, with precision being lower for earlier RDKs. Two alternative models of working memory were compared specifically to distinguish between the contributions of different sources of error that corrupt memory (W. Zhang & S. J. Luck, 2008 vs. P. M. Bays, R. F. G. Catalao, & M. Husain, 2009). The latter provided a significantly better fit for the data, revealing that decrease in memory precision for earlier items is explained by an increase in interference from other items in a sequence rather than random guessing or a temporal decay of information. Misbinding feature attributes is an important source of error in working memory. Precision of memory for motion direction decreased when two RDKs were presented simultaneously as transparent surfaces, compared to sequential RDKs. However, precision was enhanced when one motion surface was prioritized, demonstrating that selective attention can improve recall precision. These results are consistent with a resource model that can be used as a general conceptual framework for understanding working memory across a range of visual features.

Identification of Microbial Profile of Koji Using Single Molecule, Real-Time Sequencing Technology.

PubMed

Hui, Wenyan; Hou, Qiangchuan; Cao, Chenxia; Xu, Haiyan; Zhen, Yi; Kwok, Lai-Yu; Sun, Tiansong; Zhang, Heping; Zhang, Wenyi

2017-05-01

Koji is a kind of Japanese traditional fermented starter that has been used for centuries. Many fermented foods are made from koji, such as sake, miso, and soy sauce. This study used the single molecule real-time sequencing technology (SMRT) to investigate the bacterial and fungal microbiota of 3 Japanese koji samples. After SMRT analysis, a total of 39121 high-quality sequences were generated, including 14354 bacterial and 24767 fungal sequence reads. The high-quality gene sequences were assigned to 5 bacterial and 2 fungal plyla, dominated by Proteobacteria and Ascomycota, respectively. At the genus level, Ochrobactrum and Wickerhamomyces were the most abundant bacterial and fungal genera, respectively. The predominant bacterial and fungal species were Ochrobactrum lupini and Wickerhamomyces anomalus, respectively. Our study profiled the microbiota composition of 3 Japanese koji samples to the species level precision. The results may be useful for further development of traditional fermented products, especially optimization of koji preparation. Meanwhile, this study has demonstrated that SMRT is a robust tool for analyzing the microbial composition in food samples. © 2017 Institute of Food Technologists®.

Grouping in Short-Term Memory: Do Oscillators Code the Positions of Items?

ERIC Educational Resources Information Center

Ng, Honey L. H.; Maybery, Murray T.

2005-01-01

According to several current models of short-term memory, items are retained in order by associating them with positional codes. The models differ as to whether temporal oscillators provide those codes. The authors examined errors in recall of sequences comprising 2 groups of 4 consonants. A critical manipulation was the precise timing of items…

Assessing Developmental Trajectories of Sexual Minority Youth: Discrepant Findings from a Life History Calendar and a Self-Administered Survey

ERIC Educational Resources Information Center

Fisher, Colleen M.

2012-01-01

Research suggests that the timing and sequence of sexual identity development milestones impact myriad health and mental health outcomes for sexual minority youth. Because these milestone events are typically assessed retrospectively, traditional data collection approaches are limited by recall bias and lack of precision in the recording of…

A primer on precision medicine informatics.

PubMed

Sboner, Andrea; Elemento, Olivier

2016-01-01

In this review, we describe key components of a computational infrastructure for a precision medicine program that is based on clinical-grade genomic sequencing. Specific aspects covered in this review include software components and hardware infrastructure, reporting, integration into Electronic Health Records for routine clinical use and regulatory aspects. We emphasize informatics components related to reproducibility and reliability in genomic testing, regulatory compliance, traceability and documentation of processes, integration into clinical workflows, privacy requirements, prioritization and interpretation of results to report based on clinical needs, rapidly evolving knowledge base of genomic alterations and clinical treatments and return of results in a timely and predictable fashion. We also seek to differentiate between the use of precision medicine in germline and cancer. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The dynamics of genome replication using deep sequencing

PubMed Central

Müller, Carolin A.; Hawkins, Michelle; Retkute, Renata; Malla, Sunir; Wilson, Ray; Blythe, Martin J.; Nakato, Ryuichiro; Komata, Makiko; Shirahige, Katsuhiko; de Moura, Alessandro P.S.; Nieduszynski, Conrad A.

2014-01-01

Eukaryotic genomes are replicated from multiple DNA replication origins. We present complementary deep sequencing approaches to measure origin location and activity in Saccharomyces cerevisiae. Measuring the increase in DNA copy number during a synchronous S-phase allowed the precise determination of genome replication. To map origin locations, replication forks were stalled close to their initiation sites; therefore, copy number enrichment was limited to origins. Replication timing profiles were generated from asynchronous cultures using fluorescence-activated cell sorting. Applying this technique we show that the replication profiles of haploid and diploid cells are indistinguishable, indicating that both cell types use the same cohort of origins with the same activities. Finally, increasing sequencing depth allowed the direct measure of replication dynamics from an exponentially growing culture. This is the first time this approach, called marker frequency analysis, has been successfully applied to a eukaryote. These data provide a high-resolution resource and methodological framework for studying genome biology. PMID:24089142

Simultaneous digital quantification and fluorescence-based size characterization of massively parallel sequencing libraries.

PubMed

Laurie, Matthew T; Bertout, Jessica A; Taylor, Sean D; Burton, Joshua N; Shendure, Jay A; Bielas, Jason H

2013-08-01

Due to the high cost of failed runs and suboptimal data yields, quantification and determination of fragment size range are crucial steps in the library preparation process for massively parallel sequencing (or next-generation sequencing). Current library quality control methods commonly involve quantification using real-time quantitative PCR and size determination using gel or capillary electrophoresis. These methods are laborious and subject to a number of significant limitations that can make library calibration unreliable. Herein, we propose and test an alternative method for quality control of sequencing libraries using droplet digital PCR (ddPCR). By exploiting a correlation we have discovered between droplet fluorescence and amplicon size, we achieve the joint quantification and size determination of target DNA with a single ddPCR assay. We demonstrate the accuracy and precision of applying this method to the preparation of sequencing libraries.

OPTIMA: sensitive and accurate whole-genome alignment of error-prone genomic maps by combinatorial indexing and technology-agnostic statistical analysis.

PubMed

Verzotto, Davide; M Teo, Audrey S; Hillmer, Axel M; Nagarajan, Niranjan

2016-01-01

Resolution of complex repeat structures and rearrangements in the assembly and analysis of large eukaryotic genomes is often aided by a combination of high-throughput sequencing and genome-mapping technologies (for example, optical restriction mapping). In particular, mapping technologies can generate sparse maps of large DNA fragments (150 kilo base pairs (kbp) to 2 Mbp) and thus provide a unique source of information for disambiguating complex rearrangements in cancer genomes. Despite their utility, combining high-throughput sequencing and mapping technologies has been challenging because of the lack of efficient and sensitive map-alignment algorithms for robustly aligning error-prone maps to sequences. We introduce a novel seed-and-extend glocal (short for global-local) alignment method, OPTIMA (and a sliding-window extension for overlap alignment, OPTIMA-Overlap), which is the first to create indexes for continuous-valued mapping data while accounting for mapping errors. We also present a novel statistical model, agnostic with respect to technology-dependent error rates, for conservatively evaluating the significance of alignments without relying on expensive permutation-based tests. We show that OPTIMA and OPTIMA-Overlap outperform other state-of-the-art approaches (1.6-2 times more sensitive) and are more efficient (170-200 %) and precise in their alignments (nearly 99 % precision). These advantages are independent of the quality of the data, suggesting that our indexing approach and statistical evaluation are robust, provide improved sensitivity and guarantee high precision.

Black-blood native T1 mapping: Blood signal suppression for reduced partial voluming in the myocardium.

PubMed

Weingärtner, Sebastian; Meßner, Nadja M; Zöllner, Frank G; Akçakaya, Mehmet; Schad, Lothar R

2017-08-01

To study the feasibility of black-blood contrast in native T 1 mapping for reduction of partial voluming at the blood-myocardium interface. A saturation pulse prepared heart-rate-independent inversion recovery (SAPPHIRE) T 1 mapping sequence was combined with motion-sensitized driven-equilibrium (MSDE) blood suppression for black-blood T 1 mapping at 3 Tesla. Phantom scans were performed to assess the T 1 time accuracy. In vivo black-blood and conventional SAPPHIRE T 1 mapping was performed in eight healthy subjects and analyzed for T 1 times, precision, and inter- and intraobserver variability. Furthermore, manually drawn regions of interest (ROIs) in all T 1 maps were dilated and eroded to analyze the dependence of septal T 1 times on the ROI thickness. Phantom results and in vivo myocardial T 1 times show comparable accuracy with black-blood compared to conventional SAPPHIRE (in vivo: black-blood: 1562 ± 56 ms vs. conventional: 1583 ± 58 ms, P = 0.20); Using black-blood SAPPHIRE precision was significantly lower (standard deviation: 133.9 ± 24.6 ms vs. 63.1 ± 6.4 ms, P < .0001), and blood T 1 time measurement was not possible. Significantly increased interobserver interclass correlation coefficient (ICC) (0.996 vs. 0.967, P = 0.011) and similar intraobserver ICC (0.979 vs. 0.939, P = 0.11) was obtained with the black-blood sequence. Conventional SAPPHIRE showed strong dependence on the ROI thickness (R 2 = 0.99). No such trend was observed using the black-blood approach (R 2 = 0.29). Black-blood SAPPHIRE successfully eliminates partial voluming at the blood pool in native myocardial T 1 mapping while providing accurate T 1 times, albeit at a reduced precision. Magn Reson Med 78:484-493, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Application of polymer sensitive MRI sequence to localization of EEG electrodes.

PubMed

Butler, Russell; Gilbert, Guillaume; Descoteaux, Maxime; Bernier, Pierre-Michel; Whittingstall, Kevin

2017-02-15

The growing popularity of simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) opens up the possibility of imaging EEG electrodes while the subject is in the scanner. Such information could be useful for improving the fusion of EEG-fMRI datasets. Here, we report for the first time how an ultra-short echo time (UTE) MR sequence can image the materials of an MR-compatible EEG cap, finding that electrodes and some parts of the wiring are visible in a high resolution UTE. Using these images, we developed a segmentation procedure to obtain electrode coordinates based on voxel intensity from the raw UTE, using hand labeled coordinates as the starting point. We were able to visualize and segment 95% of EEG electrodes using a short (3.5min) UTE sequence. We provide scripts and template images so this approach can now be easily implemented to obtain precise, subject-specific EEG electrode positions while adding minimal acquisition time to the simultaneous EEG-fMRI protocol. T1 gel artifacts are not robust enough to localize all electrodes across subjects, the polymers composing Brainvision cap electrodes are not visible on a T1, and adding T1 visible materials to the EEG cap is not always possible. We therefore consider our method superior to existing methods for obtaining electrode positions in the scanner, as it is hardware free and should work on a wide range of materials (caps). EEG electrode positions are obtained with high precision and no additional hardware. Copyright © 2016 Elsevier B.V. All rights reserved.

A Segmentation Method for Lung Parenchyma Image Sequences Based on Superpixels and a Self-Generating Neural Forest

PubMed Central

Liao, Xiaolei; Zhao, Juanjuan; Jiao, Cheng; Lei, Lei; Qiang, Yan; Cui, Qiang

2016-01-01

Background Lung parenchyma segmentation is often performed as an important pre-processing step in the computer-aided diagnosis of lung nodules based on CT image sequences. However, existing lung parenchyma image segmentation methods cannot fully segment all lung parenchyma images and have a slow processing speed, particularly for images in the top and bottom of the lung and the images that contain lung nodules. Method Our proposed method first uses the position of the lung parenchyma image features to obtain lung parenchyma ROI image sequences. A gradient and sequential linear iterative clustering algorithm (GSLIC) for sequence image segmentation is then proposed to segment the ROI image sequences and obtain superpixel samples. The SGNF, which is optimized by a genetic algorithm (GA), is then utilized for superpixel clustering. Finally, the grey and geometric features of the superpixel samples are used to identify and segment all of the lung parenchyma image sequences. Results Our proposed method achieves higher segmentation precision and greater accuracy in less time. It has an average processing time of 42.21 seconds for each dataset and an average volume pixel overlap ratio of 92.22 ± 4.02% for four types of lung parenchyma image sequences. PMID:27532214

Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution

PubMed Central

2017-01-01

Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. PMID:28637852

A Wide-field Survey for Transiting Hot Jupiters and Eclipsing Pre-main-sequence Binaries in Young Stellar Associations

NASA Astrophysics Data System (ADS)

Oelkers, Ryan J.; Macri, Lucas M.; Marshall, Jennifer L.; DePoy, Darren L.; Lambas, Diego G.; Colazo, Carlos; Stringer, Katelyn

2016-09-01

The past two decades have seen a significant advancement in the detection, classification, and understanding of exoplanets and binaries. This is due, in large part, to the increase in use of small-aperture telescopes (<20 cm) to survey large areas of the sky to milli-mag precision with rapid cadence. The vast majority of the planetary and binary systems studied to date consists of main-sequence or evolved objects, leading to a dearth of knowledge of properties at early times (<50 Myr). Only a dozen binaries and one candidate transiting Hot Jupiter are known among pre-main-sequence objects, yet these are the systems that can provide the best constraints on stellar formation and planetary migration models. The deficiency in the number of well characterized systems is driven by the inherent and aperiodic variability found in pre-main-sequence objects, which can mask and mimic eclipse signals. Hence, a dramatic increase in the number of young systems with high-quality observations is highly desirable to guide further theoretical developments. We have recently completed a photometric survey of three nearby (<150 pc) and young (<50 Myr) moving groups with a small-aperture telescope. While our survey reached the requisite photometric precision, the temporal coverage was insufficient to detect Hot Jupiters. Nevertheless, we discovered 346 pre-main-sequence binary candidates, including 74 high-priority objects for further study. This paper includes data taken at The McDonald Observatory of The University of Texas at Austin.

Santorini eruption radiocarbon dated to 1627-1600 B.C.

PubMed

Friedrich, Walter L; Kromer, Bernd; Friedrich, Michael; Heinemeier, Jan; Pfeiffer, Tom; Talamo, Sahra

2006-04-28

Precise and direct dating of the Minoan eruption of Santorini (Thera) in Greece, a global Bronze Age time marker, has been made possible by the unique find of an olive tree, buried alive in life position by the tephra (pumice and ashes) on Santorini. We applied so-called radiocarbon wiggle-matching to a carbon-14 sequence of tree-ring segments to constrain the eruption date to the range 1627-1600 B.C. with 95.4% probability. Our result is in the range of previous, less precise, and less direct results of several scientific dating methods, but it is a century earlier than the date derived from traditional Egyptian chronologies.

Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects.

PubMed

Zhang, Xiaoyan; Marjani, Sadie L; Hu, Zhaoyang; Weissman, Sherman M; Pan, Xinghua; Wu, Shixiu

2016-03-15

Advances in genomic technology have enabled the faithful detection and measurement of mutations and the gene expression profile of cancer cells at the single-cell level. Recently, several single-cell sequencing methods have been developed that permit the comprehensive and precise analysis of the cancer-cell genome, transcriptome, and epigenome. The use of these methods to analyze cancer cells has led to a series of unanticipated discoveries, such as the high heterogeneity and stochastic changes in cancer-cell populations, the new driver mutations and the complicated clonal evolution mechanisms, and the novel identification of biomarkers of variant tumors. These methods and the knowledge gained from their utilization could potentially improve the early detection and monitoring of rare cancer cells, such as circulating tumor cells and disseminated tumor cells, and promote the development of personalized and highly precise cancer therapy. Here, we discuss the current methods for single cancer-cell sequencing, with a strong focus on those practically used or potentially valuable in cancer research, including single-cell isolation, whole genome and transcriptome amplification, epigenome profiling, multi-dimensional sequencing, and next-generation sequencing and analysis. We also examine the current applications, challenges, and prospects of single cancer-cell sequencing. ©2016 American Association for Cancer Research.

Sequencing of bimaxillary surgery in the correction of vertical maxillary excess: retrospective study.

PubMed

Salmen, F S; de Oliveira, T F M; Gabrielli, M A C; Pereira Filho, V A; Real Gabrielli, M F

2018-06-01

The aim of this study was to evaluate the precision of bimaxillary surgery performed to correct vertical maxillary excess, when the procedure is sequenced with mandibular surgery first or maxillary surgery first. Thirty-two patients, divided into two groups, were included in this retrospective study. Group 1 comprised patients who received bimaxillary surgery following the classical sequence with repositioning of the maxilla first. Patients in group 2 received bimaxillary surgery, but the mandible was operated on first. The precision of the maxillomandibular repositioning was determined by comparison of the digital prediction and postoperative tracings superimposed on the cranial base. The data were tabulated and analyzed statistically. In this sample, both surgical sequences provided adequate clinical accuracy. The classical sequence, repositioning the maxilla first, resulted in greater accuracy for A-point and the upper incisor edge vertical position. Repositioning the mandible first allowed greater precision in the vertical position of pogonion. In conclusion, although both surgical sequences may be used, repositioning the mandible first will result in greater imprecision in relation to the predictive tracing than repositioning the maxilla first. The classical sequence resulted in greater accuracy in the vertical position of the maxilla, which is key for aesthetics. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Harnessing Whole Genome Sequencing in Medical Mycology.

PubMed

Cuomo, Christina A

2017-01-01

Comparative genome sequencing studies of human fungal pathogens enable identification of genes and variants associated with virulence and drug resistance. This review describes current approaches, resources, and advances in applying whole genome sequencing to study clinically important fungal pathogens. Genomes for some important fungal pathogens were only recently assembled, revealing gene family expansions in many species and extreme gene loss in one obligate species. The scale and scope of species sequenced is rapidly expanding, leveraging technological advances to assemble and annotate genomes with higher precision. By using iteratively improved reference assemblies or those generated de novo for new species, recent studies have compared the sequence of isolates representing populations or clinical cohorts. Whole genome approaches provide the resolution necessary for comparison of closely related isolates, for example, in the analysis of outbreaks or sampled across time within a single host. Genomic analysis of fungal pathogens has enabled both basic research and diagnostic studies. The increased scale of sequencing can be applied across populations, and new metagenomic methods allow direct analysis of complex samples.

Flexible taxonomic assignment of ambiguous sequencing reads

PubMed Central

2011-01-01

Background To characterize the diversity of bacterial populations in metagenomic studies, sequencing reads need to be accurately assigned to taxonomic units in a given reference taxonomy. Reads that cannot be reliably assigned to a unique leaf in the taxonomy (ambiguous reads) are typically assigned to the lowest common ancestor of the set of species that match it. This introduces a potentially severe error in the estimation of bacteria present in the sample due to false positives, since all species in the subtree rooted at the ancestor are implicitly assigned to the read even though many of them may not match it. Results We present a method that maps each read to a node in the taxonomy that minimizes a penalty score while balancing the relevance of precision and recall in the assignment through a parameter q. This mapping can be obtained in time linear in the number of matching sequences, because LCA queries to the reference taxonomy take constant time. When applied to six different metagenomic datasets, our algorithm produces different taxonomic distributions depending on whether coverage or precision is maximized. Including information on the quality of the reads reduces the number of unassigned reads but increases the number of ambiguous reads, stressing the relevance of our method. Finally, two measures of performance are described and results with a set of artificially generated datasets are discussed. Conclusions The assignment strategy of sequencing reads introduced in this paper is a versatile and a quick method to study bacterial communities. The bacterial composition of the analyzed samples can vary significantly depending on how ambiguous reads are assigned depending on the value of the q parameter. Validation of our results in an artificial dataset confirm that a combination of values of q produces the most accurate results. PMID:21211059

Assessment of an automated capillary system for Plasmodium vivax microsatellite genotyping.

PubMed

Manrique, Paulo; Hoshi, Mari; Fasabi, Manuel; Nolasco, Oscar; Yori, Pablo; Calderón, Martiza; Gilman, Robert H; Kosek, Margaret N; Vinetz, Joseph M; Gamboa, Dionicia

2015-08-21

Several platforms have been used to generate the primary data for microsatellite analysis of malaria parasite genotypes. Each has relative advantages but share a limitation of being time- and cost-intensive. A commercially available automated capillary gel cartridge system was assessed in the microsatellite analysis of Plasmodium vivax diversity in the Peruvian Amazon. The reproducibility and accuracy of a commercially-available automated capillary system, QIAxcel, was assessed using a sequenced PCR product of 227 base pairs. This product was measured 42 times, then 27 P. vivax samples from Peruvian Amazon subjects were analyzed with this instrument using five informative microsatellites. Results from the QIAxcel system were compared with a Sanger-type sequencing machine, the ABI PRISM(®) 3100 Genetic Analyzer. Significant differences were seen between the sequenced amplicons and the results from the QIAxcel instrument. Different runs, plates and cartridges yielded significantly different results. Additionally, allele size decreased with each run by 0.045, or 1 bp, every three plates. QIAxcel and ABI PRISM systems differed in giving different values than those obtained by ABI PRISM, and too many (i.e. inaccurate) alleles per locus were also seen with the automated instrument. While P. vivax diversity could generally be estimated using an automated capillary gel cartridge system, the data demonstrate that this system is not sufficiently precise for reliably identifying parasite strains via microsatellite analysis. This conclusion reached after systematic analysis was due both to inadequate precision and poor reproducibility in measuring PCR product size.

Noise and drift analysis of non-equally spaced timing data

NASA Technical Reports Server (NTRS)

Vernotte, F.; Zalamansky, G.; Lantz, E.

1994-01-01

Generally, it is possible to obtain equally spaced timing data from oscillators. The measurement of the drifts and noises affecting oscillators is then performed by using a variance (Allan variance, modified Allan variance, or time variance) or a system of several variances (multivariance method). However, in some cases, several samples, or even several sets of samples, are missing. In the case of millisecond pulsar timing data, for instance, observations are quite irregularly spaced in time. Nevertheless, since some observations are very close together (one minute) and since the timing data sequence is very long (more than ten years), information on both short-term and long-term stability is available. Unfortunately, a direct variance analysis is not possible without interpolating missing data. Different interpolation algorithms (linear interpolation, cubic spline) are used to calculate variances in order to verify that they neither lose information nor add erroneous information. A comparison of the results of the different algorithms is given. Finally, the multivariance method was adapted to the measurement sequence of the millisecond pulsar timing data: the responses of each variance of the system are calculated for each type of noise and drift, with the same missing samples as in the pulsar timing sequence. An estimation of precision, dynamics, and separability of this method is given.

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods

PubMed Central

de Bresser, Jeroen; Hendrikse, Jeroen; Siero, Jeroen C. W.; Petersen, Esben T.; De Vis, Jill B.

2018-01-01

Objective In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. Materials and methods Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). Results The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson’s correlation coefficients >0.83, R2 .67–.97). The results from the downsampled data and the high-resolution data were similar. Conclusion Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed. PMID:29672584

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods.

PubMed

van der Kleij, Lisa A; de Bresser, Jeroen; Hendrikse, Jeroen; Siero, Jeroen C W; Petersen, Esben T; De Vis, Jill B

2018-01-01

In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson's correlation coefficients >0.83, R2 .67-.97). The results from the downsampled data and the high-resolution data were similar. Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed.

Sampling through time and phylodynamic inference with coalescent and birth–death models

PubMed Central

Volz, Erik M.; Frost, Simon D. W.

2014-01-01

Many population genetic models have been developed for the purpose of inferring population size and growth rates from random samples of genetic data. We examine two popular approaches to this problem, the coalescent and the birth–death-sampling model (BDM), in the context of estimating population size and birth rates in a population growing exponentially according to the birth–death branching process. For sequences sampled at a single time, we found the coalescent and the BDM gave virtually indistinguishable results in terms of the growth rates and fraction of the population sampled, even when sampling from a small population. For sequences sampled at multiple time points, we find that the birth–death model estimators are subject to large bias if the sampling process is misspecified. Since BDMs incorporate a model of the sampling process, we show how much of the statistical power of BDMs arises from the sequence of sample times and not from the genealogical tree. This motivates the development of a new coalescent estimator, which is augmented with a model of the known sampling process and is potentially more precise than the coalescent that does not use sample time information. PMID:25401173

Timeliner: Automating Procedures on the ISS

NASA Technical Reports Server (NTRS)

Brown, Robert; Braunstein, E.; Brunet, Rick; Grace, R.; Vu, T.; Zimpfer, Doug; Dwyer, William K.; Robinson, Emily

2002-01-01

Timeliner has been developed as a tool to automate procedural tasks. These tasks may be sequential tasks that would typically be performed by a human operator, or precisely ordered sequencing tasks that allow autonomous execution of a control process. The Timeliner system includes elements for compiling and executing sequences that are defined in the Timeliner language. The Timeliner language was specifically designed to allow easy definition of scripts that provide sequencing and control of complex systems. The execution environment provides real-time monitoring and control based on the commands and conditions defined in the Timeliner language. The Timeliner sequence control may be preprogrammed, compiled from Timeliner "scripts," or it may consist of real-time, interactive inputs from system operators. In general, the Timeliner system lowers the workload for mission or process control operations. In a mission environment, scripts can be used to automate spacecraft operations including autonomous or interactive vehicle control, performance of preflight and post-flight subsystem checkouts, or handling of failure detection and recovery. Timeliner may also be used for mission payload operations, such as stepping through pre-defined procedures of a scientific experiment.

Stochastic precision analysis of 2D cardiac strain estimation in vivo

NASA Astrophysics Data System (ADS)

Bunting, E. A.; Provost, J.; Konofagou, E. E.

2014-11-01

Ultrasonic strain imaging has been applied to echocardiography and carries great potential to be used as a tool in the clinical setting. Two-dimensional (2D) strain estimation may be useful when studying the heart due to the complex, 3D deformation of the cardiac tissue. Increasing the framerate used for motion estimation, i.e. motion estimation rate (MER), has been shown to improve the precision of the strain estimation, although maintaining the spatial resolution necessary to view the entire heart structure in a single heartbeat remains challenging at high MERs. Two previously developed methods, the temporally unequispaced acquisition sequence (TUAS) and the diverging beam sequence (DBS), have been used in the past to successfully estimate in vivo axial strain at high MERs without compromising spatial resolution. In this study, a stochastic assessment of 2D strain estimation precision is performed in vivo for both sequences at varying MERs (65, 272, 544, 815 Hz for TUAS; 250, 500, 1000, 2000 Hz for DBS). 2D incremental strains were estimated during left ventricular contraction in five healthy volunteers using a normalized cross-correlation function and a least-squares strain estimator. Both sequences were shown capable of estimating 2D incremental strains in vivo. The conditional expected value of the elastographic signal-to-noise ratio (E(SNRe|ɛ)) was used to compare strain estimation precision of both sequences at multiple MERs over a wide range of clinical strain values. The results here indicate that axial strain estimation precision is much more dependent on MER than lateral strain estimation, while lateral estimation is more affected by strain magnitude. MER should be increased at least above 544 Hz to avoid suboptimal axial strain estimation. Radial and circumferential strain estimations were influenced by the axial and lateral strain in different ways. Furthermore, the TUAS and DBS were found to be of comparable precision at similar MERs.

Protein contact prediction by integrating deep multiple sequence alignments, coevolution and machine learning.

PubMed

Adhikari, Badri; Hou, Jie; Cheng, Jianlin

2018-03-01

In this study, we report the evaluation of the residue-residue contacts predicted by our three different methods in the CASP12 experiment, focusing on studying the impact of multiple sequence alignment, residue coevolution, and machine learning on contact prediction. The first method (MULTICOM-NOVEL) uses only traditional features (sequence profile, secondary structure, and solvent accessibility) with deep learning to predict contacts and serves as a baseline. The second method (MULTICOM-CONSTRUCT) uses our new alignment algorithm to generate deep multiple sequence alignment to derive coevolution-based features, which are integrated by a neural network method to predict contacts. The third method (MULTICOM-CLUSTER) is a consensus combination of the predictions of the first two methods. We evaluated our methods on 94 CASP12 domains. On a subset of 38 free-modeling domains, our methods achieved an average precision of up to 41.7% for top L/5 long-range contact predictions. The comparison of the three methods shows that the quality and effective depth of multiple sequence alignments, coevolution-based features, and machine learning integration of coevolution-based features and traditional features drive the quality of predicted protein contacts. On the full CASP12 dataset, the coevolution-based features alone can improve the average precision from 28.4% to 41.6%, and the machine learning integration of all the features further raises the precision to 56.3%, when top L/5 predicted long-range contacts are evaluated. And the correlation between the precision of contact prediction and the logarithm of the number of effective sequences in alignments is 0.66. © 2017 Wiley Periodicals, Inc.

PreCisIon: PREdiction of CIS-regulatory elements improved by gene's positION.

PubMed

Elati, Mohamed; Nicolle, Rémy; Junier, Ivan; Fernández, David; Fekih, Rim; Font, Julio; Képès, François

2013-02-01

Conventional approaches to predict transcriptional regulatory interactions usually rely on the definition of a shared motif sequence on the target genes of a transcription factor (TF). These efforts have been frustrated by the limited availability and accuracy of TF binding site motifs, usually represented as position-specific scoring matrices, which may match large numbers of sites and produce an unreliable list of target genes. To improve the prediction of binding sites, we propose to additionally use the unrelated knowledge of the genome layout. Indeed, it has been shown that co-regulated genes tend to be either neighbors or periodically spaced along the whole chromosome. This study demonstrates that respective gene positioning carries significant information. This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon. To optimize this combination, PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position. This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence, genome layout or on novel criteria. With the current state of the art, PreCisIon consistently improves methods based on sequence information only. This is shown by implementing a cross-validation analysis of the 20 major TFs from two phylogenetically remote model organisms. For Bacillus subtilis and Escherichia coli, respectively, PreCisIon achieves on average an area under the receiver operating characteristic curve of 70 and 60%, a sensitivity of 80 and 70% and a specificity of 60 and 56%. The newly predicted gene targets are demonstrated to be functionally consistent with previously known targets, as assessed by analysis of Gene Ontology enrichment or of the relevant literature and databases.

High precision electric gate for time-of-flight ion mass spectrometers

NASA Technical Reports Server (NTRS)

Sittler, Edward C. (Inventor)

2011-01-01

A time-of-flight mass spectrometer having a chamber with electrodes to generate an electric field in the chamber and electric gating for allowing ions with a predetermined mass and velocity into the electric field. The design uses a row of very thin parallel aligned wires that are pulsed in sequence so the ion can pass through the gap of two parallel plates, which are biased to prevent passage of the ion. This design by itself can provide a high mass resolution capability and a very precise start pulse for an ion mass spectrometer. Furthermore, the ion will only pass through the chamber if it is within a wire diameter of the first wire when it is pulsed and has the right speed so it is near all other wires when they are pulsed.

An overview on genome organization of marine organisms.

PubMed

Costantini, Maria

2015-12-01

In this review we will concentrate on some general genome features of marine organisms and their evolution, ranging from vertebrate to invertebrates until unicellular organisms. Before genome sequencing, the ultracentrifugation in CsCl led to high resolution of mammalian DNA (without seeing at the sequence). The analytical profile of human DNA showed that the vertebrate genome is a mosaic of isochores, typically megabase-size DNA segments that belong in a small number of families characterized by different GC levels. The recent availability of a number of fully sequenced genomes allowed mapping very precisely the isochores, based on DNA sequences. Since isochores are tightly linked to biological properties such as gene density, replication timing and recombination, the new level of detail provided by the isochore map helped the understanding of genome structure, function and evolution. This led the current level of knowledge and to further insights. Copyright © 2015. Published by Elsevier B.V.

An Indian eye to personalized medicine.

PubMed

Jauhari, Shaurya; Rizvi, S A M

2015-04-01

Acknowledging the successful sequencing of the human genome and the valuable insights it has rendered, genetic drafting of non-human organisms can further enhance the understanding of modern biology. The price of sequencing technology has plummeted with time, and there is a noticeable enhancement in its implementation and recurrent usage. Sequenced genome information can be contained in a microarray chip, and then processed by a computer system for inferring analytics and predictions. Specifically, smart cards have been significantly applicable to assimilate and retrieve complex data, with ease and implicit mobility. Herein, we propose "The G-Card", a development with respect to the prevalent smart card, and an extension to the Electronic Health Record (EHR), that will hold the genome sequence of an individual, so that the medical practitioner can better investigate irregularities in a patient's health and hence recommend a precise prognosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

High-precision relocation for aftershocks of the 2016 ML 5.8 Gyeongju earthquake in South Korea: Stress partitioning controlled by complex fault systems

NASA Astrophysics Data System (ADS)

Woo, J. U.; Rhie, J.; Kang, T. S.; Kim, S.; Chai, G.; Cho, E.

2017-12-01

Complex inherent fault system is one of key factors controlling the main shock occurrence and the pattern of aftershock sequence. Many field studies have shown that the fault systems in the Korean Peninsula are complex because they formed by various tectonic events since Proterozoic. Apart from that the mainshock is the largest one (ML 5.8) ever recorded in South Korea, the Gyeongju earthquake sequence shows particularly interesting features: ML 5.1 event preceded ML 5.8 event by 50 min and they are located closely to each other ( 1 km). In addition, ML 4.5 event occurred 2 3 km away from the two events after a week of the mainshock. Considering reported focal mechanisms and hypocenters of the three major events, it is unlikely that the earthquake sequence occurs on a single fault plane. To depict the detailed fault geometry associated with the sequence, we precisely determine the relative locations of 1,400 aftershocks recorded by 27 broadband stations, which started to be deployed less than one hour after the mainshock. Double difference algorithm is applied using relative travel time measurements by a waveform cross-correlation method. Relocated hypocenters show that a major fault striking NE-SW and some minor faults get involved in the sequence. In particular, aftershocks immediately following ML 4.5 event seem to occur on a fault striking NW-SE, which is orthogonal to the strike of a major fault. We expect that the Gyeongju earthquake sequence resulted from the stress transfer controlled by the complex inherent fault system in this region.

Optical joint correlator for real-time image tracking and retinal surgery

NASA Technical Reports Server (NTRS)

Juday, Richard D. (Inventor)

1991-01-01

A method for tracking an object in a sequence of images is described. Such sequence of images may, for example, be a sequence of television frames. The object in the current frame is correlated with the object in the previous frame to obtain the relative location of the object in the two frames. An optical joint transform correlator apparatus is provided to carry out the process. Such joint transform correlator apparatus forms the basis for laser eye surgical apparatus where an image of the fundus of an eyeball is stabilized and forms the basis for the correlator apparatus to track the position of the eyeball caused by involuntary movement. With knowledge of the eyeball position, a surgical laser can be precisely pointed toward a position on the retina.

The proteolytic processing site of the precursor of lysyl oxidase.

PubMed Central

Cronshaw, A D; Fothergill-Gilmore, L A; Hulmes, D J

1995-01-01

The precise cleavage site of the N-terminal propeptide region of the precursor of lysyl oxidase has not yet been established, due to N-terminal blocking of the mature protein. Using a combination of peptide fragmentation, amino acid sequencing, time-of-flight m.s. and partial chemical unblocking procedures, it is shown that the mature form of lysyl oxidase begins at residue Asp-169 of the precursor protein (numbered according to the human sequence). The cleavage site is 28 residues to the C-terminal side of the site previously suggested on the basis of apparant molecular mass by SDS/PAGE, with the consequence that the two putative, N-linked glycosylation sites and the position of the Arg/Gln sequence polymorphism are now all in the precursor region. PMID:7864821

Integrated circuit layer image segmentation

NASA Astrophysics Data System (ADS)

Masalskis, Giedrius; Petrauskas, Romas

2010-09-01

In this paper we present IC layer image segmentation techniques which are specifically created for precise metal layer feature extraction. During our research we used many samples of real-life de-processed IC metal layer images which were obtained using optical light microscope. We have created sequence of various image processing filters which provides segmentation results of good enough precision for our application. Filter sequences were fine tuned to provide best possible results depending on properties of IC manufacturing process and imaging technology. Proposed IC image segmentation filter sequences were experimentally tested and compared with conventional direct segmentation algorithms.

Precision medicine in the age of big data: The present and future role of large-scale unbiased sequencing in drug discovery and development.

PubMed

Vicini, P; Fields, O; Lai, E; Litwack, E D; Martin, A-M; Morgan, T M; Pacanowski, M A; Papaluca, M; Perez, O D; Ringel, M S; Robson, M; Sakul, H; Vockley, J; Zaks, T; Dolsten, M; Søgaard, M

2016-02-01

High throughput molecular and functional profiling of patients is a key driver of precision medicine. DNA and RNA characterization has been enabled at unprecedented cost and scale through rapid, disruptive progress in sequencing technology, but challenges persist in data management and interpretation. We analyze the state-of-the-art of large-scale unbiased sequencing in drug discovery and development, including technology, application, ethical, regulatory, policy and commercial considerations, and discuss issues of LUS implementation in clinical and regulatory practice. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system

PubMed Central

2010-01-01

Background Cell motility is a critical parameter in many physiological as well as pathophysiological processes. In time-lapse video microscopy, manual cell tracking remains the most common method of analyzing migratory behavior of cell populations. In addition to being labor-intensive, this method is susceptible to user-dependent errors regarding the selection of "representative" subsets of cells and manual determination of precise cell positions. Results We have quantitatively analyzed these error sources, demonstrating that manual cell tracking of pancreatic cancer cells lead to mis-calculation of migration rates of up to 410%. In order to provide for objective measurements of cell migration rates, we have employed multi-target tracking technologies commonly used in radar applications to develop fully automated cell identification and tracking system suitable for high throughput screening of video sequences of unstained living cells. Conclusion We demonstrate that our automatic multi target tracking system identifies cell objects, follows individual cells and computes migration rates with high precision, clearly outperforming manual procedures. PMID:20377897

Gene mutation-based and specific therapies in precision medicine.

PubMed

Wang, Xiangdong

2016-04-01

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide-ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses. © 2015 The Author. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Development of a screening method for genetically modified soybean by plasmid-based quantitative competitive polymerase chain reaction.

PubMed

Shimizu, Eri; Kato, Hisashi; Nakagawa, Yuki; Kodama, Takashi; Futo, Satoshi; Minegishi, Yasutaka; Watanabe, Takahiro; Akiyama, Hiroshi; Teshima, Reiko; Furui, Satoshi; Hino, Akihiro; Kitta, Kazumi

2008-07-23

A novel type of quantitative competitive polymerase chain reaction (QC-PCR) system for the detection and quantification of the Roundup Ready soybean (RRS) was developed. This system was designed based on the advantage of a fully validated real-time PCR method used for the quantification of RRS in Japan. A plasmid was constructed as a competitor plasmid for the detection and quantification of genetically modified soy, RRS. The plasmid contained the construct-specific sequence of RRS and the taxon-specific sequence of lectin1 (Le1), and both had 21 bp oligonucleotide insertion in the sequences. The plasmid DNA was used as a reference molecule instead of ground seeds, which enabled us to precisely and stably adjust the copy number of targets. The present study demonstrated that the novel plasmid-based QC-PCR method could be a simple and feasible alternative to the real-time PCR method used for the quantification of genetically modified organism contents.

Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing.

PubMed

Euskirchen, Philipp; Bielle, Franck; Labreche, Karim; Kloosterman, Wigard P; Rosenberg, Shai; Daniau, Mailys; Schmitt, Charlotte; Masliah-Planchon, Julien; Bourdeaut, Franck; Dehais, Caroline; Marie, Yannick; Delattre, Jean-Yves; Idbaih, Ahmed

2017-11-01

Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e.g., for 1p/19q-codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A, and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within 6 h and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas, and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2, and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations, and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource-restricted settings.

Precise Ionosphere Monitoring via a DSFH Satellite TT&C Link

NASA Astrophysics Data System (ADS)

Chen, Xiao; Li, Guangxia; Li, Zhiqiang; Yue, Chao

2014-11-01

A phase-coherent and frequency-hopped PN ranging system was developed, originally for the purpose of anti-jamming TT&C (tracking, telemetry and telecommand) of military satellites of China, including the Beidou-2 navigation satellites. The key innovation in the synchronization of this system is the unambiguous phase recovery of direct sequence and frequency hopping (DSFH) spread spectrum signal and the correction of frequency-dependent phase rotation caused by ionosphere. With synchronization achieved, a TEC monitoring algorithm based on maximum likelihood (ML) principle is proposed and its measuring precision is analyzed through ground simulation, onboard confirmation tests will be performed when transionosphere DSFH links are established in 2014. The measuring precision of TEC exceeds that obtained from GPS receiver data because the measurement is derived from unambiguous carrier phase estimates, not pseudorange estimates. The observation results from TT&C stations can provide real time regional ionosphere TEC estimation.

Precise auditory-vocal mirroring in neurons for learned vocal communication.

PubMed

Prather, J F; Peters, S; Nowicki, S; Mooney, R

2008-01-17

Brain mechanisms for communication must establish a correspondence between sensory and motor codes used to represent the signal. One idea is that this correspondence is established at the level of single neurons that are active when the individual performs a particular gesture or observes a similar gesture performed by another individual. Although neurons that display a precise auditory-vocal correspondence could facilitate vocal communication, they have yet to be identified. Here we report that a certain class of neurons in the swamp sparrow forebrain displays a precise auditory-vocal correspondence. We show that these neurons respond in a temporally precise fashion to auditory presentation of certain note sequences in this songbird's repertoire and to similar note sequences in other birds' songs. These neurons display nearly identical patterns of activity when the bird sings the same sequence, and disrupting auditory feedback does not alter this singing-related activity, indicating it is motor in nature. Furthermore, these neurons innervate striatal structures important for song learning, raising the possibility that singing-related activity in these cells is compared to auditory feedback to guide vocal learning.

Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

PubMed

Warnock, Rachel C M; Yang, Ziheng; Donoghue, Philip C J

2017-06-28

Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. © 2017 The Authors.

Another heritage from the RNA world: self-excision of intron sequence from nuclear pre-tRNAs.

PubMed

Weber, U; Beier, H; Gross, H J

1996-06-15

The intervening sequences of nuclear tRNA precursors are known to be excised by tRNA splicing endonuclease. We show here that a T7 transcript corresponding to a pre-tRNA(Tyr) from Arabidopsis thaliana has a highly specific activity for autolytic intron excision. Self-cleavage occurs precisely at the authentic 3'-splice site and at the phosphodiester bond one nucleotide downstream of the authentic 5'-splice site. The reaction results in fragments with 2',3'-cyclic phosphate and 5'-OH termini. It is resistant to proteinase K and/or SDS treatment and is not inhibited by added tRNA. The self-cleavage depends on Mg2+ and is stimulated by spermine and Triton X-100. A set of sequence variants at the cleavage sites has been analysed for autolytic intron excision and, in parallel, for enzymatic in vitro splicing in wheat germ S23 extract. Single-stranded loops are a prerequisite for both reactions. Self-cleavage not only occurs at pyrimidine-A but also at U-U bonds. Since intron self-excision is only about five times slower than the enzymatic intron excision in a wheat germ S23 extract, we propose that the splicing endonuclease may function by improving the preciseness and efficiency of an inherent pre-tRNA self-cleavage activity.

Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care

PubMed Central

Rennert, Hanna; Eng, Kenneth; Zhang, Tuo; Tan, Adrian; Xiang, Jenny; Romanel, Alessandro; Kim, Robert; Tam, Wayne; Liu, Yen-Chun; Bhinder, Bhavneet; Cyrta, Joanna; Beltran, Himisha; Robinson, Brian; Mosquera, Juan Miguel; Fernandes, Helen; Demichelis, Francesca; Sboner, Andrea; Kluk, Michael; Rubin, Mark A; Elemento, Olivier

2016-01-01

We describe Exome Cancer Test v1.0 (EXaCT-1), the first New York State-Department of Health-approved whole-exome sequencing (WES)-based test for precision cancer care. EXaCT-1 uses HaloPlex (Agilent) target enrichment followed by next-generation sequencing (Illumina) of tumour and matched constitutional control DNA. We present a detailed clinical development and validation pipeline suitable for simultaneous detection of somatic point/indel mutations and copy-number alterations (CNAs). A computational framework for data analysis, reporting and sign-out is also presented. For the validation, we tested EXaCT-1 on 57 tumours covering five distinct clinically relevant mutations. Results demonstrated elevated and uniform coverage compatible with clinical testing as well as complete concordance in variant quality metrics between formalin-fixed paraffin embedded and fresh-frozen tumours. Extensive sensitivity studies identified limits of detection threshold for point/indel mutations and CNAs. Prospective analysis of 337 cancer cases revealed mutations in clinically relevant genes in 82% of tumours, demonstrating that EXaCT-1 is an accurate and sensitive method for identifying actionable mutations, with reasonable costs and time, greatly expanding its utility for advanced cancer care. PMID:28781886

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

PubMed

Zhang, Boyang; Huang, Kunlun; Zhu, Liye; Luo, Yunbo; Xu, Wentao

2017-07-01

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

Protein Sequence Classification with Improved Extreme Learning Machine Algorithms

PubMed Central

2014-01-01

Precisely classifying a protein sequence from a large biological protein sequences database plays an important role for developing competitive pharmacological products. Comparing the unseen sequence with all the identified protein sequences and returning the category index with the highest similarity scored protein, conventional methods are usually time-consuming. Therefore, it is urgent and necessary to build an efficient protein sequence classification system. In this paper, we study the performance of protein sequence classification using SLFNs. The recent efficient extreme learning machine (ELM) and its invariants are utilized as the training algorithms. The optimal pruned ELM is first employed for protein sequence classification in this paper. To further enhance the performance, the ensemble based SLFNs structure is constructed where multiple SLFNs with the same number of hidden nodes and the same activation function are used as ensembles. For each ensemble, the same training algorithm is adopted. The final category index is derived using the majority voting method. Two approaches, namely, the basic ELM and the OP-ELM, are adopted for the ensemble based SLFNs. The performance is analyzed and compared with several existing methods using datasets obtained from the Protein Information Resource center. The experimental results show the priority of the proposed algorithms. PMID:24795876

Sequential associative memory with nonuniformity of the layer sizes.

PubMed

Teramae, Jun-Nosuke; Fukai, Tomoki

2007-01-01

Sequence retrieval has a fundamental importance in information processing by the brain, and has extensively been studied in neural network models. Most of the previous sequential associative memory embedded sequences of memory patterns have nearly equal sizes. It was recently shown that local cortical networks display many diverse yet repeatable precise temporal sequences of neuronal activities, termed "neuronal avalanches." Interestingly, these avalanches displayed size and lifetime distributions that obey power laws. Inspired by these experimental findings, here we consider an associative memory model of binary neurons that stores sequences of memory patterns with highly variable sizes. Our analysis includes the case where the statistics of these size variations obey the above-mentioned power laws. We study the retrieval dynamics of such memory systems by analytically deriving the equations that govern the time evolution of macroscopic order parameters. We calculate the critical sequence length beyond which the network cannot retrieve memory sequences correctly. As an application of the analysis, we show how the present variability in sequential memory patterns degrades the power-law lifetime distribution of retrieved neural activities.

Stock price forecasting based on time series analysis

NASA Astrophysics Data System (ADS)

Chi, Wan Le

2018-05-01

Using the historical stock price data to set up a sequence model to explain the intrinsic relationship of data, the future stock price can forecasted. The used models are auto-regressive model, moving-average model and autoregressive-movingaverage model. The original data sequence of unit root test was used to judge whether the original data sequence was stationary. The non-stationary original sequence as a first order difference needed further processing. Then the stability of the sequence difference was re-inspected. If it is still non-stationary, the second order differential processing of the sequence is carried out. Autocorrelation diagram and partial correlation diagram were used to evaluate the parameters of the identified ARMA model, including coefficients of the model and model order. Finally, the model was used to forecast the fitting of the shanghai composite index daily closing price with precision. Results showed that the non-stationary original data series was stationary after the second order difference. The forecast value of shanghai composite index daily closing price was closer to actual value, indicating that the ARMA model in the paper was a certain accuracy.

Islander: A database of precisely mapped genomic islands in tRNA and tmRNA genes

DOE PAGES

Hudson, Corey M.; Lau, Britney Y.; Williams, Kelly P.

2014-11-05

Genomic islands are mobile DNAs that are major agents of bacterial and archaeal evolution. Integration into prokaryotic chromosomes usually occurs site-specifically at tRNA or tmRNA gene (together, tDNA) targets, catalyzed by tyrosine integrases. This splits the target gene, yet sequences within the island restore the disrupted gene; the regenerated target and its displaced fragment precisely mark the endpoints of the island. We applied this principle to search for islands in genomic DNA sequences. Our algorithm identifies tDNAs, finds fragments of those tDNAs in the same replicon and removes unlikely candidate islands through a series of filters. A search for islandsmore » in 2168 whole prokaryotic genomes produced 3919 candidates. The website Islander (recently moved to http://bioinformatics.sandia.gov/islander/) presents these precisely mapped candidate islands, the gene content and the island sequence. The algorithm further insists that each island encode an integrase, and attachment site sequence identity is carefully noted; therefore, the database also serves in the study of integrase site-specificity and its evolution.« less

An improved chronology for the Lateglacial palaeoenvironmental record of Lake Haemelsee, Germany: challenges for independent site comparisons

NASA Astrophysics Data System (ADS)

Lane, Christine; Brauer, Achim; Ramsey Christopher, Bronk; Engels, Stefan; Haliuc, Aritina; Hoek, Wim; Hubay, Katalin; Jones, Gwydion; Sachse, Dirk; Staff, Richard; Turner, Falko; Wagner-Cremer, Frederike

2016-04-01

Exploring temporal and spatial variability of environmental response to climatic changes requires the comparison of widespread palaeoenvironmental sequences on their own, independently-derived, age models. High precision age-models can be constructed using statistical methods to combine absolute and relative age estimates measured using a range of techniques. Such an approach may help to highlight otherwise unrecognised uncertainties, where a single dating method has been applied in isolation. Radiocarbon dating, tephrochronology and varve counting have been combined within a Bayesian depositional model to build a chronology for a sediment sequence from Lake Haemelsee (Northern Germany) that continuously covers the entire Lateglacial and early Holocene. Each of the dating techniques used brought its own challenges. Radiocarbon dates provide the only absolute ages measured directly in the record, however a low macrofossil content led to small sample sizes and a limited number of low precision dates. A floating varved interval provided restricted but very precise relative dating for sediments covering the Allerød to Younger Dryas transition. Well-spaced, visible and crypto- tephra layers, including the widespread Laacher See , Vedde Ash, Askja-S and Saksunarvatn tephra layers, allow absolute ages for the tephra layers established in other locations to be imported into the Haemelsee sequence. These layers also provide multiple tie-lines that allow the Haemelsee sequences to be directly compared at particular moments in time, and within particular intervals, to other important Lateglacial archives. However, selecting the "best" published tephra ages to use in the Haemelsee age model is not simple and risks biasing comparison of the palaeoenvironmental record to fit one or another comparative archive. Here we investigate the use of multiple age models for the Haemelsee record, in order to retain an independent approach to investigating the environmental transitions of the Lateglacial to Early Holocene.

In defence of story-telling.

PubMed

Currie, Adrian; Sterelny, Kim

2017-04-01

We argue that narratives are central to the success of historical reconstruction. Narrative explanation involves tracing causal trajectories across time. The construction of narrative, then, often involves postulating relatively speculative causal connections between comparatively well-established events. But speculation is not always idle or harmful: it also aids in overcoming local underdetermination by forming scaffolds from which new evidence becomes relevant. Moreover, as our understanding of the past's causal milieus become richer, the constraints on narrative plausibility become increasingly strict: a narrative's admissibility does not turn on mere logical consistency with background data. Finally, narrative explanation and explanation generated by simple, formal models complement one another. Where models often achieve isolation and precision at the cost of simplification and abstraction, narratives can track complex changes in a trajectory over time at the cost of simplicity and precision. In combination both allow us to understand and explain highly complex historical sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Building a Lego wall: Sequential action selection.

PubMed

Arnold, Amy; Wing, Alan M; Rotshtein, Pia

2017-05-01

The present study draws together two distinct lines of enquiry into the selection and control of sequential action: motor sequence production and action selection in everyday tasks. Participants were asked to build 2 different Lego walls. The walls were designed to have hierarchical structures with shared and dissociated colors and spatial components. Participants built 1 wall at a time, under low and high load cognitive states. Selection times for correctly completed trials were measured using 3-dimensional motion tracking. The paradigm enabled precise measurement of the timing of actions, while using real objects to create an end product. The experiment demonstrated that action selection was slowed at decision boundary points, relative to boundaries where no between-wall decision was required. Decision points also affected selection time prior to the actual selection window. Dual-task conditions increased selection errors. Errors mostly occurred at boundaries between chunks and especially when these required decisions. The data support hierarchical control of sequenced behavior. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Time-resolved fluorescence imaging of slab gels for lifetime base-calling in DNA sequencing applications.

PubMed

Lassiter, S J; Stryjewski, W; Legendre, B L; Erdmann, R; Wahl, M; Wurm, J; Peterson, R; Middendorf, L; Soper, S A

2000-11-01

A compact time-resolved near-IR fluorescence imager was constructed to obtain lifetime and intensity images of DNA sequencing slab gels. The scanner consisted of a microscope body with f/1.2 relay optics onto which was mounted a pulsed diode laser (repetition rate 80 MHz, lasing wavelength 680 nm, average power 5 mW), filtering optics, and a large photoactive area (diameter 500 microns) single-photon avalanche diode that was actively quenched to provide a large dynamic operating range. The time-resolved data were processed using electronics configured in a conventional time-correlated single-photon-counting format with all of the counting hardware situated on a PC card resident on the computer bus. The microscope head produced a timing response of 450 ps (fwhm) in a scanning mode, allowing the measurement of subnano-second lifetimes. The time-resolved microscope head was placed in an automated DNA sequencer and translated across a 21-cm-wide gel plate in approximately 6 s (scan rate 3.5 cm/s) with an accumulation time per pixel of 10 ms. The sampling frequency was 0.17 Hz (duty cycle 0.0017), sufficient to prevent signal aliasing during the electrophoresis separation. Software (written in Visual Basic) allowed acquisition of both the intensity image and lifetime analysis of DNA bands migrating through the gel in real time. Using a dual-labeling (IRD700 and Cy5.5 labeling dyes)/two-lane sequencing strategy, we successfully read 670 bases of a control M13mp18 ssDNA template using lifetime identification. Comparison of the reconstructed sequence with the known sequence of the phage indicated the number of miscalls was only 2, producing an error rate of approximately 0.3% (identification accuracy 99.7%). The lifetimes were calculated using maximum likelihood estimators and allowed on-line determinations with high precision, even when short integration times were used to construct the decay profiles. Comparison of the lifetime base calling to a single-dye/four-lane sequencing strategy indicated similar results in terms of miscalls, but reduced insertion and deletion errors using lifetime identification methods, improving the overall read accuracy.

The fourth annual BRDS on genome editing and silencing for precision medicines

PubMed Central

Chaudhary, Amit Kumar; Bhattarai, Rajan Sharma; Mahato, Ram I.

2018-01-01

Precision medicine is promising for treating human diseases, as it focuses on tailoring drugs to a patient’s genes, environment, and lifestyle. The need for personalized medicines has opened the doors for turning nucleic acids into therapeutics. Although gene therapy has the potential to treat and cure genetic and acquired diseases, it needs to overcome certain obstacles before creating the overall prescription drugs. Recent advancement in the life science has helped to understand the effective manipulation and delivery of genome-engineering tools better. The use of sequence-specific nucleases allows genetic changes in human cells to be easily made with higher efficiency and precision than before. Nanotechnology has made rapid advancement in the field of drug delivery, but the delivery of nucleic acids presents unique challenges. Also, designing efficient and short time-consuming genome-editing tools with negligible off-target effects are in high demand for precision medicine. In the fourth annual Biopharmaceutical Research and Development Symposium (BRDS) held at the University of Nebraska Medical Center (UNMC) on September 7–8, 2017, we covered different facets of developing tools for precision medicine for therapeutic and diagnosis of genetic disorders. PMID:29209906

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

PubMed

Lèbre, Sophie; Michel, Christian J

2013-10-01

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

Windowed R-PDLF recoupling: a flexible and reliable tool to characterize molecular dynamics.

PubMed

Gansmüller, Axel; Simorre, Jean-Pierre; Hediger, Sabine

2013-09-01

This work focuses on the improvement of the R-PDLF heteronuclear recoupling scheme, a method that allows quantification of molecular dynamics up to the microsecond timescale in heterogeneous materials. We show how the stability of the sequence towards rf-imperfections, one of the main sources of error of this technique, can be improved by the insertion of windows without irradiation into the basic elements of the symmetry-based recoupling sequence. The impact of this modification on the overall performance of the sequence in terms of scaling factor and homonuclear decoupling efficiency is evaluated. This study indicates the experimental conditions for which precise and reliable measurement of dipolar couplings can be obtained using the popular R18(1)(7) recoupling sequence, as well as alternative symmetry-based R sequences suited for fast MAS conditions. An analytical expression for the recoupled dipolar modulation has been derived that applies to a whole class of sequences with similar recoupling properties as R18(1)(7). This analytical expression provides an efficient and precise way to extract dipolar couplings from the experimental dipolar modulation curves. We hereby provide helpful tools and information for tailoring R-PDLF recoupling schemes to specific sample properties and hardware capabilities. This approach is particularly well suited for the study of materials with strong and heterogeneous molecular dynamics where a precise measurement of dipolar couplings is crucial. Copyright © 2013 Elsevier Inc. All rights reserved.

Simultaneous Quantitative MRI Mapping of T1, T2* and Magnetic Susceptibility with Multi-Echo MP2RAGE

PubMed Central

Kober, Tobias; Möller, Harald E.; Schäfer, Andreas

2017-01-01

The knowledge of relaxation times is essential for understanding the biophysical mechanisms underlying contrast in magnetic resonance imaging. Quantitative experiments, while offering major advantages in terms of reproducibility, may benefit from simultaneous acquisitions. In this work, we demonstrate the possibility of simultaneously recording relaxation-time and susceptibility maps with a prototype Multi-Echo (ME) Magnetization-Prepared 2 RApid Gradient Echoes (MP2RAGE) sequence. T1 maps can be obtained using the MP2RAGE sequence, which is relatively insensitive to inhomogeneities of the radio-frequency transmit field, B1+. As an extension, multiple gradient echoes can be acquired in each of the MP2RAGE readout blocks, which permits the calculation of T2* and susceptibility maps. We used computer simulations to explore the effects of the parameters on the precision and accuracy of the mapping. In vivo parameter maps up to 0.6 mm nominal resolution were acquired at 7 T in 19 healthy volunteers. Voxel-by-voxel correlations and the test-retest reproducibility were used to assess the reliability of the results. When using optimized paramenters, T1 maps obtained with ME-MP2RAGE and standard MP2RAGE showed excellent agreement for the whole range of values found in brain tissues. Simultaneously obtained T2* and susceptibility maps were of comparable quality as Fast Low-Angle SHot (FLASH) results. The acquisition times were more favorable for the ME-MP2RAGE (≈ 19 min) sequence as opposed to the sum of MP2RAGE (≈ 12 min) and FLASH (≈ 10 min) acquisitions. Without relevant sacrifice in accuracy, precision or flexibility, the multi-echo version may yield advantages in terms of reduced acquisition time and intrinsic co-registration, provided that an appropriate optimization of the acquisition parameters is performed. PMID:28081157

[Calm thinking for precision medicine of breast cancer in the boom].

PubMed

Jiang, Z F; Xu, F R

2017-02-01

In the past two years, researchers have been exploring the precision medicine. Thanks to the development of sequence industry and clinical study, the big data about the precision medicine have been more and more sufficient. However, how to deal with the precision data is still a question for clinicians. We focus on the hot issues that disturb clinicians most, wanting to help them to make suitable decisions between the traditional and precision medicine of breast cancer. We believe the precision medicine is on the way.

Intact Protein Analysis at 21 Tesla and X-Ray Crystallography Define Structural Differences in Single Amino Acid Variants of Human Mitochondrial Branched-Chain Amino Acid Aminotransferase 2 (BCAT2)

NASA Astrophysics Data System (ADS)

Anderson, Lissa C.; Håkansson, Maria; Walse, Björn; Nilsson, Carol L.

2017-09-01

Structural technologies are an essential component in the design of precision therapeutics. Precision medicine entails the development of therapeutics directed toward a designated target protein, with the goal to deliver the right drug to the right patient at the right time. In the field of oncology, protein structural variants are often associated with oncogenic potential. In a previous proteogenomic screen of patient-derived glioblastoma (GBM) tumor materials, we identified a sequence variant of human mitochondrial branched-chain amino acid aminotransferase 2 as a putative factor of resistance of GBM to standard-of-care-treatments. The enzyme generates glutamate, which is neurotoxic. To elucidate structural coordinates that may confer altered substrate binding or activity of the variant BCAT2 T186R, a 45 kDa protein, we applied combined ETD and CID top-down mass spectrometry in a LC-FT-ICR MS at 21 T, and X-Ray crystallography in the study of both the variant and non-variant intact proteins. The combined ETD/CID fragmentation pattern allowed for not only extensive sequence coverage but also confident localization of the amino acid variant to its position in the sequence. The crystallographic experiments confirmed the hypothesis generated by in silico structural homology modeling, that the Lys59 side-chain of BCAT2 may repulse the Arg186 in the variant protein (PDB code: 5MPR), leading to destabilization of the protein dimer and altered enzyme kinetics. Taken together, the MS and novel 3D structural data give us reason to further pursue BCAT2 T186R as a precision drug target in GBM. [Figure not available: see fulltext.

The infinitesimal operator for the semigroup of the Frobenius-Perron operator from image sequence data: vector fields and transport barriers from movies.

PubMed

Santitissadeekorn, N; Bollt, E M

2007-06-01

In this paper, we present an approach to approximate the Frobenius-Perron transfer operator from a sequence of time-ordered images, that is, a movie dataset. Unlike time-series data, successive images do not provide a direct access to a trajectory of a point in a phase space; more precisely, a pixel in an image plane. Therefore, we reconstruct the velocity field from image sequences based on the infinitesimal generator of the Frobenius-Perron operator. Moreover, we relate this problem to the well-known optical flow problem from the computer vision community and we validate the continuity equation derived from the infinitesimal operator as a constraint equation for the optical flow problem. Once the vector field and then a discrete transfer operator are found, then, in addition, we present a graph modularity method as a tool to discover basin structure in the phase space. Together with a tool to reconstruct a velocity field, this graph-based partition method provides us with a way to study transport behavior and other ergodic properties of measurable dynamical systems captured only through image sequences.

Temporal precision and the capacity of auditory-verbal short-term memory.

PubMed

Gilbert, Rebecca A; Hitch, Graham J; Hartley, Tom

2017-12-01

The capacity of serially ordered auditory-verbal short-term memory (AVSTM) is sensitive to the timing of the material to be stored, and both temporal processing and AVSTM capacity are implicated in the development of language. We developed a novel "rehearsal-probe" task to investigate the relationship between temporal precision and the capacity to remember serial order. Participants listened to a sub-span sequence of spoken digits and silently rehearsed the items and their timing during an unfilled retention interval. After an unpredictable delay, a tone prompted report of the item being rehearsed at that moment. An initial experiment showed cyclic distributions of item responses over time, with peaks preserving serial order and broad, overlapping tails. The spread of the response distributions increased with additional memory load and correlated negatively with participants' auditory digit spans. A second study replicated the negative correlation and demonstrated its specificity to AVSTM by controlling for differences in visuo-spatial STM and nonverbal IQ. The results are consistent with the idea that a common resource underpins both the temporal precision and capacity of AVSTM. The rehearsal-probe task may provide a valuable tool for investigating links between temporal processing and AVSTM capacity in the context of speech and language abilities.

Precision shock tuning on the national ignition facility.

PubMed

Robey, H F; Celliers, P M; Kline, J L; Mackinnon, A J; Boehly, T R; Landen, O L; Eggert, J H; Hicks, D; Le Pape, S; Farley, D R; Bowers, M W; Krauter, K G; Munro, D H; Jones, O S; Milovich, J L; Clark, D; Spears, B K; Town, R P J; Haan, S W; Dixit, S; Schneider, M B; Dewald, E L; Widmann, K; Moody, J D; Döppner, T D; Radousky, H B; Nikroo, A; Kroll, J J; Hamza, A V; Horner, J B; Bhandarkar, S D; Dzenitis, E; Alger, E; Giraldez, E; Castro, C; Moreno, K; Haynam, C; LaFortune, K N; Widmayer, C; Shaw, M; Jancaitis, K; Parham, T; Holunga, D M; Walters, C F; Haid, B; Malsbury, T; Trummer, D; Coffee, K R; Burr, B; Berzins, L V; Choate, C; Brereton, S J; Azevedo, S; Chandrasekaran, H; Glenzer, S; Caggiano, J A; Knauer, J P; Frenje, J A; Casey, D T; Johnson, M Gatu; Séguin, F H; Young, B K; Edwards, M J; Van Wonterghem, B M; Kilkenny, J; MacGowan, B J; Atherton, J; Lindl, J D; Meyerhofer, D D; Moses, E

2012-05-25

Ignition implosions on the National Ignition Facility [J. D. Lindl et al., Phys. Plasmas 11, 339 (2004)] are underway with the goal of compressing deuterium-tritium fuel to a sufficiently high areal density (ρR) to sustain a self-propagating burn wave required for fusion power gain greater than unity. These implosions are driven with a very carefully tailored sequence of four shock waves that must be timed to very high precision to keep the fuel entropy and adiabat low and ρR high. The first series of precision tuning experiments on the National Ignition Facility, which use optical diagnostics to directly measure the strength and timing of all four shocks inside a hohlraum-driven, cryogenic liquid-deuterium-filled capsule interior have now been performed. The results of these experiments are presented demonstrating a significant decrease in adiabat over previously untuned implosions. The impact of the improved shock timing is confirmed in related deuterium-tritium layered capsule implosions, which show the highest fuel compression (ρR~1.0 g/cm(2)) measured to date, exceeding the previous record [V. Goncharov et al., Phys. Rev. Lett. 104, 165001 (2010)] by more than a factor of 3. The experiments also clearly reveal an issue with the 4th shock velocity, which is observed to be 20% slower than predictions from numerical simulation.

Impact of simulated three-dimensional perception on precision of depth judgements, technical performance and perceived workload in laparoscopy.

PubMed

Sakata, S; Grove, P M; Hill, A; Watson, M O; Stevenson, A R L

2017-07-01

This study compared precision of depth judgements, technical performance and workload using two-dimensional (2D) and three-dimensional (3D) laparoscopic displays across different viewing distances. It also compared the accuracy of 3D displays with natural viewing, along with the relationship between stereoacuity and 3D laparoscopic performance. A counterbalanced within-subjects design with random assignment to testing sequences was used. The system could display 2D or 3D images with the same set-up. A Howard-Dolman apparatus assessed precision of depth judgements, and three laparoscopic tasks (peg transfer, navigation in space and suturing) assessed performance (time to completion). Participants completed tasks in all combinations of two viewing modes (2D, 3D) and two viewing distances (1 m, 3 m). Other measures administered included the National Aeronautics and Space Administration Task Load Index (perceived workload) and the Randot ® Stereotest (stereoacuity). Depth judgements were 6·2 times as precise at 1 m and 3·0 times as precise at 3 m using 3D versus 2D displays (P < 0·001). Participants performed all laparoscopic tasks faster in 3D at both 1 and 3 m (P < 0.001), with mean completion times up to 64 per cent shorter for 3D versus 2D displays. Workload was lower for 3D displays (up to 34 per cent) than for 2D displays at both viewing distances (P < 0·001). Greater viewing distance inhibited performance for two laparoscopic tasks, and increased perceived workload for all three (P < 0·001). Higher stereoacuity was associated with shorter completion times for the navigating in space task performed in 3D at 1 m (r = - 0·40, P = 0·001). 3D displays offer large improvements over 2D displays in precision of depth judgements, technical performance and perceived workload. © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Efficient and precise calculation of the b-matrix elements in diffusion-weighted imaging pulse sequences.

PubMed

Zubkov, Mikhail; Stait-Gardner, Timothy; Price, William S

2014-06-01

Precise NMR diffusion measurements require detailed knowledge of the cumulative dephasing effect caused by the numerous gradient pulses present in most NMR pulse sequences. This effect, which ultimately manifests itself as the diffusion-related NMR signal attenuation, is usually described by the b-value or the b-matrix in the case of multidirectional diffusion weighting, the latter being common in diffusion-weighted NMR imaging. Neglecting some of the gradient pulses introduces an error in the calculated diffusion coefficient reaching in some cases 100% of the expected value. Therefore, ensuring the b-matrix calculation includes all the known gradient pulses leads to significant error reduction. Calculation of the b-matrix for simple gradient waveforms is rather straightforward, yet it grows cumbersome when complexly shaped and/or numerous gradient pulses are introduced. Making three broad assumptions about the gradient pulse arrangement in a sequence results in an efficient framework for calculation of b-matrices as well providing some insight into optimal gradient pulse placement. The framework allows accounting for the diffusion-sensitising effect of complexly shaped gradient waveforms with modest computational time and power. This is achieved by using the b-matrix elements of the simple unmodified pulse sequence and minimising the integration of the complexly shaped gradient waveform in the modified sequence. Such re-evaluation of the b-matrix elements retains all the analytical relevance of the straightforward approach, yet at least halves the amount of symbolic integration required. The application of the framework is demonstrated with the evaluation of the expression describing the diffusion-sensitizing effect, caused by different bipolar gradient pulse modules. Copyright © 2014 Elsevier Inc. All rights reserved.

Bidirectional Retroviral Integration Site PCR Methodology and Quantitative Data Analysis Workflow.

PubMed

Suryawanshi, Gajendra W; Xu, Song; Xie, Yiming; Chou, Tom; Kim, Namshin; Chen, Irvin S Y; Kim, Sanggu

2017-06-14

Integration Site (IS) assays are a critical component of the study of retroviral integration sites and their biological significance. In recent retroviral gene therapy studies, IS assays, in combination with next-generation sequencing, have been used as a cell-tracking tool to characterize clonal stem cell populations sharing the same IS. For the accurate comparison of repopulating stem cell clones within and across different samples, the detection sensitivity, data reproducibility, and high-throughput capacity of the assay are among the most important assay qualities. This work provides a detailed protocol and data analysis workflow for bidirectional IS analysis. The bidirectional assay can simultaneously sequence both upstream and downstream vector-host junctions. Compared to conventional unidirectional IS sequencing approaches, the bidirectional approach significantly improves IS detection rates and the characterization of integration events at both ends of the target DNA. The data analysis pipeline described here accurately identifies and enumerates identical IS sequences through multiple steps of comparison that map IS sequences onto the reference genome and determine sequencing errors. Using an optimized assay procedure, we have recently published the detailed repopulation patterns of thousands of Hematopoietic Stem Cell (HSC) clones following transplant in rhesus macaques, demonstrating for the first time the precise time point of HSC repopulation and the functional heterogeneity of HSCs in the primate system. The following protocol describes the step-by-step experimental procedure and data analysis workflow that accurately identifies and quantifies identical IS sequences.

Clostridium sphenoides Chronic Osteomyelitis Diagnosed Via Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry, Conflicting With 16S rRNA Sequencing but Confirmed by Whole Genome Sequencing.

PubMed

Perkins, Matthew J; Snesrud, Erik; McGann, Patrick; Duplessis, Christopher A

2017-01-01

We report a case of successful treatment of chronic osteomyelitis (emanating from contaminated soil exposure) caused by Clostridium sphenoides, an organism infrequently identified as a cause of human infection and more saliently osteomyelitis (only 1 reported case in the literature). Additional impetus for reporting this case resides in the insights gained regarding pathogen identification exploiting sophisticated molecular platforms coupled to traditional microbial culture-based methods. The fastidious nature of cultivating anaerobic organisms required initial attempts at 16S rRNA sequencing to identify a Clostridium species (Clostridium celerecrescens). However, on exploiting matrix-assisted laser desorption ionization time of flight (MALDI TOF) technology, C. sphenoides was identified, and confirmed on whole genome sequencing. The discrepancies noted in the varying platforms require vigilance to seek complementary testing for conflicting results. Although highly accurate, the MALDI TOF and 16S rRNA sequencing platforms are not immune to false identification particularly in differentiating closely related organisms. More germane, whole genome sequencing should be entertained when conflicting results are obtained from MALDI TOF and 16S rRNA sequencing. Precise species and/or strain level identification can be clinically relevant as antimicrobial sensitivity profiles may be discrepant between closely related species influencing clinical outcomes. Thus, it is incumbent on us to strive to acquire the correct species characterization when resources allow to dictate optimal treatment. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Characterization of the uncertainty of divergence time estimation under relaxed molecular clock models using multiple loci.

PubMed

Zhu, Tianqi; Dos Reis, Mario; Yang, Ziheng

2015-03-01

Genetic sequence data provide information about the distances between species or branch lengths in a phylogeny, but not about the absolute divergence times or the evolutionary rates directly. Bayesian methods for dating species divergences estimate times and rates by assigning priors on them. In particular, the prior on times (node ages on the phylogeny) incorporates information in the fossil record to calibrate the molecular tree. Because times and rates are confounded, our posterior time estimates will not approach point values even if an infinite amount of sequence data are used in the analysis. In a previous study we developed a finite-sites theory to characterize the uncertainty in Bayesian divergence time estimation in analysis of large but finite sequence data sets under a strict molecular clock. As most modern clock dating analyses use more than one locus and are conducted under relaxed clock models, here we extend the theory to the case of relaxed clock analysis of data from multiple loci (site partitions). Uncertainty in posterior time estimates is partitioned into three sources: Sampling errors in the estimates of branch lengths in the tree for each locus due to limited sequence length, variation of substitution rates among lineages and among loci, and uncertainty in fossil calibrations. Using a simple but analogous estimation problem involving the multivariate normal distribution, we predict that as the number of loci ([Formula: see text]) goes to infinity, the variance in posterior time estimates decreases and approaches the infinite-data limit at the rate of 1/[Formula: see text], and the limit is independent of the number of sites in the sequence alignment. We then confirmed the predictions by using computer simulation on phylogenies of two or three species, and by analyzing a real genomic data set for six primate species. Our results suggest that with the fossil calibrations fixed, analyzing multiple loci or site partitions is the most effective way for improving the precision of posterior time estimation. However, even if a huge amount of sequence data is analyzed, considerable uncertainty will persist in time estimates. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society of Systematic Biologists.

Population control of self-replicating systems

NASA Technical Reports Server (NTRS)

Mccord, R. L.

1982-01-01

The literature concerning fibonacci sequence and the mathematics of self replication are reviewed. One option allows each primary to generate n-replicas, one in each sequential time frame after its own generation with no restrictions on the number of ancestors per replica. The state vector of the replicas in an efficient manner is determined. Option-B has a fixed number of replicas per primary and no restrictions on the number of ancestors for a replica. Any element fij represents the number of elements of type-j in time frame k+1 generated from type-i in time frame k. Option-D is a diagonal matrix whose eigenvalues are precisely those of f.

Structural analysis of the HLA-A/HLA-F subregion: Precise localization of two new multigene families closely associated with the HLA class I sequences

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

Pichon, L.; Carn, G.; Bouric, P.

1996-03-01

Positional cloning strategies for the hemochromatosis gene have previously concentrated on a target area restricted to a maximum genomic expanse of 400 kb around the HLA-A and HLA-F loci. Recently, the candidate region has been extended to 2-3 Mb on the distal side of the MHC. In this study, 10 coding sequences [hemochromatosis candidate genes (HCG) I to X] were isolated by cDNA selection using YACs covering the HLA-A/HLA-F subregion. Two of these (HCG II and HCG IV) belong to multigene families, as well as other sequences already described in this region, i.e., P5, pMC 6.7, and HLA class I.more » Fingerprinting of the four YACSs overlapping the region was performed and allowed partial localization of the different multigene family sequences on each YAC without defining their exact positions. Fingerprinting on cosmids isolated from the ICRF chromosome 6-specific cosmid library allowed more precise localization of the redundant sequences in all of the multigene families and revealed their apparent organization in clusters. Further examination of these intertwined sequences demonstrated that this structural organization resulted from a succession of complex phenomena, including duplications and contractions. This study presents a precise description of the structural organization of the HLA-A/HLA-F region and a determination of the sequences involved in the megabase size polymorphism observed among the A3, A24, and A31 haplotypes. 29 refs., 2 figs., 2 tabs.« less

Efficiency Benefits Using the Terminal Area Precision Scheduling and Spacing System

NASA Technical Reports Server (NTRS)

Thipphavong, Jane; Swenson, Harry N.; Lin, Paul; Seo, Anthony Y.; Bagasol, Leonard N.

2011-01-01

NASA has developed a capability for terminal area precision scheduling and spacing (TAPSS) to increase the use of fuel-efficient arrival procedures during periods of traffic congestion at a high-density airport. Sustained use of fuel-efficient procedures throughout the entire arrival phase of flight reduces overall fuel burn, greenhouse gas emissions and noise pollution. The TAPSS system is a 4D trajectory-based strategic planning and control tool that computes schedules and sequences for arrivals to facilitate optimal profile descents. This paper focuses on quantifying the efficiency benefits associated with using the TAPSS system, measured by reduction of level segments during aircraft descent and flight distance and time savings. The TAPSS system was tested in a series of human-in-the-loop simulations and compared to current procedures. Compared to the current use of the TMA system, simulation results indicate a reduction of total level segment distance by 50% and flight distance and time savings by 7% in the arrival portion of flight (200 nm from the airport). The TAPSS system resulted in aircraft maintaining continuous descent operations longer and with more precision, both achieved under heavy traffic demand levels.

Fast H-DROP: A thirty times accelerated version of H-DROP for interactive SVM-based prediction of helical domain linkers

NASA Astrophysics Data System (ADS)

Richa, Tambi; Ide, Soichiro; Suzuki, Ryosuke; Ebina, Teppei; Kuroda, Yutaka

2017-02-01

Efficient and rapid prediction of domain regions from amino acid sequence information alone is often required for swift structural and functional characterization of large multi-domain proteins. Here we introduce Fast H-DROP, a thirty times accelerated version of our previously reported H-DROP (Helical Domain linker pRediction using OPtimal features), which is unique in specifically predicting helical domain linkers (boundaries). Fast H-DROP, analogously to H-DROP, uses optimum features selected from a set of 3000 ones by combining a random forest and a stepwise feature selection protocol. We reduced the computational time from 8.5 min per sequence in H-DROP to 14 s per sequence in Fast H-DROP on an 8 Xeon processor Linux server by using SWISS-PROT instead of Genbank non-redundant (nr) database for generating the PSSMs. The sensitivity and precision of Fast H-DROP assessed by cross-validation were 33.7 and 36.2%, which were merely 2% lower than that of H-DROP. The reduced computational time of Fast H-DROP, without affecting prediction performances, makes it more interactive and user-friendly. Fast H-DROP and H-DROP are freely available from http://domserv.lab.tuat.ac.jp/.

A bioinformatics approach for identifying transgene insertion sites using whole genome sequencing data.

PubMed

Park, Doori; Park, Su-Hyun; Ban, Yong Wook; Kim, Youn Shic; Park, Kyoung-Cheul; Kim, Nam-Soo; Kim, Ju-Kon; Choi, Ik-Young

2017-08-15

Genetically modified crops (GM crops) have been developed to improve the agricultural traits of modern crop cultivars. Safety assessments of GM crops are of paramount importance in research at developmental stages and before releasing transgenic plants into the marketplace. Sequencing technology is developing rapidly, with higher output and labor efficiencies, and will eventually replace existing methods for the molecular characterization of genetically modified organisms. To detect the transgenic insertion locations in the three GM rice gnomes, Illumina sequencing reads are mapped and classified to the rice genome and plasmid sequence. The both mapped reads are classified to characterize the junction site between plant and transgene sequence by sequence alignment. Herein, we present a next generation sequencing (NGS)-based molecular characterization method, using transgenic rice plants SNU-Bt9-5, SNU-Bt9-30, and SNU-Bt9-109. Specifically, using bioinformatics tools, we detected the precise insertion locations and copy numbers of transfer DNA, genetic rearrangements, and the absence of backbone sequences, which were equivalent to results obtained from Southern blot analyses. NGS methods have been suggested as an effective means of characterizing and detecting transgenic insertion locations in genomes. Our results demonstrate the use of a combination of NGS technology and bioinformatics approaches that offers cost- and time-effective methods for assessing the safety of transgenic plants.

Gaia-GBOT asteroid finding programme (gbot.obspm.fr)

NASA Astrophysics Data System (ADS)

Bouquillon, Sébastien; Altmann, Martin; Taris, Francois; Barache, Christophe; Carlucci, Teddy; Tanga, Paolo; Thuillot, William; Marchant, Jon; Steele, Iain; Lister, Tim; Berthier, Jerome; Carry, Benoit; David, Pedro; Cellino, Alberto; Hestroffer, Daniel J.; Andrei, Alexandre Humberto; Smart, Ricky

2016-10-01

The Ground Based Optical Tracking group (GBOT) consists of about ten scientists involved in the Gaia mission by ESA. Its main task is the optical tracking of the Gaia satellite itself [1]. This novel tracking method in addition to radiometric standard ones is necessary to ensure that the Gaia mission goal in terms of astrometric precision level is reached for all objects. This optical tracking is based on daily observations performed throughout the mission by using the optical CCDs of ESO's VST in Chile, of Liverpool Telescope in La Palma and of the two LCOGT's Faulkes Telescopes in Hawaii and Australia. Each night, GBOT attempts to obtain a sequence of frames covering a 20 min total period and close to Gaia meridian transit time. In each sequence, Gaia is seen as a faint moving object (Rmag ~ 21, speed > 1"/min) and its daily astrometric accuracy has to be better than 0.02" to meet the Gaia mission requirements. The GBOT Astrometric Reduction Pipeline (GARP) [2] has been specifically developed to reach this precision.More recently, a secondary task has been assigned to GBOT which consists detecting and analysing Solar System Objects (SSOs) serendipitously recorded in the GBOT data. Indeed, since Gaia oscillates around the Sun-Earth L2 point, the fields of GBOT observations are near the Ecliptic and roughly located opposite to the Sun which is advantageous for SSO observations and studies. In particular, these SSO data can potentially be very useful to help in the determination of their absolute magnitudes, with important applications to the scientific exploitation of the WISE and Gaia missions. For these reasons, an automatic SSO detection system has been created to identify moving objects in GBOT sequences of observations. Since the beginning of 2015, this SSO detection system, added to GARP for performing high precision astrometry for SSOs, is fully operational. To this date, around 9000 asteroids have been detected. The mean delay between the time of observation and the submission of the SSO reduction results to the MPC is less than 12 hours allowing rapid follow up of new objects.[1] Altmann et al. 2014, SPIE, 9149.[2] Bouquillon et al. 2014, SPIE, 9152.

Measuring Time-of-Flight in an Ultrasonic LPS System Using Generalized Cross-Correlation

PubMed Central

Villladangos, José Manuel; Ureña, Jesús; García, Juan Jesús; Mazo, Manuel; Hernández, Álvaro; Jiménez, Ana; Ruíz, Daniel; De Marziani, Carlos

2011-01-01

In this article, a time-of-flight detection technique in the frequency domain is described for an ultrasonic Local Positioning System (LPS) based on encoded beacons. Beacon transmissions have been synchronized and become simultaneous by means of the DS-CDMA (Direct-Sequence Code Division Multiple Access) technique. Every beacon has been associated to a 255-bit Kasami code. The detection of signal arrival instant at the receiver, from which the distance to each beacon can be obtained, is based on the application of the Generalized Cross-Correlation (GCC), by using the cross-spectral density between the received signal and the sequence to be detected. Prior filtering to enhance the frequency components around the carrier frequency (40 kHz) has improved estimations when obtaining the correlation function maximum, which implies an improvement in distance measurement precision. Positioning has been achieved by using hyperbolic trilateration, based on the Time Differences of Arrival (TDOA) between a reference beacon and the others. PMID:22346645

Measuring time-of-flight in an ultrasonic LPS system using generalized cross-correlation.

PubMed

Villladangos, José Manuel; Ureña, Jesús; García, Juan Jesús; Mazo, Manuel; Hernández, Alvaro; Jiménez, Ana; Ruíz, Daniel; De Marziani, Carlos

2011-01-01

In this article, a time-of-flight detection technique in the frequency domain is described for an ultrasonic local positioning system (LPS) based on encoded beacons. Beacon transmissions have been synchronized and become simultaneous by means of the DS-CDMA (direct-sequence code Division multiple access) technique. Every beacon has been associated to a 255-bit Kasami code. The detection of signal arrival instant at the receiver, from which the distance to each beacon can be obtained, is based on the application of the generalized cross-correlation (GCC), by using the cross-spectral density between the received signal and the sequence to be detected. Prior filtering to enhance the frequency components around the carrier frequency (40 kHz) has improved estimations when obtaining the correlation function maximum, which implies an improvement in distance measurement precision. Positioning has been achieved by using hyperbolic trilateration, based on the time differences of arrival (TDOA) between a reference beacon and the others.

Ogden R. Lindsley and the historical development of precision teaching

PubMed Central

Potts, Lisa; Eshleman, John W.; Cooper, John O.

1993-01-01

This paper presents the historical developments of precision teaching, a technological offshoot of radical behaviorism and free-operant conditioning. The sequence progresses from the scientific precursors of precision teaching and the beginnings of precision teaching to principal developments since 1965. Information about the persons, events, and accomplishments presented in this chronology was compiled in several ways. Journals, books, and conference presentations provided the essential information. The most important source for this account was Ogden Lindsley himself, because Lindsley and his students established the basic practices that define precision teaching. PMID:22478145

Current-day precision oncology: from cancer prevention, screening, drug development, and treatment - have we fallen short of the promise?

PubMed

Morgan, Gilberto; Aftimos, Philippe; Awada, Ahmad

2016-09-01

Precision oncology has been a strategy of prevention, screening, and treatment. Although much has been invested, have the results fallen so far short of the promise? The advancement of technology and research has opened new doors, yet a variety of pitfalls are present. This review presents the successes, failures, and opportunities of precision oncology in the current landscape. The use of targeted gene sequencing and the overwhelming results of superresponders have generated much excitement and support for precision oncology from the medical community. Despite notable successes, many challenges still pave the way of precision oncology: intratumoral heterogeneity, the need for serial biopsies, availability of treatments, target prioritization, ethical issues with germline incidental findings, medical education, clinical trial design, and costs. Precision oncology shows much potential through the use of next-generation sequencing and molecular advances, but does this potential warrant the investment? There are many obstacles on the way of this technology that should make us question if the investment (both monetary and man-hours) will live up to the promise. The review aims to not criticize this technology, but to give a realistic view of where we are, especially regarding cancer treatment and prevention.

Precision Medicine in Gastrointestinal Pathology.

PubMed

Wang, David H; Park, Jason Y

2016-05-01

-Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs. -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.

Efficient and Accurate Algorithm for Cleaved Fragments Prediction (CFPA) in Protein Sequences Dataset Based on Consensus and Its Variants: A Novel Degradomics Prediction Application.

PubMed

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges; Hajj, Hazem; Kobeissy, Firas H

2017-01-01

Degradomics is a novel discipline that involves determination of the proteases/substrate fragmentation profile, called the substrate degradome, and has been recently applied in different disciplines. A major application of degradomics is its utility in the field of biomarkers where the breakdown products (BDPs) of different protease have been investigated. Among the major proteases assessed, calpain and caspase proteases have been associated with the execution phases of the pro-apoptotic and pro-necrotic cell death, generating caspase/calpain-specific cleaved fragments. The distinction between calpain and caspase protein fragments has been applied to distinguish injury mechanisms. Advanced proteomics technology has been used to identify these BDPs experimentally. However, it has been a challenge to identify these BDPs with high precision and efficiency, especially if we are targeting a number of proteins at one time. In this chapter, we present a novel bioinfromatic detection method that identifies BDPs accurately and efficiently with validation against experimental data. This method aims at predicting the consensus sequence occurrences and their variants in a large set of experimentally detected protein sequences based on state-of-the-art sequence matching and alignment algorithms. After detection, the method generates all the potential cleaved fragments by a specific protease. This space and time-efficient algorithm is flexible to handle the different orientations that the consensus sequence and the protein sequence can take before cleaving. It is O(mn) in space complexity and O(Nmn) in time complexity, with N number of protein sequences, m length of the consensus sequence, and n length of each protein sequence. Ultimately, this knowledge will subsequently feed into the development of a novel tool for researchers to detect diverse types of selected BDPs as putative disease markers, contributing to the diagnosis and treatment of related disorders.

Quantifying Genome Editing Outcomes at Endogenous Loci using SMRT Sequencing

PubMed Central

Clark, Joseph; Punjya, Niraj; Sebastiano, Vittorio; Bao, Gang; Porteus, Matthew H

2014-01-01

SUMMARY Targeted genome editing with engineered nucleases has transformed the ability to introduce precise sequence modifications at almost any site within the genome. A major obstacle to probing the efficiency and consequences of genome editing is that no existing method enables the frequency of different editing events to be simultaneously measured across a cell population at any endogenous genomic locus. We have developed a novel method for quantifying individual genome editing outcomes at any site of interest using single molecule real time (SMRT) DNA sequencing. We show that this approach can be applied at various loci, using multiple engineered nuclease platforms including TALENs, RNA guided endonucleases (CRISPR/Cas9), and ZFNs, and in different cell lines to identify conditions and strategies in which the desired engineering outcome has occurred. This approach facilitates the evaluation of new gene editing technologies and permits sensitive quantification of editing outcomes in almost every experimental system used. PMID:24685129

New method of extracting information of arterial oxygen saturation based on ∑ | 𝚫 |

NASA Astrophysics Data System (ADS)

Dai, Wenting; Lin, Ling; Li, Gang

2017-04-01

Noninvasive detection of oxygen saturation with near-infrared spectroscopy has been widely used in clinics. In order to further enhance its detection precision and reliability, this paper proposes a method of time domain absolute difference summation (∑|Δ|) based on a dynamic spectrum. In this method, the ratio of absolute differences between intervals of two differential sampling points at the same moment on logarithm photoplethysmography signals of red and infrared light was obtained in turn, and then they obtained a ratio sequence which was screened with a statistical method. Finally, use the summation of the screened ratio sequence as the oxygen saturation coefficient Q. We collected 120 reference samples of SpO2 and then compared the result of two methods, which are ∑|Δ| and peak-peak. Average root-mean-square errors of the two methods were 3.02% and 6.80%, respectively, in the 20 cases which were selected randomly. In addition, the average variance of Q of the 10 samples, which were obtained by the new method, reduced to 22.77% of that obtained by the peak-peak method. Comparing with the commercial product, the new method makes the results more accurate. Theoretical and experimental analysis indicates that the application of the ∑|Δ| method could enhance the precision and reliability of oxygen saturation detection in real time.

New method of extracting information of arterial oxygen saturation based on ∑|𝚫 |

NASA Astrophysics Data System (ADS)

Wenting, Dai; Ling, Lin; Gang, Li

2017-04-01

Noninvasive detection of oxygen saturation with near-infrared spectroscopy has been widely used in clinics. In order to further enhance its detection precision and reliability, this paper proposes a method of time domain absolute difference summation (∑|Δ|) based on a dynamic spectrum. In this method, the ratio of absolute differences between intervals of two differential sampling points at the same moment on logarithm photoplethysmography signals of red and infrared light was obtained in turn, and then they obtained a ratio sequence which was screened with a statistical method. Finally, use the summation of the screened ratio sequence as the oxygen saturation coefficient Q. We collected 120 reference samples of SpO2 and then compared the result of two methods, which are ∑|Δ| and peak-peak. Average root-mean-square errors of the two methods were 3.02% and 6.80%, respectively, in the 20 cases which were selected randomly. In addition, the average variance of Q of the 10 samples, which were obtained by the new method, reduced to 22.77% of that obtained by the peak-peak method. Comparing with the commercial product, the new method makes the results more accurate. Theoretical and experimental analysis indicates that the application of the ∑|Δ| method could enhance the precision and reliability of oxygen saturation detection in real time.

Protected quantum computing: interleaving gate operations with dynamical decoupling sequences.

PubMed

Zhang, Jingfu; Souza, Alexandre M; Brandao, Frederico Dias; Suter, Dieter

2014-02-07

Implementing precise operations on quantum systems is one of the biggest challenges for building quantum devices in a noisy environment. Dynamical decoupling attenuates the destructive effect of the environmental noise, but so far, it has been used primarily in the context of quantum memories. Here, we experimentally demonstrate a general scheme for combining dynamical decoupling with quantum logical gate operations using the example of an electron-spin qubit of a single nitrogen-vacancy center in diamond. We achieve process fidelities >98% for gate times that are 2 orders of magnitude longer than the unprotected dephasing time T2.

Winnowing sequences from a database search.

PubMed

Berman, P; Zhang, Z; Wolf, Y I; Koonin, E V; Miller, W

2000-01-01

In database searches for sequence similarity, matches to a distinct sequence region (e.g., protein domain) are frequently obscured by numerous matches to another region of the same sequence. In order to cope with this problem, algorithms are developed to discard redundant matches. One model for this problem begins with a list of intervals, each with an associated score; each interval gives the range of positions in the query sequence that align to a database sequence, and the score is that of the alignment. If interval I is contained in interval J, and I's score is less than J's, then I is said to be dominated by J. The problem is then to identify each interval that is dominated by at least K other intervals, where K is a given level of "tolerable redundancy." An algorithm is developed to solve the problem in O(N log N) time and O(N*) space, where N is the number of intervals and N* is a precisely defined value that never exceeds N and is frequently much smaller. This criterion for discarding database hits has been implemented in the Blast program, as illustrated herein with examples. Several variations and extensions of this approach are also described.

Precise U-Pb Zircon Constraints on the Earliest Magmatic History of the Carolina Terrane.

PubMed

Wortman; Samson; Hibbard

2000-05-01

The early magmatic and tectonic history of the Carolina terrane and its possible affinities with other Neoproterozoic circum-Atlantic arc terranes have been poorly understood, in large part because of a lack of reliable geochronological data. Precise U-Pb zircon dates for the Virgilina sequence, the oldest exposed part, constrain the timing of the earliest known stage of magmatism in the terrane and of the Virgilina orogeny. A flow-banded rhyolite sampled from a metavolcanic sequence near Chapel Hill, North Carolina, yielded a U-Pb zircon date of 632.9 +2.6/-1.9 Ma. A granitic unit of the Chapel Hill pluton, which intrudes the metavolcanic sequence, yielded a nearly identical U-Pb zircon date of 633 +2/-1.5 Ma, interpreted as its crystallization age. A felsic gneiss and a dacitic tuff from the Hyco Formation yielded U-Pb zircon dates of 619.9 +4.5/-3 Ma and 615.7 +3.7/-1.9 Ma, respectively. Diorite and granite of the Flat River complex have indistinguishable U-Pb upper-intercept dates of 613.9 +1.6/-1.5 Ma and 613.4 +2.8/-2 Ma. The Osmond biotite-granite gneiss, which intruded the Hyco Formation before the Virgilina orogeny, crystallized at 612.4 +5.2/-1.7 Ma. Granite of the Roxboro pluton, an intrusion that postdated the Virgilina orogeny, yielded a U-Pb upper intercept date of 546.5 +3.0/-2.4 Ma, interpreted as the time of its crystallization. These new dates both provide the first reliable estimates of the age of the Virgilina sequence and document that the earliest known stage of magmatism in the Carolina terrane had begun by 633 +2/-1.5 Ma and continued at least until 612.4 +5.2/-1.7 Ma, an interval of approximately 25 m.yr. Timing of the Virgilina orogeny is bracketed between 612.4 +5.2/-1.7 Ma and 586+/-10 Ma (reported age of the upper Uwharrie Formation). The U-Pb systematics of all units studied in the Virgilina sequence are simple and lack any evidence of an older xenocrystic zircon component, which would indicate the presence of a continental-type basement. This observation, together with the juvenile Nd isotopic character of the Virgilina volcanic arc sequence, suggests that the oldest part of the Carolina terrane was built on oceanic crust away from a continental crustal influence.

Gaussian signal relaxation around spin echoes: Implications for precise reversible transverse relaxation quantification of pulmonary tissue at 1.5 and 3 Tesla.

PubMed

Zapp, Jascha; Domsch, Sebastian; Weingärtner, Sebastian; Schad, Lothar R

2017-05-01

To characterize the reversible transverse relaxation in pulmonary tissue and to study the benefit of a quadratic exponential (Gaussian) model over the commonly used linear exponential model for increased quantification precision. A point-resolved spectroscopy sequence was used for comprehensive sampling of the relaxation around spin echoes. Measurements were performed in an ex vivo tissue sample and in healthy volunteers at 1.5 Tesla (T) and 3 T. The goodness of fit using χred2 and the precision of the fitted relaxation time by means of its confidence interval were compared between the two relaxation models. The Gaussian model provides enhanced descriptions of pulmonary relaxation with lower χred2 by average factors of 4 ex vivo and 3 in volunteers. The Gaussian model indicates higher sensitivity to tissue structure alteration with increased precision of reversible transverse relaxation time measurements also by average factors of 4 ex vivo and 3 in volunteers. The mean relaxation times of the Gaussian model in volunteers are T2,G' = (1.97 ± 0.27) msec at 1.5 T and T2,G' = (0.83 ± 0.21) msec at 3 T. Pulmonary signal relaxation was found to be accurately modeled as Gaussian, providing a potential biomarker T2,G' with high sensitivity. Magn Reson Med 77:1938-1945, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

A semi-Markov model for mitosis segmentation in time-lapse phase contrast microscopy image sequences of stem cell populations.

PubMed

Liu, An-An; Li, Kang; Kanade, Takeo

2012-02-01

We propose a semi-Markov model trained in a max-margin learning framework for mitosis event segmentation in large-scale time-lapse phase contrast microscopy image sequences of stem cell populations. Our method consists of three steps. First, we apply a constrained optimization based microscopy image segmentation method that exploits phase contrast optics to extract candidate subsequences in the input image sequence that contains mitosis events. Then, we apply a max-margin hidden conditional random field (MM-HCRF) classifier learned from human-annotated mitotic and nonmitotic sequences to classify each candidate subsequence as a mitosis or not. Finally, a max-margin semi-Markov model (MM-SMM) trained on manually-segmented mitotic sequences is utilized to reinforce the mitosis classification results, and to further segment each mitosis into four predefined temporal stages. The proposed method outperforms the event-detection CRF model recently reported by Huh as well as several other competing methods in very challenging image sequences of multipolar-shaped C3H10T1/2 mesenchymal stem cells. For mitosis detection, an overall precision of 95.8% and a recall of 88.1% were achieved. For mitosis segmentation, the mean and standard deviation for the localization errors of the start and end points of all mitosis stages were well below 1 and 2 frames, respectively. In particular, an overall temporal location error of 0.73 ± 1.29 frames was achieved for locating daughter cell birth events.

Memetic algorithms for de novo motif-finding in biomedical sequences.

PubMed

Bi, Chengpeng

2012-09-01

The objectives of this study are to design and implement a new memetic algorithm for de novo motif discovery, which is then applied to detect important signals hidden in various biomedical molecular sequences. In this paper, memetic algorithms are developed and tested in de novo motif-finding problems. Several strategies in the algorithm design are employed that are to not only efficiently explore the multiple sequence local alignment space, but also effectively uncover the molecular signals. As a result, there are a number of key features in the implementation of the memetic motif-finding algorithm (MaMotif), including a chromosome replacement operator, a chromosome alteration-aware local search operator, a truncated local search strategy, and a stochastic operation of local search imposed on individual learning. To test the new algorithm, we compare MaMotif with a few of other similar algorithms using simulated and experimental data including genomic DNA, primary microRNA sequences (let-7 family), and transmembrane protein sequences. The new memetic motif-finding algorithm is successfully implemented in C++, and exhaustively tested with various simulated and real biological sequences. In the simulation, it shows that MaMotif is the most time-efficient algorithm compared with others, that is, it runs 2 times faster than the expectation maximization (EM) method and 16 times faster than the genetic algorithm-based EM hybrid. In both simulated and experimental testing, results show that the new algorithm is compared favorably or superior to other algorithms. Notably, MaMotif is able to successfully discover the transcription factors' binding sites in the chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) data, correctly uncover the RNA splicing signals in gene expression, and precisely find the highly conserved helix motif in the transmembrane protein sequences, as well as rightly detect the palindromic segments in the primary microRNA sequences. The memetic motif-finding algorithm is effectively designed and implemented, and its applications demonstrate it is not only time-efficient, but also exhibits excellent performance while compared with other popular algorithms. Copyright © 2012 Elsevier B.V. All rights reserved.

QCScreen: a software tool for data quality control in LC-HRMS based metabolomics.

PubMed

Simader, Alexandra Maria; Kluger, Bernhard; Neumann, Nora Katharina Nicole; Bueschl, Christoph; Lemmens, Marc; Lirk, Gerald; Krska, Rudolf; Schuhmacher, Rainer

2015-10-24

Metabolomics experiments often comprise large numbers of biological samples resulting in huge amounts of data. This data needs to be inspected for plausibility before data evaluation to detect putative sources of error e.g. retention time or mass accuracy shifts. Especially in liquid chromatography-high resolution mass spectrometry (LC-HRMS) based metabolomics research, proper quality control checks (e.g. for precision, signal drifts or offsets) are crucial prerequisites to achieve reliable and comparable results within and across experimental measurement sequences. Software tools can support this process. The software tool QCScreen was developed to offer a quick and easy data quality check of LC-HRMS derived data. It allows a flexible investigation and comparison of basic quality-related parameters within user-defined target features and the possibility to automatically evaluate multiple sample types within or across different measurement sequences in a short time. It offers a user-friendly interface that allows an easy selection of processing steps and parameter settings. The generated results include a coloured overview plot of data quality across all analysed samples and targets and, in addition, detailed illustrations of the stability and precision of the chromatographic separation, the mass accuracy and the detector sensitivity. The use of QCScreen is demonstrated with experimental data from metabolomics experiments using selected standard compounds in pure solvent. The application of the software identified problematic features, samples and analytical parameters and suggested which data files or compounds required closer manual inspection. QCScreen is an open source software tool which provides a useful basis for assessing the suitability of LC-HRMS data prior to time consuming, detailed data processing and subsequent statistical analysis. It accepts the generic mzXML format and thus can be used with many different LC-HRMS platforms to process both multiple quality control sample types as well as experimental samples in one or more measurement sequences.

Precision Medicine and the Changing Landscape of Research Ethics.

PubMed

Hammer, Marilyn J

2016-03-01

President Barack Obama announced the launch of the National Institutes of Health Precision Medicine Initiative® (PMI) in January 2015. Precision medicine includes the concept of individualized or personalized medicine at a more exact level through advances in science and technology, such as genetics and genomics sequencing. Although many disease processes will be investigated through the precision medicine lens for greater understanding and improved treatment responses, oncology research and translation to practice is leading the initiative's debut, referred to as the near-term focus.

A new approach to investigate an eruptive paroxysmal sequence using camera and strainmeter networks: Lessons from the 3-5 December 2015 activity at Etna volcano

NASA Astrophysics Data System (ADS)

Bonaccorso, A.; Calvari, S.

2017-10-01

Explosive sequences are quite common at basaltic and andesitic volcanoes worldwide. Studies aimed at short-term forecasting are usually based on seismic and ground deformation measurements, which can be used to constrain the source region and quantify the magma volume involved in the eruptive process. However, during single episodes of explosive sequences, integration of camera remote sensing and geophysical data are scant in literature, and the total volume of pyroclastic products is not determined. In this study, we calculate eruption parameters for four powerful lava fountains occurring at the main and oldest Mt. Etna summit crater, Voragine, between 3 and 5 December 2015. These episodes produced impressive eruptive columns and plume clouds, causing lapilli and ash fallout to more than 100 km away. We analyse these paroxysmal events by integrating the images recorded by a network of monitoring cameras and the signals from three high-precision borehole strainmeters. From the camera images we calculated the total erupted volume of fluids (gas plus pyroclastics), inferring amounts from 1.9 ×109 m3 (first event) to 0.86 ×109 m3 (third event). Strain changes recorded during the first and most powerful event were used to constrain the depth of the source. The ratios of strain changes recorded at two stations during the four lava fountains were used to constrain the pyroclastic fraction for each eruptive event. The results revealed that the explosive sequence was characterized by a decreasing trend of erupted pyroclastics with time, going from 41% (first event) to 13% (fourth event) of the total erupted pyroclastic volume. Moreover, the volume ratio fluid/pyroclastic decreased markedly in the fourth and last event. To the best of our knowledge, this is the first time ever that erupted volumes of both fluid and pyroclastics have been estimated for an explosive sequence from a monitoring system using permanent cameras and high precision strainmeters. During future explosive paroxysmal sequences this new approach might help in monitoring their evolution also to understand when/if they are going to finish. Knowledge of the total gas and pyroclastic fractions erupted during each lava fountain episode would improve our understanding of their processes and eruptive behaviour.

ABI Base Recall: Automatic Correction and Ends Trimming of DNA Sequences.

PubMed

Elyazghi, Zakaria; Yazouli, Loubna El; Sadki, Khalid; Radouani, Fouzia

2017-12-01

Automated DNA sequencers produce chromatogram files in ABI format. When viewing chromatograms, some ambiguities are shown at various sites along the DNA sequences, because the program implemented in the sequencing machine and used to call bases cannot always precisely determine the right nucleotide, especially when it is represented by either a broad peak or a set of overlaying peaks. In such cases, a letter other than A, C, G, or T is recorded, most commonly N. Thus, DNA sequencing chromatograms need manual examination: checking for mis-calls and truncating the sequence when errors become too frequent. The purpose of this paper is to develop a program allowing the automatic correction of these ambiguities. This application is a Web-based program powered by Shiny and runs under R platform for an easy exploitation. As a part of the interface, we added the automatic ends clipping option, alignment against reference sequences, and BLAST. To develop and test our tool, we collected several bacterial DNA sequences from different laboratories within Institut Pasteur du Maroc and performed both manual and automatic correction. The comparison between the two methods was carried out. As a result, we note that our program, ABI base recall, accomplishes good correction with a high accuracy. Indeed, it increases the rate of identity and coverage and minimizes the number of mismatches and gaps, hence it provides solution to sequencing ambiguities and saves biologists' time and labor.

Acceleration of the Smith-Waterman algorithm using single and multiple graphics processors

NASA Astrophysics Data System (ADS)

Khajeh-Saeed, Ali; Poole, Stephen; Blair Perot, J.

2010-06-01

Finding regions of similarity between two very long data streams is a computationally intensive problem referred to as sequence alignment. Alignment algorithms must allow for imperfect sequence matching with different starting locations and some gaps and errors between the two data sequences. Perhaps the most well known application of sequence matching is the testing of DNA or protein sequences against genome databases. The Smith-Waterman algorithm is a method for precisely characterizing how well two sequences can be aligned and for determining the optimal alignment of those two sequences. Like many applications in computational science, the Smith-Waterman algorithm is constrained by the memory access speed and can be accelerated significantly by using graphics processors (GPUs) as the compute engine. In this work we show that effective use of the GPU requires a novel reformulation of the Smith-Waterman algorithm. The performance of this new version of the algorithm is demonstrated using the SSCA#1 (Bioinformatics) benchmark running on one GPU and on up to four GPUs executing in parallel. The results indicate that for large problems a single GPU is up to 45 times faster than a CPU for this application, and the parallel implementation shows linear speed up on up to 4 GPUs.

A new method to cluster genomes based on cumulative Fourier power spectrum.

PubMed

Dong, Rui; Zhu, Ziyue; Yin, Changchuan; He, Rong L; Yau, Stephen S-T

2018-06-20

Analyzing phylogenetic relationships using mathematical methods has always been of importance in bioinformatics. Quantitative research may interpret the raw biological data in a precise way. Multiple Sequence Alignment (MSA) is used frequently to analyze biological evolutions, but is very time-consuming. When the scale of data is large, alignment methods cannot finish calculation in reasonable time. Therefore, we present a new method using moments of cumulative Fourier power spectrum in clustering the DNA sequences. Each sequence is translated into a vector in Euclidean space. Distances between the vectors can reflect the relationships between sequences. The mapping between the spectra and moment vector is one-to-one, which means that no information is lost in the power spectra during the calculation. We cluster and classify several datasets including Influenza A, primates, and human rhinovirus (HRV) datasets to build up the phylogenetic trees. Results show that the new proposed cumulative Fourier power spectrum is much faster and more accurately than MSA and another alignment-free method known as k-mer. The research provides us new insights in the study of phylogeny, evolution, and efficient DNA comparison algorithms for large genomes. The computer programs of the cumulative Fourier power spectrum are available at GitHub (https://github.com/YaulabTsinghua/cumulative-Fourier-power-spectrum). Copyright © 2018. Published by Elsevier B.V.

The in-plant evaluation of a uranium NDA system

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

Sprinkle, J.K. Jr.; Baxman, H.R.; Langner, D.G.

1979-12-31

The Los Alamos Scientific Laboratory has an unirradiated enriched uranium reprocessing facility. Various types of solutions are generated in this facility, including distillates and raffinates containing ppm of uranium and concentrated solutions with up to 400 grams U/t. In addition to uranyl nitrate and HNO{sub 3}, the solutions may also contain zirconium, niobium, fluoride, and small amounts of many metals. A uranium solution assay system (USAS) has been installed to allow accurate and more timely process control, accountability, and criticality data to be obtained. The USAS assays are made by a variety of techniques that depend upon state-of-the-art high-resolution Ge(Li)more » gamma-ray spectroscopy integrated with an interactive, user-oriented computer software package. Tight control of the system`s performance is maintained by constantly monitoring the USAS status. Daily measurement control sequences are required, and the user is forced by the software to perform these sequences. Routine assays require 400 or 1000 seconds for a precision of 0.5% over the concentration range of 5--400 g/t. A comparison of the USAS precision and accuracy with that obtained by traditional destructive analytical chemistry techniques (colorimetric and volumetric) is presented.« less

The in-plant evaluation of a uranium NDA system

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

Sprinkle, J.K. Jr.; Baxman, H.R.; Langner, D.G.

1979-01-01

The Los Alamos Scientific Laboratory has an unirradiated enriched uranium reprocessing facility. Various types of solutions are generated in this facility, including distillates and raffinates containing ppm of uranium and concentrated solutions with up to 400 grams U/t. In addition to uranyl nitrate and HNO{sub 3}, the solutions may also contain zirconium, niobium, fluoride, and small amounts of many metals. A uranium solution assay system (USAS) has been installed to allow accurate and more timely process control, accountability, and criticality data to be obtained. The USAS assays are made by a variety of techniques that depend upon state-of-the-art high-resolution Ge(Li)more » gamma-ray spectroscopy integrated with an interactive, user-oriented computer software package. Tight control of the system's performance is maintained by constantly monitoring the USAS status. Daily measurement control sequences are required, and the user is forced by the software to perform these sequences. Routine assays require 400 or 1000 seconds for a precision of 0.5% over the concentration range of 5--400 g/t. A comparison of the USAS precision and accuracy with that obtained by traditional destructive analytical chemistry techniques (colorimetric and volumetric) is presented.« less

RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PubMed

Xiong, Hui Y; Alipanahi, Babak; Lee, Leo J; Bretschneider, Hannes; Merico, Daniele; Yuen, Ryan K C; Hua, Yimin; Gueroussov, Serge; Najafabadi, Hamed S; Hughes, Timothy R; Morris, Quaid; Barash, Yoseph; Krainer, Adrian R; Jojic, Nebojsa; Scherer, Stephen W; Blencowe, Benjamin J; Frey, Brendan J

2015-01-09

To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic and exonic variants revealed widespread patterns of mutation-driven aberrant splicing. Intronic disease mutations that are more than 30 nucleotides from any splice site alter splicing nine times as often as common variants, and missense exonic disease mutations that have the least impact on protein function are five times as likely as others to alter splicing. We detected tens of thousands of disease-causing mutations, including those involved in cancers and spinal muscular atrophy. Examination of intronic and exonic variants found using whole-genome sequencing of individuals with autism revealed misspliced genes with neurodevelopmental phenotypes. Our approach provides evidence for causal variants and should enable new discoveries in precision medicine. Copyright © 2015, American Association for the Advancement of Science.

Quantum measurement and orientation tracking of fluorescent nanodiamonds inside living cells

NASA Astrophysics Data System (ADS)

McGuinness, L. P.; Yan, Y.; Stacey, A.; Simpson, D. A.; Hall, L. T.; MacLaurin, D.; Prawer, S.; Mulvaney, P.; Wrachtrup, J.; Caruso, F.; Scholten, R. E.; Hollenberg, L. C. L.

2011-06-01

Fluorescent particles are routinely used to probe biological processes. The quantum properties of single spins within fluorescent particles have been explored in the field of nanoscale magnetometry, but not yet in biological environments. Here, we demonstrate optically detected magnetic resonance of individual fluorescent nanodiamond nitrogen-vacancy centres inside living human HeLa cells, and measure their location, orientation, spin levels and spin coherence times with nanoscale precision. Quantum coherence was measured through Rabi and spin-echo sequences over long (>10 h) periods, and orientation was tracked with effective 1° angular precision over acquisition times of 89 ms. The quantum spin levels served as fingerprints, allowing individual centres with identical fluorescence to be identified and tracked simultaneously. Furthermore, monitoring decoherence rates in response to changes in the local environment may provide new information about intracellular processes. The experiments reported here demonstrate the viability of controlled single spin probes for nanomagnetometry in biological systems, opening up a host of new possibilities for quantum-based imaging in the life sciences.

Experimental study of the role of trap symmetry in an atom-chip interferometer above the Bose–Einstein condensation threshold

NASA Astrophysics Data System (ADS)

Dupont-Nivet, M.; Demur, R.; Westbrook, C. I.; Schwartz, S.

2018-04-01

We report the experimental study of an atom-chip interferometer using ultracold rubidium 87 atoms above the Bose–Einstein condensation threshold. The observed dependence of the contrast decay time with temperature and with the degree of symmetry of the traps during the interferometer sequence is in good agreement with theoretical predictions published in Dupont-Nivet et al (2016 New J. Phys. 18 113012). These results pave the way for precision measurements with trapped thermal atoms.

Edge enhancement of color images using a digital micromirror device.

PubMed

Di Martino, J Matías; Flores, Jorge L; Ayubi, Gastón A; Alonso, Julia R; Fernández, Ariel; Ferrari, José A

2012-06-01

A method for orientation-selective enhancement of edges in color images is proposed. The method utilizes the capacity of digital micromirror devices to generate a positive and a negative color replica of the image used as input. When both images are slightly displaced and imagined together, one obtains an image with enhanced edges. The proposed technique does not require a coherent light source or precise alignment. The proposed method could be potentially useful for processing large image sequences in real time. Validation experiments are presented.

Subangstrom Measurements of Enzyme Function Using a Biological Nanopore, SPRNT.

PubMed

Laszlo, A H; Derrrington, I M; Gundlach, J H

2017-01-01

Nanopores are emerging as new single-molecule tools in the study of enzymes. Based on the progress in nanopore sequencing of DNA, a tool called Single-molecule Picometer Resolution Nanopore Tweezers (SPRNT) was developed to measure the movement of enzymes along DNA in real time. In this new method, an enzyme is loaded onto a DNA (or RNA) molecule. A single-stranded DNA end of this complex is drawn into a nanopore by an electrostatic potential that is applied across the pore. The single-stranded DNA passes through the pore's constriction until the enzyme comes into contact with the pore. Further progression of the DNA through the pore is then controlled by the enzyme. An ion current that flows through the pore's constriction is modulated by the DNA in the constriction. Analysis of ion current changes reveals the advance of the DNA with high spatiotemporal precision, thereby providing a real-time record of the enzyme's activity. Using an engineered version of the protein nanopore MspA, SPRNT has spatial resolution as small as 40pm at millisecond timescales, while simultaneously providing the DNA's sequence within the enzyme. In this chapter, SPRNT is introduced and its extraordinary potential is exemplified using the helicase Hel308. Two distinct substates are observed for each one-nucleotide advance; one of these about half-nucleotide long steps is ATP dependent and the other is ATP independent. The spatiotemporal resolution of this low-cost single-molecule technique lifts the study of enzymes to a new level of precision, enabling exploration of hitherto unobservable enzyme dynamics in real time. © 2017 Elsevier Inc. All rights reserved.

Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics.

PubMed

Collins, Dearbhaile C; Sundar, Raghav; Lim, Joline S J; Yap, Timothy A

2017-01-01

Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize treatment efficacy and minimize toxicity. Utilizing these different targeted agents in combination or in sequence may further delay resistance to treatments and prolong antitumor responses. Remarkable progress in the field of immunotherapy adds another layer of complexity to the management of cancer patients. Corresponding advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs act synergistically to further precision medicine. Ongoing hurdles such as clonal evolution, intra- and intertumor heterogeneity, and varied mechanisms of drug resistance continue to be challenges to overcome. Large-scale data-sharing and collaborative networks using next-generation sequencing (NGS) platforms promise to take us further into the cancer 'ome' than ever before, with the goal of achieving successful precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

SAR operational aspects

NASA Astrophysics Data System (ADS)

Holmdahl, P. E.; Ellis, A. B. E.; Moeller-Olsen, P.; Ringgaard, J. P.

1981-12-01

The basic requirements of the SAR ground segment of ERS-1 are discussed. A system configuration for the real time data acquisition station and the processing and archive facility is depicted. The functions of a typical SAR processing unit (SPU) are specified, and inputs required for near real time and full precision, deferred time processing are described. Inputs and the processing required for provision of these inputs to the SPU are dealt with. Data flow through the systems, and normal and nonnormal operational sequence, are outlined. Prerequisites for maintaining overall performance are identified, emphasizing quality control. The most demanding tasks to be performed by the front end are defined in order to determine types of processors and peripherals which comply with throughput requirements.

On improving the speed and reliability of T2-Relaxation-Under-Spin-Tagging (TRUST) MRI

PubMed Central

Xu, Feng; Uh, Jinsoo; Liu, Peiying; Lu, Hanzhang

2011-01-01

A T2-Relaxation-Under-Spin-Tagging (TRUST) technique was recently developed to estimate cerebral blood oxygenation, providing potentials for non-invasive assessment of the brain's oxygen consumption. A limitation of the current sequence is the need for long TR, as shorter TR causes an over-estimation in blood R2. The present study proposes a post-saturation TRUST by placing a non-selective 90° pulse after the signal acquisition to reset magnetization in the whole brain. This scheme was found to eliminate estimation bias at a slight cost of precision. To improve the precision, TE of the sequence was optimized and it was found that a modest TE shortening of 3.4ms can reduce the estimation error by 49%. We recommend the use of post-saturation TRUST sequence with a TR of 3000ms and a TE of 3.6ms, which allows the determination of global venous oxygenation with scan duration of 1 minute 12 seconds and an estimation precision of ±1% (in units of oxygen saturation percentage). PMID:22127845

The sequence measurement system of the IR camera

NASA Astrophysics Data System (ADS)

Geng, Ai-hui; Han, Hong-xia; Zhang, Hai-bo

2011-08-01

Currently, the IR cameras are broadly used in the optic-electronic tracking, optic-electronic measuring, fire control and optic-electronic countermeasure field, but the output sequence of the most presently applied IR cameras in the project is complex and the giving sequence documents from the leave factory are not detailed. Aiming at the requirement that the continuous image transmission and image procession system need the detailed sequence of the IR cameras, the sequence measurement system of the IR camera is designed, and the detailed sequence measurement way of the applied IR camera is carried out. The FPGA programming combined with the SignalTap online observation way has been applied in the sequence measurement system, and the precise sequence of the IR camera's output signal has been achieved, the detailed document of the IR camera has been supplied to the continuous image transmission system, image processing system and etc. The sequence measurement system of the IR camera includes CameraLink input interface part, LVDS input interface part, FPGA part, CameraLink output interface part and etc, thereinto the FPGA part is the key composed part in the sequence measurement system. Both the video signal of the CmaeraLink style and the video signal of LVDS style can be accepted by the sequence measurement system, and because the image processing card and image memory card always use the CameraLink interface as its input interface style, the output signal style of the sequence measurement system has been designed into CameraLink interface. The sequence measurement system does the IR camera's sequence measurement work and meanwhile does the interface transmission work to some cameras. Inside the FPGA of the sequence measurement system, the sequence measurement program, the pixel clock modification, the SignalTap file configuration and the SignalTap online observation has been integrated to realize the precise measurement to the IR camera. Te sequence measurement program written by the verilog language combining the SignalTap tool on line observation can count the line numbers in one frame, pixel numbers in one line and meanwhile account the line offset and row offset of the image. Aiming at the complex sequence of the IR camera's output signal, the sequence measurement system of the IR camera accurately measures the sequence of the project applied camera, supplies the detailed sequence document to the continuous system such as image processing system and image transmission system and gives out the concrete parameters of the fval, lval, pixclk, line offset and row offset. The experiment shows that the sequence measurement system of the IR camera can get the precise sequence measurement result and works stably, laying foundation for the continuous system.

Characterization of emergent synaptic topologies in noisy neural networks

NASA Astrophysics Data System (ADS)

Miller, Aaron James

Learned behaviors are one of the key contributors to an animal's ultimate survival. It is widely believed that the brain's microcircuitry undergoes structural changes when a new behavior is learned. In particular, motor learning, during which an animal learns a sequence of muscular movements, often requires precisely-timed coordination between muscles and becomes very natural once ingrained. Experiments show that neurons in the motor cortex exhibit precisely-timed spike activity when performing a learned motor behavior, and constituent stereotypical elements of the behavior can last several hundred milliseconds. The subject of this manuscript concerns how organized synaptic structures that produce stereotypical spike sequences emerge from random, dynamical networks. After a brief introduction in Chapter 1, we begin Chapter 2 by introducing a spike-timing-dependent plasticity (STDP) rule that defines how the activity of the network drives changes in network topology. The rule is then applied to idealized networks of leaky integrate-and-fire neurons (LIF). These neurons are not subjected to the variability that typically characterize neurons in vivo. In noiseless networks, synapses develop closed loops of strong connectivity that reproduce stereotypical, precisely-timed spike patterns from an initially random network. We demonstrate the characteristics of the asymptotic synaptic configuration are dependent on the statistics of the initial random network. The spike timings of the neurons simulated in Chapter 2 are generated exactly by a computationally economical, nonlinear mapping which is extended to LIF neurons injected with fluctuating current in Chapter 3. Development of an economical mapping that incorporates noise provides a practical solution to the long simulation times required to produce asymptotic synaptic topologies in networks with STDP in the presence of realistic neuronal variability. The mapping relies on generating numerical solutions to the dynamics of a LIF neuron subjected to Gaussian white noise (GWN). The system reduces to the Ornstein-Uhlenbeck first passage time problem, the solution of which we build into the mapping method of Chapter 2. We demonstrate that simulations using the stochastic mapping have reduced computation time compared to traditional Runge-Kutta methods by more than a factor of 150. In Chapter 4, we use the stochastic mapping to study the dynamics of emerging synaptic topologies in noisy networks. With the addition of membrane noise, networks with dynamical synapses can admit states in which the distribution of the synaptic weights is static under spontaneous activity, but the random connectivity between neurons is dynamical. The widely cited problem of instabilities in networks with STDP is avoided with the implementation of a synaptic decay and an activation threshold on each synapse. When such networks are presented with stimulus modeled by a focused excitatory current, chain-like networks can emerge with the addition of an axon-remodeling plasticity rule, a topological constraint on the connectivity modeling the finite resources available to each neuron. The emergent topologies are the result of an iterative stochastic process. The dynamics of the growth process suggest a strong interplay between the network topology and the spike sequences they produce during development. Namely, the existence of an embedded spike sequence alters the distribution of synaptic weights through the entire network. The roles of model parameters that affect the interplay between network structure and activity are elucidated. Finally, we propose two mathematical growth models, which are complementary, that capture the essence of the growth dynamics observed in simulations. In Chapter 5, we present an extension of the stochastic mapping that allows the possibility of neuronal cooperation. We demonstrate that synaptic topologies admitting stereotypical sequences can emerge in yet higher, biologically realistic levels of membrane potential variability when neurons cooperate to innervate shared targets. The structure that is most robust to the variability is that of a synfire chain. The principles of growth dynamics detailed in Chapter 4 are the same that sculpt the emergent synfire topologies. We conclude by discussing avenues for extensions of these results.

Novel methodologies for spectral classification of exon and intron sequences

NASA Astrophysics Data System (ADS)

Kwan, Hon Keung; Kwan, Benjamin Y. M.; Kwan, Jennifer Y. Y.

2012-12-01

Digital processing of a nucleotide sequence requires it to be mapped to a numerical sequence in which the choice of nucleotide to numeric mapping affects how well its biological properties can be preserved and reflected from nucleotide domain to numerical domain. Digital spectral analysis of nucleotide sequences unfolds a period-3 power spectral value which is more prominent in an exon sequence as compared to that of an intron sequence. The success of a period-3 based exon and intron classification depends on the choice of a threshold value. The main purposes of this article are to introduce novel codes for 1-sequence numerical representations for spectral analysis and compare them to existing codes to determine appropriate representation, and to introduce novel thresholding methods for more accurate period-3 based exon and intron classification of an unknown sequence. The main findings of this study are summarized as follows: Among sixteen 1-sequence numerical representations, the K-Quaternary Code I offers an attractive performance. A windowed 1-sequence numerical representation (with window length of 9, 15, and 24 bases) offers a possible speed gain over non-windowed 4-sequence Voss representation which increases as sequence length increases. A winner threshold value (chosen from the best among two defined threshold values and one other threshold value) offers a top precision for classifying an unknown sequence of specified fixed lengths. An interpolated winner threshold value applicable to an unknown and arbitrary length sequence can be estimated from the winner threshold values of fixed length sequences with a comparable performance. In general, precision increases as sequence length increases. The study contributes an effective spectral analysis of nucleotide sequences to better reveal embedded properties, and has potential applications in improved genome annotation.

Massively parallel sequencing of 32 forensic markers using the Precision ID GlobalFiler™ NGS STR Panel and the Ion PGM™ System.

PubMed

Wang, Zheng; Zhou, Di; Wang, Hui; Jia, Zhenjun; Liu, Jing; Qian, Xiaoqin; Li, Chengtao; Hou, Yiping

2017-11-01

Massively parallel sequencing (MPS) technologies have proved capable of sequencing the majority of the key forensic STR markers. By MPS, not only the repeat-length size but also sequence variations could be detected. Recently, Thermo Fisher Scientific has designed an advanced MPS 32-plex panel, named the Precision ID GlobalFiler™ NGS STR Panel, where the primer set has been designed specifically for the purpose of MPS technologies and the data analysis are supported by a new version HID STR Genotyper Plugin (V4.0). In this study, a series of experiments that evaluated concordance, reliability, sensitivity of detection, mixture analysis, and the ability to analyze case-type and challenged samples were conducted. In addition, 106 unrelated Han individuals were sequenced to perform genetic analyses of allelic diversity. As expected, MPS detected broader allele variations and gained higher power of discrimination and exclusion rate. MPS results were found to be concordant with current capillary electrophoresis methods, and single source complete profiles could be obtained stably using as little as 100pg of input DNA. Moreover, this MPS panel could be adapted to case-type samples and partial STR genotypes of the minor contributor could be detected up to 19:1 mixture. Aforementioned results indicate that the Precision ID GlobalFiler™ NGS STR Panel is reliable, robust and reproducible and have the potential to be used as a tool for human forensics. Copyright © 2017 Elsevier B.V. All rights reserved.

Progress of targeted genome modification approaches in higher plants.

PubMed

Cardi, Teodoro; Neal Stewart, C

2016-07-01

Transgene integration in plants is based on illegitimate recombination between non-homologous sequences. The low control of integration site and number of (trans/cis)gene copies might have negative consequences on the expression of transferred genes and their insertion within endogenous coding sequences. The first experiments conducted to use precise homologous recombination for gene integration commenced soon after the first demonstration that transgenic plants could be produced. Modern transgene targeting categories used in plant biology are: (a) homologous recombination-dependent gene targeting; (b) recombinase-mediated site-specific gene integration; (c) oligonucleotide-directed mutagenesis; (d) nuclease-mediated site-specific genome modifications. New tools enable precise gene replacement or stacking with exogenous sequences and targeted mutagenesis of endogeneous sequences. The possibility to engineer chimeric designer nucleases, which are able to target virtually any genomic site, and use them for inducing double-strand breaks in host DNA create new opportunities for both applied plant breeding and functional genomics. CRISPR is the most recent technology available for precise genome editing. Its rapid adoption in biological research is based on its inherent simplicity and efficacy. Its utilization, however, depends on available sequence information, especially for genome-wide analysis. We will review the approaches used for genome modification, specifically those for affecting gene integration and modification in higher plants. For each approach, the advantages and limitations will be noted. We also will speculate on how their actual commercial development and implementation in plant breeding will be affected by governmental regulations.

Quasi-metagenomics and realtime sequencing aided detection and subtyping of Salmonella enterica from food samples.

PubMed

Hyeon, Ji-Yeon; Li, Shaoting; Mann, David A; Zhang, Shaokang; Li, Zhen; Chen, Yi; Deng, Xiangyu

2017-12-01

Metagenomics analysis of food samples promises isolation-independent detection and subtyping of foodborne bacterial pathogens in a single workflow. Selective concentration of Salmonella genomic DNA through immunomagnetic separation (IMS) and multiple displacement amplification (MDA) were shown to shorten culture enrichment of Salmonella -spiked raw chicken breast samples by over 12 hours while permitting serotyping and high-fidelity single nucleotide polymorphisms (SNP) typing of the pathogen using short shotgun sequencing reads. The herein termed quasi-metagenomics approach was evaluated on Salmonella -spiked lettuce and black peppercorn samples as well as retail chicken parts naturally contaminated with different serotypes of Salmonella. Between 8 and 24 h culture enrichment was required for detecting and subtyping naturally occurring Salmonella from unspiked chicken parts compared with 4 to 12 h culture enrichment when Salmonella -spiked food samples were analyzed, indicating the likely need for longer culture enrichment to revive low levels of stressed or injured Salmonella cells in food. Further acceleration of the workflow was achieved by real-time nanopore sequencing. After 1.5 hours of analysis on a potable sequencer, sufficient data were generated from sequencing IMS-MDA product of a cultured-enriched lettuce sample to allow serotyping and robust phylogenetic placement of the inoculated isolate. Importance Both culture enrichment and next-generation sequencing remain to be time-consuming processes for food testing where rapid methods for pathogen detection are widely available. Our study demonstrated substantial acceleration of the respective process through IMS-MDA and real-time nanopore sequencing. In one example, the combined use of the two methods delivered a less than 24 h turnaround time from a Salmonella -contaminated lettuce sample to phylogenetic identification of the pathogen. Improved efficiency like this is important for further expanding the use of whole genome and metagenomics sequencing in microbial analysis of food. Our results suggest the potential of the quasi-metagenomics approach in areas where rapid detection and subtyping of foodborne pathogens is important, such as foodborne outbreak response and precision tracking and monitoring of foodborne pathogens in production environments and supply chains. Copyright © 2017 American Society for Microbiology.

On the phylogenetic placement of human T cell leukemia virus type 1 sequences associated with an Andean mummy.

PubMed

Coulthart, Michael B; Posada, David; Crandall, Keith A; Dekaban, Gregory A

2006-03-01

Recently, the putative finding of ancient human T cell leukemia virus type 1 (HTLV-1) long terminal repeat (LTR) DNA sequences in association with a 1500-year-old Chilean mummy has stirred vigorous debate. The debate is based partly on the inherent uncertainties associated with phylogenetic reconstruction when only short sequences of closely related genotypes are available. However, a full analysis of what phylogenetic information is present in the mummy data has not previously been published, leaving open the question of what precisely is the range of admissible interpretation. To fulfill this need, we re-analyzed the mummy data in a new way. We first performed phylogenetic analysis of 188 published LTR DNA sequences from extant strains belonging to the HTLV-1 Cosmopolitan clade, using the method of statistical parsimony which is designed both to optimize phylogenetic resolution among sequences with little evolutionary divergence, and to permit precise mapping of individual sequence mutations onto branches of a divergence network. We then deduced possible phylogenetic positions for the two main categories of published Chilean mummy sequences, based on their published 157-nucleotide LTR sequences. The possible phylogenetic placements for one of the mummy sequence categories are consistent with a modern origin. However, one of these placements for the other mummy sequence category falls very close to the root of the Cosmopolitan clade, consistent with an ancient origin for both this mummy sequence and the Cosmopolitan clade.

pyGeno: A Python package for precision medicine and proteogenomics.

PubMed

Daouda, Tariq; Perreault, Claude; Lemieux, Sébastien

2016-01-01

pyGeno is a Python package mainly intended for precision medicine applications that revolve around genomics and proteomics. It integrates reference sequences and annotations from Ensembl, genomic polymorphisms from the dbSNP database and data from next-gen sequencing into an easy to use, memory-efficient and fast framework, therefore allowing the user to easily explore subject-specific genomes and proteomes. Compared to a standalone program, pyGeno gives the user access to the complete expressivity of Python, a general programming language. Its range of application therefore encompasses both short scripts and large scale genome-wide studies.

pyGeno: A Python package for precision medicine and proteogenomics

PubMed Central

Daouda, Tariq; Perreault, Claude; Lemieux, Sébastien

2016-01-01

pyGeno is a Python package mainly intended for precision medicine applications that revolve around genomics and proteomics. It integrates reference sequences and annotations from Ensembl, genomic polymorphisms from the dbSNP database and data from next-gen sequencing into an easy to use, memory-efficient and fast framework, therefore allowing the user to easily explore subject-specific genomes and proteomes. Compared to a standalone program, pyGeno gives the user access to the complete expressivity of Python, a general programming language. Its range of application therefore encompasses both short scripts and large scale genome-wide studies. PMID:27785359

Detecting Nano-Scale Vibrations in Rotating Devices by Using Advanced Computational Methods

PubMed Central

del Toro, Raúl M.; Haber, Rodolfo E.; Schmittdiel, Michael C.

2010-01-01

This paper presents a computational method for detecting vibrations related to eccentricity in ultra precision rotation devices used for nano-scale manufacturing. The vibration is indirectly measured via a frequency domain analysis of the signal from a piezoelectric sensor attached to the stationary component of the rotating device. The algorithm searches for particular harmonic sequences associated with the eccentricity of the device rotation axis. The detected sequence is quantified and serves as input to a regression model that estimates the eccentricity. A case study presents the application of the computational algorithm during precision manufacturing processes. PMID:22399918

Materials and methods for stabilizing nanoparticles in salt solutions

DOEpatents

Robinson, David Bruce; Zuckermann, Ronald; Buffleben, George M.

2013-06-11

Sequence-specific polymers are proving to be a powerful approach to assembly and manipulation of matter on the nanometer scale. Ligands that are peptoids, or sequence-specific N-functional glycine oligomers, allow precise and flexible control over the arrangement of binding groups, steric spacers, charge, and other functionality. We have synthesized short peptoids that can prevent the aggregation of gold nanoparticles in high-salt environments including divalent salt, and allow co-adsorption of a single DNA molecule. This degree of precision and versatility is likely to prove essential in bottom-up assembly of nanostructures and in biomedical applications of nanomaterials.

Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data

PubMed Central

Watson, Christopher M.; Crinnion, Laura A.; Gurgel‐Gianetti, Juliana; Harrison, Sally M.; Daly, Catherine; Antanavicuite, Agne; Lascelles, Carolina; Markham, Alexander F.; Pena, Sergio D. J.; Bonthron, David T.

2015-01-01

ABSTRACT Autozygosity mapping is a powerful technique for the identification of rare, autosomal recessive, disease‐causing genes. The ease with which this category of disease gene can be identified has greatly increased through the availability of genome‐wide SNP genotyping microarrays and subsequently of exome sequencing. Although these methods have simplified the generation of experimental data, its analysis, particularly when disparate data types must be integrated, remains time consuming. Moreover, the huge volume of sequence variant data generated from next generation sequencing experiments opens up the possibility of using these data instead of microarray genotype data to identify disease loci. To allow these two types of data to be used in an integrated fashion, we have developed AgileVCFMapper, a program that performs both the mapping of disease loci by SNP genotyping and the analysis of potentially deleterious variants using exome sequence variant data, in a single step. This method does not require microarray SNP genotype data, although analysis with a combination of microarray and exome genotype data enables more precise delineation of disease loci, due to superior marker density and distribution. PMID:26037133

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.

The Early to Middle Triassic continental-marine transition of NW Bulgaria: sedimentology, palynology and sequence stratigraphy

NASA Astrophysics Data System (ADS)

Ajdanlijsky, George; Götz, Annette E.; Strasser, André

2018-04-01

Sedimentary facies and cycles of the Triassic continental-marine transition of NW Bulgaria are documented in detail from reference sections along the Iskar river gorge between the villages of Tserovo and Opletnya. The depositional environments evolved from anastomosing and meandering river systems in the Petrohan Terrigenous Group to mixed fluvial and tidal settings in the Svidol Formation, and to peritidal and shallow-marine conditions in the Opletnya Member of the Mogila Formation. For the first time, the palynostratigraphic data presented here allow for dating the transitional interval and for the precise identification of a major sequence boundary between the Petrohan Terrigenous Group and the Svidol Formation (Iskar Carbonate Group). This boundary most probably corresponds to the major sequence boundary Ol4 occurring in the upper Olenekian of the Tethyan realm and thus enables interregional correlation. The identification of regionally traceable sequence boundaries based on biostratigraphic age control is a first step towards a more accurate stratigraphic correlation and palaeogeographic interpretation of the Early to early Middle Triassic in NW Bulgaria.

Comparison of manual and automated AmpliSeq™ workflows in the typing of a Somali population with the Precision ID Identity Panel.

PubMed

van der Heijden, Suzanne; de Oliveira, Susanne Juel; Kampmann, Marie-Louise; Børsting, Claus; Morling, Niels

2017-11-01

The Precision ID Identity Panel was used to type 109 Somali individuals in order to obtain allele frequencies for the Somali population. These frequencies were used to establish a Somali HID-SNP database, which will be used for the biostatistic calculations in family and immigration cases. Genotypes obtained with the Precision ID Identity Panel were found to be almost in complete concordance with genotypes obtained with the SNPforID PCR-SBE-CE assay. In seven SNP loci, silent alleles were identified, of which most were previously described in the literature. The project also set out to compare different AmpliSeq™ workflows to investigate the possibility of using automated library building in forensic genetic case work. In order to do so, the SNP typing of the Somalis was performed using three different workflows: 1) manual library building and sequencing on the Ion PGM™, 2) automated library building using the Biomek ® 3000 and sequencing on the Ion PGM™, and 3) automated library building using the Ion Chef™ and sequencing on the Ion S5™. AmpliSeq™ workflows were compared based on coverage, locus balance, noise, and heterozygote balance. Overall, the Ion Chef™/Ion S5™ workflow was found to give the best results and required least hands-on time in the laboratory. However, the Ion Chef™/Ion S5™ workflow was also the most expensive. The number of libraries that may be constructed in one Ion Chef™ library building run was limited to eight, which is too little for high throughput workflows. The Biomek ® 3000/Ion PGM™ workflow was found to perform similarly to the manual/Ion PGM™ workflow. This argues for the use of automated library building in forensic genetic case work. Automated library building decreases the workload of the laboratory staff, decreases the risk of pipetting errors, and simplifies the daily workflow in forensic genetic laboratories. Copyright © 2017 Elsevier B.V. All rights reserved.

Poliovirus replication proteins: RNA sequence encoding P3-1b and the sites of proteolytic processing

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

Semler, B.L.; Anderson, C.W.; Kitamura, N.

1981-06-01

A partial amino-terminal amino acid sequence of each of the major proteins encoded by the replicase region of the poliovirus genome has been determined. A comparison of this sequence information with the amino acid sequence predicted from the RNA sequence that has been determined for the 3' region of the poliovirus genome has allowed us to locate precisely the proteolytic cleavage sites at which the initial polyprotein is processed to create the poliovirus products P3-1b (NCVP1b), P3-2 (NCVP2), P3-4b (NCVP4b), and P3-7c (NCVP7c). For each of these products, as well as for the small genome-linked protein VPg, proteolytic cleavage occursmore » between a glutamine and a glycine residue to create the amino terminus of each protein. This result suggests that a single proteinase may be responsible for all of these cleavages. The sequence data also allow the precise positioning of the genome-linked protein VPg within the precursor P3-1b just proximal to the amino terminus of polypeptide P3-2.« less

Short memory fuzzy fusion image recognition schema employing spatial and Fourier descriptors

NASA Astrophysics Data System (ADS)

Raptis, Sotiris N.; Tzafestas, Spyros G.

2001-03-01

Single images quite often do not bear enough information for precise interpretation due to a variety of reasons. Multiple image fusion and adequate integration recently became the state of the art in the pattern recognition field. In this paper presented here and enhanced multiple observation schema is discussed investigating improvements to the baseline fuzzy- probabilistic image fusion methodology. The first innovation introduced consists in considering only a limited but seemingly ore effective part of the uncertainty information obtained by a certain time restricting older uncertainty dependencies and alleviating computational burden that is now needed for short sequence (stored into memory) of samples. The second innovation essentially grouping them into feature-blind object hypotheses. Experiment settings include a sequence of independent views obtained by camera being moved around the investigated object.

Calibration of the Late Cretaceous to Paleocene geomagnetic polarity and astrochronological time scales: new results from high-precision U-Pb geochronology

NASA Astrophysics Data System (ADS)

Ramezani, Jahandar; Clyde, William; Wang, Tiantian; Johnson, Kirk; Bowring, Samuel

2016-04-01

Reversals in the Earth's magnetic polarity are geologically abrupt events of global magnitude that makes them ideal timelines for stratigraphic correlation across a variety of depositional environments, especially where diagnostic marine fossils are absent. Accurate and precise calibration of the Geomagnetic Polarity Timescale (GPTS) is thus essential to the reconstruction of Earth history and to resolving the mode and tempo of biotic and environmental change in deep time. The Late Cretaceous - Paleocene GPTS is of particular interest as it encompasses a critical period of Earth history marked by the Cretaceous greenhouse climate, the peak of dinosaur diversity, the end-Cretaceous mass extinction and its paleoecological aftermaths. Absolute calibration of the GPTS has been traditionally based on sea-floor spreading magnetic anomaly profiles combined with local magnetostratigraphic sequences for which a numerical age model could be established by interpolation between an often limited number of 40Ar/39Ar dates from intercalated volcanic ash deposits. Although the Neogene part of the GPTS has been adequately calibrated using cyclostratigraphy-based, astrochronological schemes, the application of these approaches to pre-Neogene parts of the timescale has been complicated given the uncertainties of the orbital models and the chaotic behavior of the solar system this far back in time. Here we present refined chronostratigraphic frameworks based on high-precision U-Pb geochronology of ash beds from the Western Interior Basin of North America and the Songliao Basin of Northeast China that places tight temporal constraints on the Late Cretaceous to Paleocene GPTS, either directly or by testing their astrochronological underpinnings. Further application of high-precision radioisotope geochronology and calibrated astrochronology promises a complete and robust Cretaceous-Paleogene GPTS, entirely independent of sea-floor magnetic anomaly profiles.

Probabilistic metrology or how some measurement outcomes render ultra-precise estimates

NASA Astrophysics Data System (ADS)

Calsamiglia, J.; Gendra, B.; Muñoz-Tapia, R.; Bagan, E.

2016-10-01

We show on theoretical grounds that, even in the presence of noise, probabilistic measurement strategies (which have a certain probability of failure or abstention) can provide, upon a heralded successful outcome, estimates with a precision that exceeds the deterministic bounds for the average precision. This establishes a new ultimate bound on the phase estimation precision of particular measurement outcomes (or sequence of outcomes). For probe systems subject to local dephasing, we quantify such precision limit as a function of the probability of failure that can be tolerated. Our results show that the possibility of abstaining can set back the detrimental effects of noise.

An efficient and accurate approach to MTE-MART for time-resolved tomographic PIV

NASA Astrophysics Data System (ADS)

Lynch, K. P.; Scarano, F.

2015-03-01

The motion-tracking-enhanced MART (MTE-MART; Novara et al. in Meas Sci Technol 21:035401, 2010) has demonstrated the potential to increase the accuracy of tomographic PIV by the combined use of a short sequence of non-simultaneous recordings. A clear bottleneck of the MTE-MART technique has been its computational cost. For large datasets comprising time-resolved sequences, MTE-MART becomes unaffordable and has been barely applied even for the analysis of densely seeded tomographic PIV datasets. A novel implementation is proposed for tomographic PIV image sequences, which strongly reduces the computational burden of MTE-MART, possibly below that of regular MART. The method is a sequential algorithm that produces a time-marching estimation of the object intensity field based on an enhanced guess, which is built upon the object reconstructed at the previous time instant. As the method becomes effective after a number of snapshots (typically 5-10), the sequential MTE-MART (SMTE) is most suited for time-resolved sequences. The computational cost reduction due to SMTE simply stems from the fewer MART iterations required for each time instant. Moreover, the method yields superior reconstruction quality and higher velocity field measurement precision when compared with both MART and MTE-MART. The working principle is assessed in terms of computational effort, reconstruction quality and velocity field accuracy with both synthetic time-resolved tomographic images of a turbulent boundary layer and two experimental databases documented in the literature. The first is the time-resolved data of flow past an airfoil trailing edge used in the study of Novara and Scarano (Exp Fluids 52:1027-1041, 2012); the second is a swirling jet in a water flow. In both cases, the effective elimination of ghost particles is demonstrated in number and intensity within a short temporal transient of 5-10 frames, depending on the seeding density. The increased value of the velocity space-time correlation coefficient demonstrates the increased velocity field accuracy of SMTE compared with MART.

The cyclic and fractal seismic series preceding an mb 4.8 earthquake on 1980 February 14 near the Virgin Islands

USGS Publications Warehouse

Varnes, D.J.; Bufe, C.G.

1996-01-01

Seismic activity in the 10 months preceding the 1980 February 14, mb 4.8 earthquake in the Virgin Islands, reported on by Frankel in 1982, consisted of four principal cycles. Each cycle began with a relatively large event or series of closely spaced events, and the duration of the cycles progressively shortened by a factor of about 3/4. Had this regular shortening of the cycles been recognized prior to the earthquake, the time of the next episode of setsmicity (the main shock) might have been closely estimated 41 days in advance. That this event could be much larger than the previous events is indicated from time-to-failure analysis of the accelerating rise in released seismic energy, using a non-linear time- and slip-predictable foreshock model. Examination of the timing of all events in the sequence shows an even higher degree of order. Rates of seismicity, measured by consecutive interevent times, when plotted on an iteration diagram of a rate versus the succeeding rate, form a triangular circulating trajectory. The trajectory becomes an ascending helix if extended in a third dimension, time. This construction reveals additional and precise relations among the time intervals between times of relatively high or relatively low rates of seismic activity, including period halving and doubling. The set of 666 time intervals between all possible pairs of the 37 recorded events appears to be a fractal; the set of time points that define the intervals has a finite, non-integer correlation dimension of 0.70. In contrast, the average correlation dimension of 50 random sequences of 37 events is significantly higher, dose to 1.0. In a similar analysis, the set of distances between pairs of epicentres has a fractal correlation dimension of 1.52. Well-defined cycles, numerous precise ratios among time intervals, and a non-random temporal fractal dimension suggest that the seismic series is not a random process, but rather the product of a deterministic dynamic system.

Spatiotemporal Patterns of Contact Across the Rat Vibrissal Array During Exploratory Behavior

PubMed Central

Hobbs, Jennifer A.; Towal, R. Blythe; Hartmann, Mitra J. Z.

2016-01-01

The rat vibrissal system is an important model for the study of somatosensation, but the small size and rapid speed of the vibrissae have precluded measuring precise vibrissal-object contact sequences during behavior. We used a laser light sheet to quantify, with 1 ms resolution, the spatiotemporal structure of whisker-surface contact as five naïve rats freely explored a flat, vertical glass wall. Consistent with previous work, we show that the whisk cycle cannot be uniquely defined because different whiskers often move asynchronously, but that quasi-periodic (~8 Hz) variations in head velocity represent a distinct temporal feature on which to lock analysis. Around times of minimum head velocity, whiskers protract to make contact with the surface, and then sustain contact with the surface for extended durations (~25–60 ms) before detaching. This behavior results in discrete temporal windows in which large numbers of whiskers are in contact with the surface. These “sustained collective contact intervals” (SCCIs) were observed on 100% of whisks for all five rats. The overall spatiotemporal structure of the SCCIs can be qualitatively predicted based on information about head pose and the average whisk cycle. In contrast, precise sequences of whisker-surface contact depend on detailed head and whisker kinematics. Sequences of vibrissal contact were highly variable, equally likely to propagate in all directions across the array. Somewhat more structure was found when sequences of contacts were examined on a row-wise basis. In striking contrast to the high variability associated with contact sequences, a consistent feature of each SCCI was that the contact locations of the whiskers on the glass converged and moved more slowly on the sheet. Together, these findings lead us to propose that the rat uses a strategy of “windowed sampling” to extract an object's spatial features: specifically, the rat spatially integrates quasi-static mechanical signals across whiskers during the period of sustained contact, resembling an “enclosing” haptic procedure. PMID:26778990

Single-Center Experience with a Targeted Next Generation Sequencing Assay for Assessment of Relevant Somatic Alterations in Solid Tumors.

PubMed

Paasinen-Sohns, Aino; Koelzer, Viktor H; Frank, Angela; Schafroth, Julian; Gisler, Aline; Sachs, Melanie; Graber, Anne; Rothschild, Sacha I; Wicki, Andreas; Cathomas, Gieri; Mertz, Kirsten D

2017-03-01

Companion diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. Here we report the clinical application and validation of the Oncomine Focus Assay (OFA), an integrated, commercially available next-generation sequencing (NGS) assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance. Two independent patient cohorts were investigated to define the workflow, turnaround times, feasibility, and reliability of OFA targeted sequencing in clinical application and using archival material. Cohort I consisted of 59 diagnostic clinical samples from the daily routine submitted for molecular testing over a 4-month time period. Cohort II consisted of 39 archival melanoma samples that were up to 15years old. Libraries were prepared from isolated nucleic acids and sequenced on the Ion Torrent PGM sequencer. Sequencing datasets were analyzed using the Ion Reporter software. Genomic alterations were identified and validated by orthogonal conventional assays including pyrosequencing and immunohistochemistry. Sequencing results of both cohorts, including archival formalin-fixed, paraffin-embedded material stored up to 15years, were consistent with published variant frequencies. A concordance of 100% between established assays and OFA targeted NGS was observed. The OFA workflow enabled a turnaround of 3½ days. Taken together, OFA was found to be a convenient tool for fast, reliable, broadly applicable and cost-effective targeted NGS of tumor samples in routine diagnostics. Thus, OFA has strong potential to become an important asset for precision oncology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Massively parallel sequencing of 124 SNPs included in the precision ID identity panel in three East Asian minority ethnicities.

PubMed

Liu, Jing; Wang, Zheng; He, Guanglin; Zhao, Xueying; Wang, Mengge; Luo, Tao; Li, Chengtao; Hou, Yiping

2018-07-01

Massively parallel sequencing (MPS) technologies can sequence many targeted regions of multiple samples simultaneously and are gaining great interest in the forensic community. The Precision ID Identity Panel contains 90 autosomal SNPs and 34 upper Y-Clade SNPs, which was designed with small amplicons and optimized for forensic degraded or challenging samples. Here, 184 unrelated individuals from three East Asian minority ethnicities (Tibetan, Uygur and Hui) were analyzed using the Precision ID Identity Panel and the Ion PGM System. The sequencing performance and corresponding forensic statistical parameters of this MPS-SNP panel were investigated. The inter-population relationships and substructures among three investigated populations and 30 worldwide populations were further investigated using PCA, MDS, cladogram and STRUCTURE. No significant deviation from Hardy-Weinberg equilibrium (HWE) and Linkage Disequilibrium (LD) tests was observed across all 90 autosomal SNPs. The combined matching probability (CMP) for Tibetan, Uygur and Hui were 2.5880 × 10 -33 , 1.7480 × 10 -35 and 4.6326 × 10 -34 respectively, and the combined power of exclusion (CPE) were 0.999999386152271, 0.999999607712827 and 0.999999696360182 respectively. For 34 Y-SNPs, only 16 haplogroups were obtained, but the haplogroup distributions differ among the three populations. Tibetans from the Sino-Tibetan population and Hui with multiple ethnicities with an admixture population have genetic affinity with East Asian populations, while Uygurs of a Eurasian admixture population have similar genetic components to the South Asian populations and are distributed between East Asian and European populations. The aforementioned results suggest that the Precision ID Identity Panel is informative and polymorphic in three investigated populations and could be used as an effective tool for human forensics. Copyright © 2018 Elsevier B.V. All rights reserved.

Oligonucleotide recombination enabled site-specific mutagenesis in bacteria

USDA-ARS?s Scientific Manuscript database

Recombineering refers to a strategy for engineering DNA sequences using a specialized mode of homologous recombination. This technology can be used for rapidly constructing precise changes in bacterial genome sequences in vivo. Oligo recombination is one type of recombineering that uses ssDNA olig...

Comparison of pulse sequences for R1-based electron paramagnetic resonance oxygen imaging.

PubMed

Epel, Boris; Halpern, Howard J

2015-05-01

Electron paramagnetic resonance (EPR) spin-lattice relaxation (SLR) oxygen imaging has proven to be an indispensable tool for assessing oxygen partial pressure in live animals. EPR oxygen images show remarkable oxygen accuracy when combined with high precision and spatial resolution. Developing more effective means for obtaining SLR rates is of great practical, biological and medical importance. In this work we compared different pulse EPR imaging protocols and pulse sequences to establish advantages and areas of applicability for each method. Tests were performed using phantoms containing spin probes with oxygen concentrations relevant to in vivo oxymetry. We have found that for small animal size objects the inversion recovery sequence combined with the filtered backprojection reconstruction method delivers the best accuracy and precision. For large animals, in which large radio frequency energy deposition might be critical, free induction decay and three pulse stimulated echo sequences might find better practical usage. Copyright © 2015 Elsevier Inc. All rights reserved.

A Highly Flexible, Automated System Providing Reliable Sample Preparation in Element- and Structure-Specific Measurements.

PubMed

Vorberg, Ellen; Fleischer, Heidi; Junginger, Steffen; Liu, Hui; Stoll, Norbert; Thurow, Kerstin

2016-10-01

Life science areas require specific sample pretreatment to increase the concentration of the analytes and/or to convert the analytes into an appropriate form for the detection and separation systems. Various workstations are commercially available, allowing for automated biological sample pretreatment. Nevertheless, due to the required temperature, pressure, and volume conditions in typical element and structure-specific measurements, automated platforms are not suitable for analytical processes. Thus, the purpose of the presented investigation was the design, realization, and evaluation of an automated system ensuring high-precision sample preparation for a variety of analytical measurements. The developed system has to enable system adaption and high performance flexibility. Furthermore, the system has to be capable of dealing with the wide range of required vessels simultaneously, allowing for less cost and time-consuming process steps. However, the system's functionality has been confirmed in various validation sequences. Using element-specific measurements, the automated system was up to 25% more precise compared to the manual procedure and as precise as the manual procedure using structure-specific measurements. © 2015 Society for Laboratory Automation and Screening.

Simulation evaluation of TIMER, a time-based, terminal air traffic, flow-management concept

NASA Technical Reports Server (NTRS)

Credeur, Leonard; Capron, William R.

1989-01-01

A description of a time-based, extended terminal area ATC concept called Traffic Intelligence for the Management of Efficient Runway scheduling (TIMER) and the results of a fast-time evaluation are presented. The TIMER concept is intended to bridge the gap between today's ATC system and a future automated time-based ATC system. The TIMER concept integrates en route metering, fuel-efficient cruise and profile descents, terminal time-based sequencing and spacing together with computer-generated controller aids, to improve delivery precision for fuller use of runway capacity. Simulation results identify and show the effects and interactions of such key variables as horizon of control location, delivery time error at both the metering fix and runway threshold, aircraft separation requirements, delay discounting, wind, aircraft heading and speed errors, and knowledge of final approach speed.

DNA sequence alignment by microhomology sampling during homologous recombination

PubMed Central

Qi, Zhi; Redding, Sy; Lee, Ja Yil; Gibb, Bryan; Kwon, YoungHo; Niu, Hengyao; Gaines, William A.; Sung, Patrick

2015-01-01

Summary Homologous recombination (HR) mediates the exchange of genetic information between sister or homologous chromatids. During HR, members of the RecA/Rad51 family of recombinases must somehow search through vast quantities of DNA sequence to align and pair ssDNA with a homologous dsDNA template. Here we use single-molecule imaging to visualize Rad51 as it aligns and pairs homologous DNA sequences in real-time. We show that Rad51 uses a length-based recognition mechanism while interrogating dsDNA, enabling robust kinetic selection of 8-nucleotide (nt) tracts of microhomology, which kinetically confines the search to sites with a high probability of being a homologous target. Successful pairing with a 9th nucleotide coincides with an additional reduction in binding free energy and subsequent strand exchange occurs in precise 3-nt steps, reflecting the base triplet organization of the presynaptic complex. These findings provide crucial new insights into the physical and evolutionary underpinnings of DNA recombination. PMID:25684365

Escherichia coli K-12: a cooperatively developed annotation snapshot—2005

PubMed Central

Riley, Monica; Abe, Takashi; Arnaud, Martha B.; Berlyn, Mary K.B.; Blattner, Frederick R.; Chaudhuri, Roy R.; Glasner, Jeremy D.; Horiuchi, Takashi; Keseler, Ingrid M.; Kosuge, Takehide; Mori, Hirotada; Perna, Nicole T.; Plunkett, Guy; Rudd, Kenneth E.; Serres, Margrethe H.; Thomas, Gavin H.; Thomson, Nicholas R.; Wishart, David; Wanner, Barry L.

2006-01-01

The goal of this group project has been to coordinate and bring up-to-date information on all genes of Escherichia coli K-12. Annotation of the genome of an organism entails identification of genes, the boundaries of genes in terms of precise start and end sites, and description of the gene products. Known and predicted functions were assigned to each gene product on the basis of experimental evidence or sequence analysis. Since both kinds of evidence are constantly expanding, no annotation is complete at any moment in time. This is a snapshot analysis based on the most recent genome sequences of two E.coli K-12 bacteria. An accurate and up-to-date description of E.coli K-12 genes is of particular importance to the scientific community because experimentally determined properties of its gene products provide fundamental information for annotation of innumerable genes of other organisms. Availability of the complete genome sequence of two K-12 strains allows comparison of their genotypes and mutant status of alleles. PMID:16397293

Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

PubMed

Cho, Anna; Seong, Moon-Woo; Lim, Byung Chan; Lee, Hwa Jeen; Byeon, Jung Hye; Kim, Seung Soo; Kim, Soo Yeon; Choi, Sun Ah; Wong, Ai-Lynn; Lee, Jeongho; Kim, Jon Soo; Ryu, Hye Won; Lee, Jin Sook; Kim, Hunmin; Hwang, Hee; Choi, Ji Eun; Kim, Ki Joong; Hwang, Young Seung; Hong, Ki Ho; Park, Seungman; Cho, Sung Im; Lee, Seung Jun; Park, Hyunwoong; Seo, Soo Hyun; Park, Sung Sup; Chae, Jong Hee

2017-05-01

Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017. © 2016 Wiley Periodicals, Inc.

Testing Astronomical and 40Ar/39Ar Timescales for the K/Pg Boundary Interval Using High-Resolution Magnetostratigraphy and U-Pb Geochronology in the Denver Basin of Colorado

NASA Astrophysics Data System (ADS)

Clyde, W.; Bowring, S. A.; Johnson, K. R.; Ramezani, J.; Jones, M. M.

2015-12-01

Accurate and precise calibration of the Geomagnetic Polarity Timescale (GPTS) in absolute time is critical for resolving rates of geological and biological processes which in turn help constrain the underlying causes of those processes. Numerical calibration of the GPTS was traditionally carried out by interpolation between a limited number of 40Ar/39Ar dated volcanic ash deposits from superpositional sequences with well-defined magnetostratigraphies. More recently, the Neogene part of the GPTS has been calibrated using high-resolution astrochronological methods, however the application of these approaches to pre-Neogene parts of the timescale is controversial given the uncertainties in relevant orbital parameters this far back in time and differing interpretations of local cyclostratigraphic records. The Cretaceous-Paleogene (K/Pg) boundary interval is a good example, where various astronomical and 40Ar/39Ar calibrations have been proposed with varying degrees of agreement. The Denver Basin (Colorado, USA) contains one of the most complete stratigraphic sequences across the K/Pg boundary in the world, preserving evidence of bolide impact as well as biotic extinction and recovery in a thick stratigraphic package that is accessible by both core and outcrop. We present a series of high-precision U-Pb age determinations from interbedded volcanic ash deposits within a tightly constrained magnetobiostratigraphic framework across the K/Pg boundary in the Denver Basin. This new timeline provides a precise absolute age for the K/Pg boundary, constrains the ages of magnetic polarity Chrons C28 to C30, and provides a direct and independent test of early Paleogene astronomical and 40Ar/39Ar based timescales. Temporal calibration of fossil pollen evidence of the "fern spike" in the Denver Basin shows that plant extinctions peaked within ~50-500 years of the bolide impact and primary productivity recovered ~500-5000 years after the impact.

A field ornithologist’s guide to genomics: Practical considerations for ecology and conservation

USGS Publications Warehouse

Oyler-McCance, Sara J.; Oh, Kevin; Langin, Kathryn; Aldridge, Cameron L.

2016-01-01

Vast improvements in sequencing technology have made it practical to simultaneously sequence millions of nucleotides distributed across the genome, opening the door for genomic studies in virtually any species. Ornithological research stands to benefit in three substantial ways. First, genomic methods enhance our ability to parse and simultaneously analyze both neutral and non-neutral genomic regions, thus providing insight into adaptive evolution and divergence. Second, the sheer quantity of sequence data generated by current sequencing platforms allows increased precision and resolution in analyses. Third, high-throughput sequencing can benefit applications that focus on a small number of loci that are otherwise prohibitively expensive, time-consuming, and technically difficult using traditional sequencing methods. These advances have improved our ability to understand evolutionary processes like speciation and local adaptation, but they also offer many practical applications in the fields of population ecology, migration tracking, conservation planning, diet analyses, and disease ecology. This review provides a guide for field ornithologists interested in incorporating genomic approaches into their research program, with an emphasis on techniques related to ecology and conservation. We present a general overview of contemporary genomic approaches and methods, as well as important considerations when selecting a genomic technique. We also discuss research questions that are likely to benefit from utilizing high-throughput sequencing instruments, highlighting select examples from recent avian studies.

Digital PCR analysis of circulating nucleic acids.

PubMed

Hudecova, Irena

2015-10-01

Detection of plasma circulating nucleic acids (CNAs) requires the use of extremely sensitive and precise methods. The commonly used quantitative real-time polymerase chain reaction (PCR) poses certain technical limitations in relation to the precise measurement of CNAs whereas the costs of massively parallel sequencing are still relatively high. Digital PCR (dPCR) now represents an affordable and powerful single molecule counting strategy to detect minute amounts of genetic material with performance surpassing many quantitative methods. Microfluidic (chip) and emulsion (droplet)-based technologies have already been integrated into platforms offering hundreds to millions of nanoliter- or even picoliter-scale reaction partitions. The compelling observations reported in the field of cancer research, prenatal testing, transplantation medicine and virology support translation of this technology into routine use. Extremely sensitive plasma detection of rare mutations originating from tumor or placental cells among a large background of homologous sequences facilitates unraveling of the early stages of cancer or the detection of fetal mutations. Digital measurement of quantitative changes in plasma CNAs associated with cancer or graft rejection provides valuable information on the monitoring of disease burden or the recipient's immune response and subsequent therapy treatment. Furthermore, careful quantitative assessment of the viral load offers great value for effective monitoring of antiviral therapy for immunosuppressed or transplant patients. The present review describes the inherent features of dPCR that make it exceptionally robust in precise and sensitive quantification of CNAs. Moreover, I provide an insight into the types of potential clinical applications that have been developed by researchers to date. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The String Stability of a Trajectory-Based Interval Management Algorithm in the Midterm Airspace

NASA Technical Reports Server (NTRS)

Swieringa, Kurt A.

2015-01-01

NASA's first Air Traffic Management (ATM) Technology Demonstration (ATD-1) was created to facilitate the transition of mature ATM technologies from the laboratory to operational use. The technologies selected for demonstration are the Traffic Management Advisor with Terminal Metering (TMA-TM), which provides precise time-based scheduling in the terminal airspace; Controller Managed Spacing (CMS), which provides terminal controllers with decision support tools enabling precise schedule conformance; and Interval Management (IM), which consists of flight deck automation that enables aircraft to achieve or maintain a precise spacing interval behind a target aircraft. As the percentage of IM equipped aircraft increases, controllers may provide IM clearances to sequences, or strings, of IM-equipped aircraft. It is important for these strings to maintain stable performance. This paper describes an analytic analysis of the string stability of the latest version of NASA's IM algorithm and a fast-time simulation designed to characterize the string performance of the IM algorithm. The analytic analysis showed that the spacing algorithm has stable poles, indicating that a spacing error perturbation will be reduced as a function of string position. The fast-time simulation investigated IM operations at two airports using constraints associated with the midterm airspace, including limited information of the target aircraft's intended speed profile and limited information of the wind forecast on the target aircraft's route. The results of the fast-time simulation demonstrated that the performance of the spacing algorithm is acceptable for strings of moderate length; however, there is some degradation in IM performance as a function of string position.

Short-term data forecasting based on wavelet transformation and chaos theory

NASA Astrophysics Data System (ADS)

Wang, Yi; Li, Cunbin; Zhang, Liang

2017-09-01

A sketch of wavelet transformation and its application was given. Concerning the characteristics of time sequence, Haar wavelet was used to do data reduction. After processing, the effect of “data nail” on forecasting was reduced. Chaos theory was also introduced, a new chaos time series forecasting flow based on wavelet transformation was proposed. The largest Lyapunov exponent was larger than zero from small data sets, it verified the data change behavior still met chaotic behavior. Based on this, chaos time series to forecast short-term change behavior could be used. At last, the example analysis of the price from a real electricity market showed that the forecasting method increased the precision of the forecasting more effectively and steadily.

Microfluidic single-cell whole-transcriptome sequencing.

PubMed

Streets, Aaron M; Zhang, Xiannian; Cao, Chen; Pang, Yuhong; Wu, Xinglong; Xiong, Liang; Yang, Lu; Fu, Yusi; Zhao, Liang; Tang, Fuchou; Huang, Yanyi

2014-05-13

Single-cell whole-transcriptome analysis is a powerful tool for quantifying gene expression heterogeneity in populations of cells. Many techniques have, thus, been recently developed to perform transcriptome sequencing (RNA-Seq) on individual cells. To probe subtle biological variation between samples with limiting amounts of RNA, more precise and sensitive methods are still required. We adapted a previously developed strategy for single-cell RNA-Seq that has shown promise for superior sensitivity and implemented the chemistry in a microfluidic platform for single-cell whole-transcriptome analysis. In this approach, single cells are captured and lysed in a microfluidic device, where mRNAs with poly(A) tails are reverse-transcribed into cDNA. Double-stranded cDNA is then collected and sequenced using a next generation sequencing platform. We prepared 94 libraries consisting of single mouse embryonic cells and technical replicates of extracted RNA and thoroughly characterized the performance of this technology. Microfluidic implementation increased mRNA detection sensitivity as well as improved measurement precision compared with tube-based protocols. With 0.2 M reads per cell, we were able to reconstruct a majority of the bulk transcriptome with 10 single cells. We also quantified variation between and within different types of mouse embryonic cells and found that enhanced measurement precision, detection sensitivity, and experimental throughput aided the distinction between biological variability and technical noise. With this work, we validated the advantages of an early approach to single-cell RNA-Seq and showed that the benefits of combining microfluidic technology with high-throughput sequencing will be valuable for large-scale efforts in single-cell transcriptome analysis.

Bringing Precision Medicine to Community Oncologists.

PubMed

2017-01-01

Quest Diagnostics has teamed up with Memorial Sloan Kettering Cancer Center and IBM Watson Health to offer IBM Watson Genomics to its network of community cancer centers and hospitals. This new service aims to advance precision medicine by combining genomic tumor sequencing with the power of cognitive computing. ©2017 American Association for Cancer Research.

Metagenomic Taxonomy-Guided Database-Searching Strategy for Improving Metaproteomic Analysis.

PubMed

Xiao, Jinqiu; Tanca, Alessandro; Jia, Ben; Yang, Runqing; Wang, Bo; Zhang, Yu; Li, Jing

2018-04-06

Metaproteomics provides a direct measure of the functional information by investigating all proteins expressed by a microbiota. However, due to the complexity and heterogeneity of microbial communities, it is very hard to construct a sequence database suitable for a metaproteomic study. Using a public database, researchers might not be able to identify proteins from poorly characterized microbial species, while a sequencing-based metagenomic database may not provide adequate coverage for all potentially expressed protein sequences. To address this challenge, we propose a metagenomic taxonomy-guided database-search strategy (MT), in which a merged database is employed, consisting of both taxonomy-guided reference protein sequences from public databases and proteins from metagenome assembly. By applying our MT strategy to a mock microbial mixture, about two times as many peptides were detected as with the metagenomic database only. According to the evaluation of the reliability of taxonomic attribution, the rate of misassignments was comparable to that obtained using an a priori matched database. We also evaluated the MT strategy with a human gut microbial sample, and we found 1.7 times as many peptides as using a standard metagenomic database. In conclusion, our MT strategy allows the construction of databases able to provide high sensitivity and precision in peptide identification in metaproteomic studies, enabling the detection of proteins from poorly characterized species within the microbiota.

Technological advances in precision medicine and drug development.

PubMed

Maggi, Elaine; Patterson, Nicole E; Montagna, Cristina

New technologies are rapidly becoming available to expand the arsenal of tools accessible for precision medicine and to support the development of new therapeutics. Advances in liquid biopsies, which analyze cells, DNA, RNA, proteins, or vesicles isolated from the blood, have gained particular interest for their uses in acquiring information reflecting the biology of tumors and metastatic tissues. Through advancements in DNA sequencing that have merged unprecedented accuracy with affordable cost, personalized treatments based on genetic variations are becoming a real possibility. Extraordinary progress has been achieved in the development of biological therapies aimed to even further advance personalized treatments. We provide a summary of current and future applications of blood based liquid biopsies and how new technologies are utilized for the development of biological therapeutic treatments. We discuss current and future sequencing methods with an emphasis on how technological advances will support the progress in the field of precision medicine.

Taxator-tk: precise taxonomic assignment of metagenomes by fast approximation of evolutionary neighborhoods

PubMed Central

Dröge, J.; Gregor, I.; McHardy, A. C.

2015-01-01

Motivation: Metagenomics characterizes microbial communities by random shotgun sequencing of DNA isolated directly from an environment of interest. An essential step in computational metagenome analysis is taxonomic sequence assignment, which allows identifying the sequenced community members and reconstructing taxonomic bins with sequence data for the individual taxa. For the massive datasets generated by next-generation sequencing technologies, this cannot be performed with de-novo phylogenetic inference methods. We describe an algorithm and the accompanying software, taxator-tk, which performs taxonomic sequence assignment by fast approximate determination of evolutionary neighbors from sequence similarities. Results: Taxator-tk was precise in its taxonomic assignment across all ranks and taxa for a range of evolutionary distances and for short as well as for long sequences. In addition to the taxonomic binning of metagenomes, it is well suited for profiling microbial communities from metagenome samples because it identifies bacterial, archaeal and eukaryotic community members without being affected by varying primer binding strengths, as in marker gene amplification, or copy number variations of marker genes across different taxa. Taxator-tk has an efficient, parallelized implementation that allows the assignment of 6 Gb of sequence data per day on a standard multiprocessor system with 10 CPU cores and microbial RefSeq as the genomic reference data. Availability and implementation: Taxator-tk source and binary program files are publicly available at http://algbio.cs.uni-duesseldorf.de/software/. Contact: Alice.McHardy@uni-duesseldorf.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25388150

Linear and nonlinear frequency- and time-domain spectroscopy with multiple frequency combs.

PubMed

Bennett, Kochise; Rouxel, Jeremy R; Mukamel, Shaul

2017-09-07

Two techniques that employ equally spaced trains of optical pulses to map an optical high frequency into a low frequency modulation of the signal that can be detected in real time are compared. The development of phase-stable optical frequency combs has opened up new avenues to metrology and spectroscopy. The ability to generate a series of frequency spikes with precisely controlled separation permits a fast, highly accurate sampling of the material response. Recently, pairs of frequency combs with slightly different repetition rates have been utilized to down-convert material susceptibilities from the optical to microwave regime where they can be recorded in real time. We show how this one-dimensional dual comb technique can be extended to multiple dimensions by using several combs. We demonstrate how nonlinear susceptibilities can be quickly acquired using this technique. In a second class of techniques, sequences of ultrafast mode locked laser pulses are used to recover pathways of interactions contributing to nonlinear susceptibilities by using a photo-acoustic modulation varying along the sequences. We show that these techniques can be viewed as a time-domain analog of the multiple frequency comb scheme.

Tone series and the nature of working memory capacity development.

PubMed

Clark, Katherine M; Hardman, Kyle O; Schachtman, Todd R; Saults, J Scott; Glass, Bret A; Cowan, Nelson

2018-04-01

Recent advances in understanding visual working memory, the limited information held in mind for use in ongoing processing, are extended here to examine auditory working memory development. Research with arrays of visual objects has shown how to distinguish the capacity, in terms of the number of objects retained, from the precision of the object representations. We adapt the technique to sequences of nonmusical tones, in an investigation including children (6-13 years, N = 84) and adults (26-50 years, N = 31). For each series of 1 to 4 tones, the participant responded by using an 80-choice scale to try to reproduce the tone at a queried serial position. Despite the much longer-lasting usefulness of sensory memory for tones compared with visual objects, the observed tone capacity was similar to previous findings for visual capacity. The results also constrain theories of childhood working memory development, indicating increases with age in both the capacity and the precision of the tone representations, similar to the visual studies, rather than age differences in time-based memory decay. The findings, including patterns of correlations between capacity, precision, and some auxiliary tasks and questionnaires, establish capacity and precision as dissociable processes and place important constraints on various hypotheses of working memory development. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

Gilbert, Jack A.; Quinn, Robert A.; Debelius, Justine

Rapid advances in DNA sequencing, metabolomics, proteomics and computation dramatically increase accessibility of microbiome studies and identify links between the microbiome and disease. Microbial time-series and multiple molecular perspectives enable Microbiome-Wide Association Studies (MWAS), analogous to Genome-Wide Association Studies (GWAS). Rapid research advances point towards actionable results, although approved clinical tests based on MWAS are still in the future. Appreciating the complexity of interactions between diet, chemistry, health and the microbiome, and determining the frequency of observations needed to capture and integrate this dynamic interface, is paramount for addressing the need for personalized and precision microbiome-based diagnostics and therapies.

Precise chronology of differentiation of developing human primary dentition.

PubMed

Hu, Xuefeng; Xu, Shan; Lin, Chensheng; Zhang, Lishan; Chen, YiPing; Zhang, Yanding

2014-02-01

While correlation of developmental stage with embryonic age of the human primary dentition has been well documented, the available information regarding the differentiation timing of the primary teeth was largely based on the observation of initial mineralization and varies significantly. In this study, we aimed to document precise differentiation timing of the developing human primary dentition. We systematically examined the expression of odontogenic differentiation markers along with the formation of mineralized tissue in each developing maxillary and mandibular teeth from human embryos with well-defined embryonic age. We show that, despite that all primary teeth initiate development at the same time, odontogenic differentiation begins in the maxillary incisors at the 15th week and in the mandibular incisors at the 16th week of gestation, followed by the canine, the first primary premolar, and the second primary premolar at a week interval sequentially. Despite that the mandibular primary incisors erupt earlier than the maxillary incisors, this distal to proximal sequential differentiation of the human primary dentition coincides in general with the sequence of tooth eruption. Our results provide an accurate chronology of odontogenic differentiation of the developing human primary dentition, which could be used as reference for future studies of human tooth development.

Estimate of within population incremental selection through branch imbalance in lineage trees

PubMed Central

Liberman, Gilad; Benichou, Jennifer I.C.; Maman, Yaakov; Glanville, Jacob; Alter, Idan; Louzoun, Yoram

2016-01-01

Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here provide for the first time such a detailed method and show its precision in multiple cases of micro-evolution. The proposed method is a novel mixed lineage tree/sequence based method to detect within population selection as defined by the effect of mutations on the average number of offspring. Specifically, we propose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. The method requires a high enough number of sequences, and a large enough number of independent mutations. It assumes that all mutations are independent events. It does not require of a baseline model and is practically not affected by sampling biases. We show the method's wide applicability by testing it on multiple cases of micro-evolution. We show that it can detect genes and inter-genic regions using the selection rate and detect selection pressures in viral proteins and in the immune response to pathogens. PMID:26586802

Scalable hybrid computation with spikes.

PubMed

Sarpeshkar, Rahul; O'Halloran, Micah

2002-09-01

We outline a hybrid analog-digital scheme for computing with three important features that enable it to scale to systems of large complexity: First, like digital computation, which uses several one-bit precise logical units to collectively compute a precise answer to a computation, the hybrid scheme uses several moderate-precision analog units to collectively compute a precise answer to a computation. Second, frequent discrete signal restoration of the analog information prevents analog noise and offset from degrading the computation. And, third, a state machine enables complex computations to be created using a sequence of elementary computations. A natural choice for implementing this hybrid scheme is one based on spikes because spike-count codes are digital, while spike-time codes are analog. We illustrate how spikes afford easy ways to implement all three components of scalable hybrid computation. First, as an important example of distributed analog computation, we show how spikes can create a distributed modular representation of an analog number by implementing digital carry interactions between spiking analog neurons. Second, we show how signal restoration may be performed by recursive spike-count quantization of spike-time codes. And, third, we use spikes from an analog dynamical system to trigger state transitions in a digital dynamical system, which reconfigures the analog dynamical system using a binary control vector; such feedback interactions between analog and digital dynamical systems create a hybrid state machine (HSM). The HSM extends and expands the concept of a digital finite-state-machine to the hybrid domain. We present experimental data from a two-neuron HSM on a chip that implements error-correcting analog-to-digital conversion with the concurrent use of spike-time and spike-count codes. We also present experimental data from silicon circuits that implement HSM-based pattern recognition using spike-time synchrony. We outline how HSMs may be used to perform learning, vector quantization, spike pattern recognition and generation, and how they may be reconfigured.

NMR and enzymology of modified DNA/protein interactions

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

Kennedy, M.A.

1994-12-31

We have found distinct DNA structure and base dynamics precisely at the TpA cleavage site in the TTTAAA AHA III endonuclease restriction sequence. Hence, the unusual base stacking and mobility found in this sequence may be important to the mechanism of enzymatic cleavage of the phophodiester bond.

An Improved Algorithm for Predicting Free Recalls

ERIC Educational Resources Information Center

Laming, Donald

2008-01-01

Laming [Laming, D. (2006). "Predicting free recalls." "Journal of Experimental Psychology: Learning, Memory, and Cognition," 32, 1146-1163] has shown that, in a free-recall experiment in which the participants rehearsed out loud, entire sequences of recalls could be predicted, to a useful degree of precision, from the prior sequences of stimuli…

Highly Precise and Developmentally Programmed Genome Assembly in Paramecium Requires Ligase IV–Dependent End Joining

PubMed Central

Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D.; Malinsky, Sophie; Bétermier, Mireille

2011-01-01

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5′ overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi–mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5′-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3′ ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a “cut-and-close” mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics. PMID:21533177

Highly precise and developmentally programmed genome assembly in Paramecium requires ligase IV-dependent end joining.

PubMed

Kapusta, Aurélie; Matsuda, Atsushi; Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D; Malinsky, Sophie; Bétermier, Mireille

2011-04-01

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5' overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi-mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5'-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3' ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a "cut-and-close" mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics.

Magnetophoretic circuits for digital control of single particles and cells

NASA Astrophysics Data System (ADS)

Lim, Byeonghwa; Reddy, Venu; Hu, Xinghao; Kim, Kunwoo; Jadhav, Mital; Abedini-Nassab, Roozbeh; Noh, Young-Woock; Lim, Yong Taik; Yellen, Benjamin B.; Kim, Cheolgi

2014-05-01

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines. The magnetic patterns passively control particles similar to electrical conductors, diodes and capacitors. The current lines actively switch particles between different tracks similar to gated electrical transistors. When combined into arrays and driven by a rotating magnetic field clock, these integrated circuits have general multiplexing properties and enable the precise control of magnetizable objects.

Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

PubMed Central

Kandel, Pujan; Wallace, Michael B.

2018-01-01

Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer. PMID:29463004

[Imaging of gliomas].

PubMed

Martin-Duverneuil, N; Guillevin, R; Chiras, J

2008-11-01

The imaging of gliomas, as well as diffuse infiltrative gliomas or as more recently individualized entities, has been profoundly modified these last years. Correlated with the classic morphological MRI, numerous new sequences have appeared that allowed a more metabolic approach of the tumors, such as diffusion, perfusion--related to angiogenesis--and spectroscopy--reflecting metabolic data. Their development in daily practice allows to precise the diagnostic, to definite the more active areas (correlated with the hyperperfused or more metabolic active areas in relation with the Ki67 index) and so optimize the biopsy and/or evaluate the evolution of the lesion. When associated, they allow also and perhaps especially to precise the diagnostic, particularly with other tumoral masses such as lymphomas or metastases that can present misleading patterns, but also with other more benign lesions such as abcesses. Always critically analysed, and reevaluated along the time if necessary, they can sometimes help the histological diagnosis, but never can be used in place of it.

VaDiR: an integrated approach to Variant Detection in RNA.

PubMed

Neums, Lisa; Suenaga, Seiji; Beyerlein, Peter; Anders, Sara; Koestler, Devin; Mariani, Andrea; Chien, Jeremy

2018-02-01

Advances in next-generation DNA sequencing technologies are now enabling detailed characterization of sequence variations in cancer genomes. With whole-genome sequencing, variations in coding and non-coding sequences can be discovered. But the cost associated with it is currently limiting its general use in research. Whole-exome sequencing is used to characterize sequence variations in coding regions, but the cost associated with capture reagents and biases in capture rate limit its full use in research. Additional limitations include uncertainty in assigning the functional significance of the mutations when these mutations are observed in the non-coding region or in genes that are not expressed in cancer tissue. We investigated the feasibility of uncovering mutations from expressed genes using RNA sequencing datasets with a method called Variant Detection in RNA(VaDiR) that integrates 3 variant callers, namely: SNPiR, RVBoost, and MuTect2. The combination of all 3 methods, which we called Tier 1 variants, produced the highest precision with true positive mutations from RNA-seq that could be validated at the DNA level. We also found that the integration of Tier 1 variants with those called by MuTect2 and SNPiR produced the highest recall with acceptable precision. Finally, we observed a higher rate of mutation discovery in genes that are expressed at higher levels. Our method, VaDiR, provides a possibility of uncovering mutations from RNA sequencing datasets that could be useful in further functional analysis. In addition, our approach allows orthogonal validation of DNA-based mutation discovery by providing complementary sequence variation analysis from paired RNA/DNA sequencing datasets.

Bragg gravity-gradiometer using the 1S0–3P1 intercombination transition of 88Sr

NASA Astrophysics Data System (ADS)

del Aguila, R. P.; Mazzoni, T.; Hu, L.; Salvi, L.; Tino, G. M.; Poli, N.

2018-04-01

We present a gradiometer based on matter-wave interference of alkaline-earth-metal atoms, namely 88Sr. The coherent manipulation of the atomic external degrees of freedom is obtained by large-momentum-transfer Bragg diffraction, driven by laser fields detuned away from the narrow 1S0–3P1 intercombination transition. We use a well-controlled artificial gradient, realized by changing the relative frequencies of the Bragg pulses during the interferometer sequence, in order to characterize the sensitivity of the gradiometer. The sensitivity reaches 1.5 × 10‑5 s‑2 for an interferometer time of 20 ms, limited only by geometrical constraints. We observed extremely low sensitivity of the gradiometric phase to magnetic field gradients, approaching a value 104 times lower than the sensitivity of alkali-atom based gradiometers, limited by the interferometer sensitivity. An efficient double-launch technique employing accelerated red vertical lattices from a single magneto-optical trap cloud is also demonstrated. These results highlight strontium as an ideal candidate for precision measurements of gravity gradients, with potential application in future precision tests of fundamental physics.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence.

PubMed

Chang, Andrew; Bosnyak, Dan J; Trainor, Laurel J

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15-25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15-20 Hz) was larger around 200-300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both "when" (timing) upcoming sounds will occur as well as the prediction precision error of "what" (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception.

The time of appearance and disappearance of fetal DNA from the maternal circulation.

PubMed

Thomas, M R; Tutschek, B; Frost, A; Rodeck, C H; Yazdani, N; Craft, I; Williamson, R

1995-07-01

A single copy Y-chromosome DNA sequence was amplified using the polymerase chain reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy through an in vitro fertilization (IVF) programme. The time of conception was known precisely and was confirmed by serial ultrasound scans. Conceptions were dated as the number of weeks after fertilization plus 2, to give a time equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y-chromosome-specific DNA was detected in all pregnancies with a male fetus (18/30). The earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1 day. Y-chromosome-specific sequences were no longer detected in any of the male pregnancies 8 weeks after delivery. No Y-chromosome sequences were detected in any of the pregnancies where only female babies were delivered. This demonstrates that fetal DNA appears in the maternal circulation early in the first trimester, that it can be identified in all pregnancies tested by 7 weeks, that it continues to be present throughout pregnancy, and that it has been cleared from the maternal circulation 2 months after parturition. Early non-invasive prenatal diagnosis for aneuploidies and inherited disorders will be possible in all pregnancies if fetal cells can be isolated free from maternal contamination (or identified accurately in the presence of maternal cells) without problems of contamination from previous pregnancies.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence

PubMed Central

Chang, Andrew; Bosnyak, Dan J.; Trainor, Laurel J.

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15–25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15–20 Hz) was larger around 200–300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both “when” (timing) upcoming sounds will occur as well as the prediction precision error of “what” (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception. PMID:27014138

Pore Pressure Pulse Drove the 2012 Emilia (Italy) Series of Earthquakes

NASA Astrophysics Data System (ADS)

Pezzo, Giuseppe; De Gori, Pasquale; Lucente, Francesco Pio; Chiarabba, Claudio

2018-01-01

The 2012 Emilia earthquakes sequence is the first debated case in Italy of destructive event possibly induced by anthropic activity. During this sequence, two main earthquakes occurred separated by 9 days on contiguous thrust faults. Scientific commissions engaged by the Italian government reported complementary scenarios on the potential trigger mechanism ascribable to exploitation of a nearby oil field. In this study, we combine a refined geodetic source model constrained by precise aftershock locations and an improved tomographic model of the area to define the geometrical relation between the activated faults and investigate possible triggering mechanisms. An aftershock decay rate that deviates from the classical Omori-like pattern and Vp/Vs changes along the fault system suggests that natural pore pressure pulse drove the space-time evolution of seismicity and the activation of the second main shock.

Micropreparative capillary gel electrophoresis of DNA: rapid expressed sequence tag library construction.

PubMed

Shi, Liang; Khandurina, Julia; Ronai, Zsolt; Li, Bi-Yu; Kwan, Wai King; Wang, Xun; Guttman, András

2003-01-01

A capillary gel electrophoresis based automated DNA fraction collection technique was developed to support a novel DNA fragment-pooling strategy for expressed sequence tag (EST) library construction. The cDNA population is first cleaved by BsaJ I and EcoR I restriction enzymes, and then subpooled by selective ligation with specific adapters followed by polymerase chain reaction (PCR) amplification and labeling. Combination of this cDNA fingerprinting method with high-resolution capillary gel electrophoresis separation and precise fractionation of individual cDNA transcript representatives avoids redundant fragment selection and concomitant repetitive sequencing of abundant transcripts. Using a computer-controlled capillary electrophoresis device the transcript representatives were separated by their size and fractions were automatically collected in every 30 s into 96-well plates. The high resolving power of the sieving matrix ensured sequencing grade separation of the DNA fragments (i.e., single-base resolution) and successful fraction collection. Performance and precision of the fraction collection procedure was validated by PCR amplification of the collected DNA fragments followed by capillary electrophoresis analysis for size and purity verification. The collected and PCR-amplified transcript representatives, ranging up to several hundred base pairs, were then sequenced to create an EST library.

Precision Teaching a Foundational Motor Skill to a Child with Autism

ERIC Educational Resources Information Center

Fabrizio, Michael A.; Schirmer, Kristin; King, Amy; Diakite, Ami; Stovel, Leah

2007-01-01

Since the early work of Anne Desjardin (1980) and others, Precision Teachers have developed Big 6+6 skills in their students' repertoires when needed. In this article, the authors present the Standard Celeration Chart (SCC) which documents how they analyzed the Big 6+6 skill of "squeeze" in terms of arranging sequences of instruction. The SCC…

An Improved Source-Scanning Algorithm for Locating Earthquake Clusters or Aftershock Sequences

NASA Astrophysics Data System (ADS)

Liao, Y.; Kao, H.; Hsu, S.

2010-12-01

The Source-scanning Algorithm (SSA) was originally introduced in 2004 to locate non-volcanic tremors. Its application was later expanded to the identification of earthquake rupture planes and the near-real-time detection and monitoring of landslides and mud/debris flows. In this study, we further improve SSA for the purpose of locating earthquake clusters or aftershock sequences when only a limited number of waveform observations are available. The main improvements include the application of a ground motion analyzer to separate P and S waves, the automatic determination of resolution based on the grid size and time step of the scanning process, and a modified brightness function to utilize constraints from multiple phases. Specifically, the improved SSA (named as ISSA) addresses two major issues related to locating earthquake clusters/aftershocks. The first one is the massive amount of both time and labour to locate a large number of seismic events manually. And the second one is to efficiently and correctly identify the same phase across the entire recording array when multiple events occur closely in time and space. To test the robustness of ISSA, we generate synthetic waveforms consisting of 3 separated events such that individual P and S phases arrive at different stations in different order, thus making correct phase picking nearly impossible. Using these very complicated waveforms as the input, the ISSA scans all model space for possible combination of time and location for the existence of seismic sources. The scanning results successfully associate various phases from each event at all stations, and correctly recover the input. To further demonstrate the advantage of ISSA, we apply it to the waveform data collected by a temporary OBS array for the aftershock sequence of an offshore earthquake southwest of Taiwan. The overall signal-to-noise ratio is inadequate for locating small events; and the precise arrival times of P and S phases are difficult to determine. We use one of the largest aftershocks that can be located by conventional methods as our reference event to calibrate the controlling parameters of ISSA. These parameters include the overall Vp/Vs ratio (because a precise S velocity model was unavailable), the length of scanning time window, and the weighting factor for each station. Our results show that ISSA is not only more efficient in locating earthquake clusters/aftershocks, but also capable of identifying many events missed by conventional phase-picking methods.

High precision calcium isotope analysis using 42Ca-48Ca double-spike TIMS technique

NASA Astrophysics Data System (ADS)

Feng, L.; Zhou, L.; Gao, S.; Tong, S. Y.; Zhou, M. L.

2014-12-01

Double spike techniques are widely used for determining calcium isotopic compositions of natural samples. The most important factor controlling precision of the double spike technique is the choice of appropriate spike isotope pair, the composition of double spikes and the ratio of spike to sample（CSp/CN）. We propose an optimal 42Ca-48Ca double spike protocol which yields the best internal precision for calcium isotopic composition determinations among all kinds of spike pairs and various spike compositions and ratios of spike to sample, as predicted by linear error propagation method. It is suggested to use spike composition of 42Ca/(42Ca+48Ca) = 0.44 mol/mol and CSp/(CN+ CSp)= 0.12mol/mol because it takes both advantages of the largest mass dispersion between 42Ca and 48Ca (14%) and lowest spike cost. Spiked samples were purified by pass through homemade micro-column filled with Ca special resin. K, Ti and other interference elements were completely separated, while 100% calcium was recovered with negligible blank. Data collection includes integration time, idle time, focus and peakcenter frequency, which were all carefully designed for the highest internal precision and lowest analysis time. All beams were automatically measured in a sequence by Triton TIMS so as to eliminate difference of analytical conditions between samples and standards, and also to increase the analytical throughputs. The typical internal precision of 100 duty cycles for one beam is 0.012‒0.015 ‰ (2δSEM), which agrees well with the predicted internal precision of 0.0124 ‰ (2δSEM). Our methods improve internal precisions by a factor of 2‒10 compared to previous methods of determination of calcium isotopic compositions by double spike TIMS. We analyzed NIST SRM 915a, NIST SRM 915b and Pacific Seawater as well as interspersed geological samples during two months. The obtained average δ44/40Ca (all relative to NIST SRM 915a) is 0.02 ± 0.02 ‰ (n=28), 0.72±0.04 ‰ (n=10) and 1.93±0.03 ‰ (n=21) for NIST SRM 915a, NIST SRM 915b and Pacific Seawater, respectively. The long-term reproducibility is 0.10‰ (2 δSD), which is comparable to the best external precision of 0.04 ‰ (2 δSD) of previous methods, but our sample throughputs are doubled with significant reduction in amount of spike used for single samples.

Enhancing the detection of barcoded reads in high throughput DNA sequencing data by controlling the false discovery rate.

PubMed

Buschmann, Tilo; Zhang, Rong; Brash, Douglas E; Bystrykh, Leonid V

2014-08-07

DNA barcodes are short unique sequences used to label DNA or RNA-derived samples in multiplexed deep sequencing experiments. During the demultiplexing step, barcodes must be detected and their position identified. In some cases (e.g., with PacBio SMRT), the position of the barcode and DNA context is not well defined. Many reads start inside the genomic insert so that adjacent primers might be missed. The matter is further complicated by coincidental similarities between barcode sequences and reference DNA. Therefore, a robust strategy is required in order to detect barcoded reads and avoid a large number of false positives or negatives.For mass inference problems such as this one, false discovery rate (FDR) methods are powerful and balanced solutions. Since existing FDR methods cannot be applied to this particular problem, we present an adapted FDR method that is suitable for the detection of barcoded reads as well as suggest possible improvements. In our analysis, barcode sequences showed high rates of coincidental similarities with the Mus musculus reference DNA. This problem became more acute when the length of the barcode sequence decreased and the number of barcodes in the set increased. The method presented in this paper controls the tail area-based false discovery rate to distinguish between barcoded and unbarcoded reads. This method helps to establish the highest acceptable minimal distance between reads and barcode sequences. In a proof of concept experiment we correctly detected barcodes in 83% of the reads with a precision of 89%. Sensitivity improved to 99% at 99% precision when the adjacent primer sequence was incorporated in the analysis. The analysis was further improved using a paired end strategy. Following an analysis of the data for sequence variants induced in the Atp1a1 gene of C57BL/6 murine melanocytes by ultraviolet light and conferring resistance to ouabain, we found no evidence of cross-contamination of DNA material between samples. Our method offers a proper quantitative treatment of the problem of detecting barcoded reads in a noisy sequencing environment. It is based on the false discovery rate statistics that allows a proper trade-off between sensitivity and precision to be chosen.

16S rRNA Gene Sequencing, Multilocus Sequence Analysis, and Mass Spectrometry Identification of the Proposed New Species “Clostridium neonatale”

PubMed Central

Bouvet, Philippe; Ferraris, Laurent; Dauphin, Brunhilde; Popoff, Michel-Robert; Butel, Marie Jose

2014-01-01

In 2002, an outbreak of necrotizing enterocolitis in a Canadian neonatal intensive care unit was associated with a proposed novel species of Clostridium, “Clostridium neonatale.” To date, there are no data about the isolation, identification, or clinical significance of this species. Additionally, C. neonatale has not been formally classified as a new species, rendering its identification challenging. Indeed, the C. neonatale 16S rRNA gene sequence shows high similarity to another Clostridium species involved in neonatal necrotizing enterocolitis, Clostridium butyricum. By performing a polyphasic study combining phylogenetic analysis (16S rRNA gene sequencing and multilocus sequence analysis) and phenotypic characterization with mass spectrometry, we demonstrated that C. neonatale is a new species within the Clostridium genus sensu stricto, for which we propose the name Clostridium neonatale sp. nov. Now that the status of C. neonatale has been clarified, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) can be used for better differential identification of C. neonatale and C. butyricum clinical isolates. This is necessary to precisely define the role and clinical significance of C. neonatale, a species that may have been misidentified and underrepresented during previous neonatal necrotizing enterocolitis studies. PMID:25232167

Apollo Mission Techniques Lunar Orbit Activities - Part 1a

NASA Technical Reports Server (NTRS)

Interbartolo, Michael A.

2009-01-01

This slide presentation reviews the planned sequence of events and the rationale for all lunar missions, and the flight experiences and lessons learned for the lunar orbit activities from a trajectory perspective. Shown are trajectories which include the moon's position at the various stages in the complete trip from launch, to the return and reentry. Included in the presentation are objectives and the sequence of events,for the Apollo 8, and Apollo 10. This is followed by a discussion of Apollo 11, including: the primary mission objective, the sequence of events, and the flight experience. The next mission discussed was Apollo 12. It reviews the objectives, the ground tracking, procedure changes, and the sequence of events. The aborted Apollo 13 mission is reviewed, including the objectives, and the sequence of events. Brief summaries of the flight experiences for Apollo 14-16 are reviewed. The flight sequence of events of Apollo 17 are discussed. In summary each mission consistently performing precision landings required that Apollo lunar orbit activities devote considerable attention to: (1) Improving fidelity of lunar gravity models, (2) Maximizing availability of ground tracking, (3) Minimizing perturbations on the trajectory, (4) Maximizing LM propellant reserves for hover time. Also the use of radial separation maneuvers (1) allows passive re-rendezvous after each rev, but ... (2) sensitive to small dispersions in initial sep direction

Quantitation of next generation sequencing library preparation protocol efficiencies using droplet digital PCR assays - a systematic comparison of DNA library preparation kits for Illumina sequencing.

PubMed

Aigrain, Louise; Gu, Yong; Quail, Michael A

2016-06-13

The emergence of next-generation sequencing (NGS) technologies in the past decade has allowed the democratization of DNA sequencing both in terms of price per sequenced bases and ease to produce DNA libraries. When it comes to preparing DNA sequencing libraries for Illumina, the current market leader, a plethora of kits are available and it can be difficult for the users to determine which kit is the most appropriate and efficient for their applications; the main concerns being not only cost but also minimal bias, yield and time efficiency. We compared 9 commercially available library preparation kits in a systematic manner using the same DNA sample by probing the amount of DNA remaining after each protocol steps using a new droplet digital PCR (ddPCR) assay. This method allows the precise quantification of fragments bearing either adaptors or P5/P7 sequences on both ends just after ligation or PCR enrichment. We also investigated the potential influence of DNA input and DNA fragment size on the final library preparation efficiency. The overall library preparations efficiencies of the libraries show important variations between the different kits with the ones combining several steps into a single one exhibiting some final yields 4 to 7 times higher than the other kits. Detailed ddPCR data also reveal that the adaptor ligation yield itself varies by more than a factor of 10 between kits, certain ligation efficiencies being so low that it could impair the original library complexity and impoverish the sequencing results. When a PCR enrichment step is necessary, lower adaptor-ligated DNA inputs leads to greater amplification yields, hiding the latent disparity between kits. We describe a ddPCR assay that allows us to probe the efficiency of the most critical step in the library preparation, ligation, and to draw conclusion on which kits is more likely to preserve the sample heterogeneity and reduce the need of amplification.

CRISPR-Cas9-Edited Site Sequencing (CRES-Seq): An Efficient and High-Throughput Method for the Selection of CRISPR-Cas9-Edited Clones.

PubMed

Veeranagouda, Yaligara; Debono-Lagneaux, Delphine; Fournet, Hamida; Thill, Gilbert; Didier, Michel

2018-01-16

The emergence of clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) gene editing systems has enabled the creation of specific mutants at low cost, in a short time and with high efficiency, in eukaryotic cells. Since a CRISPR-Cas9 system typically creates an array of mutations in targeted sites, a successful gene editing project requires careful selection of edited clones. This process can be very challenging, especially when working with multiallelic genes and/or polyploid cells (such as cancer and plants cells). Here we described a next-generation sequencing method called CRISPR-Cas9 Edited Site Sequencing (CRES-Seq) for the efficient and high-throughput screening of CRISPR-Cas9-edited clones. CRES-Seq facilitates the precise genotyping up to 96 CRISPR-Cas9-edited sites (CRES) in a single MiniSeq (Illumina) run with an approximate sequencing cost of $6/clone. CRES-Seq is particularly useful when multiple genes are simultaneously targeted by CRISPR-Cas9, and also for screening of clones generated from multiallelic genes/polyploid cells. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

A Spiking Neural Network System for Robust Sequence Recognition.

PubMed

Yu, Qiang; Yan, Rui; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

2016-03-01

This paper proposes a biologically plausible network architecture with spiking neurons for sequence recognition. This architecture is a unified and consistent system with functional parts of sensory encoding, learning, and decoding. This is the first systematic model attempting to reveal the neural mechanisms considering both the upstream and the downstream neurons together. The whole system is a consistent temporal framework, where the precise timing of spikes is employed for information processing and cognitive computing. Experimental results show that the system is competent to perform the sequence recognition, being robust to noisy sensory inputs and invariant to changes in the intervals between input stimuli within a certain range. The classification ability of the temporal learning rule used in the system is investigated through two benchmark tasks that outperform the other two widely used learning rules for classification. The results also demonstrate the computational power of spiking neurons over perceptrons for processing spatiotemporal patterns. In summary, the system provides a general way with spiking neurons to encode external stimuli into spatiotemporal spikes, to learn the encoded spike patterns with temporal learning rules, and to decode the sequence order with downstream neurons. The system structure would be beneficial for developments in both hardware and software.

Precision Medicine, Cardiovascular Disease and Hunting Elephants.

PubMed

Joyner, Michael J

2016-01-01

Precision medicine postulates improved prediction, prevention, diagnosis and treatment of disease based on patient specific factors especially DNA sequence (i.e., gene) variants. Ideas related to precision medicine stem from the much anticipated "genetic revolution in medicine" arising seamlessly from the human genome project (HGP). In this essay I deconstruct the concept of precision medicine and raise questions about the validity of the paradigm in general and its application to cardiovascular disease. Thus far precision medicine has underperformed based on the vision promulgated by enthusiasts. While niche successes for precision medicine are likely, the promises of broad based transformation should be viewed with skepticism. Open discussion and debate related to precision medicine are urgently needed to avoid misapplication of resources, hype, iatrogenic interventions, and distraction from established approaches with ongoing utility. Failure to engage in such debate will lead to negative unintended consequences from a revolution that might never come. Copyright © 2016 Elsevier Inc. All rights reserved.

Speed, Accuracy, and Serial Order in Sequence Production

ERIC Educational Resources Information Center

Pfordresher, Peter Q.; Palmer, Caroline; Jungers, Melissa K.

2007-01-01

The production of complex sequences like music or speech requires the rapid and temporally precise production of events (e.g., notes and chords), often at fast rates. Memory retrieval in these circumstances may rely on the simultaneous activation of both the current event and the surrounding context (Lashley, 1951). We describe an extension to a…

A unique chromatin complex occupies young α-satellite arrays of human centromeres

PubMed Central

Henikoff, Jorja G.; Thakur, Jitendra; Kasinathan, Sivakanthan; Henikoff, Steven

2015-01-01

The intractability of homogeneous α-satellite arrays has impeded understanding of human centromeres. Artificial centromeres are produced from higher-order repeats (HORs) present at centromere edges, although the exact sequences and chromatin conformations of centromere cores remain unknown. We use high-resolution chromatin immunoprecipitation (ChIP) of centromere components followed by clustering of sequence data as an unbiased approach to identify functional centromere sequences. We find that specific dimeric α-satellite units shared by multiple individuals dominate functional human centromeres. We identify two recently homogenized α-satellite dimers that are occupied by precisely positioned CENP-A (cenH3) nucleosomes with two ~100–base pair (bp) DNA wraps in tandem separated by a CENP-B/CENP-C–containing linker, whereas pericentromeric HORs show diffuse positioning. Precise positioning is largely maintained, whereas abundance decreases exponentially with divergence, which suggests that young α-satellite dimers with paired ~100-bp particles mediate evolution of functional human centromeres. Our unbiased strategy for identifying functional centromeric sequences should be generally applicable to tandem repeat arrays that dominate the centromeres of most eukaryotes. PMID:25927077

A real time genotyping PCR assay for polyomavirus BK.

PubMed

Gard, Lilli; Niesters, Hubert G M; Riezebos-Brilman, Annelies

2015-09-01

Polyomavirus BK (BKV) may cause nephropathy in renal transplant recipients and hemorrhagic cystitis in bone marrow recipients. We developed real-time PCRs (RT-PCR) to determine easily and rapidly the different BKV genotypes (BKGT) (I-IV). On the VP1 gene a duplex of RT-PCRs was developed and validated to differentiate the four main BKGT. 212 BKV positive samples (21 plasma, 191 urine) were tested with these specific PCRs. Of these 212 samples, 55 PCR results were additionally confirmed by sequencing a VP1 gene fragment (nucleotide 1630-1956). For every genotype, a highly specific, precise and internally controlled assay was developed with a limit of detection of log 3 copies per ml. In 18 (8.5%) of these samples genotyping was not successful due to a low viral load. By sequence analysis, the genotype of 46 out of 55 and 2 out of 4 samples with double infection could be confirmed. This study describes RT-PCRs for detection of the main BKGT. It proved to be rapid, cheap and sensitive compared to sequencing. Double infections can also be detected. This method will be of value to investigate the role of BKV infection in relation to the genotype. Copyright © 2015 Elsevier B.V. All rights reserved.

Ns-scaled time-gated fluorescence lifetime imaging for forensic document examination

NASA Astrophysics Data System (ADS)

Zhong, Xin; Wang, Xinwei; Zhou, Yan

2018-01-01

A method of ns-scaled time-gated fluorescence lifetime imaging (TFLI) is proposed to distinguish different fluorescent substances in forensic document examination. Compared with Video Spectral Comparator (VSC) which can examine fluorescence intensity images only, TFLI can detect questioned documents like falsification or alteration. TFLI system can enhance weak signal by accumulation method. The two fluorescence intensity images of the interval delay time tg are acquired by ICCD and fitted into fluorescence lifetime image. The lifetimes of fluorescence substances are represented by different colors, which make it easy to detect the fluorescent substances and the sequence of handwritings. It proves that TFLI is a powerful tool for forensic document examination. Furthermore, the advantages of TFLI system are ns-scaled precision preservation and powerful capture capability.

Measurement of hyperpolarized gas diffusion at very short time scales

PubMed Central

Carl, Michael; Wilson Miller, G.; Mugler, John P.; Rohrbaugh, Scott; Tobias, William A.; Cates, Gordon D.

2007-01-01

We present a new pulse sequence for measuring very-short-time-scale restricted diffusion of hyperpolarized noble gases. The pulse sequence is based on concatenating a large number of bipolar diffusion-sensitizing gradients to increase the diffusion attenuation of the MR signal while maintaining a fundamentally short diffusion time. However, it differs in several respects from existing methods that use oscillating diffusion gradients for this purpose. First, a wait time is inserted between neighboring pairs of gradient pulses; second, consecutive pulse pairs may be applied along orthogonal axes; and finally, the diffusion-attenuated signal is not simply read out at the end of the gradient train but is periodically sampled during the wait times between neighboring pulse pairs. The first two features minimize systematic differences between the measured (apparent) diffusion coefficient and the actual time-dependent diffusivity, while the third feature optimizes the use of the available MR signal to improve the precision of the diffusivity measurement in the face of noise. The benefits of this technique are demonstrated using theoretical calculations, Monte-Carlo simulations of gas diffusion in simple geometries, and experimental phantom measurements in a glass sphere containing hyperpolarized 3He gas. The advantages over the conventional single-bipolar approach were found to increase with decreasing diffusion time, and thus represent a significant step toward making accurate surface-to-volume measurements in the lung airspaces. PMID:17936048

Towards real-time thermometry using simultaneous multislice MRI

NASA Astrophysics Data System (ADS)

Borman, P. T. S.; Bos, C.; de Boorder, T.; Raaymakers, B. W.; Moonen, C. T. W.; Crijns, S. P. M.

2016-09-01

MR-guided thermal therapies, such as high-intensity focused ultrasound (MRgHIFU) and laser-induced thermal therapy (MRgLITT) are increasingly being applied in oncology and neurology. MRI is used for guidance since it can measure temperature noninvasively based on the proton resonance frequency shift (PRFS). For therapy guidance using PRFS thermometry, high temporal resolution and large spatial coverage are desirable. We propose to use the parallel imaging technique simultaneous multislice (SMS) in combination with controlled aliasing (CAIPIRINHA) to accelerate the acquisition. We compare this with the sensitivity encoding (SENSE) acceleration technique. Two experiments were performed to validate that SMS can be used to increase the spatial coverage or the temporal resolution. The first was performed in agar gel using LITT heating and a gradient-echo sequence with echo-planar imaging (EPI), and the second was performed in bovine muscle using HIFU heating and a gradient-echo sequence without EPI. In both experiments temperature curves from an unaccelerated scan and from SMS, SENSE, and SENSE/SMS accelerated scans were compared. The precision was quantified by a standard deviation analysis of scans without heating. Both experiments showed a good agreement between the temperature curves obtained from the unaccelerated, and SMS accelerated scans, confirming that accuracy was maintained during SMS acceleration. The standard deviations of the temperature measurements obtained with SMS were significantly smaller than when SENSE was used, implying that SMS allows for higher acceleration. In the LITT and HIFU experiments SMS factors up to 4 and 3 were reached, respectively, with a loss of precision of less than a factor of 3. Based on these results we conclude that SMS acceleration of PRFS thermometry is a valuable addition to SENSE, because it allows for a higher temporal resolution or bigger spatial coverage, with a higher precision.

Generalized Autobalanced Ramsey Spectroscopy of Clock Transitions

NASA Astrophysics Data System (ADS)

Yudin, V. I.; Taichenachev, A. V.; Basalaev, M. Yu.; Zanon-Willette, T.; Pollock, J. W.; Shuker, M.; Donley, E. A.; Kitching, J.

2018-05-01

When performing precision measurements, the quantity being measured is often perturbed by the measurement process itself. Such measurements include precision frequency measurements for atomic clock applications carried out with Ramsey spectroscopy. With the aim of eliminating probe-induced perturbations, a method of generalized autobalanced Ramsey spectroscopy (GABRS) is presented and rigorously substantiated. The usual local-oscillator frequency control loop is augmented with a second control loop derived from secondary Ramsey sequences interspersed with the primary sequences and with a different Ramsey period. This second loop feeds back to a secondary clock variable and ultimately compensates for the perturbation of the clock frequency caused by the measurements in the first loop. We show that such a two-loop scheme can lead to perfect compensation for measurement-induced light shifts and does not suffer from the effects of relaxation, time-dependent pulse fluctuations and phase-jump modulation errors that are typical of other hyper-Ramsey schemes. Several variants of GABRS are explored based on different secondary variables including added relative phase shifts between Ramsey pulses, external frequency-step compensation, and variable second-pulse duration. We demonstrate that a universal antisymmetric error signal, and hence perfect compensation at a finite modulation amplitude, is generated only if an additional frequency step applied during both Ramsey pulses is used as the concomitant variable parameter. This universal technique can be applied to the fields of atomic clocks, high-resolution molecular spectroscopy, magnetically induced and two-photon probing schemes, Ramsey-type mass spectrometry, and the field of precision measurements. Some variants of GABRS can also be applied for rf atomic clocks using coherent-population-trapping-based Ramsey spectroscopy of the two-photon dark resonance.

Improved blood velocity measurements with a hybrid image filtering and iterative Radon transform algorithm

PubMed Central

Chhatbar, Pratik Y.; Kara, Prakash

2013-01-01

Neural activity leads to hemodynamic changes which can be detected by functional magnetic resonance imaging (fMRI). The determination of blood flow changes in individual vessels is an important aspect of understanding these hemodynamic signals. Blood flow can be calculated from the measurements of vessel diameter and blood velocity. When using line-scan imaging, the movement of blood in the vessel leads to streaks in space-time images, where streak angle is a function of the blood velocity. A variety of methods have been proposed to determine blood velocity from such space-time image sequences. Of these, the Radon transform is relatively easy to implement and has fast data processing. However, the precision of the velocity measurements is dependent on the number of Radon transforms performed, which creates a trade-off between the processing speed and measurement precision. In addition, factors like image contrast, imaging depth, image acquisition speed, and movement artifacts especially in large mammals, can potentially lead to data acquisition that results in erroneous velocity measurements. Here we show that pre-processing the data with a Sobel filter and iterative application of Radon transforms address these issues and provide more accurate blood velocity measurements. Improved signal quality of the image as a result of Sobel filtering increases the accuracy and the iterative Radon transform offers both increased precision and an order of magnitude faster implementation of velocity measurements. This algorithm does not use a priori knowledge of angle information and therefore is sensitive to sudden changes in blood flow. It can be applied on any set of space-time images with red blood cell (RBC) streaks, commonly acquired through line-scan imaging or reconstructed from full-frame, time-lapse images of the vasculature. PMID:23807877

Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine | Office of Cancer Genomics

Cancer.gov

Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial.

Human genomics projects and precision medicine.

PubMed

Carrasco-Ramiro, F; Peiró-Pastor, R; Aguado, B

2017-09-01

The completion of the Human Genome Project (HGP) in 2001 opened the floodgates to a deeper understanding of medicine. There are dozens of HGP-like projects which involve from a few tens to several million genomes currently in progress, which vary from having specialized goals or a more general approach. However, data generation, storage, management and analysis in public and private cloud computing platforms have raised concerns about privacy and security. The knowledge gained from further research has changed the field of genomics and is now slowly permeating into clinical medicine. The new precision (personalized) medicine, where genome sequencing and data analysis are essential components, allows tailored diagnosis and treatment according to the information from the patient's own genome and specific environmental factors. P4 (predictive, preventive, personalized and participatory) medicine is introducing new concepts, challenges and opportunities. This review summarizes current sequencing technologies, concentrates on ongoing human genomics projects, and provides some examples in which precision medicine has already demonstrated clinical impact in diagnosis and/or treatment.

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

PubMed

Yu, Chen; Liu, Yanxia; Ma, Tianhua; Liu, Kai; Xu, Shaohua; Zhang, Yu; Liu, Honglei; La Russa, Marie; Xie, Min; Ding, Sheng; Qi, Lei S

2015-02-05

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Defining precision: The precision medicine initiative trials NCI-MPACT and NCI-MATCH.

PubMed

Coyne, Geraldine O'Sullivan; Takebe, Naoko; Chen, Alice P

"Precision" trials, using rationally incorporated biomarker targets and molecularly selective anticancer agents, have become of great interest to both patients and their physicians. In the endeavor to test the cornerstone premise of precision oncotherapy, that is, determining if modulating a specific molecular aberration in a patient's tumor with a correspondingly specific therapeutic agent improves clinical outcomes, the design of clinical trials with embedded genomic characterization platforms which guide therapy are an increasing challenge. The National Cancer Institute Precision Medicine Initiative is an unprecedented large interdisciplinary collaborative effort to conceptualize and test the feasibility of trials incorporating sequencing platforms and large-scale bioinformatics processing that are not currently uniformly available to patients. National Cancer Institute-Molecular Profiling-based Assignment of Cancer Therapy and National Cancer Institute-Molecular Analysis for Therapy Choice are 2 genomic to phenotypic trials under this National Cancer Institute initiative, where treatment is selected according to predetermined genetic alterations detected using next-generation sequencing technology across a broad range of tumor types. In this article, we discuss the objectives and trial designs that have enabled the public-private partnerships required to complete the scale of both trials, as well as interim trial updates and strategic considerations that have driven data analysis and targeted therapy assignment, with the intent of elucidating further the benefits of this treatment approach for patients. Copyright © 2017. Published by Elsevier Inc.

Precision global health in the digital age.

PubMed

Flahault, Antoine; Geissbuhler, Antoine; Guessous, Idris; Guérin, Philippe; Bolon, Isabelle; Salathé, Marcel; Escher, Gérard

2017-04-19

Precision global health is an approach similar to precision medicine, which facilitates, through innovation and technology, better targeting of public health interventions on a global scale, for the purpose of maximising their effectiveness and relevance. Illustrative examples include: the use of remote sensing data to fight vector-borne diseases; large databases of genomic sequences of foodborne pathogens helping to identify origins of outbreaks; social networks and internet search engines for tracking communicable diseases; cell phone data in humanitarian actions; drones to deliver healthcare services in remote and secluded areas. Open science and data sharing platforms are proposed for fostering international research programmes under fair, ethical and respectful conditions. Innovative education, such as massive open online courses or serious games, can promote wider access to training in public health and improving health literacy. The world is moving towards learning healthcare systems. Professionals are equipped with data collection and decision support devices. They share information, which are complemented by external sources, and analysed in real time using machine learning techniques. They allow for the early detection of anomalies, and eventually guide appropriate public health interventions. This article shows how information-driven approaches, enabled by digital technologies, can help improving global health with greater equity.

WebLogo

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

Crooks, Gavin E.

WebLogo is a web based application designed to make the generation of sequence logos as easy and painless as possible. Sequesnce logos are a graphical representation of an amino acid or nucleic acid multiple sequence alignment developed by Tom Schneider and Mike Stephens. Each logo consists of stacks of symbols, one stack for each position in the sequence. The overall height of the stack indicates the sequence conservation at that position, while the height of symbols within the stack indicates the relative frequency of each amino or nucleic acid at that position. In general, a sequence logo provides a richermore » and more precise description of, for example, a binding site, than would a consensus sequence.« less

Supervised Learning for Detection of Duplicates in Genomic Sequence Databases.

PubMed

Chen, Qingyu; Zobel, Justin; Zhang, Xiuzhen; Verspoor, Karin

2016-01-01

First identified as an issue in 1996, duplication in biological databases introduces redundancy and even leads to inconsistency when contradictory information appears. The amount of data makes purely manual de-duplication impractical, and existing automatic systems cannot detect duplicates as precisely as can experts. Supervised learning has the potential to address such problems by building automatic systems that learn from expert curation to detect duplicates precisely and efficiently. While machine learning is a mature approach in other duplicate detection contexts, it has seen only preliminary application in genomic sequence databases. We developed and evaluated a supervised duplicate detection method based on an expert curated dataset of duplicates, containing over one million pairs across five organisms derived from genomic sequence databases. We selected 22 features to represent distinct attributes of the database records, and developed a binary model and a multi-class model. Both models achieve promising performance; under cross-validation, the binary model had over 90% accuracy in each of the five organisms, while the multi-class model maintains high accuracy and is more robust in generalisation. We performed an ablation study to quantify the impact of different sequence record features, finding that features derived from meta-data, sequence identity, and alignment quality impact performance most strongly. The study demonstrates machine learning can be an effective additional tool for de-duplication of genomic sequence databases. All Data are available as described in the supplementary material.

Precise and rapid isotopomic analysis by (1)H-(13)C 2D NMR: Application to triacylglycerol matrices.

PubMed

Merchak, Noelle; Silvestre, Virginie; Rouger, Laetitia; Giraudeau, Patrick; Rizk, Toufic; Bejjani, Joseph; Akoka, Serge

2016-08-15

An optimized HSQC sequence was tested and applied to triacylglycerol matrices to determine their isotopic and metabolomic profiles. Spectral aliasing and non-uniform sampling approaches were used to decrease the experimental time and to improve the resolution, respectively. An excellent long-term repeatability of signal integrals was achieved enabling to perform isotopic measurements. Thirty-two commercial vegetable oils were analyzed by this methodology. The results show that this method can be used to classify oil samples according to their geographical and botanical origins. Copyright © 2016 Elsevier B.V. All rights reserved.

Compact Integration of a GSM-19 Magnetic Sensor with High-Precision Positioning using VRS GNSS Technology

PubMed Central

Martín, Angel; Padín, Jorge; Anquela, Ana Belén; Sánchez, Juán; Belda, Santiago

2009-01-01

Magnetic data consists of a sequence of collected points with spatial coordinates and magnetic information. The spatial location of these points needs to be as exact as possible in order to develop a precise interpretation of magnetic anomalies. GPS is a valuable tool for accomplishing this objective, especially if the RTK approach is used. In this paper the VRS (Virtual Reference Station) technique is introduced as a new approach for real-time positioning of magnetic sensors. The main advantages of the VRS approach are, firstly, that only a single GPS receiver is needed (no base station is necessary), reducing field work and equipment costs. Secondly, VRS can operate at distances separated 50–70 km from the reference stations without degrading accuracy. A compact integration of a GSM-19 magnetometer sensor with a geodetic GPS antenna is presented; this integration does not diminish the operational flexibility of the original magnetometer and can work with the VRS approach. The coupled devices were tested in marshlands around Gandia, a city located approximately 100 km South of Valencia (Spain), thought to be the site of a Roman cemetery. The results obtained show adequate geometry and high-precision positioning for the structures to be studied (a comparison with the original low precision GPS of the magnetometer is presented). Finally, the results of the magnetic survey are of great interest for archaeological purposes. PMID:22574055

Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae

PubMed Central

Zowawi, Hosam M.; Forde, Brian M.; Alfaresi, Mubarak; Alzarouni, Abdulqadir; Farahat, Yasser; Chong, Teik-Min; Yin, Wai-Fong; Chan, Kok-Gan; Li, Jian; Schembri, Mark A.; Beatson, Scott A.; Paterson, David L.

2015-01-01

Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-blaOXA-181 mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics. PMID:26478520

Identification of neutral tumor evolution across cancer types

PubMed Central

Barnes, Chris P; Graham, Trevor A; Sottoriva, Andrea

2016-01-01

Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power-law fits with high precision 323 of 904 cancers from 14 types, selected from different cohorts. In malignancies identified as neutral, all clonal selection occurred prior to the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intra-tumor heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intra-tumor heterogeneity. PMID:26780609

Peregrine

PubMed Central

Langevin, Stanley A.; Bent, Zachary W.; Solberg, Owen D.; Curtis, Deanna J.; Lane, Pamela D.; Williams, Kelly P.; Schoeniger, Joseph S.; Sinha, Anupama; Lane, Todd W.; Branda, Steven S.

2013-01-01

Use of second generation sequencing (SGS) technologies for transcriptional profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of RNA abundances with unprecedented specificity and sensitivity and the discovery of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the RNA starting material into cDNA flanked by platform-specific adaptor sequences. Each of the published methods and commercial kits currently available for RNA-Seq library preparation suffers from at least one major drawback, including long processing times, large starting material requirements, uneven coverage, loss of strand information and high cost. We report the development of a new RNA-Seq library preparation technique that produces representative, strand-specific RNA-Seq libraries from small amounts of starting material in a fast, simple and cost-effective manner. Additionally, we have developed a new quantitative PCR-based assay for precisely determining the number of PCR cycles to perform for optimal enrichment of the final library, a key step in all SGS library preparation workflows. PMID:23558773

Mapping DNA methylation by transverse current sequencing: Reduction of noise from neighboring nucleotides

NASA Astrophysics Data System (ADS)

Alvarez, Jose; Massey, Steven; Kalitsov, Alan; Velev, Julian

Nanopore sequencing via transverse current has emerged as a competitive candidate for mapping DNA methylation without needed bisulfite-treatment, fluorescent tag, or PCR amplification. By eliminating the error producing amplification step, long read lengths become feasible, which greatly simplifies the assembly process and reduces the time and the cost inherent in current technologies. However, due to the large error rates of nanopore sequencing, single base resolution has not been reached. A very important source of noise is the intrinsic structural noise in the electric signature of the nucleotide arising from the influence of neighboring nucleotides. In this work we perform calculations of the tunneling current through DNA molecules in nanopores using the non-equilibrium electron transport method within an effective multi-orbital tight-binding model derived from first-principles calculations. We develop a base-calling algorithm accounting for the correlations of the current through neighboring bases, which in principle can reduce the error rate below any desired precision. Using this method we show that we can clearly distinguish DNA methylation and other base modifications based on the reading of the tunneling current.

THE MASTER PROTOCOL CONCEPT

PubMed Central

Allegra, Carmen J.

2015-01-01

During the past decade, biomedical technologies have undergone an explosive evolution---from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars---to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demand the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study). PMID:26433553

Function-based classification of carbohydrate-active enzymes by recognition of short, conserved peptide motifs.

PubMed

Busk, Peter Kamp; Lange, Lene

2013-06-01

Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold.

PubMed

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel; Ten Have, Arjen

2018-01-01

Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold

PubMed Central

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel

2018-01-01

Background Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. Results HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. Conclusions HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER. PMID:29579071

a Fast Segmentation Algorithm for C-V Model Based on Exponential Image Sequence Generation

NASA Astrophysics Data System (ADS)

Hu, J.; Lu, L.; Xu, J.; Zhang, J.

2017-09-01

For the island coastline segmentation, a fast segmentation algorithm for C-V model method based on exponential image sequence generation is proposed in this paper. The exponential multi-scale C-V model with level set inheritance and boundary inheritance is developed. The main research contributions are as follows: 1) the problems of the "holes" and "gaps" are solved when extraction coastline through the small scale shrinkage, low-pass filtering and area sorting of region. 2) the initial value of SDF (Signal Distance Function) and the level set are given by Otsu segmentation based on the difference of reflection SAR on land and sea, which are finely close to the coastline. 3) the computational complexity of continuous transition are successfully reduced between the different scales by the SDF and of level set inheritance. Experiment results show that the method accelerates the acquisition of initial level set formation, shortens the time of the extraction of coastline, at the same time, removes the non-coastline body part and improves the identification precision of the main body coastline, which automates the process of coastline segmentation.

Automatic seed selection for segmentation of liver cirrhosis in laparoscopic sequences

NASA Astrophysics Data System (ADS)

Sinha, Rahul; Marcinczak, Jan Marek; Grigat, Rolf-Rainer

2014-03-01

For computer aided diagnosis based on laparoscopic sequences, image segmentation is one of the basic steps which define the success of all further processing. However, many image segmentation algorithms require prior knowledge which is given by interaction with the clinician. We propose an automatic seed selection algorithm for segmentation of liver cirrhosis in laparoscopic sequences which assigns each pixel a probability of being cirrhotic liver tissue or background tissue. Our approach is based on a trained classifier using SIFT and RGB features with PCA. Due to the unique illumination conditions in laparoscopic sequences of the liver, a very low dimensional feature space can be used for classification via logistic regression. The methodology is evaluated on 718 cirrhotic liver and background patches that are taken from laparoscopic sequences of 7 patients. Using a linear classifier we achieve a precision of 91% in a leave-one-patient-out cross-validation. Furthermore, we demonstrate that with logistic probability estimates, seeds with high certainty of being cirrhotic liver tissue can be obtained. For example, our precision of liver seeds increases to 98.5% if only seeds with more than 95% probability of being liver are used. Finally, these automatically selected seeds can be used as priors in Graph Cuts which is demonstrated in this paper.

Electro-optic modulation for high-speed characterization of entangled photon pairs

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

Lukens, Joseph M.; Odele, Ogaga D.; Leaird, Daniel E.

In this study, we demonstrate a new biphoton manipulation and characterization technique based on electro-optic intensity modulation and time shifting. By applying fast modulation signals with a sharply peaked cross-correlation to each photon from an entangled pair, it is possible to measure temporal correlations with significantly higher precision than that attainable using standard single-photon detection. Low-duty-cycle pulses and maximal-length sequences are considered as modulation functions, reducing the time spread in our correlation measurement by a factor of five compared to our detector jitter. With state-of-the-art electro-optic components, we expect the potential to surpass the speed of any single-photon detectors currentlymore » available.« less

Electro-optic modulation for high-speed characterization of entangled photon pairs

DOE PAGES

Lukens, Joseph M.; Odele, Ogaga D.; Leaird, Daniel E.; ...

2015-11-10

In this study, we demonstrate a new biphoton manipulation and characterization technique based on electro-optic intensity modulation and time shifting. By applying fast modulation signals with a sharply peaked cross-correlation to each photon from an entangled pair, it is possible to measure temporal correlations with significantly higher precision than that attainable using standard single-photon detection. Low-duty-cycle pulses and maximal-length sequences are considered as modulation functions, reducing the time spread in our correlation measurement by a factor of five compared to our detector jitter. With state-of-the-art electro-optic components, we expect the potential to surpass the speed of any single-photon detectors currentlymore » available.« less

A supervised learning rule for classification of spatiotemporal spike patterns.

PubMed

Lilin Guo; Zhenzhong Wang; Adjouadi, Malek

2016-08-01

This study introduces a novel supervised algorithm for spiking neurons that take into consideration synapse delays and axonal delays associated with weights. It can be utilized for both classification and association and uses several biologically influenced properties, such as axonal and synaptic delays. This algorithm also takes into consideration spike-timing-dependent plasticity as in Remote Supervised Method (ReSuMe). This paper focuses on the classification aspect alone. Spiked neurons trained according to this proposed learning rule are capable of classifying different categories by the associated sequences of precisely timed spikes. Simulation results have shown that the proposed learning method greatly improves classification accuracy when compared to the Spike Pattern Association Neuron (SPAN) and the Tempotron learning rule.

HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology

PubMed Central

Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C.; Sahinalp, S. Cenk

2017-01-01

Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the “random walk facility location” (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: “multihitting time,” the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients’ survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. PMID:28768687

Robust one-Tube Ω-PCR Strategy Accelerates Precise Sequence Modification of Plasmids for Functional Genomics

PubMed Central

Chen, Letian; Wang, Fengpin; Wang, Xiaoyu; Liu, Yao-Guang

2013-01-01

Functional genomics requires vector construction for protein expression and functional characterization of target genes; therefore, a simple, flexible and low-cost molecular manipulation strategy will be highly advantageous for genomics approaches. Here, we describe a Ω-PCR strategy that enables multiple types of sequence modification, including precise insertion, deletion and substitution, in any position of a circular plasmid. Ω-PCR is based on an overlap extension site-directed mutagenesis technique, and is named for its characteristic Ω-shaped secondary structure during PCR. Ω-PCR can be performed either in two steps, or in one tube in combination with exonuclease I treatment. These strategies have wide applications for protein engineering, gene function analysis and in vitro gene splicing. PMID:23335613

Optical resonance imaging: An optical analog to MRI with sub-diffraction-limited capabilities.

PubMed

Allodi, Marco A; Dahlberg, Peter D; Mazuski, Richard J; Davis, Hunter C; Otto, John P; Engel, Gregory S

2016-12-21

We propose here optical resonance imaging (ORI), a direct optical analog to magnetic resonance imaging (MRI). The proposed pulse sequence for ORI maps space to time and recovers an image from a heterodyne-detected third-order nonlinear photon echo measurement. As opposed to traditional photon echo measurements, the third pulse in the ORI pulse sequence has significant pulse-front tilt that acts as a temporal gradient. This gradient couples space to time by stimulating the emission of a photon echo signal from different lateral spatial locations of a sample at different times, providing a widefield ultrafast microscopy. We circumvent the diffraction limit of the optics by mapping the lateral spatial coordinate of the sample with the emission time of the signal, which can be measured to high precision using interferometric heterodyne detection. This technique is thus an optical analog of MRI, where magnetic-field gradients are used to localize the spin-echo emission to a point below the diffraction limit of the radio-frequency wave used. We calculate the expected ORI signal using 15 fs pulses and 87° of pulse-front tilt, collected using f /2 optics and find a two-point resolution 275 nm using 800 nm light that satisfies the Rayleigh criterion. We also derive a general equation for resolution in optical resonance imaging that indicates that there is a possibility of superresolution imaging using this technique. The photon echo sequence also enables spectroscopic determination of the input and output energy. The technique thus correlates the input energy with the final position and energy of the exciton.

WebLogo: A Sequence Logo Generator

PubMed Central

Crooks, Gavin E.; Hon, Gary; Chandonia, John-Marc; Brenner, Steven E.

2004-01-01

WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment. Sequence logos provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive. Each logo consists of stacks of letters, one stack for each position in the sequence. The overall height of each stack indicates the sequence conservation at that position (measured in bits), whereas the height of symbols within the stack reflects the relative frequency of the corresponding amino or nucleic acid at that position. WebLogo has been enhanced recently with additional features and options, to provide a convenient and highly configurable sequence logo generator. A command line interface and the complete, open WebLogo source code are available for local installation and customization. PMID:15173120

Mitogenome Phylogenetics: The Impact of Using Single Regions and Partitioning Schemes on Topology, Substitution Rate and Divergence Time Estimation

PubMed Central

Duchêne, Sebastián; Archer, Frederick I.; Vilstrup, Julia; Caballero, Susana; Morin, Phillip A.

2011-01-01

The availability of mitochondrial genome sequences is growing as a result of recent technological advances in molecular biology. In phylogenetic analyses, the complete mitogenome is increasingly becoming the marker of choice, usually providing better phylogenetic resolution and precision relative to traditional markers such as cytochrome b (CYTB) and the control region (CR). In some cases, the differences in phylogenetic estimates between mitogenomic and single-gene markers have yielded incongruent conclusions. By comparing phylogenetic estimates made from different genes, we identified the most informative mitochondrial regions and evaluated the minimum amount of data necessary to reproduce the same results as the mitogenome. We compared results among individual genes and the mitogenome for recently published complete mitogenome datasets of selected delphinids (Delphinidae) and killer whales (genus Orcinus). Using Bayesian phylogenetic methods, we investigated differences in estimation of topologies, divergence dates, and clock-like behavior among genes for both datasets. Although the most informative regions were not the same for each taxonomic group (COX1, CYTB, ND3 and ATP6 for Orcinus, and ND1, COX1 and ND4 for Delphinidae), in both cases they were equivalent to less than a quarter of the complete mitogenome. This suggests that gene information content can vary among groups, but can be adequately represented by a portion of the complete sequence. Although our results indicate that complete mitogenomes provide the highest phylogenetic resolution and most precise date estimates, a minimum amount of data can be selected using our approach when the complete sequence is unavailable. Studies based on single genes can benefit from the addition of a few more mitochondrial markers, producing topologies and date estimates similar to those obtained using the entire mitogenome. PMID:22073275

A multilevel ant colony optimization algorithm for classical and isothermic DNA sequencing by hybridization with multiplicity information available.

PubMed

Kwarciak, Kamil; Radom, Marcin; Formanowicz, Piotr

2016-04-01

The classical sequencing by hybridization takes into account a binary information about sequence composition. A given element from an oligonucleotide library is or is not a part of the target sequence. However, the DNA chip technology has been developed and it enables to receive a partial information about multiplicity of each oligonucleotide the analyzed sequence consist of. Currently, it is not possible to assess the exact data of such type but even partial information should be very useful. Two realistic multiplicity information models are taken into consideration in this paper. The first one, called "one and many" assumes that it is possible to obtain information if a given oligonucleotide occurs in a reconstructed sequence once or more than once. According to the second model, called "one, two and many", one is able to receive from biochemical experiment information if a given oligonucleotide is present in an analyzed sequence once, twice or at least three times. An ant colony optimization algorithm has been implemented to verify the above models and to compare with existing algorithms for sequencing by hybridization which utilize the additional information. The proposed algorithm solves the problem with any kind of hybridization errors. Computational experiment results confirm that using even the partial information about multiplicity leads to increased quality of reconstructed sequences. Moreover, they also show that the more precise model enables to obtain better solutions and the ant colony optimization algorithm outperforms the existing ones. Test data sets and the proposed ant colony optimization algorithm are available on: http://bioserver.cs.put.poznan.pl/download/ACO4mSBH.zip. Copyright © 2016 Elsevier Ltd. All rights reserved.

The determination of high-resolution spatio-temporal glacier motion fields from time-lapse sequences

NASA Astrophysics Data System (ADS)

Schwalbe, Ellen; Maas, Hans-Gerd

2017-12-01

This paper presents a comprehensive method for the determination of glacier surface motion vector fields at high spatial and temporal resolution. These vector fields can be derived from monocular terrestrial camera image sequences and are a valuable data source for glaciological analysis of the motion behaviour of glaciers. The measurement concepts for the acquisition of image sequences are presented, and an automated monoscopic image sequence processing chain is developed. Motion vector fields can be derived with high precision by applying automatic subpixel-accuracy image matching techniques on grey value patterns in the image sequences. Well-established matching techniques have been adapted to the special characteristics of the glacier data in order to achieve high reliability in automatic image sequence processing, including the handling of moving shadows as well as motion effects induced by small instabilities in the camera set-up. Suitable geo-referencing techniques were developed to transform image measurements into a reference coordinate system.The result of monoscopic image sequence analysis is a dense raster of glacier surface point trajectories for each image sequence. Each translation vector component in these trajectories can be determined with an accuracy of a few centimetres for points at a distance of several kilometres from the camera. Extensive practical validation experiments have shown that motion vector and trajectory fields derived from monocular image sequences can be used for the determination of high-resolution velocity fields of glaciers, including the analysis of tidal effects on glacier movement, the investigation of a glacier's motion behaviour during calving events, the determination of the position and migration of the grounding line and the detection of subglacial channels during glacier lake outburst floods.

Diagnostics based on nucleic acid sequence variant profiling: PCR, hybridization, and NGS approaches.

PubMed

Khodakov, Dmitriy; Wang, Chunyan; Zhang, David Yu

2016-10-01

Nucleic acid sequence variations have been implicated in many diseases, and reliable detection and quantitation of DNA/RNA biomarkers can inform effective therapeutic action, enabling precision medicine. Nucleic acid analysis technologies being translated into the clinic can broadly be classified into hybridization, PCR, and sequencing, as well as their combinations. Here we review the molecular mechanisms of popular commercial assays, and their progress in translation into in vitro diagnostics. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Precise detection of chromosomal translocation or inversion breakpoints by whole-genome sequencing.

PubMed

Suzuki, Toshifumi; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Miyake, Noriko; Saitsu, Hirotomo; Takeda, Satoru; Matsumoto, Naomichi

2014-12-01

Structural variations (SVs), including translocations, inversions, deletions and duplications, are potentially associated with Mendelian diseases and contiguous gene syndromes. Determination of SV-related breakpoints at the nucleotide level is important to reveal the genetic causes for diseases. Whole-genome sequencing (WGS) by next-generation sequencers is expected to determine structural abnormalities more directly and efficiently than conventional methods. In this study, 14 SVs (9 balanced translocations, 1 inversion and 4 microdeletions) in 9 patients were analyzed by WGS with a shallow (5 × ) to moderate read coverage (20 × ). Among 28 breakpoints (as each SV has two breakpoints), 19 SV breakpoints had been determined previously at the nucleotide level by any other methods and 9 were uncharacterized. BreakDancer and Integrative Genomics Viewer determined 20 breakpoints (16 translocation, 2 inversion and 2 deletion breakpoints), but did not detect 8 breakpoints (2 translocation and 6 deletion breakpoints). These data indicate the efficacy of WGS for the precise determination of translocation and inversion breakpoints.

Super-resolution imaging applied to moving object tracking

NASA Astrophysics Data System (ADS)

Swalaganata, Galandaru; Ratna Sulistyaningrum, Dwi; Setiyono, Budi

2017-10-01

Moving object tracking in a video is a method used to detect and analyze changes that occur in an object that being observed. Visual quality and the precision of the tracked target are highly wished in modern tracking system. The fact that the tracked object does not always seem clear causes the tracking result less precise. The reasons are low quality video, system noise, small object, and other factors. In order to improve the precision of the tracked object especially for small object, we propose a two step solution that integrates a super-resolution technique into tracking approach. First step is super-resolution imaging applied into frame sequences. This step was done by cropping the frame in several frame or all of frame. Second step is tracking the result of super-resolution images. Super-resolution image is a technique to obtain high-resolution images from low-resolution images. In this research single frame super-resolution technique is proposed for tracking approach. Single frame super-resolution was a kind of super-resolution that it has the advantage of fast computation time. The method used for tracking is Camshift. The advantages of Camshift was simple calculation based on HSV color that use its histogram for some condition and color of the object varies. The computational complexity and large memory requirements required for the implementation of super-resolution and tracking were reduced and the precision of the tracked target was good. Experiment showed that integrate a super-resolution imaging into tracking technique can track the object precisely with various background, shape changes of the object, and in a good light conditions.

The Origin of Time in the Songbird Motor Pathway

NASA Astrophysics Data System (ADS)

Long, Michael

2010-03-01

Many complex behaviors, like speech or music, have a hierarchical organization with structure on many timescales. How does the brain control the timing and ordering of behavioral sequences? Do different circuits control different timescales of the behavior? To begin answering these questions, we use temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We found that cooling premotor nucleus HVC (high vocal center) uniformly slows song speed by up to 40% while only slightly altering the acoustic structure, whereas cooling downstream motor nucleus RA (robust nucleus of the arcopallium) has no observable effect on song timing, despite a marked affect of RA spiking activity. To better understand the circuit mechanisms of precise premotor timing, we perform intracellular recordings in RA-projecting HVC neurons during singing. Our observations suggest highly ordered dynamics within HVC which are consistent with a synfire-like neuronal architecture.

An analysis of the uncertainty and bias in DCE-MRI measurements using the spoiled gradient-recalled echo pulse sequence.

PubMed

Subashi, Ergys; Choudhury, Kingshuk R; Johnson, G Allan

2014-03-01

The pharmacokinetic parameters derived from dynamic contrast-enhanced (DCE) MRI have been used in more than 100 phase I trials and investigator led studies. A comparison of the absolute values of these quantities requires an estimation of their respective probability distribution function (PDF). The statistical variation of the DCE-MRI measurement is analyzed by considering the fundamental sources of error in the MR signal intensity acquired with the spoiled gradient-echo (SPGR) pulse sequence. The variance in the SPGR signal intensity arises from quadrature detection and excitation flip angle inconsistency. The noise power was measured in 11 phantoms of contrast agent concentration in the range [0-1] mM (in steps of 0.1 mM) and in onein vivo acquisition of a tumor-bearing mouse. The distribution of the flip angle was determined in a uniform 10 mM CuSO4 phantom using the spin echo double angle method. The PDF of a wide range of T1 values measured with the varying flip angle (VFA) technique was estimated through numerical simulations of the SPGR equation. The resultant uncertainty in contrast agent concentration was incorporated in the most common model of tracer exchange kinetics and the PDF of the derived pharmacokinetic parameters was studied numerically. The VFA method is an unbiased technique for measuringT1 only in the absence of bias in excitation flip angle. The time-dependent concentration of the contrast agent measured in vivo is within the theoretically predicted uncertainty. The uncertainty in measuring K(trans) with SPGR pulse sequences is of the same order, but always higher than, the uncertainty in measuring the pre-injection longitudinal relaxation time (T10). The lowest achievable bias/uncertainty in estimating this parameter is approximately 20%-70% higher than the bias/uncertainty in the measurement of the pre-injection T1 map. The fractional volume parameters derived from the extended Tofts model were found to be extremely sensitive to the variance in signal intensity. The SNR of the pre-injection T1 map indicates the limiting precision with which K(trans) can be calculated. Current small-animal imaging systems and pulse sequences robust to motion artifacts have the capacity for reproducible quantitative acquisitions with DCE-MRI. In these circumstances, it is feasible to achieve a level of precision limited only by physiologic variability.

Novel Bioinformatics-Based Approach for Proteomic Biomarkers Prediction of Calpain-2 & Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein

NASA Astrophysics Data System (ADS)

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges; Kobeissy, Firas

2017-01-01

The crucial biological role of proteases has been visible with the development of degradomics discipline involved in the determination of the proteases/substrates resulting in breakdown-products (BDPs) that can be utilized as putative biomarkers associated with different biological-clinical significance. In the field of cancer biology, matrix metalloproteinases (MMPs) have shown to result in MMPs-generated protein BDPs that are indicative of malignant growth in cancer, while in the field of neural injury, calpain-2 and caspase-3 proteases generate BDPs fragments that are indicative of different neural cell death mechanisms in different injury scenarios. Advanced proteomic techniques have shown a remarkable progress in identifying these BDPs experimentally. In this work, we present a bioinformatics-based prediction method that identifies protease-associated BDPs with high precision and efficiency. The method utilizes state-of-the-art sequence matching and alignment algorithms. It starts by locating consensus sequence occurrences and their variants in any set of protein substrates, generating all fragments resulting from cleavage. The complexity exists in space O(mn) as well as in O(Nmn) time, where N, m, and n are the number of protein sequences, length of the consensus sequence, and length per protein sequence, respectively. Finally, the proposed methodology is validated against βII-spectrin protein, a brain injury validated biomarker.

Spirit Movie of Phobos Eclipse, Sol 675

NASA Technical Reports Server (NTRS)

2005-01-01

[figure removed for brevity, see original site] Spirit Phobos Eclipse Animation

NASA's Mars Exploration Rover Spirit observed the Martian moon Phobos entering the shadow of Mars during the night of the rover's 675th sol (Nov. 27, 2005). The panoramic camera captured 16 images, spaced 10 seconds apart, covering the period from when Phobos was in full sunlight to when it was entirely in shadow. As with our own Moon during lunar eclipses on Earth, even when in the planet's shadow, Phobos was not entirely dark. The small amount of light still visible from Phobos is a kind of 'Mars-shine' -- sunlight reflected through Mars' atmosphere and into the shadowed region.

This clip is a sequence of the 16 images showing the eclipse at about 10 times normal speed. It shows the movement of Phobos from left to right as the moon enters the shadow. Scientists are using information about the precise timing of Martian moon eclipses gained from observations such as these to refine calculations about the orbital path of Phobos. The precise position of Phobos will be important to any future spacecraft taking detailed pictures of the moon or landing on its surface.

The Molecular Landscape of Recurrent and Metastatic Head and Neck Cancers

PubMed Central

Morris, Luc G. T.; Chandramohan, Raghu; West, Lyndsay; Zehir, Ahmet; Chakravarty, Debyani; Pfister, David G.; Wong, Richard J.; Lee, Nancy Y.; Sherman, Eric J.; Baxi, Shrujal S.; Ganly, Ian; Singh, Bhuvanesh; Shah, Jatin P.; Shaha, Ashok R.; Boyle, Jay O.; Patel, Snehal G.; Roman, Benjamin R.; Barker, Christopher A.; McBride, Sean M.; Chan, Timothy A.; Dogan, Snjezana; Hyman, David M.; Berger, Michael F.; Solit, David B.; Riaz, Nadeem; Ho, Alan L.

2016-01-01

IMPORTANCE Recurrent and/or metastatic head and neck cancer is usually incurable. Implementation of precision oncology for these patients has been limited by incomplete understanding of the molecular alterations underlying advanced disease. At the same time, the molecular profiles of many rare head and neck cancer types are unknown. These significant gaps in knowledge need to be addressed to rationally devise new therapies. OBJECTIVE To illuminate the distinct biology of recurrent and metastatic head and neck cancers and review implementation of precision oncology for patients with advanced disease. DESIGN, SETTING, AND PARTICIPANTS After exclusions, 151 patients with advanced, treatment-resistant head and neck tumors, including squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), and other salivary and cutaneous cancers, whose tumors were sequenced between January 2014 and July 2015 at Memorial Sloan Kettering were recruited. Next-generation sequencing of tumors as part of clinical care included high-depth (median 600×) exonic coverage of 410 cancer genes and whole-genome copy number analysis. INTERVENTIONS Next-generation sequencing of tumors and matched normal DNA. MAIN OUTCOMES AND MEASURES Feasibility, the frequency of actionable molecular alterations, the effect on decision making, and identification of alterations associated with recurrent and metastatic disease. RESULTS Overall, 151 patients (95 men and 56 women; mean [range] age, 61.8 [17-100] years) were included in the study. Next-generation sequencing ultimately guided therapy in 21 of 151 patients (14%) (13 of 53 [25%] of patients with HNSCC) by refining diagnoses and matching patients to specific therapies, in some cases with dramatic responses on basket studies. Molecular alterations were potentially actionable in 28 of 135 patients (21%). The genetic profiles of recurrent and metastatic tumors were often distinct from primary tumors. Compared to primary human papillomavirus (HPV)-positive tumors, many recurrent and metastatic HPV-positive tumors exhibited a molecular profile more similar to HPV-negative tumors, including enriched frequencies of TP53 mutation (3 of 20 tumors [15%]), whole genome duplication (5 of 20 tumors [25%]), and 3p deletion (11 of 20 tumors [55%]). There were high rates of TERT promoter mutation in recurrent and metastatic HPV-negative HNSCC (13 of 30 tumors [43%]), cutaneous SCC (11 of 21 tumors [52%]), basal cell carcinoma (3 of 4 tumors [75%]), and ACC (5 of 36 tumors [14%]). Activating NOTCH1 mutations were enriched in metastatic ACCs (8 of 36 tumors [22%]). CONCLUSIONS AND RELEVANCE These findings reveal the molecular landscape of advanced disease and rare cancer subtypes, both predominant challenges in head and neck oncology. To understand the repertoire of targetable alterations in advanced cancers, it is necessary to sequence recurrent and metastatic tumors. These data are important first steps toward implementation of precision head and neck oncology. PMID:27442865

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba’s Fruit Eating Bat, Carollia perspicillata

PubMed Central

Kordes, Sebastian; Kössl, Manfred

2017-01-01

Abstract For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units’ responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams. PMID:29242823

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba's Fruit Eating Bat, Carollia perspicillata.

PubMed

Beetz, M Jerome; Kordes, Sebastian; García-Rosales, Francisco; Kössl, Manfred; Hechavarría, Julio C

2017-01-01

For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units' responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams.

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

Hardware-In-The-Loop Testing of Continuous Control Algorithms for a Precision Formation Flying Demonstration Mission

NASA Technical Reports Server (NTRS)

Naasz, Bo J.; Burns, Richard D.; Gaylor, David; Higinbotham, John

2004-01-01

A sample mission sequence is defined for a low earth orbit demonstration of Precision Formation Flying (PFF). Various guidance navigation and control strategies are discussed for use in the PFF experiment phases. A sample PFF experiment is implemented and tested in a realistic Hardware-in-the-Loop (HWIL) simulation using the Formation Flying Test Bed (FFTB) at NASA's Goddard Space Flight Center.

Precision medicine for cancer with next-generation functional diagnostics.

PubMed

Friedman, Adam A; Letai, Anthony; Fisher, David E; Flaherty, Keith T

2015-12-01

Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies. Recently, several 'next-generation' functional diagnostic technologies have been reported, including novel methods for tumour manipulation, molecularly precise assays of tumour responses and device-based in situ approaches; these address the limitations of the older generation of chemosensitivity tests. The promise of these new technologies suggests a future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients.

Myocardial T1 mapping at 3.0 tesla using an inversion recovery spoiled gradient echo readout and bloch equation simulation with slice profile correction (BLESSPC) T1 estimation algorithm.

PubMed

Shao, Jiaxin; Rapacchi, Stanislas; Nguyen, Kim-Lien; Hu, Peng

2016-02-01

To develop an accurate and precise myocardial T1 mapping technique using an inversion recovery spoiled gradient echo readout at 3.0 Tesla (T). The modified Look-Locker inversion-recovery (MOLLI) sequence was modified to use fast low angle shot (FLASH) readout, incorporating a BLESSPC (Bloch Equation Simulation with Slice Profile Correction) T1 estimation algorithm, for accurate myocardial T1 mapping. The FLASH-MOLLI with BLESSPC fitting was compared with different approaches and sequences with regards to T1 estimation accuracy, precision and image artifact based on simulation, phantom studies, and in vivo studies of 10 healthy volunteers and three patients at 3.0 Tesla. The FLASH-MOLLI with BLESSPC fitting yields accurate T1 estimation (average error = -5.4 ± 15.1 ms, percentage error = -0.5% ± 1.2%) for T1 from 236-1852 ms and heart rate from 40-100 bpm in phantom studies. The FLASH-MOLLI sequence prevented off-resonance artifacts in all 10 healthy volunteers at 3.0T. In vivo, there was no significant difference between FLASH-MOLLI-derived myocardial T1 values and "ShMOLLI+IE" derived values (1458.9 ± 20.9 ms versus 1464.1 ± 6.8 ms, P = 0.50); However, the average precision by FLASH-MOLLI was significantly better than that generated by "ShMOLLI+IE" (1.84 ± 0.36% variance versus 3.57 ± 0.94%, P < 0.001). The FLASH-MOLLI with BLESSPC fitting yields accurate and precise T1 estimation, and eliminates banding artifacts associated with bSSFP at 3.0T. © 2015 Wiley Periodicals, Inc.

Design and characterization of a nanopore-coupled polymerase for single-molecule DNA sequencing by synthesis on an electrode array

PubMed Central

Stranges, P. Benjamin; Palla, Mirkó; Kalachikov, Sergey; Nivala, Jeff; Dorwart, Michael; Trans, Andrew; Kumar, Shiv; Porel, Mintu; Chien, Minchen; Tao, Chuanjuan; Morozova, Irina; Li, Zengmin; Shi, Shundi; Aberra, Aman; Arnold, Cleoma; Yang, Alexander; Aguirre, Anne; Harada, Eric T.; Korenblum, Daniel; Pollard, James; Bhat, Ashwini; Gremyachinskiy, Dmitriy; Bibillo, Arek; Chen, Roger; Davis, Randy; Russo, James J.; Fuller, Carl W.; Roever, Stefan; Ju, Jingyue; Church, George M.

2016-01-01

Scalable, high-throughput DNA sequencing is a prerequisite for precision medicine and biomedical research. Recently, we presented a nanopore-based sequencing-by-synthesis (Nanopore-SBS) approach, which used a set of nucleotides with polymer tags that allow discrimination of the nucleotides in a biological nanopore. Here, we designed and covalently coupled a DNA polymerase to an α-hemolysin (αHL) heptamer using the SpyCatcher/SpyTag conjugation approach. These porin–polymerase conjugates were inserted into lipid bilayers on a complementary metal oxide semiconductor (CMOS)-based electrode array for high-throughput electrical recording of DNA synthesis. The designed nanopore construct successfully detected the capture of tagged nucleotides complementary to a DNA base on a provided template. We measured over 200 tagged-nucleotide signals for each of the four bases and developed a classification method to uniquely distinguish them from each other and background signals. The probability of falsely identifying a background event as a true capture event was less than 1.2%. In the presence of all four tagged nucleotides, we observed sequential additions in real time during polymerase-catalyzed DNA synthesis. Single-polymerase coupling to a nanopore, in combination with the Nanopore-SBS approach, can provide the foundation for a low-cost, single-molecule, electronic DNA-sequencing platform. PMID:27729524

Molecular Cloning of Drebrin: Progress and Perspectives.

PubMed

Kojima, Nobuhiko

2017-01-01

Chicken drebrin isoforms were first identified in the optic tectum of developing brain. Although the time course of protein expression was different in each drebrin isoform, the similarity between their protein structures was suggested by biochemical analysis of purified protein. To determine their protein structures, the cloning of drebrin cDNAs was conducted. Comparison between the cDNA sequences shows that all drebrin cDNAs are identical except that the internal insertion sequences are present or absent in their sequences. Chicken drebrin are now classified into three isoforms, namely, drebrins E1, E2, and A. Genomic cloning demonstrated that the three isoforms are generated by an alternative splicing of individual exons encoding the insertion sequences from single drebrin gene. The mechanism should be precisely regulated in cell-type-specific and developmental stage-specific fashion. Drebrin protein, which is well conserved in various vertebrate species, although mammalian drebrin has only two isoforms, namely, drebrin E and drebrin A, is different from chicken drebrin that has three isoforms. Drebrin belongs to an actin-depolymerizing factor homology (ADF-H) domain protein family. Besides the ADF-H domain, drebrin has other domains, including the actin-binding domain and Homer-binding motifs. Diversity of protein isoform and multiple domains of drebrin could interact differentially with the actin cytoskeleton and other intracellular proteins and regulate diverse cellular processes.

bpRNA: large-scale automated annotation and analysis of RNA secondary structure.

PubMed

Danaee, Padideh; Rouches, Mason; Wiley, Michelle; Deng, Dezhong; Huang, Liang; Hendrix, David

2018-05-09

While RNA secondary structure prediction from sequence data has made remarkable progress, there is a need for improved strategies for annotating the features of RNA secondary structures. Here, we present bpRNA, a novel annotation tool capable of parsing RNA structures, including complex pseudoknot-containing RNAs, to yield an objective, precise, compact, unambiguous, easily-interpretable description of all loops, stems, and pseudoknots, along with the positions, sequence, and flanking base pairs of each such structural feature. We also introduce several new informative representations of RNA structure types to improve structure visualization and interpretation. We have further used bpRNA to generate a web-accessible meta-database, 'bpRNA-1m', of over 100 000 single-molecule, known secondary structures; this is both more fully and accurately annotated and over 20-times larger than existing databases. We use a subset of the database with highly similar (≥90% identical) sequences filtered out to report on statistical trends in sequence, flanking base pairs, and length. Both the bpRNA method and the bpRNA-1m database will be valuable resources both for specific analysis of individual RNA molecules and large-scale analyses such as are useful for updating RNA energy parameters for computational thermodynamic predictions, improving machine learning models for structure prediction, and for benchmarking structure-prediction algorithms.

Functional sequencing read annotation for high precision microbiome analysis

PubMed Central

Zhu, Chengsheng; Miller, Maximilian; Marpaka, Srinayani; Vaysberg, Pavel; Rühlemann, Malte C; Wu, Guojun; Heinsen, Femke-Anouska; Tempel, Marie; Zhao, Liping; Lieb, Wolfgang; Franke, Andre; Bromberg, Yana

2018-01-01

Abstract The vast majority of microorganisms on Earth reside in often-inseparable environment-specific communities—microbiomes. Meta-genomic/-transcriptomic sequencing could reveal the otherwise inaccessible functionality of microbiomes. However, existing analytical approaches focus on attributing sequencing reads to known genes/genomes, often failing to make maximal use of available data. We created faser (functional annotation of sequencing reads), an algorithm that is optimized to map reads to molecular functions encoded by the read-correspondent genes. The mi-faser microbiome analysis pipeline, combining faser with our manually curated reference database of protein functions, accurately annotates microbiome molecular functionality. mi-faser’s minutes-per-microbiome processing speed is significantly faster than that of other methods, allowing for large scale comparisons. Microbiome function vectors can be compared between different conditions to highlight environment-specific and/or time-dependent changes in functionality. Here, we identified previously unseen oil degradation-specific functions in BP oil-spill data, as well as functional signatures of individual-specific gut microbiome responses to a dietary intervention in children with Prader–Willi syndrome. Our method also revealed variability in Crohn's Disease patient microbiomes and clearly distinguished them from those of related healthy individuals. Our analysis highlighted the microbiome role in CD pathogenicity, demonstrating enrichment of patient microbiomes in functions that promote inflammation and that help bacteria survive it. PMID:29194524

Repeating aftershocks of the great 2004 Sumatra and 2005 Nias earthquakes

NASA Astrophysics Data System (ADS)

Yu, Wen-che; Song, Teh-Ru Alex; Silver, Paul G.

2013-05-01

We investigate repeating aftershocks associated with the great 2004 Sumatra-Andaman (Mw 9.2) and 2005 Nias-Simeulue (Mw 8.6) earthquakes by cross-correlating waveforms recorded by the regional seismographic station PSI and teleseismic stations. We identify 10 and 18 correlated aftershock sequences associated with the great 2004 Sumatra and 2005 Nias earthquakes, respectively. The majority of the correlated aftershock sequences are located near the down-dip end of a large afterslip patch. We determine the precise relative locations of event pairs among these sequences and estimate the source rupture areas. The correlated event pairs identified are appropriately referred to as repeating aftershocks, in that the source rupture areas are comparable and significantly overlap within a sequence. We use the repeating aftershocks to estimate afterslip based on the slip-seismic moment scaling relationship and to infer the temporal decay rate of the recurrence interval. The estimated afterslip resembles that measured from the near-field geodetic data to the first order. The decay rate of repeating aftershocks as a function of lapse time t follows a power-law decay 1/tp with the exponent p in the range 0.8-1.1. Both types of observations indicate that repeating aftershocks are governed by post-seismic afterslip.

Quantum sequencing: opportunities and challenges

NASA Astrophysics Data System (ADS)

di Ventra, Massimiliano

Personalized or precision medicine refers to the ability of tailoring drugs to the specific genome and transcriptome of each individual. It is however not yet feasible due the high costs and slow speed of present DNA sequencing methods. I will discuss a sequencing protocol that requires the measurement of the distributions of transverse tunneling currents during the translocation of single-stranded DNA into nanochannels. I will show that such a quantum sequencing approach can reach unprecedented speeds, without requiring any chemical preparation, amplification or labeling. I will discuss recent experiments that support these theoretical predictions, the advantages of this approach over other sequencing methods, and stress the challenges that need to be overcome to render it commercially viable.

Flight Test Result for the Ground-Based Radio Navigation System Sensor with an Unmanned Air Vehicle

PubMed Central

Jang, Jaegyu; Ahn, Woo-Guen; Seo, Seungwoo; Lee, Jang Yong; Park, Jun-Pyo

2015-01-01

The Ground-based Radio Navigation System (GRNS) is an alternative/backup navigation system based on time synchronized pseudolites. It has been studied for some years due to the potential vulnerability issue of satellite navigation systems (e.g., GPS or Galileo). In the framework of our study, a periodic pulsed sequence was used instead of the randomized pulse sequence recommended as the RTCM (radio technical commission for maritime services) SC (special committee)-104 pseudolite signal, as a randomized pulse sequence with a long dwell time is not suitable for applications requiring high dynamics. This paper introduces a mathematical model of the post-correlation output in a navigation sensor, showing that the aliasing caused by the additional frequency term of a periodic pulsed signal leads to a false lock (i.e., Doppler frequency bias) during the signal acquisition process or in the carrier tracking loop of the navigation sensor. We suggest algorithms to resolve the frequency false lock issue in this paper, relying on the use of a multi-correlator. A flight test with an unmanned helicopter was conducted to verify the implemented navigation sensor. The results of this analysis show that there were no false locks during the flight test and that outliers stem from bad dilution of precision (DOP) or fluctuations in the received signal quality. PMID:26569251

Emulating JWST Exoplanet Transit Observations in a Testbed laboratory experiment

NASA Astrophysics Data System (ADS)

Touli, D.; Beichman, C. A.; Vasisht, G.; Smith, R.; Krist, J. E.

2014-12-01

The transit technique is used for the detection and characterization of exoplanets. The combination of transit and radial velocity (RV) measurements gives information about a planet's radius and mass, respectively, leading to an estimate of the planet's density (Borucki et al. 2011) and therefore to its composition and evolutionary history. Transit spectroscopy can provide information on atmospheric composition and structure (Fortney et al. 2013). Spectroscopic observations of individual planets have revealed atomic and molecular species such as H2O, CO2 and CH4 in atmospheres of planets orbiting bright stars, e.g. Deming et al. (2013). The transit observations require extremely precise photometry. For instance, Jupiter transit results to a 1% brightness decrease of a solar type star while the Earth causes only a 0.0084% decrease (84 ppm). Spectroscopic measurements require still greater precision <30ppm. The Precision Projector Laboratory (PPL) is a collaboration between the Jet Propulsion Laboratory (JPL) and California Institute of Technology (Caltech) to characterize and validate detectors through emulation of science images. At PPL we have developed a testbed to project simulated spectra and other images onto a HgCdTe array in order to assess precision photometry for transits, weak lensing etc. for Explorer concepts like JWST, WFIRST, EUCLID. In our controlled laboratory experiment, the goal is to demonstrate ability to extract weak transit spectra as expected for NIRCam, NIRIS and NIRSpec. Two lamps of variable intensity, along with spectral line and photometric simulation masks emulate the signals from a star-only, from a planet-only and finally, from a combination of a planet + star. Three masks have been used to simulate spectra in monochromatic light. These masks, which are fabricated at JPL, have a length of 1000 pixels and widths of 2 pixels, 10 pixels and 1 pixel to correspond respectively to the noted above JWST instruments. From many-hour long observing sequences, we obtain time series photometry with deliberate offsets introduced to test sensitivity to pointing jitter and other effects. We can modify the star-planet brightness contrast by factors up to 10^4:1. With cross correlation techniques we calculate positional shifts which are then used to decorrelate the effects of vertical and lateral offsets due to turbulence and instrumental vibrations on the photometry. Using Principal Component Analysis (PCA), we reject correlated temporal noise to achieve a precision lower than 50 ppm (Clanton et al. 2012). In our current work, after decorrelation of vertical and lateral offsets along with PCA, we achieve a precision of sim20 ppm. To assess the photometric precision we use the Allan variance (Allan 1987). This statistical method is used to characterize noise and stability as it indicates shot noise limited performance. Testbed experiments are ongoing to provide quantitative information on the achievable spectroscopic precision using realistic exoplanet spectra with the goal to define optimized data acquisition sequences for use, for example, with the James Webb Space Telescope.

Model-free aftershock forecasts constructed from similar sequences in the past

NASA Astrophysics Data System (ADS)

van der Elst, N.; Page, M. T.

2017-12-01

The basic premise behind aftershock forecasting is that sequences in the future will be similar to those in the past. Forecast models typically use empirically tuned parametric distributions to approximate past sequences, and project those distributions into the future to make a forecast. While parametric models do a good job of describing average outcomes, they are not explicitly designed to capture the full range of variability between sequences, and can suffer from over-tuning of the parameters. In particular, parametric forecasts may produce a high rate of "surprises" - sequences that land outside the forecast range. Here we present a non-parametric forecast method that cuts out the parametric "middleman" between training data and forecast. The method is based on finding past sequences that are similar to the target sequence, and evaluating their outcomes. We quantify similarity as the Poisson probability that the observed event count in a past sequence reflects the same underlying intensity as the observed event count in the target sequence. Event counts are defined in terms of differential magnitude relative to the mainshock. The forecast is then constructed from the distribution of past sequences outcomes, weighted by their similarity. We compare the similarity forecast with the Reasenberg and Jones (RJ95) method, for a set of 2807 global aftershock sequences of M≥6 mainshocks. We implement a sequence-specific RJ95 forecast using a global average prior and Bayesian updating, but do not propagate epistemic uncertainty. The RJ95 forecast is somewhat more precise than the similarity forecast: 90% of observed sequences fall within a factor of two of the median RJ95 forecast value, whereas the fraction is 85% for the similarity forecast. However, the surprise rate is much higher for the RJ95 forecast; 10% of observed sequences fall in the upper 2.5% of the (Poissonian) forecast range. The surprise rate is less than 3% for the similarity forecast. The similarity forecast may be useful to emergency managers and non-specialists when confidence or expertise in parametric forecasting may be lacking. The method makes over-tuning impossible, and minimizes the rate of surprises. At the least, this forecast constitutes a useful benchmark for more precisely tuned parametric forecasts.

Robust double gain unscented Kalman filter for small satellite attitude estimation

NASA Astrophysics Data System (ADS)

Cao, Lu; Yang, Weiwei; Li, Hengnian; Zhang, Zhidong; Shi, Jianjun

2017-08-01

Limited by the low precision of small satellite sensors, the estimation theories with high performance remains the most popular research topic for the attitude estimation. The Kalman filter (KF) and its extensions have been widely applied in the satellite attitude estimation and achieved plenty of achievements. However, most of the existing methods just take use of the current time-step's priori measurement residuals to complete the measurement update and state estimation, which always ignores the extraction and utilization of the previous time-step's posteriori measurement residuals. In addition, the uncertainty model errors always exist in the attitude dynamic system, which also put forward the higher performance requirements for the classical KF in attitude estimation problem. Therefore, the novel robust double gain unscented Kalman filter (RDG-UKF) is presented in this paper to satisfy the above requirements for the small satellite attitude estimation with the low precision sensors. It is assumed that the system state estimation errors can be exhibited in the measurement residual; therefore, the new method is to derive the second Kalman gain Kk2 for making full use of the previous time-step's measurement residual to improve the utilization efficiency of the measurement data. Moreover, the sequence orthogonal principle and unscented transform (UT) strategy are introduced to robust and enhance the performance of the novel Kalman Filter in order to reduce the influence of existing uncertainty model errors. Numerical simulations show that the proposed RDG-UKF is more effective and robustness in dealing with the model errors and low precision sensors for the attitude estimation of small satellite by comparing with the classical unscented Kalman Filter (UKF).

CRISPR-Cas9 technology: applications in genome engineering, development of sequence-specific antimicrobials, and future prospects.

PubMed

de la Fuente-Núñez, César; Lu, Timothy K

2017-02-20

The development of CRISPR-Cas9 technology has revolutionized our ability to edit DNA and to modulate expression levels of genes of interest, thus providing powerful tools to accelerate the precise engineering of a wide range of organisms. In addition, the CRISPR-Cas system can be harnessed to design "precision" antimicrobials that target bacterial pathogens in a DNA sequence-specific manner. This capability will enable killing of drug-resistant microbes by selectively targeting genes involved in antibiotic resistance, biofilm formation and virulence. Here, we review the origins and mechanistic basis of CRISPR-Cas systems, discuss how this technology can be leveraged to provide a range of applications in both eukaryotic and prokaryotic systems, and finish by outlining limitations and future prospects.

A peripheral component interconnect express-based scalable and highly integrated pulsed spectrometer for solution state dynamic nuclear polarization.

PubMed

He, Yugui; Feng, Jiwen; Zhang, Zhi; Wang, Chao; Wang, Dong; Chen, Fang; Liu, Maili; Liu, Chaoyang

2015-08-01

High sensitivity, high data rates, fast pulses, and accurate synchronization all represent challenges for modern nuclear magnetic resonance spectrometers, which make any expansion or adaptation of these devices to new techniques and experiments difficult. Here, we present a Peripheral Component Interconnect Express (PCIe)-based highly integrated distributed digital architecture pulsed spectrometer that is implemented with electron and nucleus double resonances and is scalable specifically for broad dynamic nuclear polarization (DNP) enhancement applications, including DNP-magnetic resonance spectroscopy/imaging (DNP-MRS/MRI). The distributed modularized architecture can implement more transceiver channels flexibly to meet a variety of MRS/MRI instrumentation needs. The proposed PCIe bus with high data rates can significantly improve data transmission efficiency and communication reliability and allow precise control of pulse sequences. An external high speed double data rate memory chip is used to store acquired data and pulse sequence elements, which greatly accelerates the execution of the pulse sequence, reduces the TR (time of repetition) interval, and improves the accuracy of TR in imaging sequences. Using clock phase-shift technology, we can produce digital pulses accurately with high timing resolution of 1 ns and narrow widths of 4 ns to control the microwave pulses required by pulsed DNP and ensure overall system synchronization. The proposed spectrometer is proved to be both feasible and reliable by observation of a maximum signal enhancement factor of approximately -170 for (1)H, and a high quality water image was successfully obtained by DNP-enhanced spin-echo (1)H MRI at 0.35 T.

A peripheral component interconnect express-based scalable and highly integrated pulsed spectrometer for solution state dynamic nuclear polarization

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

He, Yugui; Liu, Chaoyang, E-mail: chyliu@wipm.ac.cn; State Key Laboratory of Magnet Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071

2015-08-15

High sensitivity, high data rates, fast pulses, and accurate synchronization all represent challenges for modern nuclear magnetic resonance spectrometers, which make any expansion or adaptation of these devices to new techniques and experiments difficult. Here, we present a Peripheral Component Interconnect Express (PCIe)-based highly integrated distributed digital architecture pulsed spectrometer that is implemented with electron and nucleus double resonances and is scalable specifically for broad dynamic nuclear polarization (DNP) enhancement applications, including DNP-magnetic resonance spectroscopy/imaging (DNP-MRS/MRI). The distributed modularized architecture can implement more transceiver channels flexibly to meet a variety of MRS/MRI instrumentation needs. The proposed PCIe bus with highmore » data rates can significantly improve data transmission efficiency and communication reliability and allow precise control of pulse sequences. An external high speed double data rate memory chip is used to store acquired data and pulse sequence elements, which greatly accelerates the execution of the pulse sequence, reduces the TR (time of repetition) interval, and improves the accuracy of TR in imaging sequences. Using clock phase-shift technology, we can produce digital pulses accurately with high timing resolution of 1 ns and narrow widths of 4 ns to control the microwave pulses required by pulsed DNP and ensure overall system synchronization. The proposed spectrometer is proved to be both feasible and reliable by observation of a maximum signal enhancement factor of approximately −170 for {sup 1}H, and a high quality water image was successfully obtained by DNP-enhanced spin-echo {sup 1}H MRI at 0.35 T.« less

F-16 Instructional Sequencing Plan Report.

DTIC Science & Technology

1981-03-01

information). 2. Interference (learning of some tasks interferes with the learning of other tasks when they possess similar but confusing differences ...profound effect on the total training expense. This increases the desirability of systematic, precise methods of syllabus generation. Inherent in a given...the expensive to acquire. resource. Least cost The syllabus must Select sequences which provide a least total make maximum use of cost method of

Formulaic Sequence(FS) Cannot Be an Umbrella Term in SLA: Focusing on Psycholinguistic FSs and Their Identifcation

ERIC Educational Resources Information Center

Myles, Florence; Cordier, Caroline

2017-01-01

The term "formulaic sequence" (FS) is used with a multiplicity of meanings in the SLA literature, some overlapping but others not, and researchers are not always clear in defining precisely what they are investigating, or in limiting the implicational domain of their findings to the type of formulaicity they focus on. The first part of…

De novo assembly and phasing of a Korean human genome.

PubMed

Seo, Jeong-Sun; Rhie, Arang; Kim, Junsoo; Lee, Sangjin; Sohn, Min-Hwan; Kim, Chang-Uk; Hastie, Alex; Cao, Han; Yun, Ji-Young; Kim, Jihye; Kuk, Junho; Park, Gun Hwa; Kim, Juhyeok; Ryu, Hanna; Kim, Jongbum; Roh, Mira; Baek, Jeonghun; Hunkapiller, Michael W; Korlach, Jonas; Shin, Jong-Yeon; Kim, Changhoon

2016-10-13

Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing, next-generation mapping, microfluidics-based linked reads, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.

A knowledge engineering approach to recognizing and extracting sequences of nucleic acids from scientific literature.

PubMed

García-Remesal, Miguel; Maojo, Victor; Crespo, José

2010-01-01

In this paper we present a knowledge engineering approach to automatically recognize and extract genetic sequences from scientific articles. To carry out this task, we use a preliminary recognizer based on a finite state machine to extract all candidate DNA/RNA sequences. The latter are then fed into a knowledge-based system that automatically discards false positives and refines noisy and incorrectly merged sequences. We created the knowledge base by manually analyzing different manuscripts containing genetic sequences. Our approach was evaluated using a test set of 211 full-text articles in PDF format containing 3134 genetic sequences. For such set, we achieved 87.76% precision and 97.70% recall respectively. This method can facilitate different research tasks. These include text mining, information extraction, and information retrieval research dealing with large collections of documents containing genetic sequences.

Sequence-Mandated, Distinct Assembly of Giant Molecules

DOE PAGES

Zhang, Wei; Lu, Xinlin; Mao, Jialin; ...

2017-10-24

Although controlling the primary structure of synthetic polymers is itself a great challenge, the potential of sequence control for tailoring hierarchical structures remains to be exploited, especially in the creation of new and unconventional phases. A series of model amphiphilic chain-like giant molecules was designed and synthesized by interconnecting both hydrophobic and hydrophilic molecular nanoparticles in precisely defined sequence and composition to investigate their sequence-dependent phase structures. Not only compositional variation changed the self-assembled supramolecular phases, but also specific sequences induce unconventional phase formation, including Frank-Kasper phases. The formation mechanism was attributed to the conformational change driven by the collectivemore » hydrogen bonding and the sequence-mandated topology of the molecules. Lastly, these results show that sequence control in synthetic polymers can have a dramatic impact on polymer properties and self-assembly.« less

Sequence-Mandated, Distinct Assembly of Giant Molecules

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

Zhang, Wei; Lu, Xinlin; Mao, Jialin

Although controlling the primary structure of synthetic polymers is itself a great challenge, the potential of sequence control for tailoring hierarchical structures remains to be exploited, especially in the creation of new and unconventional phases. A series of model amphiphilic chain-like giant molecules was designed and synthesized by interconnecting both hydrophobic and hydrophilic molecular nanoparticles in precisely defined sequence and composition to investigate their sequence-dependent phase structures. Not only compositional variation changed the self-assembled supramolecular phases, but also specific sequences induce unconventional phase formation, including Frank-Kasper phases. The formation mechanism was attributed to the conformational change driven by the collectivemore » hydrogen bonding and the sequence-mandated topology of the molecules. Lastly, these results show that sequence control in synthetic polymers can have a dramatic impact on polymer properties and self-assembly.« less

Integration of phytochemicals and phytotherapy into cancer precision medicine.

PubMed

Efferth, Thomas; Saeed, Mohamed E M; Mirghani, Elhaj; Alim, Awadh; Yassin, Zahir; Saeed, Elfatih; Khalid, Hassan E; Daak, Salah

2017-07-25

Concepts of individualized therapy in the 1970s and 1980s attempted to develop predictive in vitro tests for individual drug responsiveness without reaching clinical routine. Precision medicine attempts to device novel individual cancer therapy strategies. Using bioinformatics, relevant knowledge is extracted from huge data amounts. However, tumor heterogeneity challenges chemotherapy due to genetically and phenotypically different cell subpopulations, which may lead to refractory tumors. Natural products always served as vital resources for cancer therapy (e.g., Vinca alkaloids, camptothecin, paclitaxel, etc.) and are also sources for novel drugs. Targeted drugs developed to specifically address tumor-related proteins represent the basis of precision medicine. Natural products from plants represent excellent resource for targeted therapies. Phytochemicals and herbal mixtures act multi-specifically, i.e. they attack multiple targets at the same time. Network pharmacology facilitates the identification of the complexity of pharmacogenomic networks and new signaling networks that are distorted in tumors. In the present review, we give a conceptual overview, how the problem of drug resistance may be approached by integrating phytochemicals and phytotherapy into academic western medicine. Modern technology platforms (e.g. "-omics" technologies, DNA/RNA sequencing, and network pharmacology) can be applied for diverse treatment modalities such as cytotoxic and targeted chemotherapy as well as phytochemicals and phytotherapy. Thereby, these technologies represent an integrative momentum to merge the best of two worlds: clinical oncology and traditional medicine. In conclusion, the integration of phytochemicals and phytotherapy into cancer precision medicine represents a valuable asset to chemically synthesized chemicals and therapeutic antibodies.

Comprehensive analysis of the T-cell receptor beta chain gene in rhesus monkey by high throughput sequencing

PubMed Central

Li, Zhoufang; Liu, Guangjie; Tong, Yin; Zhang, Meng; Xu, Ying; Qin, Li; Wang, Zhanhui; Chen, Xiaoping; He, Jiankui

2015-01-01

Profiling immune repertoires by high throughput sequencing enhances our understanding of immune system complexity and immune-related diseases in humans. Previously, cloning and Sanger sequencing identified limited numbers of T cell receptor (TCR) nucleotide sequences in rhesus monkeys, thus their full immune repertoire is unknown. We applied multiplex PCR and Illumina high throughput sequencing to study the TCRβ of rhesus monkeys. We identified 1.26 million TCRβ sequences corresponding to 643,570 unique TCRβ sequences and 270,557 unique complementarity-determining region 3 (CDR3) gene sequences. Precise measurements of CDR3 length distribution, CDR3 amino acid distribution, length distribution of N nucleotide of junctional region, and TCRV and TCRJ gene usage preferences were performed. A comprehensive profile of rhesus monkey immune repertoire might aid human infectious disease studies using rhesus monkeys. PMID:25961410

Ethical considerations of neuro-oncology trial design in the era of precision medicine.

PubMed

Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

2017-08-01

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

Automatic pose correction for image-guided nonhuman primate brain surgery planning

NASA Astrophysics Data System (ADS)

Ghafurian, Soheil; Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

2016-03-01

Intracranial delivery of recombinant DNA and neurochemical analysis in nonhuman primate (NHP) requires precise targeting of various brain structures via imaging derived coordinates in stereotactic surgeries. To attain targeting precision, the surgical planning needs to be done on preoperative three dimensional (3D) CT and/or MR images, in which the animals head is fixed in a pose identical to the pose during the stereotactic surgery. The matching of the image to the pose in the stereotactic frame can be done manually by detecting key anatomical landmarks on the 3D MR and CT images such as ear canal and ear bar zero position. This is not only time intensive but also prone to error due to the varying initial poses in the images which affects both the landmark detection and rotation estimation. We have introduced a fast, reproducible, and semi-automatic method to detect the stereotactic coordinate system in the image and correct the pose. The method begins with a rigid registration of the subject images to an atlas and proceeds to detect the anatomical landmarks through a sequence of optimization, deformable and multimodal registration algorithms. The results showed similar precision (maximum difference of 1.71 in average in-plane rotation) to a manual pose correction.

Temporal Precision of Neuronal Information in a Rapid Perceptual Judgment

PubMed Central

Ghose, Geoffrey M.; Harrison, Ian T.

2009-01-01

In many situations, such as pedestrians crossing a busy street or prey evading predators, rapid decisions based on limited perceptual information are critical for survival. The brevity of these perceptual judgments constrains how neuronal signals are integrated or pooled over time because the underlying sequence of processes, from sensation to perceptual evaluation to motor planning and execution, all occur within several hundred milliseconds. Because most previous physiological studies of these processes have relied on tasks requiring considerably longer temporal integration, the neuronal basis of such rapid decisions remains largely unexplored. In this study, we examine the temporal precision of neuronal activity associated with a rapid perceptual judgment. We find that the activity of individual neurons over tens of milliseconds can reliably convey information about sensory events and was well correlated with the animals' judgments. There was a strong correlation between sensory reliability and the correlation with behavioral choice, suggesting that rapid decisions were preferentially based on the most reliable sensory signals. We also find that a simple model in which the responses of a small number of individual neurons (<5) are summed can completely explain behavioral performance. These results suggest that neuronal circuits are sufficiently precise to allow for cognitive decisions to be based on small numbers of action potentials from highly reliable neurons. PMID:19109454

Temporal precision of neuronal information in a rapid perceptual judgment.

PubMed

Ghose, Geoffrey M; Harrison, Ian T

2009-03-01

In many situations, such as pedestrians crossing a busy street or prey evading predators, rapid decisions based on limited perceptual information are critical for survival. The brevity of these perceptual judgments constrains how neuronal signals are integrated or pooled over time because the underlying sequence of processes, from sensation to perceptual evaluation to motor planning and execution, all occur within several hundred milliseconds. Because most previous physiological studies of these processes have relied on tasks requiring considerably longer temporal integration, the neuronal basis of such rapid decisions remains largely unexplored. In this study, we examine the temporal precision of neuronal activity associated with a rapid perceptual judgment. We find that the activity of individual neurons over tens of milliseconds can reliably convey information about sensory events and was well correlated with the animals' judgments. There was a strong correlation between sensory reliability and the correlation with behavioral choice, suggesting that rapid decisions were preferentially based on the most reliable sensory signals. We also find that a simple model in which the responses of a small number of individual neurons (<5) are summed can completely explain behavioral performance. These results suggest that neuronal circuits are sufficiently precise to allow for cognitive decisions to be based on small numbers of action potentials from highly reliable neurons.

A Phylogenomic Assessment of Ancient Polyploidy and Genome Evolution across the Poales

PubMed Central

McKain, Michael R.; Tang, Haibao; McNeal, Joel R.; Ayyampalayam, Saravanaraj; Davis, Jerrold I.; dePamphilis, Claude W.; Givnish, Thomas J.; Pires, J. Chris; Stevenson, Dennis Wm.; Leebens-Mack, James H.

2016-01-01

Comparisons of flowering plant genomes reveal multiple rounds of ancient polyploidy characterized by large intragenomic syntenic blocks. Three such whole-genome duplication (WGD) events, designated as rho (ρ), sigma (σ), and tau (τ), have been identified in the genomes of cereal grasses. Precise dating of these WGD events is necessary to investigate how they have influenced diversification rates, evolutionary innovations, and genomic characteristics such as the GC profile of protein-coding sequences. The timing of these events has remained uncertain due to the paucity of monocot genome sequence data outside the grass family (Poaceae). Phylogenomic analysis of protein-coding genes from sequenced genomes and transcriptome assemblies from 35 species, including representatives of all families within the Poales, has resolved the timing of rho and sigma relative to speciation events and placed tau prior to divergence of Asparagales and the commelinids but after divergence with eudicots. Examination of gene family phylogenies indicates that rho occurred just prior to the diversification of Poaceae and sigma occurred before early diversification of Poales lineages but after the Poales-commelinid split. Additional lineage-specific WGD events were identified on the basis of the transcriptome data. Gene families exhibiting high GC content are underrepresented among those with duplicate genes that persisted following these genome duplications. However, genome duplications had little overall influence on lineage-specific changes in the GC content of coding genes. Improved resolution of the timing of WGD events in monocot history provides evidence for the influence of polyploidization on functional evolution and species diversification. PMID:26988252

MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

PubMed

Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

2017-04-01

To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Hardware fault insertion and instrumentation system: Mechanization and validation

NASA Technical Reports Server (NTRS)

Benson, J. W.

1987-01-01

Automated test capability for extensive low-level hardware fault insertion testing is developed. The test capability is used to calibrate fault detection coverage and associated latency times as relevant to projecting overall system reliability. Described are modifications made to the NASA Ames Reconfigurable Flight Control System (RDFCS) Facility to fully automate the total test loop involving the Draper Laboratories' Fault Injector Unit. The automated capability provided included the application of sequences of simulated low-level hardware faults, the precise measurement of fault latency times, the identification of fault symptoms, and bulk storage of test case results. A PDP-11/60 served as a test coordinator, and a PDP-11/04 as an instrumentation device. The fault injector was controlled by applications test software in the PDP-11/60, rather than by manual commands from a terminal keyboard. The time base was especially developed for this application to use a variety of signal sources in the system simulator.

Video time encoding machines.

PubMed

Lazar, Aurel A; Pnevmatikakis, Eftychios A

2011-03-01

We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value.

Video Time Encoding Machines

PubMed Central

Lazar, Aurel A.; Pnevmatikakis, Eftychios A.

2013-01-01

We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value. PMID:21296708

High-Precision 40Ar/39Ar dating of the Deccan Traps

NASA Astrophysics Data System (ADS)

Sprain, C. J.; Renne, P. R.; Richards, M. A.; Self, S.; Vanderkluysen, L.; Pande, K.; Morgan, L. E.; Cosca, M. A.

2015-12-01

The Deccan Traps (DT) have been strongly implicated over the past thirty years as a potential cause of the mass extinctions at the Cretaceous-Paleogene boundary (KPB). While a broad coincidence between the DT eruptions and the KPB is increasingly clear, variables such as tempo, volume of eruptions, and amount of associated climate-modifying volatiles, are too poorly constrained to properly assess causality. In order to appropriately test whether the DT played a role in the mass extinctions a high-precision geochronologic framework defining the timing and tempo of volcanic eruptions is needed. Recent high-precision U/Pb dating of zircons from inferred paleosols (red boles) and melt segregation horizons is the only available geochronology of the DT that is sufficiently precise to resolve age differences of less than 100 ka (Schoene et al., 2015). While this technique can achieve high-precision dates for individual zircon crystals, protracted age distributions may not include the actual eruption age. Moreover, the applicability of U/Pb dating in the DT is limited as suitable material is only sporadically present and therefore the technique is unlikely to achieve the resolution necessary to assess the tempo of DT eruptions. To mediate these limitations, we present new high-precision 40Ar/39Ar ages for plagioclase separated from the lava flows sampled from each of ten chemostratigraphically-defined formations within the Western Ghats. Multiple (N = 1-4) plateau ages from each sample and detailed neutron fluence monitoring during irradiation yield ages with precision commonly better than 100 ka (1 sigma). Results provide the first precise location of the KPB within the DT eruption sequence, which approximately coincides with major changes in eruption frequency, flow-field volumes, extent of crustal contamination, and degree of fractionation. Collectively, these results suggest that a state shift occurred in the DT magma system within ~50 ka of the Chicxulub impact, consistent with transient effects of seismic energy associated with the impact. Further, our new data invalidate the concept of three discrete eruption pulses in the Western Ghats (Chenet et al., 2007, 2009; Keller et al., 2008) and rather indicate only a sharp increase in mean volumetric eruption rates near the KPB.

A >400 kyrs archive of sedimentation in Scladina cave (Belgium)

NASA Astrophysics Data System (ADS)

Vonhof, Hubert; Bonjean, Dominique; Pirson, Stéphane; van der Lubbe, Jeroen; Hellstrom, John; Scholz, Denis; Verheyden, Sophie

2017-04-01

Scladina Cave, near the Meuse River in Belgium, is well-known for its well preserved Neanderthal fossils and stone tools. Cave research started in the 1970's, when archeological findings near the entrance of the cave initiated a long-running excavation programme in the -at that time- almost completely sediment-infilled cave. Over the past decades, a wealth of mammal fossils, stone tools, and a mandible of a Neanderthal child were found, and the complex sedimentary context of the cave strata was reconstructed in high detail. Crucial to understanding the cave stratigraphy is the construction of an absolutely dated age model. Until recently, this age model was based on a number of OSL ages, pollen stratigraphy and a few U-series ages on flowstone and stalagmite calcite. These U-series ages, however, had much lower precision than can be obtained by modern MC-ICP-MS techniques. In this study, we present new and more precise U-series ages for the major flow stone levels in Scladina Cave (upper stratigraphical sequence), and two flowstone levels from Sous-Saint-Paul Cave (lower stratigraphical sequence). The oldest flow stone layer dates back to > 400 ka, and the youngest represents the Holocene. The age model shows that flow stone formation typically occurred during warm climate conditions. These findings help to improve the existing age model for Scladina Cave significantly, and place better constraints on the age of individual fossils, and fossil assemblages in the cave.

Detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR) and molecular characterization in cervical cancer cells.

PubMed

Luft, F; Klaes, R; Nees, M; Dürst, M; Heilmann, V; Melsheimer, P; von Knebel Doeberitz, M

2001-04-01

Human papillomavirus (HPV) genomes usually persist as episomal molecules in HPV associated preneoplastic lesions whereas they are frequently integrated into the host cell genome in HPV-related cancers cells. This suggests that malignant conversion of HPV-infected epithelia is linked to recombination of cellular and viral sequences. Due to technical limitations, precise sequence information on viral-cellular junctions were obtained only for few cell lines and primary lesions. In order to facilitate the molecular analysis of genomic HPV integration, we established a ligation-mediated PCR assay for the detection of integrated papillomavirus sequences (DIPS-PCR). DIPS-PCR was initially used to amplify genomic viral-cellular junctions from HPV-associated cervical cancer cell lines (C4-I, C4-II, SW756, and HeLa) and HPV-immortalized keratinocyte lines (HPKIA, HPKII). In addition to junctions already reported in public data bases, various new fusion fragments were identified. Subsequently, 22 different viral-cellular junctions were amplified from 17 cervical carcinomas and 1 vulval intraepithelial neoplasia (VIN III). Sequence analysis of each junction revealed that the viral E1 open reading frame (ORF) was fused to cellular sequences in 20 of 22 (91%) cases. Chromosomal integration loci mapped to chromosomes 1 (2n), 2 (3n), 7 (2n), 8 (3n), 10 (1n), 14 (5n), 16 (1n), 17 (2n), and mitochondrial DNA (1n), suggesting random distribution of chromosomal integration sites. Precise sequence information obtained by DIPS-PCR was further used to monitor the monoclonal origin of 4 cervical cancers, 1 case of recurrent premalignant lesions and 1 lymph node metastasis. Therefore, DIPS-PCR might allow efficient therapy control and prediction of relapse in patients with HPV-associated anogenital cancers. Copyright 2001 Wiley-Liss, Inc.

An ultra-low cost NMR device with arbitrary pulse programming

NASA Astrophysics Data System (ADS)

Chen, Hsueh-Ying; Kim, Yaewon; Nath, Pulak; Hilty, Christian

2015-06-01

Ultra-low cost, general purpose electronics boards featuring microprocessors or field programmable gate arrays (FPGA) are reaching capabilities sufficient for direct implementation of NMR spectrometers. We demonstrate a spectrometer based on such a board, implemented with a minimal need for the addition of custom electronics and external components. This feature allows such a spectrometer to be readily implemented using typical knowledge present in an NMR laboratory. With FPGA technology, digital tasks are performed with precise timing, without the limitation of predetermined hardware function. In this case, the FPGA is used for programming of arbitrarily timed pulse sequence events, and to digitally generate required frequencies. Data acquired from a 0.53 T permanent magnet serves as a demonstration of the flexibility of pulse programming for diverse experiments. Pulse sequences applied include a spin-lattice relaxation measurement using a pulse train with small-flip angle pulses, and a Carr-Purcell-Meiboom-Gill experiment with phase cycle. Mixing of NMR signals with a digitally generated, 4-step phase-cycled reference frequency is further implemented to achieve sequential quadrature detection. The flexibility in hardware implementation permits tailoring this type of spectrometer for applications such as relaxometry, polarimetry, diffusometry or NMR based magnetometry.

Transient extracellular glutamate events in the basolateral amygdala track reward seeking actions

PubMed Central

Wassum, KM; Tolosa, VM; Tseng, TC; Balleine, BW; Monbouquette, HG; Maidment, NT

2012-01-01

The ability to make rapid, informed decisions about whether or not to engage in a sequence of actions to earn reward is essential for survival. Modeling in rodents has demonstrated a critical role for the basolateral amygdala (BLA) in such reward-seeking actions, but the precise neurochemical underpinnings are not well understood. Taking advantage of recent advancements in biosensor technologies, we made spatially discrete near-real time extracellular recordings of the major excitatory transmitter, glutamate, in the BLA of rats performing a self-paced lever-pressing sequence task for sucrose reward. This allowed us to detect rapid transient fluctuations in extracellular BLA glutamate time-locked to action performance. These glutamate transients tended to precede lever pressing actions and were markedly increased in frequency when rats were engaged in such reward seeking actions. Based on muscimol and tetrodotoxin microinfusions these glutamate transients appeared to originate from the terminals of neurons with cell bodies in the orbital frontal cortex. Importantly, glutamate transient amplitude and frequency fluctuated with the value of the earned reward and positively predicted lever pressing rate. Such novel rapid glutamate recordings during instrumental performance identify a role for glutamatergic signaling within the BLA in instrumental reward-seeking actions. PMID:22357857

A novel alignment-free method for detection of lateral genetic transfer based on TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Ragan, Mark A

2016-07-25

Lateral genetic transfer (LGT) plays an important role in the evolution of microbes. Existing computational methods for detecting genomic regions of putative lateral origin scale poorly to large data. Here, we propose a novel method based on TF-IDF (Term Frequency-Inverse Document Frequency) statistics to detect not only regions of lateral origin, but also their origin and direction of transfer, in sets of hierarchically structured nucleotide or protein sequences. This approach is based on the frequency distributions of k-mers in the sequences. If a set of contiguous k-mers appears sufficiently more frequently in another phyletic group than in its own, we infer that they have been transferred from the first group to the second. We performed rigorous tests of TF-IDF using simulated and empirical datasets. With the simulated data, we tested our method under different parameter settings for sequence length, substitution rate between and within groups and post-LGT, deletion rate, length of transferred region and k size, and found that we can detect LGT events with high precision and recall. Our method performs better than an established method, ALFY, which has high recall but low precision. Our method is efficient, with runtime increasing approximately linearly with sequence length.

A novel hybrid method of beta-turn identification in protein using binary logistic regression and neural network

PubMed Central

Asghari, Mehdi Poursheikhali; Hayatshahi, Sayyed Hamed Sadat; Abdolmaleki, Parviz

2012-01-01

From both the structural and functional points of view, β-turns play important biological roles in proteins. In the present study, a novel two-stage hybrid procedure has been developed to identify β-turns in proteins. Binary logistic regression was initially used for the first time to select significant sequence parameters in identification of β-turns due to a re-substitution test procedure. Sequence parameters were consisted of 80 amino acid positional occurrences and 20 amino acid percentages in sequence. Among these parameters, the most significant ones which were selected by binary logistic regression model, were percentages of Gly, Ser and the occurrence of Asn in position i+2, respectively, in sequence. These significant parameters have the highest effect on the constitution of a β-turn sequence. A neural network model was then constructed and fed by the parameters selected by binary logistic regression to build a hybrid predictor. The networks have been trained and tested on a non-homologous dataset of 565 protein chains. With applying a nine fold cross-validation test on the dataset, the network reached an overall accuracy (Qtotal) of 74, which is comparable with results of the other β-turn prediction methods. In conclusion, this study proves that the parameter selection ability of binary logistic regression together with the prediction capability of neural networks lead to the development of more precise models for identifying β-turns in proteins. PMID:27418910

A novel hybrid method of beta-turn identification in protein using binary logistic regression and neural network.

PubMed

Asghari, Mehdi Poursheikhali; Hayatshahi, Sayyed Hamed Sadat; Abdolmaleki, Parviz

2012-01-01

From both the structural and functional points of view, β-turns play important biological roles in proteins. In the present study, a novel two-stage hybrid procedure has been developed to identify β-turns in proteins. Binary logistic regression was initially used for the first time to select significant sequence parameters in identification of β-turns due to a re-substitution test procedure. Sequence parameters were consisted of 80 amino acid positional occurrences and 20 amino acid percentages in sequence. Among these parameters, the most significant ones which were selected by binary logistic regression model, were percentages of Gly, Ser and the occurrence of Asn in position i+2, respectively, in sequence. These significant parameters have the highest effect on the constitution of a β-turn sequence. A neural network model was then constructed and fed by the parameters selected by binary logistic regression to build a hybrid predictor. The networks have been trained and tested on a non-homologous dataset of 565 protein chains. With applying a nine fold cross-validation test on the dataset, the network reached an overall accuracy (Qtotal) of 74, which is comparable with results of the other β-turn prediction methods. In conclusion, this study proves that the parameter selection ability of binary logistic regression together with the prediction capability of neural networks lead to the development of more precise models for identifying β-turns in proteins.

Two-Stage orders sequencing system for mixed-model assembly

NASA Astrophysics Data System (ADS)

Zemczak, M.; Skolud, B.; Krenczyk, D.

2015-11-01

In the paper, the authors focus on the NP-hard problem of orders sequencing, formulated similarly to Car Sequencing Problem (CSP). The object of the research is the assembly line in an automotive industry company, on which few different models of products, each in a certain number of versions, are assembled on the shared resources, set in a line. Such production type is usually determined as a mixed-model production, and arose from the necessity of manufacturing customized products on the basis of very specific orders from single clients. The producers are nowadays obliged to provide each client the possibility to determine a huge amount of the features of the product they are willing to buy, as the competition in the automotive market is large. Due to the previously mentioned nature of the problem (NP-hard), in the given time period only satisfactory solutions are sought, as the optimal solution method has not yet been found. Most of the researchers that implemented inaccurate methods (e.g. evolutionary algorithms) to solving sequencing problems dropped the research after testing phase, as they were not able to obtain reproducible results, and met problems while determining the quality of the received solutions. Therefore a new approach to solving the problem, presented in this paper as a sequencing system is being developed. The sequencing system consists of a set of determined rules, implemented into computer environment. The system itself works in two stages. First of them is connected with the determination of a place in the storage buffer to which certain production orders should be sent. In the second stage of functioning, precise sets of sequences are determined and evaluated for certain parts of the storage buffer under certain criteria.

Identification of Medically Important Yeasts Using PCR-Based Detection of DNA Sequence Polymorphisms in the Internal Transcribed Spacer 2 Region of the rRNA Genes

PubMed Central

Chen, Y. C.; Eisner, J. D.; Kattar, M. M.; Rassoulian-Barrett, S. L.; LaFe, K.; Yarfitz, S. L.; Limaye, A. P.; Cookson, B. T.

2000-01-01

Identification of medically relevant yeasts can be time-consuming and inaccurate with current methods. We evaluated PCR-based detection of sequence polymorphisms in the internal transcribed spacer 2 (ITS2) region of the rRNA genes as a means of fungal identification. Clinical isolates (401), reference strains (6), and type strains (27), representing 34 species of yeasts were examined. The length of PCR-amplified ITS2 region DNA was determined with single-base precision in less than 30 min by using automated capillary electrophoresis. Unique, species-specific PCR products ranging from 237 to 429 bp were obtained from 92% of the clinical isolates. The remaining 8%, divided into groups with ITS2 regions which differed by ≤2 bp in mean length, all contained species-specific DNA sequences easily distinguishable by restriction enzyme analysis. These data, and the specificity of length polymorphisms for identifying yeasts, were confirmed by DNA sequence analysis of the ITS2 region from 93 isolates. Phenotypic and ITS2-based identification was concordant for 427 of 434 yeast isolates examined using sequence identity of ≥99%. Seven clinical isolates contained ITS2 sequences that did not agree with their phenotypic identification, and ITS2-based phylogenetic analyses indicate the possibility of new or clinically unusual species in the Rhodotorula and Candida genera. This work establishes an initial database, validated with over 400 clinical isolates, of ITS2 length and sequence polymorphisms for 34 species of yeasts. We conclude that size and restriction analysis of PCR-amplified ITS2 region DNA is a rapid and reliable method to identify clinically significant yeasts, including potentially new or emerging pathogenic species. PMID:10834993

High-Precision 40Ar/39Ar dating of the Deccan Traps

NASA Astrophysics Data System (ADS)

Sprain, C. J.; Renne, P. R.; Fendley, I.; Pande, K.; Self, S.; Vanderkluysen, L.; Richards, M. A.

2017-12-01

Almost forty years ago it was first hypothesized that greenhouse gases emitted from the Deccan Traps (DT) played a role in the Cretaceous-Paleogene boundary (KPB) mass extinction (McLean 1979, 1980, 1985). At that time, this hypothesis was dismissed due to insufficient geochronology and new evidence that a bolide impact coincided with the KPB. Since then, evidence such as records of protracted extinction and climate change in the Late Cretaceous, in addition to new high-precision geochronology of the DT, has bolstered the Deccan hypothesis. Recently, many models have been produced to simulate how DT volcanism may have perturbed global ecosystems. However, modeled outcomes are largely dependent upon variables such as the amount and species of gas released and the tempo of eruptions, which are not well constrained (Self et al., 2014). To better constrain climatic models and better understand the role DT volcanism played in the KPB extinction, we developed a high-precision geochronologic framework defining the timing and tempo of DT eruptions within the Western Ghats using high-precision 40Ar/39Ar geochronology. Our new results show that the DT erupted relatively continuously starting 66.4 Ma and extending to at least 65.3 Ma with no hiatuses longer than 50 ka, invalidating the concept of three discrete eruption pulses in the Western Ghats (Chenet et al., 2007, 2009; Keller et al., 2008). Our new data further provide the first precise location of the KPB within the DT sequence and place this boundary at or near the Lonavala-Wai subgroup transition, roughly coincident with major changes in eruption frequency, flow-field volumes, and extent of crustal magma contamination. Taken together, these results suggest that a state shift occurred in the DT magmatic system around the time of the Chicxulub impact, consistent with the impact triggering hypothesis of Richards et al. (2015). Our work further shows that over 80% of the estimated volume of the DT within the Western Ghats erupted in 600 ka; however, 70% of this volume, erupted after the KPB calling for a reassessment of the role of DT volcanism played in the KPB mass extinction and subsequent recovery. It is important to note that current volume estimates are likely to change as we work to improve understanding of the distribution of chemical formations, both on and offshore.

Topographic Mapmaking.

ERIC Educational Resources Information Center

Meunier, Tony K.

1980-01-01

The making of topographic maps is described as a sequence of the following steps: establishment of control, photogrammetry and field operations, annotation of photographs, stereoplatting, editing, preparation of color-separation plates, and printing. Precise standards are emphasized. (Author/SA)

Shaping the spectrum of random-phase radar waveforms

DOEpatents

Doerry, Armin W.; Marquette, Brandeis

2017-05-09

The various technologies presented herein relate to generation of a desired waveform profile in the form of a spectrum of apparently random noise (e.g., white noise or colored noise), but with precise spectral characteristics. Hence, a waveform profile that could be readily determined (e.g., by a spoofing system) is effectively obscured. Obscuration is achieved by dividing the waveform into a series of chips, each with an assigned frequency, wherein the sequence of chips are subsequently randomized. Randomization can be a function of the application of a key to the chip sequence. During processing of the echo pulse, a copy of the randomized transmitted pulse is recovered or regenerated against which the received echo is correlated. Hence, with the echo energy range-compressed in this manner, it is possible to generate a radar image with precise impulse response.

Nanopore sequencing of drug-resistance-associated genes in malaria parasites, Plasmodium falciparum.

PubMed

Runtuwene, Lucky R; Tuda, Josef S B; Mongan, Arthur E; Makalowski, Wojciech; Frith, Martin C; Imwong, Mallika; Srisutham, Suttipat; Nguyen Thi, Lan Anh; Tuan, Nghia Nguyen; Eshita, Yuki; Maeda, Ryuichiro; Yamagishi, Junya; Suzuki, Yutaka

2018-05-29

Here, we report the application of a portable sequencer, MinION, for genotyping the malaria parasite Plasmodium falciparum. In the present study, an amplicon mixture of nine representative genes causing resistance to anti-malaria drugs is diagnosed. First, we developed the procedure for four laboratory strains (3D7, Dd2, 7G8, and K1), and then applied the developed procedure to ten clinical samples. We sequenced and re-sequenced the samples using the obsolete flow cell R7.3 and the most recent flow cell R9.4. Although the average base-call accuracy of the MinION sequencer was 74.3%, performing >50 reads at a given position improves the accuracy of the SNP call, yielding a precision and recall rate of 0.92 and 0.8, respectively, with flow cell R7.3. These numbers increased significantly with flow cell R9.4, in which the precision and recall are 1 and 0.97, respectively. Based on the SNP information, the drug resistance status in ten clinical samples was inferred. We also analyzed K13 gene mutations from 54 additional clinical samples as a proof of concept. We found that a novel amino-acid changing variation is dominant in this area. In addition, we performed a small population-based analysis using 3 and 5 cases (K13) and 10 and 5 cases (PfCRT) from Thailand and Vietnam, respectively. We identified distinct genotypes from the respective regions. This approach will change the standard methodology for the sequencing diagnosis of malaria parasites, especially in developing countries.

Cloning and sequence analysis of complementary DNA encoding an aberrantly rearranged human T-cell gamma chain.

PubMed Central

Dialynas, D P; Murre, C; Quertermous, T; Boss, J M; Leiden, J M; Seidman, J G; Strominger, J L

1986-01-01

Complementary DNA (cDNA) encoding a human T-cell gamma chain has been cloned and sequenced. At the junction of the variable and joining regions, there is an apparent deletion of two nucleotides in the human cDNA sequence relative to the murine gamma-chain cDNA sequence, resulting simultaneously in the generation of an in-frame stop codon and in a translational frameshift. For this reason, the sequence presented here encodes an aberrantly rearranged human T-cell gamma chain. There are several surprising differences between the deduced human and murine gamma-chain amino acid sequences. These include poor homology in the variable region, poor homology in a discrete segment of the constant region precisely bounded by the expected junctions of exon CII, and the presence in the human sequence of five potential sites for N-linked glycosylation. Images PMID:3458221

Influence of Layup Sequence on the Surface Accuracy of Carbon Fiber Composite Space Mirrors

NASA Astrophysics Data System (ADS)

Yang, Zhiyong; Liu, Qingnian; Zhang, Boming; Xu, Liang; Tang, Zhanwen; Xie, Yongjie

2018-04-01

Layup sequence is directly related to stiffness and deformation resistance of the composite space mirror, and error caused by layup sequence can affect the surface precision of composite mirrors evidently. Variation of layup sequence with the same total thickness of composite space mirror changes surface form of the composite mirror, which is the focus of our study. In our research, the influence of varied quasi-isotropic stacking sequences and random angular deviation on the surface accuracy of composite space mirrors was investigated through finite element analyses (FEA). We established a simulation model for the studied concave mirror with 500 mm diameter, essential factors of layup sequences and random angular deviations on different plies were discussed. Five guiding findings were described in this study. Increasing total plies, optimizing stacking sequence and keeping consistency of ply alignment in ply placement are effective to improve surface accuracy of composite mirror.

FANTOM5 CAGE profiles of human and mouse samples.

PubMed

Noguchi, Shuhei; Arakawa, Takahiro; Fukuda, Shiro; Furuno, Masaaki; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Kaida, Kaoru; Kaiho, Ai; Kanamori-Katayama, Mutsumi; Kawashima, Tsugumi; Kojima, Miki; Kubosaki, Atsutaka; Manabe, Ri-Ichiroh; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakazato, Kenichi; Ninomiya, Noriko; Nishiyori-Sueki, Hiromi; Noma, Shohei; Saijyo, Eri; Saka, Akiko; Sakai, Mizuho; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Watanabe, Shoko; Yoshida, Shigehiro; Arner, Peter; Axton, Richard A; Babina, Magda; Baillie, J Kenneth; Barnett, Timothy C; Beckhouse, Anthony G; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Carlisle, Ailsa J; Clevers, Hans C; Davis, Carrie A; Detmar, Michael; Dohi, Taeko; Edge, Albert S B; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Eslami, Afsaneh; Fagiolini, Michela; Fairbairn, Lynsey; Farach-Carson, Mary C; Faulkner, Geoffrey J; Ferrai, Carmelo; Fisher, Malcolm E; Forrester, Lesley M; Fujita, Rie; Furusawa, Jun-Ichi; Geijtenbeek, Teunis B; Gingeras, Thomas; Goldowitz, Daniel; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J; Hamaguchi, Masahide; Hara, Mitsuko; Hasegawa, Yuki; Herlyn, Meenhard; Heutink, Peter; Hitchens, Kelly J; Hume, David A; Ikawa, Tomokatsu; Ishizu, Yuri; Kai, Chieko; Kawamoto, Hiroshi; Kawamura, Yuki I; Kempfle, Judith S; Kenna, Tony J; Kere, Juha; Khachigian, Levon M; Kitamura, Toshio; Klein, Sarah; Klinken, S Peter; Knox, Alan J; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Lee, Weonju; Lennartsson, Andreas; Mackay-Sim, Alan; Mejhert, Niklas; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Morris, Kelly J; Motohashi, Hozumi; Mummery, Christine L; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Pradhan-Bhatt, Swati; Qin, Xian-Yang; Rehli, Michael; Rizzu, Patrizia; Roy, Sugata; Sajantila, Antti; Sakaguchi, Shimon; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schmidl, Christian; Schneider, Claudio; Schulze-Tanzil, Gundula G; Schwegmann, Anita; Sheng, Guojun; Shin, Jay W; Sugiyama, Daisuke; Sugiyama, Takaaki; Summers, Kim M; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tomoiu, Andru; Toyoda, Hiroo; van de Wetering, Marc; van den Berg, Linda M; Verardo, Roberto; Vijayan, Dipti; Wells, Christine A; Winteringham, Louise N; Wolvetang, Ernst; Yamaguchi, Yoko; Yamamoto, Masayuki; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Yonekura, Yohei; Zhang, Peter G; Zucchelli, Silvia; Abugessaisa, Imad; Arner, Erik; Harshbarger, Jayson; Kondo, Atsushi; Lassmann, Timo; Lizio, Marina; Sahin, Serkan; Sengstag, Thierry; Severin, Jessica; Shimoji, Hisashi; Suzuki, Masanori; Suzuki, Harukazu; Kawai, Jun; Kondo, Naoto; Itoh, Masayoshi; Daub, Carsten O; Kasukawa, Takeya; Kawaji, Hideya; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide

2017-08-29

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

FANTOM5 CAGE profiles of human and mouse samples

PubMed Central

Noguchi, Shuhei; Arakawa, Takahiro; Fukuda, Shiro; Furuno, Masaaki; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Kaida, Kaoru; Kaiho, Ai; Kanamori-Katayama, Mutsumi; Kawashima, Tsugumi; Kojima, Miki; Kubosaki, Atsutaka; Manabe, Ri-ichiroh; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakazato, Kenichi; Ninomiya, Noriko; Nishiyori-Sueki, Hiromi; Noma, Shohei; Saijyo, Eri; Saka, Akiko; Sakai, Mizuho; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Watanabe, Shoko; Yoshida, Shigehiro; Arner, Peter; Axton, Richard A.; Babina, Magda; Baillie, J. Kenneth; Barnett, Timothy C.; Beckhouse, Anthony G.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Carlisle, Ailsa J.; Clevers, Hans C.; Davis, Carrie A.; Detmar, Michael; Dohi, Taeko; Edge, Albert S.B.; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Eslami, Afsaneh; Fagiolini, Michela; Fairbairn, Lynsey; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Ferrai, Carmelo; Fisher, Malcolm E.; Forrester, Lesley M.; Fujita, Rie; Furusawa, Jun-ichi; Geijtenbeek, Teunis B.; Gingeras, Thomas; Goldowitz, Daniel; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Hasegawa, Yuki; Herlyn, Meenhard; Heutink, Peter; Hitchens, Kelly J.; Hume, David A.; Ikawa, Tomokatsu; Ishizu, Yuri; Kai, Chieko; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klein, Sarah; Klinken, S. Peter; Knox, Alan J.; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Lee, Weonju; Lennartsson, Andreas; Mackay-sim, Alan; Mejhert, Niklas; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Morris, Kelly J.; Motohashi, Hozumi; Mummery, Christine L.; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Pradhan-Bhatt, Swati; Qin, Xian-Yang; Rehli, Michael; Rizzu, Patrizia; Roy, Sugata; Sajantila, Antti; Sakaguchi, Shimon; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schmidl, Christian; Schneider, Claudio; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sheng, Guojun; Shin, Jay W.; Sugiyama, Daisuke; Sugiyama, Takaaki; Summers, Kim M.; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tomoiu, Andru; Toyoda, Hiroo; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Yamaguchi, Yoko; Yamamoto, Masayuki; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Yonekura, Yohei; Zhang, Peter G.; Zucchelli, Silvia; Abugessaisa, Imad; Arner, Erik; Harshbarger, Jayson; Kondo, Atsushi; Lassmann, Timo; Lizio, Marina; Sahin, Serkan; Sengstag, Thierry; Severin, Jessica; Shimoji, Hisashi; Suzuki, Masanori; Suzuki, Harukazu; Kawai, Jun; Kondo, Naoto; Itoh, Masayoshi; Daub, Carsten O.; Kasukawa, Takeya; Kawaji, Hideya; Carninci, Piero; Forrest, Alistair R.R.; Hayashizaki, Yoshihide

2017-01-01

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities. PMID:28850106

Peregrine: A rapid and unbiased method to produce strand-specific RNA-Seq libraries from small quantities of starting material.

PubMed

Langevin, Stanley A; Bent, Zachary W; Solberg, Owen D; Curtis, Deanna J; Lane, Pamela D; Williams, Kelly P; Schoeniger, Joseph S; Sinha, Anupama; Lane, Todd W; Branda, Steven S

2013-04-01

Use of second generation sequencing (SGS) technologies for transcriptional profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of RNA abundances with unprecedented specificity and sensitivity and the discovery of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the RNA starting material into cDNA flanked by platform-specific adaptor sequences. Each of the published methods and commercial kits currently available for RNA-Seq library preparation suffers from at least one major drawback, including long processing times, large starting material requirements, uneven coverage, loss of strand information and high cost. We report the development of a new RNA-Seq library preparation technique that produces representative, strand-specific RNA-Seq libraries from small amounts of starting material in a fast, simple and cost-effective manner. Additionally, we have developed a new quantitative PCR-based assay for precisely determining the number of PCR cycles to perform for optimal enrichment of the final library, a key step in all SGS library preparation workflows.

Combined analysis of fourteen nuclear genes refines the Ursidae phylogeny.

PubMed

Pagès, Marie; Calvignac, Sébastien; Klein, Catherine; Paris, Mathilde; Hughes, Sandrine; Hänni, Catherine

2008-04-01

Despite numerous studies, questions remain about the evolutionary history of Ursidae and additional independent genetic markers were needed to elucidate these ambiguities. For this purpose, we sequenced ten nuclear genes for all the eight extant bear species. By combining these new sequences with those of four other recently published nuclear markers, we provide new insights into the phylogenetic relationships of the Ursidae family members. The hypothesis that the giant panda was the first species to diverge among ursids is definitively confirmed and the precise branching order within the Ursus genus is clarified for the first time. Moreover, our analyses indicate that the American and the Asiatic black bears do not cluster as sister taxa, as had been previously hypothesised. Sun and sloth bears clearly appear as the most basal ursine species but uncertainties about their exact relationships remain. Since our larger dataset did not enable us to clarify this last question, identifying rare genomic changes in bear genomes could be a promising solution for further studies.

Emulating JWST/NIRCam Exoplanet Transit Observations in a Testbed laboratory experiment

NASA Astrophysics Data System (ADS)

Touli-Lebreton, D.; Vasisht, G.; Smith, R.; Krist, J.; Beichman, C.

2014-03-01

The transit technique is used for the detection and characterization of exoplanets. The combination of a transit measurement with a radial velocity measurement gives information about a planet's radius and mass, respectively, leading to an estimate of the planet's density and therefore to its composition and evolutionary history. Spectroscopic observations of individual planets have revealed atomic and molecular species such as H2O, CO2 and CH4 in atmospheres of planets orbiting bright stars, e.g. Deming et al 2013. These transit observations require extremely precise photometry. For instance, Jupiter transit results to a 1% brightness decrease of a solar type star while the Earth causes only a 0.0084% decrease (84 ppm). In our controlled laboratory experiment, we use a H2RG detector, two lamps of variable intensity, along with spectral line and photometric simulation masks to emulate the signals from a star-only, from a planet-only and finally, from a combination of a planet + star. Two masks have been used to simulate spectra in monochromatic light. The masks are 1040 pixels in length with one mask having a 2-pixel width and the other a 10-pixel width. From many-hour long observing sequences we obtain time series photometry with deliberate offsets introduced to test sensitivity to pointing jitter and other effects. We can modify the star- planet brightness contrast by factors up to 104:1. With cross correlation techniques we calculate positional shifts which are then used to decorrelate the effects of vertical and lateral offsets due to turbulence and instrumental vibrations on the photometry. Using Principal Component Analysis (PCA), we reject correlated temporal noise to achieve a precision lower than 50 ppm (Clanton et al 2012). Testbed experiments are ongoing to provide quantitative information on the achievable spectroscopic precision using realistic exoplanet spectra with the goal to define optimized data acquisition sequences for use, for example, with the James Webb Space Telescope.

Real-Time Reliability Verification for UAV Flight Control System Supporting Airworthiness Certification.

PubMed

Xu, Haiyang; Wang, Ping

2016-01-01

In order to verify the real-time reliability of unmanned aerial vehicle (UAV) flight control system and comply with the airworthiness certification standard, we proposed a model-based integration framework for modeling and verification of time property. Combining with the advantages of MARTE, this framework uses class diagram to create the static model of software system, and utilizes state chart to create the dynamic model. In term of the defined transformation rules, the MARTE model could be transformed to formal integrated model, and the different part of the model could also be verified by using existing formal tools. For the real-time specifications of software system, we also proposed a generating algorithm for temporal logic formula, which could automatically extract real-time property from time-sensitive live sequence chart (TLSC). Finally, we modeled the simplified flight control system of UAV to check its real-time property. The results showed that the framework could be used to create the system model, as well as precisely analyze and verify the real-time reliability of UAV flight control system.

Real-Time Reliability Verification for UAV Flight Control System Supporting Airworthiness Certification

PubMed Central

Xu, Haiyang; Wang, Ping

2016-01-01

In order to verify the real-time reliability of unmanned aerial vehicle (UAV) flight control system and comply with the airworthiness certification standard, we proposed a model-based integration framework for modeling and verification of time property. Combining with the advantages of MARTE, this framework uses class diagram to create the static model of software system, and utilizes state chart to create the dynamic model. In term of the defined transformation rules, the MARTE model could be transformed to formal integrated model, and the different part of the model could also be verified by using existing formal tools. For the real-time specifications of software system, we also proposed a generating algorithm for temporal logic formula, which could automatically extract real-time property from time-sensitive live sequence chart (TLSC). Finally, we modeled the simplified flight control system of UAV to check its real-time property. The results showed that the framework could be used to create the system model, as well as precisely analyze and verify the real-time reliability of UAV flight control system. PMID:27918594

Stress Drop and Directivity Patterns Observed in Small-Magnitude (

NASA Astrophysics Data System (ADS)

Ruhl, C. J.; Hatch, R. L.; Abercrombie, R. E.; Smith, K.

2017-12-01

Recent improvements in seismic instrumentation and network coverage in the Reno, NV area have provided high-quality records of abundant microseismicity, including several swarms and clusters. Here, we discuss stress drop and directivity patterns of small-magnitude seismicity in the 2008 Mw4.9 Mogul earthquake swarm in Reno, NV and in the nearby region of an ML3.2 sequence near Virginia City, NV. In both sequences, double-difference relocated earthquakes cluster on multiple distinct structures consistent with focal mechanism and moment tensor fault plane solutions. Both sequences also show migration potentially related to fluid flow. We estimate corner frequency and stress drop using EGF-derived spectral ratios, convolving earthquake pairs (target*EGF) such that we preserve phase and recover source-time functions (STF) on a station-by-station basis. We then stack individual STFs per station for all EGF-target pairs per target earthquake, increasing the signal-to-noise of our results. By applying an azimuthal- and incidence-angle-dependent stretching factor to STFs in the time domain, we are able to invert for rupture directivity and velocity assuming both unilateral and bilateral rupture. Earthquakes in both sequences, some as low as ML2.1, show strong unilateral directivity consistent with independent fault plane solutions. We investigate and compare the relationship between rupture and migration directions on subfaults within each sequence. Average stress drops for both sequences are 4 MPa, but there is large variation in individual estimates for both sequences. Although this variation is not explained simply by any one parameter (e.g., depth), spatiotemporal variation in the Mogul swarm is distinct: coherent clusters of high and low stress drop earthquakes along the mainshock fault plane are seen, and high-stress-drop foreshocks correlate with an area of reduced aftershock productivity. These observations are best explained by a difference in rheology along the fault plane. The unprecedented detail achieved for these small magnitude earthquakes confirms that stress drop, when measured precisely, is a valuable observation of physically-meaningful fault zone properties and earthquake behavior.

Reassessment of the source of the 1976 Friuli, NE Italy, earthquake sequence from the joint inversion of high-precision levelling and triangulation data

NASA Astrophysics Data System (ADS)

Cheloni, D.; D'Agostino, N.; D'Anastasio, E.; Selvaggi, G.

2012-08-01

In this study, we revisit the mechanism of the 1976 Friuli (NE Italy) earthquake sequence (main shocks Mw 6.4, 5.9 and 6.0). We present a new source model that simultaneously fits all the available geodetic measurements of the observed deformation. We integrate triangulation measurements, which have never been previously used in the source modelling of this sequence, with high-precision levelling that covers the epicentral area. We adopt a mixed linear/non-linear optimization scheme, in which we iteratively search for the best-fitting solution by performing several linear slip inversions while varying fault location using a grid search method. Our preferred solution consists of a shallow north-dipping fault plane with assumed azimuth of 282° and accommodating a reverse dextral slip of about 1 m. The estimated geodetic moment is 6.6 × 1018 Nm (Mw 6.5), in agreement with seismological estimates. Yet, our preferred model shows that the geodetic solution is consistent with the activation of a single fault system during the entire sequence, the surface expression of which could be associated with the Buia blind thrust, supporting the hypothesis that the main activity of the Eastern Alps occurs close to the relief margin, as observed in other mountain belts. The retrieved slip pattern consists of a main coseismic patch located 3-5 km depth, in good agreement with the distribution of the main shocks. Additional slip is required in the shallower portions of the fault to reproduce the local uplift observed in the region characterized by Quaternary active folding. We tentatively interpret this patch as postseismic deformation (afterslip) occurring at the edge of the main coseismic patch. Finally, our rupture plane spatially correlates with the area of the locked fault determined from interseismic measurements, supporting the hypothesis that interseismic slip on the creeping dislocation causes strain to accumulate on the shallow (above ˜10 km depth) locked section. Assuming that all the long-term accommodation between Adria and Eurasia is seismically released, a time span of 500-700 years of strain-accumulating plate motion would result in a 1976-like earthquake.

Precision medicine: In need of guidance and surveillance.

PubMed

Lin, Jian-Zhen; Long, Jun-Yu; Wang, An-Qiang; Zheng, Ying; Zhao, Hai-Tao

2017-07-28

Precision medicine, currently a hotspot in mainstream medicine, has been strongly promoted in recent years. With rapid technological development, such as next-generation sequencing, and fierce competition in molecular targeted drug exploitation, precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine - especially in the prevention and treatment of tumors - is far from satisfactory; however, the aims of precision medicine deserve approval. Thus, this medical approach is currently in its infancy; it has promising prospects, but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs, precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network, integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition, multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support, and its development demands directed momentum. We propose three kinds of impetus (research, application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application.

Precision medicine: In need of guidance and surveillance

PubMed Central

Lin, Jian-Zhen; Long, Jun-Yu; Wang, An-Qiang; Zheng, Ying; Zhao, Hai-Tao

2017-01-01

Precision medicine, currently a hotspot in mainstream medicine, has been strongly promoted in recent years. With rapid technological development, such as next-generation sequencing, and fierce competition in molecular targeted drug exploitation, precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine - especially in the prevention and treatment of tumors - is far from satisfactory; however, the aims of precision medicine deserve approval. Thus, this medical approach is currently in its infancy; it has promising prospects, but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs, precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network, integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition, multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support, and its development demands directed momentum. We propose three kinds of impetus (research, application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application. PMID:28811702

Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing

PubMed Central

Weirather, Jason L.; Afshar, Pegah Tootoonchi; Clark, Tyson A.; Tseng, Elizabeth; Powers, Linda S.; Underwood, Jason G.; Zabner, Joseph; Korlach, Jonas; Wong, Wing Hung; Au, Kin Fai

2015-01-01

We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine fusion sites and identify and quantify fusion isoforms. IDP-fusion is the first method to study gene fusion events by integrating Third Generation Sequencing long reads and Second Generation Sequencing short reads. We applied IDP-fusion to PacBio data and Illumina data from the MCF-7 breast cancer cells. Compared with the existing tools, IDP-fusion detects fusion genes at higher precision and a very low false positive rate. The results show that IDP-fusion will be useful for unraveling the complexity of multiple fusion splices and fusion isoforms within tumorigenesis-relevant fusion genes. PMID:26040699

Sequencing the Connectome

PubMed Central

Zador, Anthony M.; Dubnau, Joshua; Oyibo, Hassana K.; Zhan, Huiqing; Cao, Gang; Peikon, Ian D.

2012-01-01

Connectivity determines the function of neural circuits. Historically, circuit mapping has usually been viewed as a problem of microscopy, but no current method can achieve high-throughput mapping of entire circuits with single neuron precision. Here we describe a novel approach to determining connectivity. We propose BOINC (“barcoding of individual neuronal connections”), a method for converting the problem of connectivity into a form that can be read out by high-throughput DNA sequencing. The appeal of using sequencing is that its scale—sequencing billions of nucleotides per day is now routine—is a natural match to the complexity of neural circuits. An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution could transform neuroscience research. PMID:23109909

Fundamental limits of scintillation detector timing precision

NASA Astrophysics Data System (ADS)

Derenzo, Stephen E.; Choong, Woon-Seng; Moses, William W.

2014-07-01

In this paper we review the primary factors that affect the timing precision of a scintillation detector. Monte Carlo calculations were performed to explore the dependence of the timing precision on the number of photoelectrons, the scintillator decay and rise times, the depth of interaction uncertainty, the time dispersion of the optical photons (modeled as an exponential decay), the photodetector rise time and transit time jitter, the leading-edge trigger level, and electronic noise. The Monte Carlo code was used to estimate the practical limits on the timing precision for an energy deposition of 511 keV in 3 mm × 3 mm × 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are consistent with the best experimental literature values. We then calculated the timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0 ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0 to 0.5 ns fwhm, and A from 10 to 10 000 photoelectrons per ns decay time. Since the timing precision R was found to depend on A-1/2 more than any other factor, we tabulated the parameter B, where R = BA-1/2. An empirical analytical formula was found that fit the tabulated values of B with an rms deviation of 2.2% of the value of B. The theoretical lower bound of the timing precision was calculated for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm photodetector time jitter. The lower bound was at most 15% lower than leading-edge timing discrimination for A from 10 to 10 000 photoelectrons ns-1. A timing precision of 8 ps fwhm should be possible for an energy deposition of 511 keV using currently available photodetectors if a theoretically possible scintillator were developed that could produce 10 000 photoelectrons ns-1.

Fundamental Limits of Scintillation Detector Timing Precision

PubMed Central

Derenzo, Stephen E.; Choong, Woon-Seng; Moses, William W.

2014-01-01

In this paper we review the primary factors that affect the timing precision of a scintillation detector. Monte Carlo calculations were performed to explore the dependence of the timing precision on the number of photoelectrons, the scintillator decay and rise times, the depth of interaction uncertainty, the time dispersion of the optical photons (modeled as an exponential decay), the photodetector rise time and transit time jitter, the leading-edge trigger level, and electronic noise. The Monte Carlo code was used to estimate the practical limits on the timing precision for an energy deposition of 511 keV in 3 mm × 3 mm × 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are consistent with the best experimental literature values. We then calculated the timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0 ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0 to 0.5 ns fwhm, and A from 10 to 10,000 photoelectrons per ns decay time. Since the timing precision R was found to depend on A−1/2 more than any other factor, we tabulated the parameter B, where R = BA−1/2. An empirical analytical formula was found that fit the tabulated values of B with an rms deviation of 2.2% of the value of B. The theoretical lower bound of the timing precision was calculated for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm photodetector time jitter. The lower bound was at most 15% lower than leading-edge timing discrimination for A from 10 to 10,000 photoelectrons/ns. A timing precision of 8 ps fwhm should be possible for an energy deposition of 511 keV using currently available photodetectors if a theoretically possible scintillator were developed that could produce 10,000 photoelectrons/ns. PMID:24874216

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

Barnes, Sydney A.; Weingrill, Joerg; Fritzewski, Dario

We report rotation periods for 20 cool (FGK) main sequence member stars of the 4 Gyr-old open cluster M67 (=NGC 2682), obtained by analyzing data from Campaign 5 of the K2 mission with the Kepler Space Telescope . The rotation periods delineate a sequence in the color–period diagram (CPD) of increasing period with redder color. This sequence represents a cross-section at the cluster age of the surface P = P ( t , M ), suggested in prior work to extend to at least solar age. The current Sun is located marginally (approximately 1 σ ) above M67 in themore » CPD, as its relative age leads us to expect, and lies on the P = P ( t , M ) surface to within measurement precision. We therefore conclude that the solar rotation rate is normal as compared with cluster stars, a fact that strengthens the solar–stellar connection. The agreement between the M67 rotation period measurements and prior predictions further implies that rotation periods, especially when coupled with appropriate supporting work such as spectroscopy, can provide reliable ages via gyrochronology for other similar FGK dwarfs from the early main sequence to solar age and likely until the main sequence turnoff. The M67 rotators have a rotational age of 4.2 Gyr with a standard deviation of 0.7 Gyr, implying that similar field stars can be age-dated to precisions of ∼17%. The rotational age of the M67 cluster as a whole is therefore 4.2 Gyr, but with a lower (averaged) uncertainty of 0.2 Gyr.« less

Inter-laboratory evaluation of the EUROFORGEN Global ancestry-informative SNP panel by massively parallel sequencing using the Ion PGM™.

PubMed

Eduardoff, M; Gross, T E; Santos, C; de la Puente, M; Ballard, D; Strobl, C; Børsting, C; Morling, N; Fusco, L; Hussing, C; Egyed, B; Souto, L; Uacyisrael, J; Syndercombe Court, D; Carracedo, Á; Lareu, M V; Schneider, P M; Parson, W; Phillips, C; Parson, W; Phillips, C

2016-07-01

The EUROFORGEN Global ancestry-informative SNP (AIM-SNPs) panel is a forensic multiplex of 128 markers designed to differentiate an individual's ancestry from amongst the five continental population groups of Africa, Europe, East Asia, Native America, and Oceania. A custom multiplex of AmpliSeq™ PCR primers was designed for the Global AIM-SNPs to perform massively parallel sequencing using the Ion PGM™ system. This study assessed individual SNP genotyping precision using the Ion PGM™, the forensic sensitivity of the multiplex using dilution series, degraded DNA plus simple mixtures, and the ancestry differentiation power of the final panel design, which required substitution of three original ancestry-informative SNPs with alternatives. Fourteen populations that had not been previously analyzed were genotyped using the custom multiplex and these studies allowed assessment of genotyping performance by comparison of data across five laboratories. Results indicate a low level of genotyping error can still occur from sequence misalignment caused by homopolymeric tracts close to the target SNP, despite careful scrutiny of candidate SNPs at the design stage. Such sequence misalignment required the exclusion of component SNP rs2080161 from the Global AIM-SNPs panel. However, the overall genotyping precision and sensitivity of this custom multiplex indicates the Ion PGM™ assay for the Global AIM-SNPs is highly suitable for forensic ancestry analysis with massively parallel sequencing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Precise determination, cross-recognition, and functional analysis of the double-strand origins of the rolling-circle replication plasmids in haloarchaea.

PubMed

Zhou, Ligang; Zhou, Meixian; Sun, Chaomin; Han, Jing; Lu, Qiuhe; Zhou, Jian; Xiang, Hua

2008-08-01

The precise nick site in the double-strand origin (DSO) of pZMX201, a 1,668-bp rolling-circle replication (RCR) plasmid from the haloarchaeon Natrinema sp. CX2021, was determined by electron microscopy and DSO mapping. In this plasmid, DSO nicking occurred between residues C404 and G405 within a heptanucleotide sequence (TCTC/GGC) located in the stem region of an imperfect hairpin structure. This nick site sequence was conserved among the haloarchaeal RCR plasmids, including pNB101, suggesting that the DSO nick site might be the same for all members of this plasmid family. Interestingly, the DSOs of pZMX201 and pNB101 were found to be cross-recognized in RCR initiation and termination in a hybrid plasmid system. Mutation analysis of the DSO from pZMX201 (DSO(Z)) in this hybrid plasmid system revealed that: (i) the nucleotides in the middle of the conserved TCTCGGC sequence play more-important roles in the initiation and termination process; (ii) the left half of the hairpin structure is required for initiation but not for termination; and (iii) a 36-bp sequence containing TCTCGGC and the downstream sequence is essential and sufficient for termination. In conclusion, these haloarchaeal plasmids, with novel features that are different from the characteristics of both single-stranded DNA phages and bacterial RCR plasmids, might serve as a good model for studying the evolution of RCR replicons.

Long-term influence of asteroids on planet longitudes and chaotic dynamics of the solar system

NASA Astrophysics Data System (ADS)

Woillez, E.; Bouchet, F.

2017-11-01

Over timescales much longer than an orbital period, the solar system exhibits large-scale chaotic behavior and can thus be viewed as a stochastic dynamical system. The aim of the present paper is to compare different sources of stochasticity in the solar system. More precisely we studied the importance of the long term influence of asteroids on the chaotic dynamics of the solar system. We show that the effects of asteroids on planets is similar to a white noise process, when those effects are considered on a timescale much larger than the correlation time τϕ ≃ 104 yr of asteroid trajectories. We computed the timescale τe after which the effects of the stochastic evolution of the asteroids lead to a loss of information for the initial conditions of the perturbed Laplace-Lagrange secular dynamics. The order of magnitude of this timescale is precisely determined by theoretical argument, and we find that τe ≃ 104 Myr. Although comparable to the full main-sequence lifetime of the sun, this timescale is considerably longer than the Lyapunov time τI ≃ 10 Myr of the solar system without asteroids. This shows that the external sources of chaos arise as a small perturbation in the stochastic secular behavior of the solar system, rather due to intrinsic chaos.

Collaborative Manufacturing for Small-Medium Enterprises

NASA Astrophysics Data System (ADS)

Irianto, D.

2016-02-01

Manufacturing systems involve decisions concerning production processes, capacity, planning, and control. In a MTO manufacturing systems, strategic decisions concerning fulfilment of customer requirement, manufacturing cost, and due date of delivery are the most important. In order to accelerate the decision making process, research on decision making structure when receiving order and sequencing activities under limited capacity is required. An effective decision making process is typically required by small-medium components and tools maker as supporting industries to large industries. On one side, metal small-medium enterprises are expected to produce parts, components or tools (i.e. jigs, fixture, mold, and dies) with high precision, low cost, and exact delivery time. On the other side, a metal small- medium enterprise may have weak bargaining position due to aspects such as low production capacity, limited budget for material procurement, and limited high precision machine and equipment. Instead of receiving order exclusively, a small-medium enterprise can collaborate with other small-medium enterprise in order to fulfill requirements high quality, low manufacturing cost, and just in time delivery. Small-medium enterprises can share their best capabilities to form effective supporting industries. Independent body such as community service at university can take a role as a collaboration manager. The Laboratory of Production Systems at Bandung Institute of Technology has implemented shared manufacturing systems for small-medium enterprise collaboration.

Genetics Home Reference: SOX2 anophthalmia syndrome

MedlinePlus

... and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. Mol Vis. 2008 Mar 24;14:583-92. ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Precise GPS ephemerides from DMA and NGS tested by time transfer

NASA Technical Reports Server (NTRS)

Lewandowski, Wlodzimierz W.; Petit, Gerard; Thomas, Claudine

1992-01-01

It was shown that the use of the Defense Mapping Agency's (DMA) precise ephemerides brings a significant improvement to the accuracy of GPS time transfer. At present a new set of precise ephemerides produced by the National Geodetic Survey (NGS) has been made available to the timing community. This study demonstrates that both types of precise ephemerides improve long-distance GPS time transfer and remove the effects of Selective Availability (SA) degradation of broadcast ephemerides. The issue of overcoming SA is also discussed in terms of the routine availability of precise ephemerides.

Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

PubMed

Li, Hui; Stoddard, Mark B; Wang, Shuyi; Blair, Lily M; Giorgi, Elena E; Parrish, Erica H; Learn, Gerald H; Hraber, Peter; Goepfert, Paul A; Saag, Michael S; Denny, Thomas N; Haynes, Barton F; Hahn, Beatrice H; Ribeiro, Ruy M; Perelson, Alan S; Korber, Bette T; Bhattacharya, Tanmoy; Shaw, George M

2012-01-01

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.

Evaluating approaches to find exon chains based on long reads.

PubMed

Kuosmanen, Anna; Norri, Tuukka; Mäkinen, Veli

2018-05-01

Transcript prediction can be modeled as a graph problem where exons are modeled as nodes and reads spanning two or more exons are modeled as exon chains. Pacific Biosciences third-generation sequencing technology produces significantly longer reads than earlier second-generation sequencing technologies, which gives valuable information about longer exon chains in a graph. However, with the high error rates of third-generation sequencing, aligning long reads correctly around the splice sites is a challenging task. Incorrect alignments lead to spurious nodes and arcs in the graph, which in turn lead to incorrect transcript predictions. We survey several approaches to find the exon chains corresponding to long reads in a splicing graph, and experimentally study the performance of these methods using simulated data to allow for sensitivity/precision analysis. Our experiments show that short reads from second-generation sequencing can be used to significantly improve exon chain correctness either by error-correcting the long reads before splicing graph creation, or by using them to create a splicing graph on which the long-read alignments are then projected. We also study the memory and time consumption of various modules, and show that accurate exon chains lead to significantly increased transcript prediction accuracy. The simulated data and in-house scripts used for this article are available at http://www.cs.helsinki.fi/group/gsa/exon-chains/exon-chains-bib.tar.bz2.

Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

PubMed Central

Li, Hui; Stoddard, Mark B.; Wang, Shuyi; Blair, Lily M.; Giorgi, Elena E.; Parrish, Erica H.; Learn, Gerald H.; Hraber, Peter; Goepfert, Paul A.; Saag, Michael S.; Denny, Thomas N.; Haynes, Barton F.; Hahn, Beatrice H.; Ribeiro, Ruy M.; Perelson, Alan S.; Korber, Bette T.; Bhattacharya, Tanmoy; Shaw, George M.

2012-01-01

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures. PMID:22927816

TU-H-CAMPUS-IeP2-01: Quantitative Evaluation of PROPELLER DWI Using QIBA Diffusion Phantom

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

Yung, J; Ai, H; Liu, H

Purpose: The purpose of this study is to determine the quantitative variability of apparent diffusion coefficient (ADC) values when varying imaging parameters in a diffusion-weighted (DW) fast spin echo (FSE) sequence with Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) k-space trajectory. Methods: Using a 3T MRI scanner, a NIST traceable, quantitative magnetic resonance imaging (MRI) diffusion phantom (High Precision Devices, Inc, Boulder, Colorado) consisting of 13 vials filled with various concentrations of polymer polyvinylpyrrolidone (PVP) in aqueous solution was imaged with a standard Quantitative Imaging Biomarkers Alliance (QIBA) DWI spin echo, echo planar imaging (SE EPI) acquisition. Themore » same phantom was then imaged with a DWI PROPELLER sequence at varying echo train lengths (ETL) of 8, 20, and 32, as well as b-values of 400, 900, and 2000. QIBA DWI phantom analysis software was used to generate ADC maps and create region of interests (ROIs) for quantitative measurements of each vial. Mean and standard deviations of the ROIs were compared. Results: The SE EPI sequence generated ADC values that showed very good agreement with the known ADC values of the phantom (r2 = 0.9995, slope = 1.0061). The ADC values measured from the PROPELLER sequences were inflated, but were highly correlated with an r2 range from 0.8754 to 0.9880. The PROPELLER sequence with an ETL=20 and b-value of 0 and 2000 showed the closest agreement (r2 = 0.9034, slope = 0.9880). Conclusion: The DW PROPELLER sequence is promising for quantitative evaluation of ADC values. A drawback of the PROPELLER sequence is the longer acquisition time. The 180° refocusing pulses may also cause the observed increase in ADC values compared to the standard SE EPI DW sequence. However, the FSE sequence offers an advantage with in-plane motion and geometric distortion which will be investigated in future studies.« less

Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

PubMed

Esposito, Joseph J; Sammons, Scott A; Frace, A Michael; Osborne, John D; Olsen-Rasmussen, Melissa; Zhang, Ming; Govil, Dhwani; Damon, Inger K; Kline, Richard; Laker, Miriam; Li, Yu; Smith, Geoffrey L; Meyer, Hermann; Leduc, James W; Wohlhueter, Robert M

2006-08-11

Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

Next-Generation Sequencing: The Translational Medicine Approach from “Bench to Bedside to Population”

PubMed Central

Beigh, Mohammad Muzafar

2016-01-01

Humans have predicted the relationship between heredity and diseases for a long time. Only in the beginning of the last century, scientists begin to discover the connotations between different genes and disease phenotypes. Recent trends in next-generation sequencing (NGS) technologies have brought a great momentum in biomedical research that in turn has remarkably augmented our basic understanding of human biology and its associated diseases. State-of-the-art next generation biotechnologies have started making huge strides in our current understanding of mechanisms of various chronic illnesses like cancers, metabolic disorders, neurodegenerative anomalies, etc. We are experiencing a renaissance in biomedical research primarily driven by next generation biotechnologies like genomics, transcriptomics, proteomics, metabolomics, lipidomics etc. Although genomic discoveries are at the forefront of next generation omics technologies, however, their implementation into clinical arena had been painstakingly slow mainly because of high reaction costs and unavailability of requisite computational tools for large-scale data analysis. However rapid innovations and steadily lowering cost of sequence-based chemistries along with the development of advanced bioinformatics tools have lately prompted launching and implementation of large-scale massively parallel genome sequencing programs in different fields ranging from medical genetics, infectious biology, agriculture sciences etc. Recent advances in large-scale omics-technologies is bringing healthcare research beyond the traditional “bench to bedside” approach to more of a continuum that will include improvements, in public healthcare and will be primarily based on predictive, preventive, personalized, and participatory medicine approach (P4). Recent large-scale research projects in genetic and infectious disease biology have indicated that massively parallel whole-genome/whole-exome sequencing, transcriptome analysis, and other functional genomic tools can reveal large number of unique functional elements and/or markers that otherwise would be undetected by traditional sequencing methodologies. Therefore, latest trends in the biomedical research is giving birth to the new branch in medicine commonly referred to as personalized and/or precision medicine. Developments in the post-genomic era are believed to completely restructure the present clinical pattern of disease prevention and treatment as well as methods of diagnosis and prognosis. The next important step in the direction of the precision/personalized medicine approach should be its early adoption in clinics for future medical interventions. Consequently, in coming year’s next generation biotechnologies will reorient medical practice more towards disease prediction and prevention approaches rather than curing them at later stages of their development and progression, even at wider population level(s) for general public healthcare system. PMID:28930123

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

Motor control by precisely timed spike patterns

PubMed Central

Srivastava, Kyle H.; Holmes, Caroline M.; Vellema, Michiel; Pack, Andrea R.; Elemans, Coen P. H.; Nemenman, Ilya; Sober, Samuel J.

2017-01-01

A fundamental problem in neuroscience is understanding how sequences of action potentials (“spikes”) encode information about sensory signals and motor outputs. Although traditional theories assume that this information is conveyed by the total number of spikes fired within a specified time interval (spike rate), recent studies have shown that additional information is carried by the millisecond-scale timing patterns of action potentials (spike timing). However, it is unknown whether or how subtle differences in spike timing drive differences in perception or behavior, leaving it unclear whether the information in spike timing actually plays a role in brain function. By examining the activity of individual motor units (the muscle fibers innervated by a single motor neuron) and manipulating patterns of activation of these neurons, we provide both correlative and causal evidence that the nervous system uses millisecond-scale variations in the timing of spikes within multispike patterns to control a vertebrate behavior—namely, respiration in the Bengalese finch, a songbird. These findings suggest that a fundamental assumption of current theories of motor coding requires revision. PMID:28100491

Precision Medicine: From Science To Value.

PubMed

Ginsburg, Geoffrey S; Phillips, Kathryn A

2018-05-01

Precision medicine is making an impact on patients, health care delivery systems, and research participants in ways that were only imagined fifteen years ago when the human genome was first sequenced. Discovery of disease-causing and drug-response genetic variants has accelerated, while adoption into clinical medicine has lagged. We define precision medicine and the stakeholder community required to enable its integration into research and health care. We explore the intersection of data science, analytics, and precision medicine in the formation of health systems that carry out research in the context of clinical care and that optimize the tools and information used to deliver improved patient outcomes. We provide examples of real-world impact and conclude with a policy and economic agenda necessary for the adoption of this new paradigm of health care both in the United States and globally.

Moral Duties of Genomics Researchers: Why Personalized Medicine Requires a Collective Approach.

PubMed

Vos, Shoko; van Delden, Johannes J M; van Diest, Paul J; Bredenoord, Annelien L

2017-02-01

Advances in genome sequencing together with the introduction of personalized medicine offer promising new avenues for research and precision treatment, particularly in the field of oncology. At the same time, the convergence of genomics, bioinformatics, and the collection of human tissues and patient data creates novel moral duties for researchers. After all, unprecedented amounts of potentially sensitive information are being generated. Over time, traditional research ethics principles aimed at protecting individual participants have become supplemented with social obligations related to the interests of society and the research enterprise at large, illustrating that genomic medicine is also a social endeavor. In this review we provide a comprehensive assembly of moral duties that have been attributed to genomics researchers and offer suggestions for responsible advancement of personalized genomic cancer care. Copyright © 2016 Elsevier Ltd. All rights reserved.

The applications of liquid biopsy in resistance surveillance of anaplastic lymphoma kinase inhibitor.

PubMed

Chen, Yating; Guo, Wenjie; Fan, Junsheng; Chen, Yuqing; Zhang, Xiaoli; Chen, Xin; Luo, Peng

2017-01-01

With the clinical promotion of precision medicine and individualized medical care, molecular targeted medicine has been used to treat non-small cell lung cancer (NSCLC) patients and proved to be significantly effective. Anaplastic lymphoma kinase (ALK) inhibitor is one of the most important specific therapeutic agents for patients with ALK-positive NSCLC. It can extend the survival of patients. However, resistance to the ALK inhibitor inevitably develops in the application process. So, the real-time resistance surveillance is particularly important, and liquid biopsy is one of the most potential inspection methods. Circulating tumor cells, circulating free tumor DNA and exosome in body fluid are used as the main detection biomarkers to reflect the occurrence of resistance in real time through sequencing or counting and then to guide the follow-up treatment.

Molecular Pathology: A Requirement for Precision Medicine in Cancer.

PubMed

Dietel, Manfred

2016-01-01

The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc.) to be applicable for formalin-fixed paraffin-embedded tissue. Reading a patient's tissue as 'deeply' as possible and obtaining information on the morphological, genetic, proteomic and epigenetic background are the tasks of pathologists and molecular biologists and provide the clinicians with information relevant for precision medicine. Intensified cooperation between clinicians and pathologists will provide the basis of improved clinical drug selection and guide development of new cancer gene therapies and molecularly targeted drugs by research units and the pharmaceutical industry. © 2016 S. Karger GmbH, Freiburg.

Dynamic CRM occupancy reflects a temporal map of developmental progression.

PubMed

Wilczyński, Bartek; Furlong, Eileen E M

2010-06-22

Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression.

Discordant 14C ages from buried tidal-marsh soils in the Cascadia subduction zone, southern Oregon coast

USGS Publications Warehouse

Nelson, A.R.

1992-01-01

Peaty, tidal-marsh soils interbedded with estuarine mud in late Holocene stratigraphic sequences near Coos Bay, Oregon, may have been submerged and buried during great (M > 8) subduction earthquakes, smaller localized earthquakes, or by nontectonic processes. Radiocarbon dating might help distinguish among these alternatives by showing that soils at different sites were submerged at different times along this part of the Cascadia subduction zone. But comparison of conventional 14C ages for different materials from the same buried soils shows that they contain materials that differ in age by many hundreds of years. Errors in calibrated soil ages represent about the same length of time as recurrence times for submergence events (150-500 yr)-this similarity precludes using conventional 14C ages to distinguish buried soils along the southern Oregon coast. Accelerator mass spectrometer 14C ages of carefully selected macrofossils from the tops of peaty soils should provide more precise estimates of the times of submergence events. ?? 1992.

An analysis of the uncertainty and bias in DCE-MRI measurements using the spoiled gradient-recalled echo pulse sequence

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

Subashi, Ergys; Choudhury, Kingshuk R.; Johnson, G. Allan, E-mail: gjohnson@duke.edu

2014-03-15

Purpose: The pharmacokinetic parameters derived from dynamic contrast-enhanced (DCE) MRI have been used in more than 100 phase I trials and investigator led studies. A comparison of the absolute values of these quantities requires an estimation of their respective probability distribution function (PDF). The statistical variation of the DCE-MRI measurement is analyzed by considering the fundamental sources of error in the MR signal intensity acquired with the spoiled gradient-echo (SPGR) pulse sequence. Methods: The variance in the SPGR signal intensity arises from quadrature detection and excitation flip angle inconsistency. The noise power was measured in 11 phantoms of contrast agentmore » concentration in the range [0–1] mM (in steps of 0.1 mM) and in onein vivo acquisition of a tumor-bearing mouse. The distribution of the flip angle was determined in a uniform 10 mM CuSO{sub 4} phantom using the spin echo double angle method. The PDF of a wide range of T1 values measured with the varying flip angle (VFA) technique was estimated through numerical simulations of the SPGR equation. The resultant uncertainty in contrast agent concentration was incorporated in the most common model of tracer exchange kinetics and the PDF of the derived pharmacokinetic parameters was studied numerically. Results: The VFA method is an unbiased technique for measuringT1 only in the absence of bias in excitation flip angle. The time-dependent concentration of the contrast agent measured in vivo is within the theoretically predicted uncertainty. The uncertainty in measuring K{sup trans} with SPGR pulse sequences is of the same order, but always higher than, the uncertainty in measuring the pre-injection longitudinal relaxation time (T1{sub 0}). The lowest achievable bias/uncertainty in estimating this parameter is approximately 20%–70% higher than the bias/uncertainty in the measurement of the pre-injection T1 map. The fractional volume parameters derived from the extended Tofts model were found to be extremely sensitive to the variance in signal intensity. The SNR of the pre-injection T1 map indicates the limiting precision with which K{sup trans} can be calculated. Conclusions: Current small-animal imaging systems and pulse sequences robust to motion artifacts have the capacity for reproducible quantitative acquisitions with DCE-MRI. In these circumstances, it is feasible to achieve a level of precision limited only by physiologic variability.« less

Sequence verification of synthetic DNA by assembly of sequencing reads

PubMed Central

Wilson, Mandy L.; Cai, Yizhi; Hanlon, Regina; Taylor, Samantha; Chevreux, Bastien; Setubal, João C.; Tyler, Brett M.; Peccoud, Jean

2013-01-01

Gene synthesis attempts to assemble user-defined DNA sequences with base-level precision. Verifying the sequences of construction intermediates and the final product of a gene synthesis project is a critical part of the workflow, yet one that has received the least attention. Sequence validation is equally important for other kinds of curated clone collections. Ensuring that the physical sequence of a clone matches its published sequence is a common quality control step performed at least once over the course of a research project. GenoREAD is a web-based application that breaks the sequence verification process into two steps: the assembly of sequencing reads and the alignment of the resulting contig with a reference sequence. GenoREAD can determine if a clone matches its reference sequence. Its sophisticated reporting features help identify and troubleshoot problems that arise during the sequence verification process. GenoREAD has been experimentally validated on thousands of gene-sized constructs from an ORFeome project, and on longer sequences including whole plasmids and synthetic chromosomes. Comparing GenoREAD results with those from manual analysis of the sequencing data demonstrates that GenoREAD tends to be conservative in its diagnostic. GenoREAD is available at www.genoread.org. PMID:23042248

The AMBRE project: The thick thin disk and thin thick disk of the Milky Way

NASA Astrophysics Data System (ADS)

Hayden, M. R.; Recio-Blanco, A.; de Laverny, P.; Mikolaitis, S.; Worley, C. C.

2017-11-01

We analyze 494 main sequence turnoff and subgiant stars from the AMBRE:HARPS survey. These stars have accurate astrometric information from Gaia DR1, providing reliable age estimates with relative uncertainties of ±1 or 2 Gyr and allowing precise orbital determinations. The sample is split based on chemistry into a low-[Mg/Fe] sequence, which are often identified as thin disk stellar populations, and high-[Mg/Fe] sequence, which are often associated with thick disk stellar populations. We find that the high-[Mg/Fe] chemical sequence has extended star formation for several Gyr and is coeval with the oldest stars of the low-[Mg/Fe] chemical sequence: both the low- and high-[Mg/Fe] sequences were forming stars at the same time. We find that the high-[Mg/Fe] stellar populations are only vertically extended for the oldest, most-metal poor and highest [Mg/Fe] stars. When comparing vertical velocity dispersion for the low- and high-[Mg/Fe] sequences, the high-[Mg/Fe] sequence has lower vertical velocity dispersion than the low-[Mg/Fe] sequence for stars of similar age. This means that identifying either group as thin or thick disk based on chemistry is misleading. The stars belonging to the high-[Mg/Fe] sequence have perigalacticons that originate in the inner disk, while the perigalacticons of stars on the low-[Mg/Fe] sequence are generally around the solar neighborhood. From the orbital properties of the stars, the high-[Mg/Fe] and low-[Mg/Fe] sequences are most likely a reflection of the chemical enrichment history of the inner and outer disk populations, respectively; radial mixing causes both populations to be observed in situ at the solar position. Based on these results, we emphasize that it is important to be clear in defining what populations are being referenced when using the terms thin and thick disk, and that ideally the term thick disk should be reserved for purely geometric definitions to avoid confusion and be consistent with definitions in external galaxies.

Design and Research of the Sewage Treatment Control System

NASA Astrophysics Data System (ADS)

Chu, J.; Hu, W. W.

Due to the rapid development of China's economy, the water pollution has become a problem that we have to face. In particular, how to deal with industrial wastewater has become a top priority. In wastewater treatment, the control system based on PLC has met the design requirement in real-time, reliability, precision and so on. The integration of sequence control and process control in PLC, has the characteristics of high reliability, simple network, convenient and flexible use. PLC is a powerful tool for small and medium-sized industrial automation. Therefore, the sewage treatment control system take PLC as the core of control system, can nicely solve the problem of industrial wastewater in a certain extent.

Can genomics deliver climate-change ready crops?

PubMed

Varshney, Rajeev K; Singh, Vikas K; Kumar, Arvind; Powell, Wayne; Sorrells, Mark E

2018-04-20

Development of climate resilient crops with accelerating genetic gains in crops will require integration of different disciplines/technologies, to see the impact in the farmer's field. In this review, we summarize how we are utilizing our germplasm collections to identify superior alleles/haplotypes through NGS based sequencing approaches and how genomics-enabled technologies together with precise phenotyping are being used in crop breeding. Pre-breeding and genomics-assisted breeding approaches are contributing to the more efficient development of climate-resilient crops. It is anticipated that the integration of several disciplines/technologies will result in the delivery of climate change ready crops in less time. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Gilbert, Jack A.; Quinn, Robert A.; Debelius, Justine

Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramountmore » for developing precision diagnostics and therapies that are based on the microbiome.« less

Design automation techniques for custom LSI arrays

NASA Technical Reports Server (NTRS)

Feller, A.

1975-01-01

The standard cell design automation technique is described as an approach for generating random logic PMOS, CMOS or CMOS/SOS custom large scale integration arrays with low initial nonrecurring costs and quick turnaround time or design cycle. The system is composed of predesigned circuit functions or cells and computer programs capable of automatic placement and interconnection of the cells in accordance with an input data net list. The program generates a set of instructions to drive an automatic precision artwork generator. A series of support design automation and simulation programs are described, including programs for verifying correctness of the logic on the arrays, performing dc and dynamic analysis of MOS devices, and generating test sequences.

A high-order time-accurate interrogation method for time-resolved PIV

NASA Astrophysics Data System (ADS)

Lynch, Kyle; Scarano, Fulvio

2013-03-01

A novel method is introduced for increasing the accuracy and extending the dynamic range of time-resolved particle image velocimetry (PIV). The approach extends the concept of particle tracking velocimetry by multiple frames to the pattern tracking by cross-correlation analysis as employed in PIV. The working principle is based on tracking the patterned fluid element, within a chosen interrogation window, along its individual trajectory throughout an image sequence. In contrast to image-pair interrogation methods, the fluid trajectory correlation concept deals with variable velocity along curved trajectories and non-zero tangential acceleration during the observed time interval. As a result, the velocity magnitude and its direction are allowed to evolve in a nonlinear fashion along the fluid element trajectory. The continuum deformation (namely spatial derivatives of the velocity vector) is accounted for by adopting local image deformation. The principle offers important reductions of the measurement error based on three main points: by enlarging the temporal measurement interval, the relative error becomes reduced; secondly, the random and peak-locking errors are reduced by the use of least-squares polynomial fits to individual trajectories; finally, the introduction of high-order (nonlinear) fitting functions provides the basis for reducing the truncation error. Lastly, the instantaneous velocity is evaluated as the temporal derivative of the polynomial representation of the fluid parcel position in time. The principal features of this algorithm are compared with a single-pair iterative image deformation method. Synthetic image sequences are considered with steady flow (translation, shear and rotation) illustrating the increase of measurement precision. An experimental data set obtained by time-resolved PIV measurements of a circular jet is used to verify the robustness of the method on image sequences affected by camera noise and three-dimensional motions. In both cases, it is demonstrated that the measurement time interval can be significantly extended without compromising the correlation signal-to-noise ratio and with no increase of the truncation error. The increase of velocity dynamic range scales more than linearly with the number of frames included for the analysis, which supersedes by one order of magnitude the pair correlation by window deformation. The main factors influencing the performance of the method are discussed, namely the number of images composing the sequence and the polynomial order chosen to represent the motion throughout the trajectory.

MRI-Only Based Radiotherapy Treatment Planning for the Rat Brain on a Small Animal Radiation Research Platform (SARRP).

PubMed

Gutierrez, Shandra; Descamps, Benedicte; Vanhove, Christian

2015-01-01

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR sequences. Six rat heads were imaged, each with one CT and five MR sequences. The MR sequences were: T1-weighted, T2-weighted, zero-echo time (ZTE), and two ultra-short echo time sequences with 20 μs (UTE1) and 2 ms (UTE2) echo times. CT data were manually segmented into air, soft tissue, and bone to obtain the RTP reference. Bias field corrected MR images were automatically segmented into the same tissue classes using a fuzzy c-means segmentation algorithm with multiple images as input. Similarities between segmented CT and automatic segmented MR (ASMR) images were evaluated using Dice coefficient. Three ASMR images with high similarity index were used for further RTP. Three beam arrangements were investigated. Dose distributions were compared by analysing dose volume histograms. The highest Dice coefficients were obtained for the ZTE-UTE2 combination and for the T1-UTE1-T2 combination when ZTE was unavailable. Both combinations, along with UTE1-UTE2, often used to generate ASMR images, were used for further RTP. Using 1 beam, MR based RTP underestimated the dose to be delivered to the target (range: 1.4%-7.6%). When more complex beam configurations were used, the calculated dose using the ZTE-UTE2 combination was the most accurate, with 0.7% deviation from CT, compared to 0.8% for T1-UTE1-T2 and 1.7% for UTE1-UTE2. The presented MR-only based workflow for RTP on a SARRP enables both accurate organ delineation and dose calculations using multiple MR sequences. This method can be useful in longitudinal studies where CT's cumulative radiation dose might contribute to the total dose.

MRI-Only Based Radiotherapy Treatment Planning for the Rat Brain on a Small Animal Radiation Research Platform (SARRP)

PubMed Central

Gutierrez, Shandra; Descamps, Benedicte; Vanhove, Christian

2015-01-01

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR sequences. Six rat heads were imaged, each with one CT and five MR sequences. The MR sequences were: T1-weighted, T2-weighted, zero-echo time (ZTE), and two ultra-short echo time sequences with 20 μs (UTE1) and 2 ms (UTE2) echo times. CT data were manually segmented into air, soft tissue, and bone to obtain the RTP reference. Bias field corrected MR images were automatically segmented into the same tissue classes using a fuzzy c-means segmentation algorithm with multiple images as input. Similarities between segmented CT and automatic segmented MR (ASMR) images were evaluated using Dice coefficient. Three ASMR images with high similarity index were used for further RTP. Three beam arrangements were investigated. Dose distributions were compared by analysing dose volume histograms. The highest Dice coefficients were obtained for the ZTE-UTE2 combination and for the T1-UTE1-T2 combination when ZTE was unavailable. Both combinations, along with UTE1-UTE2, often used to generate ASMR images, were used for further RTP. Using 1 beam, MR based RTP underestimated the dose to be delivered to the target (range: 1.4%-7.6%). When more complex beam configurations were used, the calculated dose using the ZTE-UTE2 combination was the most accurate, with 0.7% deviation from CT, compared to 0.8% for T1-UTE1-T2 and 1.7% for UTE1-UTE2. The presented MR-only based workflow for RTP on a SARRP enables both accurate organ delineation and dose calculations using multiple MR sequences. This method can be useful in longitudinal studies where CT’s cumulative radiation dose might contribute to the total dose. PMID:26633302

High Precision Prediction of Functional Sites in Protein Structures

PubMed Central

Buturovic, Ljubomir; Wong, Mike; Tang, Grace W.; Altman, Russ B.; Petkovic, Dragutin

2014-01-01

We address the problem of assigning biological function to solved protein structures. Computational tools play a critical role in identifying potential active sites and informing screening decisions for further lab analysis. A critical parameter in the practical application of computational methods is the precision, or positive predictive value. Precision measures the level of confidence the user should have in a particular computed functional assignment. Low precision annotations lead to futile laboratory investigations and waste scarce research resources. In this paper we describe an advanced version of the protein function annotation system FEATURE, which achieved 99% precision and average recall of 95% across 20 representative functional sites. The system uses a Support Vector Machine classifier operating on the microenvironment of physicochemical features around an amino acid. We also compared performance of our method with state-of-the-art sequence-level annotator Pfam in terms of precision, recall and localization. To our knowledge, no other functional site annotator has been rigorously evaluated against these key criteria. The software and predictive models are incorporated into the WebFEATURE service at http://feature.stanford.edu/wf4.0-beta. PMID:24632601

NIH announces the launch of 3 integrated precision medicine trials: ALCHEMIST

Cancer.gov

The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST, will identify early-stage lung cancer patients with tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against

Targeted Quantitation of Proteins by Mass Spectrometry

PubMed Central

2013-01-01

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

Anchor-Free Localization Method for Mobile Targets in Coal Mine Wireless Sensor Networks

PubMed Central

Pei, Zhongmin; Deng, Zhidong; Xu, Shuo; Xu, Xiao

2009-01-01

Severe natural conditions and complex terrain make it difficult to apply precise localization in underground mines. In this paper, an anchor-free localization method for mobile targets is proposed based on non-metric multi-dimensional scaling (Multi-dimensional Scaling: MDS) and rank sequence. Firstly, a coal mine wireless sensor network is constructed in underground mines based on the ZigBee technology. Then a non-metric MDS algorithm is imported to estimate the reference nodes’ location. Finally, an improved sequence-based localization algorithm is presented to complete precise localization for mobile targets. The proposed method is tested through simulations with 100 nodes, outdoor experiments with 15 ZigBee physical nodes, and the experiments in the mine gas explosion laboratory with 12 ZigBee nodes. Experimental results show that our method has better localization accuracy and is more robust in underground mines. PMID:22574048

Anchor-free localization method for mobile targets in coal mine wireless sensor networks.

PubMed

Pei, Zhongmin; Deng, Zhidong; Xu, Shuo; Xu, Xiao

2009-01-01

Severe natural conditions and complex terrain make it difficult to apply precise localization in underground mines. In this paper, an anchor-free localization method for mobile targets is proposed based on non-metric multi-dimensional scaling (Multi-dimensional Scaling: MDS) and rank sequence. Firstly, a coal mine wireless sensor network is constructed in underground mines based on the ZigBee technology. Then a non-metric MDS algorithm is imported to estimate the reference nodes' location. Finally, an improved sequence-based localization algorithm is presented to complete precise localization for mobile targets. The proposed method is tested through simulations with 100 nodes, outdoor experiments with 15 ZigBee physical nodes, and the experiments in the mine gas explosion laboratory with 12 ZigBee nodes. Experimental results show that our method has better localization accuracy and is more robust in underground mines.

A Model Program for Translational Medicine in Epilepsy Genetics

PubMed Central

Smith, Lacey A.; Ullmann, Jeremy F. P.; Olson, Heather E.; El Achkar, Christelle M.; Truglio, Gessica; Kelly, McKenna; Rosen-Sheidley, Beth; Poduri, Annapurna

2017-01-01

Recent technological advances in gene sequencing have led to a rapid increase in gene discovery in epilepsy. However, the ability to assess pathogenicity of variants, provide functional analysis, and develop targeted therapies has not kept pace with rapid advances in sequencing technology. Thus, although clinical genetic testing may lead to a specific molecular diagnosis for some patients, test results often lead to more questions than answers. As the field begins to focus on therapeutic applications of genetic diagnoses using precision medicine, developing processes that offer more than equivocal test results is essential. The success of precision medicine in epilepsy relies on establishing a correct genetic diagnosis, analyzing functional consequences of genetic variants, screening potential therapeutics in the preclinical laboratory setting, and initiating targeted therapy trials for patients. We describe the structure of a comprehensive, pediatric Epilepsy Genetics Program that can serve as a model for translational medicine in epilepsy. PMID:28056630

Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing.

PubMed

Liu, Zhen; Lu, Zongyang; Yang, Guang; Huang, Shisheng; Li, Guanglei; Feng, Songjie; Liu, Yajing; Li, Jianan; Yu, Wenxia; Zhang, Yu; Chen, Jia; Sun, Qiang; Huang, Xingxu

2018-06-14

A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to-G base editing by using a combination of ABE and SaBE3, thus creating mouse model harboring multiple mutations. We also demonstrate the specificity of ABE by deep sequencing and whole-genome sequencing (WGS). Taken together, ABE is highly efficient and precise in vivo, making it feasible to model and potentially cure relevant genetic diseases.

Targeted quantitation of proteins by mass spectrometry.

PubMed

Liebler, Daniel C; Zimmerman, Lisa J

2013-06-04

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement.

Digital detection of endonuclease mediated gene disruption in the HIV provirus

PubMed Central

Sedlak, Ruth Hall; Liang, Shu; Niyonzima, Nixon; De Silva Feelixge, Harshana S.; Roychoudhury, Pavitra; Greninger, Alexander L.; Weber, Nicholas D.; Boissel, Sandrine; Scharenberg, Andrew M.; Cheng, Anqi; Magaret, Amalia; Bumgarner, Roger; Stone, Daniel; Jerome, Keith R.

2016-01-01

Genome editing by designer nucleases is a rapidly evolving technology utilized in a highly diverse set of research fields. Among all fields, the T7 endonuclease mismatch cleavage assay, or Surveyor assay, is the most commonly used tool to assess genomic editing by designer nucleases. This assay, while relatively easy to perform, provides only a semi-quantitative measure of mutation efficiency that lacks sensitivity and accuracy. We demonstrate a simple droplet digital PCR assay that quickly quantitates a range of indel mutations with detection as low as 0.02% mutant in a wild type background and precision (≤6%CV) and accuracy superior to either mismatch cleavage assay or clonal sequencing when compared to next-generation sequencing. The precision and simplicity of this assay will facilitate comparison of gene editing approaches and their optimization, accelerating progress in this rapidly-moving field. PMID:26829887

DNA-based identification of forensically important species of Sarcophagidae (Insecta: Diptera) from Rio de Janeiro, Brazil.

PubMed

Napoleão, K S; Mello-Patiu, C A; Oliveira-Costa, J; Takiya, D M; Silva, R; Moura-Neto, R S

2016-05-06

Sarcophagidae, or flesh flies, are of great importance in forensic entomology, but their effective application requires precise taxonomic identification, which relies almost exclusively on characteristics of the male genitalia. Given that female flies and larvae are most abundant in animal carcasses or on corpses, precise morphological identification can be difficult; therefore, DNA sequencing can be an additional tool for use in taxonomic identification. This paper analyzes part of the mitochondrial cytochrome c oxidase subunit I (COI) gene from three Sarcophagidae species of forensic importance in the City of Rio de Janeiro: Oxysarcodexia fluminensis, Peckia chrysostoma, and Peckia intermutans. COI fragments of 400 bp from 36 specimens of these three species were sequenced. No intraspecific differences were found among specimens of O. fluminensis, but P. chrysostoma and P. intermutans each had two haplotypes, ranging from 0 to 0.7%. The interspecific divergence was 8.5-11.6%, corroborating previously reported findings.

Rapid oxygenation of Earth's atmosphere 2.33 billion years ago.

PubMed

Luo, Genming; Ono, Shuhei; Beukes, Nicolas J; Wang, David T; Xie, Shucheng; Summons, Roger E

2016-05-01

Molecular oxygen (O2) is, and has been, a primary driver of biological evolution and shapes the contemporary landscape of Earth's biogeochemical cycles. Although "whiffs" of oxygen have been documented in the Archean atmosphere, substantial O2 did not accumulate irreversibly until the Early Paleoproterozoic, during what has been termed the Great Oxygenation Event (GOE). The timing of the GOE and the rate at which this oxygenation took place have been poorly constrained until now. We report the transition (that is, from being mass-independent to becoming mass-dependent) in multiple sulfur isotope signals of diagenetic pyrite in a continuous sedimentary sequence in three coeval drill cores in the Transvaal Supergroup, South Africa. These data precisely constrain the GOE to 2.33 billion years ago. The new data suggest that the oxygenation occurred rapidly-within 1 to 10 million years-and was followed by a slower rise in the ocean sulfate inventory. Our data indicate that a climate perturbation predated the GOE, whereas the relationships among GOE, "Snowball Earth" glaciation, and biogeochemical cycling will require further stratigraphic correlation supported with precise chronologies and paleolatitude reconstructions.

System-state and operating condition sensitive control method and apparatus for electric power delivery systems

NASA Technical Reports Server (NTRS)

Burns, III, William Wesley (Inventor); Wilson, Thomas George (Inventor)

1978-01-01

This invention provides a method and apparatus for determining a precise switching sequence for the power switching elements of electric power delivery systems of the on-off switching type and which enables extremely fast transient response, precise regulation and highly stable operation. The control utilizes the values of the power delivery system power handling network components, a desired output characteristic, a system timing parameter, and the externally imposed operating conditions to determine where steady state operations should be in order to yield desired output characteristics for the given system specifications. The actual state of the power delivery system is continuously monitored and compared to a state-space boundary which is derived from the desired equilibrium condition, and from the information obtained from this comparison, the system is moved to the desired equilibrium condition in one cycle of switching control. Since the controller continuously monitors the power delivery system's externally imposed operating conditions, a change in the conditions is immediately sensed and a new equilibrium condition is determined and achieved, again in a single cycle of switching control.

Method of high precision interval measurement in pulse laser ranging system

NASA Astrophysics Data System (ADS)

Wang, Zhen; Lv, Xin-yuan; Mao, Jin-jin; Liu, Wei; Yang, Dong

2013-09-01

Laser ranging is suitable for laser system, for it has the advantage of high measuring precision, fast measuring speed,no cooperative targets and strong resistance to electromagnetic interference,the measuremen of laser ranging is the key paremeters affecting the performance of the whole system.The precision of the pulsed laser ranging system was decided by the precision of the time interval measurement, the principle structure of laser ranging system was introduced, and a method of high precision time interval measurement in pulse laser ranging system was established in this paper.Based on the analysis of the factors which affected the precision of range measure,the pulse rising edges discriminator was adopted to produce timing mark for the start-stop time discrimination,and the TDC-GP2 high precision interval measurement system based on TMS320F2812 DSP was designed to improve the measurement precision.Experimental results indicate that the time interval measurement method in this paper can obtain higher range accuracy. Compared with the traditional time interval measurement system,the method simplifies the system design and reduce the influence of bad weather conditions,furthermore,it satisfies the requirements of low costs and miniaturization.

High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling

PubMed Central

Jones, Joshua D.; Chung, Betty Y.-W.; Siddell, Stuart G.; Brierley, Ian

2016-01-01

Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global “snap-shot” of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus. PMID:26919232

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective.

PubMed

Chen, Guoli; Yang, Zhaohai; Eshleman, James R; Netto, George J; Lin, Ming-Tseh

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

DNA and RNA sequencing by nanoscale reading through programmable electrophoresis and nanoelectrode-gated tunneling and dielectric detection

DOEpatents

Lee, James W.; Thundat, Thomas G.

2005-06-14

An apparatus and method for performing nucleic acid (DNA and/or RNA) sequencing on a single molecule. The genetic sequence information is obtained by probing through a DNA or RNA molecule base by base at nanometer scale as though looking through a strip of movie film. This DNA sequencing nanotechnology has the theoretical capability of performing DNA sequencing at a maximal rate of about 1,000,000 bases per second. This enhanced performance is made possible by a series of innovations including: novel applications of a fine-tuned nanometer gap for passage of a single DNA or RNA molecule; thin layer microfluidics for sample loading and delivery; and programmable electric fields for precise control of DNA or RNA movement. Detection methods include nanoelectrode-gated tunneling current measurements, dielectric molecular characterization, and atomic force microscopy/electrostatic force microscopy (AFM/EFM) probing for nanoscale reading of the nucleic acid sequences.

Value-based genomics.

PubMed

Gong, Jun; Pan, Kathy; Fakih, Marwan; Pal, Sumanta; Salgia, Ravi

2018-03-20

Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge. In this review, we highlight available data through a pre-established and conceptualized framework for evaluating value-based medicine to assess the cost (efficiency), clinical benefit (effectiveness), and toxicity (safety) of genomic profiling in cancer care. We also provide perspectives on future directions of next-generation sequencing from targeted panels to whole-exome or whole-genome sequencing and describe potential strategies needed to attain value-based genomics.

Value-based genomics

PubMed Central

Gong, Jun; Pan, Kathy; Fakih, Marwan; Pal, Sumanta; Salgia, Ravi

2018-01-01

Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge. In this review, we highlight available data through a pre-established and conceptualized framework for evaluating value-based medicine to assess the cost (efficiency), clinical benefit (effectiveness), and toxicity (safety) of genomic profiling in cancer care. We also provide perspectives on future directions of next-generation sequencing from targeted panels to whole-exome or whole-genome sequencing and describe potential strategies needed to attain value-based genomics. PMID:29644010

Comparison of potassium and sodium binding in vivo and in agarose samples using TQTPPI pulse sequence

NASA Astrophysics Data System (ADS)

Schepkin, Victor D.; Neubauer, Andreas; Nagel, Armin M.; Budinger, Thomas F.

2017-04-01

Potassium and sodium specific binding in vivo were explored at 21.1 T by triple quantum (TQ) magnetic resonance (MR) signals without filtration to achieve high sensitivities and precise quantifications. The pulse sequence used time proportional phase increments (TPPI). During simultaneous phase-time increments, it provided total single quantum (SQ) and TQ MR signals in the second dimension at single and triple quantum frequencies, respectively. The detection of both TQ and SQ signals was performed at identical experimental conditions and the resulting TQ signal equals 60 ± 3% of the SQ signal when all ions experience sufficient time for binding. In a rat head in vivo the TQ percentage relative to SQ for potassium is 41.5 ± 3% and for sodium is 16.1 ± 1%. These percentages were compared to the matching values in an agarose tissue model with MR relaxation times similar to those of mammalian brain tissue. The sodium TQ signal in agarose samples decreased in the presence of potassium, suggesting a competitive binding of potassium relative to sodium ions for the same binding sites. The TQTPPI signals correspond to almost two times more effective binding of potassium than sodium. In vivo, up to ∼69% of total potassium and ∼27% of total sodium can be regarded as bound or experiencing an association time in the range of several milliseconds. Experimental data analyses show that more than half of the in vivo total sodium TQ signal could be from extracellular space, which is an important factor for quantification of intracellular MR signals.

New high-precision orbital and physical parameters of the double-lined low-mass spectroscopic binary BY Draconis

NASA Astrophysics Data System (ADS)

Hełminiak, K. G.; Konacki, M.; Muterspaugh, M. W.; Browne, S. E.; Howard, A. W.; Kulkarni, S. R.

2012-01-01

We present the most precise to date orbital and physical parameters of the well-known short period (P= 5.975 d), eccentric (e= 0.3) double-lined spectroscopic binary BY Draconis (BY Dra), a prototype of a class of late-type, active, spotted flare stars. We calculate the full spectroscopic/astrometric orbital solution by combining our precise radial velocities (RVs) and the archival astrometric measurements from the Palomar Testbed Interferometer (PTI). The RVs were derived based on the high-resolution echelle spectra taken between 2004 and 2008 with the Keck I/high-resolution echelle spectrograph, Shane/CAT/HamSpec and TNG/SARG telescopes/spectrographs using our novel iodine-cell technique for double-lined binary stars. The RVs and available PTI astrometric data spanning over eight years allow us to reach 0.2-0.5 per cent level of precision in Msin 3i and the parallax but the geometry of the orbit (i≃ 154°) hampers the absolute mass precision to 3.3 per cent, which is still an order of magnitude better than for previous studies. We compare our results with a set of Yonsei-Yale theoretical stellar isochrones and conclude that BY Dra is probably a main-sequence system more metal rich than the Sun. Using the orbital inclination and the available rotational velocities of the components, we also conclude that the rotational axes of the components are likely misaligned with the orbital angular momentum. Given BY Dra's main-sequence status, late spectral type and the relatively short orbital period, its high orbital eccentricity and probable spin-orbit misalignment are not in agreement with the tidal theory. This disagreement may possibly be explained by smaller rotational velocities of the components and the presence of a substellar mass companion to BY Dra AB.

A new geochemical instrument for the precise measurement of isotopic ratios and trace species in planetary atmospheres

NASA Astrophysics Data System (ADS)

Chassefiere, E.; Jambon, A.; Berthelier, J.-J.; Sarda, Ph.; Agrinier, P.

2003-04-01

The technique of GCMS analysis, which has been used with a great success on several past planetary missions, is not adapted for precise measurements of the isotopic composition of planetary atmospheres (noble gases, stable isotopes), and volatile outgassed products from solid sample pyrolysis. Static mass spectrometry, coupled with gas separation by cryo-separation, and chemical trapping, is commonly used in the laboratory to study volatiles extracted from terrestrial and meteoritic samples. This technique allows to reach a precision on isotopic ratios of the order of a few 0.1 ppm for a typical amount of gas of a few micromoles. We are presently studying an instrument based on the same principle for space exploration applications. The PALOMA instrument (PAyload for Local Observation of Mars Atmosphere) will be proposed in response to the AO for the instrumentation of the NASA Mars Smart Lander mission, planned to be launched in 2009. It might be part as well of the EXOMARS mission presently studied at ESA in the frame of the Aurora program. The miniaturization of major key elements, like the cryogenic device, the mass spectrometer, the line and its ensemble of valves, is presently led in our laboratories under CNES funding. The instrument consists of : (i) a gas purification and separation line, using techniques of cryogenic and chemical trapping, and possibly membrane permeation for molecular hydrogen analysis, (ii) a mass spectrometer working in static mode, without carrier gas (both time-of-flight and magnetic solutions are studied), (iii) a turbo-molecular pump that provides the required level of vacuum in the separation line and in the spectrometer. In the specific case of Mars, it is designed to work during typically 2 years (about 1000 measurement cycles), in order to perform accurate measurements of molecular, elemental and isotopic composition and of their diurnal/seasonal variations. The gas is sampled directly from the ambient atmosphere, without need for an external sample distribution system. The general characteristics of the instrument are as following . The mass is 6 kg, for a size of 30 x 30 x 20 cm. The required power, averaged over a complete measurement cycle, is 20 W (peak value : 30 W). The total energy required for one sequence is 100 Wh. This number must be considered as an upper limit, and corresponds to the most complex sequence (noble gas isotope analysis). Sequences used for stable isotopes measurement, and atmospheric molecular composition (trace gases of geological and/or astrobiological interest), are expected to be simpler, and less power-consuming. The anticipated volume of data produced by one observation sequence is estimated to be in the 3-6 kb range. The gas is sampled directly from the ambient atmosphere.

Multi-level machine learning prediction of protein-protein interactions in Saccharomyces cerevisiae.

PubMed

Zubek, Julian; Tatjewski, Marcin; Boniecki, Adam; Mnich, Maciej; Basu, Subhadip; Plewczynski, Dariusz

2015-01-01

Accurate identification of protein-protein interactions (PPI) is the key step in understanding proteins' biological functions, which are typically context-dependent. Many existing PPI predictors rely on aggregated features from protein sequences, however only a few methods exploit local information about specific residue contacts. In this work we present a two-stage machine learning approach for prediction of protein-protein interactions. We start with the carefully filtered data on protein complexes available for Saccharomyces cerevisiae in the Protein Data Bank (PDB) database. First, we build linear descriptions of interacting and non-interacting sequence segment pairs based on their inter-residue distances. Secondly, we train machine learning classifiers to predict binary segment interactions for any two short sequence fragments. The final prediction of the protein-protein interaction is done using the 2D matrix representation of all-against-all possible interacting sequence segments of both analysed proteins. The level-I predictor achieves 0.88 AUC for micro-scale, i.e., residue-level prediction. The level-II predictor improves the results further by a more complex learning paradigm. We perform 30-fold macro-scale, i.e., protein-level cross-validation experiment. The level-II predictor using PSIPRED-predicted secondary structure reaches 0.70 precision, 0.68 recall, and 0.70 AUC, whereas other popular methods provide results below 0.6 threshold (recall, precision, AUC). Our results demonstrate that multi-scale sequence features aggregation procedure is able to improve the machine learning results by more than 10% as compared to other sequence representations. Prepared datasets and source code for our experimental pipeline are freely available for download from: http://zubekj.github.io/mlppi/ (open source Python implementation, OS independent).

The neural dynamics of song syntax in songbirds

NASA Astrophysics Data System (ADS)

Jin, Dezhe

2010-03-01

Songbird is ``the hydrogen atom'' of the neuroscience of complex, learned vocalizations such as human speech. Songs of Bengalese finch consist of sequences of syllables. While syllables are temporally stereotypical, syllable sequences can vary and follow complex, probabilistic syntactic rules, which are rudimentarily similar to grammars in human language. Songbird brain is accessible to experimental probes, and is understood well enough to construct biologically constrained, predictive computational models. In this talk, I will discuss the structure and dynamics of neural networks underlying the stereotypy of the birdsong syllables and the flexibility of syllable sequences. Recent experiments and computational models suggest that a syllable is encoded in a chain network of projection neurons in premotor nucleus HVC (proper name). Precisely timed spikes propagate along the chain, driving vocalization of the syllable through downstream nuclei. Through a computational model, I show that that variable syllable sequences can be generated through spike propagations in a network in HVC in which the syllable-encoding chain networks are connected into a branching chain pattern. The neurons mutually inhibit each other through the inhibitory HVC interneurons, and are driven by external inputs from nuclei upstream of HVC. At a branching point that connects the final group of a chain to the first groups of several chains, the spike activity selects one branch to continue the propagation. The selection is probabilistic, and is due to the winner-take-all mechanism mediated by the inhibition and noise. The model predicts that the syllable sequences statistically follow partially observable Markov models. Experimental results supporting this and other predictions of the model will be presented. We suggest that the syntax of birdsong syllable sequences is embedded in the connection patterns of HVC projection neurons.

Application of Genomic Technologies to the Breeding of Trees

PubMed Central

Badenes, Maria L.; Fernández i Martí, Angel; Ríos, Gabino; Rubio-Cabetas, María J.

2016-01-01

The recent introduction of next generation sequencing (NGS) technologies represents a major revolution in providing new tools for identifying the genes and/or genomic intervals controlling important traits for selection in breeding programs. In perennial fruit trees with long generation times and large sizes of adult plants, the impact of these techniques is even more important. High-throughput DNA sequencing technologies have provided complete annotated sequences in many important tree species. Most of the high-throughput genotyping platforms described are being used for studies of genetic diversity and population structure. Dissection of complex traits became possible through the availability of genome sequences along with phenotypic variation data, which allow to elucidate the causative genetic differences that give rise to observed phenotypic variation. Association mapping facilitates the association between genetic markers and phenotype in unstructured and complex populations, identifying molecular markers for assisted selection and breeding. Also, genomic data provide in silico identification and characterization of genes and gene families related to important traits, enabling new tools for molecular marker assisted selection in tree breeding. Deep sequencing of transcriptomes is also a powerful tool for the analysis of precise expression levels of each gene in a sample. It consists in quantifying short cDNA reads, obtained by NGS technologies, in order to compare the entire transcriptomes between genotypes and environmental conditions. The miRNAs are non-coding short RNAs involved in the regulation of different physiological processes, which can be identified by high-throughput sequencing of RNA libraries obtained by reverse transcription of purified short RNAs, and by in silico comparison with known miRNAs from other species. All together, NGS techniques and their applications have increased the resources for plant breeding in tree species, closing the former gap of genetic tools between trees and annual species. PMID:27895664

Application of Genomic Technologies to the Breeding of Trees.

PubMed

Badenes, Maria L; Fernández I Martí, Angel; Ríos, Gabino; Rubio-Cabetas, María J

2016-01-01

The recent introduction of next generation sequencing (NGS) technologies represents a major revolution in providing new tools for identifying the genes and/or genomic intervals controlling important traits for selection in breeding programs. In perennial fruit trees with long generation times and large sizes of adult plants, the impact of these techniques is even more important. High-throughput DNA sequencing technologies have provided complete annotated sequences in many important tree species. Most of the high-throughput genotyping platforms described are being used for studies of genetic diversity and population structure. Dissection of complex traits became possible through the availability of genome sequences along with phenotypic variation data, which allow to elucidate the causative genetic differences that give rise to observed phenotypic variation. Association mapping facilitates the association between genetic markers and phenotype in unstructured and complex populations, identifying molecular markers for assisted selection and breeding. Also, genomic data provide in silico identification and characterization of genes and gene families related to important traits, enabling new tools for molecular marker assisted selection in tree breeding. Deep sequencing of transcriptomes is also a powerful tool for the analysis of precise expression levels of each gene in a sample. It consists in quantifying short cDNA reads, obtained by NGS technologies, in order to compare the entire transcriptomes between genotypes and environmental conditions. The miRNAs are non-coding short RNAs involved in the regulation of different physiological processes, which can be identified by high-throughput sequencing of RNA libraries obtained by reverse transcription of purified short RNAs, and by in silico comparison with known miRNAs from other species. All together, NGS techniques and their applications have increased the resources for plant breeding in tree species, closing the former gap of genetic tools between trees and annual species.

Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir resistance mutations in chronic hepatitis B.

PubMed

Ahn, Sang Hoon; Chun, Ji-Yong; Shin, Soo-Kyung; Park, Jun Yong; Yoo, Wangdon; Hong, Sun Pyo; Kim, Soo-Ok; Han, Kwang-Hyub

2013-12-01

Molecular diagnostic methods have enabled the rapid diagnosis of drug-resistant mutations in hepatitis B virus (HBV) and have reduced both unnecessary therapeutic interventions and medical costs. In this study we evaluated the analytical and clinical performances of the HepB Typer-Entecavir kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations. The HepB Typer-Entecavir kit was evaluated for its limit of detection, interference, cross-reactivity, and precision using HBV reference standards made by diluting high-titer viral stocks in HBV-negative human serum. The performance of the HepB Typer-Entecavir kit for detecting mutations related to entecavir resistance was compared with direct sequencing for 396 clinical samples from 108 patients. Using the reference standards, the detection limit of the HepB Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity was observed, and elevated levels of various interfering substances did not adversely affect its analytical performance. The precision test conducted by repetitive analysis of 2,400 replicates with reference standards at various concentrations showed 99.9% agreement (2398/2400). The overall concordance rate between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical samples was 99.5%. The HepB Typer-Entecavir kit showed high reliability and precision, and comparable sensitivity and specificity for detecting mutant virus populations in reference and clinical samples in comparison with direct sequencing. Therefore, this assay would be clinically useful in the diagnosis of entecavir-resistance-associated mutations in chronic hepatitis B.

Composite x-ray image assembly for large-field digital mammography with one- and two-dimensional positioning of a focal plane array

NASA Technical Reports Server (NTRS)

Halama, G.; McAdoo, J.; Liu, H.

1998-01-01

To demonstrate the feasibility of a novel large-field digital mammography technique, a 1024 x 1024 pixel Loral charge-coupled device (CCD) focal plane array (FPA) was positioned in a mammographic field with one- and two-dimensional scan sequences to obtain 950 x 1800 pixel and 3600 x 3600 pixel composite images, respectively. These experiments verify that precise positioning of FPAs produced seamless composites and that the CCD mosaic concept has potential for high-resolution, large-field imaging. The proposed CCD mosaic concept resembles a checkerboard pattern with spacing left between the CCDs for the driver and readout electronics. To obtain a complete x-ray image, the mosaic must be repositioned four times, with an x-ray exposure at each position. To reduce the patient dose, a lead shield with appropriately patterned holes is placed between the x-ray source and the patient. The high-precision motorized translation stages and the fiber-coupled-scintillating-screen-CCD sensor assembly were placed in the position usually occupied by the film cassette. Because of the high mechanical precision, seamless composites were constructed from the subimages. This paper discusses the positioning, image alignment procedure, and composite image results. The paper only addresses the formation of a seamless composite image from subimages and will not consider the effects of the lead shield, multiple CCDs, or the speed of motion.

Digital encoding of cellular mRNAs enabling precise and absolute gene expression measurement by single-molecule counting.

PubMed

Fu, Glenn K; Wilhelmy, Julie; Stern, David; Fan, H Christina; Fodor, Stephen P A

2014-03-18

We present a new approach for the sensitive detection and accurate quantitation of messenger ribonucleic acid (mRNA) gene transcripts in single cells. First, the entire population of mRNAs is encoded with molecular barcodes during reverse transcription. After amplification of the gene targets of interest, molecular barcodes are counted by sequencing or scored on a simple hybridization detector to reveal the number of molecules in the starting sample. Since absolute quantities are measured, calibration to standards is unnecessary, and many of the relative quantitation challenges such as polymerase chain reaction (PCR) bias are avoided. We apply the method to gene expression analysis of minute sample quantities and demonstrate precise measurements with sensitivity down to sub single-cell levels. The method is an easy, single-tube, end point assay utilizing standard thermal cyclers and PCR reagents. Accurate and precise measurements are obtained without any need for cycle-to-cycle intensity-based real-time monitoring or physical partitioning into multiple reactions (e.g., digital PCR). Further, since all mRNA molecules are encoded with molecular barcodes, amplification can be used to generate more material for multiple measurements and technical replicates can be carried out on limited samples. The method is particularly useful for small sample quantities, such as single-cell experiments. Digital encoding of cellular content preserves true abundance levels and overcomes distortions introduced by amplification.

A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

PubMed

Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

2017-04-01

After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

Evaluation of the Precision ID Ancestry Panel for crime case work: A SNP typing assay developed for typing of 165 ancestral informative markers.

PubMed

Pereira, Vania; Mogensen, Helle S; Børsting, Claus; Morling, Niels

2017-05-01

The application of massive parallel sequencing (MPS) methodologies in forensic genetics is promising and it is gradually being implemented in forensic genetic case work. One of the major advantages of these technologies is that several traditional electrophoresis assays can be combined into one single MPS assay. This reduces both the amount of sample used and the time of the investigations. This study assessed the utility of the Precision ID Ancestry Panel (Thermo Fisher Scientific, Waltham, USA) in forensic genetics. This assay was developed for the Ion Torrent PGM™ System and genotypes 165 ancestry informative SNPs. The performance of the assay and the accompanying software solution for ancestry inference was assessed by typing 142 Danes and 98 Somalis. Locus balance, heterozygote balance, and noise levels were calculated and future analysis criteria for crime case work were estimated. Overall, the Precision ID Ancestry Panel performed well, and only minor changes to the recommended protocol were implemented. Three out of the 165 loci (rs459920, rs7251928, and rs7722456) had consistently poor performance, mainly due to misalignment of homopolymeric stretches. We suggest that these loci should be excluded from the analyses. The different statistical methods for reporting ancestry in forensic genetic case work are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Precise Time - Naval Oceanography Portal

Science.gov Websites

section Advanced Search... Sections Home Time Earth Orientation Astronomy Meteorology Oceanography Ice You are here: Home › USNO › Precise Time USNO Logo USNO Navigation Master Clock GPS Display Clocks TWSTT Telephone Time NTP Info Precise Time The U. S. Naval Observatory is charged with maintaining the

MultiGeMS: detection of SNVs from multiple samples using model selection on high-throughput sequencing data.

PubMed

Murillo, Gabriel H; You, Na; Su, Xiaoquan; Cui, Wei; Reilly, Muredach P; Li, Mingyao; Ning, Kang; Cui, Xinping

2016-05-15

Single nucleotide variant (SNV) detection procedures are being utilized as never before to analyze the recent abundance of high-throughput DNA sequencing data, both on single and multiple sample datasets. Building on previously published work with the single sample SNV caller genotype model selection (GeMS), a multiple sample version of GeMS (MultiGeMS) is introduced. Unlike other popular multiple sample SNV callers, the MultiGeMS statistical model accounts for enzymatic substitution sequencing errors. It also addresses the multiple testing problem endemic to multiple sample SNV calling and utilizes high performance computing (HPC) techniques. A simulation study demonstrates that MultiGeMS ranks highest in precision among a selection of popular multiple sample SNV callers, while showing exceptional recall in calling common SNVs. Further, both simulation studies and real data analyses indicate that MultiGeMS is robust to low-quality data. We also demonstrate that accounting for enzymatic substitution sequencing errors not only improves SNV call precision at low mapping quality regions, but also improves recall at reference allele-dominated sites with high mapping quality. The MultiGeMS package can be downloaded from https://github.com/cui-lab/multigems xinping.cui@ucr.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Droplet digital PCR technology promises new applications and research areas.

PubMed

Manoj, P

2016-01-01

Digital Polymerase Chain Reaction (dPCR) is used to quantify nucleic acids and its applications are in the detection and precise quantification of low-level pathogens, rare genetic sequences, quantification of copy number variants, rare mutations and in relative gene expressions. Here the PCR is performed in large number of reaction chambers or partitions and the reaction is carried out in each partition individually. This separation allows a more reliable collection and sensitive measurement of nucleic acid. Results are calculated by counting amplified target sequence (positive droplets) and the number of partitions in which there is no amplification (negative droplets). The mean number of target sequences was calculated by Poisson Algorithm. Poisson correction compensates the presence of more than one copy of target gene in any droplets. The method provides information with accuracy and precision which is highly reproducible and less susceptible to inhibitors than qPCR. It has been demonstrated in studying variations in gene sequences, such as copy number variants and point mutations, distinguishing differences between expression of nearly identical alleles, assessment of clinically relevant genetic variations and it is routinely used for clonal amplification of samples for NGS methods. dPCR enables more reliable predictors of tumor status and patient prognosis by absolute quantitation using reference normalizations. Rare mitochondrial DNA deletions associated with a range of diseases and disorders as well as aging can be accurately detected with droplet digital PCR.

An indicator gene to demonstrate intracellular transposition of defective retroviruses.

PubMed Central

Heidmann, T; Heidmann, O; Nicolas, J F

1988-01-01

An indicator gene for detection and quantitation of RNA-mediated transposition was constructed (neoRT). It was inserted into a Moloney murine leukemia provirus (Mo-MLV) deleted for the envelope gene to test for intracellular transposition of defective retroviruses [Mo-MLV(neo)RT]. NeoRT contains the selectable neo gene (which confers resistance to the drug G418), inactivated by a polyadenylylation sequence inserted between the neo promotor and coding sequence. The polyadenylylation sequence is flanked (on the antisense strand of the DNA) by a donor and an acceptor splice site so as to be removed upon passage of the provirus through an RNA intermediate. 3T3 cells transfected with the defective Mo-MLV(neo)RT provirus are sensitive to G418. After trans-complementation with Mo-MLV, viral transcripts confer resistance to G418 upon infection of test cells. In the resistant cells, the polyadenylylation sequence has been removed, as a result in most cases of precise splicing of the intronic domain. Retrotransposition of the defective Mo-MLV(neo)RT provirus was demonstrated by submitting transfected G418-sensitive clones to selection. Between 1 and 10 G418-resistant clones were obtained per 10(7) cells. Several possess additional copies, with evidence for precise removal of the intronic domain. By using target test cells in coculture experiments, extracellular intermediates of retrotransposition could not be detected. Images PMID:2832848

ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials

Cancer.gov

ALCHEMIST represents three integrated, precision medicine trials that are designed to identify people with early-stage lung cancer who have tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those mol

Evidence for Long-Timescale Patterns of Synaptic Inputs in CA1 of Awake Behaving Mice.

PubMed

Kolb, Ilya; Talei Franzesi, Giovanni; Wang, Michael; Kodandaramaiah, Suhasa B; Forest, Craig R; Boyden, Edward S; Singer, Annabelle C

2018-02-14

Repeated sequences of neural activity are a pervasive feature of neural networks in vivo and in vitro In the hippocampus, sequential firing of many neurons over periods of 100-300 ms reoccurs during behavior and during periods of quiescence. However, it is not known whether the hippocampus produces longer sequences of activity or whether such sequences are restricted to specific network states. Furthermore, whether long repeated patterns of activity are transmitted to single cells downstream is unclear. To answer these questions, we recorded intracellularly from hippocampal CA1 of awake, behaving male mice to examine both subthreshold activity and spiking output in single neurons. In eight of nine recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or "repeats." Repeats generally were high-amplitude, nonoscillatory events reoccurring with 10 ms precision. Using statistical controls, we determined that repeats occurred more often than would be expected from unstructured network activity (e.g., by chance). Most spikes occurred during a repeat, and when a repeat contained a spike, the spike reoccurred with precision on the order of ≤20 ms, showing that long repeated patterns of subthreshold activity are strongly connected to spike output. Unexpectedly, we found that repeats occurred independently of classic hippocampal network states like theta oscillations or sharp-wave ripples. Together, these results reveal surprisingly long patterns of repeated activity in the hippocampal network that occur nonstochastically, are transmitted to single downstream neurons, and strongly shape their output. This suggests that the timescale of information transmission in the hippocampal network is much longer than previously thought. SIGNIFICANCE STATEMENT We found long (≥900 ms), repeated, subthreshold patterns of activity in CA1 of awake, behaving mice. These repeated patterns ("repeats") occurred more often than expected by chance and with 10 ms precision. Most spikes occurred within repeats and reoccurred with a precision on the order of 20 ms. Surprisingly, there was no correlation between repeat occurrence and classical network states such as theta oscillations and sharp-wave ripples. These results provide strong evidence that long patterns of activity are repeated and transmitted to downstream neurons, suggesting that the hippocampus can generate longer sequences of repeated activity than previously thought. Copyright © 2018 the authors 0270-6474/18/381822-14$15.00/0.

Touch imprint cytology with massively parallel sequencing (TIC-seq): a simple and rapid method to snapshot genetic alterations in tumors.

PubMed

Amemiya, Kenji; Hirotsu, Yosuke; Goto, Taichiro; Nakagomi, Hiroshi; Mochizuki, Hitoshi; Oyama, Toshio; Omata, Masao

2016-12-01

Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors. We prepared FFPE tissues and TIC specimens from tumors in nine lung cancer patients and one patient with breast cancer. We found that the quality and quantity of TIC DNA was higher than that of FFPE DNA, which requires microdissection to enrich DNA from target tissues. Targeted sequencing using a next-generation sequencer obtained sufficient sequence data using TIC DNA. Most (92%) somatic mutations in lung primary tumors were found to be consistent between TIC and FFPE DNA. We also applied TIC DNA to primary and metastatic tumor tissues to analyze tumor heterogeneity in a breast cancer patient, and showed that common and distinct mutations among primary and metastatic sites could be classified into two distinct histological subtypes. TIC-seq is an alternative and feasible method to analyze genomic alterations in tumors by simply touching the cut surface of specimens to slides. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

CoVaCS: a consensus variant calling system.

PubMed

Chiara, Matteo; Gioiosa, Silvia; Chillemi, Giovanni; D'Antonio, Mattia; Flati, Tiziano; Picardi, Ernesto; Zambelli, Federico; Horner, David Stephen; Pesole, Graziano; Castrignanò, Tiziana

2018-02-05

The advent and ongoing development of next generation sequencing technologies (NGS) has led to a rapid increase in the rate of human genome re-sequencing data, paving the way for personalized genomics and precision medicine. The body of genome resequencing data is progressively increasing underlining the need for accurate and time-effective bioinformatics systems for genotyping - a crucial prerequisite for identification of candidate causal mutations in diagnostic screens. Here we present CoVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation. Extensive tests on a gold standard benchmark data-set -the NA12878 Illumina platinum genome- confirm that call-sets based on our consensus strategy are completely in line with those attained by similar command line based approaches, and far more accurate than call-sets from any individual tool. Importantly our system exhibits better sensitivity and higher specificity than equivalent commercial software. CoVaCS offers optimized pipelines integrating state of the art tools for variant calling and annotation for whole genome sequencing (WGS), whole-exome sequencing (WES) and target-gene sequencing (TGS) data. The system is currently hosted at Cineca, and offers the speed of a HPC computing facility, a crucial consideration when large numbers of samples must be analysed. Importantly, all the analyses are performed automatically allowing high reproducibility of the results. As such, we believe that CoVaCS can be a valuable tool for the analysis of human genome resequencing studies. CoVaCS is available at: https://bioinformatics.cineca.it/covacs .

Investigation of modulation parameters in multiplexing gas chromatography.

PubMed

Trapp, Oliver

2010-10-22

Combination of information technology and separation sciences opens a new avenue to achieve high sample throughputs and therefore is of great interest to bypass bottlenecks in catalyst screening of parallelized reactors or using multitier well plates in reaction optimization. Multiplexing gas chromatography utilizes pseudo-random injection sequences derived from Hadamard matrices to perform rapid sample injections which gives a convoluted chromatogram containing the information of a single sample or of several samples with similar analyte composition. The conventional chromatogram is obtained by application of the Hadamard transform using the known injection sequence or in case of several samples an averaged transformed chromatogram is obtained which can be used in a Gauss-Jordan deconvolution procedure to obtain all single chromatograms of the individual samples. The performance of such a system depends on the modulation precision and on the parameters, e.g. the sequence length and modulation interval. Here we demonstrate the effects of the sequence length and modulation interval on the deconvoluted chromatogram, peak shapes and peak integration for sequences between 9-bit (511 elements) and 13-bit (8191 elements) and modulation intervals Δt between 5 s and 500 ms using a mixture of five components. It could be demonstrated that even for high-speed modulation at time intervals of 500 ms the chromatographic information is very well preserved and that the separation efficiency can be improved by very narrow sample injections. Furthermore this study shows that the relative peak areas in multiplexed chromatograms do not deviate from conventionally recorded chromatograms. Copyright © 2010 Elsevier B.V. All rights reserved.

BigQ: a NoSQL based framework to handle genomic variants in i2b2.

PubMed

Gabetta, Matteo; Limongelli, Ivan; Rizzo, Ettore; Riva, Alberto; Segagni, Daniele; Bellazzi, Riccardo

2015-12-29

Precision medicine requires the tight integration of clinical and molecular data. To this end, it is mandatory to define proper technological solutions able to manage the overwhelming amount of high throughput genomic data needed to test associations between genomic signatures and human phenotypes. The i2b2 Center (Informatics for Integrating Biology and the Bedside) has developed a widely internationally adopted framework to use existing clinical data for discovery research that can help the definition of precision medicine interventions when coupled with genetic data. i2b2 can be significantly advanced by designing efficient management solutions of Next Generation Sequencing data. We developed BigQ, an extension of the i2b2 framework, which integrates patient clinical phenotypes with genomic variant profiles generated by Next Generation Sequencing. A visual programming i2b2 plugin allows retrieving variants belonging to the patients in a cohort by applying filters on genomic variant annotations. We report an evaluation of the query performance of our system on more than 11 million variants, showing that the implemented solution scales linearly in terms of query time and disk space with the number of variants. In this paper we describe a new i2b2 web service composed of an efficient and scalable document-based database that manages annotations of genomic variants and of a visual programming plug-in designed to dynamically perform queries on clinical and genetic data. The system therefore allows managing the fast growing volume of genomic variants and can be used to integrate heterogeneous genomic annotations.

A feasible high spatiotemporal resolution breast DCE-MRI protocol for clinical settings.

PubMed

Tudorica, Luminita A; Oh, Karen Y; Roy, Nicole; Kettler, Mark D; Chen, Yiyi; Hemmingson, Stephanie L; Afzal, Aneela; Grinstead, John W; Laub, Gerhard; Li, Xin; Huang, Wei

2012-11-01

Three dimensional bilateral imaging is the standard for most clinical breast dynamic contrast-enhanced (DCE) MRI protocols. Because of high spatial resolution (sRes) requirement, the typical 1-2 min temporal resolution (tRes) afforded by a conventional full-k-space-sampling gradient echo (GRE) sequence precludes meaningful and accurate pharmacokinetic analysis of DCE time-course data. The commercially available, GRE-based, k-space undersampling and data sharing TWIST (time-resolved angiography with stochastic trajectories) sequence was used in this study to perform DCE-MRI exams on thirty one patients (with 36 suspicious breast lesions) before their biopsies. The TWIST DCE-MRI was immediately followed by a single-frame conventional GRE acquisition. Blinded from each other, three radiologist readers assessed agreements in multiple lesion morphology categories between the last set of TWIST DCE images and the conventional GRE images. Fleiss' κ test was used to evaluate inter-reader agreement. The TWIST DCE time-course data were subjected to quantitative pharmacokinetic analyses. With a four-channel phased-array breast coil, the TWIST sequence produced DCE images with 20 s or less tRes and ~ 1.0×1.0×1.4 mm(3) sRes. There were no significant differences in signal-to-noise (P=.45) and contrast-to-noise (P=.51) ratios between the TWIST and conventional GRE images. The agreements in morphology evaluations between the two image sets were excellent with the intra-reader agreement ranging from 79% for mass margin to 100% for mammographic density and the inter-reader κ value ranging from 0.54 (P<.0001) for lesion size to 1.00 (P<.0001) for background parenchymal enhancement. Quantitative analyses of the DCE time-course data provided higher breast cancer diagnostic accuracy (91% specificity at 100% sensitivity) than the current clinical practice of morphology and qualitative kinetics assessments. The TWIST sequence may be used in clinical settings to acquire high spatiotemporal resolution breast DCE-MRI images for both precise lesion morphology characterization and accurate pharmacokinetic analysis. Copyright © 2012 Elsevier Inc. All rights reserved.

Rupture processes of the 2013-2014 Minab earthquake sequence, Iran

NASA Astrophysics Data System (ADS)

Kintner, Jonas A.; Ammon, Charles J.; Cleveland, K. Michael; Herman, Matthew

2018-06-01

We constrain epicentroid locations, magnitudes and depths of moderate-magnitude earthquakes in the 2013-2014 Minab sequence using surface-wave cross-correlations, surface-wave spectra and teleseismic body-wave modelling. We estimate precise relative locations of 54 Mw ≥ 3.8 earthquakes using 48 409 teleseismic, intermediate-period Rayleigh and Love-wave cross-correlation measurements. To reduce significant regional biases in our relative locations, we shift the relative locations to align the Mw 6.2 main-shock centroid to a location derived from an independent InSAR fault model. Our relocations suggest that the events lie along a roughly east-west trend that is consistent with the faulting geometry in the GCMT catalogue. The results support previous studies that suggest the sequence consists of left-lateral strain release, but better defines the main-shock fault length and shows that most of the Mw ≥ 5.0 aftershocks occurred on one or two similarly oriented structures. We also show that aftershock activity migrated westwards along strike, away from the main shock, suggesting that Coulomb stress transfer played a role in the fault failure. We estimate the magnitudes of the relocated events using surface-wave cross-correlation amplitudes and find good agreement with the GCMT moment magnitudes for the larger events and underestimation of small-event size by catalogue MS. In addition to clarifying details of the Minab sequence, the results demonstrate that even in tectonically complex regions, relative relocation using teleseismic surface waves greatly improves the precision of relative earthquake epicentroid locations and can facilitate detailed tectonic analyses of remote earthquake sequences.

Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

PubMed Central

Blount, Benjamin A.; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions. PMID:22442681

Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology.

PubMed

Blount, Benjamin A; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex "multi-wire" logic functions.

SparkSeq: fast, scalable and cloud-ready tool for the interactive genomic data analysis with nucleotide precision.

PubMed

Wiewiórka, Marek S; Messina, Antonio; Pacholewska, Alicja; Maffioletti, Sergio; Gawrysiak, Piotr; Okoniewski, Michał J

2014-09-15

Many time-consuming analyses of next -: generation sequencing data can be addressed with modern cloud computing. The Apache Hadoop-based solutions have become popular in genomics BECAUSE OF: their scalability in a cloud infrastructure. So far, most of these tools have been used for batch data processing rather than interactive data querying. The SparkSeq software has been created to take advantage of a new MapReduce framework, Apache Spark, for next-generation sequencing data. SparkSeq is a general-purpose, flexible and easily extendable library for genomic cloud computing. It can be used to build genomic analysis pipelines in Scala and run them in an interactive way. SparkSeq opens up the possibility of customized ad hoc secondary analyses and iterative machine learning algorithms. This article demonstrates its scalability and overall fast performance by running the analyses of sequencing datasets. Tests of SparkSeq also prove that the use of cache and HDFS block size can be tuned for the optimal performance on multiple worker nodes. Available under open source Apache 2.0 license: https://bitbucket.org/mwiewiorka/sparkseq/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Classification of motor intent in transradial amputees using sonomyography and spatio-temporal image analysis

NASA Astrophysics Data System (ADS)

Hariharan, Harishwaran; Aklaghi, Nima; Baker, Clayton A.; Rangwala, Huzefa; Kosecka, Jana; Sikdar, Siddhartha

2016-04-01

In spite of major advances in biomechanical design of upper extremity prosthetics, these devices continue to lack intuitive control. Conventional myoelectric control strategies typically utilize electromyography (EMG) signal amplitude sensed from forearm muscles. EMG has limited specificity in resolving deep muscle activity and poor signal-to-noise ratio. We have been investigating alternative control strategies that rely on real-time ultrasound imaging that can overcome many of the limitations of EMG. In this work, we present an ultrasound image sequence classification method that utilizes spatiotemporal features to describe muscle activity and classify motor intent. Ultrasound images of the forearm muscles were obtained from able-bodied subjects and a trans-radial amputee while they attempted different hand movements. A grid-based approach is used to test the feasibility of using spatio-temporal features by classifying hand motions performed by the subjects. Using the leave-one-out cross validation on image sequences acquired from able-bodied subjects, we observe that the grid-based approach is able to discern four hand motions with 95.31% accuracy. In case of the trans-radial amputee, we are able to discern three hand motions with 80% accuracy. In a second set of experiments, we study classification accuracy by extracting spatio-temporal sub-sequences the depict activity due to the motion of local anatomical interfaces. Short time and space limited cuboidal sequences are initially extracted and assigned an optical flow behavior label, based on a response function. The image space is clustered based on the location of cuboids and features calculated from the cuboids in each cluster. Using sequences of known motions, we extract feature vectors that describe said motion. A K-nearest neighbor classifier is designed for classification experiments. Using the leave-one-out cross validation on image sequences for an amputee subject, we demonstrate that the classifier is able to discern three important hand motions with an accuracy of 93.33% accuracy, 91-100% precision and 80-100% recall rate. We anticipate that ultrasound imaging based methods will address some limitations of conventional myoelectric sensing, while adding advantages inherent to ultrasound imaging.

The 2011 Hawthorne, Nevada, Earthquake Sequence; Shallow Normal Faulting

NASA Astrophysics Data System (ADS)

Smith, K. D.; Johnson, C.; Davies, J. A.; Agbaje, T.; Knezevic Antonijevic, S.; Kent, G.

2011-12-01

An energetic sequence of shallow earthquakes that began in early March 2011 in western Nevada, near the community of Hawthorne, has slowly decreased in intensity through mid-2011. To date about 1300 reviewed earthquake locations have been compiled; we have computed moment tensors for the larger earthquakes and have developed a set of high-precision locations for all reviewed events. The sequence to date has included over 50 earthquakes ML 3 and larger with the largest at Mw 4.6. Three 6-channel portable stations configured with broadband sensors and accelerometers were installed by April 20. Data from the portable instruments is telemetered through NSL's microwave backbone to Reno where it is integrated with regional network data for real-time notifications, ShakeMaps, and routine event analysis. The data is provided in real-time to NEIC, CISN and the IRIS DMC. The sequence is located in a remote area about 15-20 km southwest of Hawthorne in the footwall block of the Wassuk Range fault system. An initial concern was that the sequence might be associated with volcanic processes due to the proximity of late Quaternary volcanic flows; there have been no volcanic signatures observed in near source seismograms. An additional concern, as the sequence has proceeded, was a clear progression eastward toward the Wassuk Range front fault. The east dipping range bounding fault is capable of M 7+ events, and poses a significant hazard to the community of Hawthorne and local military facilities. The Hawthorne Army Depot is an ordinance storage facility and the nation's storage site for surplus mercury. The sequence is within what has been termed the 'Mina Deflection' of the Central Walker Lane Belt. Faulting along the Whiskey Flat section of the Wassuk front fault would be primarily down-to-the-east, with an E-W extension direction; moment tensors for the 2011 earthquake show a range of extension directions from E-W to NW-SE, suggesting a possible dextral component to the Wassuk Range front fault at this latitude. At least two faults have been imaged within the sequence; these structures are at shallow depth (3-6 km), strike NE, and dip ~NW. Prior to temporary station installation event depths were poorly constrained, with the nearest network station 25 km from the source area. Early sequence moment tensor solutions show depths are on the order of 2-6 km and locations using the near source stations also confirm the shallow depths of the Hawthorne sequence. S-P times of 0.5 sec and less have been observed on a near-source station, illustrating extremely shallow source depths for some events. Along with the 2011 Hawthorne activity, very shallow depths in Nevada have been observed from near source stations in the 2008 west Reno earthquake sequence (primarily strike-slip faulting; main shock Mw 5.0) and the 1993 Rock Valley sequence in southern NNSS (strike-slip faulting; main shock Mw 4.0). These shallow sequences tend to include high rates of low magnitude earthquakes continuing over several months duration.

Signatures of progenitors of Type Ia supernovae

NASA Astrophysics Data System (ADS)

Hoeflich, P.; Chakraborty, S.; Comaskey, W.; Fisher, A.; Hristov, B.; Collins, D.; Diamond, T. R.; Dragulin, P.; Hsiao, E. Y.; Sadler, B.

Thermonuclear Supernovae (SNe Ia) are one of the building blocks of modern cosmology and laboratories for the explosion physics of White Dwarf star/s (WD) in close binary systems. The second star may be a WD (double degenerate systems, DD), or a non-degenerated star (SD) with a main sequence star, red giant or a helium star as companion \\citep{branch95,nomoto03,wang2012}. Light curves and spectra of the explosion look similar because a 'stellar amnesia' \\citep{h06}. Basic nuclear physics determines the progenitor structure and the explosion physics, breaking the link between progenitor evolution, and the explosion, resulting in three main classes of explosion scenarios: a) dynamical merging of two WD and a heating on time scales of seconds \\citep{webbink84,isern11}, b) surface helium detonations on top of a WD which ignite the central C/O by a detonation wave traveling inwards \\citep{n82,hk96,Kromer2010}; c) compressional heating in an accreting WD approaching the Chandrasekar mass on time of up to 108 years which may originated from SD and DD systems \\citep{WI73,Piersanti2004}. Simulations of the explosions depend on the inital conditions at the onset of the explosions, namely the mass and angular momentum of the WD(s). For all scenarios, diversity in SNe Ia must be expected because the WD originates from a range of Main Sequence masses (MMS < 8 M_⊙) and metallicities Z. Moreover, there is growing evidence that magnetic fields B may have to be added to the 'mix'. Only with recent advances in observations ranging from X-ray to radio, high precision spectroscopy, polarimetry and photometry and in the time-domain astronomy we obtain constraints for progenitor, on the explosion scenarios and links emerge between the progenitors and their environment with LCs and spectral signatures needed for high precision cosmology. It is too early to give final answers but we present our personal view. We will give some examples from the theory point of view and discuss future prospects with upcoming ground based, ELT, GMT and space based such as JWST, Euclide and WFIRST instruments.

RetroTector online, a rational tool for analysis of retroviral elements in small and medium size vertebrate genomic sequences

PubMed Central

Sperber, Göran; Lövgren, Anders; Eriksson, Nils-Einar; Benachenhou, Farid; Blomberg, Jonas

2009-01-01

Background The rapid accumulation of genomic information in databases necessitates rapid and specific algorithms for extracting biologically meaningful information. More or less complete retroviral sequences, also called proviral or endogenous retroviral sequences; ERVs, constitutes at least 5% of vertebrate genomes. After infecting the host, these retroviruses have integrated in germ line cells, and have then been carried in genomes for at least several 100 million years. A better understanding of structure and function of these sequences can have profound biological and medical consequences. Methods RetroTector© (ReTe) is a platform-independent Java program for identification and characterization of proviral sequences in vertebrate genomes. The full ReTe requires a local installation with a MySQL database. Although not overly complicated, the installation may take some time. A "light" version of ReTe, (RetroTector online; ROL) which does not require specific installation procedures is provided, via the World Wide Web. Results ROL was implemented under the Batchelor web interface (A Lövgren et al). It allows both GenBank accession number, file and FASTA cut-and-paste admission of sequences (5 to 10 000 kilobases). Up to ten submissions can be done simultaneously, allowing batch analysis of <= 100 Megabases. Jobs are shown in an IP-number specific list. Results are text files, and can be viewed with the program, RetroTectorViewer.jar (at the same site), which has the full graphical capabilities of the basic ReTe program. A detailed analysis of any retroviral sequences found in the submitted sequence is graphically presented, exportable in standard formats. With the current server, a complete analysis of a 1 Megabase sequence is complete in 10 minutes. It is possible to mask nonretroviral repetitive sequences in the submitted sequence, using host genome specific "brooms", which increase specificity. Discussion Proviral sequences can be hard to recognize, especially if the integration occurred many million years ago. Precise delineation of LTR, gag, pro, pol and env can be difficult, requiring manual work. ROL is a way of simplifying these tasks. Conclusion ROL provides 1. annotation and presentation of known retroviral sequences, 2. detection of proviral chains in unknown genomic sequences, with up to 100 Mbase per submission. PMID:19534753

RetroTector online, a rational tool for analysis of retroviral elements in small and medium size vertebrate genomic sequences.

PubMed

Sperber, Göran; Lövgren, Anders; Eriksson, Nils-Einar; Benachenhou, Farid; Blomberg, Jonas

2009-06-16

The rapid accumulation of genomic information in databases necessitates rapid and specific algorithms for extracting biologically meaningful information. More or less complete retroviral sequences, also called proviral or endogenous retroviral sequences; ERVs, constitutes at least 5% of vertebrate genomes. After infecting the host, these retroviruses have integrated in germ line cells, and have then been carried in genomes for at least several 100 million years. A better understanding of structure and function of these sequences can have profound biological and medical consequences. RetroTector (ReTe) is a platform-independent Java program for identification and characterization of proviral sequences in vertebrate genomes. The full ReTe requires a local installation with a MySQL database. Although not overly complicated, the installation may take some time. A "light" version of ReTe, (RetroTector online; ROL) which does not require specific installation procedures is provided, via the World Wide Web. ROL http://www.fysiologi.neuro.uu.se/jbgs/ was implemented under the Batchelor web interface (A Lövgren et al). It allows both GenBank accession number, file and FASTA cut-and-paste admission of sequences (5 to 10,000 kilobases). Up to ten submissions can be done simultaneously, allowing batch analysis of

Proportional spike-timing precision and firing reliability underlie efficient temporal processing of periodicity and envelope shape cues

PubMed Central

Zheng, Y.

2013-01-01

Temporal sound cues are essential for sound recognition, pitch, rhythm, and timbre perception, yet how auditory neurons encode such cues is subject of ongoing debate. Rate coding theories propose that temporal sound features are represented by rate tuned modulation filters. However, overwhelming evidence also suggests that precise spike timing is an essential attribute of the neural code. Here we demonstrate that single neurons in the auditory midbrain employ a proportional code in which spike-timing precision and firing reliability covary with the sound envelope cues to provide an efficient representation of the stimulus. Spike-timing precision varied systematically with the timescale and shape of the sound envelope and yet was largely independent of the sound modulation frequency, a prominent cue for pitch. In contrast, spike-count reliability was strongly affected by the modulation frequency. Spike-timing precision extends from sub-millisecond for brief transient sounds up to tens of milliseconds for sounds with slow-varying envelope. Information theoretic analysis further confirms that spike-timing precision depends strongly on the sound envelope shape, while firing reliability was strongly affected by the sound modulation frequency. Both the information efficiency and total information were limited by the firing reliability and spike-timing precision in a manner that reflected the sound structure. This result supports a temporal coding strategy in the auditory midbrain where proportional changes in spike-timing precision and firing reliability can efficiently signal shape and periodicity temporal cues. PMID:23636724

Proceedings of the Fourth Precise Time and Time Interval Planning Meeting

NASA Technical Reports Server (NTRS)

Acrivos, H. N. (Compiler); Wardrip, S. C. (Compiler)

1972-01-01

The proceedings of a conference on Precise Time and Time Interval Planning are presented. The subjects discussed include the following: (1) satellite timing techniques, precision frequency sources, and very long baseline interferometry, (2) frequency stabilities and communications, and (3) very low frequency and ultrahigh frequency propagation and use. Emphasis is placed on the accuracy of time discrimination obtained with time measuring equipment and specific applications of time measurement to military operations and civilian research projects.

Finger Forces in Clarinet Playing

PubMed Central

Hofmann, Alex; Goebl, Werner

2016-01-01

Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17) and professional clarinettists (N = 6) were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 × 2 × 2 design (register: low–high; tempo: slow–fast, dynamics: soft–loud). There was an additional condition controlled by the experimenter, which determined the expression levels (low–high) of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions). The melody was performed in three tempo conditions (slow, medium, fast) in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (Fmean) and peak force (Fmax) were calculated. The overall finger forces were low (Fmean = 1.17 N, Fmax = 3.05 N) compared to those on other musical instruments (e.g., guitar). Participants applied the largest finger forces during the high expression level performance conditions (Fmean = 1.21 N). For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (Fmean = 0.54 N). Such sensor instruments provide useful insights into player-instrument interactions and can also be used in the future to give feedback to students in various learning and practising situations. PMID:27540367

AN ASTEROID BELT INTERPRETATION FOR THE TIMING VARIATIONS OF THE MILLISECOND PULSAR B1937+21

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

Shannon, R. M.; Cordes, J. M.; Metcalfe, T. S.

Pulsar timing observations have revealed companions to neutron stars that include other neutron stars, white dwarfs, main-sequence stars, and planets. We demonstrate that the correlated and apparently stochastic residual times of arrival from the millisecond pulsar B1937+21 are consistent with the signature of an asteroid belt having a total mass {approx}< 0.05 M{sub Circled-Plus }. Unlike the solar system's asteroid belt, the best fit pulsar asteroid belt extends over a wide range of radii, consistent with the absence of any shepherding companions. We suggest that any pulsar that has undergone accretion-driven spin-up and subsequently evaporated its companion may harbor orbitingmore » asteroid mass objects. The resulting timing variations may fundamentally limit the timing precision of some of the other millisecond pulsars. Observational tests of the asteroid belt model include identifying periodicities from individual asteroids, which are difficult; testing for statistical stationarity, which becomes possible when observations are conducted over a longer observing span; and searching for reflected radio emission.« less

Inferring the demographic history from DNA sequences: An importance sampling approach based on non-homogeneous processes.

PubMed

Ait Kaci Azzou, S; Larribe, F; Froda, S

2016-10-01

In Ait Kaci Azzou et al. (2015) we introduced an Importance Sampling (IS) approach for estimating the demographic history of a sample of DNA sequences, the skywis plot. More precisely, we proposed a new nonparametric estimate of a population size that changes over time. We showed on simulated data that the skywis plot can work well in typical situations where the effective population size does not undergo very steep changes. In this paper, we introduce an iterative procedure which extends the previous method and gives good estimates under such rapid variations. In the iterative calibrated skywis plot we approximate the effective population size by a piecewise constant function, whose values are re-estimated at each step. These piecewise constant functions are used to generate the waiting times of non homogeneous Poisson processes related to a coalescent process with mutation under a variable population size model. Moreover, the present IS procedure is based on a modified version of the Stephens and Donnelly (2000) proposal distribution. Finally, we apply the iterative calibrated skywis plot method to a simulated data set from a rapidly expanding exponential model, and we show that the method based on this new IS strategy correctly reconstructs the demographic history. Copyright © 2016. Published by Elsevier Inc.

Object tracking with adaptive HOG detector and adaptive Rao-Blackwellised particle filter

NASA Astrophysics Data System (ADS)

Rosa, Stefano; Paleari, Marco; Ariano, Paolo; Bona, Basilio

2012-01-01

Scenarios for a manned mission to the Moon or Mars call for astronaut teams to be accompanied by semiautonomous robots. A prerequisite for human-robot interaction is the capability of successfully tracking humans and objects in the environment. In this paper we present a system for real-time visual object tracking in 2D images for mobile robotic systems. The proposed algorithm is able to specialize to individual objects and to adapt to substantial changes in illumination and object appearance during tracking. The algorithm is composed by two main blocks: a detector based on Histogram of Oriented Gradient (HOG) descriptors and linear Support Vector Machines (SVM), and a tracker which is implemented by an adaptive Rao-Blackwellised particle filter (RBPF). The SVM is re-trained online on new samples taken from previous predicted positions. We use the effective sample size to decide when the classifier needs to be re-trained. Position hypotheses for the tracked object are the result of a clustering procedure applied on the set of particles. The algorithm has been tested on challenging video sequences presenting strong changes in object appearance, illumination, and occlusion. Experimental tests show that the presented method is able to achieve near real-time performances with a precision of about 7 pixels on standard video sequences of dimensions 320 × 240.

Fractionating nonword repetition: The contributions of short-term memory and oromotor praxis are different

PubMed Central

Alcock, Katherine J.; Carey, Daniel; Bergström, Lina; Karmiloff-Smith, Annette; Dick, Frederic

2017-01-01

The ability to reproduce novel words is a sensitive marker of language impairment across a variety of developmental disorders. Nonword repetition tasks are thought to reflect phonological short-term memory skills. Yet, when children hear and then utter a word for the first time, they must transform a novel speech signal into a series of coordinated, precisely timed oral movements. Little is known about how children’s oromotor speed, planning and co-ordination abilities might influence their ability to repeat novel nonwords, beyond the influence of higher-level cognitive and linguistic skills. In the present study, we tested 35 typically developing children between the ages of 5−8 years on measures of nonword repetition, digit span, memory for non-verbal sequences, reading fluency, oromotor praxis, and oral diadochokinesis. We found that oromotor praxis uniquely predicted nonword repetition ability in school-age children, and that the variance it accounted for was additional to that of digit span, memory for non-verbal sequences, articulatory rate (measured by oral diadochokinesis) as well as reading fluency. We conclude that the ability to compute and execute novel sensorimotor transformations affects the production of novel words. These results have important implications for understanding motor/language relations in neurodevelopmental disorders. PMID:28704379

Specific contributions of basal ganglia and cerebellum to the neural tracking of rhythm.

PubMed

Nozaradan, Sylvie; Schwartze, Michael; Obermeier, Christian; Kotz, Sonja A

2017-10-01

How specific brain networks track rhythmic sensory input over time remains a challenge in neuroimaging work. Here we show that subcortical areas, namely the basal ganglia and the cerebellum, specifically contribute to the neural tracking of rhythm. We tested patients with focal lesions in either of these areas and healthy controls by means of electroencephalography (EEG) while they listened to rhythmic sequences known to induce selective neural tracking at a frequency corresponding to the most-often perceived pulse-like beat. Both patients and controls displayed neural responses to the rhythmic sequences. However, these response patterns were different across groups, with patients showing reduced tracking at beat frequency, especially for the more challenging rhythms. In the cerebellar patients, this effect was specific to the rhythm played at a fast tempo, which places high demands on the temporally precise encoding of events. In contrast, basal ganglia patients showed more heterogeneous responses at beat frequency specifically for the most complex rhythm, which requires more internal generation of the beat. These findings provide electrophysiological evidence that these subcortical structures selectively shape the neural representation of rhythm. Moreover, they suggest that the processing of rhythmic auditory input relies on an extended cortico-subcortico-cortical functional network providing specific timing and entrainment sensitivities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Data-Aware Retrodiction for Asynchronous Harmonic Measurement in a Cyber-Physical Energy System.

PubMed

Liu, Youda; Wang, Xue; Liu, Yanchi; Cui, Sujin

2016-08-18

Cyber-physical energy systems provide a networked solution for safety, reliability and efficiency problems in smart grids. On the demand side, the secure and trustworthy energy supply requires real-time supervising and online power quality assessing. Harmonics measurement is necessary in power quality evaluation. However, under the large-scale distributed metering architecture, harmonic measurement faces the out-of-sequence measurement (OOSM) problem, which is the result of latencies in sensing or the communication process and brings deviations in data fusion. This paper depicts a distributed measurement network for large-scale asynchronous harmonic analysis and exploits a nonlinear autoregressive model with exogenous inputs (NARX) network to reorder the out-of-sequence measuring data. The NARX network gets the characteristics of the electrical harmonics from practical data rather than the kinematic equations. Thus, the data-aware network approximates the behavior of the practical electrical parameter with real-time data and improves the retrodiction accuracy. Theoretical analysis demonstrates that the data-aware method maintains a reasonable consumption of computing resources. Experiments on a practical testbed of a cyber-physical system are implemented, and harmonic measurement and analysis accuracy are adopted to evaluate the measuring mechanism under a distributed metering network. Results demonstrate an improvement of the harmonics analysis precision and validate the asynchronous measuring method in cyber-physical energy systems.

Network Design in Close-Range Photogrammetry with Short Baseline Images

NASA Astrophysics Data System (ADS)

Barazzetti, L.

2017-08-01

The avaibility of automated software for image-based 3D modelling has changed the way people acquire images for photogrammetric applications. Short baseline images are required to match image points with SIFT-like algorithms, obtaining more images than those necessary for "old fashioned" photogrammetric projects based on manual measurements. This paper describes some considerations on network design for short baseline image sequences, especially on precision and reliability of bundle adjustment. Simulated results reveal that the large number of 3D points used for image orientation has very limited impact on network precision.

Design and Validation of CRISPR/Cas9 Systems for Targeted Gene Modification in Induced Pluripotent Stem Cells.

PubMed

Lee, Ciaran M; Zhu, Haibao; Davis, Timothy H; Deshmukh, Harshahardhan; Bao, Gang

2017-01-01

The CRISPR/Cas9 system is a powerful tool for precision genome editing. The ability to accurately modify genomic DNA in situ with single nucleotide precision opens up new possibilities for not only basic research but also biotechnology applications and clinical translation. In this chapter, we outline the procedures for design, screening, and validation of CRISPR/Cas9 systems for targeted modification of coding sequences in the human genome and how to perform genome editing in induced pluripotent stem cells with high efficiency and specificity.

Proceedings of the 7th Annual Precise Time and Time Interval (PTTI) Applications and Planning Meeting

NASA Technical Reports Server (NTRS)

1975-01-01

The Proceedings contain the papers presented at the Seventh Annual Precise Time and Time Interval (PTTI) Applications and Planning Meeting and the edited record of the discussion period following each paper. This meeting provided a forum to promote more effective, efficient, economical and skillful applications of PTTI technology to the many problem areas to which PTTI offers solutions. Specifically the purpose of the meeting is to: disseminate, coordinate, and exchange practical information associated with precise time and frequency; acquaint systems engineers, technicians and managers with precise time and frequency technology and its applications; and review present and future requirements for PTTI.

High-precision U-Pb zircon geochronological constraints on the End-Triassic Mass Extinction, the late Triassic Astronomical Time Scale and geochemical evolution of CAMP magmatism

NASA Astrophysics Data System (ADS)

Blackburn, T. J.; Olsen, P. E.; Bowring, S. A.; McLean, N. M.; Kent, D. V.; Puffer, J. H.; McHone, G.; Rasbury, T.

2012-12-01

Mass extinction events that punctuate Earth's history have had a large influence on the evolution, diversity and composition of our planet's biosphere. The approximate temporal coincidence between the five major extinction events over the last 542 million years and the eruption of Large Igneous Provinces (LIPs) has led to the speculation that climate and environmental perturbations generated by the emplacement of a large volume of magma in a short period of time triggered each global biologic crisis. Establishing a causal link between extinction and the onset and tempo of LIP eruption has proved difficult because of the geographic separation between LIP volcanic deposits and stratigraphic sequences preserving evidence of the extinction. In most cases, the uncertainties on available radioisotopic dates used to correlate between geographically separated study areas often exceed the duration of both the extinction interval and LIP volcanism by an order of magnitude. The "end-Triassic extinction" (ETE) is one of the "big five" and is characterized by the disappearance of several terrestrial and marine species and dominance of Dinosaurs for the next 134 million years. Speculation on the cause has centered on massive climate perturbations thought to accompany the eruption of flood basalts related to the Central Atlantic Magmatic Province (CAMP), the most aerially extensive and volumetrically one of the largest LIPs on Earth. Despite an approximate temporal coincidence between extinction and volcanism, there lacks evidence placing the eruption of CAMP prior to or at the initiation of the extinction. Estimates of the timing and/or duration of CAMP volcanism provided by astrochronology and Ar-Ar geochronology differ by an order of magnitude, precluding high-precision tests of the relationship between LIP volcanism and the mass extinction, the causes of which are dependent upon the rate of magma eruption. Here we present high precision zircon U-Pb ID-TIMS geochronologic data for eight CAMP flows and sills from the eastern U.S. and Morocco. These data are used first to independently test the astronomically calibrated time scale and sediment accumulation rates within the Triassic-Jurassic rift basins along the eastern North America. The U-Pb, paleontological, magnetostratigraphic and astronomical data are combined to constrain the onset and duration of the CAMP and clarify the temporal relationship between the CAMP and the ETE. The dataset together allows more precise estimates of eruptive volume per unit time, a requirement for rigorous evaluation of climate-driven models for the extinction.

Compressed normalized block difference for object tracking

NASA Astrophysics Data System (ADS)

Gao, Yun; Zhang, Dengzhuo; Cai, Donglan; Zhou, Hao; Lan, Ge

2018-04-01

Feature extraction is very important for robust and real-time tracking. Compressive sensing provided a technical support for real-time feature extraction. However, all existing compressive tracking were based on compressed Haar-like feature, and how to compress many more excellent high-dimensional features is worth researching. In this paper, a novel compressed normalized block difference feature (CNBD) was proposed. For resisting noise effectively in a highdimensional normalized pixel difference feature (NPD), a normalized block difference feature extends two pixels in the original formula of NPD to two blocks. A CNBD feature can be obtained by compressing a normalized block difference feature based on compressive sensing theory, with the sparse random Gaussian matrix as the measurement matrix. The comparative experiments of 7 trackers on 20 challenging sequences showed that the tracker based on CNBD feature can perform better than other trackers, especially than FCT tracker based on compressed Haar-like feature, in terms of AUC, SR and Precision.

Domain decomposition methods for systems of conservation laws: Spectral collocation approximations

NASA Technical Reports Server (NTRS)

Quarteroni, Alfio

1989-01-01

Hyperbolic systems of conversation laws are considered which are discretized in space by spectral collocation methods and advanced in time by finite difference schemes. At any time-level a domain deposition method based on an iteration by subdomain procedure was introduced yielding at each step a sequence of independent subproblems (one for each subdomain) that can be solved simultaneously. The method is set for a general nonlinear problem in several space variables. The convergence analysis, however, is carried out only for a linear one-dimensional system with continuous solutions. A precise form of the error reduction factor at each iteration is derived. Although the method is applied here to the case of spectral collocation approximation only, the idea is fairly general and can be used in a different context as well. For instance, its application to space discretization by finite differences is straight forward.

RepeatsDB-lite: a web server for unit annotation of tandem repeat proteins.

PubMed

Hirsh, Layla; Paladin, Lisanna; Piovesan, Damiano; Tosatto, Silvio C E

2018-05-09

RepeatsDB-lite (http://protein.bio.unipd.it/repeatsdb-lite) is a web server for the prediction of repetitive structural elements and units in tandem repeat (TR) proteins. TRs are a widespread but poorly annotated class of non-globular proteins carrying heterogeneous functions. RepeatsDB-lite extends the prediction to all TR types and strongly improves the performance both in terms of computational time and accuracy over previous methods, with precision above 95% for solenoid structures. The algorithm exploits an improved TR unit library derived from the RepeatsDB database to perform an iterative structural search and assignment. The web interface provides tools for analyzing the evolutionary relationships between units and manually refine the prediction by changing unit positions and protein classification. An all-against-all structure-based sequence similarity matrix is calculated and visualized in real-time for every user edit. Reviewed predictions can be submitted to RepeatsDB for review and inclusion.

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

Miall, A.D.

The basic premise of the recent Exxon cycle chart, that there exists a globally correlatable suite of third-order eustatic cycles, remains unproven. Many of the tests of this premise are based on circular reasoning. The implied precision of the Exxon global cycle chart is not supportable, because it is greater than that of the best available chronostratigraphic techniques, such as those used to construct the global standard time scale. Correlations of new stratigraphic sections with the Exxon chart will almost always succeed, because there are so many Exxon sequence-boundary events from which to choose. This is demonstrated by the usemore » of four synthetic sections constructed from tables of random numbers. A minimum of 77% successful correlations of random events with the Exxon chart was achieved. The existing cycle chart represents an amalgam of regional and local tectonic events and probably also includes unrecognized miscorrelations. It is of questionable value as an independent standard of geologic time.« less

Three-dimensional face pose detection and tracking using monocular videos: tool and application.

PubMed

Dornaika, Fadi; Raducanu, Bogdan

2009-08-01

Recently, we have proposed a real-time tracker that simultaneously tracks the 3-D head pose and facial actions in monocular video sequences that can be provided by low quality cameras. This paper has two main contributions. First, we propose an automatic 3-D face pose initialization scheme for the real-time tracker by adopting a 2-D face detector and an eigenface system. Second, we use the proposed methods-the initialization and tracking-for enhancing the human-machine interaction functionality of an AIBO robot. More precisely, we show how the orientation of the robot's camera (or any active vision system) can be controlled through the estimation of the user's head pose. Applications based on head-pose imitation such as telepresence, virtual reality, and video games can directly exploit the proposed techniques. Experiments on real videos confirm the robustness and usefulness of the proposed methods.

The ALFA (Activity Log Files Aggregation) toolkit: a method for precise observation of the consultation.

PubMed

de Lusignan, Simon; Kumarapeli, Pushpa; Chan, Tom; Pflug, Bernhard; van Vlymen, Jeremy; Jones, Beryl; Freeman, George K

2008-09-08

There is a lack of tools to evaluate and compare Electronic patient record (EPR) systems to inform a rational choice or development agenda. To develop a tool kit to measure the impact of different EPR system features on the consultation. We first developed a specification to overcome the limitations of existing methods. We divided this into work packages: (1) developing a method to display multichannel video of the consultation; (2) code and measure activities, including computer use and verbal interactions; (3) automate the capture of nonverbal interactions; (4) aggregate multiple observations into a single navigable output; and (5) produce an output interpretable by software developers. We piloted this method by filming live consultations (n = 22) by 4 general practitioners (GPs) using different EPR systems. We compared the time taken and variations during coded data entry, prescribing, and blood pressure (BP) recording. We used nonparametric tests to make statistical comparisons. We contrasted methods of BP recording using Unified Modeling Language (UML) sequence diagrams. We found that 4 channels of video were optimal. We identified an existing application for manual coding of video output. We developed in-house tools for capturing use of keyboard and mouse and to time stamp speech. The transcript is then typed within this time stamp. Although we managed to capture body language using pattern recognition software, we were unable to use this data quantitatively. We loaded these observational outputs into our aggregation tool, which allows simultaneous navigation and viewing of multiple files. This also creates a single exportable file in XML format, which we used to develop UML sequence diagrams. In our pilot, the GP using the EMIS LV (Egton Medical Information Systems Limited, Leeds, UK) system took the longest time to code data (mean 11.5 s, 95% CI 8.7-14.2). Nonparametric comparison of EMIS LV with the other systems showed a significant difference, with EMIS PCS (Egton Medical Information Systems Limited, Leeds, UK) (P = .007), iSoft Synergy (iSOFT, Banbury, UK) (P = .014), and INPS Vision (INPS, London, UK) (P = .006) facilitating faster coding. In contrast, prescribing was fastest with EMIS LV (mean 23.7 s, 95% CI 20.5-26.8), but nonparametric comparison showed no statistically significant difference. UML sequence diagrams showed that the simplest BP recording interface was not the easiest to use, as users spent longer navigating or looking up previous blood pressures separately. Complex interfaces with free-text boxes left clinicians unsure of what to add. The ALFA method allows the precise observation of the clinical consultation. It enables rigorous comparison of core elements of EPR systems. Pilot data suggests its capacity to demonstrate differences between systems. Its outputs could provide the evidence base for making more objective choices between systems.

Combining high-speed SVM learning with CNN feature encoding for real-time target recognition in high-definition video for ISR missions

NASA Astrophysics Data System (ADS)

Kroll, Christine; von der Werth, Monika; Leuck, Holger; Stahl, Christoph; Schertler, Klaus

2017-05-01

For Intelligence, Surveillance, Reconnaissance (ISR) missions of manned and unmanned air systems typical electrooptical payloads provide high-definition video data which has to be exploited with respect to relevant ground targets in real-time by automatic/assisted target recognition software. Airbus Defence and Space is developing required technologies for real-time sensor exploitation since years and has combined the latest advances of Deep Convolutional Neural Networks (CNN) with a proprietary high-speed Support Vector Machine (SVM) learning method into a powerful object recognition system with impressive results on relevant high-definition video scenes compared to conventional target recognition approaches. This paper describes the principal requirements for real-time target recognition in high-definition video for ISR missions and the Airbus approach of combining an invariant feature extraction using pre-trained CNNs and the high-speed training and classification ability of a novel frequency-domain SVM training method. The frequency-domain approach allows for a highly optimized implementation for General Purpose Computation on a Graphics Processing Unit (GPGPU) and also an efficient training of large training samples. The selected CNN which is pre-trained only once on domain-extrinsic data reveals a highly invariant feature extraction. This allows for a significantly reduced adaptation and training of the target recognition method for new target classes and mission scenarios. A comprehensive training and test dataset was defined and prepared using relevant high-definition airborne video sequences. The assessment concept is explained and performance results are given using the established precision-recall diagrams, average precision and runtime figures on representative test data. A comparison to legacy target recognition approaches shows the impressive performance increase by the proposed CNN+SVM machine-learning approach and the capability of real-time high-definition video exploitation.

Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification.

PubMed

Li, Hui; Stoddard, Mark B; Wang, Shuyi; Giorgi, Elena E; Blair, Lily M; Learn, Gerald H; Hahn, Beatrice H; Alter, Harvey J; Busch, Michael P; Fierer, Daniel S; Ribeiro, Ruy M; Perelson, Alan S; Bhattacharya, Tanmoy; Shaw, George M

2016-01-01

Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and development of an effective vaccine. A precise molecular identification of transmitted/founder (T/F) HCV genomes that lead to productive clinical infection could play a critical role in vaccine research, as it has for HIV-1. However, the replication schema of these two RNA viruses differ substantially, as do viral responses to innate and adaptive host defenses. These differences raise questions as to the certainty of T/F HCV genome inferences, particularly in cases where multiple closely related sequence lineages have been observed. To clarify these issues and distinguish between competing models of early HCV diversification, we examined seven cases of acute HCV infection in humans and chimpanzees, including three examples of virus transmission between linked donors and recipients. Using single-genome sequencing (SGS) of plasma vRNA, we found that inferred T/F sequences in recipients were identical to viral sequences in their respective donors. Early in infection, HCV genomes generally evolved according to a simple model of random evolution where the coalescent corresponded to the T/F sequence. Closely related sequence lineages could be explained by high multiplicity infection from a donor whose viral sequences had undergone a pretransmission bottleneck due to treatment, immune selection, or recent infection. These findings validate SGS, together with mathematical modeling and phylogenetic analysis, as a novel strategy to infer T/F HCV genome sequences. Despite the recent development of highly effective, interferon-sparing anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and the development of an effective vaccine, which could be facilitated by a precise molecular identification of transmitted/founder (T/F) viral genomes and their progeny. We used single-genome sequencing to show that inferred HCV T/F sequences in recipients were identical to viral sequences in their respective donors and that viral genomes generally evolved early in infection according to a simple model of random sequence evolution. Altogether, the findings validate T/F genome inferences and illustrate how T/F sequence identification can illuminate studies of HCV transmission, immunopathogenesis, drug resistance development, and vaccine protection, including sieving effects on breakthrough virus strains. Copyright © 2015 Li et al.

The Zodiacal Exoplanets in Time (ZEIT) Survey

NASA Astrophysics Data System (ADS)

Mann, Andrew; Gaidos, Eric; Newton, Elisabeth R.; Rizzuto, Aaron C.; Vanderburg, Andrew; Mace, Gregory N.; Kraus, Adam L.

2017-01-01

Planets and their host stars evolve with time, and the first few hundred million years are thought to be the most formative. However, the majority of known exoplanets orbit stars older than the timescales of interest (>1 Gyr). We have launched the Zodiacal Exoplanets in Time (ZEIT) survey with the goal of identifying and characterizing young (<1 Gyr) transiting planets. To this end, we have utilized high-precision photometry of nearby young clusters and stellar associations taken as part of the K2 mission. Thus far we have discovered transiting planets in the Hyades and Praesepe clusters (˜800 Myr), and the Upper Scorpius OB association (˜11 Myr), but interestingly none in the Pleiades (˜125 Myr). These discoveries can be used to set limits on the migration timescale, estimate atmosphere loss around young planets, and provide independent tests of pre-main sequence stellar models. Here I overview some key science results from our survey and briefly discuss our plans to identify more young planetary systems.

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

PubMed Central

Ribot, Emeline J; Gaudet, Jeffrey M; Chen, Yuhua; Gilbert, Kyle M; Foster, Paula J

2014-01-01

Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR). Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC) without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron. PMID:24748787

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence.

PubMed

Ribot, Emeline J; Gaudet, Jeffrey M; Chen, Yuhua; Gilbert, Kyle M; Foster, Paula J

2014-01-01

Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR). Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC) without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron.

Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer.

PubMed

De Luca, Francesca; Rotunno, Giada; Salvianti, Francesca; Galardi, Francesca; Pestrin, Marta; Gabellini, Stefano; Simi, Lisa; Mancini, Irene; Vannucchi, Alessandro Maria; Pazzagli, Mario; Di Leo, Angelo; Pinzani, Pamela

2016-05-03

Circulating Tumor Cells (CTCs) represent a "liquid biopsy" of the tumor potentially allowing real-time monitoring of cancer biology and therapies in individual patients.The purpose of the study was to explore the applicability of a protocol for the molecular characterization of single CTCs by Next Generation Sequencing (NGS) in order to investigate cell heterogeneity and provide a tool for a personalized medicine approach.CTCs were enriched and enumerated by CellSearch in blood from four metastatic breast cancer patients and singularly isolated by DEPArray. Upon whole genome amplification 3-5 single CTCs per patient were analyzed by NGS for 50 cancer-related genes.We found 51 sequence variants in 25 genes. We observed inter- and intra-patient heterogeneity in the mutational status of CTCs.The highest number of somatic deleterious mutations was found in the gene TP53, whose mutation is associated with adverse prognosis in breast cancer.The discordance between the mutational status of the primary tumor and CTCs observed in 3 patients suggests that, in advanced stages of cancer, CTC characteristics are more closely linked to the dynamic modifications of the disease status.In one patient the mutational profiles of CTCs before and during treatment shared only few sequence variants.This study supports the applicability of a non-invasive approach based on the liquid biopsy in metastatic breast cancer patients which, in perspective, should allow investigating the clonal evolution of the tumor for the development of new therapeutic strategies in precision medicine.

Department of Defense Precise Time and Time Interval program improvement plan

NASA Technical Reports Server (NTRS)

Bowser, J. R.

1981-01-01

The United States Naval Observatory is responsible for ensuring uniformity in precise time and time interval operations including measurements, the establishment of overall DOD requirements for time and time interval, and the accomplishment of objectives requiring precise time and time interval with minimum cost. An overview of the objectives, the approach to the problem, the schedule, and a status report, including significant findings relative to organizational relationships, current directives, principal PTTI users, and future requirements as currently identified by the users are presented.

Improving livestock for agriculture - technological progress from random transgenesis to precision genome editing heralds a new era.

PubMed

Laible, Götz; Wei, Jingwei; Wagner, Stefan

2015-01-01

Humans have a long history in shaping the genetic makeup of livestock to optimize production and meet growing human demands for food and other animal products. Until recently, this has only been possible through traditional breeding and selection, which is a painstakingly slow process of accumulating incremental gains over a long period. The development of transgenic livestock technology offers a more direct approach with the possibility for making genetic improvements with greater impact and within a single generation. However, initially the technology was hampered by technical difficulties and limitations, which have now largely been overcome by progressive improvements over the past 30 years. Particularly, the advent of genome editing in combination with homologous recombination has added a new level of efficiency and precision that holds much promise for the genetic improvement of livestock using the increasing knowledge of the phenotypic impact of genetic sequence variants. So far not a single line of transgenic livestock has gained approval for commercialization. The step change to genome-edited livestock with precise sequence changes may accelerate the path to market, provided applications of this new technology for agriculture can deliver, in addition to economic incentives for producers, also compelling benefits for animals, consumers, and the environment. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precision oncology: origins, optimism, and potential.

PubMed

Prasad, Vinay; Fojo, Tito; Brada, Michael

2016-02-01

Imatinib, the first and arguably the best targeted therapy, became the springboard for developing drugs aimed at molecular targets deemed crucial to tumours. As this development unfolded, a revolution in the speed and cost of genetic sequencing occurred. The result--an armamentarium of drugs and an array of molecular targets--set the stage for precision oncology, a hypothesis that cancer treatment could be markedly improved if therapies were guided by a tumour's genomic alterations. Drawing lessons from the biological basis of cancer and recent empirical investigations, we take a more measured view of precision oncology's promise. Ultimately, the promise is not our concern, but the threshold at which we declare success. We review reports of precision oncology alongside those of precision diagnostics and novel radiotherapy approaches. Although confirmatory evidence is scarce, these interventions have been widely endorsed. We conclude that the current path will probably not be successful or, at a minimum, will have to undergo substantive adjustments before it can be successful. For the sake of patients with cancer, we hope one form of precision oncology will deliver on its promise. However, until confirmatory studies are completed, precision oncology remains unproven, and as such, a hypothesis in need of rigorous testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo gene correction with targeted sequence substitution through microhomology-mediated end joining.

PubMed

Shin, Jeong Hong; Jung, Soobin; Ramakrishna, Suresh; Kim, Hyongbum Henry; Lee, Junwon

2018-07-07

Genome editing technology using programmable nucleases has rapidly evolved in recent years. The primary mechanism to achieve precise integration of a transgene is mainly based on homology-directed repair (HDR). However, an HDR-based genome-editing approach is less efficient than non-homologous end-joining (NHEJ). Recently, a microhomology-mediated end-joining (MMEJ)-based transgene integration approach was developed, showing feasibility both in vitro and in vivo. We expanded this method to achieve targeted sequence substitution (TSS) of mutated sequences with normal sequences using double-guide RNAs (gRNAs), and a donor template flanking the microhomologies and target sequence of the gRNAs in vitro and in vivo. Our method could realize more efficient sequence substitution than the HDR-based method in vitro using a reporter cell line, and led to the survival of a hereditary tyrosinemia mouse model in vivo. The proposed MMEJ-based TSS approach could provide a novel therapeutic strategy, in addition to HDR, to achieve gene correction from a mutated sequence to a normal sequence. Copyright © 2018 Elsevier Inc. All rights reserved.

Error analysis of high-rate GNSS precise point positioning for seismic wave measurement

NASA Astrophysics Data System (ADS)

Shu, Yuanming; Shi, Yun; Xu, Peiliang; Niu, Xiaoji; Liu, Jingnan

2017-06-01

High-rate GNSS precise point positioning (PPP) has been playing a more and more important role in providing precise positioning information in fast time-varying environments. Although kinematic PPP is commonly known to have a precision of a few centimeters, the precision of high-rate PPP within a short period of time has been reported recently with experiments to reach a few millimeters in the horizontal components and sub-centimeters in the vertical component to measure seismic motion, which is several times better than the conventional kinematic PPP practice. To fully understand the mechanism of mystified excellent performance of high-rate PPP within a short period of time, we have carried out a theoretical error analysis of PPP and conducted the corresponding simulations within a short period of time. The theoretical analysis has clearly indicated that the high-rate PPP errors consist of two types: the residual systematic errors at the starting epoch, which affect high-rate PPP through the change of satellite geometry, and the time-varying systematic errors between the starting epoch and the current epoch. Both the theoretical error analysis and simulated results are fully consistent with and thus have unambiguously confirmed the reported high precision of high-rate PPP, which has been further affirmed here by the real data experiments, indicating that high-rate PPP can indeed achieve the millimeter level of precision in the horizontal components and the sub-centimeter level of precision in the vertical component to measure motion within a short period of time. The simulation results have clearly shown that the random noise of carrier phases and higher order ionospheric errors are two major factors to affect the precision of high-rate PPP within a short period of time. The experiments with real data have also indicated that the precision of PPP solutions can degrade to the cm level in both the horizontal and vertical components, if the geometry of satellites is rather poor with a large DOP value.

Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing.

PubMed

Weirather, Jason L; Afshar, Pegah Tootoonchi; Clark, Tyson A; Tseng, Elizabeth; Powers, Linda S; Underwood, Jason G; Zabner, Joseph; Korlach, Jonas; Wong, Wing Hung; Au, Kin Fai

2015-10-15

We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine fusion sites and identify and quantify fusion isoforms. IDP-fusion is the first method to study gene fusion events by integrating Third Generation Sequencing long reads and Second Generation Sequencing short reads. We applied IDP-fusion to PacBio data and Illumina data from the MCF-7 breast cancer cells. Compared with the existing tools, IDP-fusion detects fusion genes at higher precision and a very low false positive rate. The results show that IDP-fusion will be useful for unraveling the complexity of multiple fusion splices and fusion isoforms within tumorigenesis-relevant fusion genes. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle.

PubMed

Mikheikin, Andrey; Olsen, Anita; Leslie, Kevin; Russell-Pavier, Freddie; Yacoot, Andrew; Picco, Loren; Payton, Oliver; Toor, Amir; Chesney, Alden; Gimzewski, James K; Mishra, Bud; Reed, Jason

2017-11-21

Progress in whole-genome sequencing using short-read (e.g., <150 bp), next-generation sequencing technologies has reinvigorated interest in high-resolution physical mapping to fill technical gaps that are not well addressed by sequencing. Here, we report two technical advances in DNA nanotechnology and single-molecule genomics: (1) we describe a labeling technique (CRISPR-Cas9 nanoparticles) for high-speed AFM-based physical mapping of DNA and (2) the first successful demonstration of using DVD optics to image DNA molecules with high-speed AFM. As a proof of principle, we used this new "nanomapping" method to detect and map precisely BCL2-IGH translocations present in lymph node biopsies of follicular lymphoma patents. This HS-AFM "nanomapping" technique can be complementary to both sequencing and other physical mapping approaches.

Magnetic resonance for laryngeal cancer.

PubMed

Maroldi, Roberto; Ravanelli, Marco; Farina, Davide

2014-04-01

This review summarizes the most recent experiences on the integration of magnetic resonance in assessing the local extent of laryngeal cancer and detecting submucosal recurrences. Advances in magnetic resonance have been characterized by the development of technical solutions that shorten the acquisition time, thereby reducing motion artifacts, and increase the spatial resolution. Phased-array surface coils, directly applied to the neck, enable the use of parallel-imaging techniques, which greatly reduce the acquisition time, and amplify the signal intensity, being closer to the larynx. One of the most important drawbacks of this technique is the small field-of-view, restricting the imaged area to the larynx. Furthermore, diffusion-weighted imaging (DWI) has increased the set of magnetic resonance sequences. Differently from computed tomography (CT), which has only two variables (precontrast/postcontrast), magnetic resonance is based on a multiparameter analysis (T2-weighting and T1-weighting, DWI, and postcontrast acquisition). This multiparameter approach amplifies the contrast resolution. It has, also, permitted to differentiate scar tissue (after laser resection) from submucosal recurrent disease. In addition, DWI sequences have the potential of a more precise discrimination of peritumoral edema from neoplastic tissue, which may lead to improve the assessment of paraglottic space invasion. Magnetic resonance of the larynx is technically challenging. The use of surface coils and motion-reducing techniques is critical to achieve adequate image quality. The intrinsic high-contrast resolution is further increased by the integration of information from different sequences. When CT has not been conclusive, magnetic resonance is indicated in the pretreatment local assessment and in the suspicion of submucosal recurrence.

Discovery of 100K SNP array and its utilization in sugarcane

USDA-ARS?s Scientific Manuscript database

Next generation sequencing (NGS) enable us to identify thousands of single nucleotide polymorphisms (SNPs) marker for genotyping and fingerprinting. However, the process requires very precise bioinformatics analysis and filtering process. High throughput SNP array with predefined genomic location co...

Supertitrations: High-Precision Methods.

ERIC Educational Resources Information Center

Guenther, W. B.

1988-01-01

Offers challenging work at a higher level of technique than most students meet in elementary laboratory work. Uses a combined weight and volumetric sequence not shown in textbooks. Notes modern rapid balances help lower evaporation loss during weighings. Discusses the balance, weights, and buoyancy considerations. (MVL)

The promise and challenge of high-throughput sequencing of the antibody repertoire

PubMed Central

Georgiou, George; Ippolito, Gregory C; Beausang, John; Busse, Christian E; Wardemann, Hedda; Quake, Stephen R

2014-01-01

Efforts to determine the antibody repertoire encoded by B cells in the blood or lymphoid organs using high-throughput DNA sequencing technologies have been advancing at an extremely rapid pace and are transforming our understanding of humoral immune responses. Information gained from high-throughput DNA sequencing of immunoglobulin genes (Ig-seq) can be applied to detect B-cell malignancies with high sensitivity, to discover antibodies specific for antigens of interest, to guide vaccine development and to understand autoimmunity. Rapid progress in the development of experimental protocols and informatics analysis tools is helping to reduce sequencing artifacts, to achieve more precise quantification of clonal diversity and to extract the most pertinent biological information. That said, broader application of Ig-seq, especially in clinical settings, will require the development of a standardized experimental design framework that will enable the sharing and meta-analysis of sequencing data generated by different laboratories. PMID:24441474

Characterization of DNA-protein interactions using high-throughput sequencing data from pulldown experiments

NASA Astrophysics Data System (ADS)

Moreland, Blythe; Oman, Kenji; Curfman, John; Yan, Pearlly; Bundschuh, Ralf

Methyl-binding domain (MBD) protein pulldown experiments have been a valuable tool in measuring the levels of methylated CpG dinucleotides. Due to the frequent use of this technique, high-throughput sequencing data sets are available that allow a detailed quantitative characterization of the underlying interaction between methylated DNA and MBD proteins. Analyzing such data sets, we first found that two such proteins cannot bind closer to each other than 2 bp, consistent with structural models of the DNA-protein interaction. Second, the large amount of sequencing data allowed us to find rather weak but nevertheless clearly statistically significant sequence preferences for several bases around the required CpG. These results demonstrate that pulldown sequencing is a high-precision tool in characterizing DNA-protein interactions. This material is based upon work supported by the National Science Foundation under Grant No. DMR-1410172.

Factors Affecting Wound Healing

PubMed Central

Guo, S.; DiPietro, L.A.

2010-01-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

Factors affecting wound healing.

PubMed

Guo, S; Dipietro, L A

2010-03-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds.

The 26th Annual Precise Time and Time Interval (PTTI) Applications and Planning Meeting

NASA Technical Reports Server (NTRS)

Sydnor, Richard (Editor)

1995-01-01

This document is a compilation of technical papers presented at the 26th Annual PTTI Applications and Planning Meeting. Papers are in the following categories: (1) Recent developments in rubidium, cesium, and hydrogen-based frequency standards, and in cryogenic and trapped-ion technology; (2) International and transnational applications of Precise Time and Time Interval technology with emphasis on satellite laser tracking, GLONASS timing, intercomparison of national time scales and international telecommunications; (3) Applications of Precise Time and Time Interval technology to the telecommunications, power distribution, platform positioning, and geophysical survey industries; (4) Applications of PTTI technology to evolving military communications and navigation systems; and (5) Dissemination of precise time and frequency by means of GPS, GLONASS, MILSTAR, LORAN, and synchronous communications satellites.

The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization

PubMed Central

van der Steen, M. C. (Marieke); Keller, Peter E.

2013-01-01

A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM. PMID:23772211

Design of Conditionally Active STATs: Insights into STAT Activation and Gene Regulatory Function

PubMed Central

Milocco, Lawrence H.; Haslam, Jennifer A.; Rosen, Jonathan; Seidel, H. Martin

1999-01-01

The STAT (signal transducer and activator of transcription) signaling pathway is activated by a large number of cytokines and growth factors. We sought to design a conditionally active STAT that could not only provide insight into basic questions about STAT function but also serve as a powerful tool to determine the precise biological role of STATs. To this end, we have developed a conditionally active STAT by fusing STATs with the ligand-binding domain of the estrogen receptor (ER). We have demonstrated that the resulting STAT-ER chimeras are estrogen-inducible transcription factors that retain the functional and biochemical characteristics of the cognate wild-type STATs. In addition, these tools have allowed us to evaluate separately the contribution of tyrosine phosphorylation and dimerization to STAT function. We have for the first time provided experimental data supporting the model that the only apparent role of STAT tyrosine phosphorylation is to drive dimerization, as dimerization alone is sufficient to unmask a latent STAT nuclear localization sequence and induce nuclear translocation, sequence-specific DNA binding, and transcriptional activity. PMID:10082558

New insights into replication origin characteristics in metazoans

PubMed Central

Puy, Aurore; Rialle, Stéphanie; Kaplan, Noam; Segal, Eran

2012-01-01

We recently reported the identification and characterization of DNA replication origins (Oris) in metazoan cell lines. Here, we describe additional bioinformatic analyses showing that the previously identified GC-rich sequence elements form origin G-rich repeated elements (OGREs) that are present in 67% to 90% of the DNA replication origins from Drosophila to human cells, respectively. Our analyses also show that initiation of DNA synthesis takes place precisely at 160 bp (Drosophila) and 280 bp (mouse) from the OGRE. We also found that in most CpG islands, an OGRE is positioned in opposite orientation on each of the two DNA strands and detected two sites of initiation of DNA synthesis upstream or downstream of each OGRE. Conversely, Oris not associated with CpG islands have a single initiation site. OGRE density along chromosomes correlated with previously published replication timing data. Ori sequences centered on the OGRE are also predicted to have high intrinsic nucleosome occupancy. Finally, OGREs predict G-quadruplex structures at Oris that might be structural elements controlling the choice or activation of replication origins. PMID:22373526

Conflict adaptation in patients diagnosed with schizophrenia.

PubMed

Abrahamse, Elger; Ruitenberg, Marit; Boddewyn, Sarah; Oreel, Edith; de Schryver, Maarten; Morrens, Manuel; van Dijck, Jean-Philippe

2017-11-01

Cognitive control impairments may contribute strongly to the overall cognitive deficits observed in patients diagnosed with schizophrenia. In the current study we explore a specific cognitive control function referred to as conflict adaptation. Previous studies on conflict adaptation in schizophrenia showed equivocal results, and, moreover, were plagued by confounded research designs. Here we assessed for the first time conflict adaptation in schizophrenia with a design that avoided the major confounds of feature integration and stimulus-response contingency learning. Sixteen patients diagnosed with schizophrenia and sixteen healthy, matched controls performed a vocal Stroop task to determine the congruency sequence effect - a marker of conflict adaptation. A reliable congruency sequence effect was observed for both healthy controls and patients diagnosed with schizophrenia. These findings indicate that schizophrenia is not necessarily accompanied by impaired conflict adaptation. As schizophrenia has been related to abnormal functioning in core conflict adaptation areas such as anterior cingulate and dorsolateral prefrontal cortex, further research is required to better understand the precise impact of such abnormal brain functioning at the behavioral level. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteogenomic studies on cancer drug resistance: towards biomarker discovery and target identification.

PubMed

Fu, Shuyue; Liu, Xiang; Luo, Maochao; Xie, Ke; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

2017-04-01

Chemoresistance is a major obstacle for current cancer treatment. Proteogenomics is a powerful multi-omics research field that uses customized protein sequence databases generated by genomic and transcriptomic information to identify novel genes (e.g. noncoding, mutation and fusion genes) from mass spectrometry-based proteomic data. By identifying aberrations that are differentially expressed between tumor and normal pairs, this approach can also be applied to validate protein variants in cancer, which may reveal the response to drug treatment. Areas covered: In this review, we will present recent advances in proteogenomic investigations of cancer drug resistance with an emphasis on integrative proteogenomic pipelines and the biomarker discovery which contributes to achieving the goal of using precision/personalized medicine for cancer treatment. Expert commentary: The discovery and comprehensive understanding of potential biomarkers help identify the cohort of patients who may benefit from particular treatments, and will assist real-time clinical decision-making to maximize therapeutic efficacy and minimize adverse effects. With the development of MS-based proteomics and NGS-based sequencing, a growing number of proteogenomic tools are being developed specifically to investigate cancer drug resistance.

ORCAN-a web-based meta-server for real-time detection and functional annotation of orthologs.

PubMed

Zielezinski, Andrzej; Dziubek, Michal; Sliski, Jan; Karlowski, Wojciech M

2017-04-15

ORCAN (ORtholog sCANner) is a web-based meta-server for one-click evolutionary and functional annotation of protein sequences. The server combines information from the most popular orthology-prediction resources, including four tools and four online databases. Functional annotation utilizes five additional comparisons between the query and identified homologs, including: sequence similarity, protein domain architectures, functional motifs, Gene Ontology term assignments and a list of associated articles. Furthermore, the server uses a plurality-based rating system to evaluate the orthology relationships and to rank the reference proteins by their evolutionary and functional relevance to the query. Using a dataset of ∼1 million true yeast orthologs as a sample reference set, we show that combining multiple orthology-prediction tools in ORCAN increases the sensitivity and precision by 1-2 percent points. The service is available for free at http://www.combio.pl/orcan/ . wmk@amu.edu.pl. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir resistance mutations in chronic hepatitis B

PubMed Central

Ahn, Sang Hoon; Chun, Ji-Yong; Shin, Soo-Kyung; Park, Jun Yong; Yoo, Wangdon; Hong, Sun Pyo; Han, Kwang-Hyub

2013-01-01

Background/Aims Molecular diagnostic methods have enabled the rapid diagnosis of drug-resistant mutations in hepatitis B virus (HBV) and have reduced both unnecessary therapeutic interventions and medical costs. In this study we evaluated the analytical and clinical performances of the HepB Typer-Entecavir kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations. Methods The HepB Typer-Entecavir kit was evaluated for its limit of detection, interference, cross-reactivity, and precision using HBV reference standards made by diluting high-titer viral stocks in HBV-negative human serum. The performance of the HepB Typer-Entecavir kit for detecting mutations related to entecavir resistance was compared with direct sequencing for 396 clinical samples from 108 patients. Results Using the reference standards, the detection limit of the HepB Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity was observed, and elevated levels of various interfering substances did not adversely affect its analytical performance. The precision test conducted by repetitive analysis of 2,400 replicates with reference standards at various concentrations showed 99.9% agreement (2398/2400). The overall concordance rate between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical samples was 99.5%. Conclusions The HepB Typer-Entecavir kit showed high reliability and precision, and comparable sensitivity and specificity for detecting mutant virus populations in reference and clinical samples in comparison with direct sequencing. Therefore, this assay would be clinically useful in the diagnosis of entecavir-resistance-associated mutations in chronic hepatitis B. PMID:24459645

TOWARD PRECISE AGES FOR SINGLE STARS IN THE FIELD. GYROCHRONOLOGY CONSTRAINTS AT SEVERAL Gyr USING WIDE BINARIES. I. AGES FOR INITIAL SAMPLE

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

Chaname, Julio; Ramirez, Ivan

2012-02-10

We present a program designed to obtain age-rotation measurements of solar-type dwarfs to be used in the calibration of gyrochronology relations at ages of several Gyr. This is a region of parameter space crucial for the large-scale study of the Milky Way, and where the only constraint available today is that provided by the Sun. Our program takes advantage of a set of wide binaries selected so that one component is an evolved star and the other is a main-sequence star of FGK type. In this way, we obtain the age of the system from the evolved star, while themore » rotational properties of the main-sequence component provide the information relevant for gyrochronology regarding the spin-down of solar-type stars. By mining currently available catalogs of wide binaries, we assemble a sample of 37 pairs well positioned for our purposes: 19 with turnoff or subgiant primaries and 18 with white dwarf components. Using high-resolution optical spectroscopy, we measure precise stellar parameters for a subset of 15 of the pairs with turnoff/subgiant components and use these to derive isochronal ages for the corresponding systems. Ages for 16 of the 18 pairs with white dwarf components are taken from the literature. The ages of this initial sample of 31 wide binaries range from 1 to 9 Gyr, with precisions better than {approx}20% for almost half of these systems. When combined with measurements of the rotation period of their main-sequence components, these wide binary systems would potentially provide a similar number of points useful for the calibration of gyrochronology relations at very old ages.« less

Whole Genome Sequences of Three Treponema pallidum ssp. pertenue Strains: Yaws and Syphilis Treponemes Differ in Less than 0.2% of the Genome Sequence

PubMed Central

Chen, Lei; Pospíšilová, Petra; Strouhal, Michal; Qin, Xiang; Mikalová, Lenka; Norris, Steven J.; Muzny, Donna M.; Gibbs, Richard A.; Fulton, Lucinda L.; Sodergren, Erica; Weinstock, George M.; Šmajs, David

2012-01-01

Background The yaws treponemes, Treponema pallidum ssp. pertenue (TPE) strains, are closely related to syphilis causing strains of Treponema pallidum ssp. pallidum (TPA). Both yaws and syphilis are distinguished on the basis of epidemiological characteristics, clinical symptoms, and several genetic signatures of the corresponding causative agents. Methodology/Principal Findings To precisely define genetic differences between TPA and TPE, high-quality whole genome sequences of three TPE strains (Samoa D, CDC-2, Gauthier) were determined using next-generation sequencing techniques. TPE genome sequences were compared to four genomes of TPA strains (Nichols, DAL-1, SS14, Chicago). The genome structure was identical in all three TPE strains with similar length ranging between 1,139,330 bp and 1,139,744 bp. No major genome rearrangements were found when compared to the four TPA genomes. The whole genome nucleotide divergence (dA) between TPA and TPE subspecies was 4.7 and 4.8 times higher than the observed nucleotide diversity (π) among TPA and TPE strains, respectively, corresponding to 99.8% identity between TPA and TPE genomes. A set of 97 (9.9%) TPE genes encoded proteins containing two or more amino acid replacements or other major sequence changes. The TPE divergent genes were mostly from the group encoding potential virulence factors and genes encoding proteins with unknown function. Conclusions/Significance Hypothetical genes, with genetic differences, consistently found between TPE and TPA strains are candidates for syphilitic treponemes virulence factors. Seventeen TPE genes were predicted under positive selection, and eleven of them coded either for predicted exported proteins or membrane proteins suggesting their possible association with the cell surface. Sequence changes between TPE and TPA strains and changes specific to individual strains represent suitable targets for subspecies- and strain-specific molecular diagnostics. PMID:22292095

BayesMotif: de novo protein sorting motif discovery from impure datasets.

PubMed

Hu, Jianjun; Zhang, Fan

2010-01-18

Protein sorting is the process that newly synthesized proteins are transported to their target locations within or outside of the cell. This process is precisely regulated by protein sorting signals in different forms. A major category of sorting signals are amino acid sub-sequences usually located at the N-terminals or C-terminals of protein sequences. Genome-wide experimental identification of protein sorting signals is extremely time-consuming and costly. Effective computational algorithms for de novo discovery of protein sorting signals is needed to improve the understanding of protein sorting mechanisms. We formulated the protein sorting motif discovery problem as a classification problem and proposed a Bayesian classifier based algorithm (BayesMotif) for de novo identification of a common type of protein sorting motifs in which a highly conserved anchor is present along with a less conserved motif regions. A false positive removal procedure is developed to iteratively remove sequences that are unlikely to contain true motifs so that the algorithm can identify motifs from impure input sequences. Experiments on both implanted motif datasets and real-world datasets showed that the enhanced BayesMotif algorithm can identify anchored sorting motifs from pure or impure protein sequence dataset. It also shows that the false positive removal procedure can help to identify true motifs even when there is only 20% of the input sequences containing true motif instances. We proposed BayesMotif, a novel Bayesian classification based algorithm for de novo discovery of a special category of anchored protein sorting motifs from impure datasets. Compared to conventional motif discovery algorithms such as MEME, our algorithm can find less-conserved motifs with short highly conserved anchors. Our algorithm also has the advantage of easy incorporation of additional meta-sequence features such as hydrophobicity or charge of the motifs which may help to overcome the limitations of PWM (position weight matrix) motif model.

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

PubMed Central

Chen, Guoli; Yang, Zhaohai; Eshleman, James R.; Netto, George J.

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional “one test-one drug” assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC. PMID:27699178

Science 101: How Do Atomic Clocks Work?

ERIC Educational Resources Information Center

Science and Children, 2008

2008-01-01

You might be wondering why in the world we need such precise measures of time. Well, many systems we use everyday, such as Global Positioning Systems, require precise synchronization of time. This comes into play in telecommunications and wireless communications, also. For purely scientific reasons, we can use precise measurement of time to…

Time Delay Embedding Increases Estimation Precision of Models of Intraindividual Variability

ERIC Educational Resources Information Center

von Oertzen, Timo; Boker, Steven M.

2010-01-01

This paper investigates the precision of parameters estimated from local samples of time dependent functions. We find that "time delay embedding," i.e., structuring data prior to analysis by constructing a data matrix of overlapping samples, increases the precision of parameter estimates and in turn statistical power compared to standard…

Nonpareil 3: Fast Estimation of Metagenomic Coverage and Sequence Diversity.

PubMed

Rodriguez-R, Luis M; Gunturu, Santosh; Tiedje, James M; Cole, James R; Konstantinidis, Konstantinos T

2018-01-01

Estimations of microbial community diversity based on metagenomic data sets are affected, often to an unknown degree, by biases derived from insufficient coverage and reference database-dependent estimations of diversity. For instance, the completeness of reference databases cannot be generally estimated since it depends on the extant diversity sampled to date, which, with the exception of a few habitats such as the human gut, remains severely undersampled. Further, estimation of the degree of coverage of a microbial community by a metagenomic data set is prohibitively time-consuming for large data sets, and coverage values may not be directly comparable between data sets obtained with different sequencing technologies. Here, we extend Nonpareil, a database-independent tool for the estimation of coverage in metagenomic data sets, to a high-performance computing implementation that scales up to hundreds of cores and includes, in addition, a k -mer-based estimation as sensitive as the original alignment-based version but about three hundred times as fast. Further, we propose a metric of sequence diversity ( N d ) derived directly from Nonpareil curves that correlates well with alpha diversity assessed by traditional metrics. We use this metric in different experiments demonstrating the correlation with the Shannon index estimated on 16S rRNA gene profiles and show that N d additionally reveals seasonal patterns in marine samples that are not captured by the Shannon index and more precise rankings of the magnitude of diversity of microbial communities in different habitats. Therefore, the new version of Nonpareil, called Nonpareil 3, advances the toolbox for metagenomic analyses of microbiomes. IMPORTANCE Estimation of the coverage provided by a metagenomic data set, i.e., what fraction of the microbial community was sampled by DNA sequencing, represents an essential first step of every culture-independent genomic study that aims to robustly assess the sequence diversity present in a sample. However, estimation of coverage remains elusive because of several technical limitations associated with high computational requirements and limiting statistical approaches to quantify diversity. Here we described Nonpareil 3, a new bioinformatics algorithm that circumvents several of these limitations and thus can facilitate culture-independent studies in clinical or environmental settings, independent of the sequencing platform employed. In addition, we present a new metric of sequence diversity based on rarefied coverage and demonstrate its use in communities from diverse ecosystems.

Testing Models of Stellar Structure and Evolution I. Comparison with Detached Eclipsing Binaries

NASA Astrophysics Data System (ADS)

del Burgo, C.; Allende Prieto, C.

2018-05-01

We present the results of an analysis aimed at testing the accuracy and precision of the PARSEC v1.2S library of stellar evolution models, combined with a Bayesian approach, to infer stellar parameters. We mainly employ the online DEBCat catalogue by Southworth, a compilation of detached eclipsing binary systems with published measurements of masses and radii to ˜ 2 per cent precision. We select a sample of 318 binary components, with masses between 0.10 and 14.5 solar units, and distances between 1.3 pc and ˜ 8 kpc for Galactic objects and ˜ 44-68 kpc for the extragalactic ones. The Bayesian analysis applied takes on input effective temperature, radius, and [Fe/H], and their uncertainties, returning theoretical predictions for other stellar parameters. From the comparison with dynamical masses, we conclude inferred masses are precisely derived for stars on the main-sequence and in the core-helium-burning phase, with respective uncertainties of 4 per cent and 7 per cent, on average. Subgiants and red giants masses are predicted within 14 per cent, and early asymptotic giant branch stars within 24 per cent. These results are helpful to further improve the models, in particular for advanced evolutionary stages for which our understanding is limited. We obtain distances and ages for the binary systems and compare them, whenever possible, with precise literature estimates, finding excellent agreement. We discuss evolutionary effects and the challenges associated with the inference of stellar ages from evolutionary models. We also provide useful polynomial fittings to theoretical zero-age main-sequence relations.

An integrated pipeline for next generation sequencing and annotation of the complete mitochondrial genome of the giant intestinal fluke, Fasciolopsis buski (Lankester, 1857) Looss, 1899

PubMed Central

Biswal, Devendra Kumar; Ghatani, Sudeep; Shylla, Jollin A.; Sahu, Ranjana; Mullapudi, Nandita

2013-01-01

Helminths include both parasitic nematodes (roundworms) and platyhelminths (trematode and cestode flatworms) that are abundant, and are of clinical importance. The genetic characterization of parasitic flatworms using advanced molecular tools is central to the diagnosis and control of infections. Although the nuclear genome houses suitable genetic markers (e.g., in ribosomal (r) DNA) for species identification and molecular characterization, the mitochondrial (mt) genome consistently provides a rich source of novel markers for informative systematics and epidemiological studies. In the last decade, there have been some important advances in mtDNA genomics of helminths, especially lung flukes, liver flukes and intestinal flukes. Fasciolopsis buski, often called the giant intestinal fluke, is one of the largest digenean trematodes infecting humans and found primarily in Asia, in particular the Indian subcontinent. Next-generation sequencing (NGS) technologies now provide opportunities for high throughput sequencing, assembly and annotation within a short span of time. Herein, we describe a high-throughput sequencing and bioinformatics pipeline for mt genomics for F. buski that emphasizes the utility of short read NGS platforms such as Ion Torrent and Illumina in successfully sequencing and assembling the mt genome using innovative approaches for PCR primer design as well as assembly. We took advantage of our NGS whole genome sequence data (unpublished so far) for F. buski and its comparison with available data for the Fasciola hepatica mtDNA as the reference genome for design of precise and specific primers for amplification of mt genome sequences from F. buski. A long-range PCR was carried out to create an NGS library enriched in mt DNA sequences. Two different NGS platforms were employed for complete sequencing, assembly and annotation of the F. buski mt genome. The complete mt genome sequences of the intestinal fluke comprise 14,118 bp and is thus the shortest trematode mitochondrial genome sequenced to date. The noncoding control regions are separated into two parts by the tRNA-Gly gene and don’t contain either tandem repeats or secondary structures, which are typical for trematode control regions. The gene content and arrangement are identical to that of F. hepatica. The F. buski mtDNA genome has a close resemblance with F. hepatica and has a similar gene order tallying with that of other trematodes. The mtDNA for the intestinal fluke is reported herein for the first time by our group that would help investigate Fasciolidae taxonomy and systematics with the aid of mtDNA NGS data. More so, it would serve as a resource for comparative mitochondrial genomics and systematic studies of trematode parasites. PMID:24255820

Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.

PubMed

Baynam, Gareth; Bowman, Faye; Lister, Karla; Walker, Caroline E; Pachter, Nicholas; Goldblatt, Jack; Boycott, Kym M; Gahl, William A; Kosaki, Kenjiro; Adachi, Takeya; Ishii, Ken; Mahede, Trinity; McKenzie, Fiona; Townshend, Sharron; Slee, Jennie; Kiraly-Borri, Cathy; Vasudevan, Anand; Hawkins, Anne; Broley, Stephanie; Schofield, Lyn; Verhoef, Hedwig; Groza, Tudor; Zankl, Andreas; Robinson, Peter N; Haendel, Melissa; Brudno, Michael; Mattick, John S; Dinger, Marcel E; Roscioli, Tony; Cowley, Mark J; Olry, Annie; Hanauer, Marc; Alkuraya, Fowzan S; Taruscio, Domenica; Posada de la Paz, Manuel; Lochmüller, Hanns; Bushby, Kate; Thompson, Rachel; Hedley, Victoria; Lasko, Paul; Mina, Kym; Beilby, John; Tifft, Cynthia; Davis, Mark; Laing, Nigel G; Julkowska, Daria; Le Cam, Yann; Terry, Sharon F; Kaufmann, Petra; Eerola, Iiro; Norstedt, Irene; Rath, Ana; Suematsu, Makoto; Groft, Stephen C; Austin, Christopher P; Draghia-Akli, Ruxandra; Weeramanthri, Tarun S; Molster, Caron; Dawkins, Hugh J S

2017-01-01

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy decisions provide the scaffolding for translation of new genomics knowledge, and catalyze transformative change in delivery of clinical services. The vignettes presented here are from an Australian perspective and are not intended to be comprehensive, but rather to provide insights into how a new and emerging 'precision public health' paradigm can improve the experiences of patients living with rare diseases, their caregivers and families.The conclusion is that genomic public health is informed by the individual and family needs, and the population health imperatives of an early and accurate diagnosis; which is the portal to best practice care. Knowledge sharing is critical for public health policy development and improving the lives of people living with rare diseases.

Dynamically heterogenous partitions and phylogenetic inference: an evaluation of analytical strategies with cytochrome b and ND6 gene sequences in cranes.

PubMed

Krajewski, C; Fain, M G; Buckley, L; King, D G

1999-11-01

ki ctes over whether molecular sequence data should be partitioned for phylogenetic analysis often confound two types of heterogeneity among partitions. We distinguish historical heterogeneity (i.e., different partitions have different evolutionary relationships) from dynamic heterogeneity (i.e., different partitions show different patterns of sequence evolution) and explore the impact of the latter on phylogenetic accuracy and precision with a two-gene, mitochondrial data set for cranes. The well-established phylogeny of cranes allows us to contrast tree-based estimates of relevant parameter values with estimates based on pairwise comparisons and to ascertain the effects of incorporating different amounts of process information into phylogenetic estimates. We show that codon positions in the cytochrome b and NADH dehydrogenase subunit 6 genes are dynamically heterogenous under both Poisson and invariable-sites + gamma-rates versions of the F84 model and that heterogeneity includes variation in base composition and transition bias as well as substitution rate. Estimates of transition-bias and relative-rate parameters from pairwise sequence comparisons were comparable to those obtained as tree-based maximum likelihood estimates. Neither rate-category nor mixed-model partitioning strategies resulted in a loss of phylogenetic precision relative to unpartitioned analyses. We suggest that weighted-average distances provide a computationally feasible alternative to direct maximum likelihood estimates of phylogeny for mixed-model analyses of large, dynamically heterogenous data sets. Copyright 1999 Academic Press.

Three-dimensional P-wave velocity structure and precise earthquake relocation at Great Sitkin Volcano, Alaska

USGS Publications Warehouse

Pesicek, Jeremy; Thurber, Clifford H.; DeShon, Heather R.; Prejean, Stephanie G.; Zhang, Haijiang

2008-01-01

Waveform cross-correlation with bispectrum verification is combined with double-difference tomography to increase the precision of earthquake locations and constrain regional 3D P-wave velocity heterogeneity at Great Sitkin volcano, Alaska. From 1999 through 2005, the Alaska Volcano Observatory (AVO) recorded ∼1700 earthquakes in the vicinity of Great Sitkin, including two ML 4.3 earthquakes that are among the largest events in the AVO catalog. The majority of earthquakes occurred during 2002 and formed two temporally and spatially separate event sequences. The first sequence began on 17 March 2002 and was centered ∼20 km west of the volcano. The second sequence occurred on the southeast flank of Great Sitkin and began 28 May 2002. It was preceded by two episodes of volcanic tremor. Earthquake relocations of this activity on the southeast flank define a vertical planar feature oriented radially from the summit and in the direction of the assumed regional maximum compressive stress due to convergence along the Alaska subduction zone. This swarm may have been caused or accompanied by the emplacement of a dike. Relocations of the mainshock–aftershock sequence occurring west of Great Sitkin are consistent with rupture on a strike-slip fault. Tomographic images support the presence of a vertically dipping fault striking parallel to the direction of convergence in this region. The remaining catalog hypocenters relocate along discrete features beneath the volcano summit; here, low P-wave velocities possibly indicate the presence of magma beneath the volcano.

Registration of Panoramic/Fish-Eye Image Sequence and LiDAR Points Using Skyline Features

PubMed Central

Zhu, Ningning; Jia, Yonghong; Ji, Shunping

2018-01-01

We propose utilizing a rigorous registration model and a skyline-based method for automatic registration of LiDAR points and a sequence of panoramic/fish-eye images in a mobile mapping system (MMS). This method can automatically optimize original registration parameters and avoid the use of manual interventions in control point-based registration methods. First, the rigorous registration model between the LiDAR points and the panoramic/fish-eye image was built. Second, skyline pixels from panoramic/fish-eye images and skyline points from the MMS’s LiDAR points were extracted, relying on the difference in the pixel values and the registration model, respectively. Third, a brute force optimization method was used to search for optimal matching parameters between skyline pixels and skyline points. In the experiments, the original registration method and the control point registration method were used to compare the accuracy of our method with a sequence of panoramic/fish-eye images. The result showed: (1) the panoramic/fish-eye image registration model is effective and can achieve high-precision registration of the image and the MMS’s LiDAR points; (2) the skyline-based registration method can automatically optimize the initial attitude parameters, realizing a high-precision registration of a panoramic/fish-eye image and the MMS’s LiDAR points; and (3) the attitude correction values of the sequences of panoramic/fish-eye images are different, and the values must be solved one by one. PMID:29883431

IBS: an illustrator for the presentation and visualization of biological sequences.

PubMed

Liu, Wenzhong; Xie, Yubin; Ma, Jiyong; Luo, Xiaotong; Nie, Peng; Zuo, Zhixiang; Lahrmann, Urs; Zhao, Qi; Zheng, Yueyuan; Zhao, Yong; Xue, Yu; Ren, Jian

2015-10-15

Biological sequence diagrams are fundamental for visualizing various functional elements in protein or nucleotide sequences that enable a summarization and presentation of existing information as well as means of intuitive new discoveries. Here, we present a software package called illustrator of biological sequences (IBS) that can be used for representing the organization of either protein or nucleotide sequences in a convenient, efficient and precise manner. Multiple options are provided in IBS, and biological sequences can be manipulated, recolored or rescaled in a user-defined mode. Also, the final representational artwork can be directly exported into a publication-quality figure. The standalone package of IBS was implemented in JAVA, while the online service was implemented in HTML5 and JavaScript. Both the standalone package and online service are freely available at http://ibs.biocuckoo.org. renjian.sysu@gmail.com or xueyu@hust.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

IBS: an illustrator for the presentation and visualization of biological sequences

PubMed Central

Liu, Wenzhong; Xie, Yubin; Ma, Jiyong; Luo, Xiaotong; Nie, Peng; Zuo, Zhixiang; Lahrmann, Urs; Zhao, Qi; Zheng, Yueyuan; Zhao, Yong; Xue, Yu; Ren, Jian

2015-01-01

Summary: Biological sequence diagrams are fundamental for visualizing various functional elements in protein or nucleotide sequences that enable a summarization and presentation of existing information as well as means of intuitive new discoveries. Here, we present a software package called illustrator of biological sequences (IBS) that can be used for representing the organization of either protein or nucleotide sequences in a convenient, efficient and precise manner. Multiple options are provided in IBS, and biological sequences can be manipulated, recolored or rescaled in a user-defined mode. Also, the final representational artwork can be directly exported into a publication-quality figure. Availability and implementation: The standalone package of IBS was implemented in JAVA, while the online service was implemented in HTML5 and JavaScript. Both the standalone package and online service are freely available at http://ibs.biocuckoo.org. Contact: renjian.sysu@gmail.com or xueyu@hust.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26069263

Performance Evaluation of Real-Time Precise Point Positioning Method

NASA Astrophysics Data System (ADS)

Alcay, Salih; Turgut, Muzeyyen

2017-12-01

Post-Processed Precise Point Positioning (PPP) is a well-known zero-difference positioning method which provides accurate and precise results. After the experimental tests, IGS Real Time Service (RTS) officially provided real time orbit and clock products for the GNSS community that allows real-time (RT) PPP applications. Different software packages can be used for RT-PPP. In this study, in order to evaluate the performance of RT-PPP, 3 IGS stations are used. Results, obtained by using BKG Ntrip Client (BNC) Software v2.12, are examined in terms of both accuracy and precision.

How Deep is Shallow? Improving Absolute and Relative Locations of Upper Crustal Seismicity in Switzerland

NASA Astrophysics Data System (ADS)

Diehl, T.; Kissling, E. H.; Singer, J.; Lee, T.; Clinton, J. F.; Waldhauser, F.; Wiemer, S.

2017-12-01

Information on the structure of upper-crustal fault systems and their connection with seismicity is key to the understanding of neotectonic processes. Precisely determined focal depths in combination with structural models can provide important insight into deformation styles of the upper crust (e.g. thin- vs. versus thick-skinned tectonics). Detailed images of seismogenic fault zones in the upper crust, on the other hand, will contribute to the assessment of the hazard related to natural and induced earthquakes, especially in regions targeted for radioactive waste repositories or geothermal energy production. The complex velocity structure of the uppermost crust and unfavorable network geometries, however, often hamper precise locations (i.e. focal depth) of shallow seismicity and therefore limit tectonic interpretations. In this study we present a new high-precision catalog of absolute locations of seismicity in Switzerland. High-quality travel-time data from local and regional earthquakes in the period 2000-2017 are used to solve the coupled hypocenter-velocity structure problem in 1D. For this purpose, the well-known VELEST inversion software was revised and extended to improve the quality assessment of travel-time data and to facilitate the identification of erroneous picks in the bulletin data. Results from the 1D inversion are used as initial parameters for a 3D local earthquake tomography. Well-studied earthquakes and high-quality quarry blasts are used to assess the quality of 1D and 3D relocations. In combination with information available from various controlled-source experiments, borehole data, and geological profiles, focal depths and associated host formations are assessed through comparison with the resolved 3D velocity structure. The new absolute locations and velocity models are used as initial values for relative double-difference relocation of earthquakes in Switzerland. Differential times are calculated from bulletin picks and waveform cross-correlation. The resulting double-difference catalog is used as a regional background catalog for a real-time double-difference approach. We will present our implementation strategy and test its performance for local applications using examples from well-recorded natural and induced earthquake sequences in Switzerland.

40Ar/39Ar dating and paleoenvironmental reconstruction of the Lower Pleistocene sequence of Kvemo-Orozmani (Republic of Georgia): New chronological constraints for Dmanisi

NASA Astrophysics Data System (ADS)

Nomade, S.; Messager, E.; Voinchet, P.; Mgeladze, A.; Guillou, H.; Ferring, R.; Lordkipanidze, D.

2010-12-01

Discovery of Early Pleistocene hominid remains about 15 years ago in Dmanisi (southwestern part of the actual Republic of Georgia) provides evidence on an early expansion of hominid out of Africa as early as the Olduvai subchron period (Gabunia et al., 2001). Two other Early Pleistocene sequences only few kilometers from Dmanisi: Zemo and Kvemo Orozmani are of prime interest to improve the dating of this exceptional site. They both display similar sediments than Dmanisi, but contrary to it, they both are overly by a lava flow allowing to precisely bracketing these sequences using radio-isotopic methods. In this contribution, we present the first high precision 40Ar/39Ar dating and paleoecological reconstruction (phytoliths record) of the Kvemo-Orozmani sequence. The 40Ar/39Ar ages we obtained on the lava flow bracketing the Kvemo Orozmani sequence are: 1.83 ± 0.02Ma and 1.77 ± 0.02Ma (95% confidence, relative to the ACR2 standard at 1.194 Ma). These numerical ages place the sequence exactly at the top of the Olduvai subchron. Furthermore, the lowermost lava flow (c.a. 1.83Ma) is only marginally younger than the lava flow found below the Dmanisi site and dated at 1.85 ± 0.01Ma (Gabunia et al.,(2000)), whereas, the uppermost one displays the same age than the one covering the Zemo Orozmani sequence (Gabunia et al., 2000) located only 2km East. Phytoliths analyses (silica opal produced by plants) show that lower part of the sequence is associated with herbaceous vegetations composed of both temperate and sub-tropical taxa whereas the upper part of the sequence shows an absence of subtropical phytoliths taxa suggesting dryer condition. The shift in the phytoliths assemblage we found in Kvemo-Orozmani is similar to the one described in Dmanisi at the top of the A stratum and corresponds paleomagnetically to the top of the Olduvai subchron (Messager et al., 2010). Both numerical ages and phytoliths assemblages we obtained suggest that the Kvemo Orozmani sequence corresponds to the period of occupation in Dmanisi and allow us to discuss both the age as well as the palaeoecological context of early hominids in Georgia. Gabunia et al., (2000), Science 288, 1019-1025; Messager et al., (2010), Palaeogeography, Palaeoclimatology, Palaeoecology, 288, 1-13

[Contribution and challenges of Big Data in oncology].

PubMed

Saintigny, Pierre; Foy, Jean-Philippe; Ferrari, Anthony; Cassier, Philippe; Viari, Alain; Puisieux, Alain

2017-03-01

Since the first draft of the human genome sequence published in 2001, the cost of sequencing has dramatically decreased. The development of new technologies such as next generation sequencing led to a comprehensive characterization of a large number of tumors of various types as well as to significant advances in precision medicine. Despite the valuable information this technological revolution has allowed to produce, the vast amount of data generated resulted in the emergence of new challenges for the biomedical community, such as data storage, processing and mining. Here, we describe the contribution and challenges of Big Data in oncology. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Somatic Point Mutation Calling in Low Cellularity Tumors

PubMed Central

Kassahn, Karin S.; Holmes, Oliver; Nones, Katia; Patch, Ann-Marie; Miller, David K.; Christ, Angelika N.; Harliwong, Ivon; Bruxner, Timothy J.; Xu, Qinying; Anderson, Matthew; Wood, Scott; Leonard, Conrad; Taylor, Darrin; Newell, Felicity; Song, Sarah; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Steptoe, Anita; Pajic, Marina; Cowley, Mark J.; Pinese, Mark; Chang, David K.; Gill, Anthony J.; Johns, Amber L.; Wu, Jianmin; Wilson, Peter J.; Fink, Lynn; Biankin, Andrew V.; Waddell, Nicola; Grimmond, Sean M.; Pearson, John V.

2013-01-01

Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/) for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform. PMID:24250782

Operon-mapper: A Web Server for Precise Operon Identification in Bacterial and Archaeal Genomes.

PubMed

Taboada, Blanca; Estrada, Karel; Ciria, Ricardo; Merino, Enrique

2018-06-19

Operon-mapper is a web server that accurately, easily, and directly predicts the operons of any bacterial or archaeal genome sequence. The operon predictions are based on the intergenic distance of neighboring genes as well as the functional relationships of their protein-coding products. To this end, Operon-mapper finds all the ORFs within a given nucleotide sequence, along with their genomic coordinates, orthology groups, and functional relationships. We believe that Operon-mapper, due to its accuracy, simplicity and speed, as well as the relevant information that it generates, will be a useful tool for annotating and characterizing genomic sequences. http://biocomputo.ibt.unam.mx/operon_mapper/.

Research on wind field algorithm of wind lidar based on BP neural network and grey prediction

NASA Astrophysics Data System (ADS)

Chen, Yong; Chen, Chun-Li; Luo, Xiong; Zhang, Yan; Yang, Ze-hou; Zhou, Jie; Shi, Xiao-ding; Wang, Lei

2018-01-01

This paper uses the BP neural network and grey algorithm to forecast and study radar wind field. In order to reduce the residual error in the wind field prediction which uses BP neural network and grey algorithm, calculating the minimum value of residual error function, adopting the residuals of the gray algorithm trained by BP neural network, using the trained network model to forecast the residual sequence, using the predicted residual error sequence to modify the forecast sequence of the grey algorithm. The test data show that using the grey algorithm modified by BP neural network can effectively reduce the residual value and improve the prediction precision.

Influence of Waveform Characteristics on LiDAR Ranging Accuracy and Precision

PubMed Central

Yang, Bingwei; Xie, Xinhao; Li, Duan

2018-01-01

Time of flight (TOF) based light detection and ranging (LiDAR) is a technology for calculating distance between start/stop signals of time of flight. In lab-built LiDAR, two ranging systems for measuring flying time between start/stop signals include time-to-digital converter (TDC) that counts time between trigger signals and analog-to-digital converter (ADC) that processes the sampled start/stop pulses waveform for time estimation. We study the influence of waveform characteristics on range accuracy and precision of two kinds of ranging system. Comparing waveform based ranging (WR) with analog discrete return system based ranging (AR), a peak detection method (WR-PK) shows the best ranging performance because of less execution time, high ranging accuracy, and stable precision. Based on a novel statistic mathematical method maximal information coefficient (MIC), WR-PK precision has a high linear relationship with the received pulse width standard deviation. Thus keeping the received pulse width of measuring a constant distance as stable as possible can improve ranging precision. PMID:29642639

A mutation in yeast mitochondrial DNA results in a precise excision of the terminal intron of the cytochrome b gene.

PubMed

Hill, J; McGraw, P; Tzagoloff, A

1985-03-25

The yeast nuclear gene CBP2 was previously proposed to code for a protein necessary for processing of the terminal intron in the cytochrome b pre-mRNA (McGraw, P., and Tzagoloff, A. (1983) J. Biol. Chem. 258, 9459-9468). In the present study we describe a mitochondrial mutation capable of suppressing the respiratory deficiency of cbp2 mutants. The mitochondrial suppressor mutation has been shown to be the result of a precise excision of the last intervening sequence from the cytochrome b gene. Strains with the altered mitochondrial DNA have normal levels of mature cytochrome b mRNA and of cytochrome b and exhibit wild type growth on glycerol. These results confirm that CBP2 codes for a protein specifically required for splicing of the cytochrome b intron and further suggest that absence of the intervening sequence does not noticeably affect the expression of respiratory function in mitochondria.