A hypothetical learning trajectory for conceptualizing matrices as linear transformations

NASA Astrophysics Data System (ADS)

Andrews-Larson, Christine; Wawro, Megan; Zandieh, Michelle

2017-08-01

In this paper, we present a hypothetical learning trajectory (HLT) aimed at supporting students in developing flexible ways of reasoning about matrices as linear transformations in the context of introductory linear algebra. In our HLT, we highlight the integral role of the instructor in this development. Our HLT is based on the 'Italicizing N' task sequence, in which students work to generate, compose, and invert matrices that correspond to geometric transformations specified within the problem context. In particular, we describe the ways in which the students develop local transformation views of matrix multiplication (focused on individual mappings of input vectors to output vectors) and extend these local views to more global views in which matrices are conceptualized in terms of how they transform a space in a coordinated way.

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

PubMed

Hirsch, B; Endris, V; Lassmann, S; Weichert, W; Pfarr, N; Schirmacher, P; Kovaleva, V; Werner, M; Bonzheim, I; Fend, F; Sperveslage, J; Kaulich, K; Zacher, A; Reifenberger, G; Köhrer, K; Stepanow, S; Lerke, S; Mayr, T; Aust, D E; Baretton, G; Weidner, S; Jung, A; Kirchner, T; Hansmann, M L; Burbat, L; von der Wall, E; Dietel, M; Hummel, M

2018-04-01

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

Modelling dynamics with context-free grammars

NASA Astrophysics Data System (ADS)

García-Huerta, Juan-M.; Jiménez-Hernández, Hugo; Herrera-Navarro, Ana-M.; Hernández-Díaz, Teresa; Terol-Villalobos, Ivan

2014-03-01

This article presents a strategy to model the dynamics performed by vehicles in a freeway. The proposal consists on encode the movement as a set of finite states. A watershed-based segmentation is used to localize regions with high-probability of motion. Each state represents a proportion of a camera projection in a two-dimensional space, where each state is associated to a symbol, such that any combination of symbols is expressed as a language. Starting from a sequence of symbols through a linear algorithm a free-context grammar is inferred. This grammar represents a hierarchical view of common sequences observed into the scene. Most probable grammar rules express common rules associated to normal movement behavior. Less probable rules express themselves a way to quantify non-common behaviors and they might need more attention. Finally, all sequences of symbols that does not match with the grammar rules, may express itself uncommon behaviors (abnormal). The grammar inference is built with several sequences of images taken from a freeway. Testing process uses the sequence of symbols emitted by the scenario, matching the grammar rules with common freeway behaviors. The process of detect abnormal/normal behaviors is managed as the task of verify if any word generated by the scenario is recognized by the grammar.

Conserved noncoding sequences conserve biological networks and influence genome evolution.

PubMed

Xie, Jianbo; Qian, Kecheng; Si, Jingna; Xiao, Liang; Ci, Dong; Zhang, Deqiang

2018-05-01

Comparative genomics approaches have identified numerous conserved cis-regulatory sequences near genes in plant genomes. Despite the identification of these conserved noncoding sequences (CNSs), our knowledge of their functional importance and selection remains limited. Here, we used a combination of DNA methylome analysis, microarray expression analyses, and functional annotation to study these sequences in the model tree Populus trichocarpa. Methylation in CG contexts and non-CG contexts was lower in CNSs, particularly CNSs in the 5'-upstream regions of genes, compared with other sites in the genome. We observed that CNSs are enriched in genes with transcription and binding functions, and this also associated with syntenic genes and those from whole-genome duplications, suggesting that cis-regulatory sequences play a key role in genome evolution. We detected a significant positive correlation between CNS number and protein interactions, suggesting that CNSs may have roles in the evolution and maintenance of biological networks. The divergence of CNSs indicates that duplication-degeneration-complementation drives the subfunctionalization of a proportion of duplicated genes from whole-genome duplication. Furthermore, population genomics confirmed that most CNSs are under strong purifying selection and only a small subset of CNSs shows evidence of adaptive evolution. These findings provide a foundation for future studies exploring these key genomic features in the maintenance of biological networks, local adaptation, and transcription.

Prediction of Human Activity by Discovering Temporal Sequence Patterns.

PubMed

Li, Kang; Fu, Yun

2014-08-01

Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units.

Single-molecule DNA unzipping reveals asymmetric modulation of a transcription factor by its binding site sequence and context

PubMed Central

Rudnizky, Sergei; Khamis, Hadeel; Malik, Omri; Squires, Allison H; Meller, Amit; Melamed, Philippa

2018-01-01

Abstract Most functional transcription factor (TF) binding sites deviate from their ‘consensus’ recognition motif, although their sites and flanking sequences are often conserved across species. Here, we used single-molecule DNA unzipping with optical tweezers to study how Egr-1, a TF harboring three zinc fingers (ZF1, ZF2 and ZF3), is modulated by the sequence and context of its functional sites in the Lhb gene promoter. We find that both the core 9 bp bound to Egr-1 in each of the sites, and the base pairs flanking them, modulate the affinity and structure of the protein–DNA complex. The effect of the flanking sequences is asymmetric, with a stronger effect for the sequence flanking ZF3. Characterization of the dissociation time of Egr-1 revealed that a local, mechanical perturbation of the interactions of ZF3 destabilizes the complex more effectively than a perturbation of the ZF1 interactions. Our results reveal a novel role for ZF3 in the interaction of Egr-1 with other proteins and the DNA, providing insight on the regulation of Lhb and other genes by Egr-1. Moreover, our findings reveal the potential of small changes in DNA sequence to alter transcriptional regulation, and may shed light on the organization of regulatory elements at promoters. PMID:29253225

Terminator Detection by Support Vector Machine Utilizing aStochastic Context-Free Grammar

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

Francis-Lyon, Patricia; Cristianini, Nello; Holbrook, Stephen

2006-12-30

A 2-stage detector was designed to find rho-independent transcription terminators in the Escherichia coli genome. The detector includes a Stochastic Context Free Grammar (SCFG) component and a Support Vector Machine (SVM) component. To find terminators, the SCFG searches the intergenic regions of nucleotide sequence for local matches to a terminator grammar that was designed and trained utilizing examples of known terminators. The grammar selects sequences that are the best candidates for terminators and assigns them a prefix, stem-loop, suffix structure using the Cocke-Younger-Kasaami (CYK) algorithm, modified to incorporate energy affects of base pairing. The parameters from this inferred structure aremore » passed to the SVM classifier, which distinguishes terminators from non-terminators that score high according to the terminator grammar. The SVM was trained with negative examples drawn from intergenic sequences that include both featureless and RNA gene regions (which were assigned prefix, stem-loop, suffix structure by the SCFG), so that it successfully distinguishes terminators from either of these. The classifier was found to be 96.4% successful during testing.« less

Fingerprints of Modified RNA Bases from Deep Sequencing Profiles.

PubMed

Kietrys, Anna M; Velema, Willem A; Kool, Eric T

2017-11-29

Posttranscriptional modifications of RNA bases are not only found in many noncoding RNAs but have also recently been identified in coding (messenger) RNAs as well. They require complex and laborious methods to locate, and many still lack methods for localized detection. Here we test the ability of next-generation sequencing (NGS) to detect and distinguish between ten modified bases in synthetic RNAs. We compare ultradeep sequencing patterns of modified bases, including miscoding, insertions and deletions (indels), and truncations, to unmodified bases in the same contexts. The data show widely varied responses to modification, ranging from no response, to high levels of mutations, insertions, deletions, and truncations. The patterns are distinct for several of the modifications, and suggest the future use of ultradeep sequencing as a fingerprinting strategy for locating and identifying modifications in cellular RNAs.

Limits of neutral drift: lessons from the in vitro evolution of two ribozymes.

PubMed

Petrie, Katherine L; Joyce, Gerald F

2014-10-01

The relative contributions of adaptive selection and neutral drift to genetic change are unknown but likely depend on the inherent abundance of functional genotypes in sequence space and how accessible those genotypes are to one another. To better understand the relative roles of selection and drift in evolution, local fitness landscapes for two different RNA ligase ribozymes were examined using a continuous in vitro evolution system under conditions that foster the capacity for neutral drift to mediate genetic change. The exploration of sequence space was accelerated by increasing the mutation rate using mutagenic nucleotide analogs. Drift was encouraged by carrying out evolution within millions of separate compartments to exploit the founder effect. Deep sequencing of individuals from the evolved populations revealed that the distribution of genotypes did not escape the starting local fitness peak, remaining clustered around the sequence used to initiate evolution. This is consistent with a fitness landscape where high-fitness genotypes are sparse and well isolated, and suggests, at least in this context, that neutral drift alone is not a primary driver of genetic change. Neutral drift does, however, provide a repository of genetic variation upon which adaptive selection can act.

Torque measurements reveal sequence-specific cooperative transitions in supercoiled DNA

PubMed Central

Oberstrass, Florian C.; Fernandes, Louis E.; Bryant, Zev

2012-01-01

B-DNA becomes unstable under superhelical stress and is able to adopt a wide range of alternative conformations including strand-separated DNA and Z-DNA. Localized sequence-dependent structural transitions are important for the regulation of biological processes such as DNA replication and transcription. To directly probe the effect of sequence on structural transitions driven by torque, we have measured the torsional response of a panel of DNA sequences using single molecule assays that employ nanosphere rotational probes to achieve high torque resolution. The responses of Z-forming d(pGpC)n sequences match our predictions based on a theoretical treatment of cooperative transitions in helical polymers. “Bubble” templates containing 50–100 bp mismatch regions show cooperative structural transitions similar to B-DNA, although less torque is required to disrupt strand–strand interactions. Our mechanical measurements, including direct characterization of the torsional rigidity of strand-separated DNA, establish a framework for quantitative predictions of the complex torsional response of arbitrary sequences in their biological context. PMID:22474350

Structural mechanics of DNA wrapping in the nucleosome.

PubMed

Battistini, Federica; Hunter, Christopher A; Gardiner, Eleanor J; Packer, Martin J

2010-02-19

Experimental X-ray crystal structures and a database of calculated structural parameters of DNA octamers were used in combination to analyse the mechanics of DNA bending in the nucleosome core complex. The 1kx5 X-ray crystal structure of the nucleosome core complex was used to determine the relationship between local structure at the base-step level and the global superhelical conformation observed for nucleosome-bound DNA. The superhelix is characterised by a large curvature (597 degrees) in one plane and very little curvature (10 degrees) in the orthogonal plane. Analysis of the curvature at the level of 10-step segments shows that there is a uniform curvature of 30 degrees per helical turn throughout most of the structure but that there are two sharper kinks of 50 degrees at +/-2 helical turns from the central dyad base pair. The curvature is due almost entirely to the base-step parameter roll. There are large periodic variations in roll, which are in phase with the helical twist and account for 500 degrees of the total curvature. Although variations in the other base-step parameters perturb the local path of the DNA, they make minimal contributions to the total curvature. This implies that DNA bending in the nucleosome is achieved using the roll-slide-twist degree of freedom previously identified as the major degree of freedom in naked DNA oligomers. The energetics of bending into a nucleosome-bound conformation were therefore analysed using a database of structural parameters that we have previously developed for naked DNA oligomers. The minimum energy roll, the roll flexibility force constant and the maximum and minimum accessible roll values were obtained for each base step in the relevant octanucleotide context to account for the effects of conformational coupling that vary with sequence context. The distribution of base-step roll values and corresponding strain energy required to bend DNA into the nucleosome-bound conformation defined by the 1kx5 structure were obtained by applying a constant bending moment. When a single bending moment was applied to the entire sequence, the local details of the calculated structure did not match the experiment. However, when local 10-step bending moments were applied separately, the calculated structure showed excellent agreement with experiment. This implies that the protein applies variable bending forces along the DNA to maintain the superhelical path required for nucleosome wrapping. In particular, the 50 degrees kinks are constraints imposed by the protein rather than a feature of the 1kx5 DNA sequence. The kinks coincide with a relatively flexible region of the sequence, and this is probably a prerequisite for high-affinity nucleosome binding, but the bending strain energy is significantly higher at these points than for the rest of the sequence. In the most rigid regions of the sequence, a higher strain energy is also required to achieve the standard 30 degrees curvature per helical turn. We conclude that matching of the DNA sequence to the local roll periodicity required to achieve bending, together with the increased flexibility required at the kinks, determines the sequence selectivity of DNA wrapping in the nucleosome. 2009 Elsevier Ltd. All rights reserved.

Local contextual processing of abstract and meaningful real-life images in professional athletes.

PubMed

Fogelson, Noa; Fernandez-Del-Olmo, Miguel; Acero, Rafael Martín

2012-05-01

We investigated the effect of abstract versus real-life meaningful images from sports on local contextual processing in two groups of professional athletes. Local context was defined as the occurrence of a short predictive series of stimuli occurring before delivery of a target event. EEG was recorded in 10 professional basketball players and 9 professional athletes of individual sports during three sessions. In each session, a different set of visual stimuli were presented: triangles facing left, up, right, or down; four images of a basketball player throwing a ball; four images of a baseball player pitching a baseball. Stimuli consisted of 15 % targets and 85 % of equal numbers of three types of standards. Recording blocks consisted of targets preceded by randomized sequences of standards and by sequences including a predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. In all three sessions, reaction times and peak P3b latencies were shorter for predicted targets compared with random targets, the last most informative stimulus of the predictive sequence induced a robust P3b, and N2 amplitude was larger for random targets compared with predicted targets. P3b and N2 peak amplitudes were larger in the professional basketball group in comparison with professional athletes of individual sports, across the three sessions. The findings of this study suggest that local contextual information is processed similarly for abstract and for meaningful images and that professional basketball players seem to allocate more attentional resources in the processing of these visual stimuli.

Telerobot control system

NASA Technical Reports Server (NTRS)

Backes, Paul G. (Inventor); Tso, Kam S. (Inventor)

1993-01-01

This invention relates to an operator interface for controlling a telerobot to perform tasks in a poorly modeled environment and/or within unplanned scenarios. The telerobot control system includes a remote robot manipulator linked to an operator interface. The operator interface includes a setup terminal, simulation terminal, and execution terminal for the control of the graphics simulator and local robot actuator as well as the remote robot actuator. These terminals may be combined in a single terminal. Complex tasks are developed from sequential combinations of parameterized task primitives and recorded teleoperations, and are tested by execution on a graphics simulator and/or local robot actuator, together with adjustable time delays. The novel features of this invention include the shared and supervisory control of the remote robot manipulator via operator interface by pretested complex tasks sequences based on sequences of parameterized task primitives combined with further teleoperation and run-time binding of parameters based on task context.

Distant neighbor base sequence context effects in human nucleotide excision repair of a benzo[a]pyrene-derived DNA lesion

PubMed Central

Cai, Yuqin; Kropachev, Konstantin; Xu, Rong; Tang, Yijin; Kolbanovskii, Marina; Kolbanovskii, Alexander; Amin, Shantu; Patel, Dinshaw J.; Broyde, Suse; Geacintov, Nicholas E.

2010-01-01

Summary The effects of non-nearest base sequences, beyond the nucleotides flanking a DNA lesion on either side, on nucleotide excision repair (NER) in extracts from human cells were investigated. We constructed two duplexes containing the same minor groove-aligned 10S (+)-trans-anti-B[a]P-N2-dG (G*) DNA adduct, derived from the environmental carcinogen benzo[a]pyrene (B[a]P): 5′-C-C-A-T-C-G*-C-T-A-C-C-3′ (CG*C-I), and 5′-C-A-C3-A4-C5-G*-C-A-C-A-C-3′ (CG*C-II). We utilized gel electrophoresis to compare the extent of DNA bending, and molecular dynamics (MD) simulations to analyze the structural characteristics of these two DNA duplexes. The NER efficiencies are 1.6 ± 0.2 times greater in the case of the CG*C-II than the CG*C-I sequence context in 135-mer duplexes. Gel electrophoresis and self-ligation circularization experiments revealed that the CG*C-II duplex is more bent than the CG*C-I duplex, while MD simulations showed that the unique -C3-A4-C5- segment in the CG*C-II duplex plays a key role. The presence of a minor groove-positioned guanine amino group, namely, the Watson-Crick partner to C3, acts as a wedge; facilitated by a highly deformable local -C3-A4- base step, this amino group allows the B[a]P ring system to produce a more enlarged minor groove in CG*C-II than in CG*C-I, as well as a local untwisting and enlarged and flexible Roll only in the CG*C-II sequence. These structural properties fit well with our prior findings that in the case of the family of minor groove 10S (+)-trans-anti-B[a]P-N2-dG lesions, flexible bends and enlarged minor groove widths (Cai et al. (2009) J. Mol. Biol., 385: 30–44) constitute NER recognition signals, and extend our understanding of sequence context effects on NER to the neighbors that are distant to the lesion. PMID:20399214

A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

PubMed

Perycz, Malgorzata; Krwawicz, Joanna; Bochtler, Matthias

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

A TALE-inspired computational screen for proteins that contain approximate tandem repeats

PubMed Central

Krwawicz, Joanna

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen. PMID:28617832

Learning Grasp Context Distinctions that Generalize

NASA Technical Reports Server (NTRS)

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

2006-01-01

Control-based approaches to grasp synthesis create grasping behavior by sequencing and combining control primitives. In the absence of any other structure, these approaches must evaluate a large number of feasible control sequences as a function of object shape, object pose, and task. This work explores a new approach to grasp synthesis that limits consideration to variations on a generalized localize-reach-grasp control policy. A new learning algorithm, known as schema structured learning, is used to learn which instantiations of the generalized policy are most likely to lead to a successful grasp in different problem contexts. Two experiments are described where Dexter, a bimanual upper torso, learns to select an appropriate grasp strategy as a function of object eccentricity and orientation. In addition, it is shown that grasp skills learned in this way can generalize to new objects. Results are presented showing that after learning how to grasp a small, representative set of objects, the robot's performance quantitatively improves for similar objects that it has not experienced before.

Domain Specificity of MAP3K Family Members, MLK and Tak1, for JNK Signaling in Drosophila

PubMed Central

Stronach, Beth; Lennox, Ashley L.; Garlena, Rebecca A.

2014-01-01

A highly diverse set of protein kinases functions as early responders in the mitogen- and stress-activated protein kinase (MAPK/SAPK) signaling pathways. For instance, humans possess 14 MAPK kinase kinases (MAP3Ks) that activate Jun kinase (JNK) signaling downstream. A major challenge is to decipher the selective and redundant functions of these upstream MAP3Ks. Taking advantage of the relative simplicity of Drosophila melanogaster as a model system, we assessed MAP3K signaling specificity in several JNK-dependent processes during development and stress response. Our approach was to generate molecular chimeras between two MAP3K family members, the mixed lineage kinase, Slpr, and the TGF-β activated kinase, Tak1, which share 32% amino acid identity across the kinase domain but otherwise differ in sequence and domain structure, and then test the contributions of various domains for protein localization, complementation of mutants, and activation of signaling. We found that overexpression of the wild-type kinases stimulated JNK signaling in alternate contexts, so cells were capable of responding to both MAP3Ks, but with distinct outcomes. Relative to wild-type, the catalytic domain swaps compensated weakly or not at all, despite having a shared substrate, the JNK kinase Hep. Tak1 C-terminal domain-containing constructs were inhibitory in Tak1 signaling contexts, including tumor necrosis factor-dependent cell death and innate immune signaling; however, depressing antimicrobial gene expression did not necessarily cause phenotypic susceptibility to infection. These same constructs were neutral in the context of Slpr-dependent developmental signaling, reflecting differential subcellular protein localization and by inference, point of activation. Altogether, our findings suggest that the selective deployment of a particular MAP3K can be attributed in part to its inherent sequence differences, cellular localization, and binding partner availability. PMID:24429281

Context and meter enhance long-range planning in music performance

PubMed Central

Mathias, Brian; Pfordresher, Peter Q.; Palmer, Caroline

2015-01-01

Neural responses demonstrate evidence of resonance, or oscillation, during the production of periodic auditory events. Music contains periodic auditory events that give rise to a sense of beat, which in turn generates a sense of meter on the basis of multiple periodicities. Metrical hierarchies may aid memory for music by facilitating similarity-based associations among sequence events at different periodic distances that unfold in longer contexts. A fundamental question is how metrical associations arising from a musical context influence memory during music performance. Longer contexts may facilitate metrical associations at higher hierarchical levels more than shorter contexts, a prediction of the range model, a formal model of planning processes in music performance (Palmer and Pfordresher, 2003; Pfordresher et al., 2007). Serial ordering errors, in which intended sequence events are produced in incorrect sequence positions, were measured as skilled pianists performed musical pieces that contained excerpts embedded in long or short musical contexts. Pitch errors arose from metrically similar positions and further sequential distances more often when the excerpt was embedded in long contexts compared to short contexts. Musicians’ keystroke intensities and error rates also revealed influences of metrical hierarchies, which differed for performances in long and short contexts. The range model accounted for contextual effects and provided better fits to empirical findings when metrical associations between sequence events were included. Longer sequence contexts may facilitate planning during sequence production by increasing conceptual similarity between hierarchically associated events. These findings are consistent with the notion that neural oscillations at multiple periodicities may strengthen metrical associations across sequence events during planning. PMID:25628550

Context-Dependent Learning in People With Parkinson's Disease.

PubMed

Lee, Ya-Yun; Winstein, Carolee J; Gordon, James; Petzinger, Giselle M; Zelinski, Elizabeth M; Fisher, Beth E

2016-01-01

Context-dependent learning is a phenomenon in which people demonstrate superior performance in the context in which they originally learned a skill but perform less well in a novel context. This study investigated context-dependent learning in people with Parkinson's disease (PD) and age-matched nondisabled adults. All participants practiced 3 finger sequences, each embedded within a unique context (colors and locations on a computer screen). One day after practice, the participants were tested either under the sequence-context associations remained the same as during practice, or the sequence-context associations were changed (SWITCH). Compared with nondisabled adults, people with PD demonstrated significantly greater decrement in performance (especially movement time) under the SWITCH condition, suggesting that individuals with PD are more context dependent than nondisabled adults.

A comparison of the effects of temporary hippocampal lesions on single and dual context versions of the olfactory sequence memory task.

PubMed

Sill, Orriana C; Smith, David M

2012-08-01

In recent years, many animal models of memory have focused on one or more of the various components of episodic memory. For example, the odor sequence memory task requires subjects to remember individual items and events (the odors) and the temporal aspects of the experience (the sequence of odor presentation). The well-known spatial context coding function of the hippocampus, as exemplified by place cell firing, may reflect the "where" component of episodic memory. In the present study, we added a contextual component to the odor sequence memory task by training rats to choose the earlier odor in one context and the later odor in another context and we compared the effects of temporary hippocampal lesions on performance of the original single context task and the new dual context task. Temporary lesions significantly impaired the single context task, although performance remained significantly above chance levels. In contrast, performance dropped all the way to chance when temporary lesions were used in the dual context task. These results demonstrate that rats can learn a dual context version of the odor sequence learning task that requires the use of contextual information along with the requirement to remember the "what" and "when" components of the odor sequence. Moreover, the addition of the contextual component made the task fully dependent on the hippocampus.

Sequence-Specific Targeting of Dosage Compensation in Drosophila Favors an Active Chromatin Context

PubMed Central

Gelbart, Marnie; Tolstorukov, Michael Y.; Plachetka, Annette; Kharchenko, Peter V.; Jung, Youngsook L.; Gorchakov, Andrey A.; Larschan, Erica; Gu, Tingting; Minoda, Aki; Riddle, Nicole C.; Schwartz, Yuri B.; Elgin, Sarah C. R.; Karpen, Gary H.; Pirrotta, Vincenzo; Kuroda, Mitzi I.; Park, Peter J.

2012-01-01

The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at “entry sites” that contain a consensus sequence motif (“MSL recognition element” or MRE). However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex) and female Kc cells (which lack the complex), we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome. PMID:22570616

CodonLogo: a sequence logo-based viewer for codon patterns.

PubMed

Sharma, Virag; Murphy, David P; Provan, Gregory; Baranov, Pavel V

2012-07-15

Conserved patterns across a multiple sequence alignment can be visualized by generating sequence logos. Sequence logos show each column in the alignment as stacks of symbol(s) where the height of a stack is proportional to its informational content, whereas the height of each symbol within the stack is proportional to its frequency in the column. Sequence logos use symbols of either nucleotide or amino acid alphabets. However, certain regulatory signals in messenger RNA (mRNA) act as combinations of codons. Yet no tool is available for visualization of conserved codon patterns. We present the first application which allows visualization of conserved regions in a multiple sequence alignment in the context of codons. CodonLogo is based on WebLogo3 and uses the same heuristics but treats codons as inseparable units of a 64-letter alphabet. CodonLogo can discriminate patterns of codon conservation from patterns of nucleotide conservation that appear indistinguishable in standard sequence logos. The CodonLogo source code and its implementation (in a local version of the Galaxy Browser) are available at http://recode.ucc.ie/CodonLogo and through the Galaxy Tool Shed at http://toolshed.g2.bx.psu.edu/.

The Selenocysteine-Specific Elongation Factor Contains Unique Sequences That Are Required for Both Nuclear Export and Selenocysteine Incorporation.

PubMed

Dubey, Aditi; Copeland, Paul R

2016-01-01

Selenocysteine (Sec) is a critical residue in at least 25 human proteins that are essential for antioxidant defense and redox signaling in cells. Sec is inserted into proteins cotranslationally by the recoding of an in-frame UGA termination codon to a Sec codon. In eukaryotes, this recoding event requires several specialized factors, including a dedicated, Sec-specific elongation factor called eEFSec, which binds Sec-tRNASec with high specificity and delivers it to the ribosome for selenoprotein production. Unlike most translation factors, including the canonical elongation factor eEF1A, eEFSec readily localizes to the nucleus of mammalian cells and shuttles between the cytoplasmic and nuclear compartments. The functional significance of eEFSec's nuclear localization has remained unclear. In this study, we have examined the subcellular localization of eEFSec in the context of altered Sec incorporation to demonstrate that reduced selenoprotein production does not correlate with changes in the nuclear localization of eEFSec. In addition, we identify several novel sequences of the protein that are essential for localization as well as Sec insertion activity, and show that eEFSec utilizes CRM1-mediated nuclear export pathway. Our findings argue for two distinct pools of eEFSec in the cell, where the cytoplasmic pool participates in Sec incorporation and the nuclear pool may be involved in an as yet unknown function.

Non-random distribution and co-localization of purine/pyrimidine-encoded information and transcriptional regulatory domains.

PubMed

Povinelli, C M

1992-01-01

In order to detect sequence-based information predictive for the location of eukaryotic transcriptional regulatory domains, the frequencies and distributions of the 36 possible purine/pyrimidine reverse complement hexamer pairs was determined for test sets of real and random sequences. The distribution of one of the hexamer pairs (RRYYRR/YYRRYY, referred to as M1) was further examined in a larger set of sequences (> 32 genes, 230 kb). Predominant clusters of M1 and the locations of eukaryotic transcriptional regulatory domains were found to be associated and non-randomly distributed along the DNA consistent with a periodicity of approximately 1.2 kb. In the context of higher ordered chromatin this would align promoters, enhancers and the predominant clusters of M1 longitudinally along one face of a 30 nm fiber. Using only information about the distribution of the M1 motif, 50-70% of a sequence could be eliminated as being unlikely to contain transcriptional regulatory domains with an 87% recovery of the regulatory domains present.

A reduced amino acid alphabet for understanding and designing protein adaptation to mutation.

PubMed

Etchebest, C; Benros, C; Bornot, A; Camproux, A-C; de Brevern, A G

2007-11-01

Protein sequence world is considerably larger than structure world. In consequence, numerous non-related sequences may adopt similar 3D folds and different kinds of amino acids may thus be found in similar 3D structures. By grouping together the 20 amino acids into a smaller number of representative residues with similar features, sequence world simplification may be achieved. This clustering hence defines a reduced amino acid alphabet (reduced AAA). Numerous works have shown that protein 3D structures are composed of a limited number of building blocks, defining a structural alphabet. We previously identified such an alphabet composed of 16 representative structural motifs (5-residues length) called Protein Blocks (PBs). This alphabet permits to translate the structure (3D) in sequence of PBs (1D). Based on these two concepts, reduced AAA and PBs, we analyzed the distributions of the different kinds of amino acids and their equivalences in the structural context. Different reduced sets were considered. Recurrent amino acid associations were found in all the local structures while other were specific of some local structures (PBs) (e.g Cysteine, Histidine, Threonine and Serine for the alpha-helix Ncap). Some similar associations are found in other reduced AAAs, e.g Ile with Val, or hydrophobic aromatic residues Trp with Phe and Tyr. We put into evidence interesting alternative associations. This highlights the dependence on the information considered (sequence or structure). This approach, equivalent to a substitution matrix, could be useful for designing protein sequence with different features (for instance adaptation to environment) while preserving mainly the 3D fold.

A Comparison of the Effects of Temporary Hippocampal Lesions on Single and Dual Context Versions of the Olfactory Sequence Memory Task

PubMed Central

Sill, Orriana C.; Smith, David M.

2012-01-01

In recent years, many animal models of memory have focused on one or more of the various components of episodic memory. For example, the odor sequence memory task requires subjects to remember individual items and events (the odors) and the temporal aspects of the experience (the sequence of odor presentation). The well-known spatial context coding function of the hippocampus, as exemplified by place cell firing, may reflect the ‘where’ component of episodic memory. In the present study, we added a contextual component to the odor sequence memory task by training rats to choose the earlier odor in one context and the later odor in another context and we compared the effects of temporary hippocampal lesions on performance of the original single context task and the new dual context task. Temporary lesions significantly impaired the single context task, although performance remained significantly above chance levels. In contrast, performance dropped all the way to chance when temporary lesions were used in the dual context task. These results demonstrate that rats can learn a dual context version of the odor sequence learning task which requires the use of contextual information along with the requirement to remember the ‘what’ and ‘when’ components of the odor sequence. Moreover, the additional requirement of context-dependent expression of the ‘what-when’ memory made the task fully dependent on the hippocampus. Moreover, the addition of the contextual component made the task fully dependent on the hippocampus. PMID:22687149

DNA sequence determinants controlling affinity, stability and shape of DNA complexes bound by the nucleoid protein Fis

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

Hancock, Stephen P.; Stella, Stefano; Cascio, Duilio

The abundant Fis nucleoid protein selectively binds poorly related DNA sequences with high affinities to regulate diverse DNA reactions. Fis binds DNA primarily through DNA backbone contacts and selects target sites by reading conformational properties of DNA sequences, most prominently intrinsic minor groove widths. High-affinity binding requires Fis-stabilized DNA conformational changes that vary depending on DNA sequence. In order to better understand the molecular basis for high affinity site recognition, we analyzed the effects of DNA sequence within and flanking the core Fis binding site on binding affinity and DNA structure. X-ray crystal structures of Fis-DNA complexes containing variable sequencesmore » in the noncontacted center of the binding site or variations within the major groove interfaces show that the DNA can adapt to the Fis dimer surface asymmetrically. We show that the presence and position of pyrimidine-purine base steps within the major groove interfaces affect both local DNA bending and minor groove compression to modulate affinities and lifetimes of Fis-DNA complexes. Sequences flanking the core binding site also modulate complex affinities, lifetimes, and the degree of local and global Fis-induced DNA bending. In particular, a G immediately upstream of the 15 bp core sequence inhibits binding and bending, and A-tracts within the flanking base pairs increase both complex lifetimes and global DNA curvatures. Taken together, our observations support a revised DNA motif specifying high-affinity Fis binding and highlight the range of conformations that Fis-bound DNA can adopt. Lastly, the affinities and DNA conformations of individual Fis-DNA complexes are likely to be tailored to their context-specific biological functions.« less

DNA sequence determinants controlling affinity, stability and shape of DNA complexes bound by the nucleoid protein Fis

DOE PAGES

Hancock, Stephen P.; Stella, Stefano; Cascio, Duilio; ...

2016-03-09

The abundant Fis nucleoid protein selectively binds poorly related DNA sequences with high affinities to regulate diverse DNA reactions. Fis binds DNA primarily through DNA backbone contacts and selects target sites by reading conformational properties of DNA sequences, most prominently intrinsic minor groove widths. High-affinity binding requires Fis-stabilized DNA conformational changes that vary depending on DNA sequence. In order to better understand the molecular basis for high affinity site recognition, we analyzed the effects of DNA sequence within and flanking the core Fis binding site on binding affinity and DNA structure. X-ray crystal structures of Fis-DNA complexes containing variable sequencesmore » in the noncontacted center of the binding site or variations within the major groove interfaces show that the DNA can adapt to the Fis dimer surface asymmetrically. We show that the presence and position of pyrimidine-purine base steps within the major groove interfaces affect both local DNA bending and minor groove compression to modulate affinities and lifetimes of Fis-DNA complexes. Sequences flanking the core binding site also modulate complex affinities, lifetimes, and the degree of local and global Fis-induced DNA bending. In particular, a G immediately upstream of the 15 bp core sequence inhibits binding and bending, and A-tracts within the flanking base pairs increase both complex lifetimes and global DNA curvatures. Taken together, our observations support a revised DNA motif specifying high-affinity Fis binding and highlight the range of conformations that Fis-bound DNA can adopt. Lastly, the affinities and DNA conformations of individual Fis-DNA complexes are likely to be tailored to their context-specific biological functions.« less

Choice of High-Efficacy Strains for the Annual Influenza Vaccine

NASA Astrophysics Data System (ADS)

Deem, Michael

2005-03-01

We introduce a model of protein evolution to explain limitations in the immune system response to vaccination and disease [1]. The phenomenon of original antigenic sin, wherein vaccination creates memory sequences that can increase susceptibility to future exposures to the same disease, is explained as stemming from localization of the immune system response in antibody sequence space. This localization is a result of the roughness in sequence space of the evolved antibody affinity constant for antigen and is observed for diseases with high year-to-year mutation rates, such as influenza. We show that the order parameter within this theory correlates well with efficacies of the H3N2 influenza A component of the annual vaccine between 1971 and 2004 [2,3]. This new measure of antigenic distance predicts vaccine efficacy significantly more accurately than do current state-of-the-art phylogenetic sequence analyses or ferret antisera inhibition assays. We discuss how this new measure of antigenic distance may be used in the context of annual influenza vaccine design and monitoring of vaccine efficacy. 1) M. W. Deem and H. Y. Lee, Phys. Rev. Lett. 91 (2003) 068101. 2) E. T. Munoz and M. W. Deem,q-bio.BM/0408016. 3) V. Gupta, D. J. Earl, and M. W. Deem, ``Choice of High-Efficacy Strains for the Annual Influenza Vaccine,'' submitted.

NG6: Integrated next generation sequencing storage and processing environment.

PubMed

Mariette, Jérôme; Escudié, Frédéric; Allias, Nicolas; Salin, Gérald; Noirot, Céline; Thomas, Sylvain; Klopp, Christophe

2012-09-09

Next generation sequencing platforms are now well implanted in sequencing centres and some laboratories. Upcoming smaller scale machines such as the 454 junior from Roche or the MiSeq from Illumina will increase the number of laboratories hosting a sequencer. In such a context, it is important to provide these teams with an easily manageable environment to store and process the produced reads. We describe a user-friendly information system able to manage large sets of sequencing data. It includes, on one hand, a workflow environment already containing pipelines adapted to different input formats (sff, fasta, fastq and qseq), different sequencers (Roche 454, Illumina HiSeq) and various analyses (quality control, assembly, alignment, diversity studies,…) and, on the other hand, a secured web site giving access to the results. The connected user will be able to download raw and processed data and browse through the analysis result statistics. The provided workflows can easily be modified or extended and new ones can be added. Ergatis is used as a workflow building, running and monitoring system. The analyses can be run locally or in a cluster environment using Sun Grid Engine. NG6 is a complete information system designed to answer the needs of a sequencing platform. It provides a user-friendly interface to process, store and download high-throughput sequencing data.

A case study analysing the process of analogy-based learning in a teaching unit about simple electric circuits

NASA Astrophysics Data System (ADS)

Paatz, Roland; Ryder, James; Schwedes, Hannelore; Scott, Philip

2004-09-01

The purpose of this case study is to analyse the learning processes of a 16-year-old student as she learns about simple electric circuits in response to an analogy-based teaching sequence. Analogical thinking processes are modelled by a sequence of four steps according to Gentner's structure mapping theory (activate base domain, postulate local matches, connect them to a global match, draw candidate inferences). We consider whether Gentner's theory can be used to account for the details of this specific teaching/learning context. The case study involved video-taping teaching and learning activities in a 10th-grade high school course in Germany. Teaching used water flow through pipes as an analogy for electrical circuits. Using Gentner's theory, relational nets were created from the student's statements at different stages of her learning. Overall, these nets reflect the four steps outlined earlier. We also consider to what extent the learning processes revealed by this case study are different from previous analyses of contexts in which no analogical knowledge is available.

The Effect of Practice Schedule on Context-Dependent Learning.

PubMed

Lee, Ya-Yun; Fisher, Beth E

2018-03-02

It is well established that random practice compared to blocked practice enhances motor learning. Additionally, while information in the environment may be incidental, learning is also enhanced when an individual performs a task within the same environmental context in which the task was originally practiced. This study aimed to disentangle the effects of practice schedule and incidental/environmental context on motor learning. Participants practiced three finger sequences under either a random or blocked practice schedule. Each sequence was associated with specific incidental context (i.e., color and location on the computer screen) during practice. The participants were tested under the conditions when the sequence-context associations remained the same or were changed from that of practice. When the sequence-context association was changed, the participants who practiced under blocked schedule demonstrated greater performance decrement than those who practiced under random schedule. The findings suggested that those participants who practiced under random schedule were more resistant to the change of environmental context.

Bicluster Pattern of Codon Context Usages between Flavivirus and Vector Mosquito Aedes aegypti: Relevance to Infection and Transcriptional Response of Mosquito Genes

PubMed Central

Behura, Susanta K.; Severson, David W.

2014-01-01

The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in most of the subtropical and tropical countries. Besides DENV, yellow fever virus (YFV) is also transmitted by A. aegypti. Susceptibility of A. aegypti to West Nile virus (WNV) has also been confirmed. Although studies have indicated correlation of codon bias between flaviviridae and their animal/insect hosts, it is not clear if codon sequences have any relation to susceptibility of A. aegypti to DENV, YFV and WNV. In the current study, usages of codon context sequences (codon pairs for neighboring amino acids) of the vector (A. aegypti) genome as well as the flaviviral genomes are investigated. We used bioinformatics methods to quantify codon context bias in a genome-wide manner of A. aegypti as well as DENV, WNV and YFV sequences. Mutual information statistics was applied to perform bicluster analysis of codon context bias between vector and flaviviral sequences. Functional relevance of the bicluster pattern was inferred from published microarray data. Our study shows that codon context bias of DENV, WNV and YFV sequences varies in a bicluster manner with that of specific sets of genes of A. aegypti. Many of these mosquito genes are known to be differentially expressed in response to flaviviral infection suggesting that codon context sequences of A. aegypti and the flaviviruses may play a role in the susceptible interaction between flaviviruses and this mosquito. The bias inusages of codon context sequences likely has a functional association with susceptibility of A. aegypti to flaviviral infection. The results from this study will allow us to conduct hypothesis driven tests to examine the role of codon contexts bias in evolution of vector-virus interactions at the molecular level. PMID:24838953

Influence of Electron–Holes on DNA Sequence-Specific Mutation Rates

PubMed Central

Suárez-Villagrán, Martha Y; Azevedo, Ricardo B R; Miller, John H

2018-01-01

Abstract Biases in mutation rate can influence molecular evolution, yielding rates of evolution that vary widely in different parts of the genome and even among neighboring nucleotides. Here, we explore one possible mechanism of influence on sequence-specific mutation rates, the electron–hole, which can localize and potentially trigger a replication mismatch. A hole is a mobile site of positive charge created during one-electron oxidation by, for example, radiation, contact with a mutagenic agent, or oxidative stress. Its quantum wavelike properties cause it to localize at various sites with probabilities that vary widely, by orders of magnitude, and depend strongly on the local sequence. We find significant correlations between hole probabilities and mutation rates within base triplets, observed in published mutation accumulation experiments on four species of bacteria. We have also computed hole probability spectra for hypervariable segment I of the human mtDNA control region, which contains several mutational hotspots, and for heptanucleotides in noncoding regions of the human genome, whose polymorphism levels have recently been reported. We observe significant correlations between hole probabilities, and context-specific mutation and substitution rates. The correlation with hole probability cannot be explained entirely by CpG methylation in the heptanucleotide data. Peaks in hole probability tend to coincide with mutational hotspots, even in mtDNA where CpG methylation is rare. Our results suggest that hole-enhanced mutational mechanisms, such as oxidation-stabilized tautomerization and base deamination, contribute to molecular evolution. PMID:29617801

Recognition of platinum-DNA adducts by HMGB1a.

PubMed

Ramachandran, Srinivas; Temple, Brenda; Alexandrova, Anastassia N; Chaney, Stephen G; Dokholyan, Nikolay V

2012-09-25

Cisplatin (CP) and oxaliplatin (OX), platinum-based drugs used widely in chemotherapy, form adducts on intrastrand guanines (5'GG) in genomic DNA. DNA damage recognition proteins, transcription factors, mismatch repair proteins, and DNA polymerases discriminate between CP- and OX-GG DNA adducts, which could partly account for differences in the efficacy, toxicity, and mutagenicity of CP and OX. In addition, differential recognition of CP- and OX-GG adducts is highly dependent on the sequence context of the Pt-GG adduct. In particular, DNA binding protein domain HMGB1a binds to CP-GG DNA adducts with up to 53-fold greater affinity than to OX-GG adducts in the TGGA sequence context but shows much smaller differences in binding in the AGGC or TGGT sequence contexts. Here, simulations of the HMGB1a-Pt-DNA complex in the three sequence contexts revealed a higher number of interface contacts for the CP-DNA complex in the TGGA sequence context than in the OX-DNA complex. However, the number of interface contacts was similar in the TGGT and AGGC sequence contexts. The higher number of interface contacts in the CP-TGGA sequence context corresponded to a larger roll of the Pt-GG base pair step. Furthermore, geometric analysis of stacking of phenylalanine 37 in HMGB1a (Phe37) with the platinated guanines revealed more favorable stacking modes correlated with a larger roll of the Pt-GG base pair step in the TGGA sequence context. These data are consistent with our previous molecular dynamics simulations showing that the CP-TGGA complex was able to sample larger roll angles than the OX-TGGA complex or either CP- or OX-DNA complexes in the AGGC or TGGT sequences. We infer that the high binding affinity of HMGB1a for CP-TGGA is due to the greater flexibility of CP-TGGA compared to OX-TGGA and other Pt-DNA adducts. This increased flexibility is reflected in the ability of CP-TGGA to sample larger roll angles, which allows for a higher number of interface contacts between the Pt-DNA adduct and HMGB1a.

A Simple Method for Visualization of Locus-Specific H4K20me1 Modifications in Living Caenorhabditis elegans Single Cells.

PubMed

Shinkai, Yoichi; Kuramochi, Masahiro; Doi, Motomichi

2018-05-03

Recently, advances in next-generation sequencing technologies have enabled genome-wide analyses of epigenetic modifications; however, it remains difficult to analyze the states of histone modifications at a single-cell resolution in living multicellular organisms because of the heterogeneity within cellular populations. Here we describe a simple method to visualize histone modifications on the specific sequence of target locus at a single-cell resolution in living Caenorhabditis elegans , by combining the LacO/LacI system and a genetically-encoded H4K20me1-specific probe, "mintbody". We demonstrate that Venus-labeled mintbody and mTurquoise2-labeled LacI can co-localize on an artificial chromosome carrying both the target locus and LacO sequences, where H4K20me1 marks the target locus. We demonstrate that our visualization method can precisely detect H4K20me1 depositions on the her-1 gene sequences on the artificial chromosome, to which the dosage compensation complex binds to regulate sex determination. The degree of H4K20me1 deposition on the her-1 sequences on the artificial chromosome correlated strongly with sex, suggesting that, using the artificial chromosome, this method can reflect context-dependent changes of H4K20me1 on endogenous genomes. Furthermore, we demonstrate live imaging of H4K20me1 depositions on the artificial chromosome. Combined with ChIP assays, this mintbody-LacO/LacI visualization method will enable analysis of developmental and context-dependent alterations of locus-specific histone modifications in specific cells and elucidation of the underlying molecular mechanisms. Copyright © 2018, G3: Genes, Genomes, Genetics.

The CanOE strategy: integrating genomic and metabolic contexts across multiple prokaryote genomes to find candidate genes for orphan enzymes.

PubMed

Smith, Adam Alexander Thil; Belda, Eugeni; Viari, Alain; Medigue, Claudine; Vallenet, David

2012-05-01

Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes), a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short). The first step locates "genomic metabolons", i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.

When global structure "Explains Away" local grammar: a Bayesian account of rule-induction in tone sequences.

PubMed

Dawson, Colin; Gerken, Louann

2011-09-01

While many constraints on learning must be relatively experience-independent, past experience provides a rich source of guidance for subsequent learning. Discovering structure in some domain can inform a learner's future hypotheses about that domain. If a general property accounts for particular sub-patterns, a rational learner should not stipulate separate explanations for each detail without additional evidence, as the general structure has "explained away" the original evidence. In a grammar-learning experiment using tone sequences, manipulating learners' prior exposure to a tone environment affects their sensitivity to the grammar-defining feature, in this case consecutive repeated tones. Grammar-learning performance is worse if context melodies are "smooth" -- when small intervals occur more than large ones -- as Smoothness is a general property accounting for a high rate of repetition. We present an idealized Bayesian model as a "best case" benchmark for learning repetition grammars. When context melodies are Smooth, the model places greater weight on the small-interval constraint, and does not learn the repetition rule as well as when context melodies are not Smooth, paralleling the human learners. These findings support an account of abstract grammar-induction in which learners rationally assess the statistical evidence for underlying structure based on a generative model of the environment. Copyright © 2010 Elsevier B.V. All rights reserved.

Definition of a high-affinity Gag recognition structure mediating packaging of a retroviral RNA genome

PubMed Central

Gherghe, Cristina; Lombo, Tania; Leonard, Christopher W.; Datta, Siddhartha A. K.; Bess, Julian W.; Gorelick, Robert J.; Rein, Alan; Weeks, Kevin M.

2010-01-01

All retroviral genomic RNAs contain a cis-acting packaging signal by which dimeric genomes are selectively packaged into nascent virions. However, it is not understood how Gag (the viral structural protein) interacts with these signals to package the genome with high selectivity. We probed the structure of murine leukemia virus RNA inside virus particles using SHAPE, a high-throughput RNA structure analysis technology. These experiments showed that NC (the nucleic acid binding domain derived from Gag) binds within the virus to the sequence UCUG-UR-UCUG. Recombinant Gag and NC proteins bound to this same RNA sequence in dimeric RNA in vitro; in all cases, interactions were strongest with the first U and final G in each UCUG element. The RNA structural context is critical: High-affinity binding requires base-paired regions flanking this motif, and two UCUG-UR-UCUG motifs are specifically exposed in the viral RNA dimer. Mutating the guanosine residues in these two motifs—only four nucleotides per genomic RNA—reduced packaging 100-fold, comparable to the level of nonspecific packaging. These results thus explain the selective packaging of dimeric RNA. This paradigm has implications for RNA recognition in general, illustrating how local context and RNA structure can create information-rich recognition signals from simple single-stranded sequence elements in large RNAs. PMID:20974908

Exact calculation of distributions on integers, with application to sequence alignment.

PubMed

Newberg, Lee A; Lawrence, Charles E

2009-01-01

Computational biology is replete with high-dimensional discrete prediction and inference problems. Dynamic programming recursions can be applied to several of the most important of these, including sequence alignment, RNA secondary-structure prediction, phylogenetic inference, and motif finding. In these problems, attention is frequently focused on some scalar quantity of interest, a score, such as an alignment score or the free energy of an RNA secondary structure. In many cases, score is naturally defined on integers, such as a count of the number of pairing differences between two sequence alignments, or else an integer score has been adopted for computational reasons, such as in the test of significance of motif scores. The probability distribution of the score under an appropriate probabilistic model is of interest, such as in tests of significance of motif scores, or in calculation of Bayesian confidence limits around an alignment. Here we present three algorithms for calculating the exact distribution of a score of this type; then, in the context of pairwise local sequence alignments, we apply the approach so as to find the alignment score distribution and Bayesian confidence limits.

PCV: An Alignment Free Method for Finding Homologous Nucleotide Sequences and its Application in Phylogenetic Study.

PubMed

Kumar, Rajnish; Mishra, Bharat Kumar; Lahiri, Tapobrata; Kumar, Gautam; Kumar, Nilesh; Gupta, Rahul; Pal, Manoj Kumar

2017-06-01

Online retrieval of the homologous nucleotide sequences through existing alignment techniques is a common practice against the given database of sequences. The salient point of these techniques is their dependence on local alignment techniques and scoring matrices the reliability of which is limited by computational complexity and accuracy. Toward this direction, this work offers a novel way for numerical representation of genes which can further help in dividing the data space into smaller partitions helping formation of a search tree. In this context, this paper introduces a 36-dimensional Periodicity Count Value (PCV) which is representative of a particular nucleotide sequence and created through adaptation from the concept of stochastic model of Kolekar et al. (American Institute of Physics 1298:307-312, 2010. doi: 10.1063/1.3516320 ). The PCV construct uses information on physicochemical properties of nucleotides and their positional distribution pattern within a gene. It is observed that PCV representation of gene reduces computational cost in the calculation of distances between a pair of genes while being consistent with the existing methods. The validity of PCV-based method was further tested through their use in molecular phylogeny constructs in comparison with that using existing sequence alignment methods.

Two Preferences in Question-Answer Sequences in Language Classroom Context

ERIC Educational Resources Information Center

Hosoda, Yuri; Aline, David

2013-01-01

Discussing two preferences associated with question-answer sequences, this study examines student responses to teacher questions in primary school English-as-a-foreign-language classes. The paper starts out with a reconsideration of institutional context, with a focus on classroom context from a conversation analysis perspective. We then introduce…

Mutagenic Spectra Arising from Replication Bypass of the 2,6-diamino-4-hydroxy-N5-methyl Formamidopyrimidine Adduct in Primate Cells

PubMed Central

Earley, Lauriel F.; Minko, Irina G.; Christov, Plamen P.; Rizzo, Carmelo J.; Lloyd, R. Stephen

2013-01-01

DNA exposures to electrophilic methylating agents that are commonly used during chemotherapeutic treatments cause diverse chemical modifications of nucleobases, with reaction at N7-dG being the most abundant. Although this base modification frequently results in destabilization of the glycosyl bond and spontaneous depurination, the adduct can react with hydroxide ion to yield a stable, ring-opened MeFapy-dG and this lesion has been reported to persist in animal tissues. Results from prior in vitro replication bypass investigations of the MeFapy-dG adduct had revealed complex spectra of replication errors that differed depending on the identity of DNA polymerase and the local sequence context. In this study, a series of nine site-specifically modified MeFapy-dG-containing oligodeoxynucleotides were engineered into a shuttle vector and subjected to replication in primate cells. In all nine sequence contexts examined, MeFapy-dG was shown to be associated with a strong mutator phenotype, predominantly causing base substitutions, with G to T transversions being most common. Single and dinucleotide deletions were also found in a subset of the sequence contexts. Interestingly, single-nucleotide deletions occurred not only at the adducted site, but also one nucleotide downstream of the adduct. Standard models for primer-template misalignment could account for some, but not all mutations observed. These data demonstrate that in addition to mutagenesis predicted from replication of DNAs containing O6-Me-dG and O4-Me-dT, the MeFapy-dG adduct likely contributes to mutagenic events following chemotherapeutic treatments. PMID:23763662

Local linear regression for function learning: an analysis based on sample discrepancy.

PubMed

Cervellera, Cristiano; Macciò, Danilo

2014-11-01

Local linear regression models, a kind of nonparametric structures that locally perform a linear estimation of the target function, are analyzed in the context of empirical risk minimization (ERM) for function learning. The analysis is carried out with emphasis on geometric properties of the available data. In particular, the discrepancy of the observation points used both to build the local regression models and compute the empirical risk is considered. This allows to treat indifferently the case in which the samples come from a random external source and the one in which the input space can be freely explored. Both consistency of the ERM procedure and approximating capabilities of the estimator are analyzed, proving conditions to ensure convergence. Since the theoretical analysis shows that the estimation improves as the discrepancy of the observation points becomes smaller, low-discrepancy sequences, a family of sampling methods commonly employed for efficient numerical integration, are also analyzed. Simulation results involving two different examples of function learning are provided.

PDNAsite: Identification of DNA-binding Site from Protein Sequence by Incorporating Spatial and Sequence Context

PubMed Central

Zhou, Jiyun; Xu, Ruifeng; He, Yulan; Lu, Qin; Wang, Hongpeng; Kong, Bing

2016-01-01

Protein-DNA interactions are involved in many fundamental biological processes essential for cellular function. Most of the existing computational approaches employed only the sequence context of the target residue for its prediction. In the present study, for each target residue, we applied both the spatial context and the sequence context to construct the feature space. Subsequently, Latent Semantic Analysis (LSA) was applied to remove the redundancies in the feature space. Finally, a predictor (PDNAsite) was developed through the integration of the support vector machines (SVM) classifier and ensemble learning. Results on the PDNA-62 and the PDNA-224 datasets demonstrate that features extracted from spatial context provide more information than those from sequence context and the combination of them gives more performance gain. An analysis of the number of binding sites in the spatial context of the target site indicates that the interactions between binding sites next to each other are important for protein-DNA recognition and their binding ability. The comparison between our proposed PDNAsite method and the existing methods indicate that PDNAsite outperforms most of the existing methods and is a useful tool for DNA-binding site identification. A web-server of our predictor (http://hlt.hitsz.edu.cn:8080/PDNAsite/) is made available for free public accessible to the biological research community. PMID:27282833

Middle Tertiary stratigraphic sequences of the San Joaquin Basin, California: Chapter 6 in Petroleum systems and geologic assessment of oil and gas in the San Joaquin Basin Province, California

USGS Publications Warehouse

Johnson, Cari L.; Graham, Stephan A.

2007-01-01

An integrated database of outcrop studies, borehole logs, and seismic-reflection profiles is used to divide Eocene through Miocene strata of the central and southern San Joaquin Basin, California, into a framework of nine stratigraphic sequences. These third- and higher-order sequences (<3 m.y. duration) comprise the principal intervals for petroleum assessment for the basin, including key reservoir and source rock intervals. Important characteristics of each sequence are discussed, including distribution and stratigraphic relationships, sedimentary facies, regional correlation, and age relations. This higher-order stratigraphic packaging represents relatively short-term fluctuations in various forcing factors including climatic effects, changes in sediment supply, local and regional tectonism, and fluctuations in global eustatic sea level. These stratigraphic packages occur within the context of second-order stratigraphic megasequences, which mainly reflect long-term tectonic basin evolution. Despite more than a century of petroleum exploration in the San Joaquin Basin, many uncertainties remain regarding the age, correlation, and origin of the third- and higher-order sequences. Nevertheless, a sequence stratigraphic approach allows definition of key intervals based on genetic affinity rather than purely lithostratigraphic relationships, and thus is useful for reconstructing the multiphase history of this basin, as well as understanding its petroleum systems.

UCSC genome browser: deep support for molecular biomedical research.

PubMed

Mangan, Mary E; Williams, Jennifer M; Lathe, Scott M; Karolchik, Donna; Lathe, Warren C

2008-01-01

The volume and complexity of genomic sequence data, and the additional experimental data required for annotation of the genomic context, pose a major challenge for display and access for biomedical researchers. Genome browsers organize this data and make it available in various ways to extract useful information to advance research projects. The UCSC Genome Browser is one of these resources. The official sequence data for a given species forms the framework to display many other types of data such as expression, variation, cross-species comparisons, and more. Visual representations of the data are available for exploration. Data can be queried with sequences. Complex database queries are also easily achieved with the Table Browser interface. Associated tools permit additional query types or access to additional data sources such as images of in situ localizations. Support for solving researcher's issues is provided with active discussion mailing lists and by providing updated training materials. The UCSC Genome Browser provides a source of deep support for a wide range of biomedical molecular research (http://genome.ucsc.edu).

Relatively Random: Context Effects on Perceived Randomness and Predicted Outcomes

ERIC Educational Resources Information Center

Matthews, William J.

2013-01-01

This article concerns the effect of context on people's judgments about sequences of chance outcomes. In Experiment 1, participants judged whether sequences were produced by random, mechanical processes (such as a roulette wheel) or skilled human action (such as basketball shots). Sequences with lower alternation rates were judged more likely to…

Sense Making in the Context of Algebraic Activities

ERIC Educational Resources Information Center

Palatnik, Alik; Koichu, Boris

2017-01-01

This article concerns student sense making in the context of algebraic activities. We present a case in which a pair of middle-school students attempts to make sense of a previously obtained by them position formula for a particular numerical sequence. The exploration of the sequence occurred in the context of two-month-long student research…

'I guess my own fancy screwed me over': transitions in drug use and the context of choice among young people entrenched in an open drug scene

PubMed Central

2010-01-01

Background There is growing interest in describing the broader risk trajectories experienced by young people who use drugs - that is, in describing the sequences of drug use transitions experienced by youth in relation to evolving understandings of risk and harm. This study sought to examine young people's perspectives regarding the evolution of their drug use in the context of a local drug scene in Vancouver, Canada. Methods Semi-structured qualitative interviews with 38 individuals recruited from a cohort of young drug users known as the At-risk Youth Study (ARYS) were supplemented by ongoing ethnographic fieldwork (e.g., observations and informal conversations with youth) conducted within the same cohort population. Interviews were transcribed verbatim and a thematic analysis was conducted. Results The majority of youth characterized past transition events as non-exceptional, largely 'spur-of-the-moment' decisions motivated by evolving feelings of curiosity. At the same time, participants' reflections indicated that the social, structural and material contexts of drug scene entrenchment play a powerful role in shaping these decisions and transition experiences. Conclusions Importantly, as young people become increasingly entrenched in the local drug scene, drug use transitions seem to constitute increasingly relevant (and even 'inevitable') choices congruent with everyday lived experience. The implications of these findings for the development of meaningful interventions for youth are discussed. PMID:20222984

Genome-wide uniformity of human ‘open’ pre-initiation complexes

PubMed Central

Lai, William K.M.; Pugh, B. Franklin

2017-01-01

Transcription of protein-coding and noncoding DNA occurs pervasively throughout the mammalian genome. Their sites of initiation are generally inferred from transcript 5′ ends and are thought to be either locally dispersed or focused. How these two modes of initiation relate is unclear. Here, we apply permanganate treatment and chromatin immunoprecipitation (PIP-seq) of initiation factors to identify the precise location of melted DNA separately associated with the preinitiation complex (PIC) and the adjacent paused complex (PC). This approach revealed the two known modes of transcription initiation. However, in contrast to prevailing views, they co-occurred within the same promoter region: initiation originating from a focused PIC, and broad nucleosome-linked initiation. PIP-seq allowed transcriptional orientation of Pol II to be determined, which may be useful near promoters where sufficient sense/anti-sense transcript mapping information is lacking. PIP-seq detected divergently oriented Pol II at both coding and noncoding promoters, as well as at enhancers. Their occupancy levels were not necessarily coupled in the two orientations. DNA sequence and shape analysis of initiation complex sites suggest that both sequence and shape contribute to specificity, but in a context-restricted manner. That is, initiation sites have the locally “best” initiator (INR) sequence and/or shape. These findings reveal a common core to pervasive Pol II initiation throughout the human genome. PMID:27927716

Higher order memories for objects encountered in different spatio-temporal contexts in mice: evidence for episodic memory.

PubMed

Dere, Ekrem; Silva, Maria A De Souza; Huston, Joseph P

2004-01-01

The ability to build higher order multi-modal memories comprising information about the spatio-temporal context of events has been termed 'episodic memory'. Deficits in episodic memory are apparent in a number of neuropsychiatric diseases. Unfortunately, the development of animal models of episodic memory has made little progress. Towards the goal of such a model we devised an object exploration task for mice, providing evidence that rodents can associate object, spatial and temporal information. In our task the mice learned the temporal sequence by which identical objects were introduced into two different contexts. The 'what' component of an episodic memory was operationalized via physically distinct objects; the 'where' component through physically different contexts, and, most importantly, the 'when' component via the context-specific inverted sequence in which four objects were presented. Our results suggest that mice are able to recollect the inverted temporal sequence in which identical objects were introduced into two distinct environments. During two consecutive test trials mice showed an inverse context-specific exploration pattern regarding identical objects that were previously encountered with even frequencies. It seems that the contexts served as discriminative stimuli signaling which of the two sequences are decisive during the two test trials.

Pseudouridines have context-dependent mutation and stop rates in high-throughput sequencing.

PubMed

Zhou, Katherine I; Clark, Wesley C; Pan, David W; Eckwahl, Matthew J; Dai, Qing; Pan, Tao

2018-05-11

The abundant RNA modification pseudouridine (Ψ) has been mapped transcriptome-wide by chemically modifying pseudouridines with carbodiimide and detecting the resulting reverse transcription stops in high-throughput sequencing. However, these methods have limited sensitivity and specificity, in part due to the use of reverse transcription stops. We sought to use mutations rather than just stops in sequencing data to identify pseudouridine sites. Here, we identify reverse transcription conditions that allow read-through of carbodiimide-modified pseudouridine (CMC-Ψ), and we show that pseudouridines in carbodiimide-treated human ribosomal RNA have context-dependent mutation and stop rates in high-throughput sequencing libraries prepared under these conditions. Furthermore, accounting for the context-dependence of mutation and stop rates can enhance the detection of pseudouridine sites. Similar approaches could contribute to the sequencing-based detection of many RNA modifications.

Coding visual features extracted from video sequences.

PubMed

Baroffio, Luca; Cesana, Matteo; Redondi, Alessandro; Tagliasacchi, Marco; Tubaro, Stefano

2014-05-01

Visual features are successfully exploited in several applications (e.g., visual search, object recognition and tracking, etc.) due to their ability to efficiently represent image content. Several visual analysis tasks require features to be transmitted over a bandwidth-limited network, thus calling for coding techniques to reduce the required bit budget, while attaining a target level of efficiency. In this paper, we propose, for the first time, a coding architecture designed for local features (e.g., SIFT, SURF) extracted from video sequences. To achieve high coding efficiency, we exploit both spatial and temporal redundancy by means of intraframe and interframe coding modes. In addition, we propose a coding mode decision based on rate-distortion optimization. The proposed coding scheme can be conveniently adopted to implement the analyze-then-compress (ATC) paradigm in the context of visual sensor networks. That is, sets of visual features are extracted from video frames, encoded at remote nodes, and finally transmitted to a central controller that performs visual analysis. This is in contrast to the traditional compress-then-analyze (CTA) paradigm, in which video sequences acquired at a node are compressed and then sent to a central unit for further processing. In this paper, we compare these coding paradigms using metrics that are routinely adopted to evaluate the suitability of visual features in the context of content-based retrieval, object recognition, and tracking. Experimental results demonstrate that, thanks to the significant coding gains achieved by the proposed coding scheme, ATC outperforms CTA with respect to all evaluation metrics.

CDinFusion – Submission-Ready, On-Line Integration of Sequence and Contextual Data

PubMed Central

Hankeln, Wolfgang; Wendel, Norma Johanna; Gerken, Jan; Waldmann, Jost; Buttigieg, Pier Luigi; Kostadinov, Ivaylo; Kottmann, Renzo; Yilmaz, Pelin; Glöckner, Frank Oliver

2011-01-01

State of the art (DNA) sequencing methods applied in “Omics” studies grant insight into the ‘blueprints’ of organisms from all domains of life. Sequencing is carried out around the globe and the data is submitted to the public repositories of the International Nucleotide Sequence Database Collaboration. However, the context in which these studies are conducted often gets lost, because experimental data, as well as information about the environment are rarely submitted along with the sequence data. If these contextual or metadata are missing, key opportunities of comparison and analysis across studies and habitats are hampered or even impossible. To address this problem, the Genomic Standards Consortium (GSC) promotes checklists and standards to better describe our sequence data collection and to promote the capturing, exchange and integration of sequence data with contextual data. In a recent community effort the GSC has developed a series of recommendations for contextual data that should be submitted along with sequence data. To support the scientific community to significantly enhance the quality and quantity of contextual data in the public sequence data repositories, specialized software tools are needed. In this work we present CDinFusion, a web-based tool to integrate contextual and sequence data in (Multi)FASTA format prior to submission. The tool is open source and available under the Lesser GNU Public License 3. A public installation is hosted and maintained at the Max Planck Institute for Marine Microbiology at http://www.megx.net/cdinfusion. The tool may also be installed locally using the open source code available at http://code.google.com/p/cdinfusion. PMID:21935468

A Project Course Sequence in Innovation and Commercialization of Medical Devices.

PubMed

Eberhardt, Alan W; Tillman, Shea; Kirkland, Brandon; Sherrod, Brandon

2017-07-01

There exists a need for educational processes in which students gain experience with design and commercialization of medical devices. This manuscript describes the implementation of, and assessment results from, the first year offering of a project course sequence in Master of Engineering (MEng) in Design and Commercialization at our institution. The three-semester course sequence focused on developing and applying hands-on skills that contribute to product development to address medical device needs found within our university hospital and local community. The first semester integrated computer-aided drawing (CAD) as preparation for manufacturing of device-related components (hand machining, computer numeric control (CNC), three-dimensional (3D) printing, and plastics molding), followed by an introduction to microcontrollers (MCUs) and printed circuit boards (PCBs) for associated electronics and control systems. In the second semester, the students applied these skills on a unified project, working together to construct and test multiple weighing scales for wheelchair users. In the final semester, the students applied industrial design concepts to four distinct device designs, including user and context reassessment, human factors (functional and aesthetic) design refinement, and advanced visualization for commercialization. The assessment results are described, along with lessons learned and plans for enhancement of the course sequence.

Mutalisk: a web-based somatic MUTation AnaLyIS toolKit for genomic, transcriptional and epigenomic signatures.

PubMed

Lee, Jongkeun; Lee, Andy Jinseok; Lee, June-Koo; Park, Jongkeun; Kwon, Youngoh; Park, Seongyeol; Chun, Hyonho; Ju, Young Seok; Hong, Dongwan

2018-05-22

Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org.

Towards Long-Range RNA Structure Prediction in Eukaryotic Genes.

PubMed

Pervouchine, Dmitri D

2018-06-15

The ability to form an intramolecular structure plays a fundamental role in eukaryotic RNA biogenesis. Proximate regions in the primary transcripts fold into a local secondary structure, which is then hierarchically assembled into a tertiary structure that is stabilized by RNA-binding proteins and long-range intramolecular base pairings. While the local RNA structure can be predicted reasonably well for short sequences, long-range structure at the scale of eukaryotic genes remains problematic from the computational standpoint. The aim of this review is to list functional examples of long-range RNA structures, to summarize current comparative methods of structure prediction, and to highlight their advances and limitations in the context of long-range RNA structures. Most comparative methods implement the “first-align-then-fold” principle, i.e., they operate on multiple sequence alignments, while functional RNA structures often reside in non-conserved parts of the primary transcripts. The opposite “first-fold-then-align” approach is currently explored to a much lesser extent. Developing novel methods in both directions will improve the performance of comparative RNA structure analysis and help discover novel long-range structures, their higher-order organization, and RNA⁻RNA interactions across the transcriptome.

Teaching Air Pollution in an Authentic Context

NASA Astrophysics Data System (ADS)

Mandrikas, Achilleas; Stavrou, Dimitrios; Skordoulis, Constantine

2017-04-01

This paper describes a teaching-learning sequence (TLS) about air pollution and the findings resulting from its implementation by pre-service elementary teachers (PET) currently undergraduate students of the Department of Primary Education in the National and Kapodistrian University of Athens, Greece. The TLS focused on the relation of air pollution with wind and topography in local conditions. An authentic context was provided to the students based on daily up-to-date meteorological data via the Internet in order to estimate air pollution. The results are encouraging given that PET can correlate wind and concentration of air pollutants through reading specialized angular diagrams and weather maps, can recognize the correlation of topography in the concentration of air pollutants, and can describe temperature inversion. However, the PET demonstrated clear difficulties in ability of orientation, in wind naming, and in interpretation of symbols on weather map. Finally, the implications on teaching air pollution are discussed.

Quantifying transfer after perceptual-motor sequence learning: how inflexible is implicit learning?

PubMed

Sanchez, Daniel J; Yarnik, Eric N; Reber, Paul J

2015-03-01

Studies of implicit perceptual-motor sequence learning have often shown learning to be inflexibly tied to the training conditions during learning. Since sequence learning is seen as a model task of skill acquisition, limits on the ability to transfer knowledge from the training context to a performance context indicates important constraints on skill learning approaches. Lack of transfer across contexts has been demonstrated by showing that when task elements are changed following training, this leads to a disruption in performance. These results have typically been taken as suggesting that the sequence knowledge relies on integrated representations across task elements (Abrahamse, Jiménez, Verwey, & Clegg, Psychon Bull Rev 17:603-623, 2010a). Using a relatively new sequence learning task, serial interception sequence learning, three experiments are reported that quantify this magnitude of performance disruption after selectively manipulating individual aspects of motor performance or perceptual information. In Experiment 1, selective disruption of the timing or order of sequential actions was examined using a novel response manipulandum that allowed for separate analysis of these two motor response components. In Experiments 2 and 3, transfer was examined after selective disruption of perceptual information that left the motor response sequence intact. All three experiments provided quantifiable estimates of partial transfer to novel contexts that suggest some level of information integration across task elements. However, the ability to identify quantifiable levels of successful transfer indicates that integration is not all-or-none and that measurement sensitivity is a key in understanding sequence knowledge representations.

Hum-mPLoc 3.0: prediction enhancement of human protein subcellular localization through modeling the hidden correlations of gene ontology and functional domain features.

PubMed

Zhou, Hang; Yang, Yang; Shen, Hong-Bin

2017-03-15

Protein subcellular localization prediction has been an important research topic in computational biology over the last decade. Various automatic methods have been proposed to predict locations for large scale protein datasets, where statistical machine learning algorithms are widely used for model construction. A key step in these predictors is encoding the amino acid sequences into feature vectors. Many studies have shown that features extracted from biological domains, such as gene ontology and functional domains, can be very useful for improving the prediction accuracy. However, domain knowledge usually results in redundant features and high-dimensional feature spaces, which may degenerate the performance of machine learning models. In this paper, we propose a new amino acid sequence-based human protein subcellular location prediction approach Hum-mPLoc 3.0, which covers 12 human subcellular localizations. The sequences are represented by multi-view complementary features, i.e. context vocabulary annotation-based gene ontology (GO) terms, peptide-based functional domains, and residue-based statistical features. To systematically reflect the structural hierarchy of the domain knowledge bases, we propose a novel feature representation protocol denoted as HCM (Hidden Correlation Modeling), which will create more compact and discriminative feature vectors by modeling the hidden correlations between annotation terms. Experimental results on four benchmark datasets show that HCM improves prediction accuracy by 5-11% and F 1 by 8-19% compared with conventional GO-based methods. A large-scale application of Hum-mPLoc 3.0 on the whole human proteome reveals proteins co-localization preferences in the cell. www.csbio.sjtu.edu.cn/bioinf/Hum-mPLoc3/. hbshen@sjtu.edu.cn. 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

When being narrow minded is a good thing: locally biased people show stronger contextual cueing.

PubMed

Bellaera, Lauren; von Mühlenen, Adrian; Watson, Derrick G

2014-01-01

Repeated contexts allow us to find relevant information more easily. Learning such contexts has been proposed to depend upon either global processing of the repeated contexts, or alternatively processing of the local region surrounding the target information. In this study, we measured the extent to which observers were by default biased to process towards a more global or local level. The findings showed that the ability to use context to help guide their search was strongly related to an observer's local/global processing bias. Locally biased people could use context to help improve their search better than globally biased people. The results suggest that the extent to which context can be used depends crucially on the observer's attentional bias and thus also to factors and influences that can change this bias.

The multivariate association between genomewide DNA methylation and climate across the range of Arabidopsis thaliana.

PubMed

Keller, Thomas E; Lasky, Jesse R; Yi, Soojin V

2016-04-01

Epigenetic changes can occur due to extracellular environmental conditions. Consequently, epigenetic mechanisms can play an intermediate role to translate environmental signals to intracellular changes. Such a role might be particularly important in plants, which often show strong local adaptation and have the potential for heritable epigenetic states. However, little is currently known about the role of epigenetic variation in the ecological mechanisms of adaptation. Here, we used multivariate redundancy analyses to examine genomewide associations between DNA methylation polymorphisms and climate variation in two independent panels of Arabidopsis accessions, including 122 Eurasian accessions as well as in a regional panel of 148 accessions in Sweden. At the single-nucleotide methylation level, climate and space (geographic spatial structure) explain small yet significant amount of variation in both panels. On the other hand, when viewed in a context of genomic clusters of methylated and unmethylated cytosines, climate and space variables explain much greater amounts of variation in DNA methylation than those explained by variation at the single-nucleotide level. We found that the single-nucleotide methylation polymorphisms with the strongest associations with climate were enriched in transposable elements and in potentially RNA-directed methylation contexts. When viewed in the context of genomic clusters, variation of DNA methylation at different sequence contexts exhibit distinctive segregation along different axes of variation in the redundancy analyses. Genomewide methylation showed much stronger associations with climate within the regional panel (Sweden) compared to the global (Eurasia). Together, these findings indicate that genetic and epigenetic variation across the genome may play a role in response to climate conditions and local adaptation. © 2016 John Wiley & Sons Ltd.

Suitability assessment of the urban water management transition in the Indonesian context - A case study of Surabaya

NASA Astrophysics Data System (ADS)

Sholihah, Mar'atus; Anityasari, Maria; Maftuhah, Diesta Iva

2017-06-01

The rapidly growing urban population, the increasing impact of climate change, and the constantly decreasing availability of the good quality water become the major triggers that force urban water professionals to continuously focus on sustainable urban water management (SUWM). The city as a focal point of population growth in the world has become a critical object for its resiliency, not only in terms of the environmental deterioration but also of the water supplies security. As a response to the current condition, the framework of urban water management transition has been introduced as a sort of transformation for a city to achieve SUWM. Water Sensitive City (WSC) is the ultimate goal of this framework which integrates water access and supply security, public health protection, flood prevention, environmental protection and livability, and economic sustainability. Recently, the urban water management transition and WSC concept are going to be implemented in some cities in Indonesia, including Surabaya. However, in addition to provide a wide range of benefits, the implementation of WSC also brings challenges. In terms of geographical and social aspect, public policy, and the citizen behavior, the cities in Indonesia are undoubtedly different with those in Australian where the concept was developed. Hence, assessing the suitability of urban water management transition in the Indonesian context can be perceived as the most important phase in this whole plan. A case study of Surabaya would be identified as a baseline to measure whether the proposed sequence of urban water management transition is suitable for Indonesian local context. The research aimed to assess the suitability of the framework to be implemented in Indonesia and to propose the modified framework which is more suitable for local context in Indonesia.

Quantifying transfer after perceptual-motor sequence learning: how inflexible is implicit learning?

PubMed Central

Sanchez, Daniel J.; Yarnik, Eric N.

2015-01-01

Studies of implicit perceptual-motor sequence learning have often shown learning to be inflexibly tied to the training conditions during learning. Since sequence learning is seen as a model task of skill acquisition, limits on the ability to transfer knowledge from the training context to a performance context indicates important constraints on skill learning approaches. Lack of transfer across contexts has been demonstrated by showing that when task elements are changed following training, this leads to a disruption in performance. These results have typically been taken as suggesting that the sequence knowledge relies on integrated representations across task elements (Abrahamse, Jiménez, Verwey, & Clegg, Psychon Bull Rev 17:603–623, 2010a). Using a relatively new sequence learning task, serial interception sequence learning, three experiments are reported that quantify this magnitude of performance disruption after selectively manipulating individual aspects of motor performance or perceptual information. In Experiment 1, selective disruption of the timing or order of sequential actions was examined using a novel response manipulandum that allowed for separate analysis of these two motor response components. In Experiments 2 and 3, transfer was examined after selective disruption of perceptual information that left the motor response sequence intact. All three experiments provided quantifiable estimates of partial transfer to novel contexts that suggest some level of information integration across task elements. However, the ability to identify quantifiable levels of successful transfer indicates that integration is not all-or-none and that measurement sensitivity is a key in understanding sequence knowledge representations. PMID:24668505

Computed tomography synthesis from magnetic resonance images in the pelvis using multiple random forests and auto-context features

NASA Astrophysics Data System (ADS)

Andreasen, Daniel; Edmund, Jens M.; Zografos, Vasileios; Menze, Bjoern H.; Van Leemput, Koen

2016-03-01

In radiotherapy treatment planning that is only based on magnetic resonance imaging (MRI), the electron density information usually obtained from computed tomography (CT) must be derived from the MRI by synthesizing a so-called pseudo CT (pCT). This is a non-trivial task since MRI intensities are neither uniquely nor quantitatively related to electron density. Typical approaches involve either a classification or regression model requiring specialized MRI sequences to solve intensity ambiguities, or an atlas-based model necessitating multiple registrations between atlases and subject scans. In this work, we explore a machine learning approach for creating a pCT of the pelvic region from conventional MRI sequences without using atlases. We use a random forest provided with information about local texture, edges and spatial features derived from the MRI. This helps to solve intensity ambiguities. Furthermore, we use the concept of auto-context by sequentially training a number of classification forests to create and improve context features, which are finally used to train a regression forest for pCT prediction. We evaluate the pCT quality in terms of the voxel-wise error and the radiologic accuracy as measured by water-equivalent path lengths. We compare the performance of our method against two baseline pCT strategies, which either set all MRI voxels in the subject equal to the CT value of water, or in addition transfer the bone volume from the real CT. We show an improved performance compared to both baseline pCTs suggesting that our method may be useful for MRI-only radiotherapy.

Loss and persistence of implicit memory for sound: evidence from auditory stream segregation context effects.

PubMed

Snyder, Joel S; Weintraub, David M

2013-07-01

An important question is the extent to which declines in memory over time are due to passive loss or active interference from other stimuli. The purpose of the present study was to determine the extent to which implicit memory effects in the perceptual organization of sound sequences are subject to loss and interference. Toward this aim, we took advantage of two recently discovered context effects in the perceptual judgments of sound patterns, one that depends on stimulus features of previous sounds and one that depends on the previous perceptual organization of these sounds. The experiments measured how listeners' perceptual organization of a tone sequence (test) was influenced by the frequency separation, or the perceptual organization, of the two preceding sequences (context1 and context2). The results demonstrated clear evidence for loss of context effects over time but little evidence for interference. However, they also revealed that context effects can be surprisingly persistent. The robust effects of loss, followed by persistence, were similar for the two types of context effects. We discuss whether the same auditory memories might contain information about basic stimulus features of sounds (i.e., frequency separation), as well as the perceptual organization of these sounds.

The influence of phonological priming on variability in articulation

NASA Astrophysics Data System (ADS)

Babel, Molly E.; Munson, Benjamin

2004-05-01

Previous research [Sevald and Dell, Cognition 53, 91-127 (1994)] has found that reiterant sequences of CVC words are produced more quickly when the prime word and target word share VC sequences (i.e., sequences like sit sick) than when they are identical (sequences like sick sick). Even slower production rates are found when primes and targets share a CV sequence (sequences like kick sick). These data have been used to support a model of speech production in which lexical items and their constituent phonemes are activated sequentially. The current experiment investigated whether phonological priming also influences variability in the acoustic characteristics of words. Specifically, we examined whether greater variability in the acoustic characteristics of target words was noted in the CV-related prime context than in the identical-prime context, and whether less variability was noted in the VC-related context. Thirty adult subjects with typical speech, language, and hearing ability produced reiterant two-word sequences that varied in their phonological similarity. The duration, first, and second formant frequencies of the target-words' vowels were measured. Preliminary analyses indicate that phonological priming does not have a systematic effect on variability in these acoustic parameters.

Recombinative Generalization: An Exploratory Study in Musical Reading

PubMed Central

Perez, William Ferreira; de Rose, Julio C

2010-01-01

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

The influence of sequence context and length on the kinetics of DNA duplex formation from complementary hairpins possessing (CNG) repeats.

PubMed

Paiva, Anthony M; Sheardy, Richard D

2005-04-20

The formation of unusual structures during DNA replication has been invoked for gene expansion in genomes possessing triplet repeat sequences, CNG, where N = A, C, G, or T. In particular, it has been suggested that the daughter strand of the leading strand partially dissociates from the parent strand and forms a hairpin. The equilibrium between the fully duplexed parent:daugter species and the parent:hairpin species is dependent upon their relative stabilities and the rates of reannealing of the daughter strand back to the parent. These stabilities and rates are ultimately influenced by the sequence context of the DNA and its length. Previous work has demonstrated that longer strands are more stable than shorter strands and that the identity of N also influences the thermal stability [Paiva, A. M.; Sheardy, R. D. Biochemistry 2004, 43, 14218-14227]. Here, we show that the rate of duplex formation from complementary hairpins is also sequence context and length dependent. In particular, longer duplexes have higher activation energies than shorter duplexes of the same sequence context. Further, [(CCG):(GGC)] duplexes have lower activation energies than corresponding [(CAG):(GTC)] duplexes of the same length. Hence, hairpins formed from long CNG sequences are more thermodynamically stable and have slower kinetics for reannealing to their complement than shorter analogues. Gene expansion can now be explained in terms of thermodynamics and kinetics.

SEQATOMS: a web tool for identifying missing regions in PDB in sequence context.

PubMed

Brandt, Bernd W; Heringa, Jaap; Leunissen, Jack A M

2008-07-01

With over 46 000 proteins, the Protein Data Bank (PDB) is the most important database with structural information of biological macromolecules. PDB files contain sequence and coordinate information. Residues present in the sequence can be absent from the coordinate section, which means their position in space is unknown. Similarity searches are routinely carried out against sequences taken from PDB SEQRES. However, there no distinction is made between residues that have a known or unknown position in the 3D protein structure. We present a FASTA sequence database that is produced by combining the sequence and coordinate information. All residues absent from the PDB coordinate section are masked with lower-case letters, thereby providing a view of these residues in the context of the entire protein sequence, which facilitates inspecting 'missing' regions. We also provide a masked version of the CATH domain database. A user-friendly BLAST interface is available for similarity searching. In contrast to standard (stand-alone) BLAST output, which only contains upper-case letters, our output retains the lower-case letters of the masked regions. Thus, our server can be used to perform BLAST searching case-sensitively. Here, we have applied it to the study of missing regions in their sequence context. SEQATOMS is available at http://www.bioinformatics.nl/tools/seqatoms/.

Wasabi: An Integrated Platform for Evolutionary Sequence Analysis and Data Visualization.

PubMed

Veidenberg, Andres; Medlar, Alan; Löytynoja, Ari

2016-04-01

Wasabi is an open source, web-based environment for evolutionary sequence analysis. Wasabi visualizes sequence data together with a phylogenetic tree within a modern, user-friendly interface: The interface hides extraneous options, supports context sensitive menus, drag-and-drop editing, and displays additional information, such as ancestral sequences, associated with specific tree nodes. The Wasabi environment supports reproducibility by automatically storing intermediate analysis steps and includes built-in functions to share data between users and publish analysis results. For computational analysis, Wasabi supports PRANK and PAGAN for phylogeny-aware alignment and alignment extension, and it can be easily extended with other tools. Along with drag-and-drop import of local files, Wasabi can access remote data through URL and import sequence data, GeneTrees and EPO alignments directly from Ensembl. To demonstrate a typical workflow using Wasabi, we reproduce key findings from recent comparative genomics studies, including a reanalysis of the EGLN1 gene from the tiger genome study: These case studies can be browsed within Wasabi at http://wasabiapp.org:8000?id=usecases. Wasabi runs inside a web browser and does not require any installation. One can start using it at http://wasabiapp.org. All source code is licensed under the AGPLv3. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A model of individualized canonical microcircuits supporting cognitive operations

PubMed Central

Peterson, Andre D. H.; Haueisen, Jens; Knösche, Thomas R.

2017-01-01

Major cognitive functions such as language, memory, and decision-making are thought to rely on distributed networks of a large number of basic elements, called canonical microcircuits. In this theoretical study we propose a novel canonical microcircuit model and find that it supports two basic computational operations: a gating mechanism and working memory. By means of bifurcation analysis we systematically investigate the dynamical behavior of the canonical microcircuit with respect to parameters that govern the local network balance, that is, the relationship between excitation and inhibition, and key intrinsic feedback architectures of canonical microcircuits. We relate the local behavior of the canonical microcircuit to cognitive processing and demonstrate how a network of interacting canonical microcircuits enables the establishment of spatiotemporal sequences in the context of syntax parsing during sentence comprehension. This study provides a framework for using individualized canonical microcircuits for the construction of biologically realistic networks supporting cognitive operations. PMID:29200435

Frustration Sculpts the Early Stages of Protein Folding.

PubMed

Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano

2015-09-07

The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visual management of large scale data mining projects.

PubMed

Shah, I; Hunter, L

2000-01-01

This paper describes a unified framework for visualizing the preparations for, and results of, hundreds of machine learning experiments. These experiments were designed to improve the accuracy of enzyme functional predictions from sequence, and in many cases were successful. Our system provides graphical user interfaces for defining and exploring training datasets and various representational alternatives, for inspecting the hypotheses induced by various types of learning algorithms, for visualizing the global results, and for inspecting in detail results for specific training sets (functions) and examples (proteins). The visualization tools serve as a navigational aid through a large amount of sequence data and induced knowledge. They provided significant help in understanding both the significance and the underlying biological explanations of our successes and failures. Using these visualizations it was possible to efficiently identify weaknesses of the modular sequence representations and induction algorithms which suggest better learning strategies. The context in which our data mining visualization toolkit was developed was the problem of accurately predicting enzyme function from protein sequence data. Previous work demonstrated that approximately 6% of enzyme protein sequences are likely to be assigned incorrect functions on the basis of sequence similarity alone. In order to test the hypothesis that more detailed sequence analysis using machine learning techniques and modular domain representations could address many of these failures, we designed a series of more than 250 experiments using information-theoretic decision tree induction and naive Bayesian learning on local sequence domain representations of problematic enzyme function classes. In more than half of these cases, our methods were able to perfectly discriminate among various possible functions of similar sequences. We developed and tested our visualization techniques on this application.

Stimulus sequence context differentially modulates inhibition-related theta and delta band activity in a go/nogo task

PubMed Central

Harper, Jeremy; Malone, Stephen M.; Bachman, Matthew D.; Bernat, Edward M.

2015-01-01

Recent work suggests that dissociable activity in theta and delta frequency bands underlies several common event-related potential (ERP) components, including the nogo N2/P3 complex, which can better index separable functional processes than traditional time-domain measures. Reports have also demonstrated that neural activity can be affected by stimulus sequence context information (i.e., the number and type of preceding stimuli). Stemming from prior work demonstrating that theta and delta index separable processes during response inhibition, the current study assessed sequence context in a Go/Nogo paradigm in which the number of go stimuli preceding each nogo was selectively manipulated. Principal component analysis (PCA) of time-frequency representations revealed differential modulation of evoked theta and delta related to sequence context, where delta increased robustly with additional preceding go stimuli, while theta did not. Findings are consistent with the view that theta indexes simpler initial salience-related processes, while delta indexes more varied and complex processes related to a variety of task parameters. PMID:26751830

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

Maximum entropy methods for extracting the learned features of deep neural networks.

PubMed

Finnegan, Alex; Song, Jun S

2017-10-01

New architectures of multilayer artificial neural networks and new methods for training them are rapidly revolutionizing the application of machine learning in diverse fields, including business, social science, physical sciences, and biology. Interpreting deep neural networks, however, currently remains elusive, and a critical challenge lies in understanding which meaningful features a network is actually learning. We present a general method for interpreting deep neural networks and extracting network-learned features from input data. We describe our algorithm in the context of biological sequence analysis. Our approach, based on ideas from statistical physics, samples from the maximum entropy distribution over possible sequences, anchored at an input sequence and subject to constraints implied by the empirical function learned by a network. Using our framework, we demonstrate that local transcription factor binding motifs can be identified from a network trained on ChIP-seq data and that nucleosome positioning signals are indeed learned by a network trained on chemical cleavage nucleosome maps. Imposing a further constraint on the maximum entropy distribution also allows us to probe whether a network is learning global sequence features, such as the high GC content in nucleosome-rich regions. This work thus provides valuable mathematical tools for interpreting and extracting learned features from feed-forward neural networks.

Local alignment of two-base encoded DNA sequence

PubMed Central

Homer, Nils; Merriman, Barry; Nelson, Stanley F

2009-01-01

Background DNA sequence comparison is based on optimal local alignment of two sequences using a similarity score. However, some new DNA sequencing technologies do not directly measure the base sequence, but rather an encoded form, such as the two-base encoding considered here. In order to compare such data to a reference sequence, the data must be decoded into sequence. The decoding is deterministic, but the possibility of measurement errors requires searching among all possible error modes and resulting alignments to achieve an optimal balance of fewer errors versus greater sequence similarity. Results We present an extension of the standard dynamic programming method for local alignment, which simultaneously decodes the data and performs the alignment, maximizing a similarity score based on a weighted combination of errors and edits, and allowing an affine gap penalty. We also present simulations that demonstrate the performance characteristics of our two base encoded alignment method and contrast those with standard DNA sequence alignment under the same conditions. Conclusion The new local alignment algorithm for two-base encoded data has substantial power to properly detect and correct measurement errors while identifying underlying sequence variants, and facilitating genome re-sequencing efforts based on this form of sequence data. PMID:19508732

Modelling and approaching pragmatic interoperability of distributed geoscience data

NASA Astrophysics Data System (ADS)

Ma, Xiaogang

2010-05-01

Interoperability of geodata, which is essential for sharing information and discovering insights within a cyberinfrastructure, is receiving increasing attention. A key requirement of interoperability in the context of geodata sharing is that data provided by local sources can be accessed, decoded, understood and appropriately used by external users. Various researchers have discussed that there are four levels in data interoperability issues: system, syntax, schematics and semantics, which respectively relate to the platform, encoding, structure and meaning of geodata. Ontology-driven approaches have been significantly studied addressing schematic and semantic interoperability issues of geodata in the last decade. There are different types, e.g. top-level ontologies, domain ontologies and application ontologies and display forms, e.g. glossaries, thesauri, conceptual schemas and logical theories. Many geodata providers are maintaining their identified local application ontologies in order to drive standardization in local databases. However, semantic heterogeneities often exist between these local ontologies, even though they are derived from equivalent disciplines. In contrast, common ontologies are being studied in different geoscience disciplines (e.g., NAMD, SWEET, etc.) as a standardization procedure to coordinate diverse local ontologies. Semantic mediation, e.g. mapping between local ontologies, or mapping local ontologies to common ontologies, has been studied as an effective way of achieving semantic interoperability between local ontologies thus reconciling semantic heterogeneities in multi-source geodata. Nevertheless, confusion still exists in the research field of semantic interoperability. One problem is caused by eliminating elements of local pragmatic contexts in semantic mediation. Comparing to the context-independent feature of a common domain ontology, local application ontologies are closely related to elements (e.g., people, time, location, intention, procedure, consequence, etc.) of local pragmatic contexts and thus context-dependent. Elimination of these elements will inevitably lead to information loss in semantic mediation between local ontologies. Correspondingly, understanding and effect of exchanged data in a new context may differ from that in its original context. Another problem is the dilemma on how to find a balance between flexibility and standardization of local ontologies, because ontologies are not fixed, but continuously evolving. It is commonly realized that we cannot use a unified ontology to replace all local ontologies because they are context-dependent and need flexibility. However, without coordination of standards, freely developed local ontologies and databases will bring enormous work of mediation between them. Finding a balance between standardization and flexibility for evolving ontologies, in a practical sense, requires negotiations (i.e. conversations, agreements and collaborations) between different local pragmatic contexts. The purpose of this work is to set up a computer-friendly model representing local pragmatic contexts (i.e. geodata sources), and propose a practical semantic negotiation procedure for approaching pragmatic interoperability between local pragmatic contexts. Information agents, objective facts and subjective dimensions are reviewed as elements of a conceptual model for representing pragmatic contexts. The author uses them to draw a practical semantic negotiation procedure approaching pragmatic interoperability of distributed geodata. The proposed conceptual model and semantic negotiation procedure were encoded with Description Logic, and then applied to analyze and manipulate semantic negotiations between different local ontologies within the National Mineral Resources Assessment (NMRA) project of China, which involves multi-source and multi-subject geodata sharing.

Sequence Variation of the tRNALeu Intron as a Marker for Genetic Diversity and Specificity of Symbiotic Cyanobacteria in Some Lichens

PubMed Central

Paulsrud, Per; Lindblad, Peter

1998-01-01

We examined the genetic diversity of Nostoc symbionts in some lichens by using the tRNALeu (UAA) intron as a genetic marker. The nucleotide sequence was analyzed in the context of the secondary structure of the transcribed intron. Cyanobacterial tRNALeu (UAA) introns were specifically amplified from freshly collected lichen samples without previous DNA extraction. The lichen species used in the present study were Nephroma arcticum, Peltigera aphthosa, P. membranacea, and P. canina. Introns with different sizes around 300 bp were consistently obtained. Multiple clones from single PCRs were screened by using their single-stranded conformational polymorphism pattern, and the nucleotide sequence was determined. No evidence for sample heterogenity was found. This implies that the symbiont in situ is not a diverse community of cyanobionts but, rather, one Nostoc strain. Furthermore, each lichen thallus contained only one intron type, indicating that each thallus is colonized only once or that there is a high degree of specificity. The same cyanobacterial intron sequence was also found in samples of one lichen species from different localities. In a phylogenetic analysis, the cyanobacterial lichen sequences grouped together with the sequences from two free-living Nostoc strains. The size differences in the intron were due to insertions and deletions in highly variable regions. The sequence data were used in discussions concerning specificity and biology of the lichen symbiosis. It is concluded that the tRNALeu (UAA) intron can be of great value when examining cyanobacterial diversity. PMID:9435083

Normal Telomere Length Maintenance in Saccharomyces cerevisiae Requires Nuclear Import of the Ever Shorter Telomeres 1 (Est1) Protein via the Importin Alpha Pathway

PubMed Central

Hawkins, Charlene

2014-01-01

The Est1 (ever shorter telomeres 1) protein is an essential component of yeast telomerase, a ribonucleoprotein complex that restores the repetitive sequences at chromosome ends (telomeres) that would otherwise be lost during DNA replication. Previous work has shown that the telomerase RNA component (TLC1) transits through the cytoplasm during telomerase biogenesis, but mechanisms of protein import have not been addressed. Here we identify three nuclear localization sequences (NLSs) in Est1p. Mutation of the most N-terminal NLS in the context of full-length Est1p reduces Est1p nuclear localization and causes telomere shortening—phenotypes that are rescued by fusion with the NLS from the simian virus 40 (SV40) large-T antigen. In contrast to that of the TLC1 RNA, Est1p nuclear import is facilitated by Srp1p, the yeast homolog of importin α. The reduction in telomere length observed at the semipermissive temperature in a srp1 mutant strain is rescued by increased Est1p expression, consistent with a defect in Est1p nuclear import. These studies suggest that at least two nuclear import pathways are required to achieve normal telomere length homeostasis in yeast. PMID:24906415

A de-identifier for medical discharge summaries.

PubMed

Uzuner, Ozlem; Sibanda, Tawanda C; Luo, Yuan; Szolovits, Peter

2008-01-01

Clinical records contain significant medical information that can be useful to researchers in various disciplines. However, these records also contain personal health information (PHI) whose presence limits the use of the records outside of hospitals. The goal of de-identification is to remove all PHI from clinical records. This is a challenging task because many records contain foreign and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These complications are compounded by the linguistic characteristics of clinical records. For example, medical discharge summaries, which are studied in this paper, are characterized by fragmented, incomplete utterances and domain-specific language; they cannot be fully processed by tools designed for lay language. In this paper, we show that we can de-identify medical discharge summaries using a de-identifier, Stat De-id, based on support vector machines and local context (F-measure=97% on PHI). Our representation of local context aids de-identification even when PHI include out-of-vocabulary words and even when PHI are ambiguous with non-PHI within the same corpus. Comparison of Stat De-id with a rule-based approach shows that local context contributes more to de-identification than dictionaries combined with hand-tailored heuristics (F-measure=85%). Comparison with two well-known named entity recognition (NER) systems, SNoW (F-measure=94%) and IdentiFinder (F-measure=36%), on five representative corpora show that when the language of documents is fragmented, a system with a relatively thorough representation of local context can be a more effective de-identifier than systems that combine (relatively simpler) local context with global context. Comparison with a Conditional Random Field De-identifier (CRFD), which utilizes global context in addition to the local context of Stat De-id, confirms this finding (F-measure=88%) and establishes that strengthening the representation of local context may be more beneficial for de-identification than complementing local with global context.

A De-identifier for Medical Discharge Summaries1

PubMed Central

Uzuner, Özlem; Sibanda, Tawanda C.; Luo, Yuan; Szolovits, Peter

2008-01-01

Objective Clinical records contain significant medical information that can be useful to researchers in various disciplines. However, these records also contain personal health information (PHI) whose presence limits the use of the records outside of hospitals. The goal of de-identification is to remove all PHI from clinical records. This is a challenging task because many records contain foreign and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These complications are compounded by the linguistic characteristics of clinical records. For example, medical discharge summaries, which are studied in this paper, are characterized by fragmented, incomplete utterances and domain-specific language; they cannot be fully processed by tools designed for lay language. Methods and Results In this paper, we show that we can de-identify medical discharge summaries using a de-identifier, Stat De-id, based on support vector machines and local context (F-measure = 97% on PHI). Our representation of local context aids de-identification even when PHI include out-of-vocabulary words and even when PHI are ambiguous with non-PHI within the same corpus. Comparison of Stat De-id with a rule-based approach shows that local context contributes more to de-identification than dictionaries combined with hand-tailored heuristics (F-measure = 85%). Comparison with two well-known named entity recognition (NER) systems, SNoW (F-measure = 94%) and IdentiFinder (F-measure = 36%), on five representative corpora show that when the language of documents is fragmented, a system with a relatively thorough representation of local context can be a more effective de-identifier than systems that combine (relatively simpler) local context with global context. Comparison with a Conditional Random Field De-identifier (CRFD), which utilizes global context in addition to the local context of Stat De-id, confirms this finding (F-measure = 88%) and establishes that strengthening the representation of local context may be more beneficial for de-identification than complementing local with global context. PMID:18053696

Hydration properties of natural and synthetic DNA sequences with methylated adenine or cytosine bases in the R.DpnI target and BDNF promoter studied by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Shanak, Siba; Helms, Volkhard

2014-12-01

Adenine and cytosine methylation are two important epigenetic modifications of DNA sequences at the levels of the genome and transcriptome. To characterize the differential roles of methylating adenine or cytosine with respect to their hydration properties, we performed conventional MD simulations and free energy perturbation calculations for two particular DNA sequences, namely the brain-derived neurotrophic factor (BDNF) promoter and the R.DpnI-bound DNA that are known to undergo methylation of C5-methyl cytosine and N6-methyl adenine, respectively. We found that a single methylated cytosine has a clearly favorable hydration free energy over cytosine since the attached methyl group has a slightly polar character. In contrast, capping the strongly polar N6 of adenine with a methyl group gives a slightly unfavorable contribution to its free energy of solvation. Performing the same demethylation in the context of a DNA double-strand gave quite similar results for the more solvent-accessible cytosine but much more unfavorable results for the rather buried adenine. Interestingly, the same demethylation reactions are far more unfavorable when performed in the context of the opposite (BDNF or R.DpnI target) sequence. This suggests a natural preference for methylation in a specific sequence context. In addition, free energy calculations for demethylating adenine or cytosine in the context of B-DNA vs. Z-DNA suggest that the conformational B-Z transition of DNA transition is rather a property of cytosine methylated sequences but is not preferable for the adenine-methylated sequences investigated here.

Hydration properties of natural and synthetic DNA sequences with methylated adenine or cytosine bases in the R.DpnI target and BDNF promoter studied by molecular dynamics simulations.

PubMed

Shanak, Siba; Helms, Volkhard

2014-12-14

Adenine and cytosine methylation are two important epigenetic modifications of DNA sequences at the levels of the genome and transcriptome. To characterize the differential roles of methylating adenine or cytosine with respect to their hydration properties, we performed conventional MD simulations and free energy perturbation calculations for two particular DNA sequences, namely the brain-derived neurotrophic factor (BDNF) promoter and the R.DpnI-bound DNA that are known to undergo methylation of C5-methyl cytosine and N6-methyl adenine, respectively. We found that a single methylated cytosine has a clearly favorable hydration free energy over cytosine since the attached methyl group has a slightly polar character. In contrast, capping the strongly polar N6 of adenine with a methyl group gives a slightly unfavorable contribution to its free energy of solvation. Performing the same demethylation in the context of a DNA double-strand gave quite similar results for the more solvent-accessible cytosine but much more unfavorable results for the rather buried adenine. Interestingly, the same demethylation reactions are far more unfavorable when performed in the context of the opposite (BDNF or R.DpnI target) sequence. This suggests a natural preference for methylation in a specific sequence context. In addition, free energy calculations for demethylating adenine or cytosine in the context of B-DNA vs. Z-DNA suggest that the conformational B-Z transition of DNA transition is rather a property of cytosine methylated sequences but is not preferable for the adenine-methylated sequences investigated here.

Context-aware and locality-constrained coding for image categorization.

PubMed

Xiao, Wenhua; Wang, Bin; Liu, Yu; Bao, Weidong; Zhang, Maojun

2014-01-01

Improving the coding strategy for BOF (Bag-of-Features) based feature design has drawn increasing attention in recent image categorization works. However, the ambiguity in coding procedure still impedes its further development. In this paper, we introduce a context-aware and locality-constrained Coding (CALC) approach with context information for describing objects in a discriminative way. It is generally achieved by learning a word-to-word cooccurrence prior to imposing context information over locality-constrained coding. Firstly, the local context of each category is evaluated by learning a word-to-word cooccurrence matrix representing the spatial distribution of local features in neighbor region. Then, the learned cooccurrence matrix is used for measuring the context distance between local features and code words. Finally, a coding strategy simultaneously considers locality in feature space and context space, while introducing the weight of feature is proposed. This novel coding strategy not only semantically preserves the information in coding, but also has the ability to alleviate the noise distortion of each class. Extensive experiments on several available datasets (Scene-15, Caltech101, and Caltech256) are conducted to validate the superiority of our algorithm by comparing it with baselines and recent published methods. Experimental results show that our method significantly improves the performance of baselines and achieves comparable and even better performance with the state of the arts.

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

PubMed

Lee, Ya-Yun; Fisher, Beth E

2017-05-22

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

Nonspatial Sequence Coding in CA1 Neurons

PubMed Central

Allen, Timothy A.; Salz, Daniel M.; McKenzie, Sam

2016-01-01

The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as “in sequence” or “out of sequence”. We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items—in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20–40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4–12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. SIGNIFICANCE STATEMENT The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal region CA1 while rats performed a nonspatial sequence memory task. We found that hippocampal neurons code for the temporal context of items (whether odors were presented in the correct or incorrect sequential position) and that this activity is linked with memory performance. The discovery of this novel form of temporal coding in hippocampal neurons advances our fundamental understanding of the neurobiology of episodic memory and will serve as a foundation for our cross-species, multitechnique approach aimed at elucidating the neural mechanisms underlying memory impairments in aging and dementia. PMID:26843637

Representation of DNA sequences in genetic codon context with applications in exon and intron prediction.

PubMed

Yin, Changchuan

2015-04-01

To apply digital signal processing (DSP) methods to analyze DNA sequences, the sequences first must be specially mapped into numerical sequences. Thus, effective numerical mappings of DNA sequences play key roles in the effectiveness of DSP-based methods such as exon prediction. Despite numerous mappings of symbolic DNA sequences to numerical series, the existing mapping methods do not include the genetic coding features of DNA sequences. We present a novel numerical representation of DNA sequences using genetic codon context (GCC) in which the numerical values are optimized by simulation annealing to maximize the 3-periodicity signal to noise ratio (SNR). The optimized GCC representation is then applied in exon and intron prediction by Short-Time Fourier Transform (STFT) approach. The results show the GCC method enhances the SNR values of exon sequences and thus increases the accuracy of predicting protein coding regions in genomes compared with the commonly used 4D binary representation. In addition, this study offers a novel way to reveal specific features of DNA sequences by optimizing numerical mappings of symbolic DNA sequences.

Formation of cis-diamminedichloroplatinum(II) 1,2-intrastrand cross-links on DNA is flanking-sequence independent.

PubMed

Burstyn, J N; Heiger-Bernays, W J; Cohen, S M; Lippard, S J

2000-11-01

Mapping of cis-diamminedichloroplatinum(II) (cis-DDP, cisplatin) DNA adducts over >3000 nucleotides was carried out using a replication blockage assay. The sites of inhibition of modified T4 DNA polymerase, also referred to as stop sites, were analyzed to determine the effects of local sequence context on the distribution of intrastrand cisplatin cross-links. In a 3120 base fragment from replicative form M13mp18 DNA containing 24.6% guanine, 25.5% thymine, 26.9% adenine and 23.0% cytosine, 166 individual stop sites were observed at a bound platinum/nucleotide ratio of 1-2 per thousand. The majority of stop sites (90%) occurred at G(n>2) sequences and the remainder were located at sites containing an AG dinucleotide. For all of the GG sites present in the mapped sequences, including those with Gn(>)2, 89% blocked replication, whereas for the AG sites only 17% blocked replication. These blockage sites were independent of flanking nucleotides in a sequence of N(1)G*G*N(2) where N(1), N(2) = A, C, G, T and G*G* indicates a 1,2-intrastrand platinum cross-link. The absence of long-range sequence dependence was confirmed by monitoring the reaction of cisplatin with a plasmid containing an 800 bp insert of the human telomere repeat sequence (TTAGGG)(n). Platination reactions monitored at several formal platinum/nucleotide ratios or as a function of time reveal that the telomere insert was not preferentially damaged by cisplatin. Both replication blockage and telomere-insert plasmid platination experiments indicate that cisplatin 1,2-intrastrand adducts do not form preferentially at G-rich sequences in vitro.

A gene-specific non-enhancer sequence is critical for expression from the promoter of the small heat shock protein gene αB-crystallin

PubMed Central

2014-01-01

Background Deciphering of the information content of eukaryotic promoters has remained confined to universal landmarks and conserved sequence elements such as enhancers and transcription factor binding motifs, which are considered sufficient for gene activation and regulation. Gene-specific sequences, interspersed between the canonical transacting factor binding sites or adjoining them within a promoter, are generally taken to be devoid of any regulatory information and have therefore been largely ignored. An unanswered question therefore is, do gene-specific sequences within a eukaryotic promoter have a role in gene activation? Here, we present an exhaustive experimental analysis of a gene-specific sequence adjoining the heat shock element (HSE) in the proximal promoter of the small heat shock protein gene, αB-crystallin (cryab). These sequences are highly conserved between the rodents and the humans. Results Using human retinal pigment epithelial cells in culture as the host, we have identified a 10-bp gene-specific promoter sequence (GPS), which, unlike an enhancer, controls expression from the promoter of this gene, only when in appropriate position and orientation. Notably, the data suggests that GPS in comparison with the HSE works in a context-independent fashion. Additionally, when moved upstream, about a nucleosome length of DNA (−154 bp) from the transcription start site (TSS), the activity of the promoter is markedly inhibited, suggesting its involvement in local promoter access. Importantly, we demonstrate that deletion of the GPS results in complete loss of cryab promoter activity in transgenic mice. Conclusions These data suggest that gene-specific sequences such as the GPS, identified here, may have critical roles in regulating gene-specific activity from eukaryotic promoters. PMID:24589182

Transcription in space--environmental vs. genetic effects on differential immune gene expression.

PubMed

Lenz, Tobias L

2015-09-01

Understanding how organisms adapt to their local environment is one of the key goals in molecular ecology. Adaptation can be achieved through qualitative changes in the coding sequence and/or quantitative changes in gene expression, where the optimal dosage of a gene's product in a given environment is being selected for. Differences in gene expression among populations inhabiting distinct environments can be suggestive of locally adapted gene regulation and have thus been studied in different species (Whitehead & Crawford ; Hodgins-Davis & Townsend ). However, in contrast to a gene's coding sequence, its expression level at a given point in time may depend on various factors, including the current environment. Although critical for understanding the extent of local adaptation, it is usually difficult to disentangle the heritable differences in gene regulation from environmental effects. In this issue of Molecular Ecology, Stutz et al. () describe an experiment in which they reciprocally transplanted three-spined sticklebacks (Gasterosteus aculeatus) between independent pairs of small and large lakes. Their experimental design allows them to attribute differences in gene expression among sticklebacks either to lake of origin or destination lake. Interestingly, they find that translocated sticklebacks show a pattern of gene expression more similar to individuals from the destination lake than to individuals from the lake of origin, suggesting that expression of the targeted genes is more strongly regulated by environmental effects than by genetics. The environmental effect by itself is not entirely surprising; however, the relative extent of it is. Especially when put in the context of local adaptation and population differentiation, as done here, these findings cast a new light onto the heritability of differential gene expression and specifically its relative importance during population divergence and ultimately ecological speciation. © 2015 John Wiley & Sons Ltd.

D-Light on promoters: a client-server system for the analysis and visualization of cis-regulatory elements

PubMed Central

2013-01-01

Background The binding of transcription factors to DNA plays an essential role in the regulation of gene expression. Numerous experiments elucidated binding sequences which subsequently have been used to derive statistical models for predicting potential transcription factor binding sites (TFBS). The rapidly increasing number of genome sequence data requires sophisticated computational approaches to manage and query experimental and predicted TFBS data in the context of other epigenetic factors and across different organisms. Results We have developed D-Light, a novel client-server software package to store and query large amounts of TFBS data for any number of genomes. Users can add small-scale data to the server database and query them in a large scale, genome-wide promoter context. The client is implemented in Java and provides simple graphical user interfaces and data visualization. Here we also performed a statistical analysis showing what a user can expect for certain parameter settings and we illustrate the usage of D-Light with the help of a microarray data set. Conclusions D-Light is an easy to use software tool to integrate, store and query annotation data for promoters. A public D-Light server, the client and server software for local installation and the source code under GNU GPL license are available at http://biwww.che.sbg.ac.at/dlight. PMID:23617301

Initialization and Restart in Stochastic Local Search: Computing a Most Probable Explanation in Bayesian Networks

NASA Technical Reports Server (NTRS)

Mengshoel, Ole J.; Wilkins, David C.; Roth, Dan

2010-01-01

For hard computational problems, stochastic local search has proven to be a competitive approach to finding optimal or approximately optimal problem solutions. Two key research questions for stochastic local search algorithms are: Which algorithms are effective for initialization? When should the search process be restarted? In the present work we investigate these research questions in the context of approximate computation of most probable explanations (MPEs) in Bayesian networks (BNs). We introduce a novel approach, based on the Viterbi algorithm, to explanation initialization in BNs. While the Viterbi algorithm works on sequences and trees, our approach works on BNs with arbitrary topologies. We also give a novel formalization of stochastic local search, with focus on initialization and restart, using probability theory and mixture models. Experimentally, we apply our methods to the problem of MPE computation, using a stochastic local search algorithm known as Stochastic Greedy Search. By carefully optimizing both initialization and restart, we reduce the MPE search time for application BNs by several orders of magnitude compared to using uniform at random initialization without restart. On several BNs from applications, the performance of Stochastic Greedy Search is competitive with clique tree clustering, a state-of-the-art exact algorithm used for MPE computation in BNs.

Extensive de novo mutation rate variation between individuals and across the genome of Chlamydomonas reinhardtii

PubMed Central

Ness, Rob W.; Morgan, Andrew D.; Vasanthakrishnan, Radhakrishnan B.; Colegrave, Nick; Keightley, Peter D.

2015-01-01

Describing the process of spontaneous mutation is fundamental for understanding the genetic basis of disease, the threat posed by declining population size in conservation biology, and much of evolutionary biology. Directly studying spontaneous mutation has been difficult, however, because new mutations are rare. Mutation accumulation (MA) experiments overcome this by allowing mutations to build up over many generations in the near absence of natural selection. Here, we sequenced the genomes of 85 MA lines derived from six genetically diverse strains of the green alga Chlamydomonas reinhardtii. We identified 6843 new mutations, more than any other study of spontaneous mutation. We observed sevenfold variation in the mutation rate among strains and that mutator genotypes arose, increasing the mutation rate approximately eightfold in some replicates. We also found evidence for fine-scale heterogeneity in the mutation rate, with certain sequence motifs mutating at much higher rates, and clusters of multiple mutations occurring at closely linked sites. There was little evidence, however, for mutation rate heterogeneity between chromosomes or over large genomic regions of 200 kbp. We generated a predictive model of the mutability of sites based on their genomic properties, including local GC content, gene expression level, and local sequence context. Our model accurately predicted the average mutation rate and natural levels of genetic diversity of sites across the genome. Notably, trinucleotides vary 17-fold in rate between the most and least mutable sites. Our results uncover a rich heterogeneity in the process of spontaneous mutation both among individuals and across the genome. PMID:26260971

Optimal habits can develop spontaneously through sensitivity to local cost

PubMed Central

Desrochers, Theresa M.; Jin, Dezhe Z.; Goodman, Noah D.; Graybiel, Ann M.

2010-01-01

Habits and rituals are expressed universally across animal species. These behaviors are advantageous in allowing sequential behaviors to be performed without cognitive overload, and appear to rely on neural circuits that are relatively benign but vulnerable to takeover by extreme contexts, neuropsychiatric sequelae, and processes leading to addiction. Reinforcement learning (RL) is thought to underlie the formation of optimal habits. However, this theoretic formulation has principally been tested experimentally in simple stimulus-response tasks with relatively few available responses. We asked whether RL could also account for the emergence of habitual action sequences in realistically complex situations in which no repetitive stimulus-response links were present and in which many response options were present. We exposed naïve macaque monkeys to such experimental conditions by introducing a unique free saccade scan task. Despite the highly uncertain conditions and no instruction, the monkeys developed a succession of stereotypical, self-chosen saccade sequence patterns. Remarkably, these continued to morph for months, long after session-averaged reward and cost (eye movement distance) reached asymptote. Prima facie, these continued behavioral changes appeared to challenge RL. However, trial-by-trial analysis showed that pattern changes on adjacent trials were predicted by lowered cost, and RL simulations that reduced the cost reproduced the monkeys’ behavior. Ultimately, the patterns settled into stereotypical saccade sequences that minimized the cost of obtaining the reward on average. These findings suggest that brain mechanisms underlying the emergence of habits, and perhaps unwanted repetitive behaviors in clinical disorders, could follow RL algorithms capturing extremely local explore/exploit tradeoffs. PMID:20974967

Motion estimation of magnetic resonance cardiac images using the Wigner-Ville and hough transforms

NASA Astrophysics Data System (ADS)

Carranza, N.; Cristóbal, G.; Bayerl, P.; Neumann, H.

2007-12-01

Myocardial motion analysis and quantification is of utmost importance for analyzing contractile heart abnormalities and it can be a symptom of a coronary artery disease. A fundamental problem in processing sequences of images is the computation of the optical flow, which is an approximation of the real image motion. This paper presents a new algorithm for optical flow estimation based on a spatiotemporal-frequency (STF) approach. More specifically it relies on the computation of the Wigner-Ville distribution (WVD) and the Hough Transform (HT) of the motion sequences. The latter is a well-known line and shape detection method that is highly robust against incomplete data and noise. The rationale of using the HT in this context is that it provides a value of the displacement field from the STF representation. In addition, a probabilistic approach based on Gaussian mixtures has been implemented in order to improve the accuracy of the motion detection. Experimental results in the case of synthetic sequences are compared with an implementation of the variational technique for local and global motion estimation, where it is shown that the results are accurate and robust to noise degradations. Results obtained with real cardiac magnetic resonance images are presented.

A hybrid spatiotemporal and Hough-based motion estimation approach applied to magnetic resonance cardiac images

NASA Astrophysics Data System (ADS)

Carranza, N.; Cristóbal, G.; Sroubek, F.; Ledesma-Carbayo, M. J.; Santos, A.

2006-08-01

Myocardial motion analysis and quantification is of utmost importance for analyzing contractile heart abnormalities and it can be a symptom of a coronary artery disease. A fundamental problem in processing sequences of images is the computation of the optical flow, which is an approximation to the real image motion. This paper presents a new algorithm for optical flow estimation based on a spatiotemporal-frequency (STF) approach, more specifically on the computation of the Wigner-Ville distribution (WVD) and the Hough Transform (HT) of the motion sequences. The later is a well-known line and shape detection method very robust against incomplete data and noise. The rationale of using the HT in this context is because it provides a value of the displacement field from the STF representation. In addition, a probabilistic approach based on Gaussian mixtures has been implemented in order to improve the accuracy of the motion detection. Experimental results with synthetic sequences are compared against an implementation of the variational technique for local and global motion estimation, where it is shown that the results obtained here are accurate and robust to noise degradations. Real cardiac magnetic resonance images have been tested and evaluated with the current method.

A tag-based approach for high-throughput analysis of CCWGG methylation.

PubMed

Denisova, Oksana V; Chernov, Andrei V; Koledachkina, Tatyana Y; Matvienko, Nicholas I

2007-10-15

Non-CpG methylation occurring in the context of CNG sequences is found in plants at a large number of genomic loci. However, there is still little information available about non-CpG methylation in mammals. Efficient methods that would allow detection of scarcely localized methylated sites in small quantities of DNA are required to elucidate the biological role of non-CpG methylation in both plants and animals. In this study, we tested a new whole genome approach to identify sites of CCWGG methylation (W is A or T), a particular case of CNG methylation, in genomic DNA. This technique is based on digestion of DNAs with methylation-sensitive restriction endonucleases EcoRII-C and AjnI. Short DNAs flanking methylated CCWGG sites (tags) are selectively purified and assembled in tandem arrays of up to nine tags. This allows high-throughput sequencing of tags, identification of flanking regions, and their exact positions in the genome. In this study, we tested specificity and efficiency of the approach.

Mechanism of Disease in early Osteoarthritis: Application of modern MR imaging techniques – A technical report

PubMed Central

Jobke, B.; Bolbos, R.; Saadat, E.; Cheng, J.; Li, X.; Majumdar, S.

2012-01-01

The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1 relaxation times with quantitative biochemical measurements of proteoglycan and collagen contents of cartilage in close synopsis with histologic morphology. A recently developed MR imaging sequence, T1, was able to detect early intracartilaginous degeneration quantitatively and also qualitatively by color mapping demonstrating a higher sensitivity than standard T2-w sequences. The results correlated highly with reduced proteoglycan content and disrupted collagen architecture as measured by biochemistry and histology. The findings lend support to a clinical implementation that allows rapid visual capturing of pathology on a local, millimeter level. Further information about articular cartilage quality otherwise not detectable in-vivo, via normal inspection, is needed for orthopedic treatment decisions in the present and future. PMID:22902064

Predicting residue-wise contact orders in proteins by support vector regression.

PubMed

Song, Jiangning; Burrage, Kevin

2006-10-03

The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences.

Characteristics of Successful Local Blended Programs in the Context of the Sloan-C Pillars

ERIC Educational Resources Information Center

Moloney, Jacqueline F.; Hickey, Charmaine P.; Bergin, Amy L.; Boccia, Judith; Polley, Kathleen; Riley, Jeannette E.

2010-01-01

Drawing on the University of Massachusetts experience in developing successful blended local programs, this paper suggests guiding principles that include mission-driven responsiveness to local contexts and partnerships; using low-cost marketing strategies available through local relationships and brand; attending to students' preferences for…

Characteristics of Successful Local Blended Programs in the Context of the Sloan-C Pillars

ERIC Educational Resources Information Center

Moloney, Jacqueline F.; Hickey, Charmaine P.; Bergin, Amy L.; Boccia, Judith; Polley, Kathleen; Riley, Jeannette E.

2007-01-01

Drawing on the University of Massachusetts experience in developing successful blended local programs, this paper suggests guiding principles that include mission-driven responsiveness to local contexts and partnerships; using low-cost marketing strategies available through local relationships and brand; attending to students' preferences for…

Targeted manipulation of leaf form via local growth repression.

PubMed

Malinowski, Robert; Kasprzewska, Ania; Fleming, Andrew J

2011-06-01

A classical view is that leaf shape is the result of local promotion of growth linked to cell proliferation. However, an alternative hypothesis is that leaf form is the result of local repression of growth in an otherwise growing system. Here we show that leaf form can indeed be manipulated in a directed fashion by local repression of growth. We show that targeting expression of an inhibitor of a cyclin-dependent kinase (KRP1) to the sinus area of developing leaves of Arabidopsis leads to local growth repression and the formation of organs with extreme lobing, including generation of leaflet-like organs. Directing KRP1 expression to other regions of the leaf using an miRNA target sequence tagging approach also leads to predictable novel leaf forms, and repression of growth in the leaf margin blocks the outgrowth of lobes, leading to a smoother perimeter. In addition, we show that decreased growth around the perimeter and across the leaf abaxial surface leads to a change in 3D form, as predicted by mechanical models of leaf growth. Our analysis provides experimental evidence that local repression of growth influences leaf shape, suggesting that it could be part of the mechanism of morphogenesis in plants in the context of an otherwise growing system. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

DNA sequence+shape kernel enables alignment-free modeling of transcription factor binding.

PubMed

Ma, Wenxiu; Yang, Lin; Rohs, Remo; Noble, William Stafford

2017-10-01

Transcription factors (TFs) bind to specific DNA sequence motifs. Several lines of evidence suggest that TF-DNA binding is mediated in part by properties of the local DNA shape: the width of the minor groove, the relative orientations of adjacent base pairs, etc. Several methods have been developed to jointly account for DNA sequence and shape properties in predicting TF binding affinity. However, a limitation of these methods is that they typically require a training set of aligned TF binding sites. We describe a sequence + shape kernel that leverages DNA sequence and shape information to better understand protein-DNA binding preference and affinity. This kernel extends an existing class of k-mer based sequence kernels, based on the recently described di-mismatch kernel. Using three in vitro benchmark datasets, derived from universal protein binding microarrays (uPBMs), genomic context PBMs (gcPBMs) and SELEX-seq data, we demonstrate that incorporating DNA shape information improves our ability to predict protein-DNA binding affinity. In particular, we observe that (i) the k-spectrum + shape model performs better than the classical k-spectrum kernel, particularly for small k values; (ii) the di-mismatch kernel performs better than the k-mer kernel, for larger k; and (iii) the di-mismatch + shape kernel performs better than the di-mismatch kernel for intermediate k values. The software is available at https://bitbucket.org/wenxiu/sequence-shape.git. rohs@usc.edu or william-noble@uw.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Sequence of contactin, a 130-kD glycoprotein concentrated in areas of interneuronal contact, defines a new member of the immunoglobulin supergene family in the nervous system

PubMed Central

1988-01-01

The primary amino acid sequence of contactin, a neuronal cell surface glycoprotein of 130 kD that is isolated in association with components of the cytoskeleton (Ranscht, B., D. J. Moss, and C. Thomas. 1984. J. Cell Biol. 99:1803-1813), was deduced from the nucleotide sequence of cDNA clones and is reported here. The cDNA sequence contains an open reading frame for a 1,071-amino acid transmembrane protein with 962 extracellular and 89 cytoplasmic amino acids. In its extracellular portion, the polypeptide features six type 1 and two type 2 repeats. The six amino-terminal type 1 repeats (I-VI) each consist of 81-99 amino acids and contain two cysteine residues that are in the right context to form globular domains as described for molecules with immunoglobulin structure. Within the proposed globular region, contactin shares 31% identical amino acids with the neural cell adhesion molecule NCAM. The two type 2 repeats (I-II) are each composed of 100 amino acids and lack cysteine residues. They are 20-31% identical to fibronectin type III repeats. Both the structural similarity of contactin to molecules of the immunoglobulin supergene family, in particular the amino acid sequence resemblance to NCAM, and its relationship to fibronectin indicate that contactin could be involved in some aspect of cellular adhesion. This suggestion is further strengthened by its localization in neuropil containing axon fascicles and synapses. PMID:3049624

Convolutional neural network architectures for predicting DNA–protein binding

PubMed Central

Zeng, Haoyang; Edwards, Matthew D.; Liu, Ge; Gifford, David K.

2016-01-01

Motivation: Convolutional neural networks (CNN) have outperformed conventional methods in modeling the sequence specificity of DNA–protein binding. Yet inappropriate CNN architectures can yield poorer performance than simpler models. Thus an in-depth understanding of how to match CNN architecture to a given task is needed to fully harness the power of CNNs for computational biology applications. Results: We present a systematic exploration of CNN architectures for predicting DNA sequence binding using a large compendium of transcription factor datasets. We identify the best-performing architectures by varying CNN width, depth and pooling designs. We find that adding convolutional kernels to a network is important for motif-based tasks. We show the benefits of CNNs in learning rich higher-order sequence features, such as secondary motifs and local sequence context, by comparing network performance on multiple modeling tasks ranging in difficulty. We also demonstrate how careful construction of sequence benchmark datasets, using approaches that control potentially confounding effects like positional or motif strength bias, is critical in making fair comparisons between competing methods. We explore how to establish the sufficiency of training data for these learning tasks, and we have created a flexible cloud-based framework that permits the rapid exploration of alternative neural network architectures for problems in computational biology. Availability and Implementation: All the models analyzed are available at http://cnn.csail.mit.edu. Contact: gifford@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307608

Equation Chapter 1 Section 1Sequence-To-Conformation Relationships of Disordered Regions Tethered to Folded Domains of Proteins.

PubMed

Mittal, Anuradha; Holehouse, Alex S; Cohan, Megan C; Pappu, Rohit V

2018-05-12

Intrinsically disordered proteins and regions (IDPs / IDRs) are characterized by well-defined sequence-to-conformation relationships (SCRs). These relationships refer to the sequence-specific preferences for average sizes, shapes, residue-specific secondary structure propensities, and amplitudes of multiscale conformational fluctuations. SCRs are discerned from the sequence-specific conformational ensembles of IDPs. A vast majority of IDPs are actually tethered to folded domains (FDs). This raises the question of whether or not SCRs inferred for IDPs are applicable to IDRs tethered to folded domains. Here, we use atomistic simulations based on a well-established forcefield paradigm and an enhanced sampling method to obtain comparative assessments of SCRs for thirteen archetypal IDRs modeled as autonomous units, as C-terminal tails connected to folded domains, and as linkers between pairs of folded domains. Our studies uncover a set of general observations regarding context-independent versus context-dependent SCRs of IDRs. SCRs are minimally perturbed upon tethering to folded domains if the IDRs are deficient in charged residues and for polyampholytic IDRs where the oppositely charged residues within the sequence of the IDR are separated into distinct blocks. In contrast, the interplay between IDRs and tethered folded domains has a significant modulatory effect on SCRs if the IDRs have intermediate fractions of charged residues or if they have sequence-intrinsic conformational preferences for canonical random coils. Our findings suggest that IDRs with context-independent SCRs might be independent evolutionary modules whereas IDRs with context-dependent intrinsic SCRs might co-evolve with the FDs to which they are tethered. Copyright © 2018. Published by Elsevier Ltd.

Infants Use Social Context to Bind Actions into a Collaborative Sequence

ERIC Educational Resources Information Center

Fawcett, Christine; Gredebäck, Gustaf

2013-01-01

Eye tracking was used to show that 18-month-old infants are sensitive to social context as a sign that others' actions are bound together as a collaborative sequence based on a joint goal. Infants observed five identical demonstrations in which Actor 1 moved a block to one location and Actor 2 moved the same block to a new location, creating…

Design of double fuzzy clustering-driven context neural networks.

PubMed

Kim, Eun-Hu; Oh, Sung-Kwun; Pedrycz, Witold

2018-08-01

In this study, we introduce a novel category of double fuzzy clustering-driven context neural networks (DFCCNNs). The study is focused on the development of advanced design methodologies for redesigning the structure of conventional fuzzy clustering-based neural networks. The conventional fuzzy clustering-based neural networks typically focus on dividing the input space into several local spaces (implied by clusters). In contrast, the proposed DFCCNNs take into account two distinct local spaces called context and cluster spaces, respectively. Cluster space refers to the local space positioned in the input space whereas context space concerns a local space formed in the output space. Through partitioning the output space into several local spaces, each context space is used as the desired (target) local output to construct local models. To complete this, the proposed network includes a new context layer for reasoning about context space in the output space. In this sense, Fuzzy C-Means (FCM) clustering is useful to form local spaces in both input and output spaces. The first one is used in order to form clusters and train weights positioned between the input and hidden layer, whereas the other one is applied to the output space to form context spaces. The key features of the proposed DFCCNNs can be enumerated as follows: (i) the parameters between the input layer and hidden layer are built through FCM clustering. The connections (weights) are specified as constant terms being in fact the centers of the clusters. The membership functions (represented through the partition matrix) produced by the FCM are used as activation functions located at the hidden layer of the "conventional" neural networks. (ii) Following the hidden layer, a context layer is formed to approximate the context space of the output variable and each node in context layer means individual local model. The outputs of the context layer are specified as a combination of both weights formed as linear function and the outputs of the hidden layer. The weights are updated using the least square estimation (LSE)-based method. (iii) At the output layer, the outputs of context layer are decoded to produce the corresponding numeric output. At this time, the weighted average is used and the weights are also adjusted with the use of the LSE scheme. From the viewpoint of performance improvement, the proposed design methodologies are discussed and experimented with the aid of benchmark machine learning datasets. Through the experiments, it is shown that the generalization abilities of the proposed DFCCNNs are better than those of the conventional FCNNs reported in the literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

BioSAVE: display of scored annotation within a sequence context.

PubMed

Pollock, Richard F; Adryan, Boris

2008-03-20

Visualization of sequence annotation is a common feature in many bioinformatics tools. For many applications it is desirable to restrict the display of such annotation according to a score cutoff, as biological interpretation can be difficult in the presence of the entire data. Unfortunately, many visualisation solutions are somewhat static in the way they handle such score cutoffs. We present BioSAVE, a sequence annotation viewer with on-the-fly selection of visualisation thresholds for each feature. BioSAVE is a versatile OS X program for visual display of scored features (annotation) within a sequence context. The program reads sequence and additional supplementary annotation data (e.g., position weight matrix matches, conservation scores, structural domains) from a variety of commonly used file formats and displays them graphically. Onscreen controls then allow for live customisation of these graphics, including on-the-fly selection of visualisation thresholds for each feature. Possible applications of the program include display of transcription factor binding sites in a genomic context or the visualisation of structural domain assignments in protein sequences and many more. The dynamic visualisation of these annotations is useful, e.g., for the determination of cutoff values of predicted features to match experimental data. Program, source code and exemplary files are freely available at the BioSAVE homepage.

BioSAVE: Display of scored annotation within a sequence context

PubMed Central

Pollock, Richard F; Adryan, Boris

2008-01-01

Background Visualization of sequence annotation is a common feature in many bioinformatics tools. For many applications it is desirable to restrict the display of such annotation according to a score cutoff, as biological interpretation can be difficult in the presence of the entire data. Unfortunately, many visualisation solutions are somewhat static in the way they handle such score cutoffs. Results We present BioSAVE, a sequence annotation viewer with on-the-fly selection of visualisation thresholds for each feature. BioSAVE is a versatile OS X program for visual display of scored features (annotation) within a sequence context. The program reads sequence and additional supplementary annotation data (e.g., position weight matrix matches, conservation scores, structural domains) from a variety of commonly used file formats and displays them graphically. Onscreen controls then allow for live customisation of these graphics, including on-the-fly selection of visualisation thresholds for each feature. Conclusion Possible applications of the program include display of transcription factor binding sites in a genomic context or the visualisation of structural domain assignments in protein sequences and many more. The dynamic visualisation of these annotations is useful, e.g., for the determination of cutoff values of predicted features to match experimental data. Program, source code and exemplary files are freely available at the BioSAVE homepage. PMID:18366701

PRIMAL: Page Rank-Based Indoor Mapping and Localization Using Gene-Sequenced Unlabeled WLAN Received Signal Strength

PubMed Central

Zhou, Mu; Zhang, Qiao; Xu, Kunjie; Tian, Zengshan; Wang, Yanmeng; He, Wei

2015-01-01

Due to the wide deployment of wireless local area networks (WLAN), received signal strength (RSS)-based indoor WLAN localization has attracted considerable attention in both academia and industry. In this paper, we propose a novel page rank-based indoor mapping and localization (PRIMAL) by using the gene-sequenced unlabeled WLAN RSS for simultaneous localization and mapping (SLAM). Specifically, first of all, based on the observation of the motion patterns of the people in the target environment, we use the Allen logic to construct the mobility graph to characterize the connectivity among different areas of interest. Second, the concept of gene sequencing is utilized to assemble the sporadically-collected RSS sequences into a signal graph based on the transition relations among different RSS sequences. Third, we apply the graph drawing approach to exhibit both the mobility graph and signal graph in a more readable manner. Finally, the page rank (PR) algorithm is proposed to construct the mapping from the signal graph into the mobility graph. The experimental results show that the proposed approach achieves satisfactory localization accuracy and meanwhile avoids the intensive time and labor cost involved in the conventional location fingerprinting-based indoor WLAN localization. PMID:26404274

DLocalMotif: a discriminative approach for discovering local motifs in protein sequences.

PubMed

Mehdi, Ahmed M; Sehgal, Muhammad Shoaib B; Kobe, Bostjan; Bailey, Timothy L; Bodén, Mikael

2013-01-01

Local motifs are patterns of DNA or protein sequences that occur within a sequence interval relative to a biologically defined anchor or landmark. Current protein motif discovery methods do not adequately consider such constraints to identify biologically significant motifs that are only weakly over-represented but spatially confined. Using negatives, i.e. sequences known to not contain a local motif, can further increase the specificity of their discovery. This article introduces the method DLocalMotif that makes use of positional information and negative data for local motif discovery in protein sequences. DLocalMotif combines three scoring functions, measuring degrees of motif over-representation, entropy and spatial confinement, specifically designed to discriminatively exploit the availability of negative data. The method is shown to outperform current methods that use only a subset of these motif characteristics. We apply the method to several biological datasets. The analysis of peroxisomal targeting signals uncovers several novel motifs that occur immediately upstream of the dominant peroxisomal targeting signal-1 signal. The analysis of proline-tyrosine nuclear localization signals uncovers multiple novel motifs that overlap with C2H2 zinc finger domains. We also evaluate the method on classical nuclear localization signals and endoplasmic reticulum retention signals and find that DLocalMotif successfully recovers biologically relevant sequence properties. http://bioinf.scmb.uq.edu.au/dlocalmotif/

The Late Pleistocene-Holocene community development in Central and SE-Europe in direct fossil record: scope of the approach, common patterns and inter-regional differences.

NASA Astrophysics Data System (ADS)

Horacek, Ivan; Lozek, Vojen

2010-05-01

The information provided by modern instrumental approaches (molecular phylogeography, ancient DNA analyses, large scale radiocarbon datings etc.) refined the knowledge on Late Quaternary faunal development and range history of particular taxa in essential way. Nevertheless, the direct fossil record remains still an essential substrate in study of that topics, and to reveal all the information, that it may provide, and integrate it with the outputs of the other approaches presents one of the essential aim of the present meeting. Unfortunately, the immediate use of fossil record for the paleoecologic and paleobiogeographic inferences is often limited by its fragmentarity (both in temporal and spatial respects), taphonomic influences and/or locally specific post-sedimentary effects which all may bias it in a considerable degree. Hence, each particular record is to be carefully reexamined in respect to all factor which may bias it - unfortunately, often it is not too easy to respond that task, particularly when the record is retrived from secondary sources. It should also be remembered that the records representing narrow time slices without a robust lithostratigraphic context do not provide any information on the historical and contextual setting of the respective faunal situation. Such information that is essential for reconstructions of paleobiogeography of community development and similar locally-sensitive phenomena can only be retrived from the continuous sedimentary series which establish the sequence of particular faunal events by direct superposition. A sufficiently dense network of such series provides than a possibility of direct inter-regional comparisons and a high resolution information on the paleobiogeography of the Late Pleistocene-Holocene rearrangements of mammalian communities, local variation in history of particular species and its community context. We illustrate productivity of such approach on with aid of the fossil record obtained from continuous sedimentary sequences from different regions of Czech Republic and Slovakia (850 community samples, 29,800 MNI) and neighbouring countries of Central Europe. Despite common general trends we demonstrated stricking local and regional specificities. Among other they include (a) continuous survival of several woodland elements (Clethrionomys glareolus, Sorex araneus, Micotus subterraneus, Microtus agrestis) throughout Weichselian (including LGM) in the Carpathians, (b) prolonged survival of the glacial elements Ochotona pusilla and Microtus gregalis in Pannonian basin and (c) Dicrostonyx gulielmi in the Carpathian foredeep, contrasting to (d) the early disappearance of them in S-Germany and Bohemia, and (e) similar difference were found also in other cenologic traits. While the glacial communities were nearly homogenous in their structure throughout whole the region, the Holocene development produced a considerable faunal provincialism, which was the most pronounced during Boreal. In contrast to central Europe, the available sequences from the SE-Europe and Asia Minor show only minute faunal changes during the Vistulian and Holocene, no essential rearrangements in community structure were observed (at least as the core species are concerned) and except for Lagurus no glacial immigrant did invade the region. At the same time a degree of local provincialism was continuously high and, in a regional scale, it continuously exceeded that of the Boreal central Europe.

Effect of sequence-dependent rigidity on plectoneme localization in dsDNA

NASA Astrophysics Data System (ADS)

Medalion, Shlomi; Rabin, Yitzhak

2016-04-01

We use Monte-Carlo simulations to study the effect of variable rigidity on plectoneme formation and localization in supercoiled double-stranded DNA. We show that the presence of soft sequences increases the number of plectoneme branches and that the edges of the branches tend to be localized at these sequences. We propose an experimental approach to test our results in vitro, and discuss the possible role played by plectoneme localization in the search process of transcription factors for their targets (promoter regions) on the bacterial genome.

The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling

PubMed Central

Habuka, Masato; Fagerberg, Linn; Hallström, Björn M.; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

2015-01-01

To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder. PMID:26694548

Symbolic emblems of the Levantine Aurignacians as a regional entity identifier (Hayonim Cave, Lower Galilee, Israel).

PubMed

Tejero, José-Miguel; Belfer-Cohen, Anna; Bar-Yosef, Ofer; Gutkin, Vitaly; Rabinovich, Rivka

2018-05-15

The Levantine Aurignacian is a unique phenomenon in the local Upper Paleolithic sequence, showing greater similarity to the West European classic Aurignacian than to the local Levantine archaeological entities preceding and following it. Herewith we highlight another unique characteristic of this entity, namely, the presence of symbolic objects in the form of notched bones (mostly gazelle scapulae) from the Aurignacian levels of Hayonim Cave, Lower Galilee, Israel. Through both macroscopic and microscopic analyses of the items, we suggest that they are not mere cut marks but rather are intentional (decorative?) human-made markings. The significance of this evidence for symbolic behavior is discussed in its chrono-cultural and geographical contexts. Notched bones are among the oldest symbolic expressions of anatomically modern humans. However, unlike other Paleolithic sites where such findings were reported in single numbers, the number of these items recovered at Hayonim Cave is sufficient to assume they possibly served as an emblem of the Levantine Aurignacian.

Mechanistic considerations on the wavelength-dependent variations of UVR genotoxicity and mutagenesis in skin: the discrimination of UVA-signature from UV-signature mutation.

PubMed

Ikehata, Hironobu

2018-05-31

Ultraviolet radiation (UVR) predominantly induces UV-signature mutations, C → T and CC → TT base substitutions at dipyrimidine sites, in the cellular and skin genome. I observed in our in vivo mutation studies of mouse skin that these UVR-specific mutations show a wavelength-dependent variation in their sequence-context preference. The C → T mutation occurs most frequently in the 5'-TCG-3' sequence regardless of the UVR wavelength, but is recovered more preferentially there as the wavelength increases, resulting in prominent occurrences exclusively in the TCG sequence in the UVA wavelength range, which I will designate as a "UVA signature" in this review. The preference of the UVB-induced C → T mutation for the sequence contexts shows a mixed pattern of UVC- and UVA-induced mutations, and a similar pattern is also observed for natural sunlight, in which UVB is the most genotoxic component. In addition, the CC → TT mutation hardly occurs at UVA1 wavelengths, although it is detected rarely but constantly in the UVC and UVB ranges. This wavelength-dependent variation in the sequence-context preference of the UVR-specific mutations could be explained by two different photochemical mechanisms of cyclobutane pyrimidine dimer (CPD) formation. The UV-signature mutations observed in the UVC and UVB ranges are known to be caused mainly by CPDs produced through the conventional singlet/triplet excitation of pyrimidine bases after the direct absorption of the UVC/UVB photon energy in those bases. On the other hand, a novel photochemical mechanism through the direct absorption of the UVR energy to double-stranded DNA, which is called "collective excitation", has been proposed for the UVA-induced CPD formation. The UVA photons directly absorbed by DNA produce CPDs with a sequence context preference different from that observed for CPDs caused by the UVC/UVB-mediated singlet/triplet excitation, causing CPD formation preferentially at thymine-containing dipyrimidine sites and probably also preferably at methyl CpG-associated dipyrimidine sites, which include the TCG sequence. In this review, I present a mechanistic consideration on the wavelength-dependent variation of the sequence context preference of the UVR-specific mutations and rationalize the proposition of the UVA-signature mutation, in addition to the UV-signature mutation.

Expanding the 2011 Prague, OK Event Catalog: Detections, Relocations, and Stress Drop Estimates

NASA Astrophysics Data System (ADS)

Clerc, F.; Cochran, E. S.; Dougherty, S. L.; Keranen, K. M.; Harrington, R. M.

2016-12-01

The Mw 5.6 earthquake occurring on 6 Nov. 2011, near Prague, OK, is thought to have been triggered by a Mw 4.8 foreshock, which was likely induced by fluid injection into local wastewater disposal wells [Keranen et al., 2013; Sumy et al., 2014]. Previous stress drop estimates for the sequence have suggested values lower than those for most Central and Eastern U.S. tectonic events of similar magnitudes [Hough, 2014; Sun & Hartzell, 2014; Sumy & Neighbors et al., 2016]. Better stress drop estimates allow more realistic assessment of seismic hazard and more effective regulation of wastewater injection. More reliable estimates of source properties may help to differentiate induced events from natural ones. Using data from local and regional networks, we perform event detections, relocations, and stress drop calculations of the Prague aftershock sequence. We use the Match & Locate method, a variation on the matched-filter method which detects events of lower magnitudes by stacking cross-correlograms from different stations [Zhang & Wen, 2013; 2015], in order to create a more complete catalog from 6 Nov to 31 Dec 2011. We then relocate the detected events using the HypoDD double-difference algorithm. Using our enhanced catalog and relocations, we examine the seismicity distribution for evidence of migration and investigate implications for triggering mechanisms. To account for path and site effects, we calculate stress drops using the Empirical Green's Function (EGF) spectral ratio method, beginning with 2730 previously relocated events. We determine whether there is a correlation between the stress drop magnitudes and the spatial and temporal distribution of events, including depth, position relative to existing faults, and proximity to injection wells. Finally, we consider the range of stress drop values and scaling with respect to event magnitudes within the context of previously published work for the Prague sequence as well as other induced and natural sequences.

Event Boundaries Trigger Rapid Memory Reinstatement of the Prior Events to Promote Their Representation in Long-Term Memory.

PubMed

Sols, Ignasi; DuBrow, Sarah; Davachi, Lila; Fuentemilla, Lluís

2017-11-20

Although everyday experiences unfold continuously over time, shifts in context, or event boundaries, can influence how those events come to be represented in memory [1-4]. Specifically, mnemonic binding across sequential representations is more challenging at context shifts, such that successful temporal associations are more likely to be formed within than across contexts [1, 2, 5-9]. However, in order to preserve a subjective sense of continuity, it is important that the memory system bridge temporally adjacent events, even if they occur in seemingly distinct contexts. Here, we used pattern similarity analysis to scalp electroencephalographic (EEG) recordings during a sequential learning task [2, 3] in humans and showed that the detection of event boundaries triggered a rapid memory reinstatement of the just-encoded sequence episode. Memory reactivation was detected rapidly (∼200-800 ms from the onset of the event boundary) and was specific to context shifts that were preceded by an event sequence with episodic content. Memory reinstatement was not observed during the sequential encoding of events within an episode, indicating that memory reactivation was induced specifically upon context shifts. Finally, the degree of neural similarity between neural responses elicited during sequence encoding and at event boundaries correlated positively with participants' ability to later link across sequences of events, suggesting a critical role in binding temporally adjacent events in long-term memory. Current results shed light onto the neural mechanisms that promote episodic encoding not only for information within the event, but also, importantly, in the ability to link across events to create a memory representation of continuous experience. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-precision spatial localization of mouse vocalizations during social interaction.

PubMed

Heckman, Jesse J; Proville, Rémi; Heckman, Gert J; Azarfar, Alireza; Celikel, Tansu; Englitz, Bernhard

2017-06-07

Mice display a wide repertoire of vocalizations that varies with age, sex, and context. Especially during courtship, mice emit ultrasonic vocalizations (USVs) of high complexity, whose detailed structure is poorly understood. As animals of both sexes vocalize, the study of social vocalizations requires attributing single USVs to individuals. The state-of-the-art in sound localization for USVs allows spatial localization at centimeter resolution, however, animals interact at closer ranges, involving tactile, snout-snout exploration. Hence, improved algorithms are required to reliably assign USVs. We develop multiple solutions to USV localization, and derive an analytical solution for arbitrary vertical microphone positions. The algorithms are compared on wideband acoustic noise and single mouse vocalizations, and applied to social interactions with optically tracked mouse positions. A novel, (frequency) envelope weighted generalised cross-correlation outperforms classical cross-correlation techniques. It achieves a median error of ~1.4 mm for noise and ~4-8.5 mm for vocalizations. Using this algorithms in combination with a level criterion, we can improve the assignment for interacting mice. We report significant differences in mean USV properties between CBA mice of different sexes during social interaction. Hence, the improved USV attribution to individuals lays the basis for a deeper understanding of social vocalizations, in particular sequences of USVs.

A microarray-based genotyping and genetic mapping approach for highly heterozygous outcrossing species enables localization of a large fraction of the unassembled Populus trichocarpa genome sequence.

PubMed

Drost, Derek R; Novaes, Evandro; Boaventura-Novaes, Carolina; Benedict, Catherine I; Brown, Ryan S; Yin, Tongming; Tuskan, Gerald A; Kirst, Matias

2009-06-01

Microarrays have demonstrated significant power for genome-wide analyses of gene expression, and recently have also revolutionized the genetic analysis of segregating populations by genotyping thousands of loci in a single assay. Although microarray-based genotyping approaches have been successfully applied in yeast and several inbred plant species, their power has not been proven in an outcrossing species with extensive genetic diversity. Here we have developed methods for high-throughput microarray-based genotyping in such species using a pseudo-backcross progeny of 154 individuals of Populus trichocarpa and P. deltoides analyzed with long-oligonucleotide in situ-synthesized microarray probes. Our analysis resulted in high-confidence genotypes for 719 single-feature polymorphism (SFP) and 1014 gene expression marker (GEM) candidates. Using these genotypes and an established microsatellite (SSR) framework map, we produced a high-density genetic map comprising over 600 SFPs, GEMs and SSRs. The abundance of gene-based markers allowed us to localize over 35 million base pairs of previously unplaced whole-genome shotgun (WGS) scaffold sequence to putative locations in the genome of P. trichocarpa. A high proportion of sampled scaffolds could be verified for their placement with independently mapped SSRs, demonstrating the previously un-utilized power that high-density genotyping can provide in the context of map-based WGS sequence reassembly. Our results provide a substantial contribution to the continued improvement of the Populus genome assembly, while demonstrating the feasibility of microarray-based genotyping in a highly heterozygous population. The strategies presented are applicable to genetic mapping efforts in all plant species with similarly high levels of genetic diversity.

VIP Barcoding: composition vector-based software for rapid species identification based on DNA barcoding.

PubMed

Fan, Long; Hui, Jerome H L; Yu, Zu Guo; Chu, Ka Hou

2014-07-01

Species identification based on short sequences of DNA markers, that is, DNA barcoding, has emerged as an integral part of modern taxonomy. However, software for the analysis of large and multilocus barcoding data sets is scarce. The Basic Local Alignment Search Tool (BLAST) is currently the fastest tool capable of handling large databases (e.g. >5000 sequences), but its accuracy is a concern and has been criticized for its local optimization. However, current more accurate software requires sequence alignment or complex calculations, which are time-consuming when dealing with large data sets during data preprocessing or during the search stage. Therefore, it is imperative to develop a practical program for both accurate and scalable species identification for DNA barcoding. In this context, we present VIP Barcoding: a user-friendly software in graphical user interface for rapid DNA barcoding. It adopts a hybrid, two-stage algorithm. First, an alignment-free composition vector (CV) method is utilized to reduce searching space by screening a reference database. The alignment-based K2P distance nearest-neighbour method is then employed to analyse the smaller data set generated in the first stage. In comparison with other software, we demonstrate that VIP Barcoding has (i) higher accuracy than Blastn and several alignment-free methods and (ii) higher scalability than alignment-based distance methods and character-based methods. These results suggest that this platform is able to deal with both large-scale and multilocus barcoding data with accuracy and can contribute to DNA barcoding for modern taxonomy. VIP Barcoding is free and available at http://msl.sls.cuhk.edu.hk/vipbarcoding/. © 2014 John Wiley & Sons Ltd.

Widespread Site-Dependent Buffering of Human Regulatory Polymorphism

PubMed Central

Kutyavin, Tanya; Stamatoyannopoulos, John A.

2012-01-01

The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence. To address this, we comprehensively analyzed heritable genome-wide binding patterns of a major sequence-specific regulator (CTCF) in relation to genetic variability in binding site sequences across a multi-generational pedigree. We localized and quantified CTCF occupancy by ChIP-seq in 12 related and unrelated individuals spanning three generations, followed by comprehensive targeted resequencing of the entire CTCF–binding landscape across all individuals. We identified hundreds of variants with reproducible quantitative effects on CTCF occupancy (both positive and negative). While these effects paralleled protein–DNA recognition energetics when averaged, they were extensively buffered by striking local context dependencies. In the significant majority of cases buffering was complete, resulting in silent variants spanning every position within the DNA recognition interface irrespective of level of binding energy or evolutionary constraint. The prevalence of complex partial or complete buffering effects severely constrained the ability to predict reliably the impact of variation within any given binding site instance. Surprisingly, 40% of variants that increased CTCF occupancy occurred at positions of human–chimp divergence, challenging the expectation that the vast majority of functional regulatory variants should be deleterious. Our results suggest that, even in the presence of “perfect” genetic information afforded by resequencing and parallel studies in multiple related individuals, genomic site-specific prediction of the consequences of individual variation in regulatory DNA will require systematic coupling with empirical functional genomic measurements. PMID:22457641

Mapping three guanine oxidation products along DNA following exposure to three types of reactive oxygen species.

PubMed

Matter, Brock; Seiler, Christopher L; Murphy, Kristopher; Ming, Xun; Zhao, Jianwei; Lindgren, Bruce; Jones, Roger; Tretyakova, Natalia

2018-06-01

Reactive oxygen and nitrogen species generated during respiration, inflammation, and immune response can damage cellular DNA, contributing to aging, cancer, and neurodegeneration. The ability of oxidized DNA bases to interfere with DNA replication and transcription is strongly influenced by their chemical structures and locations within the genome. In the present work, we examined the influence of local DNA sequence context, DNA secondary structure, and oxidant identity on the efficiency and the chemistry of guanine oxidation in the context of the Kras protooncogene. A novel isotope labeling strategy developed in our laboratory was used to accurately map the formation of 2,2-diamino-4-[(2-deoxy-β-D-erythropentofuranosyl)amino]- 5(2 H)-oxazolone (Z), 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG), and 8-nitroguanine (8-NO 2 -G) lesions along DNA duplexes following photooxidation in the presence of riboflavin, treatment with nitrosoperoxycarbonate, and oxidation in the presence of hydroxyl radicals. Riboflavin-mediated photooxidation preferentially induced OG lesions at 5' guanines within GG repeats, while treatment with nitrosoperoxycarbonate targeted 3'-guanines within GG and AG dinucleotides. Little sequence selectivity was observed following hydroxyl radical-mediated oxidation. However, Z and 8-NO 2 -G adducts were overproduced at duplex ends, irrespective of oxidant identity. Overall, our results indicate that the patterns of Z, OG, and 8-NO 2 -G adduct formation in the genome are distinct and are influenced by oxidant identity and the secondary structure of DNA. Copyright © 2018 Elsevier Inc. All rights reserved.

Taking advantage of local structure descriptors to analyze interresidue contacts in protein structures and protein complexes.

PubMed

Martin, Juliette; Regad, Leslie; Etchebest, Catherine; Camproux, Anne-Claude

2008-11-15

Interresidue protein contacts in proteins structures and at protein-protein interface are classically described by the amino acid types of interacting residues and the local structural context of the contact, if any, is described using secondary structures. In this study, we present an alternate analysis of interresidue contact using local structures defined by the structural alphabet introduced by Camproux et al. This structural alphabet allows to describe a 3D structure as a sequence of prototype fragments called structural letters, of 27 different types. Each residue can then be assigned to a particular local structure, even in loop regions. The analysis of interresidue contacts within protein structures defined using Voronoï tessellations reveals that pairwise contact specificity is greater in terms of structural letters than amino acids. Using a simple heuristic based on specificity score comparison, we find that 74% of the long-range contacts within protein structures are better described using structural letters than amino acid types. The investigation is extended to a set of protein-protein complexes, showing that the similar global rules apply as for intraprotein contacts, with 64% of the interprotein contacts best described by local structures. We then present an evaluation of pairing functions integrating structural letters to decoy scoring and show that some complexes could benefit from the use of structural letter-based pairing functions.

Localization and characterization of X chromosome inversion breakpoints separating Drosophila mojavensis and Drosophila arizonae.

PubMed

Cirulli, Elizabeth T; Noor, Mohamed A F

2007-01-01

Ectopic exchange between transposable elements or other repetitive sequences along a chromosome can produce chromosomal inversions. As a result, genome sequence studies typically find sequence similarity between corresponding inversion breakpoint regions. Here, we identify and investigate the breakpoint regions of the X chromosome inversion distinguishing Drosophila mojavensis and Drosophila arizonae. We localize one inversion breakpoint to 13.7 kb and localize the other to a 1-Mb interval. Using this localization and assuming microsynteny between Drosophila melanogaster and D. arizonae, we pinpoint likely positions of the inversion breakpoints to windows of less than 3000 bp. These breakpoints define the size of the inversion to approximately 11 Mb. However, in contrast to many other studies, we fail to find significant sequence similarity between the 2 breakpoint regions. The localization of these inversion breakpoints will facilitate future genetic and molecular evolutionary studies in this species group, an emerging model system for ecological genetics.

The eukaryotic signal sequence, YGRL, targets the chlamydial inclusion

PubMed Central

Kabeiseman, Emily J.; Cichos, Kyle H.; Moore, Elizabeth R.

2014-01-01

Understanding how host proteins are targeted to pathogen-specified organelles, like the chlamydial inclusion, is fundamentally important to understanding the biogenesis of these unique subcellular compartments and how they maintain autonomy within the cell. Syntaxin 6, which localizes to the chlamydial inclusion, contains an YGRL signal sequence. The YGRL functions to return syntaxin 6 to the trans-Golgi from the plasma membrane, and deletion of the YGRL signal sequence from syntaxin 6 also prevents the protein from localizing to the chlamydial inclusion. YGRL is one of three YXXL (YGRL, YQRL, and YKGL) signal sequences which target proteins to the trans-Golgi. We designed various constructs of eukaryotic proteins to test the specificity and propensity of YXXL sequences to target the inclusion. The YGRL signal sequence redirects proteins (e.g., Tgn38, furin, syntaxin 4) that normally do not localize to the chlamydial inclusion. Further, the requirement of the YGRL signal sequence for syntaxin 6 localization to inclusions formed by different species of Chlamydia is conserved. These data indicate that there is an inherent property of the chlamydial inclusion, which allows it to recognize the YGRL signal sequence. To examine whether this “inherent property” was protein or lipid in nature, we asked if deletion of the YGRL signal sequence from syntaxin 6 altered the ability of the protein to interact with proteins or lipids. Deletion or alteration of the YGRL from syntaxin 6 does not appreciably impact syntaxin 6-protein interactions, but does decrease syntaxin 6-lipid interactions. Intriguingly, data also demonstrate that YKGL or YQRL can successfully substitute for YGRL in localization of syntaxin 6 to the chlamydial inclusion. Importantly and for the first time, we are establishing that a eukaryotic signal sequence targets the chlamydial inclusion. PMID:25309881

Parasail: SIMD C library for global, semi-global, and local pairwise sequence alignments.

PubMed

Daily, Jeff

2016-02-10

Sequence alignment algorithms are a key component of many bioinformatics applications. Though various fast Smith-Waterman local sequence alignment implementations have been developed for x86 CPUs, most are embedded into larger database search tools. In addition, fast implementations of Needleman-Wunsch global sequence alignment and its semi-global variants are not as widespread. This article presents the first software library for local, global, and semi-global pairwise intra-sequence alignments and improves the performance of previous intra-sequence implementations. A faster intra-sequence local pairwise alignment implementation is described and benchmarked, including new global and semi-global variants. Using a 375 residue query sequence a speed of 136 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon E5-2670 24-core processor system, the highest reported for an implementation based on Farrar's 'striped' approach. Rognes's SWIPE optimal database search application is still generally the fastest available at 1.2 to at best 2.4 times faster than Parasail for sequences shorter than 500 amino acids. However, Parasail was faster for longer sequences. For global alignments, Parasail's prefix scan implementation is generally the fastest, faster even than Farrar's 'striped' approach, however the opal library is faster for single-threaded applications. The software library is designed for 64 bit Linux, OS X, or Windows on processors with SSE2, SSE41, or AVX2. Source code is available from https://github.com/jeffdaily/parasail under the Battelle BSD-style license. Applications that require optimal alignment scores could benefit from the improved performance. For the first time, SIMD global, semi-global, and local alignments are available in a stand-alone C library.

Implicit sequence learning and contextual cueing do not compete for central cognitive resources.

PubMed

Jiménez, Luis; Vázquez, Gustavo A

2011-02-01

Sequence learning and contextual cueing explore different forms of implicit learning, arising from practice with a structured serial task, or with a search task with informative contexts. We assess whether these two learning effects arise simultaneously when both remain implicit. Experiments 1 and 2 confirm that a cueing effect can be observed under a continuous setting and that there is no interference between contextual cueing and sequence learning. Experiments 3a and 3b tested whether an interference arises specifically when the sequence becomes explicit. Results show that the expression of contextual cueing disappeared in those conditions but that context information is still acquired, and it affects performance when the sequence is removed. The results are discussed in relation to the current debates about the automaticity of implicit learning, and about the role of attention in the acquisition and expression of contextual cueing. (c) 2010 APA, all rights reserved.

Gene context analysis in the Integrated Microbial Genomes (IMG) data management system.

PubMed

Mavromatis, Konstantinos; Chu, Ken; Ivanova, Natalia; Hooper, Sean D; Markowitz, Victor M; Kyrpides, Nikos C

2009-11-24

Computational methods for determining the function of genes in newly sequenced genomes have been traditionally based on sequence similarity to genes whose function has been identified experimentally. Function prediction methods can be extended using gene context analysis approaches such as examining the conservation of chromosomal gene clusters, gene fusion events and co-occurrence profiles across genomes. Context analysis is based on the observation that functionally related genes are often having similar gene context and relies on the identification of such events across phylogenetically diverse collection of genomes. We have used the data management system of the Integrated Microbial Genomes (IMG) as the framework to implement and explore the power of gene context analysis methods because it provides one of the largest available genome integrations. Visualization and search tools to facilitate gene context analysis have been developed and applied across all publicly available archaeal and bacterial genomes in IMG. These computations are now maintained as part of IMG's regular genome content update cycle. IMG is available at: http://img.jgi.doe.gov.

SubCellProt: predicting protein subcellular localization using machine learning approaches.

PubMed

Garg, Prabha; Sharma, Virag; Chaudhari, Pradeep; Roy, Nilanjan

2009-01-01

High-throughput genome sequencing projects continue to churn out enormous amounts of raw sequence data. However, most of this raw sequence data is unannotated and, hence, not very useful. Among the various approaches to decipher the function of a protein, one is to determine its localization. Experimental approaches for proteome annotation including determination of a protein's subcellular localizations are very costly and labor intensive. Besides the available experimental methods, in silico methods present alternative approaches to accomplish this task. Here, we present two machine learning approaches for prediction of the subcellular localization of a protein from the primary sequence information. Two machine learning algorithms, k Nearest Neighbor (k-NN) and Probabilistic Neural Network (PNN) were used to classify an unknown protein into one of the 11 subcellular localizations. The final prediction is made on the basis of a consensus of the predictions made by two algorithms and a probability is assigned to it. The results indicate that the primary sequence derived features like amino acid composition, sequence order and physicochemical properties can be used to assign subcellular localization with a fair degree of accuracy. Moreover, with the enhanced accuracy of our approach and the definition of a prediction domain, this method can be used for proteome annotation in a high throughput manner. SubCellProt is available at www.databases.niper.ac.in/SubCellProt.

The Sequence of Study Changes What Information Is Attended to, Encoded, and Remembered during Category Learning

ERIC Educational Resources Information Center

Carvalho, Paulo F.; Goldstone, Robert L.

2017-01-01

The sequence of study influences how we learn. Previous research has identified different sequences as potentially beneficial for learning in different contexts and with different materials. Here we investigate the mechanisms involved in inductive category learning that give rise to these sequencing effects. Across 3 experiments we show evidence…

Diff-seq: A high throughput sequencing-based mismatch detection assay for DNA variant enrichment and discovery

PubMed Central

Karas, Vlad O; Sinnott-Armstrong, Nicholas A; Varghese, Vici; Shafer, Robert W; Greenleaf, William J; Sherlock, Gavin

2018-01-01

Abstract Much of the within species genetic variation is in the form of single nucleotide polymorphisms (SNPs), typically detected by whole genome sequencing (WGS) or microarray-based technologies. However, WGS produces mostly uninformative reads that perfectly match the reference, while microarrays require genome-specific reagents. We have developed Diff-seq, a sequencing-based mismatch detection assay for SNP discovery without the requirement for specialized nucleic-acid reagents. Diff-seq leverages the Surveyor endonuclease to cleave mismatched DNA molecules that are generated after cross-annealing of a complex pool of DNA fragments. Sequencing libraries enriched for Surveyor-cleaved molecules result in increased coverage at the variant sites. Diff-seq detected all mismatches present in an initial test substrate, with specific enrichment dependent on the identity and context of the variation. Application to viral sequences resulted in increased observation of variant alleles in a biologically relevant context. Diff-Seq has the potential to increase the sensitivity and efficiency of high-throughput sequencing in the detection of variation. PMID:29361139

Learning to Teach Where You Are: Preparation for Context-Responsive Teaching in Alaska's Teacher Certification Programs

ERIC Educational Resources Information Center

Vinlove, Amy Louise

2012-01-01

Context-responsive teaching is defined in this project as teaching that responds to individual student needs and interests, linguistic backgrounds and family characteristics, the local community and the local natural environment. Context-responsive teaching, as defined in Chapter 1 of this dissertation, consolidates into one concept the…

Micro Language Planning for Multilingual Education: Agency in Local Contexts

ERIC Educational Resources Information Center

Liddicoat, Anthony J.; Taylor-Leech, Kerry

2014-01-01

This paper overviews some of the domains of application of micro-level language planning approaches to foster multilingual education. It examines the language planning of local agents and the contexts in which their work contributes to multilingual education, either to expand or limit educational possibilities. It identifies four broad contexts of…

A Reshaping of Counselling Curriculum: Responding to the Changing (Bi)Cultural Context

ERIC Educational Resources Information Center

Flintoff, Vivianne J.; Rivers, Shirley

2012-01-01

This article describes some of the local Aotearoa New Zealand context of a general "mainstream" undergraduate counselling degree. Students' learning is shaped to produce a professional practice for the local context of Aotearoa New Zealand. As counsellor educators informed by social constructionism, we detail our theoretical position and…

Age and stratigraphic context of Pliopithecus and associated fauna from Miocene sedimentary strata at Damiao, Inner Mongolia, China

NASA Astrophysics Data System (ADS)

Kaakinen, Anu; Abdul Aziz, Hayfaa; Passey, Benjamin H.; Zhang, Zhaoqun; Liu, Liping; Salminen, Johanna; Wang, Lihua; Krijgsman, Wout; Fortelius, Mikael

2015-03-01

Since the discovery of mammalian fossils in Central Inner Mongolia in the beginning of the 20th century, this area has produced a rich and diverse record of Miocene faunas. Nevertheless, the stratigraphy has remained poorly constrained owing to scattered faunal horizons and lack of continuous vertical exposures. Consequently, most age estimates of these Miocene sites are based on paleontological evidence alone, with very few sites having been dated independently. Our field investigations in Damiao, in Siziwang Qi, Inner Mongolia have yielded more than 30 new fossiliferous localities from three horizons, including a pliopithecid fauna. This study presents the litho-, bio- and magnetostratigraphy of the Damiao area and provides age estimates for the three fossil-bearing horizons. The sedimentary sequence is interpreted as the remains of a fluvial system comprising channels, subaerially exposed floodplains and floodbasin environments. The two local stratigraphic sections measured and sampled for paleomagnetic analysis coincide with species-rich vertebrate fossil localities. The paleomagnetic results and faunal evidence suggest a correlation of lowermost fossil horizon (DM16) producing relatively rich small mammal assemblage to the early Miocene chron C6Ar or C6An.1r, roughly in 20-21 Ma age range. The pliopithecid locality level (DM01) represents latest middle Miocene and has an age estimate of about 12.1 Ma while the youngest localities (DM02) with cervoids and abundant and diverse small mammal fauna represents the earliest late Miocene with an age estimate of about 11.6 Ma. Our magnetostratigraphic results confirm that the Damiao strata constitute one of the best sequences in Inner Mongolia with early, middle and late Miocene mammalian faunas in stratigraphic superposition. The results also provide constraints on the paleoenvironmental evolution and bioevents of the area. The occurrence of pliopithecid primates in the middle Miocene of Inner Mongolia suggests humid habitats and challenges the scenarios suggesting arid and highly seasonal conditions for Central Asia since Early Miocene. The presence of pliopithecids may also bear witness to locally humid environments and greater habitat heterogeneity than previously known in central Inner Mongolia.

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).

Variation in Symbiodinium ITS2 sequence assemblages among coral colonies.

PubMed

Stat, Michael; Bird, Christopher E; Pochon, Xavier; Chasqui, Luis; Chauka, Leonard J; Concepcion, Gregory T; Logan, Dan; Takabayashi, Misaki; Toonen, Robert J; Gates, Ruth D

2011-01-05

Endosymbiotic dinoflagellates in the genus Symbiodinium are fundamentally important to the biology of scleractinian corals, as well as to a variety of other marine organisms. The genus Symbiodinium is genetically and functionally diverse and the taxonomic nature of the union between Symbiodinium and corals is implicated as a key trait determining the environmental tolerance of the symbiosis. Surprisingly, the question of how Symbiodinium diversity partitions within a species across spatial scales of meters to kilometers has received little attention, but is important to understanding the intrinsic biological scope of a given coral population and adaptations to the local environment. Here we address this gap by describing the Symbiodinium ITS2 sequence assemblages recovered from colonies of the reef building coral Montipora capitata sampled across Kāne'ohe Bay, Hawai'i. A total of 52 corals were sampled in a nested design of Coral Colony(Site(Region)) reflecting spatial scales of meters to kilometers. A diversity of Symbiodinium ITS2 sequences was recovered with the majority of variance partitioning at the level of the Coral Colony. To confirm this result, the Symbiodinium ITS2 sequence diversity in six M. capitata colonies were analyzed in much greater depth with 35 to 55 clones per colony. The ITS2 sequences and quantitative composition recovered from these colonies varied significantly, indicating that each coral hosted a different assemblage of Symbiodinium. The diversity of Symbiodinium ITS2 sequence assemblages retrieved from individual colonies of M. capitata here highlights the problems inherent in interpreting multi-copy and intra-genomically variable molecular markers, and serves as a context for discussing the utility and biological relevance of assigning species names based on Symbiodinium ITS2 genotyping.

Variation in Symbiodinium ITS2 Sequence Assemblages among Coral Colonies

PubMed Central

Stat, Michael; Bird, Christopher E.; Pochon, Xavier; Chasqui, Luis; Chauka, Leonard J.; Concepcion, Gregory T.; Logan, Dan; Takabayashi, Misaki; Toonen, Robert J.; Gates, Ruth D.

2011-01-01

Endosymbiotic dinoflagellates in the genus Symbiodinium are fundamentally important to the biology of scleractinian corals, as well as to a variety of other marine organisms. The genus Symbiodinium is genetically and functionally diverse and the taxonomic nature of the union between Symbiodinium and corals is implicated as a key trait determining the environmental tolerance of the symbiosis. Surprisingly, the question of how Symbiodinium diversity partitions within a species across spatial scales of meters to kilometers has received little attention, but is important to understanding the intrinsic biological scope of a given coral population and adaptations to the local environment. Here we address this gap by describing the Symbiodinium ITS2 sequence assemblages recovered from colonies of the reef building coral Montipora capitata sampled across Kāne'ohe Bay, Hawai'i. A total of 52 corals were sampled in a nested design of Coral Colony(Site(Region)) reflecting spatial scales of meters to kilometers. A diversity of Symbiodinium ITS2 sequences was recovered with the majority of variance partitioning at the level of the Coral Colony. To confirm this result, the Symbiodinium ITS2 sequence diversity in six M. capitata colonies were analyzed in much greater depth with 35 to 55 clones per colony. The ITS2 sequences and quantitative composition recovered from these colonies varied significantly, indicating that each coral hosted a different assemblage of Symbiodinium. The diversity of Symbiodinium ITS2 sequence assemblages retrieved from individual colonies of M. capitata here highlights the problems inherent in interpreting multi-copy and intra-genomically variable molecular markers, and serves as a context for discussing the utility and biological relevance of assigning species names based on Symbiodinium ITS2 genotyping. PMID:21246044

A weighted sampling algorithm for the design of RNA sequences with targeted secondary structure and nucleotide distribution.

PubMed

Reinharz, Vladimir; Ponty, Yann; Waldispühl, Jérôme

2013-07-01

The design of RNA sequences folding into predefined secondary structures is a milestone for many synthetic biology and gene therapy studies. Most of the current software uses similar local search strategies (i.e. a random seed is progressively adapted to acquire the desired folding properties) and more importantly do not allow the user to control explicitly the nucleotide distribution such as the GC-content in their sequences. However, the latter is an important criterion for large-scale applications as it could presumably be used to design sequences with better transcription rates and/or structural plasticity. In this article, we introduce IncaRNAtion, a novel algorithm to design RNA sequences folding into target secondary structures with a predefined nucleotide distribution. IncaRNAtion uses a global sampling approach and weighted sampling techniques. We show that our approach is fast (i.e. running time comparable or better than local search methods), seedless (we remove the bias of the seed in local search heuristics) and successfully generates high-quality sequences (i.e. thermodynamically stable) for any GC-content. To complete this study, we develop a hybrid method combining our global sampling approach with local search strategies. Remarkably, our glocal methodology overcomes both local and global approaches for sampling sequences with a specific GC-content and target structure. IncaRNAtion is available at csb.cs.mcgill.ca/incarnation/. Supplementary data are available at Bioinformatics online.

DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells.

PubMed

Alexandrov, Boian S; Fukuyo, Yayoi; Lange, Martin; Horikoshi, Nobuo; Gelev, Vladimir; Rasmussen, Kim Ø; Bishop, Alan R; Usheva, Anny

2012-11-01

The genome-wide mapping of the major gene expression regulators, the transcription factors (TFs) and their DNA binding sites, is of great importance for describing cellular behavior and phenotypic diversity. Presently, the methods for prediction of genomic TF binding produce a large number of false positives, most likely due to insufficient description of the physiochemical mechanisms of protein-DNA binding. Growing evidence suggests that, in the cell, the double-stranded DNA (dsDNA) is subject to local transient strands separations (breathing) that contribute to genomic functions. By using site-specific chromatin immunopecipitations, gel shifts, BIOBASE data, and our model that accurately describes the melting behavior and breathing dynamics of dsDNA we report a specific DNA breathing profile found at YY1 binding sites in cells. We find that the genomic flanking sequence variations and SNPs, may exert long-range effects on DNA dynamics and predetermine YY1 binding. The ubiquitous TF YY1 has a fundamental role in essential biological processes by activating, initiating or repressing transcription depending upon the sequence context it binds. We anticipate that consensus binding sequences together with the related DNA dynamics profile may significantly improve the accuracy of genomic TF binding sites and TF binding-related functional SNPs.

C. elegans whole-genome sequencing reveals mutational signatures related to carcinogens and DNA repair deficiency

PubMed Central

Meier, Bettina; Cooke, Susanna L.; Weiss, Joerg; Bailly, Aymeric P.; Alexandrov, Ludmil B.; Marshall, John; Raine, Keiran; Maddison, Mark; Anderson, Elizabeth; Stratton, Michael R.; Campbell, Peter J.

2014-01-01

Mutation is associated with developmental and hereditary disorders, aging, and cancer. While we understand some mutational processes operative in human disease, most remain mysterious. We used Caenorhabditis elegans whole-genome sequencing to model mutational signatures, analyzing 183 worm populations across 17 DNA repair-deficient backgrounds propagated for 20 generations or exposed to carcinogens. The baseline mutation rate in C. elegans was approximately one per genome per generation, not overtly altered across several DNA repair deficiencies over 20 generations. Telomere erosion led to complex chromosomal rearrangements initiated by breakage–fusion–bridge cycles and completed by simultaneously acquired, localized clusters of breakpoints. Aflatoxin B1 induced substitutions of guanines in a GpC context, as observed in aflatoxin-induced liver cancers. Mutational burden increased with impaired nucleotide excision repair. Cisplatin and mechlorethamine, DNA crosslinking agents, caused dose- and genotype-dependent signatures among indels, substitutions, and rearrangements. Strikingly, both agents induced clustered rearrangements resembling “chromoanasynthesis,” a replication-based mutational signature seen in constitutional genomic disorders, suggesting that interstrand crosslinks may play a pathogenic role in such events. Cisplatin mutagenicity was most pronounced in xpf-1 mutants, suggesting that this gene critically protects cells against platinum chemotherapy. Thus, experimental model systems combined with genome sequencing can recapture and mechanistically explain mutational signatures associated with human disease. PMID:25030888

Computational tools for exploring sequence databases as a resource for antimicrobial peptides.

PubMed

Porto, W F; Pires, A S; Franco, O L

Data mining has been recognized by many researchers as a hot topic in different areas. In the post-genomic era, the growing number of sequences deposited in databases has been the reason why these databases have become a resource for novel biological information. In recent years, the identification of antimicrobial peptides (AMPs) in databases has gained attention. The identification of unannotated AMPs has shed some light on the distribution and evolution of AMPs and, in some cases, indicated suitable candidates for developing novel antimicrobial agents. The data mining process has been performed mainly by local alignments and/or regular expressions. Nevertheless, for the identification of distant homologous sequences, other techniques such as antimicrobial activity prediction and molecular modelling are required. In this context, this review addresses the tools and techniques, and also their limitations, for mining AMPs from databases. These methods could be helpful not only for the development of novel AMPs, but also for other kinds of proteins, at a higher level of structural genomics. Moreover, solving the problem of unannotated proteins could bring immeasurable benefits to society, especially in the case of AMPs, which could be helpful for developing novel antimicrobial agents and combating resistant bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

Adeno-associated virus inverted terminal repeats stimulate gene editing.

PubMed

Hirsch, M L

2015-02-01

Advancements in genome editing have relied on technologies to specifically damage DNA which, in turn, stimulates DNA repair including homologous recombination (HR). As off-target concerns complicate the therapeutic translation of site-specific DNA endonucleases, an alternative strategy to stimulate gene editing based on fragile DNA was investigated. To do this, an episomal gene-editing reporter was generated by a disruptive insertion of the adeno-associated virus (AAV) inverted terminal repeat (ITR) into the egfp gene. Compared with a non-structured DNA control sequence, the ITR induced DNA damage as evidenced by increased gamma-H2AX and Mre11 foci formation. As local DNA damage stimulates HR, ITR-mediated gene editing was investigated using DNA oligonucleotides as repair substrates. The AAV ITR stimulated gene editing >1000-fold in a replication-independent manner and was not biased by the polarity of the repair oligonucleotide. Analysis of additional human DNA sequences demonstrated stimulation of gene editing to varying degrees. In particular, inverted yet not direct, Alu repeats induced gene editing, suggesting a role for DNA structure in the repair event. Collectively, the results demonstrate that inverted DNA repeats stimulate gene editing via double-strand break repair in an episomal context and allude to efficient gene editing of the human chromosome using fragile DNA sequences.

Traveling magnetopause distortion related to a large-scale magnetosheath plasma jet: THEMIS and ground-based observations

NASA Astrophysics Data System (ADS)

Dmitriev, A. V.; Suvorova, A. V.

2012-08-01

Here, we present a case study of THEMIS and ground-based observations of the perturbed dayside magnetopause and the geomagnetic field in relation to the interaction of an interplanetary directional discontinuity (DD) with the magnetosphere on 16 June 2007. The interaction resulted in a large-scale local magnetopause distortion of an "expansion - compression - expansion" (ECE) sequence that lasted for ˜15 min. The compression was caused by a very dense, cold, and fast high-βmagnetosheath plasma flow, a so-called plasma jet, whose kinetic energy was approximately three times higher than the energy of the incident solar wind. The plasma jet resulted in the effective penetration of magnetosheath plasma inside the magnetosphere. A strong distortion of the Chapman-Ferraro current in the ECE sequence generated a tripolar magnetic pulse "decrease - peak- decrease" (DPD) that was observed at low and middle latitudes by some ground-based magnetometers of the INTERMAGNET network. The characteristics of the ECE sequence and the spatial-temporal dynamics of the DPD pulse were found to be very different from any reported patterns of DD interactions with the magnetosphere. The observed features only partially resembled structures such as FTE, hot flow anomalies, and transient density events. Thus, it is difficult to explain them in the context of existing models.

MUFOLD-SS: New deep inception-inside-inception networks for protein secondary structure prediction.

PubMed

Fang, Chao; Shang, Yi; Xu, Dong

2018-05-01

Protein secondary structure prediction can provide important information for protein 3D structure prediction and protein functions. Deep learning offers a new opportunity to significantly improve prediction accuracy. In this article, a new deep neural network architecture, named the Deep inception-inside-inception (Deep3I) network, is proposed for protein secondary structure prediction and implemented as a software tool MUFOLD-SS. The input to MUFOLD-SS is a carefully designed feature matrix corresponding to the primary amino acid sequence of a protein, which consists of a rich set of information derived from individual amino acid, as well as the context of the protein sequence. Specifically, the feature matrix is a composition of physio-chemical properties of amino acids, PSI-BLAST profile, and HHBlits profile. MUFOLD-SS is composed of a sequence of nested inception modules and maps the input matrix to either eight states or three states of secondary structures. The architecture of MUFOLD-SS enables effective processing of local and global interactions between amino acids in making accurate prediction. In extensive experiments on multiple datasets, MUFOLD-SS outperformed the best existing methods and other deep neural networks significantly. MUFold-SS can be downloaded from http://dslsrv8.cs.missouri.edu/~cf797/MUFoldSS/download.html. © 2018 Wiley Periodicals, Inc.

An In Vivo Study of Self-Regulated Study Sequencing in Introductory Psychology Courses

PubMed Central

de Leeuw, Joshua R.; Motz, Benjamin A.; Goldstone, Robert L.

2016-01-01

Study sequence can have a profound influence on learning. In this study we investigated how students decide to sequence their study in a naturalistic context and whether their choices result in improved learning. In the study reported here, 2061 undergraduate students enrolled in an Introductory Psychology course completed an online homework tutorial on measures of central tendency, a topic relevant to an exam that counted towards their grades. One group of students was enabled to choose their own study sequence during the tutorial (Self-Regulated group), while the other group of students studied the same materials in sequences chosen by other students (Yoked group). Students who chose their sequence of study showed a clear tendency to block their study by concept, and this tendency was positively associated with subsequent exam performance. In the Yoked group, study sequence had no effect on exam performance. These results suggest that despite findings that blocked study is maladaptive when assigned by an experimenter, it may actually be adaptive when chosen by the learner in a naturalistic context. PMID:27003164

An In Vivo Study of Self-Regulated Study Sequencing in Introductory Psychology Courses.

PubMed

Carvalho, Paulo F; Braithwaite, David W; de Leeuw, Joshua R; Motz, Benjamin A; Goldstone, Robert L

2016-01-01

Study sequence can have a profound influence on learning. In this study we investigated how students decide to sequence their study in a naturalistic context and whether their choices result in improved learning. In the study reported here, 2061 undergraduate students enrolled in an Introductory Psychology course completed an online homework tutorial on measures of central tendency, a topic relevant to an exam that counted towards their grades. One group of students was enabled to choose their own study sequence during the tutorial (Self-Regulated group), while the other group of students studied the same materials in sequences chosen by other students (Yoked group). Students who chose their sequence of study showed a clear tendency to block their study by concept, and this tendency was positively associated with subsequent exam performance. In the Yoked group, study sequence had no effect on exam performance. These results suggest that despite findings that blocked study is maladaptive when assigned by an experimenter, it may actually be adaptive when chosen by the learner in a naturalistic context.

Processing Dynamic Image Sequences from a Moving Sensor.

DTIC Science & Technology

1984-02-01

65 Roadsign Image Sequence ..... ................ ... 70 Roadsign Sequence with Redundant Features .. ........ . 79 Roadsign Subimage...Selected Feature Error Values .. ........ 66 2c. Industrial Image Selected Feature Local Search Values. .. .... 67 3ab. Roadsign Image Error Values...72 3c. Roadsign Image Local Search Values ............. 73 4ab. Roadsign Redundant Feature Error Values. ............ 8 4c. Roadsign

Assessing randomness and complexity in human motion trajectories through analysis of symbolic sequences

PubMed Central

Peng, Zhen; Genewein, Tim; Braun, Daniel A.

2014-01-01

Complexity is a hallmark of intelligent behavior consisting both of regular patterns and random variation. To quantitatively assess the complexity and randomness of human motion, we designed a motor task in which we translated subjects' motion trajectories into strings of symbol sequences. In the first part of the experiment participants were asked to perform self-paced movements to create repetitive patterns, copy pre-specified letter sequences, and generate random movements. To investigate whether the degree of randomness can be manipulated, in the second part of the experiment participants were asked to perform unpredictable movements in the context of a pursuit game, where they received feedback from an online Bayesian predictor guessing their next move. We analyzed symbol sequences representing subjects' motion trajectories with five common complexity measures: predictability, compressibility, approximate entropy, Lempel-Ziv complexity, as well as effective measure complexity. We found that subjects' self-created patterns were the most complex, followed by drawing movements of letters and self-paced random motion. We also found that participants could change the randomness of their behavior depending on context and feedback. Our results suggest that humans can adjust both complexity and regularity in different movement types and contexts and that this can be assessed with information-theoretic measures of the symbolic sequences generated from movement trajectories. PMID:24744716

Contextual cueing in naturalistic scenes: Global and local contexts.

PubMed

Brockmole, James R; Castelhano, Monica S; Henderson, John M

2006-07-01

In contextual cueing, the position of a target within a group of distractors is learned over repeated exposure to a display with reference to a few nearby items rather than to the global pattern created by the elements. The authors contrasted the role of global and local contexts for contextual cueing in naturalistic scenes. Experiment 1 showed that learned target positions transfer when local information is altered but not when global information is changed. Experiment 2 showed that scene-target covariation is learned more slowly when local, but not global, information is repeated across trials than when global but not local information is repeated. Thus, in naturalistic scenes, observers are biased to associate target locations with global contexts. Copyright 2006 APA, all rights reserved.

Integration Processes Compared: Cortical Differences for Consistency Evaluation and Passive Comprehension in Local and Global Coherence.

PubMed

Egidi, Giovanna; Caramazza, Alfonso

2016-10-01

This research studies the neural systems underlying two integration processes that take place during natural discourse comprehension: consistency evaluation and passive comprehension. Evaluation was operationalized with a consistency judgment task and passive comprehension with a passive listening task. Using fMRI, the experiment examined the integration of incoming sentences with more recent, local context and with more distal, global context in these two tasks. The stimuli were stories in which we manipulated the consistency of the endings with the local context and the relevance of the global context for the integration of the endings. A whole-brain analysis revealed several differences between the two tasks. Two networks previously associated with semantic processing and attention orienting showed more activation during the judgment than the passive listening task. A network previously associated with episodic memory retrieval and construction of mental scenes showed greater activity when global context was relevant, but only during the judgment task. This suggests that evaluation, more than passive listening, triggers the reinstantiation of global context and the construction of a rich mental model for the story. Finally, a network previously linked to fluent updating of a knowledge base showed greater activity for locally consistent endings than inconsistent ones, but only during passive listening, suggesting a mode of comprehension that relies on a local scope approach to language processing. Taken together, these results show that consistency evaluation and passive comprehension weigh differently on distal and local information and are implemented, in part, by different brain networks.

The elusive ideal of inclusiveness: lessons from a worldwide survey of neurologists on the ethical issues raised by whole-genome sequencing.

PubMed

Hurlimann, Thierry; Jaitovich Groisman, Iris; Godard, Béatrice

2017-04-11

The anticipation of ethical issues that may arise with the clinical use of genomic technologies is crucial to envision their future implementation in a manner sensitive to local contexts. Yet, populations in low- and middle-income countries are underrepresented in studies that aim to explore stakeholders' perspectives on the use of such technologies. Within the framework of a research project entitled "Personalized medicine in the treatment of epilepsy", we sought to increase inclusiveness by widening the reach of our survey, inviting neurologists from around the world to share their views and practices regarding the use of whole-genome sequencing in clinical neurology and its associated ethics. We discuss herein the compelling scientific and ethical reasons that led us to attempt to recruit neurologists worldwide, despite the lack, in many low- or middle-income countries, of access to genomic technologies. Recruitment procedures and their results are presented and discussed, as well as the barriers we faced. We conclude that inclusive recruitment remains a challenging, albeit necessary and legitimate, endeavour.

Programming and reprogramming sequence timing following high and low contextual interference practice.

PubMed

Wright, David L; Magnuson, Curt E; Black, Charles B

2005-09-01

Individuals practiced two unique discrete sequence production tasks that differed in their relative time profile in either a blocked or random practice schedule. Each participant was subsequently administered a "precuing" protocol to examine the cost of initially compiling or modifying the plan for an upcoming movement's relative timing. The findings indicated that, in general, random practice facilitated the programming of the required movement timing, and this was accomplished while exhibiting greater accuracy in movement production. Participants exposed to random practice exhibited the greatest motor programming benefit, when a modification to an already prepared movement timing profile was required. When movement timing was only partially constructed prior to the imperative signal, the individuals who were trained in blocked and random practice formats accrued a similar cost to complete the programming process. These data provide additional support for the recent claim of Immink & Wright (2001) that at least some of the benefit from experience in a random as opposed to blocked training context can be localized to superior development and implementation of the motor programming process before executing the movement.

Mechanism of disease in early osteoarthritis: application of modern MR imaging techniques -- a technical report.

PubMed

Jobke, Bjoern; Bolbos, Radu; Saadat, Ehsan; Cheng, Jonathan; Li, Xiaojuan; Majumdar, Sharmila

2013-01-01

The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1ρ relaxation times with quantitative biochemical measurements of proteoglycan and collagen contents of cartilage in close synopsis with histologic morphology. A recently developed MRI sequence, T1ρ, was able to detect early intracartilaginous degeneration quantitatively and also qualitatively by color mapping demonstrating a higher sensitivity than standard T2-weighted sequences. The results correlated highly with reduced proteoglycan content and disrupted collagen architecture as measured by biochemistry and histology. The findings lend support to a clinical implementation that allows rapid visual capturing of pathology on a local, millimeter level. Further information about articular cartilage quality otherwise not detectable in vivo, via normal inspection, is needed for orthopedic treatment decisions in the present and future. Copyright © 2013 Elsevier Inc. All rights reserved.

The repertoire of resistance: Non-compliance with directives in Milgram's 'obedience' experiments.

PubMed

Hollander, Matthew M

2015-09-01

This paper is the first extensive conversation-analytic study of resistance to directives in one of the most controversial series of experiments in social psychology, Stanley Milgram's 1961-1962 study of 'obedience to authority'. As such, it builds bridges between interactionist and experimental areas of social psychology that do not often communicate with one another. Using as data detailed transcripts of 117 of the original sessions representing five experimental conditions, I show how research participants' resistance to experimental progressivity takes shape against a background of directive/response and complaint/remedy conversational sequences--sequence types that project opposing and competing courses of action. In local contexts of competing sequential relevancies, participants mobilize six forms of resistance to the confederate experimenter's directives to continue. These range along a continuum of explicitness, from relatively subtle resistance that momentarily postpones continuation to techniques for explicitly trying to stop the experiment. Although both 'obedient'- and 'defiant'-outcome participants use all six of the forms, evidence is provided suggesting precisely how members of the two groups differ in manner and frequency of resistance. © 2015 The British Psychological Society.

Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome.

PubMed

Singh, Vinod Kumar; Krishnamachari, Annangarachari

2016-09-01

Genome-wide experimental studies in Saccharomyces cerevisiae reveal that autonomous replicating sequence (ARS) requires an essential consensus sequence (ACS) for replication activity. Computational studies identified thousands of ACS like patterns in the genome. However, only a few hundreds of these sites act as replicating sites and the rest are considered as dormant or evolving sites. In a bid to understand the sequence makeup of replication sites, a content and context-based analysis was performed on a set of replicating ACS sequences that binds to origin-recognition complex (ORC) denoted as ORC-ACS and non-replicating ACS sequences (nrACS), that are not bound by ORC. In this study, DNA properties such as base composition, correlation, sequence dependent thermodynamic and DNA structural profiles, and their positions have been considered for characterizing ORC-ACS and nrACS. Analysis reveals that ORC-ACS depict marked differences in nucleotide composition and context features in its vicinity compared to nrACS. Interestingly, an A-rich motif was also discovered in ORC-ACS sequences within its nucleosome-free region. Profound changes in the conformational features, such as DNA helical twist, inclination angle and stacking energy between ORC-ACS and nrACS were observed. Distribution of ACS motifs in the non-coding segments points to the locations of ORC-ACS which are found far away from the adjacent gene start position compared to nrACS thereby enabling an accessible environment for ORC-proteins. Our attempt is novel in considering the contextual view of ACS and its flanking region along with nucleosome positioning in the S. cerevisiae genome and may be useful for any computational prediction scheme.

Exploring Evolutionary Patterns in Genetic Sequence: A Computer Exercise

ERIC Educational Resources Information Center

Shumate, Alice M.; Windsor, Aaron J.

2010-01-01

The increase in publications presenting molecular evolutionary analyses and the availability of comparative sequence data through resources such as NCBI's GenBank underscore the necessity of providing undergraduates with hands-on sequence analysis skills in an evolutionary context. This need is particularly acute given that students have been…

A Probabilistic Model of Local Sequence Alignment That Simplifies Statistical Significance Estimation

PubMed Central

Eddy, Sean R.

2008-01-01

Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (λ) requires time-consuming computational simulation. Moreover, optimal alignment scores are less powerful than probabilistic scores that integrate over alignment uncertainty (“Forward” scores), but the expected distribution of Forward scores remains unknown. Here, I conjecture that both expected score distributions have simple, predictable forms when full probabilistic modeling methods are used. For a probabilistic model of local sequence alignment, optimal alignment bit scores (“Viterbi” scores) are Gumbel-distributed with constant λ = log 2, and the high scoring tail of Forward scores is exponential with the same constant λ. Simulation studies support these conjectures over a wide range of profile/sequence comparisons, using 9,318 profile-hidden Markov models from the Pfam database. This enables efficient and accurate determination of expectation values (E-values) for both Viterbi and Forward scores for probabilistic local alignments. PMID:18516236

High-speed all-optical DNA local sequence alignment based on a three-dimensional artificial neural network.

PubMed

Maleki, Ehsan; Babashah, Hossein; Koohi, Somayyeh; Kavehvash, Zahra

2017-07-01

This paper presents an optical processing approach for exploring a large number of genome sequences. Specifically, we propose an optical correlator for global alignment and an extended moiré matching technique for local analysis of spatially coded DNA, whose output is fed to a novel three-dimensional artificial neural network for local DNA alignment. All-optical implementation of the proposed 3D artificial neural network is developed and its accuracy is verified in Zemax. Thanks to its parallel processing capability, the proposed structure performs local alignment of 4 million sequences of 150 base pairs in a few seconds, which is much faster than its electrical counterparts, such as the basic local alignment search tool.

Development and evaluation of clicker methodology for introductory physics courses

NASA Astrophysics Data System (ADS)

Lee, Albert H.

Many educators understand that lectures are cost effective but not learning efficient, so continue to search for ways to increase active student participation in this traditionally passive learning environment. In-class polling systems, or "clickers", are inexpensive and reliable tools allowing students to actively participate in lectures by answering multiple-choice questions. Students assess their learning in real time by observing instant polling summaries displayed in front of them. This in turn motivates additional discussions which increase the opportunity for active learning. We wanted to develop a comprehensive clicker methodology that creates an active lecture environment for a broad spectrum of students taking introductory physics courses. We wanted our methodology to incorporate many findings of contemporary learning science. It is recognized that learning requires active construction; students need to be actively involved in their own learning process. Learning also depends on preexisting knowledge; students construct new knowledge and understandings based on what they already know and believe. Learning is context dependent; students who have learned to apply a concept in one context may not be able to recognize and apply the same concept in a different context, even when both contexts are considered to be isomorphic by experts. On this basis, we developed question sequences, each involving the same concept but having different contexts. Answer choices are designed to address students preexisting knowledge. These sequences are used with the clickers to promote active discussions and multiple assessments. We have created, validated, and evaluated sequences sufficient in number to populate all of introductory physics courses. Our research has found that using clickers with our question sequences significantly improved student conceptual understanding. Our research has also found how to best measure student conceptual gain using research-based instruments. Finally, we discovered that students need to have full access to the question sequences after lectures to reap the maximum benefit. Chapter 1 provides an introduction to our research. Chapter 2 provides a literature review relevant for our research. Chapter 3 discusses the creation of the clicker question sequences. Chapter 4 provides a picture of the validation process involving both physics experts and the introductory physics students. Chapter 5 describes how the sequences have been used with clickers in lectures. Chapter 6 provides the evaluation of the effectiveness of the clicker methodology. Chapter 7 contains a brief summary of research results and conclusions.

HASP server: a database and structural visualization platform for comparative models of influenza A hemagglutinin proteins.

PubMed

Ambroggio, Xavier I; Dommer, Jennifer; Gopalan, Vivek; Dunham, Eleca J; Taubenberger, Jeffery K; Hurt, Darrell E

2013-06-18

Influenza A viruses possess RNA genomes that mutate frequently in response to immune pressures. The mutations in the hemagglutinin genes are particularly significant, as the hemagglutinin proteins mediate attachment and fusion to host cells, thereby influencing viral pathogenicity and species specificity. Large-scale influenza A genome sequencing efforts have been ongoing to understand past epidemics and pandemics and anticipate future outbreaks. Sequencing efforts thus far have generated nearly 9,000 distinct hemagglutinin amino acid sequences. Comparative models for all publicly available influenza A hemagglutinin protein sequences (8,769 to date) were generated using the Rosetta modeling suite. The C-alpha root mean square deviations between a randomly chosen test set of models and their crystallographic templates were less than 2 Å, suggesting that the modeling protocols yielded high-quality results. The models were compiled into an online resource, the Hemagglutinin Structure Prediction (HASP) server. The HASP server was designed as a scientific tool for researchers to visualize hemagglutinin protein sequences of interest in a three-dimensional context. With a built-in molecular viewer, hemagglutinin models can be compared side-by-side and navigated by a corresponding sequence alignment. The models and alignments can be downloaded for offline use and further analysis. The modeling protocols used in the HASP server scale well for large amounts of sequences and will keep pace with expanded sequencing efforts. The conservative approach to modeling and the intuitive search and visualization interfaces allow researchers to quickly analyze hemagglutinin sequences of interest in the context of the most highly related experimental structures, and allow them to directly compare hemagglutinin sequences to each other simultaneously in their two- and three-dimensional contexts. The models and methodology have shown utility in current research efforts and the ongoing aim of the HASP server is to continue to accelerate influenza A research and have a positive impact on global public health.

Matching diagnosis and management of diabetes in pregnancy to local priorities and resources: an international approach.

PubMed

McIntyre, H David; Oats, Jeremy J N; Zeck, Willibald; Seshiah, V; Hod, Moshe

2011-11-01

The International Association of the Diabetes and Pregnancy Study Groups' (IADPSG) criteria for the diagnosis and classification of hyperglycemia in pregnancy are described and application of these in differing healthcare contexts on a worldwide basis is reported. Existing local protocols and known epidemiologic and clinical data regarding the detection and management of overt diabetes and gestational diabetes in the context of human pregnancy are considered. Although the IADPSG criteria are uniform, their introduction poses a variety of practical and technical challenges in differing healthcare contexts, both between and within countries. Knowledge of local factors will be vital in the implementation of the new guidelines and will require extensive liaison with local clinical and health policy groups. Resource availability will be critical in determining the type of treatment available in this context. The IADPSG criteria offer an important opportunity for a uniform approach to diabetes in pregnancy. Scaled implementation of these criteria adapted to a variety of local healthcare contexts should improve both research endeavors and patient care. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.. All rights reserved.

A Crystallographic Study of the Role of Sequence Context in Thymine Glycol Bypass by a Replicative DNA Polymerase Serendipitously Sheds Light on the Exonuclease Complex

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

Aller, Pierre; Duclos, Stéphanie; Wallace, Susan S.

2012-06-27

Thymine glycol (Tg) is the most common oxidation product of thymine and is known to be a strong block to replicative DNA polymerases. A previously solved structure of the bacteriophage RB69 DNA polymerase (RB69 gp43) in complex with Tg in the sequence context 5'-G-Tg-G shed light on how Tg blocks primer elongation: The protruding methyl group of the oxidized thymine displaces the adjacent 5'-G, which can no longer serve as a template for primer elongation [Aller, P., Rould, M. A., Hogg, M, Wallace, S. S. and Doublie S. (2007). A structural rationale for stalling of a replicative DNA polymerase atmore » the most common oxidative thymine lesion, thymine glycol. Proc. Natl. Acad. Sci. USA, 104, 814-818.]. Several studies showed that in the sequence context 5'-C-Tg-purine, Tg is more likely to be bypassed by Klenow fragment, an A-family DNA polymerase. We set out to investigate the role of sequence context in Tg bypass in a B-family polymerase and to solve the crystal structures of the bacteriophage RB69 DNA polymerase in complex with Tg-containing DNA in the three remaining sequence contexts: 5'-A-Tg-G, 5'-T-Tg-G, and 5'-C-Tg-G. A combination of several factors - including the associated exonuclease activity, the nature of the 3' and 5' bases surrounding Tg, and the cis-trans interconversion of Tg - influences Tg bypass. We also visualized for the first time the structure of a well-ordered exonuclease complex, allowing us to identify and confirm the role of key residues (Phe123, Met256, and Tyr257) in strand separation and in the stabilization of the primer strand in the exonuclease site.« less

Global and Local Pitch Perception in Children with Developmental Dyslexia

ERIC Educational Resources Information Center

Ziegler, Johannes C.; Pech-Georgel, Catherine; George, Florence; Foxton, Jessica M.

2012-01-01

This study investigated global versus local pitch pattern perception in children with dyslexia aged between 8 and 11 years. Children listened to two consecutive 4-tone pitch sequences while performing a same/different task. On the different trials, sequences either preserved the contour (local condition) or they violated the contour (global…

Nuclear Import of the Retrotransposon Tf1 Is Governed by a Nuclear Localization Signal That Possesses a Unique Requirement for the FXFG Nuclear Pore Factor Nup124p

PubMed Central

Dang, Van-Dinh; Levin, Henry L.

2000-01-01

Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein. PMID:11003674

Nuclear import of the retrotransposon Tf1 is governed by a nuclear localization signal that possesses a unique requirement for the FXFG nuclear pore factor Nup124p.

PubMed

Dang, V D; Levin, H L

2000-10-01

Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein.

Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A

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

Bateman, Nicholas W.; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD; Shoji, Yutaka

2016-01-01

AT-rich interactive domain-containing protein 1A (ARID1A) is a recently identified nuclear tumor suppressor frequently altered in solid tumor malignancies. We have identified a bipartite-like nuclear localization sequence (NLS) that contributes to nuclear import of ARID1A not previously described. We functionally confirm activity using GFP constructs fused with wild-type or mutant NLS sequences. We further show that cyto-nuclear localized, bipartite NLS mutant ARID1A exhibits greater stability than nuclear-localized, wild-type ARID1A. Identification of this undescribed functional NLS within ARID1A contributes vital insights to rationalize the impact of ARID1A missense mutations observed in patient tumors. - Highlights: • We have identified a bipartitemore » nuclear localization sequence (NLS) in ARID1A. • Confirmation of the NLS was performed using GFP constructs. • NLS mutant ARID1A exhibits greater stability than wild-type ARID1A.« less

[Genome-scale sequence data processing and epigenetic analysis of DNA methylation].

PubMed

Wang, Ting-Zhang; Shan, Gao; Xu, Jian-Hong; Xue, Qing-Zhong

2013-06-01

A new approach recently developed for detecting cytosine DNA methylation (mC) and analyzing the genome-scale DNA methylation profiling, is called BS-Seq which is based on bisulfite conversion of genomic DNA combined with next-generation sequencing. The method can not only provide an insight into the difference of genome-scale DNA methylation among different organisms, but also reveal the conservation of DNA methylation in all contexts and nucleotide preference for different genomic regions, including genes, exons, and repetitive DNA sequences. It will be helpful to under-stand the epigenetic impacts of cytosine DNA methylation on the regulation of gene expression and maintaining silence of repetitive sequences, such as transposable elements. In this paper, we introduce the preprocessing steps of DNA methylation data, by which cytosine (C) and guanine (G) in the reference sequence are transferred to thymine (T) and adenine (A), and cytosine in reads is transferred to thymine, respectively. We also comprehensively review the main content of the DNA methylation analysis on the genomic scale: (1) the cytosine methylation under the context of different sequences; (2) the distribution of genomic methylcytosine; (3) DNA methylation context and the preference for the nucleotides; (4) DNA- protein interaction sites of DNA methylation; (5) degree of methylation of cytosine in the different structural elements of genes. DNA methylation analysis technique provides a powerful tool for the epigenome study in human and other species, and genes and environment interaction, and founds the theoretical basis for further development of disease diagnostics and therapeutics in human.

Small-target leak detection for a closed vessel via infrared image sequences

NASA Astrophysics Data System (ADS)

Zhao, Ling; Yang, Hongjiu

2017-03-01

This paper focus on a leak diagnosis and localization method based on infrared image sequences. Some problems on high probability of false warning and negative affect for marginal information are solved by leak detection. An experimental model is established for leak diagnosis and localization on infrared image sequences. The differential background prediction is presented to eliminate the negative affect of marginal information on test vessel based on a kernel regression method. A pipeline filter based on layering voting is designed to reduce probability of leak point false warning. A synthesize leak diagnosis and localization algorithm is proposed based on infrared image sequences. The effectiveness and potential are shown for developed techniques through experimental results.

A Robust Crowdsourcing-Based Indoor Localization System.

PubMed

Zhou, Baoding; Li, Qingquan; Mao, Qingzhou; Tu, Wei

2017-04-14

WiFi fingerprinting-based indoor localization has been widely used due to its simplicity and can be implemented on the smartphones. The major drawback of WiFi fingerprinting is that the radio map construction is very labor-intensive and time-consuming. Another drawback of WiFi fingerprinting is the Received Signal Strength (RSS) variance problem, caused by environmental changes and device diversity. RSS variance severely degrades the localization accuracy. In this paper, we propose a robust crowdsourcing-based indoor localization system (RCILS). RCILS can automatically construct the radio map using crowdsourcing data collected by smartphones. RCILS abstracts the indoor map as the semantics graph in which the edges are the possible user paths and the vertexes are the location where users may take special activities. RCILS extracts the activity sequence contained in the trajectories by activity detection and pedestrian dead-reckoning. Based on the semantics graph and activity sequence, crowdsourcing trajectories can be located and a radio map is constructed based on the localization results. For the RSS variance problem, RCILS uses the trajectory fingerprint model for indoor localization. During online localization, RCILS obtains an RSS sequence and realizes localization by matching the RSS sequence with the radio map. To evaluate RCILS, we apply RCILS in an office building. Experiment results demonstrate the efficiency and robustness of RCILS.

A Robust Crowdsourcing-Based Indoor Localization System

PubMed Central

Zhou, Baoding; Li, Qingquan; Mao, Qingzhou; Tu, Wei

2017-01-01

WiFi fingerprinting-based indoor localization has been widely used due to its simplicity and can be implemented on the smartphones. The major drawback of WiFi fingerprinting is that the radio map construction is very labor-intensive and time-consuming. Another drawback of WiFi fingerprinting is the Received Signal Strength (RSS) variance problem, caused by environmental changes and device diversity. RSS variance severely degrades the localization accuracy. In this paper, we propose a robust crowdsourcing-based indoor localization system (RCILS). RCILS can automatically construct the radio map using crowdsourcing data collected by smartphones. RCILS abstracts the indoor map as the semantics graph in which the edges are the possible user paths and the vertexes are the location where users may take special activities. RCILS extracts the activity sequence contained in the trajectories by activity detection and pedestrian dead-reckoning. Based on the semantics graph and activity sequence, crowdsourcing trajectories can be located and a radio map is constructed based on the localization results. For the RSS variance problem, RCILS uses the trajectory fingerprint model for indoor localization. During online localization, RCILS obtains an RSS sequence and realizes localization by matching the RSS sequence with the radio map. To evaluate RCILS, we apply RCILS in an office building. Experiment results demonstrate the efficiency and robustness of RCILS. PMID:28420108

Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing

PubMed Central

Frederick, Donald E.; Brown, Austin; Brim, Elizabeth; Mehta, Nisarg; Vujovic, Mark

2016-01-01

Olfactory system beta (15–35 Hz) and gamma (40–110 Hz) oscillations of the local field potential in mammals have both been linked to odor learning and discrimination. Gamma oscillations represent the activity of a local network within the olfactory bulb, and beta oscillations represent engagement of a systemwide network. Here, we test whether beta and gamma oscillations represent different cognitive modes using the different demands of go/no-go and two-alternative choice tasks that previously were suggested to favor beta or gamma oscillations, respectively. We reconcile previous studies and show that both beta and gamma oscillations occur in both tasks, with gamma dominating the early odor sampling period (2–4 sniffs) and beta dominating later. The relative power and coherence of both oscillations depend separately on multiple factors within both tasks without categorical differences across tasks. While the early/gamma-associated period occurs in all trials, rats can perform above chance without the later/beta-associated period. Longer sampling, which includes beta oscillations, is associated with better performance. Gamma followed by beta oscillations therefore represents a sequence of cognitive and neural states during odor discrimination, which can be separately modified depending on the demands of a task and odor discrimination. Additionally, fast (85 Hz) and slow (70 Hz) olfactory bulb gamma oscillation sub-bands have been hypothesized to represent tufted and mitral cell networks, respectively (Manabe and Mori, 2013). We find that fast gamma favors the early and slow gamma the later (beta-dominated) odor-sampling period and that the relative contributions of these oscillations are consistent across tasks. SIGNIFICANCE STATEMENT Olfactory system gamma (40–110 Hz) and beta (15–35 Hz) oscillations of the local field potential indicate different neural firing statistics and functional circuits. We show that gamma and beta oscillations occur in stereotyped sequence during odor sampling in associative tasks, with local gamma dominating the first 250 ms of odor sniffing, followed by systemwide beta as behavioral responses are prepared. Oscillations and coupling strength between brain regions are modulated by task, odor, and learning, showing that task features can dramatically adjust the dynamics of a cortical sensory system, which changes state every ∼250 ms. Understanding cortical circuits, even at the biophysical level, depends on careful use of multiple behavioral contexts and stimuli. PMID:27445151

Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing.

PubMed

Frederick, Donald E; Brown, Austin; Brim, Elizabeth; Mehta, Nisarg; Vujovic, Mark; Kay, Leslie M

2016-07-20

Olfactory system beta (15-35 Hz) and gamma (40-110 Hz) oscillations of the local field potential in mammals have both been linked to odor learning and discrimination. Gamma oscillations represent the activity of a local network within the olfactory bulb, and beta oscillations represent engagement of a systemwide network. Here, we test whether beta and gamma oscillations represent different cognitive modes using the different demands of go/no-go and two-alternative choice tasks that previously were suggested to favor beta or gamma oscillations, respectively. We reconcile previous studies and show that both beta and gamma oscillations occur in both tasks, with gamma dominating the early odor sampling period (2-4 sniffs) and beta dominating later. The relative power and coherence of both oscillations depend separately on multiple factors within both tasks without categorical differences across tasks. While the early/gamma-associated period occurs in all trials, rats can perform above chance without the later/beta-associated period. Longer sampling, which includes beta oscillations, is associated with better performance. Gamma followed by beta oscillations therefore represents a sequence of cognitive and neural states during odor discrimination, which can be separately modified depending on the demands of a task and odor discrimination. Additionally, fast (85 Hz) and slow (70 Hz) olfactory bulb gamma oscillation sub-bands have been hypothesized to represent tufted and mitral cell networks, respectively (Manabe and Mori, 2013). We find that fast gamma favors the early and slow gamma the later (beta-dominated) odor-sampling period and that the relative contributions of these oscillations are consistent across tasks. Olfactory system gamma (40-110 Hz) and beta (15-35 Hz) oscillations of the local field potential indicate different neural firing statistics and functional circuits. We show that gamma and beta oscillations occur in stereotyped sequence during odor sampling in associative tasks, with local gamma dominating the first 250 ms of odor sniffing, followed by systemwide beta as behavioral responses are prepared. Oscillations and coupling strength between brain regions are modulated by task, odor, and learning, showing that task features can dramatically adjust the dynamics of a cortical sensory system, which changes state every ∼250 ms. Understanding cortical circuits, even at the biophysical level, depends on careful use of multiple behavioral contexts and stimuli. Copyright © 2016 the authors 0270-6474/16/367750-18$15.00/0.

Mapping the Context: Insights and Issues from Local Government Development of Music Communities

ERIC Educational Resources Information Center

Kenny, Ailbhe

2011-01-01

Recent years have revealed local government to be a fundamental stakeholder in the development of arts and music communities. This article provides a context for an exploration and study of the issues, themes and dilemmas that surround local government and music communities. In particular the article provides this examination from an Irish…

Rio Grande Basin and the modern world: Understanding scale and context

Treesearch

Joseph A. Tainter

1999-01-01

Environmental problems are social issues, embedded in economic and political contexts at the local, regional, national, and global levels. Placing environmental issues on the scale from local to global clarifies conflicts between the level at which problems originate and the level at which they must be addressed. Local issues today often originate in sources distant in...

A space-efficient algorithm for local similarities.

PubMed

Huang, X Q; Hardison, R C; Miller, W

1990-10-01

Existing dynamic-programming algorithms for identifying similar regions of two sequences require time and space proportional to the product of the sequence lengths. Often this space requirement is more limiting than the time requirement. We describe a dynamic-programming local-similarity algorithm that needs only space proportional to the sum of the sequence lengths. The method can also find repeats within a single long sequence. To illustrate the algorithm's potential, we discuss comparison of a 73,360 nucleotide sequence containing the human beta-like globin gene cluster and a corresponding 44,594 nucleotide sequence for rabbit, a problem well beyond the capabilities of other dynamic-programming software.

Quantifying Aluminum Crystal Size Part 2: The Model-Development Sequence

ERIC Educational Resources Information Center

Hjalmarson, Margret; Diefes-Dux, Heidi A.; Bowman, Keith; Zawojewski, Judith S.

2006-01-01

We have designed model-development sequences using a common context to provide authentic problem-solving experiences for first-year students. The model-development sequence takes a model-eliciting activity a step further by engaging students in the exploration and adaptation of a mathematical model (e.g., procedure, algorithm, method) for solving…

Temporal Dynamics in Auditory Perceptual Learning: Impact of Sequencing and Incidental Learning

ERIC Educational Resources Information Center

Church, Barbara A.; Mercado, Eduardo, III; Wisniewski, Matthew G.; Liu, Estella H.

2013-01-01

Training can improve perceptual sensitivities. We examined whether the temporal dynamics and the incidental versus intentional nature of training are important. Within the context of a birdsong rate discrimination task, we examined whether the sequencing of pretesting exposure to the stimuli mattered. Easy-to-hard (progressive) sequencing of…

Mapping a nucleolar targeting sequence of an RNA binding nucleolar protein, Nop25

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

Fujiwara, Takashi; Suzuki, Shunji; Kanno, Motoko

2006-06-10

Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, amore » cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine residues in the subdomain resulted in the loss of Nop25 nucleolar localization. These results suggest that the lysine and arginine residue-enriched peptide is the most prominent nucleolar targeting sequence of Nop25 and that the long stretch of basic residues might play an important role in the nucleolar localization of Nop25. Although Nop25 contained putative SUMOylation, phosphorylation and glycosylation sites, the amino acid substitution in these sites had no effect on the nucleolar localization, thus suggesting that these post-translational modifications did not contribute to the localization of Nop25 in the nucleolus. The treatment of the cells, which expressed a GFP-fusion protein with a nucleolar targeting sequence of Nop25, with RNase A resulted in a complete dislocation of the protein from the nucleolus. These data suggested that the nucleolar targeting sequence might therefore play an important role in the binding of Nop25 to RNA molecules and that the RNA binding of Nop25 might be essential for the nucleolar localization of Nop25.« less

APPLaUD: access for patients and participants to individual level uninterpreted genomic data.

PubMed

Thorogood, Adrian; Bobe, Jason; Prainsack, Barbara; Middleton, Anna; Scott, Erick; Nelson, Sarah; Corpas, Manuel; Bonhomme, Natasha; Rodriguez, Laura Lyman; Murtagh, Madeleine; Kleiderman, Erika

2018-02-17

There is a growing support for the stance that patients and research participants should have better and easier access to their raw (uninterpreted) genomic sequence data in both clinical and research contexts. We review legal frameworks and literature on the benefits, risks, and practical barriers of providing individuals access to their data. We also survey genomic sequencing initiatives that provide or plan to provide individual access. Many patients and research participants expect to be able to access their health and genomic data. Individuals have a legal right to access their genomic data in some countries and contexts. Moreover, increasing numbers of participatory research projects, direct-to-consumer genetic testing companies, and now major national sequencing initiatives grant individuals access to their genomic sequence data upon request. Drawing on current practice and regulatory analysis, we outline legal, ethical, and practical guidance for genomic sequencing initiatives seeking to offer interested patients and participants access to their raw genomic data.

Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe.

PubMed

Pratihar, Aditya S; Tripathi, Vishnu P; Yadav, Mukesh P; Dubey, Dharani D

2015-12-01

Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2004, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2004 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727- associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2004 or ars727 remains unaltered by the extended chromosomal context.

Low-rank plus sparse decomposition for exoplanet detection in direct-imaging ADI sequences. The LLSG algorithm

NASA Astrophysics Data System (ADS)

Gomez Gonzalez, C. A.; Absil, O.; Absil, P.-A.; Van Droogenbroeck, M.; Mawet, D.; Surdej, J.

2016-05-01

Context. Data processing constitutes a critical component of high-contrast exoplanet imaging. Its role is almost as important as the choice of a coronagraph or a wavefront control system, and it is intertwined with the chosen observing strategy. Among the data processing techniques for angular differential imaging (ADI), the most recent is the family of principal component analysis (PCA) based algorithms. It is a widely used statistical tool developed during the first half of the past century. PCA serves, in this case, as a subspace projection technique for constructing a reference point spread function (PSF) that can be subtracted from the science data for boosting the detectability of potential companions present in the data. Unfortunately, when building this reference PSF from the science data itself, PCA comes with certain limitations such as the sensitivity of the lower dimensional orthogonal subspace to non-Gaussian noise. Aims: Inspired by recent advances in machine learning algorithms such as robust PCA, we aim to propose a localized subspace projection technique that surpasses current PCA-based post-processing algorithms in terms of the detectability of companions at near real-time speed, a quality that will be useful for future direct imaging surveys. Methods: We used randomized low-rank approximation methods recently proposed in the machine learning literature, coupled with entry-wise thresholding to decompose an ADI image sequence locally into low-rank, sparse, and Gaussian noise components (LLSG). This local three-term decomposition separates the starlight and the associated speckle noise from the planetary signal, which mostly remains in the sparse term. We tested the performance of our new algorithm on a long ADI sequence obtained on β Pictoris with VLT/NACO. Results: Compared to a standard PCA approach, LLSG decomposition reaches a higher signal-to-noise ratio and has an overall better performance in the receiver operating characteristic space. This three-term decomposition brings a detectability boost compared to the full-frame standard PCA approach, especially in the small inner working angle region where complex speckle noise prevents PCA from discerning true companions from noise.

The immediate upstream region of the 5′-UTR from the AUG start codon has a pronounced effect on the translational efficiency in Arabidopsis thaliana

PubMed Central

Kim, Younghyun; Lee, Goeun; Jeon, Eunhyun; Sohn, Eun ju; Lee, Yongjik; Kang, Hyangju; Lee, Dong wook; Kim, Dae Heon; Hwang, Inhwan

2014-01-01

The nucleotide sequence around the translational initiation site is an important cis-acting element for post-transcriptional regulation. However, it has not been fully understood how the sequence context at the 5′-untranslated region (5′-UTR) affects the translational efficiency of individual mRNAs. In this study, we provide evidence that the 5′-UTRs of Arabidopsis genes showing a great difference in the nucleotide sequence vary greatly in translational efficiency with more than a 200-fold difference. Of the four types of nucleotides, the A residue was the most favourable nucleotide from positions −1 to −21 of the 5′-UTRs in Arabidopsis genes. In particular, the A residue in the 5′-UTR from positions −1 to −5 was required for a high-level translational efficiency. In contrast, the T residue in the 5′-UTR from positions −1 to −5 was the least favourable nucleotide in translational efficiency. Furthermore, the effect of the sequence context in the −1 to −21 region of the 5′-UTR was conserved in different plant species. Based on these observations, we propose that the sequence context immediately upstream of the AUG initiation codon plays a crucial role in determining the translational efficiency of plant genes. PMID:24084084

Categorizing the social context of the wildland urban interface: Adaptive capacity for wildfire and community "archetypes"

Treesearch

Tavis B. Paveglio; Cassandra Moseley; Matthew S. Carroll; Daniel R. Williams; Emily Jane Davis; A. Paige Fischer

2015-01-01

Understanding the local context that shapes collective response to wildfire risk continues to be a challenge for scientists and policymakers. This study utilizes and expands on a conceptual approach for understanding adaptive capacity to wildfire in a comparison of 18 past case studies. The intent is to determine whether comparison of local social context and community...

The effect of visual context on manual localization of remembered targets

NASA Technical Reports Server (NTRS)

Barry, S. R.; Bloomberg, J. J.; Huebner, W. P.

1997-01-01

This paper examines the contribution of egocentric cues and visual context to manual localization of remembered targets. Subjects pointed in the dark to the remembered position of a target previously viewed without or within a structured visual scene. Without a remembered visual context, subjects pointed to within 2 degrees of the target. The presence of a visual context with cues of straight ahead enhanced pointing performance to the remembered location of central but not off-center targets. Thus, visual context provides strong visual cues of target position and the relationship of body position to target location. Without a visual context, egocentric cues provide sufficient input for accurate pointing to remembered targets.

Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness

NASA Astrophysics Data System (ADS)

Noirel, Josselin; Simonson, Thomas

2008-11-01

Following Kimura's neutral theory of molecular evolution [M. Kimura, The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983) (reprinted in 1986)], it has become common to assume that the vast majority of viable mutations of a gene confer little or no functional advantage. Yet, in silico models of protein evolution have shown that mutational robustness of sequences could be selected for, even in the context of neutral evolution. The evolution of a biological population can be seen as a diffusion on the network of viable sequences. This network is called a "neutral network." Depending on the mutation rate μ and the population size N, the biological population can evolve purely randomly (μN ≪1) or it can evolve in such a way as to select for sequences of higher mutational robustness (μN ≫1). The stringency of the selection depends not only on the product μN but also on the exact topology of the neutral network, the special arrangement of which was named "superfunnel." Even though the relation between mutation rate, population size, and selection was thoroughly investigated, a study of the salient topological features of the superfunnel that could affect the strength of the selection was wanting. This question is addressed in this study. We use two different models of proteins: on lattice and off lattice. We compare neutral networks computed using these models to random networks. From this, we identify two important factors of the topology that determine the stringency of the selection for mutationally robust sequences. First, the presence of highly connected nodes ("hubs") in the network increases the selection for mutationally robust sequences. Second, the stringency of the selection increases when the correlation between a sequence's mutational robustness and its neighbors' increases. The latter finding relates a global characteristic of the neutral network to a local one, which is attainable through experiments or molecular modeling.

Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness.

PubMed

Noirel, Josselin; Simonson, Thomas

2008-11-14

Following Kimura's neutral theory of molecular evolution [M. Kimura, The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983) (reprinted in 1986)], it has become common to assume that the vast majority of viable mutations of a gene confer little or no functional advantage. Yet, in silico models of protein evolution have shown that mutational robustness of sequences could be selected for, even in the context of neutral evolution. The evolution of a biological population can be seen as a diffusion on the network of viable sequences. This network is called a "neutral network." Depending on the mutation rate mu and the population size N, the biological population can evolve purely randomly (muN<1) or it can evolve in such a way as to select for sequences of higher mutational robustness (muN>1). The stringency of the selection depends not only on the product muN but also on the exact topology of the neutral network, the special arrangement of which was named "superfunnel." Even though the relation between mutation rate, population size, and selection was thoroughly investigated, a study of the salient topological features of the superfunnel that could affect the strength of the selection was wanting. This question is addressed in this study. We use two different models of proteins: on lattice and off lattice. We compare neutral networks computed using these models to random networks. From this, we identify two important factors of the topology that determine the stringency of the selection for mutationally robust sequences. First, the presence of highly connected nodes ("hubs") in the network increases the selection for mutationally robust sequences. Second, the stringency of the selection increases when the correlation between a sequence's mutational robustness and its neighbors' increases. The latter finding relates a global characteristic of the neutral network to a local one, which is attainable through experiments or molecular modeling.

Functional genomics of physiological plasticity and local adaptation in killifish.

PubMed

Whitehead, Andrew; Galvez, Fernando; Zhang, Shujun; Williams, Larissa M; Oleksiak, Marjorie F

2011-01-01

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation.

Functional Genomics of Physiological Plasticity and Local Adaptation in Killifish

PubMed Central

Galvez, Fernando; Zhang, Shujun; Williams, Larissa M.; Oleksiak, Marjorie F.

2011-01-01

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation. PMID:20581107

Role of the dorsolateral prefrontal cortex in context-dependent motor performance.

PubMed

Lee, Y-Y; Winstein, C J; Fisher, B E

2016-04-01

Context-dependent motor performance is a phenomenon in which people perform better in the environmental context where they originally practised a task. Some animal and computer simulation studies have suggested that context-dependent performance may be associated with neural activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine the role of the DLPFC in context-dependent motor performance by perturbing the neural processing of the DLPFC with repetitive transcranial magnetic stimulation (rTMS) in healthy adults. Thirty healthy adults were recruited into the Control, rTMS DLPFC and rTMS Vertex groups. The participants practised three finger sequences associated with a specific incidental context (a coloured circle and a location on the computer screen). One day following practice, the rTMS groups received 1 Hz rTMS prior to the testing conditions in which the sequence-context associations remained the same as practice (SAME) or changed (SWITCH). All three groups improved significantly over practice on day 1. The second day testing results showed that the DLPFC group had a significantly lower decrease in motor performance under the SWITCH condition than the Control and Vertex groups. This finding suggests a specific role of the DLPFC in context-dependent motor performance. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Segmented-memory recurrent neural networks.

PubMed

Chen, Jinmiao; Chaudhari, Narendra S

2009-08-01

Conventional recurrent neural networks (RNNs) have difficulties in learning long-term dependencies. To tackle this problem, we propose an architecture called segmented-memory recurrent neural network (SMRNN). A symbolic sequence is broken into segments and then presented as inputs to the SMRNN one symbol per cycle. The SMRNN uses separate internal states to store symbol-level context, as well as segment-level context. The symbol-level context is updated for each symbol presented for input. The segment-level context is updated after each segment. The SMRNN is trained using an extended real-time recurrent learning algorithm. We test the performance of SMRNN on the information latching problem, the "two-sequence problem" and the problem of protein secondary structure (PSS) prediction. Our implementation results indicate that SMRNN performs better on long-term dependency problems than conventional RNNs. Besides, we also theoretically analyze how the segmented memory of SMRNN helps learning long-term temporal dependencies and study the impact of the segment length.

Patterns and processes of Late Quaternary environmental change in a montane region of southwestern Europe

NASA Astrophysics Data System (ADS)

Carrión, José S.

2002-10-01

This paper examines the Late Quaternary (c. 20,300-<505 cal yr BP) environmental history of Siles, a lake situated at 1320 m in the Segura mountains of southern Spain, with the goal of establishing the mechanisms exerting control on vegetation change. Palaeoecological indicators include pollen, microcharcoal, spores of terrestrial plants, fungi, and non-siliceous algae, and other microfossils. The Siles sequence is shown to be sensitive to climatic change, although the control exerted by climate on vegetation is ultimately shaped by disturbances and species interactions, determining the occurrence of century-scale lags and threshold responses. Biotically induced changes of vegetation are also shown at the intrazonal level of variation. The new sequence is placed in the context of two previous records to postulate a picture of Holocene environmental change for the Segura region. The existence of mid-elevation glacial refugia for a number of temperate and Mediterranean trees is shown. A mid-Holocene phase (c. 7500-5200 cal yr BP) emerges regionally as the time of maximum forest development and highest lake levels. The early Holocene occurs as a generally dry, pyrophytic period of pine forests, with grassland scrub in high altitudes, and the late Holocene as a period of protracted vegetation sensitivity, with return to development of pine forests, spread of xerophytic communities, and increased fire activity, under the context of dry spells, localized anthropogenic disturbance, and shallowing and desiccation of lakes. Several events described here correlate with established times of abrupt transitions in the climates of northern Europe, the Mediterranean basin, north Africa, and the Sahel.

Campbell's monkeys concatenate vocalizations into context-specific call sequences

PubMed Central

Ouattara, Karim; Lemasson, Alban; Zuberbühler, Klaus

2009-01-01

Primate vocal behavior is often considered irrelevant in modeling human language evolution, mainly because of the caller's limited vocal control and apparent lack of intentional signaling. Here, we present the results of a long-term study on Campbell's monkeys, which has revealed an unrivaled degree of vocal complexity. Adult males produced six different loud call types, which they combined into various sequences in highly context-specific ways. We found stereotyped sequences that were strongly associated with cohesion and travel, falling trees, neighboring groups, nonpredatory animals, unspecific predatory threat, and specific predator classes. Within the responses to predators, we found that crowned eagles triggered four and leopards three different sequences, depending on how the caller learned about their presence. Callers followed a number of principles when concatenating sequences, such as nonrandom transition probabilities of call types, addition of specific calls into an existing sequence to form a different one, or recombination of two sequences to form a third one. We conclude that these primates have overcome some of the constraints of limited vocal control by combinatorial organization. As the different sequences were so tightly linked to specific external events, the Campbell's monkey call system may be the most complex example of ‘proto-syntax’ in animal communication known to date. PMID:20007377

Confirmation of the "protein-traffic-hypothesis" and the "protein-localization-hypothesis" using the diabetes-mellitus-type-1-knock-in and transgenic-murine-models and the trepitope sequences.

PubMed

Arneth, Borros

2012-10-01

As possible mechanisms to explain the emergence of autoimmune diseases, the current author has suggested in earlier papers two new pathways: the "protein localization hypothesis" and the "protein traffic hypothesis". The "protein localization hypothesis" states that an autoimmune disease develops if a protein accumulates in a previously unoccupied compartment, that did not previously contain that protein. Similarly, the "protein traffic hypothesis" states that a sudden error within the transport of a certain protein leads to the emergence of an autoimmune disease. The current article discusses the usefulness of the different commercially available transgenic murine models of diabetes mellitus type 1 to confirm the aforementioned hypotheses. This discussion shows that several transgenic murine models of diabetes mellitus type 1 are in-line and confirm the aforementioned hypotheses. Furthermore, these hypotheses are additionally inline with the occurrence of several newly discovered protein sequences, the so-called trepitope sequences. These sequences modulate the immune response to certain proteins. The current study analyzed to what extent the hypotheses are supported by the occurrence of these new sequences. Thereby the occurrence of the trepitope sequences provides additional evidence supporting the aforementioned hypotheses. Both the "protein localization hypothesis" and the "protein traffic hypothesis" have the potential to lead to new causal therapy concepts. The "protein localization hypothesis" and the "protein traffic hypothesis" provide conceptional explanations for the diabetes mouse models as well as for the newly discovered trepitope sequences. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Context-Recognition-Aided PDR Localization Method Based on the Hidden Markov Model

PubMed Central

Lu, Yi; Wei, Dongyan; Lai, Qifeng; Li, Wen; Yuan, Hong

2016-01-01

Indoor positioning has recently become an important field of interest because global navigation satellite systems (GNSS) are usually unavailable in indoor environments. Pedestrian dead reckoning (PDR) is a promising localization technique for indoor environments since it can be implemented on widely used smartphones equipped with low cost inertial sensors. However, the PDR localization severely suffers from the accumulation of positioning errors, and other external calibration sources should be used. In this paper, a context-recognition-aided PDR localization model is proposed to calibrate PDR. The context is detected by employing particular human actions or characteristic objects and it is matched to the context pre-stored offline in the database to get the pedestrian’s location. The Hidden Markov Model (HMM) and Recursive Viterbi Algorithm are used to do the matching, which reduces the time complexity and saves the storage. In addition, the authors design the turn detection algorithm and take the context of corner as an example to illustrate and verify the proposed model. The experimental results show that the proposed localization method can fix the pedestrian’s starting point quickly and improves the positioning accuracy of PDR by 40.56% at most with perfect stability and robustness at the same time. PMID:27916922

Parasail: SIMD C library for global, semi-global, and local pairwise sequence alignments

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

Daily, Jeffrey A.

Sequence alignment algorithms are a key component of many bioinformatics applications. Though various fast Smith-Waterman local sequence alignment implementations have been developed for x86 CPUs, most are embedded into larger database search tools. In addition, fast implementations of Needleman-Wunsch global sequence alignment and its semi-global variants are not as widespread. This article presents the first software library for local, global, and semi-global pairwise intra-sequence alignments and improves the performance of previous intra-sequence implementations. As a result, a faster intra-sequence pairwise alignment implementation is described and benchmarked. Using a 375 residue query sequence a speed of 136 billion cell updates permore » second (GCUPS) was achieved on a dual Intel Xeon E5-2670 12-core processor system, the highest reported for an implementation based on Farrar’s ’striped’ approach. When using only a single thread, parasail was 1.7 times faster than Rognes’s SWIPE. For many score matrices, parasail is faster than BLAST. The software library is designed for 64 bit Linux, OS X, or Windows on processors with SSE2, SSE41, or AVX2. Source code is available from https://github.com/jeffdaily/parasail under the Battelle BSD-style license. In conclusion, applications that require optimal alignment scores could benefit from the improved performance. For the first time, SIMD global, semi-global, and local alignments are available in a stand-alone C library.« less

Parasail: SIMD C library for global, semi-global, and local pairwise sequence alignments

DOE PAGES

Daily, Jeffrey A.

2016-02-10

Sequence alignment algorithms are a key component of many bioinformatics applications. Though various fast Smith-Waterman local sequence alignment implementations have been developed for x86 CPUs, most are embedded into larger database search tools. In addition, fast implementations of Needleman-Wunsch global sequence alignment and its semi-global variants are not as widespread. This article presents the first software library for local, global, and semi-global pairwise intra-sequence alignments and improves the performance of previous intra-sequence implementations. As a result, a faster intra-sequence pairwise alignment implementation is described and benchmarked. Using a 375 residue query sequence a speed of 136 billion cell updates permore » second (GCUPS) was achieved on a dual Intel Xeon E5-2670 12-core processor system, the highest reported for an implementation based on Farrar’s ’striped’ approach. When using only a single thread, parasail was 1.7 times faster than Rognes’s SWIPE. For many score matrices, parasail is faster than BLAST. The software library is designed for 64 bit Linux, OS X, or Windows on processors with SSE2, SSE41, or AVX2. Source code is available from https://github.com/jeffdaily/parasail under the Battelle BSD-style license. In conclusion, applications that require optimal alignment scores could benefit from the improved performance. For the first time, SIMD global, semi-global, and local alignments are available in a stand-alone C library.« less

Aromatic residues engineered into the beta-turn nucleation site of ubiquitin lead to a complex folding landscape, non-native side-chain interactions, and kinetic traps.

PubMed

Rea, Anita M; Simpson, Emma R; Meldrum, Jill K; Williams, Huw E L; Searle, Mark S

2008-12-02

The fast folding of small proteins is likely to be the product of evolutionary pressures that balance the search for native-like contacts in the transition state with the minimum number of stable non-native interactions that could lead to partially folded states prone to aggregation and amyloid formation. We have investigated the effects of non-native interactions on the folding landscape of yeast ubiquitin by introducing aromatic substitutions into the beta-turn region of the N-terminal beta-hairpin, using both the native G-bulged type I turn sequence (TXTGK) as well as an engineered 2:2 XNGK type I' turn sequence. The N-terminal beta-hairpin is a recognized folding nucleation site in ubiquitin. The folding kinetics for wt-Ub (TLTGK) and the type I' turn mutant (TNGK) reveal only a weakly populated intermediate, however, substitution with X = Phe or Trp in either context results in a high propensity to form a stable compact intermediate where the initial U-->I collapse is visible as a distinct kinetic phase. The introduction of Trp into either of the two host turn sequences results in either complex multiphase kinetics with the possibility of parallel folding pathways, or formation of a highly compact I-state stabilized by non-native interactions that must unfold before refolding. Sequence substitutions with aromatic residues within a localized beta-turn capable of forming non-native hydrophobic contacts in both the native state and partially folded states has the undesirable consequence that folding is frustrated by the formation of stable compact intermediates that evolutionary pressures at the sequence level may have largely eliminated.

Programming in a Robotics Context in the Kindergarten Classroom: The Impact on Sequencing Skills

ERIC Educational Resources Information Center

Kazakoff, Elizabeth; Bers, Marina

2012-01-01

This paper examines the impact of computer programming of robots on sequencing ability in early childhood and the relationship between sequencing skills, class size, and teacher's comfort level and experience with technology. Fifty-eight children participated in the study, 54 of whom were included in data analysis. This study was conducted in two…

Metaphor as a Possible Pathway to More Formal Understanding of the Definition of Sequence Convergence

ERIC Educational Resources Information Center

Dawkins, Paul Christian

2012-01-01

This study presents how the introduction of a metaphor for sequence convergence constituted an experientially real context in which an undergraduate real analysis student developed a property-based definition of sequence convergence. I use elements from Zandieh and Rasmussen's (2010) Defining as a Mathematical Activity framework to trace the…

Molecular selection in a unified evolutionary sequence

NASA Technical Reports Server (NTRS)

Fox, S. W.

1986-01-01

With guidance from experiments and observations that indicate internally limited phenomena, an outline of unified evolutionary sequence is inferred. Such unification is not visible for a context of random matrix and random mutation. The sequence proceeds from Big Bang through prebiotic matter, protocells, through the evolving cell via molecular and natural selection, to mind, behavior, and society.

Event-Related Potentials Elicited by Pre-Attentive Emotional Changes in Temporal Context

PubMed Central

Fujimura, Tomomi; Okanoya, Kazuo

2013-01-01

The ability to detect emotional change in the environment is essential for adaptive behavior. The current study investigated whether event-related potentials (ERPs) can reflect emotional change in a visual sequence. To assess pre-attentive processing, we examined visual mismatch negativity (vMMN): the negative potentials elicited by a deviant (infrequent) stimulus embedded in a sequence of standard (frequent) stimuli. Participants in two experiments pre-attentively viewed visual sequences of Japanese kanji with different emotional connotations while ERPs were recorded. The visual sequence in Experiment 1 consisted of neutral standards and two types of emotional deviants with a strong and weak intensity. Although the results indicated that strongly emotional deviants elicited more occipital negativity than neutral standards, it was unclear whether these negativities were derived from emotional deviation in the sequence or from the emotional significance of the deviants themselves. In Experiment 2, the two identical emotional deviants were presented against different emotional standards. One type of deviants was emotionally incongruent with the standard and the other type of deviants was emotionally congruent with the standard. The results indicated that occipital negativities elicited by deviants resulted from perceptual changes in a visual sequence at a latency of 100–200 ms and from emotional changes at latencies of 200–260 ms. Contrary to the results of the ERP experiment, reaction times to deviants showed no effect of emotional context; negative stimuli were consistently detected more rapidly than were positive stimuli. Taken together, the results suggest that brain signals can reflect emotional change in a temporal context. PMID:23671693

Event-related potentials elicited by pre-attentive emotional changes in temporal context.

PubMed

Fujimura, Tomomi; Okanoya, Kazuo

2013-01-01

The ability to detect emotional change in the environment is essential for adaptive behavior. The current study investigated whether event-related potentials (ERPs) can reflect emotional change in a visual sequence. To assess pre-attentive processing, we examined visual mismatch negativity (vMMN): the negative potentials elicited by a deviant (infrequent) stimulus embedded in a sequence of standard (frequent) stimuli. Participants in two experiments pre-attentively viewed visual sequences of Japanese kanji with different emotional connotations while ERPs were recorded. The visual sequence in Experiment 1 consisted of neutral standards and two types of emotional deviants with a strong and weak intensity. Although the results indicated that strongly emotional deviants elicited more occipital negativity than neutral standards, it was unclear whether these negativities were derived from emotional deviation in the sequence or from the emotional significance of the deviants themselves. In Experiment 2, the two identical emotional deviants were presented against different emotional standards. One type of deviants was emotionally incongruent with the standard and the other type of deviants was emotionally congruent with the standard. The results indicated that occipital negativities elicited by deviants resulted from perceptual changes in a visual sequence at a latency of 100-200 ms and from emotional changes at latencies of 200-260 ms. Contrary to the results of the ERP experiment, reaction times to deviants showed no effect of emotional context; negative stimuli were consistently detected more rapidly than were positive stimuli. Taken together, the results suggest that brain signals can reflect emotional change in a temporal context.

Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A.

PubMed

Bateman, Nicholas W; Shoji, Yutaka; Conrads, Kelly A; Stroop, Kevin D; Hamilton, Chad A; Darcy, Kathleen M; Maxwell, George L; Risinger, John I; Conrads, Thomas P

2016-01-01

AT-rich interactive domain-containing protein 1A (ARID1A) is a recently identified nuclear tumor suppressor frequently altered in solid tumor malignancies. We have identified a bipartite-like nuclear localization sequence (NLS) that contributes to nuclear import of ARID1A not previously described. We functionally confirm activity using GFP constructs fused with wild-type or mutant NLS sequences. We further show that cyto-nuclear localized, bipartite NLS mutant ARID1A exhibits greater stability than nuclear-localized, wild-type ARID1A. Identification of this undescribed functional NLS within ARID1A contributes vital insights to rationalize the impact of ARID1A missense mutations observed in patient tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

Positive Evaluation of Student Answers in Classroom Instruction

ERIC Educational Resources Information Center

Margutti, Piera; Drew, Paul

2014-01-01

Within the context of teacher/whole-class instruction sequences, researchers have associated teacher evaluation of pupils' answers to forms of traditional pedagogic discourse, also referred to as "triadic dialogue", "monologic discourse", "recitation" and "Initiation-Response-Evaluation (IRE) sequences".…

A dictionary based informational genome analysis

PubMed Central

2012-01-01

Background In the post-genomic era several methods of computational genomics are emerging to understand how the whole information is structured within genomes. Literature of last five years accounts for several alignment-free methods, arisen as alternative metrics for dissimilarity of biological sequences. Among the others, recent approaches are based on empirical frequencies of DNA k-mers in whole genomes. Results Any set of words (factors) occurring in a genome provides a genomic dictionary. About sixty genomes were analyzed by means of informational indexes based on genomic dictionaries, where a systemic view replaces a local sequence analysis. A software prototype applying a methodology here outlined carried out some computations on genomic data. We computed informational indexes, built the genomic dictionaries with different sizes, along with frequency distributions. The software performed three main tasks: computation of informational indexes, storage of these in a database, index analysis and visualization. The validation was done by investigating genomes of various organisms. A systematic analysis of genomic repeats of several lengths, which is of vivid interest in biology (for example to compute excessively represented functional sequences, such as promoters), was discussed, and suggested a method to define synthetic genetic networks. Conclusions We introduced a methodology based on dictionaries, and an efficient motif-finding software application for comparative genomics. This approach could be extended along many investigation lines, namely exported in other contexts of computational genomics, as a basis for discrimination of genomic pathologies. PMID:22985068

Local neutral networks help maintain inaccurately replicating ribozymes.

PubMed

Szilágyi, András; Kun, Ádám; Szathmáry, Eörs

2014-01-01

The error threshold of replication limits the selectively maintainable genome size against recurrent deleterious mutations for most fitness landscapes. In the context of RNA replication a distinction between the genotypic and the phenotypic error threshold has been made; where the latter concerns the maintenance of secondary structure rather than sequence. RNA secondary structure is treated as a proxy for function. The phenotypic error threshold allows higher per digit mutation rates than its genotypic counterpart, and is known to increase with the frequency of neutral mutations in sequence space. Here we show that the degree of neutrality, i.e. the frequency of nearest-neighbour (one-step) neutral mutants is a remarkably accurate proxy for the overall frequency of such mutants in an experimentally verifiable formula for the phenotypic error threshold; this we achieve by the full numerical solution for the concentration of all sequences in mutation-selection balance up to length 16. We reinforce our previous result that currently known ribozymes could be selectively maintained by the accuracy known from the best available polymerase ribozymes. Furthermore, we show that in silico stabilizing selection can increase the mutational robustness of ribozymes due to the fact that they were produced by artificial directional selection in the first place. Our finding offers a better understanding of the error threshold and provides further insight into the plausibility of an ancient RNA world.

VRprofile: gene-cluster-detection-based profiling of virulence and antibiotic resistance traits encoded within genome sequences of pathogenic bacteria.

PubMed

Li, Jun; Tai, Cui; Deng, Zixin; Zhong, Weihong; He, Yongqun; Ou, Hong-Yu

2017-01-10

VRprofile is a Web server that facilitates rapid investigation of virulence and antibiotic resistance genes, as well as extends these trait transfer-related genetic contexts, in newly sequenced pathogenic bacterial genomes. The used backend database MobilomeDB was firstly built on sets of known gene cluster loci of bacterial type III/IV/VI/VII secretion systems and mobile genetic elements, including integrative and conjugative elements, prophages, class I integrons, IS elements and pathogenicity/antibiotic resistance islands. VRprofile is thus able to co-localize the homologs of these conserved gene clusters using HMMer or BLASTp searches. With the integration of the homologous gene cluster search module with a sequence composition module, VRprofile has exhibited better performance for island-like region predictions than the other widely used methods. In addition, VRprofile also provides an integrated Web interface for aligning and visualizing identified gene clusters with MobilomeDB-archived gene clusters, or a variety set of bacterial genomes. VRprofile might contribute to meet the increasing demands of re-annotations of bacterial variable regions, and aid in the real-time definitions of disease-relevant gene clusters in pathogenic bacteria of interest. VRprofile is freely available at http://bioinfo-mml.sjtu.edu.cn/VRprofile. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

C. elegans whole-genome sequencing reveals mutational signatures related to carcinogens and DNA repair deficiency.

PubMed

Meier, Bettina; Cooke, Susanna L; Weiss, Joerg; Bailly, Aymeric P; Alexandrov, Ludmil B; Marshall, John; Raine, Keiran; Maddison, Mark; Anderson, Elizabeth; Stratton, Michael R; Gartner, Anton; Campbell, Peter J

2014-10-01

Mutation is associated with developmental and hereditary disorders, aging, and cancer. While we understand some mutational processes operative in human disease, most remain mysterious. We used Caenorhabditis elegans whole-genome sequencing to model mutational signatures, analyzing 183 worm populations across 17 DNA repair-deficient backgrounds propagated for 20 generations or exposed to carcinogens. The baseline mutation rate in C. elegans was approximately one per genome per generation, not overtly altered across several DNA repair deficiencies over 20 generations. Telomere erosion led to complex chromosomal rearrangements initiated by breakage-fusion-bridge cycles and completed by simultaneously acquired, localized clusters of breakpoints. Aflatoxin B1 induced substitutions of guanines in a GpC context, as observed in aflatoxin-induced liver cancers. Mutational burden increased with impaired nucleotide excision repair. Cisplatin and mechlorethamine, DNA crosslinking agents, caused dose- and genotype-dependent signatures among indels, substitutions, and rearrangements. Strikingly, both agents induced clustered rearrangements resembling "chromoanasynthesis," a replication-based mutational signature seen in constitutional genomic disorders, suggesting that interstrand crosslinks may play a pathogenic role in such events. Cisplatin mutagenicity was most pronounced in xpf-1 mutants, suggesting that this gene critically protects cells against platinum chemotherapy. Thus, experimental model systems combined with genome sequencing can recapture and mechanistically explain mutational signatures associated with human disease. © 2014 Meier et al.; Published by Cold Spring Harbor Laboratory Press.

Use of microsatellite markers for the assessment of bambara groundnut breeding system and varietal purity before genome sequencing.

PubMed

Ho, Wai Kuan; Muchugi, Alice; Muthemba, Samuel; Kariba, Robert; Mavenkeni, Busiso Olga; Hendre, Prasad; Song, Bo; Van Deynze, Allen; Massawe, Festo; Mayes, Sean

2016-06-01

Maximizing the research output from a limited investment is often the major challenge for minor and underutilized crops. However, such crops may be tolerant to biotic and abiotic stresses and are adapted to local, marginal, and low-input environments. Their development through breeding will provide an important resource for future agricultural system resilience and diversification in the context of changing climates and the need to achieve food security. The African Orphan Crops Consortium recognizes the values of genomic resources in facilitating the improvement of such crops. Prior to beginning genome sequencing there is a need for an assessment of line varietal purity and to estimate any residual heterozygosity. Here we present an example from bambara groundnut (Vigna subterranea (L.) Verdc.), an underutilized drought tolerant African legume. Two released varieties from Zimbabwe, identified as potential genotypes for whole genome sequencing (WGS), were genotyped with 20 species-specific SSR markers. The results indicate that the cultivars are actually a mix of related inbred genotypes, and the analysis allowed a strategy of single plant selection to be used to generate non-heterogeneous DNA for WGS. The markers also confirmed very low levels of heterozygosity within individual plants. The application of a pre-screen using co-dominant microsatellite markers is expected to substantially improve the genome assembly, compared to a cultivar bulking approach that could have been adopted.

MotionFlow: Visual Abstraction and Aggregation of Sequential Patterns in Human Motion Tracking Data.

PubMed

Jang, Sujin; Elmqvist, Niklas; Ramani, Karthik

2016-01-01

Pattern analysis of human motions, which is useful in many research areas, requires understanding and comparison of different styles of motion patterns. However, working with human motion tracking data to support such analysis poses great challenges. In this paper, we propose MotionFlow, a visual analytics system that provides an effective overview of various motion patterns based on an interactive flow visualization. This visualization formulates a motion sequence as transitions between static poses, and aggregates these sequences into a tree diagram to construct a set of motion patterns. The system also allows the users to directly reflect the context of data and their perception of pose similarities in generating representative pose states. We provide local and global controls over the partition-based clustering process. To support the users in organizing unstructured motion data into pattern groups, we designed a set of interactions that enables searching for similar motion sequences from the data, detailed exploration of data subsets, and creating and modifying the group of motion patterns. To evaluate the usability of MotionFlow, we conducted a user study with six researchers with expertise in gesture-based interaction design. They used MotionFlow to explore and organize unstructured motion tracking data. Results show that the researchers were able to easily learn how to use MotionFlow, and the system effectively supported their pattern analysis activities, including leveraging their perception and domain knowledge.

Identifying metabolic enzymes with multiple types of association evidence

PubMed Central

Kharchenko, Peter; Chen, Lifeng; Freund, Yoav; Vitkup, Dennis; Church, George M

2006-01-01

Background Existing large-scale metabolic models of sequenced organisms commonly include enzymatic functions which can not be attributed to any gene in that organism. Existing computational strategies for identifying such missing genes rely primarily on sequence homology to known enzyme-encoding genes. Results We present a novel method for identifying genes encoding for a specific metabolic function based on a local structure of metabolic network and multiple types of functional association evidence, including clustering of genes on the chromosome, similarity of phylogenetic profiles, gene expression, protein fusion events and others. Using E. coli and S. cerevisiae metabolic networks, we illustrate predictive ability of each individual type of association evidence and show that significantly better predictions can be obtained based on the combination of all data. In this way our method is able to predict 60% of enzyme-encoding genes of E. coli metabolism within the top 10 (out of 3551) candidates for their enzymatic function, and as a top candidate within 43% of the cases. Conclusion We illustrate that a combination of genome context and other functional association evidence is effective in predicting genes encoding metabolic enzymes. Our approach does not rely on direct sequence homology to known enzyme-encoding genes, and can be used in conjunction with traditional homology-based metabolic reconstruction methods. The method can also be used to target orphan metabolic activities. PMID:16571130

MARs and MARBPs: key modulators of gene regulation and disease manifestation.

PubMed

Chattopadhyay, Samit; Pavithra, Lakshminarasimhan

2007-01-01

The DNA in eukaryotic genome is compartmentalized into various domains by a series of loops tethered onto the base of nuclear matrix. Scaffold/Matrix attachment regions (S/MAR) punctuate these attachment sites and govern the nuclear architecture by establishing chromatin boundaries. In this context, specific proteins that interact with and bind to MAR sequences called MAR binding proteins (MARBPs), are of paramount importance, as these sequences spool the proteins that regulate transcription, replication, repair and recombination. Recent evidences also suggest a role for these cis-acting elements in viral integration, replication and transcription, thereby affecting host immune system. Owing to the complex nature of these nucleotide sequences, less is known about the MARBPs that bind to and bring about diverse effects on chromatin architecture and gene function. Several MARBPs have been identified and characterized so far and the list is growing. The fact that most the MARBPs exist in a co-repressor/co-activator complex and bring about gene regulation makes them quintessential for cellular processes. This participation in gene regulation means that any perturbation in the regulation and levels of MARBPs could lead to disease conditions, particularly those caused by abnormal cell proliferation, like cancer. In the present chapter, we discuss the role of MARs and MARBPs in eukaryotic gene regulation, recombination, transcription and viral integration by altering the local chromatin structure and their dysregulation in disease manifestation

The role of systemic therapy in the management of sinonasal cancer: A critical review.

PubMed

Bossi, Paolo; Saba, Nabil F; Vermorken, Jan B; Strojan, Primoz; Pala, Laura; de Bree, Remco; Rodrigo, Juan Pablo; Lopez, Fernando; Hanna, Ehab Y; Haigentz, Missak; Takes, Robert P; Slootweg, Piet J; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2015-12-01

Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease. Induction chemotherapy has shown encouraging activity and could have a role in the multimodal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed. The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serine 192 in the tiny RS repeat of the adenoviral L4-33K splicing enhancer protein is essential for function and reorganization of the protein to the periphery of viral replication centers

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

Oestberg, Sara, E-mail: sara.ostberg@imbim.uu.se; Toermaenen Persson, Heidi, E-mail: heidi.tormanen.persson@imbim.uu.se; Akusjaervi, Goeran, E-mail: goran.akusjarvi@imbim.uu.se

2012-11-25

The adenovirus L4-33K protein is a key regulator involved in the temporal shift from early to late pattern of mRNA expression from the adenovirus major late transcription unit. L4-33K is a virus-encoded alternative splicing factor, which enhances processing of 3 Prime splice sites with a weak sequence context. Here we show that L4-33K expressed from a plasmid is localized at the nuclear margin of uninfected cells. During an infection L4-33K is relocalized to the periphery of E2A-72K containing viral replication centers. We also show that serine 192 in the tiny RS repeat of the conserved carboxy-terminus of L4-33K, which ismore » critical for the splicing enhancer function of L4-33K, is necessary for the nuclear localization and redistribution of the protein to viral replication sites. Collectively, our results show a good correlation between the activity of L4-33K as a splicing enhancer protein and its localization to the periphery of viral replication centers.« less

Modeling Geometric-Temporal Context With Directional Pyramid Co-Occurrence for Action Recognition.

PubMed

Yuan, Chunfeng; Li, Xi; Hu, Weiming; Ling, Haibin; Maybank, Stephen J

2014-02-01

In this paper, we present a new geometric-temporal representation for visual action recognition based on local spatio-temporal features. First, we propose a modified covariance descriptor under the log-Euclidean Riemannian metric to represent the spatio-temporal cuboids detected in the video sequences. Compared with previously proposed covariance descriptors, our descriptor can be measured and clustered in Euclidian space. Second, to capture the geometric-temporal contextual information, we construct a directional pyramid co-occurrence matrix (DPCM) to describe the spatio-temporal distribution of the vector-quantized local feature descriptors extracted from a video. DPCM characterizes the co-occurrence statistics of local features as well as the spatio-temporal positional relationships among the concurrent features. These statistics provide strong descriptive power for action recognition. To use DPCM for action recognition, we propose a directional pyramid co-occurrence matching kernel to measure the similarity of videos. The proposed method achieves the state-of-the-art performance and improves on the recognition performance of the bag-of-visual-words (BOVWs) models by a large margin on six public data sets. For example, on the KTH data set, it achieves 98.78% accuracy while the BOVW approach only achieves 88.06%. On both Weizmann and UCF CIL data sets, the highest possible accuracy of 100% is achieved.

Random digital encryption secure communication system

NASA Technical Reports Server (NTRS)

Doland, G. D. (Inventor)

1982-01-01

The design of a secure communication system is described. A product code, formed from two pseudorandom sequences of digital bits, is used to encipher or scramble data prior to transmission. The two pseudorandom sequences are periodically changed at intervals before they have had time to repeat. One of the two sequences is transmitted continuously with the scrambled data for synchronization. In the receiver portion of the system, the incoming signal is compared with one of two locally generated pseudorandom sequences until correspondence between the sequences is obtained. At this time, the two locally generated sequences are formed into a product code which deciphers the data from the incoming signal. Provision is made to ensure synchronization of the transmitting and receiving portions of the system.

Computational approaches for identification of conserved/unique binding pockets in the A chain of ricin

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

Ecale Zhou, C L; Zemla, A T; Roe, D

2005-01-29

Specific and sensitive ligand-based protein detection assays that employ antibodies or small molecules such as peptides, aptamers, or other small molecules require that the corresponding surface region of the protein be accessible and that there be minimal cross-reactivity with non-target proteins. To reduce the time and cost of laboratory screening efforts for diagnostic reagents, we developed new methods for evaluating and selecting protein surface regions for ligand targeting. We devised combined structure- and sequence-based methods for identifying 3D epitopes and binding pockets on the surface of the A chain of ricin that are conserved with respect to a set ofmore » ricin A chains and unique with respect to other proteins. We (1) used structure alignment software to detect structural deviations and extracted from this analysis the residue-residue correspondence, (2) devised a method to compare corresponding residues across sets of ricin structures and structures of closely related proteins, (3) devised a sequence-based approach to determine residue infrequency in local sequence context, and (4) modified a pocket-finding algorithm to identify surface crevices in close proximity to residues determined to be conserved/unique based on our structure- and sequence-based methods. In applying this combined informatics approach to ricin A we identified a conserved/unique pocket in close proximity (but not overlapping) the active site that is suitable for bi-dentate ligand development. These methods are generally applicable to identification of surface epitopes and binding pockets for development of diagnostic reagents, therapeutics, and vaccines.« less

Not All Order Memory Is Equal: Test Demands Reveal Dissociations in Memory for Sequence Information

ERIC Educational Resources Information Center

Jonker, Tanya R.; MacLeod, Colin M.

2017-01-01

Remembering the order of a sequence of events is a fundamental feature of episodic memory. Indeed, a number of formal models represent temporal context as part of the memory system, and memory for order has been researched extensively. Yet, the nature of the code(s) underlying sequence memory is still relatively unknown. Across 4 experiments that…

Formulaic Sequences Used by Native English Speaking Teachers in a Thai Primary School

ERIC Educational Resources Information Center

Steyn, Sunee; Jaroongkhongdach, Woravut

2016-01-01

The use of formulaic sequences in English as a Foreign Language (EFL) lessons plays an integral role in language teaching and learning, but it seems still widely neglected in the Thai school context. To call attention to this issue, this study aims at identifying formulaic sequences used in a Thai primary school. The data were taken from three…

Vocal Generalization Depends on Gesture Identity and Sequence

PubMed Central

Sober, Samuel J.

2014-01-01

Generalization, the brain's ability to transfer motor learning from one context to another, occurs in a wide range of complex behaviors. However, the rules of generalization in vocal behavior are poorly understood, and it is unknown how vocal learning generalizes across an animal's entire repertoire of natural vocalizations and sequences. Here, we asked whether generalization occurs in a nonhuman vocal learner and quantified its properties. We hypothesized that adaptive error correction of a vocal gesture produced in one sequence would generalize to the same gesture produced in other sequences. To test our hypothesis, we manipulated the fundamental frequency (pitch) of auditory feedback in Bengalese finches (Lonchura striata var. domestica) to create sensory errors during vocal gestures (song syllables) produced in particular sequences. As hypothesized, error-corrective learning on pitch-shifted vocal gestures generalized to the same gestures produced in other sequential contexts. Surprisingly, generalization magnitude depended strongly on sequential distance from the pitch-shifted syllables, with greater adaptation for gestures produced near to the pitch-shifted syllable. A further unexpected result was that nonshifted syllables changed their pitch in the direction opposite from the shifted syllables. This apparently antiadaptive pattern of generalization could not be explained by correlations between generalization and the acoustic similarity to the pitch-shifted syllable. These findings therefore suggest that generalization depends on the type of vocal gesture and its sequential context relative to other gestures and may reflect an advantageous strategy for vocal learning and maintenance. PMID:24741046

Complex Sequencing Rules of Birdsong Can be Explained by Simple Hidden Markov Processes

PubMed Central

Katahira, Kentaro; Suzuki, Kenta; Okanoya, Kazuo; Okada, Masato

2011-01-01

Complex sequencing rules observed in birdsongs provide an opportunity to investigate the neural mechanism for generating complex sequential behaviors. To relate the findings from studying birdsongs to other sequential behaviors such as human speech and musical performance, it is crucial to characterize the statistical properties of the sequencing rules in birdsongs. However, the properties of the sequencing rules in birdsongs have not yet been fully addressed. In this study, we investigate the statistical properties of the complex birdsong of the Bengalese finch (Lonchura striata var. domestica). Based on manual-annotated syllable labeles, we first show that there are significant higher-order context dependencies in Bengalese finch songs, that is, which syllable appears next depends on more than one previous syllable. We then analyze acoustic features of the song and show that higher-order context dependencies can be explained using first-order hidden state transition dynamics with redundant hidden states. This model corresponds to hidden Markov models (HMMs), well known statistical models with a large range of application for time series modeling. The song annotation with these models with first-order hidden state dynamics agreed well with manual annotation, the score was comparable to that of a second-order HMM, and surpassed the zeroth-order model (the Gaussian mixture model; GMM), which does not use context information. Our results imply that the hierarchical representation with hidden state dynamics may underlie the neural implementation for generating complex behavioral sequences with higher-order dependencies. PMID:21915345

Adaptive Local Realignment of Protein Sequences.

PubMed

DeBlasio, Dan; Kececioglu, John

2018-06-11

While mutation rates can vary markedly over the residues of a protein, multiple sequence alignment tools typically use the same values for their scoring-function parameters across a protein's entire length. We present a new approach, called adaptive local realignment, that in contrast automatically adapts to the diversity of mutation rates along protein sequences. This builds upon a recent technique known as parameter advising, which finds global parameter settings for an aligner, to now adaptively find local settings. Our approach in essence identifies local regions with low estimated accuracy, constructs a set of candidate realignments using a carefully-chosen collection of parameter settings, and replaces the region if a realignment has higher estimated accuracy. This new method of local parameter advising, when combined with prior methods for global advising, boosts alignment accuracy as much as 26% over the best default setting on hard-to-align protein benchmarks, and by 6.4% over global advising alone. Adaptive local realignment has been implemented within the Opal aligner using the Facet accuracy estimator.

Learning predictive statistics from temporal sequences: Dynamics and strategies

PubMed Central

Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew E.; Kourtzi, Zoe

2017-01-01

Human behavior is guided by our expectations about the future. Often, we make predictions by monitoring how event sequences unfold, even though such sequences may appear incomprehensible. Event structures in the natural environment typically vary in complexity, from simple repetition to complex probabilistic combinations. How do we learn these structures? Here we investigate the dynamics of structure learning by tracking human responses to temporal sequences that change in structure unbeknownst to the participants. Participants were asked to predict the upcoming item following a probabilistic sequence of symbols. Using a Markov process, we created a family of sequences, from simple frequency statistics (e.g., some symbols are more probable than others) to context-based statistics (e.g., symbol probability is contingent on preceding symbols). We demonstrate the dynamics with which individuals adapt to changes in the environment's statistics—that is, they extract the behaviorally relevant structures to make predictions about upcoming events. Further, we show that this structure learning relates to individual decision strategy; faster learning of complex structures relates to selection of the most probable outcome in a given context (maximizing) rather than matching of the exact sequence statistics. Our findings provide evidence for alternate routes to learning of behaviorally relevant statistics that facilitate our ability to predict future events in variable environments. PMID:28973111

Learning predictive statistics from temporal sequences: Dynamics and strategies.

PubMed

Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew E; Kourtzi, Zoe

2017-10-01

Human behavior is guided by our expectations about the future. Often, we make predictions by monitoring how event sequences unfold, even though such sequences may appear incomprehensible. Event structures in the natural environment typically vary in complexity, from simple repetition to complex probabilistic combinations. How do we learn these structures? Here we investigate the dynamics of structure learning by tracking human responses to temporal sequences that change in structure unbeknownst to the participants. Participants were asked to predict the upcoming item following a probabilistic sequence of symbols. Using a Markov process, we created a family of sequences, from simple frequency statistics (e.g., some symbols are more probable than others) to context-based statistics (e.g., symbol probability is contingent on preceding symbols). We demonstrate the dynamics with which individuals adapt to changes in the environment's statistics-that is, they extract the behaviorally relevant structures to make predictions about upcoming events. Further, we show that this structure learning relates to individual decision strategy; faster learning of complex structures relates to selection of the most probable outcome in a given context (maximizing) rather than matching of the exact sequence statistics. Our findings provide evidence for alternate routes to learning of behaviorally relevant statistics that facilitate our ability to predict future events in variable environments.

SW#db: GPU-Accelerated Exact Sequence Similarity Database Search.

PubMed

Korpar, Matija; Šošić, Martin; Blažeka, Dino; Šikić, Mile

2015-01-01

In recent years we have witnessed a growth in sequencing yield, the number of samples sequenced, and as a result-the growth of publicly maintained sequence databases. The increase of data present all around has put high requirements on protein similarity search algorithms with two ever-opposite goals: how to keep the running times acceptable while maintaining a high-enough level of sensitivity. The most time consuming step of similarity search are the local alignments between query and database sequences. This step is usually performed using exact local alignment algorithms such as Smith-Waterman. Due to its quadratic time complexity, alignments of a query to the whole database are usually too slow. Therefore, the majority of the protein similarity search methods prior to doing the exact local alignment apply heuristics to reduce the number of possible candidate sequences in the database. However, there is still a need for the alignment of a query sequence to a reduced database. In this paper we present the SW#db tool and a library for fast exact similarity search. Although its running times, as a standalone tool, are comparable to the running times of BLAST, it is primarily intended to be used for exact local alignment phase in which the database of sequences has already been reduced. It uses both GPU and CPU parallelization and was 4-5 times faster than SSEARCH, 6-25 times faster than CUDASW++ and more than 20 times faster than SSW at the time of writing, using multiple queries on Swiss-prot and Uniref90 databases.

Understanding the challenges of service change – learning from acute pain services in the UK

PubMed Central

Powell, AE; Davies, HTO; Bannister, J; Macrae, WA

2009-01-01

Summary Objectives To explore organizational difficulties faced when implementing national policy recommendations in local contexts. Design Qualitative case study involving semi-structured interviews with health professionals and managers working in and around acute pain services. Setting Three UK acute hospital organizations. Main outcome measures Identification of the content, context and process factors impacting on the implementation of the national policy recommendations on acute pain services; insights into and deeper understanding of the generic obstacles to change facing service improvements. Results The process of implementing policy recommendations and improving services in each of the three organizations was undermined by multiple factors relating to: doubts and disagreements about the nature of the change; challenging local organizational contexts; and the beliefs, attitudes and responses of health professionals and managers. The impact of these factors was compounded by the interaction between them. Conclusions Local implementation of national policies aimed at service improvement can be undermined by multiple interacting factors. Particularly important are the pre-existing local organizational contexts and histories, and the deeply-ingrained attitudes, beliefs and assumptions of diverse staff groups. Without close attention to all of these underlying issues and how they interact in individual organizations against the background of local and national contexts, more resources or further structural change are unlikely to deliver the intended improvements in patient care. PMID:19208870

Drawing Connections Between Local and Global Observations: An Essential Element of Geoscience Education

NASA Astrophysics Data System (ADS)

Manduca, C. A.; Mogk, D. W.

2002-12-01

One of the hallmarks of geoscience research is the process of moving between observations and interpretations on local and global scales to develop an integrated understanding of Earth processes. Understanding this interplay is an important aspect of student geoscience learning which leads to an understanding of the fundamental principles of science and geoscience and of the connections between local natural phenomena or human activity and global processes. Several techniques that engage students in inquiry and discovery (as recommended in the National Science Education Standards, NRC 1996, Shaping the Future of Undergraduate Earth Science Education, AGU, 1997) hold promise for helping students make these connections. These include the development of global data sets from local observations (e.g. GLOBE); studying small scale or local phenomenon in the context of global models (e.g. carbon storage in local vegetation and its role in the carbon cycle); or an analysis of local environmental issues in a global context (e.g. a comparison of local flooding to flooding in other countries and analysis in the context of weather, geology and development patterns). Research on learning suggests that data-rich activities linking the local and global have excellent potential for enhancing student learning because 1) students have already developed observations and interpretations of their local environment which can serve as a starting point for constructing new knowledge and 2) this context may motivate learning and develop understanding that can be transferred to other situations. (How People Learn, NRC, 2001). Faculty and teachers at two recent workshops confirm that projects that involve local or global data can engage students in learning by providing real world context, creating student ownership of the learning process, and developing scientific skills applicable to the complex problems that characterize modern science and society. Workshop participants called for increased dissemination of examples of effective practice, evaluation of the impact of data-rich activities on learning, and further development of data access infrastructure and services. (for additional workshop results and discussion see http://serc.carleton.edu/research_education/usingdata)

From psychological need satisfaction to intentional behavior: testing a motivational sequence in two behavioral contexts.

PubMed

Hagger, Martin S; Chatzisarantis, Nikos L D; Harris, Jemma

2006-02-01

The present study tested a motivational sequence in which global-level psychological need satisfaction from self-determination theory influenced intentions and behavior directly and indirectly through contextual-level motivation and situational-level decision-making constructs from the theory of planned behavior. Two samples of university students (N = 511) completed measures of global-level psychological need satisfaction, contextual-level autonomous motivation, and situational-level attitudes, subjective norms, perceived behavioral control, intentions, and behavior in two behavioral contexts: exercise and dieting. A structural equation model supported the proposed sequence in both samples. The indirect effect was present for exercise behavior, whereas both direct and indirect effects were found for dieting behavior. Findings independently supported the component theories and provided a comprehensive integrated explanation of volitional behavior.

Dendrites, deep learning, and sequences in the hippocampus.

PubMed

Bhalla, Upinder S

2017-10-12

The hippocampus places us both in time and space. It does so over remarkably large spans: milliseconds to years, and centimeters to kilometers. This works for sensory representations, for memory, and for behavioral context. How does it fit in such wide ranges of time and space scales, and keep order among the many dimensions of stimulus context? A key organizing principle for a wide sweep of scales and stimulus dimensions is that of order in time, or sequences. Sequences of neuronal activity are ubiquitous in sensory processing, in motor control, in planning actions, and in memory. Against this strong evidence for the phenomenon, there are currently more models than definite experiments about how the brain generates ordered activity. The flip side of sequence generation is discrimination. Discrimination of sequences has been extensively studied at the behavioral, systems, and modeling level, but again physiological mechanisms are fewer. It is against this backdrop that I discuss two recent developments in neural sequence computation, that at face value share little beyond the label "neural." These are dendritic sequence discrimination, and deep learning. One derives from channel physiology and molecular signaling, the other from applied neural network theory - apparently extreme ends of the spectrum of neural circuit detail. I suggest that each of these topics has deep lessons about the possible mechanisms, scales, and capabilities of hippocampal sequence computation. © 2017 Wiley Periodicals, Inc.

Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability.

PubMed

Robic, Srebrenka

2010-01-01

To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability.

Localized one-dimensional single voxel magnetic resonance spectroscopy without J coupling modulations.

PubMed

Lin, Yanqin; Lin, Liangjie; Wei, Zhiliang; Zhong, Jianhui; Chen, Zhong

2016-12-01

To acquire single voxel localized one-dimensional 1 H magnetic resonance spectroscopy (MRS) without J coupling modulations, free from amplitude and phase distortions. A pulse sequence, named PRESSIR, is developed for volume localized MRS without J modulations at arbitrary echo time (TE). The J coupling evolution is suppressed by the J-refocused module that uses a 90° pulse at the midpoint of a double spin echo. The localization performance of the PRESSIR sequence was tested with a two-compartment phantom. The proposed sequence shows similar voxel localization accuracy as PRESS. Both PRESSIR and PRESS sequences were performed on MRS brain phantom and pig brain tissue. PRESS spectra suffer from amplitude and phase distortions due to J modulations, especially under moderate and long TEs, while PRESSIR spectra are almost free from distortions. The PRESSIR sequence proposed herein enables the acquisition of single voxel in-phase MRS within a single scan. It allows an enhanced signal intensity of J coupling metabolites and reducing undesired broad resonances with short T2s while suppressing J modulations. Moreover, it provides an approach for direct measurement of nonoverlapping J coupling peaks and of transverse relaxation times T2s. Magn Reson Med 76:1661-1667, 2016. © 2015 International Society for Magnetic Resonance in Medicine. © 2015 International Society for Magnetic Resonance in Medicine.

Targeting Endoplasmic Reticulum and/or Mitochondrial Ca2+ Fluxes as Therapeutic Strategy for HCV Infection.

PubMed

Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

2018-01-01

Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca 2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

Targeting endoplasmic reticulum and/or mitochondrial Ca2+ fluxes as therapeutic strategy for HCV infection

NASA Astrophysics Data System (ADS)

Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

2018-03-01

Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

Arc Length Coding by Interference of Theta Frequency Oscillations May Underlie Context-Dependent Hippocampal Unit Data and Episodic Memory Function

ERIC Educational Resources Information Center

Hasselmo, Michael E.

2007-01-01

Many memory models focus on encoding of sequences by excitatory recurrent synapses in region CA3 of the hippocampus. However, data and modeling suggest an alternate mechanism for encoding of sequences in which interference between theta frequency oscillations encodes the position within a sequence based on spatial arc length or time. Arc length…

Comparative genomics identifies distinct lineages of S. Enteritidis from Queensland, Australia.

PubMed

Graham, Rikki M A; Hiley, Lester; Rathnayake, Irani U; Jennison, Amy V

2018-01-01

Salmonella enterica is a major cause of gastroenteritis and foodborne illness in Australia where notification rates in the state of Queensland are the highest in the country. S. Enteritidis is among the five most common serotypes reported in Queensland and it is a priority for epidemiological surveillance due to concerns regarding its emergence in Australia. Using whole genome sequencing, we have analysed the genomic epidemiology of 217 S. Enteritidis isolates from Queensland, and observed that they fall into three distinct clades, which we have differentiated as Clades A, B and C. Phage types and MLST sequence types differed between the clades and comparative genomic analysis has shown that each has a unique profile of prophage and genomic islands. Several of the phage regions present in the S. Enteritidis reference strain P125109 were absent in Clades A and C, and these clades also had difference in the presence of pathogenicity islands, containing complete SPI-6 and SPI-19 regions, while P125109 does not. Antimicrobial resistance markers were found in 39 isolates, all but one of which belonged to Clade B. Phylogenetic analysis of the Queensland isolates in the context of 170 international strains showed that Queensland Clade B isolates group together with the previously identified global clade, while the other two clades are distinct and appear largely restricted to Australia. Locally sourced environmental isolates included in this analysis all belonged to Clades A and C, which is consistent with the theory that these clades are a source of locally acquired infection, while Clade B isolates are mostly travel related.

Sequential Dependencies in Categorical Judgments of Radiographic Images

ERIC Educational Resources Information Center

Beckstead, Jason W.; Boutis, Kathy; Pecaric, Martin; Pusic, Martin V.

2017-01-01

Sequential context effects, the psychological interactions occurring between the events of successive trials when a sequence of similar stimuli are judged, have interested psychologists for decades. It has been well established that individuals exhibit sequential context effects in psychophysical experiments involving unidimensional stimuli.…

Sequence, distribution and chromosomal context of class I and class II pilin genes of Neisseria meningitidis identified in whole genome sequences

PubMed Central

2014-01-01

Background Neisseria meningitidis expresses type four pili (Tfp) which are important for colonisation and virulence. Tfp have been considered as one of the most variable structures on the bacterial surface due to high frequency gene conversion, resulting in amino acid sequence variation of the major pilin subunit (PilE). Meningococci express either a class I or a class II pilE gene and recent work has indicated that class II pilins do not undergo antigenic variation, as class II pilE genes encode conserved pilin subunits. The purpose of this work was to use whole genome sequences to further investigate the frequency and variability of the class II pilE genes in meningococcal isolate collections. Results We analysed over 600 publically available whole genome sequences of N. meningitidis isolates to determine the sequence and genomic organization of pilE. We confirmed that meningococcal strains belonging to a limited number of clonal complexes (ccs, namely cc1, cc5, cc8, cc11 and cc174) harbour a class II pilE gene which is conserved in terms of sequence and chromosomal context. We also identified pilS cassettes in all isolates with class II pilE, however, our analysis indicates that these do not serve as donor sequences for pilE/pilS recombination. Furthermore, our work reveals that the class II pilE locus lacks the DNA sequence motifs that enable (G4) or enhance (Sma/Cla repeat) pilin antigenic variation. Finally, through analysis of pilin genes in commensal Neisseria species we found that meningococcal class II pilE genes are closely related to pilE from Neisseria lactamica and Neisseria polysaccharea, suggesting horizontal transfer among these species. Conclusions Class II pilins can be defined by their amino acid sequence and genomic context and are present in meningococcal isolates which have persisted and spread globally. The absence of G4 and Sma/Cla sequences adjacent to the class II pilE genes is consistent with the lack of pilin subunit variation in these isolates, although horizontal transfer may generate class II pilin diversity. This study supports the suggestion that high frequency antigenic variation of pilin is not universal in pathogenic Neisseria. PMID:24690385

In vitro propagation of the microsporidian pathogen Brachiola algerae and studies of its chromosome and ribosomal DNA organization in the context of the complete genome sequencing project.

PubMed

Belkorchia, Abdel; Biderre, Corinne; Militon, Cécile; Polonais, Valérie; Wincker, Patrick; Jubin, Claire; Delbac, Frédéric; Peyretaillade, Eric; Peyret, Pierre

2008-03-01

Brachiola algerae has a broad host spectrum from human to mosquitoes. The successful infection of two mosquito cell lines (Mos55: embryonic cells and Sua 4.0: hemocyte-like cells) and a human cell line (HFF) highlights the efficient adaptive capacity of this microsporidian pathogen. The molecular karyotype of this microsporidian species was determined in the context of the B. algerae genome sequencing project, showing that its haploid genome consists of 30 chromosomal-sized DNAs ranging from 160 to 2240 kbp giving an estimated genome size of 23 Mbp. A contig of 12,269 bp including the DNA sequence of the B. algerae ribosomal transcription unit has been built from initial genomic sequences and the secondary structure of the large subunit rRNA constructed. The data obtained indicate that B. algerae should be an excellent parasitic model to understand genome evolution in relation to infectious capacity.

Identification of a nuclear localization sequence in the polyomavirus capsid protein VP2

NASA Technical Reports Server (NTRS)

Chang, D.; Haynes, J. I. 2nd; Brady, J. N.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

1992-01-01

A nuclear localization signal (NLS) has been identified in the C-terminal (Glu307-Glu-Asp-Gly-Pro-Gln-Lys-Lys-Lys-Arg-Arg-Leu318) amino acid sequence of the polyomavirus minor capsid protein VP2. The importance of this amino acid sequence for nuclear transport of newly synthesized VP2 was demonstrated by a genetic "subtractive" study using the constructs pSG5VP2 (expressing full-length VP2) and pSG5 delta 3VP2 (expressing truncated VP2, lacking amino acids Glu307-Leu318). These constructs were transfected into COS-7 cells, and the intracellular localization of the VP2 protein was determined by indirect immunofluorescence. These studies revealed that the full-length VP2 was localized in the nucleus, while the truncated VP2 protein was localized in the cytoplasm and not transported to the nucleus. A biochemical "additive" approach was also used to determine whether this sequence could target nonnuclear proteins to the nucleus. A synthetic peptide identical to VP2 amino acids Glu307-Leu318 was cross-linked to the nonnuclear proteins bovine serum albumin (BSA) or immunoglobulin G (IgG). The conjugates were then labeled with fluorescein isothiocyanate and microinjected into the cytoplasm of NIH 3T6 cells. Both conjugates localized in the nucleus of the microinjected cells, whereas unconjugated BSA and IgG remained in the cytoplasm. Taken together, these genetic subtractive and biochemical additive approaches have identified the C-terminal sequence of polyoma-virus VP2 (containing amino acids Glu307-Leu318) as the NLS of this protein.

Enhanced Methods for Local Ancestry Assignment in Sequenced Admixed Individuals

PubMed Central

Brown, Robert; Pasaniuc, Bogdan

2014-01-01

Inferring the ancestry at each locus in the genome of recently admixed individuals (e.g., Latino Americans) plays a major role in medical and population genetic inferences, ranging from finding disease-risk loci, to inferring recombination rates, to mapping missing contigs in the human genome. Although many methods for local ancestry inference have been proposed, most are designed for use with genotyping arrays and fail to make use of the full spectrum of data available from sequencing. In addition, current haplotype-based approaches are very computationally demanding, requiring large computational time for moderately large sample sizes. Here we present new methods for local ancestry inference that leverage continent-specific variants (CSVs) to attain increased performance over existing approaches in sequenced admixed genomes. A key feature of our approach is that it incorporates the admixed genomes themselves jointly with public datasets, such as 1000 Genomes, to improve the accuracy of CSV calling. We use simulations to show that our approach attains accuracy similar to widely used computationally intensive haplotype-based approaches with large decreases in runtime. Most importantly, we show that our method recovers comparable local ancestries, as the 1000 Genomes consensus local ancestry calls in the real admixed individuals from the 1000 Genomes Project. We extend our approach to account for low-coverage sequencing and show that accurate local ancestry inference can be attained at low sequencing coverage. Finally, we generalize CSVs to sub-continental population-specific variants (sCSVs) and show that in some cases it is possible to determine the sub-continental ancestry for short chromosomal segments on the basis of sCSVs. PMID:24743331

Epstein-Barr virus thymidine kinase is a centrosomal resident precisely localized to the periphery of centrioles.

PubMed

Gill, Michael B; Kutok, Jeffery L; Fingeroth, Joyce D

2007-06-01

The thymidine kinase (TK) encoded by Epstein-Barr virus (EBV) differs not only from that of the alphaherpesviruses but also from that of the gamma-2 herpesvirus subfamily. Because cellular location is frequently a determinant of regulatory function, to gain insight into additional role(s) of EBV TK and to uncover how the lymphocryptovirus and rhadinovirus enzymes differ, the subcellular localizations of EBV TK and the related cercopithecine herpesvirus-15 TK were investigated. We show that in contrast to those of the other family members, the gamma-1 herpesvirus TKs localize to the centrosome and even more precisely to the periphery of the centriole, tightly encircling the tubulin-rich centrioles in a microtubule-independent fashion. Centrosomal localization is observed in diverse cell types and occurs whether the protein is expressed independently or in the context of lytic EBV infection. Surprisingly, analysis of mutants revealed that the unique N-terminal domain was not critical for targeting to the centrosome, but rather, peptide sequences located C terminal to this domain were key. This is the first herpesvirus protein documented to reside in the centrosome, or microtubule-organizing center, an amembranous organelle that regulates the structural biology of the cell cycle through control of chromosome separation and cytokinesis. More recently, proteasome-mediated degradation of cell cycle regulatory proteins, production and loading of antigenic peptides onto HLA molecules, and transient homing of diverse virion proteins required for entry and/or egress have been shown to be coordinated at the centrosome. Potential implications of centrosomal localization for EBV TK function are discussed.

Attentional Flexibility During Approach and Avoidance Motivational States: The Role of Context in Shifts of Attentional Breadth

PubMed Central

Calcott, Rebecca D.; Berkman, Elliot T.

2014-01-01

In the present studies, we aimed to understand how approach and avoidance states affect attentional flexibility by examining attentional shifts on a trial-by-trial basis. We also examined how a novel construct in this area, task context, might interact with motivation to influence attentional flexibility. Participants completed a modified composite letter task in which the ratio of global to local targets was varied by block, making different levels of attentional focus beneficial to performance on different blocks. Study 1 demonstrated that, in the absence of a motivation manipulation, switch costs were lowest on blocks with an even ratio of global and local trials and were higher on blocks with an uneven ratio. Other participants completed the task while viewing pictures (Studies 2 and 3) and assuming arm positions (Studies 2 and 4) to induce approach, avoidance, and neutral motivational states. Avoidance motivation reduced switch costs in evenly proportioned contexts, whereas approach motivation reduced switch costs in mostly global contexts. Additionally, approach motivation imparted a similar switch cost magnitude across different contexts, whereas avoidance and neutral states led to variable switch costs depending on the context. Subsequent analyses revealed that these effects were driven largely by faster switching to local targets on mostly global blocks in the approach condition. These findings suggest that avoidance facilitates attentional shifts when switches are frequent, whereas approach facilitates responding to rare or unexpected local stimuli. The main implication of these results is that motivation has different effects on attentional shifts depending on the context. PMID:24294866

Face Context Influences Local Part Processing: An ERP Study.

PubMed

Zhang, Hong; Sun, Yaoru; Zhao, Lun

2017-09-01

Perception of face parts on the basis of features is thought to be different from perception of whole faces, which is more based on configural information. Face context is also suggested to play an important role in face processing. To investigate how face context influences the early-stage perception of facial local parts, we used an oddball paradigm that tested perceptual stages of face processing rather than recognition. We recorded the event-related potentials (ERPs) elicited by whole faces and face parts presented in four conditions (upright-normal, upright-thatcherised, inverted-normal and inverted-thatcherised), as well as the ERPs elicited by non-face objects (whole houses and house parts) with corresponding conditions. The results showed that face context significantly affected the N170 with increased amplitudes and earlier peak latency for upright normal faces. Removing face context delayed the P1 latency but did not affect the P1 amplitude prominently for both upright and inverted normal faces. Across all conditions, neither the N170 nor the P1 was modulated by house context. The significant changes on the N170 and P1 components revealed that face context influences local part processing at the early stage of face processing and this context effect might be specific for face perception. We further suggested that perceptions of whole faces and face parts are functionally distinguished.

Transcultural Digital Literacies: Cross-Border Connections and Self-Representations in an Online Forum

ERIC Educational Resources Information Center

Kim, Grace MyHyun

2016-01-01

Research on multicultural learning has focused on formal and local settings, such as schools, but young people are interacting with, and therefore learning from, informal settings and nonlocal contexts, including online platforms. That is, multicultural education is no longer limited to formal institutions, local contexts, or the printed word.…

Context-Aware Local Binary Feature Learning for Face Recognition.

PubMed

Duan, Yueqi; Lu, Jiwen; Feng, Jianjiang; Zhou, Jie

2018-05-01

In this paper, we propose a context-aware local binary feature learning (CA-LBFL) method for face recognition. Unlike existing learning-based local face descriptors such as discriminant face descriptor (DFD) and compact binary face descriptor (CBFD) which learn each feature code individually, our CA-LBFL exploits the contextual information of adjacent bits by constraining the number of shifts from different binary bits, so that more robust information can be exploited for face representation. Given a face image, we first extract pixel difference vectors (PDV) in local patches, and learn a discriminative mapping in an unsupervised manner to project each pixel difference vector into a context-aware binary vector. Then, we perform clustering on the learned binary codes to construct a codebook, and extract a histogram feature for each face image with the learned codebook as the final representation. In order to exploit local information from different scales, we propose a context-aware local binary multi-scale feature learning (CA-LBMFL) method to jointly learn multiple projection matrices for face representation. To make the proposed methods applicable for heterogeneous face recognition, we present a coupled CA-LBFL (C-CA-LBFL) method and a coupled CA-LBMFL (C-CA-LBMFL) method to reduce the modality gap of corresponding heterogeneous faces in the feature level, respectively. Extensive experimental results on four widely used face datasets clearly show that our methods outperform most state-of-the-art face descriptors.

Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization.

PubMed

Bedbrook, Claire N; Yang, Kevin K; Rice, Austin J; Gradinaru, Viviana; Arnold, Frances H

2017-10-01

There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare sequences in a diverse library of channelrhodopsins (ChRs) that express and localize to the plasma membrane of mammalian cells. These light-gated channel proteins of microbial origin are of interest for neuroscience applications, where expression and localization to the plasma membrane is a prerequisite for function. We trained Gaussian process (GP) classification and regression models with expression and localization data from 218 ChR chimeras chosen from a 118,098-variant library designed by SCHEMA recombination of three parent ChRs. We use these GP models to identify ChRs that express and localize well and show that our models can elucidate sequence and structure elements important for these processes. We also used the predictive models to convert a naturally occurring ChR incapable of mammalian localization into one that localizes well.

Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization

PubMed Central

Rice, Austin J.; Gradinaru, Viviana; Arnold, Frances H.

2017-01-01

There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare sequences in a diverse library of channelrhodopsins (ChRs) that express and localize to the plasma membrane of mammalian cells. These light-gated channel proteins of microbial origin are of interest for neuroscience applications, where expression and localization to the plasma membrane is a prerequisite for function. We trained Gaussian process (GP) classification and regression models with expression and localization data from 218 ChR chimeras chosen from a 118,098-variant library designed by SCHEMA recombination of three parent ChRs. We use these GP models to identify ChRs that express and localize well and show that our models can elucidate sequence and structure elements important for these processes. We also used the predictive models to convert a naturally occurring ChR incapable of mammalian localization into one that localizes well. PMID:29059183

Toward a Nonspeech Test of Auditory Cognition: Semantic Context Effects in Environmental Sound Identification in Adults of Varying Age and Hearing Abilities

PubMed Central

Sheft, Stanley; Norris, Molly; Spanos, George; Radasevich, Katherine; Formsma, Paige; Gygi, Brian

2016-01-01

Objective Sounds in everyday environments tend to follow one another as events unfold over time. The tacit knowledge of contextual relationships among environmental sounds can influence their perception. We examined the effect of semantic context on the identification of sequences of environmental sounds by adults of varying age and hearing abilities, with an aim to develop a nonspeech test of auditory cognition. Method The familiar environmental sound test (FEST) consisted of 25 individual sounds arranged into ten five-sound sequences: five contextually coherent and five incoherent. After hearing each sequence, listeners identified each sound and arranged them in the presentation order. FEST was administered to young normal-hearing, middle-to-older normal-hearing, and middle-to-older hearing-impaired adults (Experiment 1), and to postlingual cochlear-implant users and young normal-hearing adults tested through vocoder-simulated implants (Experiment 2). Results FEST scores revealed a strong positive effect of semantic context in all listener groups, with young normal-hearing listeners outperforming other groups. FEST scores also correlated with other measures of cognitive ability, and for CI users, with the intelligibility of speech-in-noise. Conclusions Being sensitive to semantic context effects, FEST can serve as a nonspeech test of auditory cognition for diverse listener populations to assess and potentially improve everyday listening skills. PMID:27893791

Prediction of cis/trans isomerization in proteins using PSI-BLAST profiles and secondary structure information.

PubMed

Song, Jiangning; Burrage, Kevin; Yuan, Zheng; Huber, Thomas

2006-03-09

The majority of peptide bonds in proteins are found to occur in the trans conformation. However, for proline residues, a considerable fraction of Prolyl peptide bonds adopt the cis form. Proline cis/trans isomerization is known to play a critical role in protein folding, splicing, cell signaling and transmembrane active transport. Accurate prediction of proline cis/trans isomerization in proteins would have many important applications towards the understanding of protein structure and function. In this paper, we propose a new approach to predict the proline cis/trans isomerization in proteins using support vector machine (SVM). The preliminary results indicated that using Radial Basis Function (RBF) kernels could lead to better prediction performance than that of polynomial and linear kernel functions. We used single sequence information of different local window sizes, amino acid compositions of different local sequences, multiple sequence alignment obtained from PSI-BLAST and the secondary structure information predicted by PSIPRED. We explored these different sequence encoding schemes in order to investigate their effects on the prediction performance. The training and testing of this approach was performed on a newly enlarged dataset of 2424 non-homologous proteins determined by X-Ray diffraction method using 5-fold cross-validation. Selecting the window size 11 provided the best performance for determining the proline cis/trans isomerization based on the single amino acid sequence. It was found that using multiple sequence alignments in the form of PSI-BLAST profiles could significantly improve the prediction performance, the prediction accuracy increased from 62.8% with single sequence to 69.8% and Matthews Correlation Coefficient (MCC) improved from 0.26 with single local sequence to 0.40. Furthermore, if coupled with the predicted secondary structure information by PSIPRED, our method yielded a prediction accuracy of 71.5% and MCC of 0.43, 9% and 0.17 higher than the accuracy achieved based on the singe sequence information, respectively. A new method has been developed to predict the proline cis/trans isomerization in proteins based on support vector machine, which used the single amino acid sequence with different local window sizes, the amino acid compositions of local sequence flanking centered proline residues, the position-specific scoring matrices (PSSMs) extracted by PSI-BLAST and the predicted secondary structures generated by PSIPRED. The successful application of SVM approach in this study reinforced that SVM is a powerful tool in predicting proline cis/trans isomerization in proteins and biological sequence analysis.

Shaping up the protein folding funnel by local interaction: lesson from a structure prediction study.

PubMed

Chikenji, George; Fujitsuka, Yoshimi; Takada, Shoji

2006-02-28

Predicting protein tertiary structure by folding-like simulations is one of the most stringent tests of how much we understand the principle of protein folding. Currently, the most successful method for folding-based structure prediction is the fragment assembly (FA) method. Here, we address why the FA method is so successful and its lesson for the folding problem. To do so, using the FA method, we designed a structure prediction test of "chimera proteins." In the chimera proteins, local structural preference is specific to the target sequences, whereas nonlocal interactions are only sequence-independent compaction forces. We find that these chimera proteins can find the native folds of the intact sequences with high probability indicating dominant roles of the local interactions. We further explore roles of local structural preference by exact calculation of the HP lattice model of proteins. From these results, we suggest principles of protein folding: For small proteins, compact structures that are fully compatible with local structural preference are few, one of which is the native fold. These local biases shape up the funnel-like energy landscape.

Shaping up the protein folding funnel by local interaction: Lesson from a structure prediction study

PubMed Central

Chikenji, George; Fujitsuka, Yoshimi; Takada, Shoji

2006-01-01

Predicting protein tertiary structure by folding-like simulations is one of the most stringent tests of how much we understand the principle of protein folding. Currently, the most successful method for folding-based structure prediction is the fragment assembly (FA) method. Here, we address why the FA method is so successful and its lesson for the folding problem. To do so, using the FA method, we designed a structure prediction test of “chimera proteins.” In the chimera proteins, local structural preference is specific to the target sequences, whereas nonlocal interactions are only sequence-independent compaction forces. We find that these chimera proteins can find the native folds of the intact sequences with high probability indicating dominant roles of the local interactions. We further explore roles of local structural preference by exact calculation of the HP lattice model of proteins. From these results, we suggest principles of protein folding: For small proteins, compact structures that are fully compatible with local structural preference are few, one of which is the native fold. These local biases shape up the funnel-like energy landscape. PMID:16488978

New powerful statistics for alignment-free sequence comparison under a pattern transfer model.

PubMed

Liu, Xuemei; Wan, Lin; Li, Jing; Reinert, Gesine; Waterman, Michael S; Sun, Fengzhu

2011-09-07

Alignment-free sequence comparison is widely used for comparing gene regulatory regions and for identifying horizontally transferred genes. Recent studies on the power of a widely used alignment-free comparison statistic D2 and its variants D*2 and D(s)2 showed that their power approximates a limit smaller than 1 as the sequence length tends to infinity under a pattern transfer model. We develop new alignment-free statistics based on D2, D*2 and D(s)2 by comparing local sequence pairs and then summing over all the local sequence pairs of certain length. We show that the new statistics are much more powerful than the corresponding statistics and the power tends to 1 as the sequence length tends to infinity under the pattern transfer model. Copyright © 2011 Elsevier Ltd. All rights reserved.

New Powerful Statistics for Alignment-free Sequence Comparison Under a Pattern Transfer Model

PubMed Central

Liu, Xuemei; Wan, Lin; Li, Jing; Reinert, Gesine; Waterman, Michael S.; Sun, Fengzhu

2011-01-01

Alignment-free sequence comparison is widely used for comparing gene regulatory regions and for identifying horizontally transferred genes. Recent studies on the power of a widely used alignment-free comparison statistic D2 and its variants D2∗ and D2s showed that their power approximates a limit smaller than 1 as the sequence length tends to infinity under a pattern transfer model. We develop new alignment-free statistics based on D2, D2∗ and D2s by comparing local sequence pairs and then summing over all the local sequence pairs of certain length. We show that the new statistics are much more powerful than the corresponding statistics and the power tends to 1 as the sequence length tends to infinity under the pattern transfer model. PMID:21723298

Library construction for next-generation sequencing: Overviews and challenges

PubMed Central

Head, Steven R.; Komori, H. Kiyomi; LaMere, Sarah A.; Whisenant, Thomas; Van Nieuwerburgh, Filip; Salomon, Daniel R.; Ordoukhanian, Phillip

2014-01-01

High-throughput sequencing, also known as next-generation sequencing (NGS), has revolutionized genomic research. In recent years, NGS technology has steadily improved, with costs dropping and the number and range of sequencing applications increasing exponentially. Here, we examine the critical role of sequencing library quality and consider important challenges when preparing NGS libraries from DNA and RNA sources. Factors such as the quantity and physical characteristics of the RNA or DNA source material as well as the desired application (i.e., genome sequencing, targeted sequencing, RNA-seq, ChIP-seq, RIP-seq, and methylation) are addressed in the context of preparing high quality sequencing libraries. In addition, the current methods for preparing NGS libraries from single cells are also discussed. PMID:24502796

Global and local pitch perception in children with developmental dyslexia.

PubMed

Ziegler, Johannes C; Pech-Georgel, Catherine; George, Florence; Foxton, Jessica M

2012-03-01

This study investigated global versus local pitch pattern perception in children with dyslexia aged between 8 and 11 years. Children listened to two consecutive 4-tone pitch sequences while performing a same/different task. On the different trials, sequences either preserved the contour (local condition) or they violated the contour (global condition). Compared to normally developing children, dyslexics showed robust pitch perception deficits in the local but not the global condition. This finding was replicated in a simple pitch direction task, which minimizes sequencing and short term memory. Results are consistent with a left-hemisphere deficit in dyslexia because local pitch changes are supposedly processed by the left hemisphere, whereas global pitch changes are processed by the right hemisphere. The present data suggest a link between impaired pitch processing and abnormal phonological development in children with dyslexia, which makes pitch pattern processing a potent tool for early diagnosis and remediation of dyslexia. Copyright © 2011 Elsevier Inc. All rights reserved.

A Competence-Based Approach to the Design of a Teaching Sequence about Oral and Dental Health and Hygiene: A Case Study

ERIC Educational Resources Information Center

Blanco-López, Ángel; Franco-Mariscal, Antonio Joaquín; España-Ramos, Enrique

2016-01-01

We present a case study to illustrate the design and implementation of a teaching sequence about oral and dental health and hygiene. This teaching sequence was aimed at year 10 students (age 15-16) and sought to develop their scientific competences. In line with the PISA assessment framework for science and the tenets of a context-based approach…

Multimodal sequence learning.

PubMed

Kemény, Ferenc; Meier, Beat

2016-02-01

While sequence learning research models complex phenomena, previous studies have mostly focused on unimodal sequences. The goal of the current experiment is to put implicit sequence learning into a multimodal context: to test whether it can operate across different modalities. We used the Task Sequence Learning paradigm to test whether sequence learning varies across modalities, and whether participants are able to learn multimodal sequences. Our results show that implicit sequence learning is very similar regardless of the source modality. However, the presence of correlated task and response sequences was required for learning to take place. The experiment provides new evidence for implicit sequence learning of abstract conceptual representations. In general, the results suggest that correlated sequences are necessary for implicit sequence learning to occur. Moreover, they show that elements from different modalities can be automatically integrated into one unitary multimodal sequence. Copyright © 2015 Elsevier B.V. All rights reserved.

Knowledge-based prediction of protein backbone conformation using a structural alphabet.

PubMed

Vetrivel, Iyanar; Mahajan, Swapnil; Tyagi, Manoj; Hoffmann, Lionel; Sanejouand, Yves-Henri; Srinivasan, Narayanaswamy; de Brevern, Alexandre G; Cadet, Frédéric; Offmann, Bernard

2017-01-01

Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.

Effect of local cultural context on the success of community-based conservation interventions.

PubMed

Waylen, Kerry A; Fischer, Anke; McGowan, Philip J K; Thirgood, Simon J; Milner-Gulland, E J

2010-08-01

Conservation interventions require evaluation to understand what factors predict success or failure. To date, there has been little systematic investigation of the effect of social and cultural context on conservation success, although a large body of literature argues it is important. We investigated whether local cultural context, particularly local institutions and the efforts of interventions to engage with this culture significantly influence conservation outcomes. We also tested the effects of community participation, conservation education, benefit provision, and market integration. We systematically reviewed the literature on community-based conservation and identified 68 interventions suitable for inclusion. We used a protocol to extract and code information and evaluated a range of measures of outcome success (attitudinal, behavioral, ecological, and economic). We also examined the association of each predictor with each outcome measure and the structure of predictor covariance. Local institutional context influenced intervention outcomes, and interventions that engaged with local institutions were more likely to succeed. Nevertheless, there was limited support for the role of community participation, conservation education, benefit provision, and market integration on intervention success. We recommend that conservation interventions seek to understand the societies they work with and tailor their activities accordingly. Systematic reviews are a valuable approach for assessing conservation evidence, although sensitive to the continuing lack of high-quality reporting on conservation interventions.

CNNH_PSS: protein 8-class secondary structure prediction by convolutional neural network with highway.

PubMed

Zhou, Jiyun; Wang, Hongpeng; Zhao, Zhishan; Xu, Ruifeng; Lu, Qin

2018-05-08

Protein secondary structure is the three dimensional form of local segments of proteins and its prediction is an important problem in protein tertiary structure prediction. Developing computational approaches for protein secondary structure prediction is becoming increasingly urgent. We present a novel deep learning based model, referred to as CNNH_PSS, by using multi-scale CNN with highway. In CNNH_PSS, any two neighbor convolutional layers have a highway to deliver information from current layer to the output of the next one to keep local contexts. As lower layers extract local context while higher layers extract long-range interdependencies, the highways between neighbor layers allow CNNH_PSS to have ability to extract both local contexts and long-range interdependencies. We evaluate CNNH_PSS on two commonly used datasets: CB6133 and CB513. CNNH_PSS outperforms the multi-scale CNN without highway by at least 0.010 Q8 accuracy and also performs better than CNF, DeepCNF and SSpro8, which cannot extract long-range interdependencies, by at least 0.020 Q8 accuracy, demonstrating that both local contexts and long-range interdependencies are indeed useful for prediction. Furthermore, CNNH_PSS also performs better than GSM and DCRNN which need extra complex model to extract long-range interdependencies. It demonstrates that CNNH_PSS not only cost less computer resource, but also achieves better predicting performance. CNNH_PSS have ability to extracts both local contexts and long-range interdependencies by combing multi-scale CNN and highway network. The evaluations on common datasets and comparisons with state-of-the-art methods indicate that CNNH_PSS is an useful and efficient tool for protein secondary structure prediction.

STELLAR: fast and exact local alignments

PubMed Central

2011-01-01

Background Large-scale comparison of genomic sequences requires reliable tools for the search of local alignments. Practical local aligners are in general fast, but heuristic, and hence sometimes miss significant matches. Results We present here the local pairwise aligner STELLAR that has full sensitivity for ε-alignments, i.e. guarantees to report all local alignments of a given minimal length and maximal error rate. The aligner is composed of two steps, filtering and verification. We apply the SWIFT algorithm for lossless filtering, and have developed a new verification strategy that we prove to be exact. Our results on simulated and real genomic data confirm and quantify the conjecture that heuristic tools like BLAST or BLAT miss a large percentage of significant local alignments. Conclusions STELLAR is very practical and fast on very long sequences which makes it a suitable new tool for finding local alignments between genomic sequences under the edit distance model. Binaries are freely available for Linux, Windows, and Mac OS X at http://www.seqan.de/projects/stellar. The source code is freely distributed with the SeqAn C++ library version 1.3 and later at http://www.seqan.de. PMID:22151882

Stratigraphy, palaeoenvironments and palaeoecology of the Loch Humphrey Burn lagerstätte and other Mississippian palaeobotanical localities of the Kilpatrick Hills, southwest Scotland

PubMed Central

Stevens, Liadan G.; Hilton, Jason

2016-01-01

Background and Aims. The largely Mississippian strata of the Kilpatrick Hills, located at the western end of the Scottish Midland Valley, enclose several macrofossil floras that together contain ca 21 organ-species of permineralised plants and ca 44 organ-species of compressed plants, here estimated to represent 25 whole-plant species (Glenarbuck = nine, Loch Humphrey Burn Lower = 11, Upper = seven). The most significant locality is the internationally important volcanigenic sequence that is reputedly intercalated within the Clyde Plateau Lava Formation at Loch Humphrey Burn, where ca 30 m of reworked tuffs and other clastic sediments enclose one of the world’s most important terrestrial lagerstätten of this period. We here explore the palaeoecology and palaeoenvironments of the locality, and elucidate its controversial age. Methods. Repeated re-excavation of key exposures allowed recognition of five main depositional units, differing in thickness from 4 m to 12 m. It also permitted detailed sampling for plant macrofossils and microfossils throughout the succession. Several approaches are integrated to re-assess the taphonomy and preservation of these exceptional plant fossils. Key Results. The deposits are rich in taxonomically diverse miospores and in toto contain at least six well-developed compression floras, together with two beds yielding nodules that enclose well-researched anatomically preserved plants permineralised in calcite. Bulk geochemistry shows that the upper nodules formed by migration of Ca with subordinate Mn and Na. Some phylogenetically important plant fossils recovered in the early 20th century have been traced to their source horizons. Trends in relative proportions of macrofossil and microfossil taxa through the sequence are only moderately congruent, perhaps reflecting the likelihood that microfossils sample the regional rather than the local flora. Conclusions. The Loch Humphrey Burn sequence encompasses a wide range of depositional environments that intercalates high-energy fluvial channels (possibly developed during flash floods in a seasonally arid environment) with lower energy flood plains and a brief lacustrine interval; all yield macrofloras typically dominated by allochthonous pteridosperms. The uppermost unit represents clastic swamps dominated by (hypo)autochthonous lycopsids and ferns s.l., and is tentatively correlated with the entire—reputedly mid-Visean—exposure at nearby Glenarbuck. Other nearby localities with rooted tree-lycopsids appear to have immediately pre-dated the onset of regional volcanism. These interpretations allow revised provenancing and dating of historical collections of key plant fossils. The late Tournaisian date previously attributed on palynological evidence to the lowest unit at Loch Humphrey Burn appears increasingly improbable when our re-appraisal of the macrofloras and microfloras is placed in the context of (a) statistical comparison with other permineralised Mississippian assemblages and (b) recent stratigraphic and geochronologic studies in the region; rather, we ascribe the entire Kilpatrick Hills sequence to the mid-Visean. Stratigraphic and palaeoenvironmental interpretations of the Mississippian rocks of the Kilpatrick Hills have especially profound implications for our understanding of the physical evolution of Scotland during the Variscan orogeny and formation of Pangea. PMID:26925325

Stratigraphy, palaeoenvironments and palaeoecology of the Loch Humphrey Burn lagerstätte and other Mississippian palaeobotanical localities of the Kilpatrick Hills, southwest Scotland.

PubMed

Bateman, Richard M; Stevens, Liadan G; Hilton, Jason

2016-01-01

Background and Aims. The largely Mississippian strata of the Kilpatrick Hills, located at the western end of the Scottish Midland Valley, enclose several macrofossil floras that together contain ca 21 organ-species of permineralised plants and ca 44 organ-species of compressed plants, here estimated to represent 25 whole-plant species (Glenarbuck = nine, Loch Humphrey Burn Lower = 11, Upper = seven). The most significant locality is the internationally important volcanigenic sequence that is reputedly intercalated within the Clyde Plateau Lava Formation at Loch Humphrey Burn, where ca 30 m of reworked tuffs and other clastic sediments enclose one of the world's most important terrestrial lagerstätten of this period. We here explore the palaeoecology and palaeoenvironments of the locality, and elucidate its controversial age. Methods. Repeated re-excavation of key exposures allowed recognition of five main depositional units, differing in thickness from 4 m to 12 m. It also permitted detailed sampling for plant macrofossils and microfossils throughout the succession. Several approaches are integrated to re-assess the taphonomy and preservation of these exceptional plant fossils. Key Results. The deposits are rich in taxonomically diverse miospores and in toto contain at least six well-developed compression floras, together with two beds yielding nodules that enclose well-researched anatomically preserved plants permineralised in calcite. Bulk geochemistry shows that the upper nodules formed by migration of Ca with subordinate Mn and Na. Some phylogenetically important plant fossils recovered in the early 20th century have been traced to their source horizons. Trends in relative proportions of macrofossil and microfossil taxa through the sequence are only moderately congruent, perhaps reflecting the likelihood that microfossils sample the regional rather than the local flora. Conclusions. The Loch Humphrey Burn sequence encompasses a wide range of depositional environments that intercalates high-energy fluvial channels (possibly developed during flash floods in a seasonally arid environment) with lower energy flood plains and a brief lacustrine interval; all yield macrofloras typically dominated by allochthonous pteridosperms. The uppermost unit represents clastic swamps dominated by (hypo)autochthonous lycopsids and ferns s.l., and is tentatively correlated with the entire-reputedly mid-Visean-exposure at nearby Glenarbuck. Other nearby localities with rooted tree-lycopsids appear to have immediately pre-dated the onset of regional volcanism. These interpretations allow revised provenancing and dating of historical collections of key plant fossils. The late Tournaisian date previously attributed on palynological evidence to the lowest unit at Loch Humphrey Burn appears increasingly improbable when our re-appraisal of the macrofloras and microfloras is placed in the context of (a) statistical comparison with other permineralised Mississippian assemblages and (b) recent stratigraphic and geochronologic studies in the region; rather, we ascribe the entire Kilpatrick Hills sequence to the mid-Visean. Stratigraphic and palaeoenvironmental interpretations of the Mississippian rocks of the Kilpatrick Hills have especially profound implications for our understanding of the physical evolution of Scotland during the Variscan orogeny and formation of Pangea.

Students' Understanding of Acids/Bases in Organic Chemistry Contexts

ERIC Educational Resources Information Center

Cartrette, David P.; Mayo, Provi M.

2011-01-01

Understanding key foundational principles is vital to learning chemistry across different contexts. One such foundational principle is the acid/base behavior of molecules. In the general chemistry sequence, the Bronsted-Lowry theory is stressed, because it lends itself well to studying equilibrium and kinetics. However, the Lewis theory of…

Reduced representation bisulphite sequencing of the cattle genome reveals DNA methylation patterns

USDA-ARS?s Scientific Manuscript database

Using reduced representation bisulphite sequencing (RRBS), we obtained the first single-base-resolution maps of bovine DNA methylation in ten somatic tissues. In total, we observed 1,868,049 cytosines in the CG-enriched regions. Similar to the methylation patterns in other species, the CG context wa...

Information Withholding as a Manipulative and Collusive Strategy in Nukulaelae Gossip.

ERIC Educational Resources Information Center

Besnier, Niko

1989-01-01

Examines the organization and function of information-withholding sequences, a conversational strategy used by participants in gossip interaction on Nukulaelae, a Polynesian Central Pacific atoll. Withholding sequences illustrate how ambiguity and repairs can be exploited to meet the communicative demands of particular interactional contexts. (62…

Teaching Integration with Layers and Representations: A Case Study

ERIC Educational Resources Information Center

Von Korff, Joshua; Rebello, N. Sanjay

2012-01-01

We designed a sequence of seven lessons to facilitate learning of integration in a physics context. We implemented this sequence with a single college sophomore, "Amber," who was concurrently enrolled in a first-semester calculus-based introductory physics course which covered topics in mechanics. We outline the philosophy underpinning these…

Teacher Deployment of "Oh" in Known-Answer Question Sequences

ERIC Educational Resources Information Center

Hosoda, Yuri

2016-01-01

This conversation analytic study describes some specific interactional contexts in which native English-speaking teachers produce "oh" in known-answer question sequences in English language classes. The data for this study come from 10 video-recorded Japanese primary school English language class sessions. The analysis identified three…

Global Literacy in Local Learning Contexts: Connecting Home and School. Routledge Research in International and Comparative Education

ERIC Educational Resources Information Center

Mount-Cors, Mary Faith

2016-01-01

Based on qualitative research focused on literacy and health from three schools in coastal Kenya, this book examines country, school, and family contexts to develop a dual-generation maternal-child model for literacy learning and to connect local-specific phenomena with national and international policy arenas. In contrast to international…

Global Trends and Local Realities: Lessons about Economic Benefits, Selves and Identity from a Swiss Context

ERIC Educational Resources Information Center

Csillagh, Virág

2015-01-01

Inspired by the unexpected results of a standardized questionnaire survey of Swiss university students' motivation and attitudes toward English, the paper discusses the influence of global and local contexts on language learners' motivation and identity. As a result of the unprecedented spread of English as a foreign language (Crystal, 2003;…

[Management of Grave's disease in the tropics (experience at Bouffard Army Hospital Center in Djibouti].

PubMed

Coulet, O; Kraemer, P; Leyral, G; Cloatre, G

2004-01-01

Based on their experience in managing Grave's disease at the Bouffard Army Hospital Center within the local health care context in Djibouti, the authors advocate surgery as the first line treatment. Medical and economical factors supporting this preference are discussed so that readers can adapt them to his own local context.

Perennial grass and native wildflowers: a synergistic approach to habitat management

USDA-ARS?s Scientific Manuscript database

A total of 19 buffer plots were established on University of Georgia experimental farms and lands near Tifton, GA in 2015. The buffer plots were assigned to a 2 x 2 design of local spatial context and irrigation. For local spatial context, ten plots were located adjacent to woodland (“T”) and ten in...

Molecular cloning and characterization of satellite DNA sequences from constitutive heterochromatin of the habu snake (Protobothrops flavoviridis, Viperidae) and the Burmese python (Python bivittatus, Pythonidae).

PubMed

Matsubara, Kazumi; Uno, Yoshinobu; Srikulnath, Kornsorn; Seki, Risako; Nishida, Chizuko; Matsuda, Yoichi

2015-12-01

Highly repetitive DNA sequences of the centromeric heterochromatin provide valuable molecular cytogenetic markers for the investigation of genomic compartmentalization in the macrochromosomes and microchromosomes of sauropsids. Here, the relationship between centromeric heterochromatin and karyotype evolution was examined using cloned repetitive DNA sequences from two snake species, the habu snake (Protobothrops flavoviridis, Crotalinae, Viperidae) and Burmese python (Python bivittatus, Pythonidae). Three satellite DNA (stDNA) families were isolated from the heterochromatin of these snakes: 168-bp PFL-MspI from P. flavoviridis and 196-bp PBI-DdeI and 174-bp PBI-MspI from P. bivittatus. The PFL-MspI and PBI-DdeI sequences were localized to the centromeric regions of most chromosomes in the respective species, suggesting that the two sequences were the major components of the centromeric heterochromatin in these organisms. The PBI-MspI sequence was localized to the pericentromeric region of four chromosome pairs. The PFL-MspI and the PBI-DdeI sequences were conserved only in the genome of closely related species, Gloydius blomhoffii (Crotalinae) and Python molurus, respectively, although their locations on the chromosomes were slightly different. In contrast, the PBI-MspI sequence was also in the genomes of P. molurus and Boa constrictor (Boidae), and additionally localized to the centromeric regions of eight chromosome pairs in B. constrictor, suggesting that this sequence originated in the genome of a common ancestor of Pythonidae and Boidae, approximately 86 million years ago. The three stDNA sequences showed no genomic compartmentalization between the macrochromosomes and microchromosomes, suggesting that homogenization of the centromeric and/or pericentromeric stDNA sequences occurred in the macrochromosomes and microchromosomes of these snakes.

TABLE D - WMO AND LOCAL (NCEP) DESCRIPTORS AS WELL AS THOSE AWAITING

Science.gov Websites

sequences common to satellite observations None 3 05 Meteorological or hydrological sequences common to Vertical sounding sequences (conventional data) None 3 10 Vertical sounding sequences (satellite data) None (satellite data) None 3 13 Sequences common to image data None 3 14 Reserved None 3 15 Oceanographic report

microRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3' untranslated region: function in replication and influence of RNA secondary structure.

PubMed

Gerresheim, Gesche K; Dünnes, Nadia; Nieder-Röhrmann, Anika; Shalamova, Lyudmila A; Fricke, Markus; Hofacker, Ivo; Höner Zu Siederdissen, Christian; Marz, Manja; Niepmann, Michael

2017-02-01

We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3'UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3'UTR target site inhibits translation directed by the HCV 5'UTR. Thus, the miR-122 target sites in the 3'-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle.

Deep sequencing of evolving pathogen populations: applications, errors, and bioinformatic solutions

PubMed Central

2014-01-01

Deep sequencing harnesses the high throughput nature of next generation sequencing technologies to generate population samples, treating information contained in individual reads as meaningful. Here, we review applications of deep sequencing to pathogen evolution. Pioneering deep sequencing studies from the virology literature are discussed, such as whole genome Roche-454 sequencing analyses of the dynamics of the rapidly mutating pathogens hepatitis C virus and HIV. Extension of the deep sequencing approach to bacterial populations is then discussed, including the impacts of emerging sequencing technologies. While it is clear that deep sequencing has unprecedented potential for assessing the genetic structure and evolutionary history of pathogen populations, bioinformatic challenges remain. We summarise current approaches to overcoming these challenges, in particular methods for detecting low frequency variants in the context of sequencing error and reconstructing individual haplotypes from short reads. PMID:24428920

The red-sequence of 72 WINGS local galaxy clusters

NASA Astrophysics Data System (ADS)

Valentinuzzi, T.; Poggianti, B. M.; Fasano, G.; D'Onofrio, M.; Moretti, A.; Ramella, M.; Biviano, A.; Fritz, J.; Varela, J.; Bettoni, D.; Vulcani, B.; Moles, M.; Couch, W. J.; Dressler, A.; Kjærgaard, P.; Omizzolo, A.; Cava, A.

2011-12-01

We study the color - magnitude red sequence and blue fraction of 72 X-ray selected galaxy clusters at z = 0.04-0.07 from the WINGS survey, searching for correlations between the characteristics of the red sequence (RS) and the environment. We consider the slope and scatter of the red sequence, the number ratio of red luminous-to-faint galaxies, the blue fraction, and the fractions of ellipticals, S0s, and spirals that compose the RS. None of these quantities correlate with the cluster velocity dispersion, X-ray luminosity, number of cluster substructures, BCG prevalence over next brightest galaxies, and the spatial concentration of ellipticals. The properties of the RS, instead, depend strongly on local galaxy density. Higher density regions have a smaller RS scatter, a higher luminous-to-faint ratio, a lower blue fraction, and a lower spiral fraction on the RS. Our results clearly illustrate the prominent effect of the local density in setting the epoch when galaxies become passive and join the red sequence, as opposed to the mass of the galaxy host structure.

Disclosure of Incidental Findings From Next-Generation Sequencing in Pediatric Genomic Research

PubMed Central

Abdul-Karim, Ruqayyah; Berkman, Benjamin E.; Wendler, David; Rid, Annette; Khan, Javed; Badgett, Tom

2013-01-01

Next-generation sequencing technologies will likely be used with increasing frequency in pediatric research. One consequence will be the increased identification of individual genomic research findings that are incidental to the aims of the research. Although researchers and ethicists have raised theoretical concerns about incidental findings in the context of genetic research, next-generation sequencing will make this once largely hypothetical concern an increasing reality. Most commentators have begun to accept the notion that there is some duty to disclose individual genetic research results to research subjects; however, the scope of that duty remains unclear. These issues are especially complicated in the pediatric setting, where subjects cannot currently but typically will eventually be able to make their own medical decisions at the age of adulthood. This article discusses the management of incidental findings in the context of pediatric genomic research. We provide an overview of the current literature and propose a framework to manage incidental findings in this unique context, based on what we believe is a limited responsibility to disclose. We hope this will be a useful source of guidance for investigators, institutional review boards, and bioethicists that anticipates the complicated ethical issues raised by advances in genomic technology. PMID:23400601

Quantitative Boltzmann-Gibbs Principles via Orthogonal Polynomial Duality

NASA Astrophysics Data System (ADS)

Ayala, Mario; Carinci, Gioia; Redig, Frank

2018-06-01

We study fluctuation fields of orthogonal polynomials in the context of particle systems with duality. We thereby obtain a systematic orthogonal decomposition of the fluctuation fields of local functions, where the order of every term can be quantified. This implies a quantitative generalization of the Boltzmann-Gibbs principle. In the context of independent random walkers, we complete this program, including also fluctuation fields in non-stationary context (local equilibrium). For other interacting particle systems with duality such as the symmetric exclusion process, similar results can be obtained, under precise conditions on the n particle dynamics.

Hypersaline groundwater genesis assessment through a multidisciplinary approach: the case of Pozzo del Sale Spring (southern Italy)

NASA Astrophysics Data System (ADS)

Celico, Fulvio; Capuano, Paolo; de Felice, Vincenzo; Naclerio, Gino

2008-11-01

A tool, based on a multidisciplinary field investigation approach for studying the characteristics of a hypersaline spring, was developed and its effectiveness tested on a spring in southern Italy; a preliminary model of the aquifer system at medium and local scale was derived. Hydrologic measurements, vertical electric soundings, and chemical and isotopic (δ18O, δ2H, 3H) analyses were undertaken, along with microbiological analyses and species identification. These demonstrate the coexistence of hypersaline and fresh water, generating a significant diversification of the groundwater hydrochemical signature. The isotopic signature shows that both types of water have a meteoric origin. Microbial contamination of fecal origin indicates the mixing of hyper- and low- saline water related to local infiltration. The hypersaline groundwater flows in confined horizons within a sequence that is mainly of fractured clays. These horizons are probably concentrated where well-developed fracture network and dissolution openings within evaporitic rocks enhance fluid flow. In a wider context, this study determines that microbiological pollution of saline groundwater may not be detected if using nonhalophilic bacterial indicators such as fecal coliforms. Fecal enterococci are better indicators, due to their higher halotolerance.

Oldest human occupation of Wallacea at Laili Cave, Timor-Leste, shows broad-spectrum foraging responses to late Pleistocene environments

NASA Astrophysics Data System (ADS)

Hawkins, Stuart; O'Connor, Sue; Maloney, Tim Ryan; Litster, Mirani; Kealy, Shimona; Fenner, Jack N.; Aplin, Ken; Boulanger, Clara; Brockwell, Sally; Willan, Richard; Piotto, Elena; Louys, Julien

2017-09-01

The Wallacea Archipelago provides an extraordinary laboratory for the study of human colonisation and adaptation, yet few detailed archaeological studies have been conducted in the region that span the earliest phase of human settlement. Laili Cave, in northern Timor-Leste, preserves the oldest human occupation in this insular region with a cultural sequence spanning 11,200 to 44,600 cal BP. Small-bodied vertebrates and invertebrates were recovered to the lowest excavated levels, associated with highly concentrated stone artefacts. We report on human behavioural adaptations within the context of Pleistocene environments and changing landscapes using zooarchaeological, stone artefact, bathymetric, and experimental isotopic analyses. Results indicate that Pleistocene humans used the abundant local chert liberally and engaged in mobile broad-spectrum exploitation of invertebrates and fishes from marine, estuarine, and freshwater environments within close proximity of Laili Cave. The faunal assemblage indicates heterogeneous but relatively stable environments during the late Pleistocene. Variability in subsistence strategies over time appears to be a response to changing landscapes and concomitant local resources. This record contrasts with marine specialisations evident from other sites in Timor-Leste and within the broader Wallacean region.

TAP score: torsion angle propensity normalization applied to local protein structure evaluation

PubMed Central

Tosatto, Silvio CE; Battistutta, Roberto

2007-01-01

Background Experimentally determined protein structures may contain errors and require validation. Conformational criteria based on the Ramachandran plot are mainly used to distinguish between distorted and adequately refined models. While the readily available criteria are sufficient to detect totally wrong structures, establishing the more subtle differences between plausible structures remains more challenging. Results A new criterion, called TAP score, measuring local sequence to structure fitness based on torsion angle propensities normalized against the global minimum and maximum is introduced. It is shown to be more accurate than previous methods at estimating the validity of a protein model in terms of commonly used experimental quality parameters on two test sets representing the full PDB database and a subset of obsolete PDB structures. Highly selective TAP thresholds are derived to recognize over 90% of the top experimental structures in the absence of experimental information. Both a web server and an executable version of the TAP score are available at . Conclusion A novel procedure for energy normalization (TAP) has significantly improved the possibility to recognize the best experimental structures. It will allow the user to more reliably isolate problematic structures in the context of automated experimental structure determination. PMID:17504537

Beamspace fast fully adaptive brain source localization for limited data sequences

NASA Astrophysics Data System (ADS)

Ravan, Maryam

2017-05-01

In the electroencephalogram (EEG) or magnetoencephalogram (MEG) context, brain source localization methods that rely on estimating second order statistics often fail when the observations are taken over a short time interval, especially when the number of electrodes is large. To address this issue, in previous study, we developed a multistage adaptive processing called fast fully adaptive (FFA) approach that can significantly reduce the required sample support while still processing all available degrees of freedom (DOFs). This approach processes the observed data in stages through a decimation procedure. In this study, we introduce a new form of FFA approach called beamspace FFA. We first divide the brain into smaller regions and transform the measured data from the source space to the beamspace in each region. The FFA approach is then applied to the beamspaced data of each region. The goal of this modification is to benefit the correlation sensitivity reduction between sources in different brain regions. To demonstrate the performance of the beamspace FFA approach in the limited data scenario, simulation results with multiple deep and cortical sources as well as experimental results are compared with regular FFA and widely used FINE approaches. Both simulation and experimental results demonstrate that the beamspace FFA method can localize different types of multiple correlated brain sources in low signal to noise ratios more accurately with limited data.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

PubMed Central

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its natural ER/Golgi maturation pathway. In contrast to cells expressing the parental MPLW515L, MPLW515L-KDEL-expressing FDC-P1 cells were unable to grow autonomously and to produce tumors in nude mice. When observed, tumor nodules resulted from in vivo selection of cells leaking the receptor at their surface. JAK2 co-immunoprecipitated with MPLW515L-KDEL but was not phosphorylated. We generated disulfide-bonded MPLW515L homodimers by the S402C substitution, both in the normal and KDEL context. Unlike MPLW515L-KDEL, MPLW515L-S402C-KDEL signaled constitutively and exhibited cell surface localization. These data establish that MPLW515L with appended JAK2 matures through the ER/Golgi system in an inactive conformation and suggest that the MPLW515L/JAK2 complex requires membrane localization for JAK2 phosphorylation, resulting in autonomous receptor signaling. PMID:19261614

Variational Dirac-Hartree-Fock calculation of the Breit interaction

NASA Astrophysics Data System (ADS)

Goldman, S. P.

1988-04-01

The calculation of the retarded version of the Breit interaction in the context of the VDHF method is discussed. With the use of Slater-type basis functions, all the terms involved can be calculated in closed form. The results are expressed as an expansion in powers of one-electron energy differences and linear combinations of hypergeometric functions. Convergence is fast and high accuracy is obtained with a small number of terms in the expansion even for high values of the nuclear charge. An added advantage is that the lowest order cancellations occurring in the retardation terms are accounted for exactly a priori. A comparison of the number of terms in the total expansion needed for an accuracy of 12 significant digits in the total energy, as well as a comparison of the results with an without retardation and in the local potential approximation, are presented for the carbon isoelectronic sequence.

Characterization of a nuclear localization signal in the foot-and-mouth disease virus polymerase

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

Sanchez-Aparicio, Maria Teresa; Rosas, Maria Flora; Sobrino, Francisco, E-mail: fsobrino@cbm.uam.es

2013-09-15

We have experimentally tested whether the MRKTKLAPT sequence in FMDV 3D protein (residues 16 to 24) can act as a nuclear localization signal (NLS). Mutants with substitutions in two basic residues within this sequence, K18E and K20E, were generated. A decreased nuclear localization was observed in transiently expressed 3D and its precursor 3CD, suggesting a role of K18 and K20 in nuclear targeting. Fusion of MRKTKLAPT to the green fluorescence protein (GFP) increased the nuclear localization of GFP, which was not observed when GFP was fused to the 3D mutated sequences. These results indicate that the sequence MRKTKLAPT can bemore » functionally considered as a NLS. When introduced in a FMDV full length RNA replacements K18E and K20E led to production of revertant viruses that replaced the acidic residues introduced (E) by K, suggesting that the presence of lysins at positions 18 and 20 of 3D is essential for virus multiplication. - Highlights: • The FMDV 3D polymerase contains a nuclear localization signal. • Replacements K18E and K20E decrease nuclear localization of 3D and its precursor 3CD. • Fusion of the MRKTKLAPT 3D motif to GFP increases the nuclear localization of GFP. • Replacements K18E and K20E abolish the ability of MRKTKLAPT to relocate GFP. • RNAs harboring replacements K18E and K20E lead to recovery of revertant FMDVs.« less

Musculoskeletal MRI findings of juvenile localized scleroderma.

PubMed

Eutsler, Eric P; Horton, Daniel B; Epelman, Monica; Finkel, Terri; Averill, Lauren W

2017-04-01

Juvenile localized scleroderma comprises a group of autoimmune conditions often characterized clinically by an area of skin hardening. In addition to superficial changes in the skin and subcutaneous tissues, juvenile localized scleroderma may involve the deep soft tissues, bones and joints, possibly resulting in functional impairment and pain in addition to cosmetic changes. There is literature documenting the spectrum of findings for deep involvement of localized scleroderma (fascia, muscles, tendons, bones and joints) in adults, but there is limited literature for the condition in children. We aimed to document the spectrum of musculoskeletal magnetic resonance imaging (MRI) findings of both superficial and deep juvenile localized scleroderma involvement in children and to evaluate the utility of various MRI sequences for detecting those findings. Two radiologists retrospectively evaluated 20 MRI studies of the extremities in 14 children with juvenile localized scleroderma. Each imaging sequence was also given a subjective score of 0 (not useful), 1 (somewhat useful) or 2 (most useful for detecting the findings). Deep tissue involvement was detected in 65% of the imaged extremities. Fascial thickening and enhancement were seen in 50% of imaged extremities. Axial T1, axial T1 fat-suppressed (FS) contrast-enhanced and axial fluid-sensitive sequences were rated most useful. Fascial thickening and enhancement were the most commonly encountered deep tissue findings in extremity MRIs of children with juvenile localized scleroderma. Because abnormalities of the skin, subcutaneous tissues and fascia tend to run longitudinally in an affected limb, axial T1, axial fluid-sensitive and axial T1-FS contrast-enhanced sequences should be included in the imaging protocol.

Vygotsky from ZPD to ZCD in Moral Education: Reshaping Western Theory and Practices in Local Context

ERIC Educational Resources Information Center

Balakrishnan, Vishalache; Claiborne, Lise Bird

2012-01-01

This article explores Vygotsky's concept of the Zone of Proximal Development (ZPD) in the Malaysian context to support local reform of the Moral Education (ME) classroom. Small groups of students in three different types of school were involved in a participant action research (PAR) project. Such classrooms in Malaysia bring together students from…

The social and environmental context of argan oil production.

PubMed

de Waroux, Yann le Polain

2013-01-01

In recent decades, argan oil has become one of the most expensive cosmetic oils on world markets. This review outlines the social and environmental context of the argan boom, highlighting its consequences on local livelihoods and conservation. It examines the claims that the argan oil boom has benefited the local population and that it encourages the conservation of argan woodlands.

Exploring the Global/Local Boundary in Education in Developing Countries: The Case of the Caribbean

ERIC Educational Resources Information Center

George, June; Lewis, Theodore

2011-01-01

This article focuses on education in developing countries in the context of globalization and with specific reference to the Caribbean. It examines the concept of globalization and related concepts and positions developing countries within this context. It explores the possibility of the creation of a third space where the local and the global can…

The Significance of Context for Curriculum Development in Engineering Education: A Case Study across Three African Countries

ERIC Educational Resources Information Center

Case, Jennifer M.; Fraser, Duncan M.; Kumar, Anil; Itika, Ambrose

2016-01-01

Curriculum reform is a key topic in the engineering education literature, but much of this discussion proceeds with little engagement with the impact of the local context in which the programme resides. This article thus seeks to understand the influence of local contextual dynamics on curriculum reform in engineering education. The empirical…

Gender differences in global-local perception? Evidence from orientation and shape judgments.

PubMed

Kimchi, Ruth; Amishav, Rama; Sulitzeanu-Kenan, Anat

2009-01-01

Direct examinations of gender differences in global-local processing are sparse, and the results are inconsistent. We examined this issue with a visuospatial judgment task and with a shape judgment task. Women and men were presented with hierarchical stimuli that varied in closure (open or closed shape) or in line orientation (oblique or horizontal/vertical) at the global or local level. The task was to classify the stimuli on the basis of the variation at the global level (global classification) or at the local level (local classification). Women's classification by closure (global or local) was more accurate than men's for stimuli that varied in closure on both levels, suggesting a female advantage in discriminating shape properties. No gender differences were observed in global-local processing bias. Women and men exhibited a global advantage, and they did not differ in their speed of global or local classification, with only one exception. Women were slower than men in local classification by orientation when the to-be-classified lines were embedded in a global line with a different orientation. This finding suggests that women are more distracted than men by misleading global oriented context when performing local orientation judgments, perhaps because women and men differ in their ability to use cognitive schemes to compensate for the distracting effects of the global context. Our findings further suggest that whether or not gender differences arise depends not only on the nature of the visual task but also on the visual context.

Score distributions of gapped multiple sequence alignments down to the low-probability tail

NASA Astrophysics Data System (ADS)

Fieth, Pascal; Hartmann, Alexander K.

2016-08-01

Assessing the significance of alignment scores of optimally aligned DNA or amino acid sequences can be achieved via the knowledge of the score distribution of random sequences. But this requires obtaining the distribution in the biologically relevant high-scoring region, where the probabilities are exponentially small. For gapless local alignments of infinitely long sequences this distribution is known analytically to follow a Gumbel distribution. Distributions for gapped local alignments and global alignments of finite lengths can only be obtained numerically. To obtain result for the small-probability region, specific statistical mechanics-based rare-event algorithms can be applied. In previous studies, this was achieved for pairwise alignments. They showed that, contrary to results from previous simple sampling studies, strong deviations from the Gumbel distribution occur in case of finite sequence lengths. Here we extend the studies to multiple sequence alignments with gaps, which are much more relevant for practical applications in molecular biology. We study the distributions of scores over a large range of the support, reaching probabilities as small as 10-160, for global and local (sum-of-pair scores) multiple alignments. We find that even after suitable rescaling, eliminating the sequence-length dependence, the distributions for multiple alignment differ from the pairwise alignment case. Furthermore, we also show that the previously discussed Gaussian correction to the Gumbel distribution needs to be refined, also for the case of pairwise alignments.

Epigenomics Reveals a Functional Genome Anatomy and a New Approach to Common Disease

PubMed Central

Feinberg, Andrew P.

2010-01-01

Standfirst header Epigenomics provides the functional context of genome sequence, analogous to the functional anatomy of the human body provided by Vesalius a half millennium ago. Much of what appear to be inconclusive genetic data for common disease could therefore become meaningful in an epigenomic context. PMID:20944596

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…

Fast neutron mutants database and web displays at SoyBase

USDA-ARS?s Scientific Manuscript database

SoyBase, the USDA-ARS soybean genetics and genomics database, has been expanded to include data for the fast neutron mutants produced by Bolon, Vance, et al. In addition to the expected text and sequence homology searches and visualization of the indels in the context of the genome sequence viewer, ...

Landscape context mediates influence of local food abundance on wetland use by wintering shorebirds in an agricultural valley

USGS Publications Warehouse

Taft, Oriane W.; Haig, Susan M.

2006-01-01

While it is widely understood that local abundance of benthic invertebrates can greatly influence the distribution and abundance of wetland birds, no studies have examined if wetland landscape context can mediate this relationship. We studied the influence of wetland food abundance and landscape context on use of agricultural wetlands by wintering dunlin (Calidris alpina) and killdeer (Charadrius vociferus) in the Willamette Valley of Oregon, USA, over two winters (1999a??2000, 2000a??2001) of differing rainfall and subsequent habitat distribution. We monitored bird use (frequency of occurrence and abundance) at a sample of wetlands differing in local food abundance (density and biomass) and landscape context [adjacent shorebird habitat (defined as ha of wet habitat with less than 50% vegetative cover and within a 2-km radius) and nearest neighbor distance]. We evaluated predictive models for bird use using linear regression and the Cp criterion to select the most parsimonious model. During the dry winter (2000a??2001), dunlin exhibited greater use of sites with higher invertebrate density and biomass but also with more adjacent shorebird habitat and closest to a wetland neighbor. However, neither landscape context nor food abundance were important predictors of dunlin use during the wet winter (1999a??2000). Use of sites by killdeer was unrelated to either local food abundance or landscape context measures during both winters. Our findings contribute to a growing recognition of the importance of landscape structure to wetland birds and highlight a number of implications for the spatial planning and enhancement of wetlands using a landscape approach.

de Bruijn cycles for neural decoding.

PubMed

Aguirre, Geoffrey Karl; Mattar, Marcelo Gomes; Magis-Weinberg, Lucía

2011-06-01

Stimulus counterbalance is critical for studies of neural habituation, bias, anticipation, and (more generally) the effect of stimulus history and context. We introduce de Bruijn cycles, a class of combinatorial objects, as the ideal source of pseudo-random stimulus sequences with arbitrary levels of counterbalance. Neuro-vascular imaging studies (such as BOLD fMRI) have an additional requirement imposed by the filtering and noise properties of the method: only some temporal frequencies of neural modulation are detectable. Extant methods of generating counterbalanced stimulus sequences yield neural modulations that are weakly (or not at all) detected by BOLD fMRI. We solve this limitation using a novel "path-guided" approach for the generation of de Bruijn cycles. The algorithm encodes a hypothesized neural modulation of specific temporal frequency within the seemingly random order of events. By positioning the modulation between the signal and noise bands of the neuro-vascular imaging method, the resulting sequence markedly improves detection power. These sequences may be used to study stimulus context and history effects in a manner not previously possible. Copyright © 2011 Elsevier Inc. All rights reserved.

Conformational Preference of ‘CαNN’ Short Peptide Motif towards Recognition of Anions

PubMed Central

Banerjee, Raja

2013-01-01

Among several ‘anion binding motifs’, the recently described ‘CαNN’ motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring ‘CαNN’ motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the ‘CαNN’ segment has an intrinsic affinity for anions. Molecular Dynamics (MD) simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the ‘CαNN’ segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the ‘CαNN’ sequence for anion recognition through “local” interaction. PMID:23516403

"We don't know her history, her background": adoptive parents' perspectives on whole genome sequencing results.

PubMed

Crouch, Julia; Yu, Joon-Ho; Shankar, Aditi G; Tabor, Holly K

2015-02-01

Exome sequencing and whole genome sequencing (ES/WGS) can provide parents with a wide range of genetic information about their children, and adoptive parents may have unique issues to consider regarding possible access to this information. The few papers published on adoption and genetics have focused on targeted genetic testing of children in the pre-adoption context. There are no data on adoptive parents' perspectives about pediatric ES/WGS, including their preferences about different kinds of results, and the potential benefits and risks of receiving results. To explore these issues, we conducted four exploratory focus groups with adoptive parents (N = 26). The majority lacked information about their children's biological family health history and ancestry, and many viewed WGS results as a way to fill in these gaps in knowledge. Some expressed concerns about protecting their children's future privacy and autonomy, but at the same time stated that WGS results could possibly help them be proactive about their children's health. A few parents expressed concerns about the risks of WGS in a pre-adoption context, specifically about decreasing a child's chance of adoption. These results suggest that issues surrounding genetic information in the post-adoption and ES/WGS contexts need to be considered, as well as concerns about risks in the pre-adoption context. A critical challenge for ES/WGS in the context of adoption will be balancing the right to know different kinds of genetic information with the right not to know. Specific guidance for geneticists and genetic counselors may be needed to maximize benefits of WGS while minimizing harms and prohibiting misuse of the information in the adoption process.

“We don’t know her history, her background”: Adoptive parents’ perspectives on whole genome sequencing results

PubMed Central

Crouch, Julia; Yu, Joon-Ho; Shankar, Aditi G.; Tabor, Holly K.

2014-01-01

Exome sequencing and whole genome sequencing (ES/WGS) can provide parents with a wide range of genetic information about their children, and adoptive parents may have unique issues to consider regarding possible access to this information. The few papers published on adoption and genetics have focused on targeted genetic testing of children in the pre-adoption context. There are no data on adoptive parent perspectives about pediatric ES/WGS, including their preferences about different kinds of results, and the potential benefits and risks of receiving results. To explore these issues, we conducted four exploratory focus groups with adoptive parents (N=26). The majority lacked information about their children’s biological family health history and ancestry, and many viewed WGS results as a way to fill in these gaps in knowledge. Some expressed concerns about protecting their children’s future privacy and autonomy, but at the same time stated that WGS results could possibly help them be proactive about their children’s health. A few parents expressed concerns about the risks of WGS in a pre-adoption context, specifically about decreasing a child’s chance of adoption. These results suggest that issues surrounding genetic information in the post-adoption and ES/WGS contexts need to be considered, as well as concerns about risks in the pre-adoption context. A critical challenge for ES/WGS in the context of adoption will be balancing the right to know different kinds of genetic information with the right not to know. Specific guidance for geneticists and genetic counselors may be needed to maximize benefits of WGS while minimizing harms and prohibiting misuse of the information in the adoption process. PMID:25011977

Whole-Genome Sequencing and Assembly with High-Throughput, Short-Read Technologies

PubMed Central

Sundquist, Andreas; Ronaghi, Mostafa; Tang, Haixu; Pevzner, Pavel; Batzoglou, Serafim

2007-01-01

While recently developed short-read sequencing technologies may dramatically reduce the sequencing cost and eventually achieve the $1000 goal for re-sequencing, their limitations prevent the de novo sequencing of eukaryotic genomes with the standard shotgun sequencing protocol. We present SHRAP (SHort Read Assembly Protocol), a sequencing protocol and assembly methodology that utilizes high-throughput short-read technologies. We describe a variation on hierarchical sequencing with two crucial differences: (1) we select a clone library from the genome randomly rather than as a tiling path and (2) we sample clones from the genome at high coverage and reads from the clones at low coverage. We assume that 200 bp read lengths with a 1% error rate and inexpensive random fragment cloning on whole mammalian genomes is feasible. Our assembly methodology is based on first ordering the clones and subsequently performing read assembly in three stages: (1) local assemblies of regions significantly smaller than a clone size, (2) clone-sized assemblies of the results of stage 1, and (3) chromosome-sized assemblies. By aggressively localizing the assembly problem during the first stage, our method succeeds in assembling short, unpaired reads sampled from repetitive genomes. We tested our assembler using simulated reads from D. melanogaster and human chromosomes 1, 11, and 21, and produced assemblies with large sets of contiguous sequence and a misassembly rate comparable to other draft assemblies. Tested on D. melanogaster and the entire human genome, our clone-ordering method produces accurate maps, thereby localizing fragment assembly and enabling the parallelization of the subsequent steps of our pipeline. Thus, we have demonstrated that truly inexpensive de novo sequencing of mammalian genomes will soon be possible with high-throughput, short-read technologies using our methodology. PMID:17534434

Household Energy Consumption: Community Context and the Fuelwood Transition*

PubMed Central

Link, Cynthia F.; Axinn, William G.; Ghimire, Dirgha J.

2012-01-01

We examine the influence of community context on change over time in households’ use of non-wood fuels. Our theoretical framework builds on sociological concepts in order to study energy consumption at the micro-level. The framework emphasizes the importance of nonfamily organizations and services in the local community as determinants of the transition from use of fuelwood to use of alternative fuels. We use multilevel longitudinal data on household fuel choice and community context from rural Nepal to provide empirical tests of our theoretical model. Results reveal that increased exposure to nonfamily organizations in the local community increases the use of alternative fuels. The findings illustrate key features of human impacts on the local environment and motivate greater incorporation of social organization into research on environmental change. PMID:23017795

Source modeling of the 2015 Mw 7.8 Nepal (Gorkha) earthquake sequence: Implications for geodynamics and earthquake hazards

NASA Astrophysics Data System (ADS)

McNamara, D. E.; Yeck, W. L.; Barnhart, W. D.; Schulte-Pelkum, V.; Bergman, E.; Adhikari, L. B.; Dixit, A.; Hough, S. E.; Benz, H. M.; Earle, P. S.

2017-09-01

The Gorkha earthquake on April 25th, 2015 was a long anticipated, low-angle thrust-faulting event on the shallow décollement between the India and Eurasia plates. We present a detailed multiple-event hypocenter relocation analysis of the Mw 7.8 Gorkha Nepal earthquake sequence, constrained by local seismic stations, and a geodetic rupture model based on InSAR and GPS data. We integrate these observations to place the Gorkha earthquake sequence into a seismotectonic context and evaluate potential earthquake hazard. Major results from this study include (1) a comprehensive catalog of calibrated hypocenters for the Gorkha earthquake sequence; (2) the Gorkha earthquake ruptured a 150 × 60 km patch of the Main Himalayan Thrust (MHT), the décollement defining the plate boundary at depth, over an area surrounding but predominantly north of the capital city of Kathmandu (3) the distribution of aftershock seismicity surrounds the mainshock maximum slip patch; (4) aftershocks occur at or below the mainshock rupture plane with depths generally increasing to the north beneath the higher Himalaya, possibly outlining a 10-15 km thick subduction channel between the overriding Eurasian and subducting Indian plates; (5) the largest Mw 7.3 aftershock and the highest concentration of aftershocks occurred to the southeast the mainshock rupture, on a segment of the MHT décollement that was positively stressed towards failure; (6) the near surface portion of the MHT south of Kathmandu shows no aftershocks or slip during the mainshock. Results from this study characterize the details of the Gorkha earthquake sequence and provide constraints on where earthquake hazard remains high, and thus where future, damaging earthquakes may occur in this densely populated region. Up-dip segments of the MHT should be considered to be high hazard for future damaging earthquakes.

Selective forces and mutational biases drive stop codon usage in the human genome: a comparison with sense codon usage.

PubMed

Trotta, Edoardo

2016-05-17

The three stop codons UAA, UAG, and UGA signal the termination of mRNA translation. As a result of a mechanism that is not adequately understood, they are normally used with unequal frequencies. In this work, we showed that selective forces and mutational biases drive stop codon usage in the human genome. We found that, in respect to sense codons, stop codon usage was affected by stronger selective forces but was less influenced by neutral mutational biases. UGA is the most frequent termination codon in human genome. However, UAA was the preferred stop codon in genes with high breadth of expression, high level of expression, AT-rich coding sequences, housekeeping functions, and in gene ontology categories with the largest deviation from expected stop codon usage. Selective forces associated with the breadth and the level of expression favoured AT-rich sequences in the mRNA region including the stop site and its proximal 3'-UTR, but acted with scarce effects on sense codons, generating two regions, upstream and downstream of the stop codon, with strongly different base composition. By favouring low levels of GC-content, selection promoted labile local secondary structures at the stop site and its proximal 3'-UTR. The compositional and structural context favoured by selection was surprisingly emphasized in the class of ribosomal proteins and was consistent with sequence elements that increase the efficiency of translational termination. Stop codons were also heterogeneously distributed among chromosomes by a mechanism that was strongly correlated with the GC-content of coding sequences. In human genome, the nucleotide composition and the thermodynamic stability of stop codon site and its proximal 3'-UTR are correlated with the GC-content of coding sequences and with the breadth and the level of gene expression. In highly expressed genes stop codon usage is compositionally and structurally consistent with highly efficient translation termination signals.

Source modeling of the 2015 Mw 7.8 Nepal (Gorkha) earthquake sequence: Implications for geodynamics and earthquake hazards

USGS Publications Warehouse

McNamara, Daniel E.; Yeck, William; Barnhart, William D.; Schulte-Pelkum, V.; Bergman, E.; Adhikari, L. B.; Dixit, Amod; Hough, S.E.; Benz, Harley M.; Earle, Paul

2017-01-01

The Gorkha earthquake on April 25th, 2015 was a long anticipated, low-angle thrust-faulting event on the shallow décollement between the India and Eurasia plates. We present a detailed multiple-event hypocenter relocation analysis of the Mw 7.8 Gorkha Nepal earthquake sequence, constrained by local seismic stations, and a geodetic rupture model based on InSAR and GPS data. We integrate these observations to place the Gorkha earthquake sequence into a seismotectonic context and evaluate potential earthquake hazard.Major results from this study include (1) a comprehensive catalog of calibrated hypocenters for the Gorkha earthquake sequence; (2) the Gorkha earthquake ruptured a ~ 150 × 60 km patch of the Main Himalayan Thrust (MHT), the décollement defining the plate boundary at depth, over an area surrounding but predominantly north of the capital city of Kathmandu (3) the distribution of aftershock seismicity surrounds the mainshock maximum slip patch; (4) aftershocks occur at or below the mainshock rupture plane with depths generally increasing to the north beneath the higher Himalaya, possibly outlining a 10–15 km thick subduction channel between the overriding Eurasian and subducting Indian plates; (5) the largest Mw 7.3 aftershock and the highest concentration of aftershocks occurred to the southeast the mainshock rupture, on a segment of the MHT décollement that was positively stressed towards failure; (6) the near surface portion of the MHT south of Kathmandu shows no aftershocks or slip during the mainshock. Results from this study characterize the details of the Gorkha earthquake sequence and provide constraints on where earthquake hazard remains high, and thus where future, damaging earthquakes may occur in this densely populated region. Up-dip segments of the MHT should be considered to be high hazard for future damaging earthquakes.

OVAS: an open-source variant analysis suite with inheritance modelling.

PubMed

Mozere, Monika; Tekman, Mehmet; Kari, Jameela; Bockenhauer, Detlef; Kleta, Robert; Stanescu, Horia

2018-02-08

The advent of modern high-throughput genetics continually broadens the gap between the rising volume of sequencing data, and the tools required to process them. The need to pinpoint a small subset of functionally important variants has now shifted towards identifying the critical differences between normal variants and disease-causing ones. The ever-increasing reliance on cloud-based services for sequence analysis and the non-transparent methods they utilize has prompted the need for more in-situ services that can provide a safer and more accessible environment to process patient data, especially in circumstances where continuous internet usage is limited. To address these issues, we herein propose our standalone Open-source Variant Analysis Sequencing (OVAS) pipeline; consisting of three key stages of processing that pertain to the separate modes of annotation, filtering, and interpretation. Core annotation performs variant-mapping to gene-isoforms at the exon/intron level, append functional data pertaining the type of variant mutation, and determine hetero/homozygosity. An extensive inheritance-modelling module in conjunction with 11 other filtering components can be used in sequence ranging from single quality control to multi-file penetrance model specifics such as X-linked recessive or mosaicism. Depending on the type of interpretation required, additional annotation is performed to identify organ specificity through gene expression and protein domains. In the course of this paper we analysed an autosomal recessive case study. OVAS made effective use of the filtering modules to recapitulate the results of the study by identifying the prescribed compound-heterozygous disease pattern from exome-capture sequence input samples. OVAS is an offline open-source modular-driven analysis environment designed to annotate and extract useful variants from Variant Call Format (VCF) files, and process them under an inheritance context through a top-down filtering schema of swappable modules, run entirely off a live bootable medium and accessed locally through a web-browser.

Finding the target sites of RNA-binding proteins

PubMed Central

Li, Xiao; Kazan, Hilal; Lipshitz, Howard D; Morris, Quaid D

2014-01-01

RNA–protein interactions differ from DNA–protein interactions because of the central role of RNA secondary structure. Some RNA-binding domains (RBDs) recognize their target sites mainly by their shape and geometry and others are sequence-specific but are sensitive to secondary structure context. A number of small- and large-scale experimental approaches have been developed to measure RNAs associated in vitro and in vivo with RNA-binding proteins (RBPs). Generalizing outside of the experimental conditions tested by these assays requires computational motif finding. Often RBP motif finding is done by adapting DNA motif finding methods; but modeling secondary structure context leads to better recovery of RBP-binding preferences. Genome-wide assessment of mRNA secondary structure has recently become possible, but these data must be combined with computational predictions of secondary structure before they add value in predicting in vivo binding. There are two main approaches to incorporating structural information into motif models: supplementing primary sequence motif models with preferred secondary structure contexts (e.g., MEMERIS and RNAcontext) and directly modeling secondary structure recognized by the RBP using stochastic context-free grammars (e.g., CMfinder and RNApromo). The former better reconstruct known binding preferences for sequence-specific RBPs but are not suitable for modeling RBPs that recognize shape and geometry of RNAs. Future work in RBP motif finding should incorporate interactions between multiple RBDs and multiple RBPs in binding to RNA. WIREs RNA 2014, 5:111–130. doi: 10.1002/wrna.1201 PMID:24217996

Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins.

PubMed

Molzan, Manuela; Ottmann, Christian

2013-03-01

Myeloid leukemia factor 1 (MLF1) is associated with the development of leukemic diseases such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, information on the physiological function of MLF1 is limited and mostly derived from studies identifying MLF1 interaction partners like CSN3, MLF1IP, MADM, Manp and the 14-3-3 proteins. The 14-3-3-binding site surrounding S34 is one of the only known functional features of the MLF1 sequence, along with one nuclear export sequence (NES) and two nuclear localization sequences (NLS). It was recently shown that the subcellular localization of mouse MLF1 is dependent on 14-3-3 proteins. Based on these findings, we investigated whether the subcellular localization of human MLF1 was also directly 14-3-3-dependent. Live cell imaging with GFP-fused human MLF1 was used to study the effects of mutations and deletions on its subcellular localization. Surprisingly, we found that the subcellular localization of full-length human MLF1 is 14-3-3-independent, and is probably regulated by other as-yet-unknown proteins.

Key factors for the implementation of successful, stand-alone village electrification schemes in Peru

NASA Astrophysics Data System (ADS)

Sanchez-Campos, Teodoro

The hypothesis of this work is that there are social, financial, technical, managerial institutional and political key factors that may either support or prevent the success of small stand alone energy systems in rural areas. This research work aims at contributing to the identification of such factors and study their relevance to the performance and sustainability of stand alone energy systems in rural areas; to meet its purpose, a wide range of literature was reviewed including rural electrification programmes and projects, research and development projects on access to electricity in rural areas, impact studies and others, and a field research survey was done the Andes and Upper Jungle regions in Peru. Nineteen possible critical factors were identified, thirteen with relevance at the local context (the community or village), and six with relevance at the national (or wider) context. From literature review it was found that the possible local critical factors were relevant only to four categories of factors instead of the six considered initially (i.e. social, financial, technological and managerial): the other two categories, political and institutional were found to be more relevant to the national context, therefore those were included in the group of possible critical factors of wider context. A series of questionnaires were designed to collect field data information, which was later used to analyse and establish the relation of each identified factor with the success of the systems studied. The survey research was implemented in 14 villages, 7 with small diesel sets and 7 with small hydropower schemes, all spread in the Andes and Upper Jungle of Peru, which were carefully selected to be representative of regions with isolated stand alone systems and with different socioeconomic background. Out of the 13 possible critical factors of local context, it was found that only 3 are really critical, the others are important but not critical; one of them (technical assistance) was found to be closely linked to national capacity, therefore for practical reasons both are considered as one critical factor or wider context. Although more research study is needed to establish a more clearer result on the factors of wider context (national context), it was found that out of the 6 factors of wider context only one appears to be critical, the other 5 are important but not critical. Therefore the summary of critical factors is as follows: a) Critical Factors of Local Context o Management o Local capacity b) Critical Factors of National Context o Technical Support/national capacity On the local factors, management appears to be the most critical of all factors, because with good management, most of the other factors can be overcome. It was also found that "The small enterprise model" tested by Practical Action on small scale hydropower schemes is proving to be successful and other organisations are starting to use it in different contexts. Therefore future research is recommended on this particular management model in order to be useful for rural electrification programmes based on decentralised energy generation systems.

Classification of Mls Point Clouds in Urban Scenes Using Detrended Geometric Features from Supervoxel-Based Local Contexts

NASA Astrophysics Data System (ADS)

Sun, Z.; Xu, Y.; Hoegner, L.; Stilla, U.

2018-05-01

In this work, we propose a classification method designed for the labeling of MLS point clouds, with detrended geometric features extracted from the points of the supervoxel-based local context. To achieve the analysis of complex 3D urban scenes, acquired points of the scene should be tagged with individual labels of different classes. Thus, assigning a unique label to the points of an object that belong to the same category plays an essential role in the entire 3D scene analysis workflow. Although plenty of studies in this field have been reported, this work is still a challenging task. Specifically, in this work: 1) A novel geometric feature extraction method, detrending the redundant and in-salient information in the local context, is proposed, which is proved to be effective for extracting local geometric features from the 3D scene. 2) Instead of using individual point as basic element, the supervoxel-based local context is designed to encapsulate geometric characteristics of points, providing a flexible and robust solution for feature extraction. 3) Experiments using complex urban scene with manually labeled ground truth are conducted, and the performance of proposed method with respect to different methods is analyzed. With the testing dataset, we have obtained a result of 0.92 for overall accuracy for assigning eight semantic classes.

ANCAC: amino acid, nucleotide, and codon analysis of COGs--a tool for sequence bias analysis in microbial orthologs.

PubMed

Meiler, Arno; Klinger, Claudia; Kaufmann, Michael

2012-09-08

The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG) within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC's NUCOCOG dataset as the largest one available for that purpose thus far. Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills.

ANCAC: amino acid, nucleotide, and codon analysis of COGs – a tool for sequence bias analysis in microbial orthologs

PubMed Central

2012-01-01

Background The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG) within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Results Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC’s NUCOCOG dataset as the largest one available for that purpose thus far. Conclusions Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills. PMID:22958836

Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions.

PubMed

Silvas, Tania V; Hou, Shurong; Myint, Wazo; Nalivaika, Ellen; Somasundaran, Mohan; Kelch, Brian A; Matsuo, Hiroshi; Kurt Yilmaz, Nese; Schiffer, Celia A

2018-05-14

The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, secondary structure, and solution pH. We identified the A3A ssDNA binding motif as (T/C)TC(A/G), which correlated with enzymatic activity. We also validated that A3A binds RNA in a sequence specific manner. A3A bound tighter to substrate binding motif within a hairpin loop compared to linear oligonucleotide, suggesting A3A affinity is modulated by substrate structure. Based on these findings and previously published A3A-ssDNA co-crystal structures, we propose a new model with intra-DNA interactions for the molecular mechanism underlying A3A sequence preference. Overall, the sequence and structural preferences identified for A3A leads to a new paradigm for identifying A3A's involvement in mutation of endogenous or exogenous DNA.

The influence of context boundaries on memory for the sequential order of events.

PubMed

DuBrow, Sarah; Davachi, Lila

2013-11-01

Episodic memory allows people to reexperience the past by recovering the sequences of events that characterize those prior experiences. Although experience is continuous, people are able to selectively retrieve and reexperience more discrete episodes from their past, raising the possibility that some elements become tightly related to each other in memory, whereas others do not. The current series of experiments was designed to ask how shifts in context during an experience influence how people remember the past. Specifically, we asked how context shifts influence the ability to remember the relative order of past events, a hallmark of episodic memory. We found that memory for the order of events was enhanced within, rather than across, context shifts, or boundaries (Experiment 1). Next, we showed that this relative enhancement in order memory was eliminated when across-item associative processing was disrupted (Experiment 2), suggesting that context shifts have a selective effect on sequential binding. Finally, we provide evidence that the act of making order memory judgments involves the reactivation of representations that bridged the tested items (Experiment 3). Together, these data suggest that boundaries may serve to parse continuous experience into sequences of contextually related events and that this organization facilitates remembering the temporal order of events that share the same context. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Solar irradiance assessment in insular areas using Himawari-8 satellite images

NASA Astrophysics Data System (ADS)

Liandrat, O.; Cros, S.; Turpin, M.; Pineau, J. F.

2016-12-01

The high amount of surface solar irradiance (SSI) in the tropics is an advantage for a profitable PV production. It will allow many tropical islands to pursue their economic growth with a clean, affordable and locally produced energy. However, the local meteorological conditions induce a very high variability which is problematic for a safe and gainful injection into the power grid. This issue is even more critical in non-interconnected territories where network stability is an absolute necessity. Therefore, the injection of PV power is legally limited in some European oversea territories. In this context, intraday irradiance forecasting (several hours ahead) is particularly useful to mitigate the production variability by reducing the cost of power storage management. At this time scale, cloud cover evolves with a stochastic behaviour not properly represented in numerical weather prediction (NWP) models. Analysing cloud motion using images from geostationary meteorological satellites is a well-known alternative to forecasting SSI up to 6 hours ahead with a better accuracy than NWP models. In this study, we present and apply our satellite-based solar irradiance forecasting methods over two measurement sites located in the field of view of the satellite Himawari-8: Cocos (Keeling) Islands (Australia) and New Caledonia (France). In particular, we converted 4 months of images from Himawari-8 visible channel into cloud index maps. Then, we applied an algorithm computing a cloud motion vector field from a short sequence of consecutive images. Comparisons between forecasted SSI at 1 hour of time horizon and collocated pyranometric measurements show a relative RMSE between 20 and 27%. Error sources related to the tropic insular context (coastal area heterogeneity, sub-pixel scale orographic cloud appearance, convective situation…) are discussed at every implementation step for the different methods.

Automated sequence-specific protein NMR assignment using the memetic algorithm MATCH.

PubMed

Volk, Jochen; Herrmann, Torsten; Wüthrich, Kurt

2008-07-01

MATCH (Memetic Algorithm and Combinatorial Optimization Heuristics) is a new memetic algorithm for automated sequence-specific polypeptide backbone NMR assignment of proteins. MATCH employs local optimization for tracing partial sequence-specific assignments within a global, population-based search environment, where the simultaneous application of local and global optimization heuristics guarantees high efficiency and robustness. MATCH thus makes combined use of the two predominant concepts in use for automated NMR assignment of proteins. Dynamic transition and inherent mutation are new techniques that enable automatic adaptation to variable quality of the experimental input data. The concept of dynamic transition is incorporated in all major building blocks of the algorithm, where it enables switching between local and global optimization heuristics at any time during the assignment process. Inherent mutation restricts the intrinsically required randomness of the evolutionary algorithm to those regions of the conformation space that are compatible with the experimental input data. Using intact and artificially deteriorated APSY-NMR input data of proteins, MATCH performed sequence-specific resonance assignment with high efficiency and robustness.

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions.

PubMed

Nishizawa, M; Nishizawa, K

2000-10-01

The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the 'between gene' GC content heterogeneity, which is linked to 'isochores', is a principal factor associated with the bias in substitution patterns in human, 'within gene' heterogeneity in nucleotide composition is also associated with such bias on a more local scale. The relationship amongst the various types of repetitiveness is discussed.

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions

PubMed Central

Nishizawa, Manami; Nishizawa, Kazuhisa

2000-01-01

The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the ‘between gene’ GC content heterogeneity, which is linked to ‘isochores’, is a principal factor associated with the bias in substitution patterns in human, ‘within gene’ heterogeneity in nucleotide composition is also associated with such bias on a more local scale. The relationship amongst the various types of repetitiveness is discussed. PMID:11000273

Dynamics of marine bacterial community diversity of the coastal waters of the reefs, inlets, and wastewater outfalls of southeast Florida

PubMed Central

Campbell, Alexandra M; Fleisher, Jay; Sinigalliano, Christopher; White, James R; Lopez, Jose V

2015-01-01

Coastal waters adjacent to populated southeast Florida possess different habitats (reefs, oceanic inlets, sewage outfalls) that may affect the composition of their inherent microbiomes. To determine variation according to site, season, and depth, over the course of 1 year, we characterized the bacterioplankton communities within 38 nearshore seawater samples derived from the Florida Area Coastal Environment (FACE) water quality survey. Six distinct coastal locales were profiled – the Port Everglades and Hillsboro Inlets, Hollywood and Broward wastewater outfalls, and associated reef sites using culture-independent, high-throughput pyrosequencing of the 16S rRNA V4 region. More than 227,000 sequences helped describe longitudinal taxonomic profiles of marine bacteria and archaea. There were 4447 unique operational taxonomic units (OTUs) identified with a mean OTU count of 5986 OTUs across all sites. Bacterial taxa varied significantly by season and by site using weighted and unweighted Unifrac, but depth was only supported by weighted Unifrac, suggesting a change due to presence/absence of certain OTUs. Abundant microbial taxa across all samples included Synechococcus, Pelagibacteraceae, Bacteroidetes, and various Proteobacteria. Unifrac analysis confirmed significant differences at inlet sites relative to reef and outfalls. Inlet-based bacterioplankton significantly differed in greater abundances of Rhodobacteraceae and Cryomorphaceae, and depletion of SAR406 sequences. This study also found higher counts of Firmicutes, Chloroflexi, and wastewater associated SBR1093 bacteria at the outfall and reef sites compared to inlet sites. This study profiles local bacterioplankton populations in a much broader context, beyond culturing and quantitative PCR, and expands upon the work completed by the National Oceanic and Atmospheric Administration FACE program. PMID:25740409

Communication during an evolving seismic sequence

NASA Astrophysics Data System (ADS)

Mucciarelli, M.; Camassi, R.

2012-04-01

Since October 2011 a seismic swarm is affecting the Pollino mountain range, southern Italy. At the abstract submission date the sequence is still ongoing, with more than 500 events with M>1, at least 40 well perceived by the population and a maximum magnitude at 3.6. The area was hit by a magnitude 5.7 event in 1998 that caused one dead, some injured and widespread damage in at least six municipalities. The population main fear is that a large event could follow the seismic swarm as it occurred at L'Aquila in 2009. Among the initiatives taken by Civil Protection at national and regional level, it was decided to try to implement at local scale two communication projects that were thought for "peace time" and not for dissemination during a seismic crisis: the "Terremoto-Io non rischio" project for general public and the "EDURISK" project for school children. The main lesson learned during the first months of the activity are: 1) it is possible to take advantage of the increased awareness and risk perception from the population to attract more citizen toward topics that could go unnoticed otherwise; 2) the Civil Protection volunteers could be a very effective mean to reach a large amount of the population, provided they are carefully trained especially when children are involved; 3) the expectations about earthquake prediction raised from media without any scientific support proved to be the most difficult to be tackled: to overcome this bias risk education in "peace time" is absolutely essential; 4) door-to-door communication is perceived much better than official press release on newspapers; 5) training of volunteers must be limited to a few basic information, with special attention to the local context.

Geometric Patterns for Neighboring Bases Near the Stacked State in Nucleic Acid Strands.

PubMed

Sedova, Ada; Banavali, Nilesh K

2017-03-14

Structural variation in base stacking has been analyzed frequently in isolated double helical contexts for nucleic acids, but not as often in nonhelical geometries or in complex biomolecular environments. In this study, conformations of two neighboring bases near their stacked state in any environment are comprehensively characterized for single-strand dinucleotide (SSD) nucleic acid crystal structure conformations. An ensemble clustering method is used to identify a reduced set of representative stacking geometries based on pairwise distances between select atoms in consecutive bases, with multiple separable conformational clusters obtained for categories divided by nucleic acid type (DNA/RNA), SSD sequence, stacking face orientation, and the presence or absence of a protein environment. For both DNA and RNA, SSD conformations are observed that are either close to the A-form, or close to the B-form, or intermediate between the two forms, or further away from either form, illustrating the local structural heterogeneity near the stacked state. Among this large variety of distinct conformations, several common stacking patterns are observed between DNA and RNA, and between nucleic acids in isolation or in complex with proteins, suggesting that these might be stable stacking orientations. Noncanonical face/face orientations of the two bases are also observed for neighboring bases in the same strand, but their frequency is much lower, with multiple SSD sequences across categories showing no occurrences of such unusual stacked conformations. The resulting reduced set of stacking geometries is directly useful for stacking-energy comparisons between empirical force fields, prediction of plausible localized variations in single-strand structures near their canonical states, and identification of analogous stacking patterns in newly solved nucleic acid containing structures.

Leveraging Distant Relatedness to Quantify Human Mutation and Gene-Conversion Rates

PubMed Central

Palamara, Pier Francesco; Francioli, Laurent C.; Wilton, Peter R.; Genovese, Giulio; Gusev, Alexander; Finucane, Hilary K.; Sankararaman, Sriram; Sunyaev, Shamil R.; de Bakker, Paul I.W.; Wakeley, John; Pe’er, Itsik; Price, Alkes L.

2015-01-01

The rate at which human genomes mutate is a central biological parameter that has many implications for our ability to understand demographic and evolutionary phenomena. We present a method for inferring mutation and gene-conversion rates by using the number of sequence differences observed in identical-by-descent (IBD) segments together with a reconstructed model of recent population-size history. This approach is robust to, and can quantify, the presence of substantial genotyping error, as validated in coalescent simulations. We applied the method to 498 trio-phased sequenced Dutch individuals and inferred a point mutation rate of 1.66 × 10−8 per base per generation and a rate of 1.26 × 10−9 for <20 bp indels. By quantifying how estimates varied as a function of allele frequency, we inferred the probability that a site is involved in non-crossover gene conversion as 5.99 × 10−6. We found that recombination does not have observable mutagenic effects after gene conversion is accounted for and that local gene-conversion rates reflect recombination rates. We detected a strong enrichment of recent deleterious variation among mismatching variants found within IBD regions and observed summary statistics of local sharing of IBD segments to closely match previously proposed metrics of background selection; however, we found no significant effects of selection on our mutation-rate estimates. We detected no evidence of strong variation of mutation rates in a number of genomic annotations obtained from several recent studies. Our analysis suggests that a mutation-rate estimate higher than that reported by recent pedigree-based studies should be adopted in the context of DNA-based demographic reconstruction. PMID:26581902

Characterization of the beta amyloid precursor protein-like gene in the central nervous system of the crab Chasmagnathus. Expression during memory consolidation.

PubMed

Fustiñana, Maria Sol; Ariel, Pablo; Federman, Noel; Freudenthal, Ramiro; Romano, Arturo

2010-09-01

Human β-amyloid, the main component in the neuritic plaques found in patients with Alzheimer's disease, is generated by cleavage of the β-amyloid precursor protein. Beyond the role in pathology, members of this protein family are synaptic proteins and have been associated with synaptogenesis, neuronal plasticity and memory, both in vertebrates and in invertebrates. Consolidation is necessary to convert a short-term labile memory to a long-term and stable form. During consolidation, gene expression and de novo protein synthesis are regulated in order to produce key proteins for the maintenance of plastic changes produced during the acquisition of new information. Here we partially cloned and sequenced the beta-amyloid precursor protein like gene homologue in the crab Chasmagnathus (cappl), showing a 37% of identity with the fruit fly Drosophila melanogaster homologue and 23% with Homo sapiens but with much higher degree of sequence similarity in certain regions. We observed a wide distribution of cappl mRNA in the nervous system as well as in muscle and gills. The protein localized in all tissues analyzed with the exception of muscle. Immunofluorescence revealed localization of cAPPL in associative and sensory brain areas. We studied gene and protein expression during long-term memory consolidation using a well characterized memory model: the context-signal associative memory in this crab species. mRNA levels varied at different time points during long-term memory consolidation and correlated with cAPPL protein levels cAPPL mRNA and protein is widely distributed in the central nervous system of the crab and the time course of expression suggests a role of cAPPL during long-term memory formation.

Biclustering as a method for RNA local multiple sequence alignment.

PubMed

Wang, Shu; Gutell, Robin R; Miranker, Daniel P

2007-12-15

Biclustering is a clustering method that simultaneously clusters both the domain and range of a relation. A challenge in multiple sequence alignment (MSA) is that the alignment of sequences is often intended to reveal groups of conserved functional subsequences. Simultaneously, the grouping of the sequences can impact the alignment; precisely the kind of dual situation biclustering is intended to address. We define a representation of the MSA problem enabling the application of biclustering algorithms. We develop a computer program for local MSA, BlockMSA, that combines biclustering with divide-and-conquer. BlockMSA simultaneously finds groups of similar sequences and locally aligns subsequences within them. Further alignment is accomplished by dividing both the set of sequences and their contents. The net result is both a multiple sequence alignment and a hierarchical clustering of the sequences. BlockMSA was tested on the subsets of the BRAliBase 2.1 benchmark suite that display high variability and on an extension to that suite to larger problem sizes. Also, alignments were evaluated of two large datasets of current biological interest, T box sequences and Group IC1 Introns. The results were compared with alignments computed by ClustalW, MAFFT, MUCLE and PROBCONS alignment programs using Sum of Pairs (SPS) and Consensus Count. Results for the benchmark suite are sensitive to problem size. On problems of 15 or greater sequences, BlockMSA is consistently the best. On none of the problems in the test suite are there appreciable differences in scores among BlockMSA, MAFFT and PROBCONS. On the T box sequences, BlockMSA does the most faithful job of reproducing known annotations. MAFFT and PROBCONS do not. On the Intron sequences, BlockMSA, MAFFT and MUSCLE are comparable at identifying conserved regions. BlockMSA is implemented in Java. Source code and supplementary datasets are available at http://aug.csres.utexas.edu/msa/

Subcellular localization of transiently expressed fluorescent fusion proteins.

PubMed

Collings, David A

2013-01-01

The recent and massive expansion in plant genomics data has generated a large number of gene sequences for which two seemingly simple questions need to be answered: where do the proteins encoded by these genes localize in cells, and what do they do? One widespread approach to answering the localization question has been to use particle bombardment to transiently express unknown proteins tagged with green fluorescent protein (GFP) or its numerous derivatives. Confocal fluorescence microscopy is then used to monitor the localization of the fluorescent protein as it hitches a ride through the cell. The subcellular localization of the fusion protein, if not immediately apparent, can then be determined by comparison to localizations generated by fluorescent protein fusions to known signalling sequences and proteins, or by direct comparison with fluorescent dyes. This review aims to be a tour guide for researchers wanting to travel this hitch-hiker's path, and for reviewers and readers who wish to understand their travel reports. It will describe some of the technology available for visualizing protein localizations, and some of the experimental approaches for optimizing and confirming localizations generated by particle bombardment in onion epidermal cells, the most commonly used experimental system. As the non-conservation of signal sequences in heterologous expression systems such as onion, and consequent mis-targeting of fusion proteins, is always a potential problem, the epidermal cells of the Argenteum mutant of pea are proposed as a model system.

Feature co-localization landscape of the human genome

PubMed Central

Ng, Siu-Kin; Hu, Taobo; Long, Xi; Chan, Cheuk-Hin; Tsang, Shui-Ying; Xue, Hong

2016-01-01

Although feature co-localizations could serve as useful guide-posts to genome architecture, a comprehensive and quantitative feature co-localization map of the human genome has been lacking. Herein we show that, in contrast to the conventional bipartite division of genomic sequences into genic and inter-genic regions, pairwise co-localizations of forty-two genomic features in the twenty-two autosomes based on 50-kb to 2,000-kb sequence windows indicate a tripartite zonal architecture comprising Genic zones enriched with gene-related features and Alu-elements; Proximal zones enriched with MIR- and L2-elements, transcription-factor-binding-sites (TFBSs), and conserved-indels (CIDs); and Distal zones enriched with L1-elements. Co-localizations between single-nucleotide-polymorphisms (SNPs) and copy-number-variations (CNVs) reveal a fraction of sequence windows displaying steeply enhanced levels of SNPs, CNVs and recombination rates that point to active adaptive evolution in such pathways as immune response, sensory perceptions, and cognition. The strongest positive co-localization observed between TFBSs and CIDs suggests a regulatory role of CIDs in cooperation with TFBSs. The positive co-localizations of cancer somatic CNVs (CNVT) with all Proximal zone and most Genic zone features, in contrast to the distinctly more restricted co-localizations exhibited by germline CNVs (CNVG), reveal disparate distributions of CNVTs and CNVGs indicative of dissimilarity in their underlying mechanisms. PMID:26854351

Magnetostratigraphic correlations of Permian-Triassic marine-to-terrestrial sections from China

USGS Publications Warehouse

Glen, J.M.G.; Nomade, S.; Lyons, J.J.; Metcalfe, I.; Mundil, R.; Renne, P.R.

2009-01-01

We have studied three Permian–Triassic (PT) localities from China as part of a combined magnetostratigraphic, 40Ar/39Ar and U–Pb radioisotopic, and biostratigraphic study aimed at resolving the temporal relations between terrestrial and marine records across the Permo-Triassic boundary, as well as the rate of the biotic recovery in the Early Triassic. The studied sections from Shangsi (Sichuan Province), Langdai (Guihzou Province), and the Junggar basin (Xinjiang Province), span marine, paralic, and terrestrial PT environments, respectively. Each of these sections was logged in detail in order to place geochronologic, paleomagnetic, geochemical, conodont and palynologic samples within a common stratigraphic context. Here we present rock-magnetic, paleomagnetic and magnetostratigraphic results from the three localities.At Shangsi, northern Sichuan Province, we sampled three sections spanning Permo-Triassic marine carbonates. Magnetostratigraphic results from the three sections indicate that the composite section contains at least eight polarity chrons and that the PT boundary occurs within a normal polarity chron a short distance above the mass extinction level and a reversed-to-normal (R-N) polarity reversal. Furthermore, the onset of the Illawarra mixed interval lies below the sampled section indicating that the uppermost Permian Changhsingian and at least part of the Wuchiapingian stages postdate the end of the Kiaman Permo-Carboniferous Reversed Superchron.At Langdai, Guizhou Province, we studied magnetostratigraphy of PT paralic mudstone and carbonate sediments in two sections. The composite section spans an R-N polarity sequence. Section-mean directions pass a fold test at the 95% confidence level, and the section-mean poles are close to the mean PT pole for the South China block. Based on biostratigraphic constraints, the R-N transition recorded at Langdai is consistent with that at Shangsi and demonstrates that the PT boundary occurred within a normal polarity chron a short distance above the mass extinction level.In the southern Junggar basin, Xinjiang Province, in northwest China, we determined the magnetostratigraphy of three sections of a terrestrial sequence. Normal and reversed polarity directions are roughly antipodal, and magnetostratigraphies from the three sections are highly consistent. Combined bio- and magneto-stratigraphy used to correlate this sequence to other PT sequences suggests that the previously-proposed biostratigraphic PT boundary in the Junggar sections was most likely misplaced by earlier workers suggesting that further work is necessary to confidently place the PT boundary there.

Lost in Time and Space: States of High Arousal Disrupt Implicit Acquisition of Spatial and Sequential Context Information

PubMed Central

Maran, Thomas; Sachse, Pierre; Martini, Markus; Weber, Barbara; Pinggera, Jakob; Zuggal, Stefan; Furtner, Marco

2017-01-01

Biased cognition during high arousal states is a relevant phenomenon in a variety of topics: from the development of post-traumatic stress disorders or stress-triggered addictive behaviors to forensic considerations regarding crimes of passion. Recent evidence indicates that arousal modulates the engagement of a hippocampus-based “cognitive” system in favor of a striatum-based “habit” system in learning and memory, promoting a switch from flexible, contextualized to more rigid, reflexive responses. Existing findings appear inconsistent, therefore it is unclear whether and which type of context processing is disrupted by enhanced arousal. In this behavioral study, we investigated such arousal-triggered cognitive-state shifts in human subjects. We validated an arousal induction procedure (three experimental conditions: violent scene, erotic scene, neutral control scene) using pupillometry (Preliminary Experiment, n = 13) and randomly administered this method to healthy young adults to examine whether high arousal states affect performance in two core domains of contextual processing, the acquisition of spatial (spatial discrimination paradigm; Experiment 1, n = 66) and sequence information (learned irrelevance paradigm; Experiment 2, n = 84). In both paradigms, spatial location and sequences were encoded incidentally and both displacements when retrieving spatial position as well as the predictability of the target by a cue in sequence learning changed stepwise. Results showed that both implicit spatial and sequence learning were disrupted during high arousal states, regardless of valence. Compared to the control group, participants in the arousal conditions showed impaired discrimination of spatial positions and abolished learning of associative sequences. Furthermore, Bayesian analyses revealed evidence against the null models. In line with recent models of stress effects on cognition, both experiments provide evidence for decreased engagement of flexible, cognitive systems supporting encoding of context information in active cognition during acute arousal, promoting reduced sensitivity for contextual details. We argue that arousal fosters cognitive adaptation towards less demanding, more present-oriented information processing, which prioritizes a current behavioral response set at the cost of contextual cues. This transient state of behavioral perseverance might reduce reliance on context information in unpredictable environments and thus represent an adaptive response in certain situations. PMID:29170634

Complementation of a red-light-indifferent cyanobacterial mutant.

PubMed Central

Chiang, G G; Schaefer, M R; Grossman, A R

1992-01-01

Many cyanobacteria alter their phycobilisome composition in response to changes in light wavelength in a process termed complementary chromatic adaptation. Mutant strains FdR1 and FdR2 of the filamentous cyanobacterium Fremyella diplosiphon are characterized by aberrant chromatic adaptation. Instead of adjusting to different wavelengths of light, FdR1 and FdR2 behave as if they are always in green light; they do not respond to red light. We have previously reported complementation of FdR1 by conjugal transfer of a wild-type genomic library. The complementing DNA has now been localized by genetic analysis to a region on the rescued genomic subclone that contains a gene designated rcaC. This region of DNA is also able to complement FdR2. Southern blot analysis of genomic DNA from FdR1 and FdR2 indicates that these strains harbor DNA insertions within the rcaC sequence that may have resulted from the activity of transposable genetic elements. The predicted amino acid sequence of RcaC shares strong identity to response regulators of bacterial two-component regulatory systems. This relationship is discussed in the context of the signal-transduction pathway mediating regulation of genes encoding phycobilisome polypeptides during chromatic adaptation. Images PMID:1409650

Conservative site-specific and single-copy transgenesis in human LINE-1 elements

PubMed Central

Vijaya Chandra, Shree Harsha; Makhija, Harshyaa; Peter, Sabrina; Myint Wai, Cho Mar; Li, Jinming; Zhu, Jindong; Ren, Zhonglu; D'Alcontres, Martina Stagno; Siau, Jia Wei; Chee, Sharon; Ghadessy, Farid John; Dröge, Peter

2016-01-01

Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage λ integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, termed attH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis through attH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional in LINE1-targeted hESCs and differentiated progenies. Furthermore, LINE-1 targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes. PMID:26673710

GTZ: a fast compression and cloud transmission tool optimized for FASTQ files.

PubMed

Xing, Yuting; Li, Gen; Wang, Zhenguo; Feng, Bolun; Song, Zhuo; Wu, Chengkun

2017-12-28

The dramatic development of DNA sequencing technology is generating real big data, craving for more storage and bandwidth. To speed up data sharing and bring data to computing resource faster and cheaper, it is necessary to develop a compression tool than can support efficient compression and transmission of sequencing data onto the cloud storage. This paper presents GTZ, a compression and transmission tool, optimized for FASTQ files. As a reference-free lossless FASTQ compressor, GTZ treats different lines of FASTQ separately, utilizes adaptive context modelling to estimate their characteristic probabilities, and compresses data blocks with arithmetic coding. GTZ can also be used to compress multiple files or directories at once. Furthermore, as a tool to be used in the cloud computing era, it is capable of saving compressed data locally or transmitting data directly into cloud by choice. We evaluated the performance of GTZ on some diverse FASTQ benchmarks. Results show that in most cases, it outperforms many other tools in terms of the compression ratio, speed and stability. GTZ is a tool that enables efficient lossless FASTQ data compression and simultaneous data transmission onto to cloud. It emerges as a useful tool for NGS data storage and transmission in the cloud environment. GTZ is freely available online at: https://github.com/Genetalks/gtz .

Sequence-dependent catalytic regulation of the SpoIIIE motor activity ensures directionality of DNA translocation.

PubMed

Chara, Osvaldo; Borges, Augusto; Milhiet, Pierre-Emmanuel; Nöllmann, Marcelo; Cattoni, Diego I

2018-03-27

Transport of cellular cargo by molecular motors requires directionality to ensure proper biological functioning. During sporulation in Bacillus subtilis, directionality of chromosome transport is mediated by the interaction between the membrane-bound DNA translocase SpoIIIE and specific octameric sequences (SRS). Whether SRS regulate directionality by recruiting and orienting SpoIIIE or by simply catalyzing its translocation activity is still unclear. By using atomic force microscopy and single-round fast kinetics translocation assays we determined the localization and dynamics of diffusing and translocating SpoIIIE complexes on DNA with or without SRS. Our findings combined with mathematical modelling revealed that SpoIIIE directionality is not regulated by protein recruitment to SRS but rather by a fine-tuned balance among the rates governing SpoIIIE-DNA interactions and the probability of starting translocation modulated by SRS. Additionally, we found that SpoIIIE can start translocation from non-specific DNA, providing an alternative active search mechanism for SRS located beyond the exploratory length defined by 1D diffusion. These findings are relevant in vivo in the context of chromosome transport through an open channel, where SpoIIIE can rapidly explore DNA while directionality is modulated by the probability of translocation initiation upon interaction with SRS versus non-specific DNA.

Challenges for geochronologies in permafrost environments: the case of Bol'shoy Lyakhovsky, Siberian Arctic

NASA Astrophysics Data System (ADS)

Wetterich, Sebastian; Fuchs, Margret; Schwamborn, Georg; Schirrmeister, Lutz

2015-04-01

Ice-bearing Quaternary deposits in permafrost environments comprise valuable archives of paleoenvironmental and palaeo-landscape dynamics over several glacial-interglacial cycles. Information on past conditions manifest in the mineralogical, organic and ice inventories. The characteristic ground ice abundance of permafrost evolves largely due to water supply by precipitation and surface run-off, while air, and consequently near-surface, temperatures control to which depth deposits freeze or thaw. This has several consequences on the continuity of permafrost sequences. Permafrost preservation or degradation depends basically on (1) climatic conditions during formation, (2) their decoupling from the active layer depth and (3) past relief conditions. In this context, warmer interstadial and interglacial periods promote permafrost degradation by ground ice melt and subsequent surface subsidence. Such processes are commonly named as thermokarst that forms basins and valleys within older deposits and creates new accumulation areas. Shifts between periglacial accumulation and erosion frequently cause gaps in permafrost sequences. This complicates geochronological interpretations as representatives of consecutive Quaternary periods may be found at laterally different positions and altitudes. Additionally, they may comprise differing sediment properties as a consequence of paleo-relief and related process dynamic. With this contribution, we discuss the challenges for establishing Quaternary geochronologies of arctic permafrost sequences using the example of Bol'shoy Lyakhovsky Island (New Siberian Archipelago). The island exposes sequences at its southern coast that are among the oldest dated Quaternary terrestrial permafrost deposits. Various proxies for paleo environmental reconstruction unravel at least three generations of cold- and warm-stage deposition ranging from the Holocene to the Eemian (MIS 5e) Interglacial, and potentially beyond that. However, the stratigraphic context is ambiguous due to the vertical discontinuity and potential hiatuses, especially for units older than the MIS 3 Interstadial. For example, stadial conditions of the MIS 4 and the MIS 6(?) are recorded in sediment units locally named as Kuchchugui Suite. The floodplain sediments are dated by AMS radiocarbon to < 53 ka BP and to 57 - 79 ka by IRSL. The lithostratigraphic context of other sites suggests Kuchchugui-like floodplain deposits that pre-date the Eemian Interglacial but remain without numerical ages so far. Despite the use of different dating methods to obtain permafrost formation ages there are still obvious discrepancies when comparing geochronological results from different physical methods. One main problem is that dating methods are generally not well established on frozen material and refer to differing permafrost components. Some of the challenges are related to unknown influences of freeze-thaw processes on chemical and physical parameters relevant for the chosen dating technique. Here, we cannot give the ultimate answer, but rather aim to highlight and discuss the advantages and drawbacks of the different dating techniques applied in our study area, including AMS radiocarbon, luminescence and radioisotope Th/U methods.

A Hidden Markov Model Approach for Simultaneously Estimating Local Ancestry and Admixture Time Using Next Generation Sequence Data in Samples of Arbitrary Ploidy

PubMed Central

Nielsen, Rasmus

2017-01-01

Admixture—the mixing of genomes from divergent populations—is increasingly appreciated as a central process in evolution. To characterize and quantify patterns of admixture across the genome, a number of methods have been developed for local ancestry inference. However, existing approaches have a number of shortcomings. First, all local ancestry inference methods require some prior assumption about the expected ancestry tract lengths. Second, existing methods generally require genotypes, which is not feasible to obtain for many next-generation sequencing projects. Third, many methods assume samples are diploid, however a wide variety of sequencing applications will fail to meet this assumption. To address these issues, we introduce a novel hidden Markov model for estimating local ancestry that models the read pileup data, rather than genotypes, is generalized to arbitrary ploidy, and can estimate the time since admixture during local ancestry inference. We demonstrate that our method can simultaneously estimate the time since admixture and local ancestry with good accuracy, and that it performs well on samples of high ploidy—i.e. 100 or more chromosomes. As this method is very general, we expect it will be useful for local ancestry inference in a wider variety of populations than what previously has been possible. We then applied our method to pooled sequencing data derived from populations of Drosophila melanogaster on an ancestry cline on the east coast of North America. We find that regions of local recombination rates are negatively correlated with the proportion of African ancestry, suggesting that selection against foreign ancestry is the least efficient in low recombination regions. Finally we show that clinal outlier loci are enriched for genes associated with gene regulatory functions, consistent with a role of regulatory evolution in ecological adaptation of admixed D. melanogaster populations. Our results illustrate the potential of local ancestry inference for elucidating fundamental evolutionary processes. PMID:28045893

Numerical studies on the link between radioisotopic signatures on Earth and the formation of the Local Bubble. I. 60Fe transport to the solar system by turbulent mixing of ejecta from nearby supernovae into a locally homogeneous interstellar medium

NASA Astrophysics Data System (ADS)

Schulreich, M. M.; Breitschwerdt, D.; Feige, J.; Dettbarn, C.

2017-08-01

Context. The discovery of radionuclides like 60Fe with half-lives of million years in deep-sea crusts and sediments offers the unique possibility to date and locate nearby supernovae. Aims: We want to quantitatively establish that the 60Fe enhancement is the result of several supernovae which are also responsible for the formation of the Local Bubble, our Galactic habitat. Methods: We performed three-dimensional hydrodynamic adaptive mesh refinement simulations (with resolutions down to subparsec scale) of the Local Bubble and the neighbouring Loop I superbubble in different homogeneous, self-gravitating environments. For setting up the Local and Loop I superbubble, we took into account the time sequence and locations of the generating core-collapse supernova explosions, which were derived from the mass spectrum of the perished members of certain stellar moving groups. The release of 60Fe and its subsequent turbulent mixing process inside the superbubble cavities was followed via passive scalars, where the yields of the decaying radioisotope were adjusted according to recent stellar evolution calculations. Results: The models are able to reproduce both the timing and the intensity of the 60Fe excess observed with rather high precision, provided that the external density does not exceed 0.3 cm-3 on average. Thus the two best-fit models presented here were obtained with background media mimicking the classical warm ionised and warm neutral medium. We also found that 60Fe (which is condensed onto dust grains) can be delivered to Earth via two physical mechanisms: either through individual fast-paced supernova blast waves, which cross the Earth's orbit sometimes even twice as a result of reflection from the Local Bubble's outer shell, or, alternatively, through the supershell of the Local Bubble itself, injecting the 60Fe content of all previous supernovae at once, but over a longer time range.

Rationalizing context-dependent performance of dynamic RNA regulatory devices.

PubMed

Kent, Ross; Halliwell, Samantha; Young, Kate; Swainston, Neil; Dixon, Neil

2018-06-21

The ability of RNA to sense, regulate and store information is an attractive attribute for a variety of functional applications including the development of regulatory control devices for synthetic biology. RNA folding and function is known to be highly context sensitive, which limits the modularity and reuse of RNA regulatory devices to control different heterologous sequences and genes. We explored the cause and effect of sequence context sensitivity for translational ON riboswitches located in the 5' UTR, by constructing and screening a library of N-terminal synonymous codon variants. By altering the N-terminal codon usage we were able to obtain RNA devices with a broad range of functional performance properties (ON, OFF, fold-change). Linear regression and calculated metrics were used to rationalize the major determining features leading to optimal riboswitch performance, and to identify multiple interactions between the explanatory metrics. Finally, partial least squared (PLS) analysis was employed in order to understand the metrics and their respective effect on performance. This PLS model was shown to provide good explanation of our library. This study provides a novel multi-variant analysis framework by which to rationalize the codon context performance of allosteric RNA-devices. The framework will also serve as a platform for future riboswitch context engineering endeavors.

Morphological and genetic evidence of contemporary intersectional hybridisation in Mediterranean Helichrysum (Asteraceae, Gnaphalieae).

PubMed

Galbany-Casals, M; Carnicero-Campmany, P; Blanco-Moreno, J M; Smissen, R D

2012-09-01

Hybridisation is considered an important evolutionary phenomenon in Gnaphalieae, but contemporary hybridisation has been little explored within the tribe. Here, hybridisation between Helichrysum orientale and Helichrysum stoechas is studied at two different localities in the islands of Crete and Rhodes (Greece). Using three different types of molecular data (AFLP, nrDNA ITS sequences and cpDNA ndhF sequences) and morphological data, the aim is to provide simultaneous and direct comparisons between molecular and morphological variation among the parental species and the studied hybrid populations. AFLP profiles, ITS sequences and morphological data support the existence of hybrids at the two localities studied, shown as morphological and genetic intermediates between the parental species. Chloroplast DNA sequences show that both parental species can act either as pollen donor or as maternal parent. Fertility of hybrids is demonstrated by the viability of seeds produced by hybrids from both localities, and the detection of a backcross specimen to H. orientale. Although there is general congruence of morphological and molecular data, the analysis of morphology and ITS sequences can fail to detect backcross hybrids. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

The use of additive and subtractive approaches to examine the nuclear localization sequence of the polyomavirus major capsid protein VP1

NASA Technical Reports Server (NTRS)

Chang, D.; Haynes, J. I. 2nd; Brady, J. N.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

1992-01-01

A nuclear localization signal (NLS) has been identified in the N-terminal (Ala1-Pro-Lys-Arg-Lys-Ser-Gly-Val-Ser-Lys-Cys11) amino acid sequence of the polyomavirus major capsid protein VP1. The importance of this amino acid sequence for nuclear transport of VP1 protein was demonstrated by a genetic "subtractive" study using the constructs pSG5VP1 (full-length VP1) and pSG5 delta 5'VP1 (truncated VP1, lacking amino acids Ala1-Cys11). These constructs were used to transfect COS-7 cells, and expression and intracellular localization of the VP1 protein was visualized by indirect immunofluorescence. These studies revealed that the full-length VP1 was expressed and localized in the nucleus, while the truncated VP1 protein was localized in the cytoplasm and not transported to the nucleus. These findings were substantiated by an "additive" approach using FITC-labeled conjugates of synthetic peptides homologous to the NLS of VP1 cross-linked to bovine serum albumin or immunoglobulin G. Both conjugates localized in the nucleus after microinjection into the cytoplasm of 3T6 cells. The importance of individual amino acids found in the basic sequence (Lys3-Arg-Lys5) of the NLS was also investigated. This was accomplished by synthesizing three additional peptides in which lysine-3 was substituted with threonine, arginine-4 was substituted with threonine, or lysine-5 was substituted with threonine. It was found that lysine-3 was crucial for nuclear transport, since substitution of this amino acid with threonine prevented nuclear localization of the microinjected, FITC-labeled conjugate.

Highly multiplexed subcellular RNA sequencing in situ

PubMed Central

Lee, Je Hyuk; Daugharthy, Evan R.; Scheiman, Jonathan; Kalhor, Reza; Ferrante, Thomas C.; Yang, Joyce L.; Terry, Richard; Jeanty, Sauveur S. F.; Li, Chao; Amamoto, Ryoji; Peters, Derek T.; Turczyk, Brian M.; Marblestone, Adam H.; Inverso, Samuel A.; Bernard, Amy; Mali, Prashant; Rios, Xavier; Aach, John; Church, George M.

2014-01-01

Understanding the spatial organization of gene expression with single nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked cDNA amplicons are sequenced within a biological sample. Using 30-base reads from 8,742 genes in situ, we examined RNA expression and localization in human primary fibroblasts using a simulated wound healing assay. FISSEQ is compatible with tissue sections and whole mount embryos, and reduces the limitations of optical resolution and noisy signals on single molecule detection. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, and can be used to investigate cellular phenotype, gene regulation, and environment in situ. PMID:24578530

Applications of nanotechnology, next generation sequencing and microarrays in biomedical research.

PubMed

Elingaramil, Sauli; Li, Xiaolong; He, Nongyue

2013-07-01

Next-generation sequencing technologies, microarrays and advances in bio nanotechnology have had an enormous impact on research within a short time frame. This impact appears certain to increase further as many biomedical institutions are now acquiring these prevailing new technologies. Beyond conventional sampling of genome content, wide-ranging applications are rapidly evolving for next-generation sequencing, microarrays and nanotechnology. To date, these technologies have been applied in a variety of contexts, including whole-genome sequencing, targeted re sequencing and discovery of transcription factor binding sites, noncoding RNA expression profiling and molecular diagnostics. This paper thus discusses current applications of nanotechnology, next-generation sequencing technologies and microarrays in biomedical research and highlights the transforming potential these technologies offer.

Designing and Evaluating a Context-Based Lesson Sequence Promoting Conceptual Coherence in Biology

ERIC Educational Resources Information Center

Ummels, M. H. J.; Kamp, M. J. A.; de Kroon, H.; Boersma, K. Th.

2015-01-01

Context-based education, in which students deal with biological concepts in a meaningful way, is showing promise in promoting the development of students' conceptual coherence. However, literature gives little guidance about how this kind of education should be designed. Therefore, our study aims at designing and evaluating the practicability of a…

Tasks in Pedagogical Context: Integrating Theory and Practice. Multilingual Matters 94.

ERIC Educational Resources Information Center

Crookes, Graham, Ed.; Gass, Susan M., Ed.

These six essays discuss the use of tasks as pedagogical tools in second language instruction, particularly in the contexts of curriculum and syllabus design. The essays are: (1) "Units of Analysis in Syllabus Design: The Case for Task" (Michael H. Long and Graham Crookes); (2) "Task-Based Syllabus Design: Selecting, Grading and Sequencing Tasks"…

In the Absence of Writhe, DNA Relieves Torsional Stress with Localized, Sequence-Dependent Structural Failure to Preserve B-form

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

Randall, Graham L.; Zechiedrich, E. L.; Pettitt, Bernard M.

2009-09-01

To understand how underwinding and overwinding the DNA helix affects its structure, we simulated 19 independent DNA systems with fixed degrees of twist using molecular dynamics in a system that does not allow writhe. Underwinding DNA induced spontaneous, sequence-dependent base flipping and local denaturation, while overwinding DNA induced the formation of Pauling-like DNA (P-DNA). The winding resulted in a bimodal state simultaneously including local structural failure and B-form DNA for both underwinding and extreme overwinding. Our simulations suggest that base flipping and local denaturation may provide a landscape influencing protein recognition of DNA sequence to affect, for examples, replication, transcriptionmore » and recombination. Additionally, our findings help explain results from singlemolecule experiments and demonstrate that elastic rod models are strictly valid on average only for unstressed or overwound DNA up to P-DNA formation. Finally, our data support a model in which base flipping can result from torsional stress.« less

Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing.

PubMed

Zhang, Jianjun; Fujimoto, Junya; Zhang, Jianhua; Wedge, David C; Song, Xingzhi; Zhang, Jiexin; Seth, Sahil; Chow, Chi-Wan; Cao, Yu; Gumbs, Curtis; Gold, Kathryn A; Kalhor, Neda; Little, Latasha; Mahadeshwar, Harshad; Moran, Cesar; Protopopov, Alexei; Sun, Huandong; Tang, Jiabin; Wu, Xifeng; Ye, Yuanqing; William, William N; Lee, J Jack; Heymach, John V; Hong, Waun Ki; Swisher, Stephen; Wistuba, Ignacio I; Futreal, P Andrew

2014-10-10

Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas. Copyright © 2014, American Association for the Advancement of Science.

Implicit Sequence Learning and Contextual Cueing Do Not Compete for Central Cognitive Resources

ERIC Educational Resources Information Center

Jimenez, Luis; Vazquez, Gustavo A.

2011-01-01

Sequence learning and contextual cueing explore different forms of implicit learning, arising from practice with a structured serial task, or with a search task with informative contexts. We assess whether these two learning effects arise simultaneously when both remain implicit. Experiments 1 and 2 confirm that a cueing effect can be observed…

State of Iowa Scope and Sequence for Vocational Home Economics.

ERIC Educational Resources Information Center

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

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

Event-Related Potentials Discriminate Familiar and Unusual Goal Outcomes in 5-Month-Olds and Adults

ERIC Educational Resources Information Center

Michel, Christine; Kaduk, Katharina; Ní Choisdealbha, Áine; Reid, Vincent M.

2017-01-01

Previous event-related potential (ERP) work has indicated that the neural processing of action sequences develops with age. Although adults and 9-month-olds use a semantic processing system, perceiving actions activates attentional processes in 7-month-olds. However, presenting a sequence of action context, action execution and action conclusion…

An analytical optimization model for infrared image enhancement via local context

NASA Astrophysics Data System (ADS)

Xu, Yongjian; Liang, Kun; Xiong, Yiru; Wang, Hui

2017-12-01

The requirement for high-quality infrared images is constantly increasing in both military and civilian areas, and it is always associated with little distortion and appropriate contrast, while infrared images commonly have some shortcomings such as low contrast. In this paper, we propose a novel infrared image histogram enhancement algorithm based on local context. By constraining the enhanced image to have high local contrast, a regularized analytical optimization model is proposed to enhance infrared images. The local contrast is determined by evaluating whether two intensities are neighbors and calculating their differences. The comparison on 8-bit images shows that the proposed method can enhance the infrared images with more details and lower noise.

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.

The Social Dynamics of Mathematics Coursetaking in High School1

PubMed Central

Frank, Kenneth A.; Muller, Chandra; Schiller, Kathryn S.; Riegle-Crumb, Catherine; Mueller, Anna Strassmann; Crosnoe, Robert; Pearson, Jennifer

2010-01-01

This study examines how high school boys’ and girls’ academic effort, in the form of math coursetaking, is influenced by members of their social contexts. The authors argue that adolescents’ social contexts are defined, in part, by clusters of students (termed “local positions”) who take courses that differentiate them from others. Using course transcript data from the recent Adolescent Health and Academic Achievement Study, the authors employ a new network algorithm to identify local positions in 78 high schools in the National Longitudinal Study of Adolescent Health. Incorporating the local positions into multilevel models of math coursetaking, the authors find that girls are highly responsive to the social norms in their local positions, which contributes to homogeneity within and heterogeneity between local positions. PMID:21031147

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

PubMed

Hamblin, Angela; Wordsworth, Sarah; Fermont, Jilles M; Page, Suzanne; Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V; Housby, Nick; Tomlinson, Ian; Taylor, Jenny C; Schuh, Anna

2017-02-01

Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers.

Continuous Timescale Long-Short Term Memory Neural Network for Human Intent Understanding

PubMed Central

Yu, Zhibin; Moirangthem, Dennis S.; Lee, Minho

2017-01-01

Understanding of human intention by observing a series of human actions has been a challenging task. In order to do so, we need to analyze longer sequences of human actions related with intentions and extract the context from the dynamic features. The multiple timescales recurrent neural network (MTRNN) model, which is believed to be a kind of solution, is a useful tool for recording and regenerating a continuous signal for dynamic tasks. However, the conventional MTRNN suffers from the vanishing gradient problem which renders it impossible to be used for longer sequence understanding. To address this problem, we propose a new model named Continuous Timescale Long-Short Term Memory (CTLSTM) in which we inherit the multiple timescales concept into the Long-Short Term Memory (LSTM) recurrent neural network (RNN) that addresses the vanishing gradient problem. We design an additional recurrent connection in the LSTM cell outputs to produce a time-delay in order to capture the slow context. Our experiments show that the proposed model exhibits better context modeling ability and captures the dynamic features on multiple large dataset classification tasks. The results illustrate that the multiple timescales concept enhances the ability of our model to handle longer sequences related with human intentions and hence proving to be more suitable for complex tasks, such as intention recognition. PMID:28878646

Transmitting Memory between and beyond Generations: The Rotterdam Bombardment in Local Memory Culture and Education from 1980 to 2015

ERIC Educational Resources Information Center

Hogervorst, Susan

2015-01-01

This article analyses three local educational projects about the Nazi bombing of Rotterdam in May 1940, all of which took place from 1980 to the present day in the context of the dynamic memory culture of the bombardment. These three contexts testify to a process by which memory, increasingly derived from authentic locations and objects instead of…

Developing Energy Technology Course for Undergraduate Engineering Management Study Program in Lake Toba Area with Particular Focus to Sustainable Energy Systems in Development Context

NASA Astrophysics Data System (ADS)

Manik, Yosef; Sinaga, Rizal; Saragi, Hadi

2018-02-01

Undergraduate Engineering Management Study Program of Institut Teknologi Del is one of the pioneers for its field in Indonesia. Located in Lake Toba Area, this study program has a mission to provide high quality Engineering Management education that produces globally competitive graduates who in turn will contribute to local development. Framing the Energy Technology course—one of the core subjects in Engineering Management Body of Knowledge—in the context of sustainable development of Lake Toba Area is very essential. Thus, one particular focus in this course is sustainable energy systems in local development context that incorporates identification and analysis of locally available energy resources. In this paper we present our experience in designing such course. In this work, we introduce the domains that shape the Engineering Management Body of Knowledge. Then, we explain the results of our evaluation on the key considerations to meet the rapidly changing needs of society in local context. Later, we present the framework of the learning outcomes and the syllabus as a result of mapping the road map with the requirement. At the end, the summary from the first two semesters of delivering this course in academic year 2015/2016 and 2016/2017 are reported.

Implementation of a web-based national child health-care programme in a local context: A complex facilitator role.

PubMed

Tell, Johanna; Olander, Ewy; Anderberg, Peter; Berglund, Johan Sanmartin

2018-02-01

The aim of this study was to investigate child health-care coordinators' experiences of being a facilitator for the implementation of a new national child health-care programme in the form of a web-based national guide. The study was based on eight remote, online focus groups, using Skype for Business. A qualitative content analysis was performed. The analysis generated three categories: adapt to a local context, transition challenges and led by strong incentives. There were eight subcategories. In the latent analysis, the theme 'Being a facilitator: a complex role' was formed to express the child health-care coordinators' experiences. Facilitating a national guideline or decision support in a local context is a complex task that requires an advocating and mediating role. For successful implementation, guidelines and decision support, such as a web-based guide and the new child health-care programme, must match professional consensus and needs and be seen as relevant by all. Participation in the development and a strong bottom-up approach was important, making the web-based guide and the programme relevant to whom it is intended to serve, and for successful implementation. The study contributes valuable knowledge when planning to implement a national web-based decision support and policy programme in a local health-care context.

Modular protein domains: an engineering approach toward functional biomaterials.

PubMed

Lin, Charng-Yu; Liu, Julie C

2016-08-01

Protein domains and peptide sequences are a powerful tool for conferring specific functions to engineered biomaterials. Protein sequences with a wide variety of functionalities, including structure, bioactivity, protein-protein interactions, and stimuli responsiveness, have been identified, and advances in molecular biology continue to pinpoint new sequences. Protein domains can be combined to make recombinant proteins with multiple functionalities. The high fidelity of the protein translation machinery results in exquisite control over the sequence of recombinant proteins and the resulting properties of protein-based materials. In this review, we discuss protein domains and peptide sequences in the context of functional protein-based materials, composite materials, and their biological applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

RNAcentral: A comprehensive database of non-coding RNA sequences

DOE PAGES

Williams, Kelly Porter; Lau, Britney Yan

2016-10-28

RNAcentral is a database of non-coding RNA (ncRNA) sequences that aggregates data from specialised ncRNA resources and provides a single entry point for accessing ncRNA sequences of all ncRNA types from all organisms. Since its launch in 2014, RNAcentral has integrated twelve new resources, taking the total number of collaborating database to 22, and began importing new types of data, such as modified nucleotides from MODOMICS and PDB. We created new species-specific identifiers that refer to unique RNA sequences within a context of single species. Furthermore, the website has been subject to continuous improvements focusing on text and sequence similaritymore » searches as well as genome browsing functionality.« less

RNAcentral: A comprehensive database of non-coding RNA sequences

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

Williams, Kelly Porter; Lau, Britney Yan

RNAcentral is a database of non-coding RNA (ncRNA) sequences that aggregates data from specialised ncRNA resources and provides a single entry point for accessing ncRNA sequences of all ncRNA types from all organisms. Since its launch in 2014, RNAcentral has integrated twelve new resources, taking the total number of collaborating database to 22, and began importing new types of data, such as modified nucleotides from MODOMICS and PDB. We created new species-specific identifiers that refer to unique RNA sequences within a context of single species. Furthermore, the website has been subject to continuous improvements focusing on text and sequence similaritymore » searches as well as genome browsing functionality.« less

The Locus analytical framework for indoor localization and tracking applications

NASA Astrophysics Data System (ADS)

Segou, Olga E.; Thomopoulos, Stelios C. A.

2015-05-01

Obtaining location information can be of paramount importance in the context of pervasive and context-aware computing applications. Many systems have been proposed to date, e.g. GPS that has been proven to offer satisfying results in outdoor areas. The increased effect of large and small scale fading in indoor environments, however, makes localization a challenge. This is particularly reflected in the multitude of different systems that have been proposed in the context of indoor localization (e.g. RADAR, Cricket etc). The performance of such systems is often validated on vastly different test beds and conditions, making performance comparisons difficult and often irrelevant. The Locus analytical framework incorporates algorithms from multiple disciplines such as channel modeling, non-uniform random number generation, computational geometry, localization, tracking and probabilistic modeling etc. in order to provide: (a) fast and accurate signal propagation simulation, (b) fast experimentation with localization and tracking algorithms and (c) an in-depth analysis methodology for estimating the performance limits of any Received Signal Strength localization system. Simulation results for the well-known Fingerprinting and Trilateration algorithms are herein presented and validated with experimental data collected in real conditions using IEEE 802.15.4 ZigBee modules. The analysis shows that the Locus framework accurately predicts the underlying distribution of the localization error and produces further estimates of the system's performance limitations (in a best-case/worst-case scenario basis).

Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

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

Bejerman, Nicolás, E-mail: n.bejerman@uq.edu.au; Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072; Giolitti, Fabián

Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cellmore » periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses.« less

Thysanophora penicillioides includes multiple genetically diverged groups that coexist respectively in Abies mariesii forests in Japan.

PubMed

Iwamoto, Susumu; Tokumasu, Seiji; Suyama, Yoshihisa; Kakishima, Makoto

2005-01-01

We investigated intraspecific diversity and genetic structures of a saprotrophic fungus--Thysanophora penicillioides--based on sequences of nuclear ribosomal internal transcribed spacer (ITS) in 15 discontinuous Abies mariesii forests of Japan. In such a well-defined morphological species, numerous unexpected ITS variations were revealed: 12 ITS sequence types detected in 254 isolates collected from 15 local populations were classified into five ITS sequence groups. Maximally, four ITS groups consisted of seven ITS types coexisting in one population. However, group 1 was dominant with approximately 65%; in particular, one haplotype, 1a, was most dominant with approximately 60% in respective populations. Therefore, few differences were recognized in genetic structure among local populations, implying that the gene flow of each lineage of the fungus occurs among local populations without geographic limitations. However, minor haplotypes in some ITS groups were found only in restricted areas, suggesting that they might expand steadily from their places of origin to neighboring A. mariesii forests. Aggregating sequence data of seven European strains and four North American strains from various substrates to those of Japanese strains, 18 ITS sequence types and 28 variable sites were recognized. They were clustered into nine lineages by phylogenetic analyses of the beta-tubulin and combined ITS and beta-tubulin datasets. According to phylogenetic species recognition by the concordance of genealogies, respective lineages correspond to phylogenetic species. Plural phylogenetic species coexist in a local population in an A. mariesii forest in Japan.

Neurophysiological correlates of relatively enhanced local visual search in autistic adolescents.

PubMed

Manjaly, Zina M; Bruning, Nicole; Neufang, Susanne; Stephan, Klaas E; Brieber, Sarah; Marshall, John C; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Fink, Gereon R

2007-03-01

Previous studies found normal or even superior performance of autistic patients on visuospatial tasks requiring local search, like the Embedded Figures Task (EFT). A well-known interpretation of this is "weak central coherence", i.e. autistic patients may show a reduced general ability to process information in its context and may therefore have a tendency to favour local over global aspects of information processing. An alternative view is that the local processing advantage in the EFT may result from a relative amplification of early perceptual processes which boosts processing of local stimulus properties but does not affect processing of global context. This study used functional magnetic resonance imaging (fMRI) in 12 autistic adolescents (9 Asperger and 3 high-functioning autistic patients) and 12 matched controls to help distinguish, on neurophysiological grounds, between these two accounts of EFT performance in autistic patients. Behaviourally, we found autistic individuals to be unimpaired during the EFT while they were significantly worse at performing a closely matched control task with minimal local search requirements. The fMRI results showed that activations specific for the local search aspects of the EFT were left-lateralised in parietal and premotor areas for the control group (as previously demonstrated for adults), whereas for the patients these activations were found in right primary visual cortex and bilateral extrastriate areas. These results suggest that enhanced local processing in early visual areas, as opposed to impaired processing of global context, is characteristic for performance of the EFT by autistic patients.

Neurophysiological correlates of relatively enhanced local visual search in autistic adolescents

PubMed Central

Manjaly, Zina M.; Bruning, Nicole; Neufang, Susanne; Stephan, Klaas E.; Brieber, Sarah; Marshall, John C.; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Fink, Gereon R.

2007-01-01

Previous studies found normal or even superior performance of autistic patients on visuospatial tasks requiring local search, like the Embedded Figures Task (EFT). A well-known interpretation of this is “weak central coherence”, i.e. autistic patients may show a reduced general ability to process information in its context and may therefore have a tendency to favour local over global aspects of information processing. An alternative view is that the local processing advantage in the EFT may result from a relative amplification of early perceptual processes which boosts processing of local stimulus properties but does not affect processing of global context. This study used functional magnetic resonance imaging (fMRI) in 12 autistic adolescents (9 Asperger and 3 high-functioning autistic patients) and 12 matched controls to help distinguish, on neurophysiological grounds, between these two accounts of EFT performance in autistic patients. Behaviourally, we found autistic individuals to be unimpaired during the EFT while they were significantly worse at performing a closely matched control task with minimal local search requirements. The fMRI results showed that activations specific for the local search aspects of the EFT were left-lateralised in parietal and premotor areas for the control group (as previously demonstrated for adults), whereas for the patients these activations were found in right primary visual cortex and bilateral extrastriate areas. These results suggest that enhanced local processing in early visual areas, as opposed to impaired processing of global context, is characteristic for performance of the EFT by autistic patients. PMID:17240169

Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes.

PubMed

Grandi, Nicole; Cadeddu, Marta; Blomberg, Jonas; Tramontano, Enzo

2016-09-09

Human endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies. In the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported. The present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date.

A modern regional geological analysis of Venezuela - lessons from a major new world oil province on exploration in mature areas

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

Daly, M.; Audemard, F.; Valdes, G.

1993-09-01

Venezuela has produced some 44 billion bbl of oil since the early part of the century. As such, it represents one of the world's major oil producers and a mature petroleum province. However, major tracts of Venezuela's sedimentary basins remain underexplored and large discoveries are still being made in new and old reservoir systems. A regional geological analysis of Venezuela, focusing on basin evolution and sequence stratigraphy and incorporating data from the three national oil companies, is presented. The analysis presents a regionally consistent tectonostratigraphic model capable of explaining the evolution of the Mesozoic and Cenozoic basins of Venezuela andmore » placing the major reservoir facies in their regional tectonic and sequence stratigraphic context. Four regional cross sections describe the stratigraphic and structural model. The model recognizes a Jurassic rifting event and inversion, succeeded by an Early Cretaceous passive margin. In western Venezuela, the Early Cretaceous passive subsidence is enhanced locally by extension related to the Colombian active margin. Venezuela experienced a major change in the Campanian with the initial collision of the Caribbean arc, recorded by foreland structuring and widespread stratigraphic changes. From the Campanian onward, the tectonostratigraphic evolution can be modeled in terms of a progressive southeast-directed arc-continent collision and the migration of the associated foredeep and rift basins. Within the tectonic framework, the major sequence stratigraphic units are identified and the reservoir distribution interpreted. This model provides a strong predictive tool to extrapolate reservoir systems into Venezuela's underexplored areas and to readdress its traditional areas.« less

Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance

PubMed Central

Ip, Camilla L. C.; Ansari, M. Azim; Wilson, Daniel J.; Espedido, Bjorn A.; Jensen, Slade O.; Bowden, Rory

2016-01-01

Enterococcus faecium, a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics of E. faecium in a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing. E. faecium was found to be subject to high rates of recombination with little evidence of sequence importation from outside the local E. faecium population. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology of E. faecium nosocomial infections and establishing routes of transmission. Several forms of the Tn1549-like element–vanB gene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances of in situ evolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium with evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient transmission events, underlining the need for careful consideration before modifying current E. faecium infection control strategies. PMID:27713836

Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance.

PubMed

van Hal, Sebastiaan J; Ip, Camilla L C; Ansari, M Azim; Wilson, Daniel J; Espedido, Bjorn A; Jensen, Slade O; Bowden, Rory

2016-01-19

Enterococcus faecium , a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics of E. faecium in a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing. E. faecium was found to be subject to high rates of recombination with little evidence of sequence importation from outside the local E. faecium population. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology of E. faecium nosocomial infections and establishing routes of transmission. Several forms of the Tn 1549 -like element- vanB gene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances of in situ evolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium with evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient transmission events, underlining the need for careful consideration before modifying current E. faecium infection control strategies.

Protein location prediction using atomic composition and global features of the amino acid sequence

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

Cherian, Betsy Sheena, E-mail: betsy.skb@gmail.com; Nair, Achuthsankar S.

2010-01-22

Subcellular location of protein is constructive information in determining its function, screening for drug candidates, vaccine design, annotation of gene products and in selecting relevant proteins for further studies. Computational prediction of subcellular localization deals with predicting the location of a protein from its amino acid sequence. For a computational localization prediction method to be more accurate, it should exploit all possible relevant biological features that contribute to the subcellular localization. In this work, we extracted the biological features from the full length protein sequence to incorporate more biological information. A new biological feature, distribution of atomic composition is effectivelymore » used with, multiple physiochemical properties, amino acid composition, three part amino acid composition, and sequence similarity for predicting the subcellular location of the protein. Support Vector Machines are designed for four modules and prediction is made by a weighted voting system. Our system makes prediction with an accuracy of 100, 82.47, 88.81 for self-consistency test, jackknife test and independent data test respectively. Our results provide evidence that the prediction based on the biological features derived from the full length amino acid sequence gives better accuracy than those derived from N-terminal alone. Considering the features as a distribution within the entire sequence will bring out underlying property distribution to a greater detail to enhance the prediction accuracy.« less

Exploring codon context bias for synthetic gene design of a thermostable invertase in Escherichia coli.

PubMed

Pek, Han Bin; Klement, Maximilian; Ang, Kok Siong; Chung, Bevan Kai-Sheng; Ow, Dave Siak-Wei; Lee, Dong-Yup

2015-01-01

Various isoforms of invertases from prokaryotes, fungi, and higher plants has been expressed in Escherichia coli, and codon optimisation is a widely-adopted strategy for improvement of heterologous enzyme expression. Successful synthetic gene design for recombinant protein expression can be done by matching its translational elongation rate against heterologous host organisms via codon optimization. Amongst the various design parameters considered for the gene synthesis, codon context bias has been relatively overlooked compared to individual codon usage which is commonly adopted in most of codon optimization tools. In addition, matching the rates of transcription and translation based on secondary structure may lead to enhanced protein folding. In this study, we evaluated codon context fitness as design criterion for improving the expression of thermostable invertase from Thermotoga maritima in Escherichia coli and explored the relevance of secondary structure regions for folding and expression. We designed three coding sequences by using (1) a commercial vendor optimized gene algorithm, (2) codon context for the whole gene, and (3) codon context based on the secondary structure regions. Then, the codon optimized sequences were transformed and expressed in E. coli. From the resultant enzyme activities and protein yield data, codon context fitness proved to have the highest activity as compared to the wild-type control and other criteria while secondary structure-based strategy is comparable to the control. Codon context bias was shown to be a relevant parameter for enhancing enzyme production in Escherichia coli by codon optimization. Thus, we can effectively design synthetic genes within heterologous host organisms using this criterion. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiple splicing defects in an intronic false exon.

PubMed

Sun, H; Chasin, L A

2000-09-01

Splice site consensus sequences alone are insufficient to dictate the recognition of real constitutive splice sites within the typically large transcripts of higher eukaryotes, and large numbers of pseudoexons flanked by pseudosplice sites with good matches to the consensus sequences can be easily designated. In an attempt to identify elements that prevent pseudoexon splicing, we have systematically altered known splicing signals, as well as immediately adjacent flanking sequences, of an arbitrarily chosen pseudoexon from intron 1 of the human hprt gene. The substitution of a 5' splice site that perfectly matches the 5' consensus combined with mutation to match the CAG/G sequence of the 3' consensus failed to get this model pseudoexon included as the central exon in a dhfr minigene context. Provision of a real 3' splice site and a consensus 5' splice site and removal of an upstream inhibitory sequence were necessary and sufficient to confer splicing on the pseudoexon. This activated context also supported the splicing of a second pseudoexon sequence containing no apparent enhancer. Thus, both the 5' splice site sequence and the polypyrimidine tract of the pseudoexon are defective despite their good agreement with the consensus. On the other hand, the pseudoexon body did not exert a negative influence on splicing. The introduction into the pseudoexon of a sequence selected for binding to ASF/SF2 or its replacement with beta-globin exon 2 only partially reversed the effect of the upstream negative element and the defective polypyrimidine tract. These results support the idea that exon-bridging enhancers are not a prerequisite for constitutive exon definition and suggest that intrinsically defective splice sites and negative elements play important roles in distinguishing the real splicing signal from the vast number of false splicing signals.

Low-power adiabatic sequences for in-vivo localized two-dimensional chemical shift correlated MR spectroscopy

PubMed Central

Andronesi, Ovidiu C.; Ramadan, Saadallah; Mountford, Carolyn E.; Sorensen, A. Gregory

2011-01-01

Novel low-power adiabatic sequences are demonstrated for in-vivo localized two-dimensional (2D) correlated MR spectroscopy, such as COSY (Correlated Spectroscopy) and TOCSY (Total Correlated Spectroscopy). The design is based on three new elements for in-vivo 2D MRS: the use of gradient modulated constant adiabaticity GOIA-W(16,4) pulses for i) localization (COSY and TOCSY) and ii) mixing (TOCSY), and iii) the use of longitudinal mixing (z-filter) for magnetization transfer during TOCSY. GOIA-W(16,4) provides accurate signal localization, and more importantly, lowers the SAR for both TOCSY mixing and localization. Longitudinal mixing improves considerably (five-folds) the efficiency of TOCSY transfer. These are markedly different from previous 1D editing TOCSY sequences using spatially non-selective pulses and transverse mixing. Fully adiabatic (adiabatic mixing with adiabatic localization) and semi-adiabatic (adiabatic mixing with non-adiabatic localization) methods for 2D TOCSY are compared. Results are presented for simulations, phantoms, and in-vivo 2D spectra from healthy volunteers and patients with brain tumors obtained on 3T clinical platforms equipped with standard hardware. To the best of our knowledge this is the first demonstration of in-vivo adiabatic 2D TOCSY and fully adiabatic 2D COSY. It is expected that these methodological developments will advance the in-vivo applicability of multi(spectrally)dimensional MRS to reliably identify metabolic biomarkers. PMID:20890988

Distinct Sequence Elements of Cyclin B1 Promote Localization to Chromatin, Centrosomes, and Kinetochores during Mitosis

PubMed Central

Bentley, Anna M.; Normand, Guillaume; Hoyt, Jonathan

2007-01-01

The mitotic cyclins promote cell division by binding and activating cyclin-dependent kinases (CDKs). Each cyclin has a unique pattern of subcellular localization that plays a vital role in regulating cell division. During mitosis, cyclin B1 is known to localize to centrosomes, microtubules, and chromatin. To determine the mechanisms of cyclin B1 localization in M phase, we imaged full-length and mutant versions of human cyclin B1-enhanced green fluorescent protein in live cells by using spinning disk confocal microscopy. In addition to centrosome, microtubule, and chromatin localization, we found that cyclin B1 also localizes to unattached kinetochores after nuclear envelope breakdown. Kinetochore recruitment of cyclin B1 required the kinetochore proteins Hec1 and Mad2, and it was stimulated by microtubule destabilization. Mutagenesis studies revealed that cyclin B1 is recruited to kinetochores through both CDK1-dependent and -independent mechanisms. In contrast, localization of cyclin B1 to chromatin and centrosomes is independent of CDK1 binding. The N-terminal domain of cyclin B1 is necessary and sufficient for chromatin association, whereas centrosome recruitment relies on sequences within the cyclin box. Our data support a role for cyclin B1 function at unattached kinetochores, and they demonstrate that separable and distinct sequence elements target cyclin B1 to kinetochores, chromatin, and centrosomes during mitosis. PMID:17881737

33 CFR 385.30 - Master Implementation Sequencing Plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Master Implementation Sequencing... Incorporating New Information Into the Plan § 385.30 Master Implementation Sequencing Plan. (a) Not later than... of Environmental Protection, and other Federal, State, and local agencies, develop a Master...

33 CFR 385.30 - Master Implementation Sequencing Plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Master Implementation Sequencing... Incorporating New Information Into the Plan § 385.30 Master Implementation Sequencing Plan. (a) Not later than... of Environmental Protection, and other Federal, State, and local agencies, develop a Master...

33 CFR 385.30 - Master Implementation Sequencing Plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Master Implementation Sequencing... Incorporating New Information Into the Plan § 385.30 Master Implementation Sequencing Plan. (a) Not later than... of Environmental Protection, and other Federal, State, and local agencies, develop a Master...

Next-generation sequencing for targeted discovery of rare mutations in rice

USDA-ARS?s Scientific Manuscript database

Advances in DNA sequencing (i.e., next-generation sequencing, NGS) have greatly increased the power and efficiency of detecting rare mutations in large mutant populations. Targeting Induced Local Lesions in Genomes (TILLING) is a reverse genetics approach for identifying gene mutations resulting fro...

Input-Specific Gain Modulation by Local Sensory Context Shapes Cortical and Thalamic Responses to Complex Sounds.

PubMed

Williamson, Ross S; Ahrens, Misha B; Linden, Jennifer F; Sahani, Maneesh

2016-07-20

Sensory neurons are customarily characterized by one or more linearly weighted receptive fields describing sensitivity in sensory space and time. We show that in auditory cortical and thalamic neurons, the weight of each receptive field element depends on the pattern of sound falling within a local neighborhood surrounding it in time and frequency. Accounting for this change in effective receptive field with spectrotemporal context improves predictions of both cortical and thalamic responses to stationary complex sounds. Although context dependence varies among neurons and across brain areas, there are strong shared qualitative characteristics. In a spectrotemporally rich soundscape, sound elements modulate neuronal responsiveness more effectively when they coincide with sounds at other frequencies, and less effectively when they are preceded by sounds at similar frequencies. This local-context-driven lability in the representation of complex sounds-a modulation of "input-specific gain" rather than "output gain"-may be a widespread motif in sensory processing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes

PubMed Central

Fong, Christine; Rohmer, Laurence; Radey, Matthew; Wasnick, Michael; Brittnacher, Mitchell J

2008-01-01

Background The conservation of gene order among prokaryotic genomes can provide valuable insight into gene function, protein interactions, or events by which genomes have evolved. Although some tools are available for visualizing and comparing the order of genes between genomes of study, few support an efficient and organized analysis between large numbers of genomes. The Prokaryotic Sequence homology Analysis Tool (PSAT) is a web tool for comparing gene neighborhoods among multiple prokaryotic genomes. Results PSAT utilizes a database that is preloaded with gene annotation, BLAST hit results, and gene-clustering scores designed to help identify regions of conserved gene order. Researchers use the PSAT web interface to find a gene of interest in a reference genome and efficiently retrieve the sequence homologs found in other bacterial genomes. The tool generates a graphic of the genomic neighborhood surrounding the selected gene and the corresponding regions for its homologs in each comparison genome. Homologs in each region are color coded to assist users with analyzing gene order among various genomes. In contrast to common comparative analysis methods that filter sequence homolog data based on alignment score cutoffs, PSAT leverages gene context information for homologs, including those with weak alignment scores, enabling a more sensitive analysis. Features for constraining or ordering results are designed to help researchers browse results from large numbers of comparison genomes in an organized manner. PSAT has been demonstrated to be useful for helping to identify gene orthologs and potential functional gene clusters, and detecting genome modifications that may result in loss of function. Conclusion PSAT allows researchers to investigate the order of genes within local genomic neighborhoods of multiple genomes. A PSAT web server for public use is available for performing analyses on a growing set of reference genomes through any web browser with no client side software setup or installation required. Source code is freely available to researchers interested in setting up a local version of PSAT for analysis of genomes not available through the public server. Access to the public web server and instructions for obtaining source code can be found at . PMID:18366802

Reprint of: Initial uncertainty impacts statistical learning in sound sequence processing.

PubMed

Todd, Juanita; Provost, Alexander; Whitson, Lisa; Mullens, Daniel

2018-05-18

This paper features two studies confirming a lasting impact of first learning on how subsequent experience is weighted in early relevance-filtering processes. In both studies participants were exposed to sequences of sound that contained a regular pattern on two different timescales. Regular patterning in sound is readily detected by the auditory system and used to form "prediction models" that define the most likely properties of sound to be encountered in a given context. The presence and strength of these prediction models is inferred from changes in automatically elicited components of auditory evoked potentials. Both studies employed sound sequences that contained both a local and longer-term pattern. The local pattern was defined by a regular repeating pure tone occasionally interrupted by a rare deviating tone (p=0.125) that was physically different (a 30msvs. 60ms duration difference in one condition and a 1000Hz vs. 1500Hz frequency difference in the other). The longer-term pattern was defined by the rate at which the two tones alternated probabilities (i.e., the tone that was first rare became common and the tone that was first common became rare). There was no task related to the tones and participants were asked to ignore them while focussing attention on a movie with subtitles. Auditory-evoked potentials revealed long lasting modulatory influences based on whether the tone was initially encountered as rare and unpredictable or common and predictable. The results are interpreted as evidence that probability (or indeed predictability) assigns a differential information-value to the two tones that in turn affects the extent to which prediction models are updated and imposed. These effects are exposed for both common and rare occurrences of the tones. The studies contribute to a body of work that reveals that probabilistic information is not faithfully represented in these early evoked potentials and instead exposes that predictability (or conversely uncertainty) may trigger value-based learning modulations even in task-irrelevant incidental learning. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Personal Genome Sequencing in Ostensibly Healthy Individuals and the PeopleSeq Consortium

PubMed Central

Linderman, Michael D.; Nielsen, Daiva E.; Green, Robert C.

2016-01-01

Thousands of ostensibly healthy individuals have had their exome or genome sequenced, but a much smaller number of these individuals have received any personal genomic results from that sequencing. We term those projects in which ostensibly healthy participants can receive sequencing-derived genetic findings and may also have access to their genomic data as participatory predispositional personal genome sequencing (PPGS). Here we are focused on genome sequencing applied in a pre-symptomatic context and so define PPGS to exclude diagnostic genome sequencing intended to identify the molecular cause of suspected or diagnosed genetic disease. In this report we describe the design of completed and underway PPGS projects, briefly summarize the results reported to date and introduce the PeopleSeq Consortium, a newly formed collaboration of PPGS projects designed to collect much-needed longitudinal outcome data. PMID:27023617

Augmenting Usability: Cultural Elicitation in HCI

NASA Astrophysics Data System (ADS)

Camara, Souleymane Boundaouda; Oyugi, Cecilia; Abdelnour-Nocera, José; Smith, Andy

This paper offers context and culture elicitation in an inter-cultural and multi-disciplinary setting of ICT design. Localised usability evaluation (LUE) is augmented with a socio-technical evaluation tool (STEM) as a methodological approach to expose and address issues in a collaborative ICT design within the Village e-Science for Life (VeSeL) project in rural Kenya. The paper argues that designers need to locally identify context and culture in situ and further explicate their implications through the design process and at the global level. Stakeholders' context, culture, decisions, agendas, expectations, disciplines and requirements need to be locally identified and globally evaluated to ensure a fit for purpose solution.

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.

Identification of two internal signal peptide sequences: critical for classical swine fever virus non-structural protein 2 to trans-localize to the endoplasmic reticulum.

PubMed

Guo, Kang-kang; Tang, Qing-hai; Zhang, Yan-ming; Kang, Kai; He, Lei

2011-05-18

The membrane topology and molecular mechanisms for endoplasmic reticulum (ER) localization of classical swine fever virus (CSFV) non-structural 2 (NS2) protien is unclear. We attempted to elucidate the subcellular localization, and the molecular mechanisms responsible for the localization of this protein in our study. The NS2 gene was amplified by reverse transcription polymerase chain reaction, with the transmembrane region and hydrophilicity of the NS2 protein was predicted by bioinformatics analysis. Twelve cDNAs of the NS2 gene were amplified by the PCR deletion method and cloned into a eukaryotic expression vector, which was transfected into a swine umbilical vein endothelial cell line (SUVEC). Subcellular localization of the NS2 protein was characterized by confocal microscopy, and western blots were carried out to analyze protein expression. Our results showed that the -NH2 terminal of the CSFV NS2 protein was highly hydrophobic and the protein localized in the ER. At least four transmembrane regions and two internal signal peptide sequences (amino acids103-138 and 220-262) were identified and thought to be critical for its trans-localization to the ER. This is the first study to identify the internal signal peptide sequences of the CSFV NS2 protein and its subcellular localization, providing the foundation for further exploration of this protein's function of this protein and its role in CSFV pathogenesis.

Protein subcellular localization prediction using artificial intelligence technology.

PubMed

Nair, Rajesh; Rost, Burkhard

2008-01-01

Proteins perform many important tasks in living organisms, such as catalysis of biochemical reactions, transport of nutrients, and recognition and transmission of signals. The plethora of aspects of the role of any particular protein is referred to as its "function." One aspect of protein function that has been the target of intensive research by computational biologists is its subcellular localization. Proteins must be localized in the same subcellular compartment to cooperate toward a common physiological function. Aberrant subcellular localization of proteins can result in several diseases, including kidney stones, cancer, and Alzheimer's disease. To date, sequence homology remains the most widely used method for inferring the function of a protein. However, the application of advanced artificial intelligence (AI)-based techniques in recent years has resulted in significant improvements in our ability to predict the subcellular localization of a protein. The prediction accuracy has risen steadily over the years, in large part due to the application of AI-based methods such as hidden Markov models (HMMs), neural networks (NNs), and support vector machines (SVMs), although the availability of larger experimental datasets has also played a role. Automatic methods that mine textual information from the biological literature and molecular biology databases have considerably sped up the process of annotation for proteins for which some information regarding function is available in the literature. State-of-the-art methods based on NNs and HMMs can predict the presence of N-terminal sorting signals extremely accurately. Ab initio methods that predict subcellular localization for any protein sequence using only the native amino acid sequence and features predicted from the native sequence have shown the most remarkable improvements. The prediction accuracy of these methods has increased by over 30% in the past decade. The accuracy of these methods is now on par with high-throughput methods for predicting localization, and they are beginning to play an important role in directing experimental research. In this chapter, we review some of the most important methods for the prediction of subcellular localization.

The Formation of Learners' Motivation to Study Physics in Terms of Sustainable Development of Education in Ukraine

ERIC Educational Resources Information Center

Korsun, Igor

2017-01-01

This study is aimed at creating a general technique for the formation of learners' interest in physics in the context of sustainable development of education. The active means of training and active learning methods are the components of this technique. The sequence of interest formation for physics in the context of sustainable development of…

Clustalnet: the joining of Clustal and CORBA.

PubMed

Campagne, F

2000-07-01

Performing sequence alignment operations from a different program than the original sequence alignment code, and/or through a network connection, is often required. Interactive alignment editors and large-scale biological data analysis are common examples where such a flexibility is important. Interoperability between the alignment engine and the client should be obtained regardless of the architectures and programming languages of the server and client. Clustalnet, a Clustal alignment CORBA server is described, which was developed on the basis of Clustalw. This server brings the robustness of the algorithms and implementations of Clustal to a new level of reuse. A Clustalnet server object can be accessed from a program, transparently through the network. We present interfaces to perform the alignment operations and to control these operations via immutable contexts. The interfaces that select the contexts do not depend on the nature of the operation to be performed, making the design modular. The IDL interfaces presented here are not specific to Clustal and can be implemented on top of different sequence alignment algorithm implementations.

Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.

PubMed

Dominguez, Daniel; Freese, Peter; Alexis, Maria S; Su, Amanda; Hochman, Myles; Palden, Tsultrim; Bazile, Cassandra; Lambert, Nicole J; Van Nostrand, Eric L; Pratt, Gabriel A; Yeo, Gene W; Graveley, Brenton R; Burge, Christopher B

2018-06-07

RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by deep sequencing of bound RNAs. These data enable construction of "RNA maps" of RBP activity without requiring crosslinking-based assays. We found an unexpectedly low diversity of RNA motifs, implying frequent convergence of binding specificity toward a relatively small set of RNA motifs, many with low compositional complexity. Offsetting this trend, however, we observed extensive preferences for contextual features distinct from short linear RNA motifs, including spaced "bipartite" motifs, biased flanking nucleotide composition, and bias away from or toward RNA structure. Our results emphasize the importance of contextual features in RNA recognition, which likely enable targeting of distinct subsets of transcripts by different RBPs that recognize the same linear motif. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Reducing DNA context dependence in bacterial promoters

PubMed Central

Carr, Swati B.; Densmore, Douglas M.

2017-01-01

Variation in the DNA sequence upstream of bacterial promoters is known to affect the expression levels of the products they regulate, sometimes dramatically. While neutral synthetic insulator sequences have been found to buffer promoters from upstream DNA context, there are no established methods for designing effective insulator sequences with predictable effects on expression levels. We address this problem with Degenerate Insulation Screening (DIS), a novel method based on a randomized 36-nucleotide insulator library and a simple, high-throughput, flow-cytometry-based screen that randomly samples from a library of 436 potential insulated promoters. The results of this screen can then be compared against a reference uninsulated device to select a set of insulated promoters providing a precise level of expression. We verify this method by insulating the constitutive, inducible, and repressible promotors of a four transcriptional-unit inverter (NOT-gate) circuit, finding both that order dependence is largely eliminated by insulation and that circuit performance is also significantly improved, with a 5.8-fold mean improvement in on/off ratio. PMID:28422998

The right inferior frontal gyrus processes nested non-local dependencies in music.

PubMed

Cheung, Vincent K M; Meyer, Lars; Friederici, Angela D; Koelsch, Stefan

2018-02-28

Complex auditory sequences known as music have often been described as hierarchically structured. This permits the existence of non-local dependencies, which relate elements of a sequence beyond their temporal sequential order. Previous studies in music have reported differential activity in the inferior frontal gyrus (IFG) when comparing regular and irregular chord-transitions based on theories in Western tonal harmony. However, it is unclear if the observed activity reflects the interpretation of hierarchical structure as the effects are confounded by local irregularity. Using functional magnetic resonance imaging (fMRI), we found that violations to non-local dependencies in nested sequences of three-tone musical motifs in musicians elicited increased activity in the right IFG. This is in contrast to similar studies in language which typically report the left IFG in processing grammatical syntax. Effects of increasing auditory working demands are moreover reflected by distributed activity in frontal and parietal regions. Our study therefore demonstrates the role of the right IFG in processing non-local dependencies in music, and suggests that hierarchical processing in different cognitive domains relies on similar mechanisms that are subserved by domain-selective neuronal subpopulations.

Dynamic learning and context-dependence in sequential, attribute-based, stated-preference valuation questions

Treesearch

Thomas P. Holmes; Kevin J. Boyle

2005-01-01

A hybrid stated-preference model is presented that combines the referendum contingent valuation response format with an experimentally designed set of attributes. A sequence of valuation questions is asked to a random sample in a mailout mail-back format. Econometric analysis shows greater discrimination between alternatives in the final choice in the sequence, and the...

The Effect of Sequence of Instruction on Students' Cognitive Preferences and Recall in the Context of a Problem-Oriented Method of Teaching.

ERIC Educational Resources Information Center

Boreham, N. C.; And Others

1985-01-01

This study investigated the effects of two sequences of instruction--theory-to-application and application-to-theory--on medical students' cognitive preferences in preclinical science teaching. Results indicate that presenting an example of the clinical application of biochemical theory before presenting the theory itself increased students'…

Transferring a Teaching Learning Sequence between Two Different Educational Contexts: The Case of Greece and Finland

ERIC Educational Resources Information Center

Spyrtou, Anna; Lavonen, Jari; Zoupidis, Anastasios; Loukomies, Anni; Pnevmatikos, Dimitris; Juuti, Kalle; Kariotoglou, Petros

2018-01-01

In the present paper, we report on the idea of exchanging educational innovations across European countries aiming to shed light on the following question: how feasible and useful is it to transfer an innovation across different national educational settings? The innovation, in this case, Inquiry-Based Teaching Learning Sequences, is recognized as…

Exploring Insight: Focus on Shifts of Attention

ERIC Educational Resources Information Center

Palatnik, Alik; Koichu, Boris

2015-01-01

The paper presents and analyses a sequence of events that preceded an insight solution to a challenging problem in the context of numerical sequences. A three­week long solution process by a pair of ninth­-grade students is analysed by means of the theory of shifts of attention. The goal for this article is to reveal the potential of this theory…

Accounting for rate-dependent category boundary shifts in speech perception.

PubMed

Bosker, Hans Rutger

2017-01-01

The perception of temporal contrasts in speech is known to be influenced by the speech rate in the surrounding context. This rate-dependent perception is suggested to involve general auditory processes because it is also elicited by nonspeech contexts, such as pure tone sequences. Two general auditory mechanisms have been proposed to underlie rate-dependent perception: durational contrast and neural entrainment. This study compares the predictions of these two accounts of rate-dependent speech perception by means of four experiments, in which participants heard tone sequences followed by Dutch target words ambiguous between /ɑs/ "ash" and /a:s/ "bait". Tone sequences varied in the duration of tones (short vs. long) and in the presentation rate of the tones (fast vs. slow). Results show that the duration of preceding tones did not influence target perception in any of the experiments, thus challenging durational contrast as explanatory mechanism behind rate-dependent perception. Instead, the presentation rate consistently elicited a category boundary shift, with faster presentation rates inducing more /a:s/ responses, but only if the tone sequence was isochronous. Therefore, this study proposes an alternative, neurobiologically plausible account of rate-dependent perception involving neural entrainment of endogenous oscillations to the rate of a rhythmic stimulus.

RISC RNA sequencing for context-specific identification of in vivo microRNA targets.

PubMed

Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

2011-01-07

MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing "seed" sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state.

Does Discourse Congruence Influence Spoken Language Comprehension before Lexical Association? Evidence from Event-Related Potentials

PubMed Central

Boudewyn, Megan A.; Gordon, Peter C.; Long, Debra; Polse, Lara; Swaab, Tamara Y.

2011-01-01

The goal of this study was to examine how lexical association and discourse congruence affect the time course of processing incoming words in spoken discourse. In an ERP norming study, we presented prime-target pairs in the absence of a sentence context to obtain a baseline measure of lexical priming. We observed a typical N400 effect when participants heard critical associated and unassociated target words in word pairs. In a subsequent experiment, we presented the same word pairs in spoken discourse contexts. Target words were always consistent with the local sentence context, but were congruent or not with the global discourse (e.g., “Luckily Ben had picked up some salt and pepper/basil”, preceded by a context in which Ben was preparing marinara sauce (congruent) or dealing with an icy walkway (incongruent). ERP effects of global discourse congruence preceded those of local lexical association, suggesting an early influence of the global discourse representation on lexical processing, even in locally congruent contexts. Furthermore, effects of lexical association occurred earlier in the congruent than incongruent condition. These results differ from those that have been obtained in studies of reading, suggesting that the effects may be unique to spoken word recognition. PMID:23002319

Ultrasonic Multiple-Access Ranging System Using Spread Spectrum and MEMS Technology for Indoor Localization

PubMed Central

Segers, Laurent; Tiete, Jelmer; Braeken, An; Touhafi, Abdellah

2014-01-01

Indoor localization of persons and objects poses a great engineering challenge. Previously developed localization systems demonstrate the use of wideband techniques in ultrasound ranging systems. Direct sequence and frequency hopping spread spectrum ultrasound signals have been proven to achieve a high level of accuracy. A novel ranging method using the frequency hopping spread spectrum with finite impulse response filtering will be investigated and compared against the direct sequence spread spectrum. In the first setup, distances are estimated in a single-access environment, while in the second setup, two senders and one receiver are used. During the experiments, the micro-electromechanical systems are used as ultrasonic sensors, while the senders were implemented using field programmable gate arrays. Results show that in a single-access environment, the direct sequence spread spectrum method offers slightly better accuracy and precision performance compared to the frequency hopping spread spectrum. When two senders are used, measurements point out that the frequency hopping spread spectrum is more robust to near-far effects than the direct sequence spread spectrum. PMID:24553084

Applications of Single-Cell Sequencing for Multiomics.

PubMed

Xu, Yungang; Zhou, Xiaobo

2018-01-01

Single-cell sequencing interrogates the sequence or chromatin information from individual cells with advanced next-generation sequencing technologies. It provides a higher resolution of cellular differences and a better understanding of the underlying genetic and epigenetic mechanisms of an individual cell in the context of its survival and adaptation to microenvironment. However, it is more challenging to perform single-cell sequencing and downstream data analysis, owing to the minimal amount of starting materials, sample loss, and contamination. In addition, due to the picogram level of the amount of nucleic acids used, heavy amplification is often needed during sample preparation of single-cell sequencing, resulting in the uneven coverage, noise, and inaccurate quantification of sequencing data. All these unique properties raise challenges in and thus high demands for computational methods that specifically fit single-cell sequencing data. We here comprehensively survey the current strategies and challenges for multiple single-cell sequencing, including single-cell transcriptome, genome, and epigenome, beginning with a brief introduction to multiple sequencing techniques for single cells.

Can legality verification enhace local rights to forest resources? Piloting the policy learning protocol in the Peruvian forest context

Treesearch

B. Cashore; I. Visseren-Hamakers; P. Caro Torres; W. de Jong; A. Denvir; D. Humphreys; Kathleen McGinley; G. Auld; S. Lupberger; C. McDermott; S. Sax; D. Yin

2016-01-01

This report, “Can Legality Verification Enhance Local Rights to Forest Resources? Piloting the policy learning protocol in the Peruvian forest context,” reports on the testing of the application of the 11-step Policy Learning Protocol in Peru in 2015-16. The Protocol (Cashore et al. 2014) enables actors to draw from international policy initiatives in order to improve...

Narratives of Food Insecurity in Tippecanoe County, Indiana: Economic Constraints in Local Meanings of Hunger.

PubMed

Dutta, Mohan Jyoti; Hingson, LaReina; Anaele, Agaptus; Sen, Soumitro; Jones, Kyle

2016-01-01

Food insecurity and its most extreme form, hunger, have increased exponentially in the United States since 2006. This essay seeks to contribute to our understanding of hunger by attending to the context of the financial crisis as an organizing frame for understanding local meanings of hunger. Within a broader framework of the culture-centered approach (CCA) that works to identify and develop locally rooted solutions to food insecurity, we describe through locally grounded stories of food insecurity the financial climate where large percentages of U.S. households have been cast into poverty because of the crash of an unregulated economy. These local understandings of hunger in the context of the economy offer entry points for organizing a food-insecure coalition that seeks to address the stigma around food insecurity.

Effectiveness of sodium azide alone compared to sodium azide in combination with methyl nitrosurea for rice mutagenesis

USDA-ARS?s Scientific Manuscript database

Rice seeds of the temperate japonica cultivar Kitaake were mutagenized with sodium azide alone and in combination with methyl nitrosourea. Using the reduced representation sequencing method Restriction Enzyme Sequence Comparative Analysis (RESCAN), the mutation densities, types and local sequence co...

Local backbone structure prediction of proteins

PubMed Central

De Brevern, Alexandre G.; Benros, Cristina; Gautier, Romain; Valadié, Hélène; Hazout, Serge; Etchebest, Catherine

2004-01-01

Summary A statistical analysis of the PDB structures has led us to define a new set of small 3D structural prototypes called Protein Blocks (PBs). This structural alphabet includes 16 PBs, each one is defined by the (φ, Ψ) dihedral angles of 5 consecutive residues. The amino acid distributions observed in sequence windows encompassing these PBs are used to predict by a Bayesian approach the local 3D structure of proteins from the sole knowledge of their sequences. LocPred is a software which allows the users to submit a protein sequence and performs a prediction in terms of PBs. The prediction results are given both textually and graphically. PMID:15724288

Ancient DNA reveals the Arctic origin of Viking Age cod from Haithabu, Germany

PubMed Central

Star, Bastiaan; Boessenkool, Sanne; Gondek, Agata T.; Nikulina, Elena A.; Hufthammer, Anne Karin; Pampoulie, Christophe; Knutsen, Halvor; André, Carl; Nistelberger, Heidi M.; Dierking, Jan; Petereit, Christoph; Heinrich, Dirk; Jakobsen, Kjetill S.; Stenseth, Nils Chr.; Jentoft, Sissel

2017-01-01

Knowledge of the range and chronology of historic trade and long-distance transport of natural resources is essential for determining the impacts of past human activities on marine environments. However, the specific biological sources of imported fauna are often difficult to identify, in particular if species have a wide spatial distribution and lack clear osteological or isotopic differentiation between populations. Here, we report that ancient fish-bone remains, despite being porous, brittle, and light, provide an excellent source of endogenous DNA (15–46%) of sufficient quality for whole-genome reconstruction. By comparing ancient sequence data to that of modern specimens, we determine the biological origin of 15 Viking Age (800–1066 CE) and subsequent medieval (1066–1280 CE) Atlantic cod (Gadus morhua) specimens from excavation sites in Germany, Norway, and the United Kingdom. Archaeological context indicates that one of these sites was a fishing settlement for the procurement of local catches, whereas the other localities were centers of trade. Fish from the trade sites show a mixed ancestry and are statistically differentiated from local fish populations. Moreover, Viking Age samples from Haithabu, Germany, are traced back to the North East Arctic Atlantic cod population that has supported the Lofoten fisheries of Norway for centuries. Our results resolve a long-standing controversial hypothesis and indicate that the marine resources of the North Atlantic Ocean were used to sustain an international demand for protein as far back as the Viking Age. PMID:28784790

Microbial diversity and impact on carbonate geochemistry across a changing geochemical gradient in a karst aquifer

PubMed Central

Gray, Cassie J; Engel, Annette S

2013-01-01

Although microbes are known to influence karst (carbonate) aquifer ecosystem-level processes, comparatively little information is available regarding the diversity of microbial activities that could influence water quality and geological modification. To assess microbial diversity in the context of aquifer geochemistry, we coupled 16S rRNA Sanger sequencing and 454 tag pyrosequencing to in situ microcosm experiments from wells that cross the transition from fresh to saline and sulfidic water in the Edwards Aquifer of central Texas, one of the largest karst aquifers in the United States. The distribution of microbial groups across the transition zone correlated with dissolved oxygen and sulfide concentration, and significant variations in community composition were explained by local carbonate geochemistry, specifically calcium concentration and alkalinity. The waters were supersaturated with respect to prevalent aquifer minerals, calcite and dolomite, but in situ microcosm experiments containing these minerals revealed significant mass loss from dissolution when colonized by microbes. Despite differences in cell density on the experimental surfaces, carbonate loss was greater from freshwater wells than saline, sulfidic wells. However, as cell density increased, which was correlated to and controlled by local geochemistry, dissolution rates decreased. Surface colonization by metabolically active cells promotes dissolution by creating local disequilibria between bulk aquifer fluids and mineral surfaces, but this also controls rates of karst aquifer modification. These results expand our understanding of microbial diversity in karst aquifers and emphasize the importance of evaluating active microbial processes that could affect carbonate weathering in the subsurface. PMID:23151637

Microbial diversity and impact on carbonate geochemistry across a changing geochemical gradient in a karst aquifer.

PubMed

Gray, Cassie J; Engel, Annette S

2013-02-01

Although microbes are known to influence karst (carbonate) aquifer ecosystem-level processes, comparatively little information is available regarding the diversity of microbial activities that could influence water quality and geological modification. To assess microbial diversity in the context of aquifer geochemistry, we coupled 16S rRNA Sanger sequencing and 454 tag pyrosequencing to in situ microcosm experiments from wells that cross the transition from fresh to saline and sulfidic water in the Edwards Aquifer of central Texas, one of the largest karst aquifers in the United States. The distribution of microbial groups across the transition zone correlated with dissolved oxygen and sulfide concentration, and significant variations in community composition were explained by local carbonate geochemistry, specifically calcium concentration and alkalinity. The waters were supersaturated with respect to prevalent aquifer minerals, calcite and dolomite, but in situ microcosm experiments containing these minerals revealed significant mass loss from dissolution when colonized by microbes. Despite differences in cell density on the experimental surfaces, carbonate loss was greater from freshwater wells than saline, sulfidic wells. However, as cell density increased, which was correlated to and controlled by local geochemistry, dissolution rates decreased. Surface colonization by metabolically active cells promotes dissolution by creating local disequilibria between bulk aquifer fluids and mineral surfaces, but this also controls rates of karst aquifer modification. These results expand our understanding of microbial diversity in karst aquifers and emphasize the importance of evaluating active microbial processes that could affect carbonate weathering in the subsurface.

Ancient DNA reveals the Arctic origin of Viking Age cod from Haithabu, Germany.

PubMed

Star, Bastiaan; Boessenkool, Sanne; Gondek, Agata T; Nikulina, Elena A; Hufthammer, Anne Karin; Pampoulie, Christophe; Knutsen, Halvor; André, Carl; Nistelberger, Heidi M; Dierking, Jan; Petereit, Christoph; Heinrich, Dirk; Jakobsen, Kjetill S; Stenseth, Nils Chr; Jentoft, Sissel; Barrett, James H

2017-08-22

Knowledge of the range and chronology of historic trade and long-distance transport of natural resources is essential for determining the impacts of past human activities on marine environments. However, the specific biological sources of imported fauna are often difficult to identify, in particular if species have a wide spatial distribution and lack clear osteological or isotopic differentiation between populations. Here, we report that ancient fish-bone remains, despite being porous, brittle, and light, provide an excellent source of endogenous DNA (15-46%) of sufficient quality for whole-genome reconstruction. By comparing ancient sequence data to that of modern specimens, we determine the biological origin of 15 Viking Age (800-1066 CE) and subsequent medieval (1066-1280 CE) Atlantic cod ( Gadus morhua ) specimens from excavation sites in Germany, Norway, and the United Kingdom. Archaeological context indicates that one of these sites was a fishing settlement for the procurement of local catches, whereas the other localities were centers of trade. Fish from the trade sites show a mixed ancestry and are statistically differentiated from local fish populations. Moreover, Viking Age samples from Haithabu, Germany, are traced back to the North East Arctic Atlantic cod population that has supported the Lofoten fisheries of Norway for centuries. Our results resolve a long-standing controversial hypothesis and indicate that the marine resources of the North Atlantic Ocean were used to sustain an international demand for protein as far back as the Viking Age.

Nanopore-CMOS Interfaces for DNA Sequencing

PubMed Central

Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim

2016-01-01

DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces. PMID:27509529

Nanopore-CMOS Interfaces for DNA Sequencing.

PubMed

Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim

2016-08-06

DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces.

RNA deep sequencing as a tool for selection of cell lines for systematic subcellular localization of all human proteins.

PubMed

Danielsson, Frida; Wiking, Mikaela; Mahdessian, Diana; Skogs, Marie; Ait Blal, Hammou; Hjelmare, Martin; Stadler, Charlotte; Uhlén, Mathias; Lundberg, Emma

2013-01-04

One of the major challenges of a chromosome-centric proteome project is to explore in a systematic manner the potential proteins identified from the chromosomal genome sequence, but not yet characterized on a protein level. Here, we describe the use of RNA deep sequencing to screen human cell lines for RNA profiles and to use this information to select cell lines suitable for characterization of the corresponding gene product. In this manner, the subcellular localization of proteins can be analyzed systematically using antibody-based confocal microscopy. We demonstrate the usefulness of selecting cell lines with high expression levels of RNA transcripts to increase the likelihood of high quality immunofluorescence staining and subsequent successful subcellular localization of the corresponding protein. The results show a path to combine transcriptomics with affinity proteomics to characterize the proteins in a gene- or chromosome-centric manner.

Streamwise-Localized Solutions with natural 1-fold symmetry

NASA Astrophysics Data System (ADS)

Altmeyer, Sebastian; Willis, Ashley; Hof, Björn

2014-11-01

It has been proposed in recent years that turbulence is organized around unstable invariant solutions, which provide the building blocks of the chaotic dynamics. In direct numerical simulations of pipe flow we show that when imposing a minimal symmetry constraint (reflection in an axial plane only) the formation of turbulence can indeed be explained by dynamical systems concepts. The hypersurface separating laminar from turbulent motion, the edge of turbulence, is spanned by the stable manifolds of an exact invariant solution, a periodic orbit of a spatially localized structure. The turbulent states themselves (turbulent puffs in this case) are shown to arise in a bifurcation sequence from a related localized solution (the upper branch orbit). The rather complex bifurcation sequence involves secondary Hopf bifurcations, frequency locking and a period doubling cascade until eventually turbulent puffs arise. In addition we report preliminary results of the transition sequence for pipe flow without symmetry constraints.

Lineage divergence detected in the malaria vector Anopheles marajoara (Diptera: Culicidae) in Amazonian Brazil

PubMed Central

2010-01-01

Background Cryptic species complexes are common among anophelines. Previous phylogenetic analysis based on the complete mtDNA COI gene sequences detected paraphyly in the Neotropical malaria vector Anopheles marajoara. The "Folmer region" detects a single taxon using a 3% divergence threshold. Methods To test the paraphyletic hypothesis and examine the utility of the Folmer region, genealogical trees based on a concatenated (white + 3' COI sequences) dataset and pairwise differentiation of COI fragments were examined. The population structure and demographic history were based on partial COI sequences for 294 individuals from 14 localities in Amazonian Brazil. 109 individuals from 12 localities were sequenced for the nDNA white gene, and 57 individuals from 11 localities were sequenced for the ribosomal DNA (rDNA) internal transcribed spacer 2 (ITS2). Results Distinct A. marajoara lineages were detected by combined genealogical analysis and were also supported among COI haplotypes using a median joining network and AMOVA, with time since divergence during the Pleistocene (<100,000 ya). COI sequences at the 3' end were more variable, demonstrating significant pairwise differentiation (3.82%) compared to the more moderate 2.92% detected by the Folmer region. Lineage 1 was present in all localities, whereas lineage 2 was restricted mainly to the west. Mismatch distributions for both lineages were bimodal, likely due to multiple colonization events and spatial expansion (~798 - 81,045 ya). There appears to be gene flow within, not between lineages, and a partial barrier was detected near Rio Jari in Amapá state, separating western and eastern populations. In contrast, both nDNA data sets (white gene sequences with or without the retention of the 4th intron, and ITS2 sequences and length) detected a single A. marajoara lineage. Conclusions Strong support for combined data with significant differentiation detected in the COI and absent in the nDNA suggest that the divergence is recent, and detectable only by the faster evolving mtDNA. A within subgenus threshold of >2% may be more appropriate among sister taxa in cryptic anopheline complexes than the standard 3%. Differences in demographic history and climatic changes may have contributed to mtDNA lineage divergence in A. marajoara. PMID:20929572

A R/K-rich motif in the C-terminal of the homeodomain is required for complete translocating of NKX2.5 protein into nucleus.

PubMed

Ouyang, Ping; Zhang, He; Fan, Zhaolan; Wei, Pei; Huang, Zhigang; Wang, Sen; Li, Tao

2016-11-05

NKX2.5 plays important roles in heart development. Being a transcription factor, NKX2.5 exerts its biological functions in nucleus. However, the sequence motif that localize NKX2.5 into nucleus is still not clear. Here, we found a R/K-rich sequence motif from Q187 to R197 (QNRRYKCKRQR) was required for exclusive nuclear localization of NKX2.5. Eight truncated plasmids (E109X, Q149X, Q170X, Q187X, Q198X, Y256X, Y259X, and C264X) which were associated with congenital heart disease (CHD) were constructed. Compared with the wild type NKX2.5, the proteins E109X, Q149X, Q170X, Q187X without intact homeodomain (HD) showed no transcriptional activity while Q198X, Y256X, Y259X and C264X with intact HD showed 50 to 66% transcriptional activity. E109X, Q149X, Q170X, Q187X without intact HD localized in the cytoplasm and nucleus simultaneously and Q198X, Y256X, Y259X and C264X with intact HD localized completely in nucleus. These results inferred the indispensability of 187QNRRYKCKRQR197 in exclusive nucleus localization. Additionally, this sequence motif was very conservative among human, mouse and rat, indicating this motif was important for NKX2.5 function. Thus, we concluded that R/K-rich sequence motif 187QNRRYKCKRQR197 played a central role for NKX2.5 nuclear localization. Our findings provided a clue to understand the mechanisms between the truncated NKX2.5 mutants and CHD. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Context-dependent colonization dynamics: Regional reward contagion drives local compression in aquatic beetles.

PubMed

Pintar, Matthew R; Resetarits, William J

2017-09-01

Habitat selection by colonizing organisms is an important factor in determining species abundance and community dynamics at multiple spatial scales. Many organisms select habitat patches based on intrinsic patch quality, but patches exist in complex landscapes linked by dispersal and colonization, forming metapopulations and metacommunities. Perceived patch quality can be influenced by neighbouring patches through spatial contagion, wherein perceived quality of one patch can extend beyond its borders and either increase or decrease the colonization of neighbouring patches and localities. These spatially explicit colonization dynamics can result in habitat compression, wherein more colonists occupy a patch or locality than in the absence of spatial context dependence. Previous work on contagion/compression focused primarily on the role of predators in driving colonization patterns. Our goal was to determine whether resource abundance can drive multi-scale colonization dynamics of aquatic beetles through the processes of contagion and compression in naturally colonized experimental pools. We established two levels (high/low quality) of within-patch resource abundances (leaf litter) using an experimental landscape of mesocosms, and assayed colonization by 35 species of aquatic beetles. Patches were arranged in localities (sets of two patches), which consisted of a combination of two patch-level resource levels in a 2 × 2 factorial design, allowing us to assay colonization at both locality and patch levels. We demonstrate that patterns of species abundance and richness of colonizing aquatic beetles are determined by patch quality and context-dependent processes at multiple spatial scales. Localities that consisted of at least one high-quality patch were colonized at equivalent rates that were higher than localities containing only low-quality patches, displaying regional reward contagion. In localities that consisted of one high- and one low-quality patch, reward contagion produced by higher leaf litter levels resulted in greater abundance of beetles in such localities, which then compressed into the highest quality patches. Our results provide further support for the critical roles of habitat selection and spatial context, particularly the quality of neighbouring habitat patches, in generating patterns of species abundances and community structure across landscapes. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Capturing community context of human response to forest disturbance by insects: a multi-method assessment

Treesearch

Hua Qin; Courtney G. Flint

2010-01-01

The socioeconomic and environmental features of local places (community context) influence the relationship between humans and their physical environment. In times of environmental disturbance, this community context is expected to influence human perceptual and behavioral responses. Residents from nine Colorado communities experiencing a large outbreak of mountain...

Imaging of glia activation in people with primary lateral sclerosis.

PubMed

Paganoni, Sabrina; Alshikho, Mohamad J; Zürcher, Nicole R; Cernasov, Paul; Babu, Suma; Loggia, Marco L; Chan, James; Chonde, Daniel B; Garcia, David Izquierdo; Catana, Ciprian; Mainero, Caterina; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

2018-01-01

Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post - mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. To localize and measure glia activation in people with PLS compared to healthy controls (HC). Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET). The radiotracer [ 11 C]-PBR28 was used to obtain PET-based measures of 18 kDa translocator protein (TSPO) expression, a marker of activated glial cells. MR techniques included a structural sequence to measure cortical thickness and diffusion tensor imaging (DTI) to assess white matter integrity. PET data showed increased [ 11 C]-PBR28 uptake in anatomically-relevant motor regions which co-localized with areas of regional gray matter atrophy and decreased subcortical fractional anisotropy. This study supports a link between glia activation and neuronal degeneration in PLS, and suggests that these disease mechanisms can be measured in vivo in PLS. Future studies are needed to determine the longitudinal changes of these imaging measures and to clarify if MR-PET with [ 11 C]-PBR28 can be used as a biomarker for drug development in the context of clinical trials for PLS.

Difficulties in Generating Specific Antibodies for Immunohistochemical Detection of Nitrosylated Tubulins

PubMed Central

Kamnev, Anton; Muhar, Matthias; Preinreich, Martina; Ammer, Hermann; Propst, Friedrich

2013-01-01

Protein S-nitrosylation, the covalent attachment of a nitroso moiety to thiol groups of specific cysteine residues, is one of the major pathways of nitric oxide signaling. Hundreds of proteins are subject to this transient post-translational modification and for some the functional consequences have been identified. Biochemical assays for the analysis of protein S-nitrosylation have been established and can be used to study if and under what conditions a given protein is S-nitrosylated. In contrast, the equally desirable subcellular localization of specific S-nitrosylated protein isoforms has not been achieved to date. In the current study we attempted to specifically localize S-nitrosylated α- and β-tubulin isoforms in primary neurons after fixation. The approach was based on in situ replacement of the labile cysteine nitroso modification with a stable tag and the subsequent use of antibodies which recognize the tag in the context of the tubulin polypeptide sequence flanking the cysteine residue of interest. We established a procedure for tagging S-nitrosylated proteins in cultured primary neurons and obtained polyclonal anti-tag antibodies capable of specifically detecting tagged proteins on immunoblots and in fixed cells. However, the antibodies were not specific for tubulin isoforms. We suggest that different tagging strategies or alternative methods such as fluorescence resonance energy transfer techniques might be more successful. PMID:23840827

Neoadjuvant radiotherapeutic strategies in pancreatic cancer

PubMed Central

Roeder, Falk

2016-01-01

This review summarizes the current status of neoadjuvant radiation approaches in the treatment of pancreatic cancer, including a description of modern radiation techniques, and an overview on the literature regarding neoadjuvant radio- or radiochemotherapeutic strategies both for resectable and irresectable pancreatic cancer. Neoadjuvant chemoradiation for locally-advanced, primarily non- or borderline resectable pancreas cancer results in secondary resectability in a substantial proportion of patients with consecutively markedly improved overall prognosis and should be considered as possible alternative in pretreatment multidisciplinary evaluations. In resectable pancreatic cancer, outstanding results in terms of response, local control and overall survival have been observed with neoadjuvant radio- or radiochemotherapy in several phase I/II trials, which justify further evaluation of this strategy. Further investigation of neoadjuvant chemoradiation strategies should be performed preferentially in randomized trials in order to improve comparability of the current results with other treatment modalities. This should include the evaluation of optimal sequencing with newer and more potent systemic induction therapy approaches. Advances in patient selection based on new molecular markers might be of crucial interest in this context. Finally modern external beam radiation techniques (intensity-modulated radiation therapy, image-guided radiation therapy and stereotactic body radiation therapy), new radiation qualities (protons, heavy ions) or combinations with alternative boosting techniques widen the therapeutic window and contribute to the reduction of toxicity. PMID:26909133

Action Spotting and Recognition Based on a Spatiotemporal Orientation Analysis.

PubMed

Derpanis, Konstantinos G; Sizintsev, Mikhail; Cannons, Kevin J; Wildes, Richard P

2013-03-01

This paper provides a unified framework for the interrelated topics of action spotting, the spatiotemporal detection and localization of human actions in video, and action recognition, the classification of a given video into one of several predefined categories. A novel compact local descriptor of video dynamics in the context of action spotting and recognition is introduced based on visual spacetime oriented energy measurements. This descriptor is efficiently computed directly from raw image intensity data and thereby forgoes the problems typically associated with flow-based features. Importantly, the descriptor allows for the comparison of the underlying dynamics of two spacetime video segments irrespective of spatial appearance, such as differences induced by clothing, and with robustness to clutter. An associated similarity measure is introduced that admits efficient exhaustive search for an action template, derived from a single exemplar video, across candidate video sequences. The general approach presented for action spotting and recognition is amenable to efficient implementation, which is deemed critical for many important applications. For action spotting, details of a real-time GPU-based instantiation of the proposed approach are provided. Empirical evaluation of both action spotting and action recognition on challenging datasets suggests the efficacy of the proposed approach, with state-of-the-art performance documented on standard datasets.

Improvements to robotics-inspired conformational sampling in rosetta.

PubMed

Stein, Amelie; Kortemme, Tanja

2013-01-01

To accurately predict protein conformations in atomic detail, a computational method must be capable of sampling models sufficiently close to the native structure. All-atom sampling is difficult because of the vast number of possible conformations and extremely rugged energy landscapes. Here, we test three sampling strategies to address these difficulties: conformational diversification, intensification of torsion and omega-angle sampling and parameter annealing. We evaluate these strategies in the context of the robotics-based kinematic closure (KIC) method for local conformational sampling in Rosetta on an established benchmark set of 45 12-residue protein segments without regular secondary structure. We quantify performance as the fraction of sub-Angstrom models generated. While improvements with individual strategies are only modest, the combination of intensification and annealing strategies into a new "next-generation KIC" method yields a four-fold increase over standard KIC in the median percentage of sub-Angstrom models across the dataset. Such improvements enable progress on more difficult problems, as demonstrated on longer segments, several of which could not be accurately remodeled with previous methods. Given its improved sampling capability, next-generation KIC should allow advances in other applications such as local conformational remodeling of multiple segments simultaneously, flexible backbone sequence design, and development of more accurate energy functions.

Improvements to Robotics-Inspired Conformational Sampling in Rosetta

PubMed Central

Stein, Amelie; Kortemme, Tanja

2013-01-01

To accurately predict protein conformations in atomic detail, a computational method must be capable of sampling models sufficiently close to the native structure. All-atom sampling is difficult because of the vast number of possible conformations and extremely rugged energy landscapes. Here, we test three sampling strategies to address these difficulties: conformational diversification, intensification of torsion and omega-angle sampling and parameter annealing. We evaluate these strategies in the context of the robotics-based kinematic closure (KIC) method for local conformational sampling in Rosetta on an established benchmark set of 45 12-residue protein segments without regular secondary structure. We quantify performance as the fraction of sub-Angstrom models generated. While improvements with individual strategies are only modest, the combination of intensification and annealing strategies into a new “next-generation KIC” method yields a four-fold increase over standard KIC in the median percentage of sub-Angstrom models across the dataset. Such improvements enable progress on more difficult problems, as demonstrated on longer segments, several of which could not be accurately remodeled with previous methods. Given its improved sampling capability, next-generation KIC should allow advances in other applications such as local conformational remodeling of multiple segments simultaneously, flexible backbone sequence design, and development of more accurate energy functions. PMID:23704889

A Context-Aware-Based Audio Guidance System for Blind People Using a Multimodal Profile Model

PubMed Central

Lin, Qing; Han, Youngjoon

2014-01-01

A wearable guidance system is designed to provide context-dependent guidance messages to blind people while they traverse local pathways. The system is composed of three parts: moving scene analysis, walking context estimation and audio message delivery. The combination of a downward-pointing laser scanner and a camera is used to solve the challenging problem of moving scene analysis. By integrating laser data profiles and image edge profiles, a multimodal profile model is constructed to estimate jointly the ground plane, object locations and object types, by using a Bayesian network. The outputs of the moving scene analysis are further employed to estimate the walking context, which is defined as a fuzzy safety level that is inferred through a fuzzy logic model. Depending on the estimated walking context, the audio messages that best suit the current context are delivered to the user in a flexible manner. The proposed system is tested under various local pathway scenes, and the results confirm its efficiency in assisting blind people to attain autonomous mobility. PMID:25302812

A single-molecule sequencing assay for the comprehensive profiling of T4 DNA ligase fidelity and bias during DNA end-joining.

PubMed

Potapov, Vladimir; Ong, Jennifer L; Langhorst, Bradley W; Bilotti, Katharina; Cahoon, Dan; Canton, Barry; Knight, Thomas F; Evans, Thomas C; Lohman, Gregory Js

2018-05-08

DNA ligases are key enzymes in molecular and synthetic biology that catalyze the joining of breaks in duplex DNA and the end-joining of DNA fragments. Ligation fidelity (discrimination against the ligation of substrates containing mismatched base pairs) and bias (preferential ligation of particular sequences over others) have been well-studied in the context of nick ligation. However, almost no data exist for fidelity and bias in end-joining ligation contexts. In this study, we applied Pacific Biosciences Single-Molecule Real-Time sequencing technology to directly sequence the products of a highly multiplexed ligation reaction. This method has been used to profile the ligation of all three-base 5'-overhangs by T4 DNA ligase under typical ligation conditions in a single experiment. We report the relative frequency of all ligation products with or without mismatches, the position-dependent frequency of each mismatch, and the surprising observation that 5'-TNA overhangs ligate extremely inefficiently compared to all other Watson-Crick pairings. The method can easily be extended to profile other ligases, end-types (e.g. blunt ends and overhangs of different lengths), and the effect of adjacent sequence on the ligation results. Further, the method has the potential to provide new insights into the thermodynamics of annealing and the kinetics of end-joining reactions.

Inferring coarse-grain histone-DNA interaction potentials from high-resolution structures of the nucleosome

NASA Astrophysics Data System (ADS)

Meyer, Sam; Everaers, Ralf

2015-02-01

The histone-DNA interaction in the nucleosome is a fundamental mechanism of genomic compaction and regulation, which remains largely unknown despite increasing structural knowledge of the complex. In this paper, we propose a framework for the extraction of a nanoscale histone-DNA force-field from a collection of high-resolution structures, which may be adapted to a larger class of protein-DNA complexes. We applied the procedure to a large crystallographic database extended by snapshots from molecular dynamics simulations. The comparison of the structural models first shows that, at histone-DNA contact sites, the DNA base-pairs are shifted outwards locally, consistent with locally repulsive forces exerted by the histones. The second step shows that the various force profiles of the structures under analysis derive locally from a unique, sequence-independent, quadratic repulsive force-field, while the sequence preferences are entirely due to internal DNA mechanics. We have thus obtained the first knowledge-derived nanoscale interaction potential for histone-DNA in the nucleosome. The conformations obtained by relaxation of nucleosomal DNA with high-affinity sequences in this potential accurately reproduce the experimental values of binding preferences. Finally we address the more generic binding mechanisms relevant to the 80% genomic sequences incorporated in nucleosomes, by computing the conformation of nucleosomal DNA with sequence-averaged properties. This conformation differs from those found in crystals, and the analysis suggests that repulsive histone forces are related to local stretch tension in nucleosomal DNA, mostly between adjacent contact points. This tension could play a role in the stability of the complex.

Understanding the local context and its possible influences on shaping, implementing and running social accountability initiatives for maternal health services in rural Democratic Republic of the Congo: a contextual factor analysis.

PubMed

Mafuta, Eric M; Hogema, Lisanne; Mambu, Thérèse N M; Kiyimbi, Pontien B; Indebe, Berthys P; Kayembe, Patrick K; De Cock Buning, Tjard; Dieleman, Marjolein A

2016-11-09

Social accountability has to be configured according to the context in which it operates. This paper aimed to identify local contextual factors in two health zones in the Democratic Republic of the Congo and discuss their possible influences on shaping, implementing and running social accountability initiatives. Data on local socio-cultural characteristics, the governance context, and socio-economic conditions related to social accountability enabling factors were collected in the two health zones using semi-structured interviews and document reviews, and were analyzed using thematic analysis. The contexts of the two health zones were similar and characterized by the existence of several community groups, similarly structured and using similar decision-making processes. They were not involved in the health sector's activities and had no link with the health committee, even though they acknowledged its existence. They were not networked as they focused on their own activities and did not have enough capacity in terms of social mobilization or exerting pressure on public authorities or providers. Women were not perceived as marginalized as they often occupied other positions in the community besides carrying out domestic tasks and participated in community groups. However, they were still subject to the local male dominance culture, which restrains their involvement in decision-making, as they tend to be less educated, unemployed and suffer from a lack of resources or specific skills. The socio-economic context is characterized by subsistence activities and a low employment rate, which limits the community members' incomes and increases their dependence on external support. The governance context was characterized by imperfect implementation of political decentralization. Community groups advocating community rights are identified as "political" and are not welcomed. The community groups seemed not to be interested in the health center's information and had no access to media as it is non-existent. The local contexts in the two health zones seemed not to be supportive of the operation of social accountability initiatives. However, they offer starting points for social accountability initiatives if better use is made of existing contextual factors, for instance by making community groups work together and improving their capacities in terms of knowledge and information.

From non-random molecular structure to life and mind

NASA Technical Reports Server (NTRS)

Fox, S. W.

1989-01-01

The evolutionary hierarchy molecular structure-->macromolecular structure-->protobiological structure-->biological structure-->biological functions has been traced by experiments. The sequence always moves through protein. Extension of the experiments traces the formation of nucleic acids instructed by proteins. The proteins themselves were, in this picture, instructed by the self-sequencing of precursor amino acids. While the sequence indicated explains the thread of the emergence of life, protein in cellular membrane also provides the only known material basis for the emergence of mind in the context of emergence of life.

Prime and prejudice: The effect of priming context and prejudicial attitudes on post-traumatic stress disorder symptoms following immigrant violence.

PubMed

Hoffman, Yaakov; Shrira, Amit; Bodner, Ehud; Ben-Ezra, Menachem

2017-08-01

The recent arrival of immigrants into many western countries has become common. Clashes between immigrants and local residents may produce acts of violence. In two studies we assessed post-traumatic stress disorder (PTSD) symptoms in local residents exposed to immigrant violence, while addressing possible effects of priming context and prejudicial attitudes. In Study 1, context was either reminiscent/non-reminiscent of experiencing African immigrant violence (researcher with same/different ethnic origin to that of perpetrators). In Study 2, context was manipulated as a negative ("illegal-migrant") or neutral ("working-immigrant") framing for African immigrants. We also examined if effects of context on trauma symptoms are moderated by prejudicial attitudes towards African immigrants. As expected, higher PTSD symptom levels were evident in the presence of traumatic (Study 1) and negative (Study 2) context, yet only in residents with high prejudicial attitudes. Results suggest that both contexts and prejudice play a role in assessment of PTSD stemming from cultural conflicts. Theoretical implications of the data in terms of PTSD memory theories, are discussed including the notion of a PTSD context theory. Practical implications pertaining to the potential compatibility of researchers and therapists with trauma victims are also addressed. Copyright © 2017. Published by Elsevier B.V.

RISC RNA sequencing for context-specific identification of in vivo miR targets

PubMed Central

Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

2010-01-01

Rationale MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. Objective To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). Methods and Results We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias, and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1,645 mRNAs consistently targeted to mouse cardiac RISCs. We employed this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing ‘seed’ sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. Conclusions RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context, and is applicable to any tissue and any disease state. Summary MicroRNAs (miRs) are key regulators of mRNA translation in health and disease. While bioinformatic predictions suggest that a single miR may target hundreds of mRNAs, the number of experimentally verified targets of miRs is low. To enable comprehensive, unbiased examination of miR targets, we have performed deep RNA sequencing of cardiac transcriptomes in parallel with cardiac RNA-induced silencing complex (RISC)-associated RNAs (the RISCome), called RISC sequencing. We developed methods that did not require cross-linking of RNAs to RISCs or amplification of mRNA prior to sequencing, making it possible to rapidly perform RISC sequencing from intact tissue while avoiding amplification bias. Comparison of RISCome with transcriptome expression defined the degree of RISC enrichment for each mRNA. The majority of the mRNAs enriched in wild-type cardiac RISComes compared to transcriptomes were bioinformatically predicted to be targets of at least 1 of 139 cardiac-expressed miRs. Programming cardiomyocyte RISCs via transgenic overexpression in adult hearts of miR-133a or miR-499, two miRs that contain entirely different ‘seed’ sequences, elicited differing profiles of RISC-targeted mRNAs. Thus, RISC sequencing represents a highly sensitive method for general RISC profiling and individual miR target identification in biological context. PMID:21030712

Teaching the 3 R's through the 3 C's: Connecting Curriculum & Community.

ERIC Educational Resources Information Center

Karner, Terrence R., Jr.; Knapp, Clifford E.; Simmert, R. Larry; Carlson, Pamela; Criswell, Marquiette R.; Arroz, Marie; Geocaris, Claudia; Roth-Longe, Jennifer

2001-01-01

Presents suggestions for class activities that integrate community resources and local contexts into curriculum and instruction. Activities include field trips to a historic one-room schoolhouse, a local track meet, a beauty salon, and local manufacturing companies; explorations of local water supply systems and community history and sociology;…

Digitisation of Local Heritage: Local Studies Collections and Digitisation in Public Libraries

ERIC Educational Resources Information Center

Smith, Lucy; Rowley, Jennifer

2012-01-01

This study explores the application of digitisation in the context of public library local studies services. Since there has been limited previous research on digitisation and local studies collections, this research makes an important contribution in profiling the current situation, and highlighting the extent to which progress is limited in the…

The Communication Skills Used by Deaf Children and Their Hearing Peers in a Question-and-Answer Game Context

ERIC Educational Resources Information Center

Toe, Dianne M.; Paatsch, Louise E.

2010-01-01

Communication is frequently characterized by a sequence of questions and answers. Little is known about how well students who are deaf or hard of hearing (deaf/HH) understand their hearing classmates in the context of an inclusive setting. This study explored the communication skills used by deaf/HH children when asking and answering questions in…

Scientific overview and historical context of the 1811-1812 new Madrid earthquake sequence

USGS Publications Warehouse

Hough, S.E.

2004-01-01

aftershock». These values are consistent with other lines of evidence, including scaling relationships. Finally, I show that accounts from the New Madrid sequence reveal evidence for remotely triggered earthquakes well outside the NMSZ. Remotely triggered earthquakes represent a potentially important new wrinkle in historic earthquake research, as their ground motions can sometimes be confused with mainshock ground motions.

Genome sequence of Aggregatibacter actinomycetemcomitans RHAA1, isolated from a rhesus macaque, an Old World primate.

PubMed

Karched, Maribasappa; Furgang, David; Planet, Paul J; DeSalle, Rob; Fine, Daniel H

2012-03-01

Aggregatibacter actinomycetemcomitans is implicated in localized aggressive periodontitis. We report the first genome sequence of an A. actinomycetemcomitans strain isolated from an Old World primate.

The Cuban “Exception”: The Development of an Advanced Scientific System in an Underdeveloped Country

NASA Astrophysics Data System (ADS)

Baracca, Angelo

Science, education, politics, social development and economics are today considered to be highly interdependent. Although none of these factors can exist on their own, they have nevertheless often been considered in isolation from one other, or studies of their interactions have been confined to the consideration of more or less local contexts. When it comes to studying the history of physics in Cuba, however, it is not only inconceivable to separate scientific developments from their social, political, and cultural contexts. But, as this volume shows, the history of physics in Cuba cannot just focus on local contexts since it is closely entangled with global history, from colonialism to the Cold War.

Earthquake Predictability: Results From Aggregating Seismicity Data And Assessment Of Theoretical Individual Cases Via Synthetic Data

NASA Astrophysics Data System (ADS)

Adamaki, A.; Roberts, R.

2016-12-01

For many years an important aim in seismological studies has been forecasting the occurrence of large earthquakes. Despite some well-established statistical behavior of earthquake sequences, expressed by e.g. the Omori law for aftershock sequences and the Gutenburg-Richter distribution of event magnitudes, purely statistical approaches to short-term earthquake prediction have in general not been successful. It seems that better understanding of the processes leading to critical stress build-up prior to larger events is necessary to identify useful precursory activity, if this exists, and statistical analyses are an important tool in this context. There has been considerable debate on the usefulness or otherwise of foreshock studies for short-term earthquake prediction. We investigate generic patterns of foreshock activity using aggregated data and by studying not only strong but also moderate magnitude events. Aggregating empirical local seismicity time series prior to larger events observed in and around Greece reveals a statistically significant increasing rate of seismicity over 20 days prior to M>3.5 earthquakes. This increase cannot be explained by tempo-spatial clustering models such as ETAS, implying genuine changes in the mechanical situation just prior to larger events and thus the possible existence of useful precursory information. Because of tempo-spatial clustering, including aftershocks to foreshocks, even if such generic behavior exists it does not necessarily follow that foreshocks have the potential to provide useful precursory information for individual larger events. Using synthetic catalogs produced based on different clustering models and different presumed system sensitivities we are now investigating to what extent the apparently established generic foreshock rate acceleration may or may not imply that the foreshocks have potential in the context of routine forecasting of larger events. Preliminary results suggest that this is the case, but that it is likely that physically-based models of foreshock clustering will be a necessary, but not necessarily sufficient, basis for successful forecasting.

Effects of the Laramide Structures on the Regional Distribution of Tight-Gas Sandstone in the Upper Mesaverde Group, Uinta Basin, Utah

NASA Astrophysics Data System (ADS)

Sitaula, R. P.; Aschoff, J.

2013-12-01

Regional-scale sequence stratigraphic correlation, well log analysis, syntectonic unconformity mapping, isopach maps, and depositional environment maps of the upper Mesaverde Group (UMG) in Uinta basin, Utah suggest higher accommodation in northeastern part (Natural Buttes area) and local development of lacustrine facies due to increased subsidence caused by uplift of San Rafael Swell (SRS) in southern and Uinta Uplift in northern parts. Recently discovered lacustrine facies in Natural Buttes area are completely different than the dominant fluvial facies in outcrops along Book Cliffs and could have implications for significant amount of tight-gas sand production from this area. Data used for sequence stratigraphic correlation, isopach maps and depositional environmental maps include > 100 well logs, 20 stratigraphic profiles, 35 sandstone thin sections and 10 outcrop-based gamma ray profiles. Seven 4th order depositional sequences (~0.5 my duration) are identified and correlated within UMG. Correlation was constructed using a combination of fluvial facies and stacking patterns in outcrops, chert-pebble conglomerates and tidally influenced strata. These surfaces were extrapolated into subsurface by matching GR profiles. GR well logs and core log of Natural Buttes area show intervals of coarsening upward patterns suggesting possible lacustrine intervals that might contain high TOC. Locally, younger sequences are completely truncated across SRS whereas older sequences are truncated and thinned toward SRS. The cycles of truncation and thinning represent phases of SRS uplift. Thinning possibly related with the Uinta Uplift is also observed in northwestern part. Paleocurrents are consistent with interpretation of periodic segmentation and deflection of sedimentation. Regional paleocurrents are generally E-NE-directed in Sequences 1-4, and N-directed in Sequences 5-7. From isopach maps and paleocurrent direction it can be interpreted that uplift of SRS changed route of sediment supply from west to southwest. Locally, paleocurrents are highly variable near SRS further suggesting UMG basin-fill was partitioned by uplift of SRS. Sandstone composition analysis also suggests the uplift of SRS causing the variation of source rocks in upper sequences than the lower sequences. In conclusion, we suggest that Uinta basin was episodically partitioned during the deposition of UMG due to uplift of Laramide structures in the basin and accommodation was localized in northeastern part. Understanding of structural controls on accommodation, sedimentation patterns and depositional environments will aid prediction of the best-producing gas reservoirs.

BLAST and FASTA similarity searching for multiple sequence alignment.

PubMed

Pearson, William R

2014-01-01

BLAST, FASTA, and other similarity searching programs seek to identify homologous proteins and DNA sequences based on excess sequence similarity. If two sequences share much more similarity than expected by chance, the simplest explanation for the excess similarity is common ancestry-homology. The most effective similarity searches compare protein sequences, rather than DNA sequences, for sequences that encode proteins, and use expectation values, rather than percent identity, to infer homology. The BLAST and FASTA packages of sequence comparison programs provide programs for comparing protein and DNA sequences to protein databases (the most sensitive searches). Protein and translated-DNA comparisons to protein databases routinely allow evolutionary look back times from 1 to 2 billion years; DNA:DNA searches are 5-10-fold less sensitive. BLAST and FASTA can be run on popular web sites, but can also be downloaded and installed on local computers. With local installation, target databases can be customized for the sequence data being characterized. With today's very large protein databases, search sensitivity can also be improved by searching smaller comprehensive databases, for example, a complete protein set from an evolutionarily neighboring model organism. By default, BLAST and FASTA use scoring strategies target for distant evolutionary relationships; for comparisons involving short domains or queries, or searches that seek relatively close homologs (e.g. mouse-human), shallower scoring matrices will be more effective. Both BLAST and FASTA provide very accurate statistical estimates, which can be used to reliably identify protein sequences that diverged more than 2 billion years ago.

Rapid evolution of cis-regulatory sequences via local point mutations

NASA Technical Reports Server (NTRS)

Stone, J. R.; Wray, G. A.

2001-01-01

Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

Weaving networks of responsibility: community work in development programs in rural Malawi.

PubMed

Rosenthal, Anat

2012-01-01

The need to cope with the impact of the AIDS epidemic on communities in Africa has resulted in the emergence of numerous community health and development programs. Initiated by governments, international nongovernmental organizations (NGOs), and local organizations, such programs target local communities with the goal of building care and support mechanisms in the local level. Based on ethnographic field research in rural Malawi, and drawing from the cross-disciplinary debate on development work, the article explores the work of an NGO offering health and care programs to orphans and vulnerable children. Through analyzing the organization's scope of work, the article demonstrates how the NGO acts to structure local social networks as instruments of care and offers a new reading of the role of NGOs in which the limitations of development work and the work of NGOs are understood within their local context and not only in the context of broad cultural critique.

Cross cultural differences in unconscious knowledge.

PubMed

Kiyokawa, Sachiko; Dienes, Zoltán; Tanaka, Daisuke; Yamada, Ayumi; Crowe, Louise

2012-07-01

Previous studies have indicated cross cultural differences in conscious processes, such that Asians have a global preference and Westerners a more analytical one. We investigated whether these biases also apply to unconscious knowledge. In Experiment 1, Japanese and UK participants memorized strings of large (global) letters made out of small (local) letters. The strings constituted one sequence of letters at a global level and a different sequence at a local level. Implicit learning occurred at the global and not the local level for the Japanese but equally at both levels for the English. In Experiment 2, the Japanese preference for global over local processing persisted even when structure existed only at the local but not global level. In Experiment 3, Japanese and UK participants were asked to attend to just one of the levels, global or local. Now the cultural groups performed similarly, indicating that the bias largely reflects preference rather than ability (although the data left room for residual ability differences). In Experiment 4, the greater global advantage of Japanese rather English was confirmed for strings made of Japanese kana rather than Roman letters. That is, the cultural difference is not due to familiarity of the sequence elements. In sum, we show for the first time that cultural biases strongly affect the type of unconscious knowledge people acquire. Copyright © 2012 Elsevier B.V. All rights reserved.

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Influence of gag and RRE Sequences on HIV-1 RNA Packaging Signal Structure and Function.

PubMed

Kharytonchyk, Siarhei; Brown, Joshua D; Stilger, Krista; Yasin, Saif; Iyer, Aishwarya S; Collins, John; Summers, Michael F; Telesnitsky, Alice

2018-07-06

The packaging signal (Ψ) and Rev-responsive element (RRE) enable unspliced HIV-1 RNAs' export from the nucleus and packaging into virions. For some retroviruses, engrafting Ψ onto a heterologous RNA is sufficient to direct encapsidation. In contrast, HIV-1 RNA packaging requires 5' leader Ψ elements plus poorly defined additional features. We previously defined minimal 5' leader sequences competitive with intact Ψ for HIV-1 packaging, and here examined the potential roles of additional downstream elements. The findings confirmed that together, HIV-1 5' leader Ψ sequences plus a nuclear export element are sufficient to specify packaging. However, RNAs trafficked using a heterologous export element did not compete well with RNAs using HIV-1's RRE. Furthermore, some RNA additions to well-packaged minimal vectors rendered them packaging-defective. These defects were rescued by extending gag sequences in their native context. To understand these packaging defects' causes, in vitro dimerization properties of RNAs containing minimal packaging elements were compared to RNAs with sequence extensions that were or were not compatible with packaging. In vitro dimerization was found to correlate with packaging phenotypes, suggesting that HIV-1 evolved to prevent 5' leader residues' base pairing with downstream residues and misfolding of the packaging signal. Our findings explain why gag sequences have been implicated in packaging and show that RRE's packaging contributions appear more specific than nuclear export alone. Paired with recent work showing that sequences upstream of Ψ can dictate RNA folds, the current work explains how genetic context of minimal packaging elements contributes to HIV-1 RNA fate determination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coding Local and Global Binary Visual Features Extracted From Video Sequences.

PubMed

Baroffio, Luca; Canclini, Antonio; Cesana, Matteo; Redondi, Alessandro; Tagliasacchi, Marco; Tubaro, Stefano

2015-11-01

Binary local features represent an effective alternative to real-valued descriptors, leading to comparable results for many visual analysis tasks while being characterized by significantly lower computational complexity and memory requirements. When dealing with large collections, a more compact representation based on global features is often preferred, which can be obtained from local features by means of, e.g., the bag-of-visual word model. Several applications, including, for example, visual sensor networks and mobile augmented reality, require visual features to be transmitted over a bandwidth-limited network, thus calling for coding techniques that aim at reducing the required bit budget while attaining a target level of efficiency. In this paper, we investigate a coding scheme tailored to both local and global binary features, which aims at exploiting both spatial and temporal redundancy by means of intra- and inter-frame coding. In this respect, the proposed coding scheme can conveniently be adopted to support the analyze-then-compress (ATC) paradigm. That is, visual features are extracted from the acquired content, encoded at remote nodes, and finally transmitted to a central controller that performs the visual analysis. This is in contrast with the traditional approach, in which visual content is acquired at a node, compressed and then sent to a central unit for further processing, according to the compress-then-analyze (CTA) paradigm. In this paper, we experimentally compare the ATC and the CTA by means of rate-efficiency curves in the context of two different visual analysis tasks: 1) homography estimation and 2) content-based retrieval. Our results show that the novel ATC paradigm based on the proposed coding primitives can be competitive with the CTA, especially in bandwidth limited scenarios.

Coding Local and Global Binary Visual Features Extracted From Video Sequences

NASA Astrophysics Data System (ADS)

Baroffio, Luca; Canclini, Antonio; Cesana, Matteo; Redondi, Alessandro; Tagliasacchi, Marco; Tubaro, Stefano

2015-11-01

Binary local features represent an effective alternative to real-valued descriptors, leading to comparable results for many visual analysis tasks, while being characterized by significantly lower computational complexity and memory requirements. When dealing with large collections, a more compact representation based on global features is often preferred, which can be obtained from local features by means of, e.g., the Bag-of-Visual-Word (BoVW) model. Several applications, including for example visual sensor networks and mobile augmented reality, require visual features to be transmitted over a bandwidth-limited network, thus calling for coding techniques that aim at reducing the required bit budget, while attaining a target level of efficiency. In this paper we investigate a coding scheme tailored to both local and global binary features, which aims at exploiting both spatial and temporal redundancy by means of intra- and inter-frame coding. In this respect, the proposed coding scheme can be conveniently adopted to support the Analyze-Then-Compress (ATC) paradigm. That is, visual features are extracted from the acquired content, encoded at remote nodes, and finally transmitted to a central controller that performs visual analysis. This is in contrast with the traditional approach, in which visual content is acquired at a node, compressed and then sent to a central unit for further processing, according to the Compress-Then-Analyze (CTA) paradigm. In this paper we experimentally compare ATC and CTA by means of rate-efficiency curves in the context of two different visual analysis tasks: homography estimation and content-based retrieval. Our results show that the novel ATC paradigm based on the proposed coding primitives can be competitive with CTA, especially in bandwidth limited scenarios.

Hidden genetic history of the Japanese sand dollar Peronella (Echinoidea: Laganidae) revealed by nuclear intron sequences.

PubMed

Endo, Megumi; Hirose, Mamiko; Honda, Masanao; Koga, Hiroyuki; Morino, Yoshiaki; Kiyomoto, Masato; Wada, Hiroshi

2018-06-15

The marine environment around Japan experienced significant changes during the Cenozoic Era. In this study, we report findings suggesting that this dynamic history left behind traces in the genome of the Japanese sand dollar species Peronella japonica and P. rubra. Although mitochondrial Cytochrome C Oxidase I sequences did not indicate fragmentation of the current local populations of P. japonica around Japan, two different types of intron sequence were found in the Alx1 locus. We inferred that past fragmentation of the populations account for the presence of two types of nuclear sequences as alleles in the Alx1 intron of P. japonica. It is likely that the split populations have intermixed in recent times; hence, we did not detect polymorphisms in the sequences reflecting the current localization of the species. In addition, we found two allelic sequences of theAlx1 intron in the sister species P. rubra. The divergence times of the two types of Alx1 intron sequences were estimated at approximately 14.9 and 4.0 million years ago for P. japonica and P. rubra, respectively. Our study indicates that information from the intron sequences of nuclear genes can enhance our understanding of past genetic events in organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Buddhism, science, and market: The globalisation of Tibetan medicine.

PubMed

Janes, Craig R

2002-01-01

In this paper I discuss the processes by which Tibetan medicine has become globalised, and the ways in which these have come to determine, constrain, and, ultimately, transform local practices of healing in both Tibet and the West. I examine the degree to which globalisation, in particular international market capitalism, operating in this case through the Chinese state, structures the content of primary medical resources, confers legitimacy to certain technologies, and sets the ground rules by which the healers in charge of deploying such technologies are set into conversation with one another. I also argue that the cultural dimensions of globalisation enter the local context through the multiple-stranded flows of people, images, and ideas, and contribute to redefinitions of identity, suffering, and body praxis among patients/consumers in diverse local contexts. I proceed within two registers of analysis. In the first, I analyse these movements in the context of Tibetan medicine as it has been transformed, practised, and used, in the Tibet Autonomous Region of China. In the second, the analytic lens shifts to a focus on Tibetan medicine as a 'global' alternative medicine in North America and Europe. The focus throughout is on the global-local dialectic: how Tibetan medicine is both produced as global commodity and consumed as 'local' tradition.

Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima

PubMed Central

Yin, Yimeng; Das, Pratyush K; Jolma, Arttu; Zhu, Fangjie; Popov, Alexander; Xu, You; Nilsson, Lennart

2018-01-01

Most transcription factors (TFs) can bind to a population of sequences closely related to a single optimal site. However, some TFs can bind to two distinct sequences that represent two local optima in the Gibbs free energy of binding (ΔG). To determine the molecular mechanism behind this effect, we solved the structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences, CAATAAA and TCGTAAA. Thermodynamic analyses by isothermal titration calorimetry revealed that both sites were bound with similar ΔG. However, the interaction with the CAA sequence was driven by change in enthalpy (ΔH), whereas the TCG site was bound with similar affinity due to smaller loss of entropy (ΔS). This thermodynamic mechanism that leads to at least two local optima likely affects many macromolecular interactions, as ΔG depends on two partially independent variables ΔH and ΔS according to the central equation of thermodynamics, ΔG = ΔH - TΔS. PMID:29638214

Infrared thermal facial image sequence registration analysis and verification

NASA Astrophysics Data System (ADS)

Chen, Chieh-Li; Jian, Bo-Lin

2015-03-01

To study the emotional responses of subjects to the International Affective Picture System (IAPS), infrared thermal facial image sequence is preprocessed for registration before further analysis such that the variance caused by minor and irregular subject movements is reduced. Without affecting the comfort level and inducing minimal harm, this study proposes an infrared thermal facial image sequence registration process that will reduce the deviations caused by the unconscious head shaking of the subjects. A fixed image for registration is produced through the localization of the centroid of the eye region as well as image translation and rotation processes. Thermal image sequencing will then be automatically registered using the two-stage genetic algorithm proposed. The deviation before and after image registration will be demonstrated by image quality indices. The results show that the infrared thermal image sequence registration process proposed in this study is effective in localizing facial images accurately, which will be beneficial to the correlation analysis of psychological information related to the facial area.

DeepLoc: prediction of protein subcellular localization using deep learning.

PubMed

Almagro Armenteros, José Juan; Sønderby, Casper Kaae; Sønderby, Søren Kaae; Nielsen, Henrik; Winther, Ole

2017-11-01

The prediction of eukaryotic protein subcellular localization is a well-studied topic in bioinformatics due to its relevance in proteomics research. Many machine learning methods have been successfully applied in this task, but in most of them, predictions rely on annotation of homologues from knowledge databases. For novel proteins where no annotated homologues exist, and for predicting the effects of sequence variants, it is desirable to have methods for predicting protein properties from sequence information only. Here, we present a prediction algorithm using deep neural networks to predict protein subcellular localization relying only on sequence information. At its core, the prediction model uses a recurrent neural network that processes the entire protein sequence and an attention mechanism identifying protein regions important for the subcellular localization. The model was trained and tested on a protein dataset extracted from one of the latest UniProt releases, in which experimentally annotated proteins follow more stringent criteria than previously. We demonstrate that our model achieves a good accuracy (78% for 10 categories; 92% for membrane-bound or soluble), outperforming current state-of-the-art algorithms, including those relying on homology information. The method is available as a web server at http://www.cbs.dtu.dk/services/DeepLoc. Example code is available at https://github.com/JJAlmagro/subcellular_localization. The dataset is available at http://www.cbs.dtu.dk/services/DeepLoc/data.php. jjalma@dtu.dk. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Plastoglobule-Targeting Competence of a Putative Transit Peptide Sequence from Rice Phytoene Synthase 2 in Plastids.

PubMed

You, Min Kyoung; Kim, Jin Hwa; Lee, Yeo Jin; Jeong, Ye Sol; Ha, Sun-Hwa

2016-12-22

Plastoglobules (PGs) are thylakoid membrane microdomains within plastids that are known as specialized locations of carotenogenesis. Three rice phytoene synthase proteins (OsPSYs) involved in carotenoid biosynthesis have been identified. Here, the N-terminal 80-amino-acid portion of OsPSY2 (PTp) was demonstrated to be a chloroplast-targeting peptide by displaying cytosolic localization of OsPSY2(ΔPTp):mCherry in rice protoplast, in contrast to chloroplast localization of OsPSY2:mCherry in a punctate pattern. The peptide sequence of a PTp was predicted to harbor two transmembrane domains eligible for a putative PG-targeting signal. To assess and enhance the PG-targeting ability of PTp, the original PTp DNA sequence ( PTp ) was modified to a synthetic DNA sequence ( stPTp ), which had 84.4% similarity to the original sequence. The motivation of this modification was to reduce the GC ratio from 75% to 65% and to disentangle the hairpin loop structures of PTp . These two DNA sequences were fused to the sequence of the synthetic green fluorescent protein (sGFP) and drove GFP expression with different efficiencies. In particular, the RNA and protein levels of stPTp-sGFP were slightly improved to 1.4-fold and 1.3-fold more than those of sGFP, respectively. The green fluorescent signals of their mature proteins were all observed as speckle-like patterns with slightly blurred stromal signals in chloroplasts. These discrete green speckles of PTp - sGFP and stPTp - sGFP corresponded exactly to the red fluorescent signal displayed by OsPSY2:mCherry in both etiolated and greening protoplasts and it is presumed to correspond to distinct PGs. In conclusion, we identified PTp as a transit peptide sequence facilitating preferential translocation of foreign proteins to PGs, and developed an improved PTp sequence, a s tPTp , which is expected to be very useful for applications in plant biotechnologies requiring precise micro-compartmental localization in plastids.

Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL): adapting the Partial Phylogenetic Profiling algorithm to scan sequences for signatures that predict protein function

PubMed Central

2010-01-01

Background Comparative genomics methods such as phylogenetic profiling can mine powerful inferences from inherently noisy biological data sets. We introduce Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL), a method that applies the Partial Phylogenetic Profiling (PPP) approach locally within a protein sequence to discover short sequence signatures associated with functional sites. The approach is based on the basic scoring mechanism employed by PPP, namely the use of binomial distribution statistics to optimize sequence similarity cutoffs during searches of partitioned training sets. Results Here we illustrate and validate the ability of the SIMBAL method to find functionally relevant short sequence signatures by application to two well-characterized protein families. In the first example, we partitioned a family of ABC permeases using a metabolic background property (urea utilization). Thus, the TRUE set for this family comprised members whose genome of origin encoded a urea utilization system. By moving a sliding window across the sequence of a permease, and searching each subsequence in turn against the full set of partitioned proteins, the method found which local sequence signatures best correlated with the urea utilization trait. Mapping of SIMBAL "hot spots" onto crystal structures of homologous permeases reveals that the significant sites are gating determinants on the cytosolic face rather than, say, docking sites for the substrate-binding protein on the extracellular face. In the second example, we partitioned a protein methyltransferase family using gene proximity as a criterion. In this case, the TRUE set comprised those methyltransferases encoded near the gene for the substrate RF-1. SIMBAL identifies sequence regions that map onto the substrate-binding interface while ignoring regions involved in the methyltransferase reaction mechanism in general. Neither method for training set construction requires any prior experimental characterization. Conclusions SIMBAL shows that, in functionally divergent protein families, selected short sequences often significantly outperform their full-length parent sequence for making functional predictions by sequence similarity, suggesting avenues for improved functional classifiers. When combined with structural data, SIMBAL affords the ability to localize and model functional sites. PMID:20102603

Proton spectral editing in the inhomogeneous radiofrequency field of a surface coil using modified stimulated echoes.

PubMed

Lahrech, H; Briguet, A

1990-11-01

It is shown that the modified stimulated echo sequence, [theta](+/- x +/- y)-t1-[theta](+ x)-t2/2-[2 theta](+ x)-t2/2- [theta](+ x)-t1-Acq(+/- x +/- y), denoted as MSTE[2 theta]x according to the exciter phase of the 2 theta pulse, is able to perform proton spectral editing without difference spectra. On the other hand, this sequence appears to be suitable for spatial localization. Sensitivity and spatial selectivity of MSTE and conventional stimulated echo sequence (STE) are briefly compared. MSTE is applied to editing lactate in the rat brain using the locally restricted excitation of a surface coil.

Coming-out across the life course: implications of age and historical context.

PubMed

Floyd, Frank J; Bakeman, Roger

2006-06-01

Effects of age and the calendar year when individuals first self-identified as gay, lesbian, or bisexual on their sexual orientation identity development were examined in a large community sample (N=767, 47% female, 18-74-years-old). These 2 variables were used to examine the timing and sequencing of 7 coming-out experiences: first awareness of same-sex attraction; first sexual experiences with opposite-sex partners; first sexual experiences with same-sex partners; self-identification as gay, lesbian, or bisexual; disclosure to someone other than a parent; disclosure to mother; and disclosure to father. The significant effects of age revealed that self-identification in adolescence as opposed to adulthood was associated with an overall young coming-out trajectory for all milestone experiences, which occurred in both earlier and recent historical contexts. Adolescents as opposed to adult self-identifiers were also more likely to demonstrate identity-centered sequences in which self-identification preceded same-sex sexual experiences, and fewer of these individuals had any heterosexual experience. Significant historical context effects indicated recent trends toward younger disclosure of orientation to others and to parents, greater likelihood of an identity-centered sequence, and younger ages for first heterosexual but not same-sex, sexual experiences. Among women, there was a recent trend toward greater likelihood of having a bisexual identity milestone. In general, the maturational effects were independent of historical context, with the exception that only adolescent self-identifiers who came out recently disclosed to others and to parents at an average age younger than 18 years. These developmental and historical trends expand on the stage-sequential framework to show how the process of sexual orientation identity development is driven by maturational factors as well as social changes.

2-D to 3-D global/local finite element analysis of cross-ply composite laminates

NASA Technical Reports Server (NTRS)

Thompson, D. Muheim; Griffin, O. Hayden, Jr.

1990-01-01

An example of two-dimensional to three-dimensional global/local finite element analysis of a laminated composite plate with a hole is presented. The 'zoom' technique of global/local analysis is used, where displacements of the global/local interface from the two-dimensional global model are applied to the edges of the three-dimensional local model. Three different hole diameters, one, three, and six inches, are considered in order to compare the effect of hole size on the three-dimensional stress state around the hole. In addition, three different stacking sequences are analyzed for the six inch hole case in order to study the effect of stacking sequence. The existence of a 'critical' hole size, where the interlaminar stresses are maximum, is indicated. Dispersion of plies at the same angle, as opposed to clustering, is found to reduce the magnitude of some interlaminar stress components and increase others.

Introduction to "The Polarities of Context in the Writing Center Conference"

ERIC Educational Resources Information Center

Lerner, Neal

2010-01-01

Janangelo's article "The Polarities of Context in the Writing Center Conference" appeared in "WCJ" in 1988, and in that piece, one he wrote as a graduate student at New York University, Jangangelo identifies what to the author is likely the central tension in writing center work: local versus general context. While other authors have explored the…

The southernmost record of a large erethizontid rodent (Hystricomorpha: Erethizontoidea) in the Pleistocene of South America: Biogeographic and paleoenvironmental implications

NASA Astrophysics Data System (ADS)

Vezzosi, Raúl I.; Kerber, Leonardo

2018-03-01

The South American porcupines (Erethizontidae) are included in two genera: Chaetomys and Coendou. The latter is a very speciose taxon, with about 13 living species. During at least the late Pliocene-early Pleistocene, erethizontids immigrated to Central and North America during the Great American Biotic Interchange. Although some Pleistocene fossils have been reported, the Quaternary history of this clade is still understudied. The only known extinct species is Coendou magnus. In this work, a fossil of a porcupine is reported from an Upper Pleistocene fluvial sedimentary sequence cropping out in the Northern Pampa geomorphological region, Santa Fe Province, Argentina. Despite this group having different living forms widely distributed in South American Neotropical woodland habitats, the Pleistocene occurrences of Erethizontidae are scarce and limited to Upper Pleistocene deposits from Bolivia, Brazil, and Uruguay. Currently, the specimen here reported represents the only Pleistocene porcupine from Argentina with a stratigraphical context. The morphological characters as well as the dimensions indicate that it is close to the Pleistocene erethizontid Coendou magnus. In this context, the presence of this erethizontid in such a southern locality, together with other taxa recorded from this site and the associated geological and paleoenvironmental evidence, indicates subtropical conditions, compared with the current conditions, which may have allowed a southern displacement of taxa more related to woodlands and xeric subtropical environments.

Statistical context shapes stimulus-specific adaptation in human auditory cortex

PubMed Central

Henry, Molly J.; Fromboluti, Elisa Kim; McAuley, J. Devin

2015-01-01

Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity. PMID:25652920

Genome Sequence of Aggregatibacter actinomycetemcomitans RHAA1, Isolated from a Rhesus Macaque, an Old World Primate

PubMed Central

Karched, Maribasappa; Furgang, David; Planet, Paul J.; DeSalle, Rob

2012-01-01

Aggregatibacter actinomycetemcomitans is implicated in localized aggressive periodontitis. We report the first genome sequence of an A. actinomycetemcomitans strain isolated from an Old World primate. PMID:22328766

Motivation of extended behaviors by anterior cingulate cortex.

PubMed

Holroyd, Clay B; Yeung, Nick

2012-02-01

Intense research interest over the past decade has yielded diverse and often discrepant theories about the function of anterior cingulate cortex (ACC). In particular, a dichotomy has emerged between neuropsychological theories suggesting a primary role for ACC in motivating or 'energizing' behavior, and neuroimaging-inspired theories emphasizing its contribution to cognitive control and reinforcement learning. To reconcile these views, we propose that ACC supports the selection and maintenance of 'options' - extended, context-specific sequences of behavior directed toward particular goals - that are learned through a process of hierarchical reinforcement learning. This theory accounts for ACC activity in relation to learning and control while simultaneously explaining the effects of ACC damage as disrupting the motivational context supporting the production of goal-directed action sequences. Copyright © 2011 Elsevier Ltd. All rights reserved.

Divisibility patterns of natural numbers on a complex network.

PubMed

Shekatkar, Snehal M; Bhagwat, Chandrasheel; Ambika, G

2015-09-16

Investigation of divisibility properties of natural numbers is one of the most important themes in the theory of numbers. Various tools have been developed over the centuries to discover and study the various patterns in the sequence of natural numbers in the context of divisibility. In the present paper, we study the divisibility of natural numbers using the framework of a growing complex network. In particular, using tools from the field of statistical inference, we show that the network is scale-free but has a non-stationary degree distribution. Along with this, we report a new kind of similarity pattern for the local clustering, which we call "stretching similarity", in this network. We also show that the various characteristics like average degree, global clustering coefficient and assortativity coefficient of the network vary smoothly with the size of the network. Using analytical arguments we estimate the asymptotic behavior of global clustering and average degree which is validated using numerical analysis.

A phase transition in energy-filtered RNA secondary structures.

PubMed

Han, Hillary S W; Reidys, Christian M

2012-10-01

In this article we study the effect of energy parameters on minimum free energy (mfe) RNA secondary structures. Employing a simplified combinatorial energy model that is only dependent on the diagram representation and is not sequence-specific, we prove the following dichotomy result. Mfe structures derived via the Turner energy parameters contain only finitely many complex irreducible substructures, and just minor parameter changes produce a class of mfe structures that contain a large number of small irreducibles. We localize the exact point at which the distribution of irreducibles experiences this phase transition from a discrete limit to a central limit distribution and, subsequently, put our result into the context of quantifying the effect of sparsification of the folding of these respective mfe structures. We show that the sparsification of realistic mfe structures leads to a constant time and space reduction, and that the sparsification of the folding of structures with modified parameters leads to a linear time and space reduction. We, furthermore, identify the limit distribution at the phase transition as a Rayleigh distribution.

Feedback and Feeding in the Context of Galaxy Evolution with SPICA: Direct Characterisation of Molecular Outflows and Inflows

NASA Astrophysics Data System (ADS)

González-Alfonso, E.; Armus, L.; Carrera, F. J.; Charmandaris, V.; Efstathiou, A.; Egami, E.; Fernández-Ontiveros, J. A.; Fischer, J.; Granato, G. L.; Gruppioni, C.; Hatziminaoglou, E.; Imanishi, M.; Isobe, N.; Kaneda, H.; Koziel-Wierzbowska, D.; Malkan, M. A.; Martín-Pintado, J.; Mateos, S.; Matsuhara, H.; Miniutti, G.; Nakagawa, T.; Pozzi, F.; Rico-Villas, F.; Rodighiero, G.; Roelfsema, P.; Spinoglio, L.; Spoon, H. W. W.; Sturm, E.; van der Tak, F.; Vignali, C.; Wang, L.

2017-11-01

A far-infrared observatory such as the SPace Infrared telescope for Cosmology and Astrophysics, with its unprecedented spectroscopic sensitivity, would unveil the role of feedback in galaxy evolution during the last 10 Gyr of the Universe (z = 1.5-2), through the use of far- and mid-infrared molecular and ionic fine structure lines that trace outflowing and infalling gas. Outflowing gas is identified in the far-infrared through P-Cygni line shapes and absorption blueshifted wings in molecular lines with high dipolar moments, and through emission line wings of fine-structure lines of ionised gas. We quantify the detectability of galaxy-scale massive molecular and ionised outflows as a function of redshift in AGN-dominated, starburst-dominated, and main-sequence galaxies, explore the detectability of metal-rich inflows in the local Universe, and describe the most significant synergies with other current and future observatories that will measure feedback in galaxies via complementary tracers at other wavelengths.

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

Larson, Natalie M.; Zok, Frank W.

One route for producing fiber-reinforced ceramic-matrix composites entails repeated impregnation and pyrolysis of a preceramic polymer in a fiber preform. The process relies crucially on the development of networks of contiguous cracks during pyrolysis, thereby allowing further impregnation to attain nearly-full densification. The present study employs in-situ x-ray computed tomography (XCT) to reveal in three dimensions the evolution of matrix structure during pyrolysis of a SiC-based preceramic polymer to 1200 °C. Observations are used to guide the development of a taxonomy of crack geometries and crack structures and to identify the temporal sequence of their formation. A quantitative analysis ismore » employed to characterize effects of local microstructural dimensions on the conditions required to form cracks of various types. Complementary measurements of gas evolution and mass loss of the preceramic polymer during pyrolysis as well as changes in mass density and Young's modulus provide context for the physical changes revealed by XCT. Furthermore, the findings provide a foundation for future development of physics-based models to guide composite fabrication processes.« less

Collective decision dynamics in the presence of external drivers

NASA Astrophysics Data System (ADS)

Bassett, Danielle S.; Alderson, David L.; Carlson, Jean M.

2012-09-01

We develop a sequence of models describing information transmission and decision dynamics for a network of individual agents subject to multiple sources of influence. Our general framework is set in the context of an impending natural disaster, where individuals, represented by nodes on the network, must decide whether or not to evacuate. Sources of influence include a one-to-many externally driven global broadcast as well as pairwise interactions, across links in the network, in which agents transmit either continuous opinions or binary actions. We consider both uniform and variable threshold rules on the individual opinion as baseline models for decision making. Our results indicate that (1) social networks lead to clustering and cohesive action among individuals, (2) binary information introduces high temporal variability and stagnation, and (3) information transmission over the network can either facilitate or hinder action adoption, depending on the influence of the global broadcast relative to the social network. Our framework highlights the essential role of local interactions between agents in predicting collective behavior of the population as a whole.

Specific interaction of capsid protein and importin-{alpha}/{beta} influences West Nile virus production

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

Bhuvanakantham, Raghavan; Chong, Mun-Keat; Ng, Mah-Lee, E-mail: micngml@nus.edu.sg

2009-11-06

West Nile virus (WNV) capsid (C) protein has been shown to enter the nucleus of infected cells. However, the mechanism by which C protein enters the nucleus is unknown. In this study, we have unveiled for the first time that nuclear transport of WNV and Dengue virus C protein is mediated by their direct association with importin-{alpha}. This interplay is mediated by the consensus sequences of bipartite nuclear localization signal located between amino acid residues 85-101 together with amino acid residues 42 and 43 of C protein. Elucidation of biological significance of importin-{alpha}/C protein interaction demonstrated that the binding efficiencymore » of this association influenced the nuclear entry of C protein and virus production. Collectively, this study illustrated the molecular mechanism by which the C protein of arthropod-borne flavivirus enters the nucleus and showed the importance of importin-{alpha}/C protein interaction in the context of flavivirus life-cycle.« less

SH2 Domains Recognize Contextual Peptide Sequence Information to Determine Selectivity*

PubMed Central

Liu, Bernard A.; Jablonowski, Karl; Shah, Eshana E.; Engelmann, Brett W.; Jones, Richard B.; Nash, Piers D.

2010-01-01

Selective ligand recognition by modular protein interaction domains is a primary determinant of specificity in signaling pathways. Src homology 2 (SH2) domains fulfill this capacity immediately downstream of tyrosine kinases, acting to recruit their host polypeptides to ligand proteins harboring phosphorylated tyrosine residues. The degree to which SH2 domains are selective and the mechanisms underlying selectivity are fundamental to understanding phosphotyrosine signaling networks. An examination of interactions between 50 SH2 domains and a set of 192 phosphotyrosine peptides corresponding to physiological motifs within FGF, insulin, and IGF-1 receptor pathways indicates that individual SH2 domains have distinct recognition properties and exhibit a remarkable degree of selectivity beyond that predicted by previously described binding motifs. The underlying basis for such selectivity is the ability of SH2 domains to recognize both permissive amino acid residues that enhance binding and non-permissive amino acid residues that oppose binding in the vicinity of the essential phosphotyrosine. Neighboring positions affect one another so local sequence context matters to SH2 domains. This complex linguistics allows SH2 domains to distinguish subtle differences in peptide ligands. This newly appreciated contextual dependence substantially increases the accessible information content embedded in the peptide ligands that can be effectively integrated to determine binding. This concept may serve more broadly as a paradigm for subtle recognition of physiological ligands by protein interaction domains. PMID:20627867

FunTree: advances in a resource for exploring and contextualising protein function evolution.

PubMed

Sillitoe, Ian; Furnham, Nicholas

2016-01-04

FunTree is a resource that brings together protein sequence, structure and functional information, including overall chemical reaction and mechanistic data, for structurally defined domain superfamilies. Developed in tandem with the CATH database, the original FunTree contained just 276 superfamilies focused on enzymes. Here, we present an update of FunTree that has expanded to include 2340 superfamilies including both enzymes and proteins with non-enzymatic functions annotated by Gene Ontology (GO) terms. This allows the investigation of how novel functions have evolved within a structurally defined superfamily and provides a means to analyse trends across many superfamilies. This is done not only within the context of a protein's sequence and structure but also the relationships of their functions. New measures of functional similarity have been integrated, including for enzymes comparisons of overall reactions based on overall bond changes, reaction centres (the local environment atoms involved in the reaction) and the sub-structure similarities of the metabolites involved in the reaction and for non-enzymes semantic similarities based on the GO. To identify and highlight changes in function through evolution, ancestral character estimations are made and presented. All this is accessible through a new re-designed web interface that can be found at http://www.funtree.info. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Roles of beta-turns in protein folding: from peptide models to protein engineering.

PubMed

Marcelino, Anna Marie C; Gierasch, Lila M

2008-05-01

Reverse turns are a major class of protein secondary structure; they represent sites of chain reversal and thus sites where the globular character of a protein is created. It has been speculated for many years that turns may nucleate the formation of structure in protein folding, as their propensity to occur will favor the approximation of their flanking regions and their general tendency to be hydrophilic will favor their disposition at the solvent-accessible surface. Reverse turns are local features, and it is therefore not surprising that their structural properties have been extensively studied using peptide models. In this article, we review research on peptide models of turns to test the hypothesis that the propensities of turns to form in short peptides will relate to the roles of corresponding sequences in protein folding. Turns with significant stability as isolated entities should actively promote the folding of a protein, and by contrast, turn sequences that merely allow the chain to adopt conformations required for chain reversal are predicted to be passive in the folding mechanism. We discuss results of protein engineering studies of the roles of turn residues in folding mechanisms. Factors that correlate with the importance of turns in folding indeed include their intrinsic stability, as well as their topological context and their participation in hydrophobic networks within the protein's structure.

Roles of β-Turns in Protein Folding: From Peptide Models to Protein Engineering

PubMed Central

Marcelino, Anna Marie C.; Gierasch, Lila M.

2010-01-01

Reverse turns are a major class of protein secondary structure; they represent sites of chain reversal and thus sites where the globular character of a protein is created. It has been speculated for many years that turns may nucleate the formation of structure in protein folding, as their propensity to occur will favor the approximation of their flanking regions and their general tendency to be hydrophilic will favor their disposition at the solvent-accessible surface. Reverse turns are local features, and it is therefore not surprising that their structural properties have been extensively studied using peptide models. In this article, we review research on peptide models of turns to test the hypothesis that the propensities of turns to form in short peptides will relate to the roles of corresponding sequences in protein folding. Turns with significant stability as isolated entities should actively promote the folding of a protein, and by contrast, turn sequences that merely allow the chain to adopt conformations required for chain reversal are predicted to be passive in the folding mechanism. We discuss results of protein engineering studies of the roles of turn residues in folding mechanisms. Factors that correlate with the importance of turns in folding indeed include their intrinsic stability, as well as their topological context and their participation in hydrophobic networks within the protein’s structure. PMID:18275088

The Next Generation Virgo Cluster Survey (NGVS). XXV. Fiducial Panchromatic Colors of Virgo Core Globular Clusters and Their Comparison to Model Predictions

NASA Astrophysics Data System (ADS)

Powalka, Mathieu; Lançon, Ariane; Puzia, Thomas H.; Peng, Eric W.; Liu, Chengze; Muñoz, Roberto P.; Blakeslee, John P.; Côté, Patrick; Ferrarese, Laura; Roediger, Joel; Sánchez-Janssen, Rúben; Zhang, Hongxin; Durrell, Patrick R.; Cuillandre, Jean-Charles; Duc, Pierre-Alain; Guhathakurta, Puragra; Gwyn, S. D. J.; Hudelot, Patrick; Mei, Simona; Toloba, Elisa

2016-11-01

The central region of the Virgo Cluster of galaxies contains thousands of globular clusters (GCs), an order of magnitude more than the number of clusters found in the Local Group. Relics of early star formation epochs in the universe, these GCs also provide ideal targets to test our understanding of the spectral energy distributions (SEDs) of old stellar populations. Based on photometric data from the Next Generation Virgo Cluster Survey (NGVS) and its near-infrared counterpart NGVS-IR, we select a robust sample of ≈ 2000 GCs with excellent photometry and tha span the full range of colors present in the Virgo core. The selection exploits the well-defined locus of GCs in the uiK diagram and the fact that the GCs are marginally resolved in the images. We show that the GCs define a narrow sequence in five-dimensional color space, with limited but real dispersion around the mean sequence. The comparison of these SEDs with the predictions of 11 widely used population synthesis models highlights differences between the models and also shows that no single model adequately matches the data in all colors. We discuss possible causes for some of these discrepancies. Forthcoming papers of this series will examine how best to estimate photometric metallicities in this context, and compare the Virgo GC colors with those in other environments.

Paleoenvironmental change as derived from loess sediment properties: Examples of last glacial loess sites from the Carpathian Basin

NASA Astrophysics Data System (ADS)

Lehmkuhl, Frank; Zeeden, Christian; Bösken, Janina; Eckmeier, Eileen; Hambach, Ulrich; Hauck, Thomas; Klasen, Nicole; Markovic, Slobodan; Obreht, Igor; Schulte, Philipp; Sümegi, Pal; Chu, Wei; Timar-Gabor, Alida; Veres, Daniel

2015-04-01

The project B1 within the CRC 806 "Our way to Europe" focuses on the "Eastern Trajectory" of modern human migration from Africa into Europe. The Middle East, and SE Europe constitute the principal areas to be investigated. SE Europe has become a special research focus since two early Homo sapiens individuals have been found at Oase Cave in the southern Banat. The fossils lack any stratigraphic context; cultural and environmental circumstances of these findings have remained unclear. In the neighbourhood of Oase Cave, however, several early Upper Palaeolithic sites, embedded in loess sequences were known since the 1950's. Some sites were re-investigated by our research team. Conceptionally we are following the idea of upland-lowland interaction, which combines parameters as sedimentary transport, sediment distribution, and paleosol development in different altitudes, all influenced by paleoclimate in space and time. Furthermore, some detailed studies concerning site-formation processes and the quality of open-air sites (sedimentary development, paleoecology, multilayering, reworking, human impact on soils and sediments) are being conducted at selected localities. Recent investigations of the loess-paleosol sequences (LPS) in SE Europe provided important environmental information which differ from "classical" ecological approaches derived from other European loess provinces. New luminescence dating results provide a sensitive chronology of environmental changes recorded in the LPS from both upland and lowland positions, giving the potential to link these.